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Eptinezumab treatment reduced acute headache medication use with corresponding reduction in migraine frequency in patients with chronic migraine and medication-overuse headache in promise-2
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Background: Eptinezumab is a monoclonal antibody that inhibits calcitonin gene‐related peptide for migraine prevention. This subgroup analysis of the PROMISE‐2 study evaluated the impact of eptinezumab on the levels of acute headache medication use in patients diagnosed with chronic migraine (CM) and medication‐overuse headache (MOH) in the PROMISE‐2 trial. Methods: PROMISE‐2 randomized patients with CM to 2 doses of eptinezumab 100, 300 mg, or placebo administered intravenously at baseline and at Week 12. Trained investigators diagnosed MOH at screening based on 3 months of medication history and in alignment with ICHD‐3b criteria. Analyses include the percentage of patients using acute medication at MOH levels for each study month (4‐week interval), the number of study months below MOH levels of acute medication use, and the reduction in acute medication use stratified by migraine responder status. MOH levels of acute medication use was defined using ICHD‐3b criteria. Results: MOH was diagnosed in 431 of 1072 patients (40.2%) treated in PROMISE‐2 (100 mg, n = 139; 300 mg, n = 147; placebo, n = 145). During Weeks 1‐4, 28.5% (100 mg) and 33.3% (300 mg) of eptinezumab‐treated patients were using acute medication at MOH levels compared with 50.7% of placebo patients. Rates of MOH levels of use were generally consistent across the study during eptinezumab treatment, with fewer eptinezumab‐treated patients using acute medication at MOH levels than placebo patients across all time points (eg, Weeks 21‐24: 100 mg, 31.5%; 300 mg, 25.6%; placebo, 36.9%). Half of the population of eptinezumab‐treated patients were below MOH thresholds of acute medication use during each of the 6 study months (100 mg, 50.5%; 300 mg, 49.5%), which was approximately twice the rate seen in placebo patients (27.1%). In patients who were ≥50% migraine responders over Weeks 1‐4, 74.0% (100 mg), 76.7% (300 mg), and 58.9% (placebo) simultaneously achieved a ≥50% reduction in total medication days, and 86.5% (100 mg), 86.6% (300 mg), and 77.6% (placebo) simultaneously achieved a ≥50% reduction in triptan days. Conclusion: These results demonstrated that eptinezumab reduced the overuse of acute headache medication within 4 weeks of initial treatment, with sustained benefit over 24 weeks. Half of eptinezumab‐treated patients were consistently below MOH thresholds of overuse for the entirety of the 24‐week treatment period, experiencing complete resolution of the MOH diagnosis.
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The comparison of flexible ureterorenoscopy and percutaneous nephrolithotomy in 20-40mm in kidney stones
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Introduction & Objective: Retrograde Intrarenal Surgery and Percutaneous Nephrolithotomy are two important treatment modalities in 20‐40mm kidney stones. The aim of our study is to compare retrograde intrarenal surgery and percutaneous nephrolithotomy in 20‐40mm kidney stones. Methods: A total of 800 patients, who applied to Urology Polyclinic of Etfal Training and Research Hospital of Sxisxli Hamidiye University of Health Sciences between May 2017 and June 2018 due to urinary system stone disease, were evaluated retrospectively. 282 patients, who have renal stones between 20mm and 40mm in size were included to the study. The demographic data of the patients are given in Table 1. Patients were randomized into two treatment groups: flexible ureterorenoscopy and percutaneous nephrolithotomy. Results: The stone‐free rate of the patients, who were applied one session of flexible ureterorenoscopy, was statistically significantly lower than the percutaneous nephrolithotomy group (p = 0,005) (Table2). There was a statistically significant difference in the complication rates of the groups (p < 0,001). The complication rate of the flexible ureterorenoscopy group was lower. Conclusions: Although percutaneous nephrolithotomy is the gold standard in the treatment of renal stones larger than 20 mm, it should be remembered that the similar success rate can be achieved with retrograde intrarenal surgical procedure with more than one session and greater than 20 mm.
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MON-156 PERITONEAL DIALYSIS SATISFACTION AND KIDNEY TRANSPLANTATION ATTITUDE AMONG CONTINUOUS AMBULATORY PERITONEAL DIALYSIS PATIENTS UNDER THE PERITONEAL DIALYSIS FIRST POLICY
Abstract:
Introduction: The Thai Peritoneal Dialysis(PD) first policy has improved survival of end‐stage renal disease patients before kidney transplantation(KT) since 2008. However, evidence on their attitude toward the policy and the KT accessibility has been lacking. This study aims to assess PD care satisfaction and KT attitude among Continuous Ambulatory Peritoneal Dialysis(CAPD) patients under the Thai PD first policy. Methods: A telephone questionnaire including demographic data, general opinion on PD first policy, PD treatment satisfaction, and KT knowledge and attitude was conducted in April 2018 among 105 randomly selected PD patients from two PD centers in a large city. Results: The mean age of PD patients was 55.71 years, and their dialysis vintage was 3.49 years on average. Majority of them were satisfied(80.00%) and very satisfied(3.81%) whereas only 1.9% expressed their dissatisfaction. Ninety‐nine patients(94.29%) agree with PD first policy, of which 67.68% stated that this policy could help reduce their expense. Of 105 patients, 25.71% declared that they had KT knowledge and 78.10% would like to undergo KT. The main motivation factor to undergo KT was the increased chance to work and contribute back to the society(47.56%). Conclusions: The Thai PD First Policy has been well received. The need for transition to KT exists and a good strategic plan to improve knowledge about and to prepare for KT is required.
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Acute alcohol, aging, and their interaction: exploring electrophysiological indices of attention
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Background: Despite increasing attention toward effects of moderate drinking lifestyles, relatively little is known about the neurocognitive effects of acute alcohol consumption in older adults. Neurophysiological alterations are associated with aging and acute alcohol consumption, suggesting potentially important interactive effects. This study examines these interactions using electrophysiological indices of visual attention. Based on available literature, our initial hypothesis was that such interactions would be evinced to a greater degree in measures of attention suppression (to irrelevant stimuli) than measures of enhancement (to relevant stimuli). Methods: Younger (25‐35 years; n = 101) and older (55‐70; n = 88) community residing adults were randomly assigned to one alcohol dose group (placebo; low [0.04%targeted BrAC]; moderate [0.065%]). Following consumption, participants completed a directed attend/ignore task requiring them to attend to relevant facial stimuli, or ignore irrelevant facial stimuli. Dependentmeasures includedmean amplitude for P1 and N1 components. Analyses of variance (2 [age group] 9 3 [dose]) were performed for each task condition and ERP component. Results: Significant age by dose interactions were detected during presentation of relevant stimuli for P1 and N1 components [F(2,140)=3.08, p = 0.05; F(2,147)=3.24, p = 0.04, respectively]. The P1 interaction was characterized by age differences at the 0.065 dose, with older participants evincing lower P1 amplitudes than older individuals (p = 0.02). No age differences were detected in either placebo or 0.04 conditions. The N1 interaction was consistent with these trends, with older adults again displaying lower amplitudes relative to younger participants (p = 0.04) at the 0.065 dose, and no age differences at other doses. No main or interactive effects were noted for irrelevant stimuli. Conclusion: Our results highlight provocative interactions between alcohol and age, which were consistent across two electrophysiological indices of visual attention. While these results are consistent with our hypothesis that older adults may be particularly sensitive to acute alcohol effects in measures of attention suppression and enhancement, they were counter to our hypothesis that these interactions would be more apparent in attentional measures during the presentation of irrelevant stimuli. The current findings contribute to a growing literature suggesting age‐related vulnerabilities to alcohol across a variety of neurocognitive processes, even at doses consistent with moderate consumption.
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A pilot study on the safety and feasibility of VL#FIA3-30-a newly developed topical agent for treating erectile dysfunction
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INTRODUCTION & OBJECTIVES: Treatment of Erectile dysfunction via application of a topical cream could be advantageous and involves fewer side‐effects. We aimed to evaluate the safety and feasibility of VL#FIA3‐30 which contains a combination of Moxisylyte, ISDN (vasoactive substances) and has a unique tunica‐penetrable delivery system. MATERIAL & METHODS: Men with IIEF‐EF 11‐19 were randomly divided into 4 groups. Group for measuring Pharmacokinetics and groups 2‐4 aimed to evaluate safety and feasibility, (differing in number of applications‐twice, 3 and 4 times) respectively. At first visit, after a two‐week wash‐out, patients underwent a physical examination and filled‐out validated sexual‐function and informational questionnaires directly‐related to the product's effect. After topical application, consecutive blood pressure (BP) measurements were done for 6hours and patients with a drop of≥20mmHg were excluded. Clinical (headache, weakness etc.) or local effects (dermal toxicity, burns, discomfort, and irritation) were recorded. IIEF‐EF and SEPs were collected before each visit. RESULTS: 32 men were included, mean IIEF‐EF 14.5. Three had a drop of>20mmHg without clinical effects and were excluded. In 8 subjects, after a single application, plasma PK levels were measured during 36hours at calculated intervals. No significant concentrations of ISDN or Moxisylyte were detected in all tested samples, as well as their active metabolites (ISMN‐2, ISMN‐5 and DAM plasma concentrations were 12.7, 15.0, 10.2 ng/ml respectively). Two patients reported a transient peri‐meatal irritation, one reported headache (without any change in BP). One‐third of patients reported significant penile engorgement, 6 and 2 patients were able to complete intercourse with and without use of medication, respectively. Only in group 4 (X4 applications, n=7), a clinically significant change was reported (mean increase in IIEF‐EF from 14.4 to 19.4). Of these, 3 reported a mean increase of 8 points. CONCLUSIONS: The use of VL#FIA3‐30 in men with ED is feasible. The promising safety allow us to now perform an in‐depth evaluation of its clinical efficacy.
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Safety and efficacy of nelarabine in children and young adults with relapsed or refractory T-lineage acute lymphoblastic leukaemia or T-lineage lymphoblastic lymphoma: results of a phase 4 study
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Nelarabine is an antineoplastic agent approved for the treatment of relapsed/refractory T‐lineage acute lymphoblastic leukaemia (T‐ALL) or T‐lineage acute lymphoblastic lymphoma (T‐LBL). The purpose of this phase 4, multicentre, single‐arm, observational, open‐label trial was to provide additional data on the safety and efficacy of nelarabine under licensed conditions of use in children and young adults <=21 years of age. Patients (N = 28) had a mean +/‐ standard deviation age of 11.5 +/‐ 4.6 years; 71% were male and 61% had a diagnosis of T‐ALL. Adverse events (AEs) and treatment‐related AEs were experienced by 46% and 21%, respectively, and included few haematological AEs and no haematological serious AEs. Neurological AEs from one of four predefined categories (peripheral and central nervous systems, mental status change and uncategorized) were reported in four patients. There were no AE‐related treatment discontinuations/withdrawals. The overall response rate was 39.3%: complete response (CR), 35.7%; CR without full haematological recovery (CR*), 3.6%. Post‐treatment stem cell transplantation was performed for 46% of the cohort. Median overall survival (OS) was 3.35 months for non‐responders and not reached for responders (CR + CR*). The response rate, median OS, and safety profile of nelarabine in this disease setting and population were consistent with those reported previously. Copyright Copyright © 2017 John Wiley & Sons Ltd
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Nordic walking may safely increase the intensity of exercise training in healthy subjects and in patients with chronic heart failure
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Background: Physical activity in patients with chronic heart failure (HF) improves the exercise capacity and quality of life, and may also reduce mortality and hospitalizations. The greatest benefits are achieved through highintensity aerobic exercises resulting in a stronger cardiorespiratory response. Nordic walking (NW), a walking technique using two poles and mimicking the movements performed while cross‐country skiing, is associated with the involvement of more muscle groups than in the case of classic walking, and should therefore make it possible to increase exercise intensity, resulting in more effective training for patients with HF Objectives: The aim of the study was to assess the feasibility and safety of the NW technique, and to compare the effort intensity while walking with and without the NW technique in both healthy subjects and in patients with chronic HF. Material and Methods: The study involved 12 healthy individuals (aged 30 +/‐ 10 years, 5 men) and 12 men with stable chronic systolic HF (aged 63 +/‐ 11 years, all categorized in New York Heart Association class II, median LVEF 30%, median peak VO2 18.25 mL/kg/min). All the participants completed two randomly assigned submaximal walking tests (one with NW poles and one without) conducted on a level treadmill for 6 min at a constant speed of 5 km/h. Results: Walking with the NW technique was feasible, safe and well tolerated in all subjects. In both the control group and the chronic HF group, walking with the NW technique increased peak VO2, RER, VE, PET CO2, HR and SBP over walking without the poles; and the fatigue grade according to the abridged Borg scale was higher. Dyspnea did not increase significantly with the NW technique. Conclusions: The NW technique can increase the intensity of aerobic training in a safe and well‐tolerated way in both healthy individuals and in patients with chronic HF. © Copyright by Wroclaw Medical University.
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Noninvasive mechanical ventilation improves breathing-swallowing interaction of ventilator dependent neuromuscular patients: a prospective crossover study
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Background Respiratory involvement in neuromuscular disorders may contribute to impaired breathingswallowing interactions, swallowing disorders and malnutrition. We investigated whether the use of non‐invasive ventilation (NIV) controlled by the patient could improve swallowing performances in a population of neuromuscular patients requiring daytime NIV. Methods Ten neuromuscular patients with severe respiratory failure requiring extensive NIV use were studied while swallowing without and with NIV (while ventilated with a modified ventilator allowing the patient to withhold ventilation as desired). Breathing‐swallowing interactions were investigated by chin electromyography, cervical piezoelectric sensor, nasal flow recording and inductive plethysmography. Two water‐bolus sizes (5 and 10ml) and a textured yogurt bolus were tested in a random order. Results NIV use significantly improved swallowing fragmentation (defined as the number of respiratory interruption of the swallowing of a single bolus) (p = 0.003) and breathing‐swallowing synchronization (with a significant increase of swallows followed by an expiration) (p <0.0001). Patient exhibited piecemeal swallowing which was not influenced by NIV use (p = 0.07). NIV use also significantly reduced dyspnea during swallowing (p = 0.04) while preserving swallowing comfort, regardless of bolus type. Conclusion The use of patient controlled NIV improves swallowing parameters in patients with severe neuromuscular respiratory failure requiring daytime NIV, without impairing swallowing comfort.
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Improvements in patient-reported outcomes following 52 weeks of treatment with certolizumab pegol in combination with methotrexate in DMARD-naive patients with severe, active and progressive rheumatoid arthritis: results from the C-early randomized, double-blind, controlled phase 3 study
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Objectives: To assess effects of CZP+MTX vs placebo (PBO)+MTX on patient reported outcomes in DMARD‐naïve patients with severe, active and progressive RA. Methods: Patients in this double‐blind randomized study (NCT01519791) were DMARD‐naïve with active RA< 1yr diagnosis at baseline (BL), fulfilling 2010 ACR/EULAR criteria; ≥ 4 swollen and ≥ 4 tender joints; DAS28[ESR]≥ 3.2; CRP≥ 10mg/L and/or ESR≥ 28mm/hr, rheumatoid factor/ACPA positive. Patients were randomized 3:1 to CZP (400mg Wks 0,2,4 then 200mg Q2W to Wk52)+MTX or PBO+MTX. MTX was initiated at 10mg/wk, increased up to 25mg/wk by Wk8, maximum tolerated dose maintained to Wk52. HAQ‐DI, PtGADA, Pain VAS, %pts achieving normative physical function (HAQ‐DI≤ 0.5), health‐related QoL (SF‐36, EQ‐5D‐3L) were assessed. At Wk52 changes from baseline (CFB) were analyzed using ANCOVA (LOCF imputation); categorical variables were analyzed using logistic regression (non‐responder imputation). Data are LS mean CFB (SE) unless otherwise specified. Results: 660 (CZP+MTX) and 219 (PBO+MTX) patients were randomized; 655 vs 213 in the full analysis set (patients with baseline and postbaselineL DAS28[ESR]). Baseline characteristics were balanced between study arms; mean (SD) HAQ‐DI= 1.6 (0.6), Pain VAS= 66.1 (22.4), PtGADA= 65.3 (22.0). At Wk52, greater improvements from baseline were observed with CZP+MTX vs PBO+MTX in HAQ‐DI (‐1.0 [0.0] vs ‐0.8 [0.0], p< 0.001; 48.1% vs 35.7% patients reached normative function), pain (‐48.5 [1.0] vs ‐44.0 [1.7], p< 0.05), PtGADA (‐46.7 [1.0] vs ‐42.0 [12.5], p< 0.05) and health‐related QoL measured by SF‐36 (physical component summary score= 12.4 [0.4] vs 10.7 [0.6], p< 0.01; mental component summary score= 8.2 [0.5] vs 6.8 [0.7]). Numerically higher proportions of CZP+MTX patients reported no problems in domains of the EQ‐5D‐3L vs PBO+MTX patients, including mobility, self‐care, usual activities, pain/discomfort and anxiety/depression. Conclusions: In DMARD‐naïve patients with severe, active and progressive RA, CZP+MTX showed greater improvements at 1‐year in physical function, pain, disease activity and health‐related QoL compared to PBO+MTX.
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I mproving patient safety after rigid bronchoscopy in adults: laryngeal mask airway versus face mask – A pilot study
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Background: There are still no clear guidelines in the literature on per procedural bronchoscopic management for anesthesiologists, and few relevant datasets are available. To obtain rapid recovery from anesthesia, it is often necessary to keep patients in the recovery room for several hours until they become clinically stable. In this study, we tested the hypothesis that the laryngeal mask airway (LMA) enables better respiratory and hemodynamic recovery than the oxygen face mask (FM) in patients undergoing rigid bronchoscopy. Methods: Twenty‐one patients undergoing elective bronchoscopy of the upper airway were randomized to ventilation assistance with FM or LMA after a rigid bronchoscopy procedure under general anesthesia. The primary endpoint was duration of post‐surgical recovery and the secondary endpoints were postoperative hemodynamic and respiratory parameters. Assessment of the study endpoints was performed by an intensive care specialist blinded to the method of ventilation used. The statistical analysis was performed using the Fisher’s Exact test for nominal data and the Student’s t‐test for continuous data. Results: There was no statistically significant difference in post‐procedural time between the two groups (P=0.972). The recovery parameters were significantly better in the LMA group than in the FM group, with significantly fewer desaturation, hypotensive, and bradycardic events (P <0.05). Conclusion: We conclude that the LMA may be safer and more comfortable than the FM in patients undergoing rigid bronchoscopy.
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Modulation of lower extremity rotational deformities using TheraTogs™ and strapping system in children with spastic diplegia
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Background: Rotational abnormalities are a common in many neuromuscular disorders, such as cerebral palsy. Objective: This study was conducted to investigate the effect of TheraTogs™ and strapping system on femoral anteversion and external tibial torsion in children with spastic diplegia and to determine its effect on the child's gait. Methods: Thirty children with spastic diplegia from both sexes were randomly assigned into two equal groups. Their age ranged from six to eight years. Control group (A) treated by a designed gait training program, study group (B) received the same program as group (A) in addition to TheraTogs™ orthotics undergarment and lower extremity strapping bilaterally. Pro‐Reflex 3‐D system was used to measure rotation angles of hip and knee joints, gait velocity and foot progression angle. Pre and post assessment were performed for both groups following 3 months intervention phase (post1), another assessment time (post2) was added in group B during wearing TheraTogs™ and strapping system. Results: There was no significant difference in all measuring variables in group (A) when comparing its pre and post assessment. Significant improvement was observed in all measuring variables in group (B) when comparing its pre, post1 and post2assessment and when comparing the post treatment results of the two groups in favor of group (B) (P‐value < 0.05). Conclusion: The current study showed positive effect of using Theratogs™ and strapping system on rotational abnormalities and gait pattern from a biomechanical perspective.
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Long-term safety and efficacy of tabalumab, an anti-B-cell activating factor monoclonal antibody, in patients with rheumatoid arthritis: a 52-week, open-label extension study
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Background/Purpose: Tabalumab, a monoclonal antibody that neutralizes membrane‐bound and soluble B cell activating factor (BAFF), has been shown to reduce rheumatoid arthritis (RA) signs and symptoms1. This open‐label study evaluated the long‐term safety and efficacy of tabalumab in RA patients (pts). Methods: This 52‐week (wk), open‐label, flexible‐dose extension study enrolled pts who completed 24 wks of a randomized, controlled trial (RCT) of tabalumab vs placebo (pb) and received study drug for ≥6 or 12 wks. Pts remained on stable MTX doses throughout. In RCT 1, pts received pb or tabalumab 30 or 80 mg IV every 3 wks for 6 wks and followed‐up for 18 wks. In RCT 2, pts received pb or tabalumab 1, 3, 10, 30, 60, or 120 mg SC every 4 wks (Q4W) for 24 wks. At extension study start, all pts received SC tabalumab 60 mg Q4W for 48 wks; a 1‐time increase to tabalumab 120 mg Q4W (60/120 mg) and 1‐time decrease to 60 mg Q4W per pt was allowed (60/120/60 mg). Results: Of those who completed RCT 1 or 2, 98% (N=182, safety population) enrolled: tabalumab 60 mg (n=60), tabalumab 60/120 mg (n=121), and 1 pt after taking tabalumab 120 mg then returned to 60 mg. Baseline (pre‐tabalumab) RA activity levels were generally higher for the 60/120 mg group. Overall, both groups appeared to maintain efficacy with long‐term treatment (Table 1). One pt died due to myocardial infarction (60/120 mg). In each group, 5% discontinued due to an adverse event (AE). There was a higher frequency of serious AEs (SAEs) and treatment‐emergent AEs (TEAEs, including severe events) as well as events of interest, including infections and injection‐site reactions in the 60/120 mg group. Most infections involved the upper respiratory tract. One pt (60/120 mg) reported a fungal skin infection. No clinically significant differences in hematologic or chemistry values, vital signs, or ECGs were seen. Total B lymphocyte counts decreased by 40% from pretabalumab baseline for all groups. The incidence of treatment‐emergent, antitabalumab antibodies was 4.4% (8/182). Table 2 shows more detailed safety data. (Figure presented).
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Efficacy of nilotinib versus high-dose imatinib in early CP chronic myeloid leukemia patients who have suboptimal molecular responses to standard-dose imatinib (re-nice multicencenter study)
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Background. Achievement of major molecular response (MMR) is a significant prognostic factor in CML as it has been shown to be associated with longer duration of complete cytogenetic response (CCyR) and long‐term progression‐free survival. In IRIS study, patients who achieved both CCyR and MMR showed higher progression‐free survival rates, compared to those who had CCyR without MMR and those who did not achieve CCyR. Compared to standard dose of imatinib, higher doses of imatinib are expected to yield higher CCyR and MMR rates, and second‐generation tyrosine kinase inhibitor, nilotinib also produces high CCyR and MMR rates in patients with CP CML who are resistant to imatinib. Aims. In this study, the efficacy of nilotinib and high‐dose imatinib was investigated in suboptimal molecular response patients who received first line imatinib therapy at a daily dose of 400 mg. Methods. Early CP CML patients who have achieved CCyR but no MMR after at least 18 months and up to 24 months (≥ 18 to ≤ 24 months) on first line imatinib therapy at a daily dose of 400 mg were enrolled in this clinical trial, and informed consents were obtained prior to participation. In nilotinib arm, patients received oral dose of 400 mg BID (800 mg/day), and patients received 800 mg/day administrated as 400 mg BID in imatinib dose‐escalation arm. To assess the drug efficacy, cytogenetics and RQ‐PCR analysis were performed at regular intervals, and baseline mutational analysis was conducted for every patient with subsequent mutational analyses performed in patients demonstrating either lack of response or disease progression. Primary endpoint is to evaluate the cumulative MMR rates by 12 months, and secondary endpoints are to evaluate the cumulative CMR rates and time to and duration of MMR and CMR during further 24 month follow‐up. Progression‐free survival and safety profiles will also be assessed as secondary endpoints. Results. A total of 21 patients were randomized into nilotinib arm (n = 10) or imatinib arm (n = 11). With a median follow‐up of 6 months (range, 1 ‐ 24 months), all patients have maintained CCyR without progression to advanced disease, and progressive decrease in BCR‐ABL transcript levels was observed in all patients. Cumulative MMR rates by 12 months were significantly higher in nilotinib arm compared to imatinib dose‐escalation arm (68.90% vs. 22.10%, P = 0.0274), and patients treated with nilotinib also showed faster molecular response rates, with 5 patients achieving MMR within 3 months of nilotinib therapy. (Figure 1) Although toxicity was observed more frequently in imatinib dose‐escalation arm, no patient required dose reduction or discontinuation of therapy due to toxicities in both randomized groups. Conclusions. These preliminary results demonstrate that BCR‐ABL transcript levels in suboptimal molecular responders progressively decrease in both (Figure presented) nilotinib and imatinib arms at a daily dose of 800 mg with higher and faster molecular responses in nilotinib arm. Through further clinical investigation on a large patient population and longer period of observation, the efficacy of early intervention of suboptimal molecular response using nilotinib or dose escalation of imatinib will be assessed.
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Analysis of the various procedures used in great saphenous vein surgery in the Czech Republic and benefit of Daflon 500 mg to postoperative symptoms
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The aim of this clinical study was to compare the intensity of postoperative pain using a 10‐cm Visual Analog Scale (VAS), a quality‐of‐life questionnaire (CIVIQ), and a patient diary between two groups of patients, consisting of: a treatment group: patients who underwent a stripping procedure of the great saphenous vein (GSV), and were treated with Daflon 500 mg®* 14 days before and 14 days after the operation, 2 tablets 500 mg/day; a control group: patients who underwent stripping of the GSV, but were not treated with Daflon 500 mg®. In addition, the two groups were also compared for the size of postoperative hematoma, analgesic consumption, and for the incidence of other symptoms associated with chronic venous disease (edema, tired and heavy legs, cramps, sensation of itching), using the VAS scale. Lastly, overall efficacy of the treatment was assessed. The present trial included 181 patients from 15 medical centers throughout the Czech Republic. High ligation and partial stripping of the GSV in one lower limb was performed in all patients (short stripping from groin to knee). Patients were randomly assigned either to the treatment group (92 patients) or to the control group (89 patients). The degree of pain and the patient's condition were evaluated by the physician 14 days prior to the surgery (D‐14), then 7 days (D7) and 14 days (D14) after surgery. Results indicated that Daflon 500 mg reduced the intensity of postoperative pain, which resulted in decreased consumption of analgesics. The size of postoperative hematoma was significantly smaller in the treatment group compared with the control group (P<0.001), and associated symptoms of CVD and quality of life were significantly better in this group. Effective phlebotropic drugs, like Daflon 500 mg, administered to patients 14 days before and 14 days after stripping surgery may improve postoperative morbidity.
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Cardiorenal Outcomes With Finerenone in Asian Patients With CKD and Type 2 Diabetes: post Hoc Analysis From FIDELIO-DKD
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Background: In FIDELIO‐DKD, finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). A post hoc analysis of FIDELIO‐DKD data was conducted to explore the cardiorenal effects of finerenone in patients from the Asian region. Methods: In FIDELIO‐DKD (NCT02540993), 5674 patients were randomized to receive finerenone or placebo, of whom 1327 were from 10 Asian countries and territories. Eligible patients had T2D, and either urine albumin‐to‐creatinine ratio (UACR) ≥30 to <300 mg/g and estimated glomerular filtration rate (eGFR) ≥25 to <60 mL/min/1.73 m2, or UACR ≥300 to ≤5000 mg/g and eGFR ≥25 to <75 mL/min/1.73 m2, and were treated with optimized renin‐angiotensin system blockade. The primary efficacy outcome was a kidney composite outcome (time to kidney failure, death from renal causes, and sustained decrease of ≥40% in eGFR from baseline). Secondary efficacy outcomes included both kidney (time to kidney failure, death from renal causes, and sustained decrease of ≥57% in eGFR from baseline) and cardiovascular (CV; time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite outcomes. Results: In the Asian subgroup, 665/1327 (50%) patients received finerenone. The finerenone cohort of the Asian subgroup showed reduced ≥40% and ≥57% eGFR kidney composite outcomes and CV composite outcome vs the placebo group (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.56‐0.87; HR=0.73, 95% CI 0.55‐0.97; and HR=0.85, 95% CI 0.59‐1.21, respectively). No apparent differences were observed between the Asian subgroup and patients from the rest of the world for these outcomes (HR=0.88, 95% CI 0.77‐1.02 [Pinteraction=0.09]; HR=0.78; 95% CI 0.64‐0.95 [Pinteraction=0.71]; and HR=0.86, 95% CI 0.74‐1.00 [Pinteraction=0.95], respectively). Finerenone demonstrated similar safety across subgroups. Conclusions: The beneficial effect of finerenone on cardiorenal outcomes in the Asian population are comparable to the overall results observed in FIDELIO‐DKD.
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Randomised, double-blind, placebo-controlled study of iguratimod in the treatment of active spondyloarthritis
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Background/Purpose: Iguratimod, also known as T‐614, is a new type of small molecule compound with anti‐inflammatory and immunomodulatory effects; It was listed in China(2011) and Japan(2012) for the treatment of rheumatoid arthritis;its safety and effectiveness have been verified in patients with rheumatoid arthritis. As Iguratimod could inhibit the production of inflammatory cytokines, such as IL‐1 and TNF; block the IL‐17 signalling pathway and inhibit cyclooxygenase, Iguratimod may be effective in the treatment of SPA/AS. However, no rigorous clinical research exists to confirm this speculation. Therefore, this study aimed to evaluate the efficacy and safety of Iguratimod in patients with active SpA Methods: Subjects with active SpA were enrolled and randomly divided into two groups at a ratio of 1:2 (placebo vs. Iguratimod). On the basis of non‐steroidal anti‐inflammatory drugs, combined treatment with Iguratimod or placebo, followed by follow‐up every 4 weeks for 24 weeks. The primary efficacy endpoint was to evaluate the alleviation rate of ASAS20; the important improvement of ASDAS and the efficacy of spinal mobility, physical function and quality of life at the 24th week. Results: A total of 48 cases in the Iguratimod group and 25 cases in the placebo group were included in the final analysis. On the 24th week, the percentage of responders to ASAS20 (80% vs. 44%) and ASAS40 (56% vs. 20%) treated with Iguratimod were significantly higher than that in the placebo group (P < 0.05). Twelve cases had gastrointestinal discomfort, of which eight were in the Iguratimod group (16.7%, one case withdrew from the study due to diarrhoea) and four were in the placebo group (16.0%). No significant difference was found between the two groups (P < 0.05). Three cases of elevated transaminase were observed in the Iguratimod group and none in the placebo group, with no significant difference (P < 0.05). Conclusion: Iguratimod could significantly reduce the symptoms and signs of patients with active SpA. It could improve the physical function and quality of life of these patients and the overall safety and tolerance are good.
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Effect of Pregabalin on Morphine Consumption, Sleep, Mood and Ability to Change Position After Colorectal Cancer Surgery
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Introduction: Pregabalin is a co‐analgesic to improve the pain control after colorectal cancer surgeries. There is less knowledge about the effect of Pregabalin on postoperative sleep and the ability to change the position of patients after surgery. This study aimed to assess the impact of Pregabalin on postoperative morphine consumption, pain, sleep, mood, and ability to change position after colorectal cancer surgery. Methods: This double‐blind, randomized, controlled, single‐center clinical trial was performed in Tehran, Iran, from June 2017 to June 2018. Seventy patients were included for colorectal cancer surgery randomly divided into two groups (A, B). Group A received two doses Pregabalin (150 mg) pre‐operative and post‐operative, and group B as a placebo was administered at the same scheme. The two groups had similar analgesia and anesthesia regimens. The pain was scored by a numerical rating scale (NRS); disturbance in sleep, and mood. The daily activity was numbered based on a scoring system such as BPI questionnaires; and, nausea‐ vomiting, morphine consumption, and fatigue headache were evaluated 48 hours after surgery. Results: Morphine consumption was lower in the Pregabalin group 24 h after surgery (P=0.01). The two groups were similar regarding sleep interference scores and side effects (P>0.05). But, mood and actions interference scores in the Pregabalin group showed a significant improvement in 48 h postoperative (P<0.05) (Table 3). Conclusion: The results showed that Pregabalin could reduce postoperative morphine consumption and improve mood and actions interference scores after colorectal cancer surgery. However, there was no difference between Pregabalin and placebo in postoperative pain management and sleep interference scores after colorectal cancer surgery.
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Demographic, clinical and forensic characteristics of alleged offenders referred to West End Specialised Hospital, Kimberley, South Africa
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The study investigated demographic, clinical and forensic characteristics of alleged offenders referred for forensic assessment. A data collection form was used to gather information from 155 offenders' clinical records. The subjects were mainly young males, aged between 18 and 35 years, with low educational levels and high unemployment rate. The most common diagnoses were substance‐related and addictive disorders, and schizophrenia spectrum and other psychotic disorders. A sizeable number of offenders were diagnosed with an intellectual disability. The comorbidity of other medical conditions such as epilepsy and HIV/AIDS was also noteworthy. In total, 55.5% of the offenders were found competent to stand trial, and 46.5% were declared criminally responsible. Offenders presenting with schizophrenia and intellectual disabilities were often declared incompetent to stand trial and were generally not responsible for alleged crimes. There was association between adjudicative competence and criminal responsibility. The results highlight effect of substances on mental illness and crime.
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Efficacy and safety outcomes in the phase 3 INO-vate trial by baseline CD22 positivity assessed by local laboratories
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Introduction: Inotuzumab ozogamicin (InO) is a CD22‐directed antibody‐calicheamicin conjugate. Patients (pts) with relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (ALL) treated with InO vs standard of care chemotherapy (SC) had significantly better response, and improved survival in INO‐VATE (NCT01564784). Based on central laboratory assessment, this favorable benefitrisk profile of InO was independent of leukemic blast CD22 positivity (≥90% vs <90%) and CD22 receptor density (quantified as Molecules of Equivalent Soluble Fluorochrome, quartile analysis). As CD22 is usually assessed in local labs in clinical practice, this study uses INO‐VATE data to investigate the relationship between baseline CD22 positivity assessed by local labs and the efficacy and safety of InO vs SC. Methods: Adult pts (≥18 yrs) with R/R CD22‐positive (based on local or central lab results) ALL in salvage 1 or 2 were randomized to InO (n=164) or SC (n=162) (details: NEJM 2016;375:740‐53). InO starting dose was 1.8 mg/m2/cycle (0.8 mg/m2 on Day 1; 0.5 mg/m2 on Days 8 & 15 of a 21‐28‐day cycle for ≤6 cycles) and reduced to 1.5 mg/m2/cycle for pts with complete remission (CR) or CR with incomplete hematologic recovery (CRi). SC included fludarabine/cytarabine [Ara‐C]/granulocyte colony‐stimulating factor, Ara‐C plus mitoxantrone, or high‐dose Ara‐C. CD22 positivity (% of leukemic blasts expressing CD22) was measured at screening by flow cytometry or immunohistochemistry. Efficacy (CR/CRi, minimal residual disease [MRD, assessed in central labs] among responders, overall survival [OS], progression‐free survival [PFS], and duration of remission [DoR]) and safety outcomes were analyzed by CD22 positivity quartiles, Quartile 1 (Q1) having the lowest and Q4 the highest CD22 positivity. Data cutoff: 04Jan2017. P‐values are 1‐sided. Results: Baseline CD22 positivity per local lab was available for 152 pts per arm. CD22 positivity (%) was comparable between treatment arms for each quartile; median (range) was 21.9 (1.0‐39.4) for InO vs 23.9 (0.0‐39.0) for SC in Q1, 55.5 (40.0‐68.9) vs 56.3 (40.0‐66.0) in Q2, 84.0 (70.0‐92.0) vs 84.0 (70.0‐ 92.9) in Q3, and 98.0 (93.0‐100.0) for both arms in Q4. CR/CRi rates showed no difference among quartiles in the InO (P=0.5906) or SC arm (P=0.2061), and were significantly higher with InO vs SC for all quartiles (Q1: 81.6% vs 41.2%, P=0.0002; Q2: 68.4% vs 36.8%, P=0.0029; Q3: 73.2% vs 27.0%, P<0.0001; Q4: 77.1% vs 20.9%, P<0.0001) (Figure). MRD negativity rates in responders were also higher with InO vs SC and the differences in the lower quartiles (Q1‐Q3) were significant (Q1: 87.1% vs 50.0%, P=0.0121; Q2: 69.2% vs 21.4%, P=0.0048; Q3: 66.7% vs 30.0%, P=0.0486; Q4: 77.8% vs 55.6%, P=0.1930) (Figure). PFS, DoR, and OS were longer with InO vs SC. The benefit of InO over SC was more evident in the higher quartiles (Q2‐4); hazard ratio (97.5% Cl) was 0.44 (0.31‐0.61) for PFS, 0.53 (0.31‐0.88) for DoR, and 0.71 (0.52‐0.99) for OS (Table). Cytopenias were the most common ≥grade 3 adverse events in the InO arm, with similar rates across the quartiles (Q1‐Q4: neutropenia: 52.6%, 47.4%, 39.0%, and 48.6%; thrombocytopenia: 34.2%, 44.7%, 46.3%, and 31.4%; febrile neutropenia: 15.8%, 28.9%, 29.3%, and 34.3%). Rates of ≥grade 3 infections were 21.1%, 26.3%, 36.6%, and 31.4% for Q1‐Q4. In InO‐treated pts, rates of ≥grade 3 hyperbilirubinemia were similar for the lower quartiles (Q1‐Q3: 5.3%, 7.9%, and 2.4%; 11.4% for Q4); rates of ≥grade 3 veno‐occlusive liver disease (VOD)/sinusoidal obstruction syndrome (SOS) within 2 years of randomization regardless of causality were 13.2%, 7.9%, 7.3%, and 17.1% in Q1‐Q4, respectively; 3 grade 5 VOD/SOS events occurred in Q1, 2 in Q4, and 0 in Q2 and Q3. Conclusions: In general, the results showed improvement in measures of efficacy for InO over SC that was comparable across all 4 CD22 positivity quartiles per local lab assessments. For DoR, PFS, and OS, there was a suggestion of greater benefit for pts in higher CD22 positivity quartiles treated with InO, though these analyses are limited by the small sample size. These trends are in alignment with those previously presented for central lab CD22 positivity and receptor density (Blood 2017;130[Suppl 1]:1272). Overall, InO demonstrated a favorable benefit/risk profile for pts with R/R B cell precursor ALL independent of local lab CD22 positivity.
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The effect of weight loss on the progression of meniscal extrusion and size in knee osteoarthritis: a post-hoc analysis of the intensive diet and exercise for arthritis (idea) trial
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Purpose: Weight loss induced by diet and exercise has beneficial effects on clinical outcomes in patients with knee osteoarthritis (OA), potentially conveyed by inflammatory and/or mechanical pathways. Meniscus extrusion has been associated with OA incidence and progression, and knee symptoms. A greater BMI may be associated with meniscal extrusion, but whether weight loss (and exercise) affects meniscal extrusion and size, and whether these represent potential mechanisms by which weight loss leads to improved clinical outcomes has not been elucidated. The objective of this study, therefore, was to test the hypothesis that weight loss, achieved by diet and/or exercise intervention, is associated with less longitudinal progression in meniscus extrusion and size. Methods: The Intensive Diet and Exercise for Arthritis trial (IDEA) was a prospective, single blind, randomized controlled trial conducted on 454 overweight and obese (BMI=27 ‐ 41 kg/m2) older adults (age ≥55yrs) with knee pain and radiographic knee OA (KLG≥2). Participants were randomized to one of three, 18‐month interventions: exercise only (E), diet only (D), or diet+exercise (D+E). In a random subsample of 106 participants, MRIs were obtained at baseline and follow‐up (E: n=36; D: n=35; D+E: n=35). The central 5 slices of the medial/lateral menisci and tibial cartilage surfaces were segmented in 91/96 coronal spoiled gradient‐echo acquisitions with fat suppression (1.5x 0.31x 0.3 mm), with blinding to intervention and acquisition order. This was assisted by concurrent display of the PDw spin echo images commonly used for radiological meniscus evaluation. Measures of meniscus position and size (Fig. 1) were calculated using custom software, including maximum and mean extrusion distance, area of the meniscus not covering (i.e. extruding) the tibial plateau, tibial coverage (by the meniscus), overlap distance between the meniscus and tibial plateau (position) as well as meniscus width and height. Regression analyses were used to examine the association between absolute weight change (in kg) and change in meniscus measures over 18 months, with and without adjustment for age, sex, and baseline parameters. Between group comparisons of longitudinal changes in meniscal extrusion and size were evaluated using ANCOVA, with and without adjustment for the measures mentioned above. Results: Weight loss evaluated across all participants was significantly associated with less longitudinal progression of medial meniscus extrusion, as well as with an actual decrease in maximum and mean medial meniscus extrusion distance over 18 months (Table 1, Fig. 2A). Relationships between weight loss and change in meniscus area not covering the tibial plateau, tibial coverage, and overlap distance in medial meniscus were consistent with those for extrusion, but did not reach statistical significance. No significant relationships were observed for the lateral meniscus (Table 1, Fig. 2B). Associations between weight change and measures of meniscus size also did not reach statistical significance (Table 1). The results for absolute change in weight (kg) presented above, were consistent with those for percentage change in weight (data not shown). In the between‐group comparisons, longitudinal change in meniscus position and size parameters were not significantly different between the interventions (data not shown). Conclusions: This is the first study to investigate the effect of weight loss, and exercise, on quantitative measures of meniscus extrusion and size. Weight loss was found to be associated with a decrease in extrusion distance of the medial meniscus over 18 months. No differences by intervention type between the groups were detected. This may be due to the small sample size and the heterogeneity of the weight loss across the intervention groups. Another limitation is that images were only available for a subset of the IDEA cohort, but a strength was the application of quantitative measurement technology. Given the relationship between quantitative measures of meniscus extrusion and knee symptoms shown previously, the current data indicate that meniscus extrusion may be one of the mechanisms by which weight loss translates into a clinical benefit. Acknowledgement: This study was supported by an OARSI collaborative scholarship and the authors would like to extend their gratitude to OARSI for this scholarship. [Figure presented] [Figure presented] [Figure presented]
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Short-Term Impact of tDCS Over the Right Inferior Frontal Cortex on Impulsive Responses in a Go/No-go Task
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Inhibitory control, a process deeply studied in laboratory settings, refers to the ability to inhibit an action once it has been initiated. A common way to process data in such tasks is to take the mean response time (RT) and error rate per participant. However, such an analysis ignores the strong dependency between spontaneous RT variations and error rate. Conditional accuracy function (CAF) is of particular interest, as by plotting the probability of a response to be correct as a function of its latency, it provides a means for studying the strength of impulsive responses associated with a higher frequency of fast response errors. This procedure was applied to a recent set of data in which the right inferior frontal gyrus (rIFG) was modulated using transcranial direct current stimulation (tDCS). Healthy participants (n = 40) were presented with a "Go/No‐go" task (click on letter M, not on letter W, session 1). Then, one subgroup (n = 20) was randomly assigned to one 20‐minutes neuromodulation session with tDCS (anodal electrode, rIFG; cathodal electrode, neck); and the other group (n = 20) to a condition with sham (placebo) tDCS. All participants were finally confronted to the same "Go/No‐go" task (session 2). The rate of commission errors (click on W) and speed of response to Go trials were similar between sessions 1 and 2 in both neuromodulation groups. However, CAF showed that active tDCS over rIFG leads to a reduction of the drop in accuracy for fast responses (suggesting less impulsivity and greater inhibitory efficiency), this effect being only visible for the first experimental block following tDCS stimulation. Overall, the present data indicate that boosting the rIFG may be useful to enhance inhibitory skills, but that CAF could be of the greatest relevance to monitor the temporal dynamics of the neuromodulation effect. Copyright © 2018, EEG and Clinical Neuroscience Society (ECNS) 2018.
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Stereotactic body radiotherapy versus transarterial chemoembolization for medium-sized hepatocellular carcinoma: a propensity score matching analysis
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Aims: Because the data that guide selection of optimal therapy for the unresectable medium‐sized (3‐8 cm) hepatocellular carcinoma (HCC) are lacking, we aim to compare stereotactic body radiotherapy (SBRT) with transarterial chemoembolization (TACE) using a propensity score matching analysis. Methods: We enrolled patients who were diagnosed with HCC, with tumors sized 3‐8 cm, and were treated with SBRT or TACE. The endpoints of the study were overall survival (OS) and infield failure‐free survival (IFFS). They were compared using 1:2 propensity score matching analysis based on sex, age, types of hepatitis, tumor size, AJCC stage, BCLC stage, Child‐Pugh classification, ECOG performance status, and new diagnosis/recurrence. Kaplan‐Meier method and Cox regression analyses were used to evaluate the outcome and prognostic factors. Results: After matching, there were 44 patients in the SBRT group and 88 patients in the TACE group. No statistically different parameters existed between the two groups. The 1, 2‐year IFFS rates were 66.0%, 53.5% in the SBRT group and 40.4%, 20.1% in the TACE groups (p = 0.001). The 1, 2‐year OS rates were 76.6%, 73.2% in the SBRT and 52.9%, 24.5% in the TACE groups (p < 0.001, fig. 1). In multivariate analysis, tumor size (hazard ratio [HR] = 1.24, p = 0.013), SBRT vs TACE (HR = 0.32, p < 0.001), ECOG (HR = 2.93, p = 0.006), Child B vs A (HR = 2.16, p = 0.010), and recurrence vs new diagnosis (HR = 1.67, p = 0.026) were associated with OS. Conclusions: For 3‐8 cm HCC, SBRT generates superior IFFS and OS when compared with TACE. Further prospective randomized trials to compare SBRT with TACE were warranted.
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Perceived impairment depends on the number of actions taken (or not) under alcohol
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Perceived impairment drives decision‐making under alcohol. Individuals who feel less impaired by alcoholmay be less cautious and thus engage in risky behaviors including driving. Consumption of alcohol also leads to the impairment of the ability to suppress inappropriate responses. However, alcohol‐induced disinhibition does not occur in all contexts in the real world. Therefore, the purpose of this study was to examine if actions taken (or not) under alcohol will impact observed inhibitory control and how behavioral control requirements under alcohol alter perceived levels of impairment. Participants (n = 40) of equal gender who were social drinkers participated in a 3 session laboratory study which involved the administration of placebo, 0.45 g/kg, and 0.65 g/kg doses of alcohol. Participants were randomly assigned to a modified cued go/no‐go reaction time task that includedmore go trials (activational condition) ormore no‐go trials (inhibitory condition). On all sessions after dose administration, participants completed their assigned cued go/no‐go computer task and gave subjective ratings of impairment. The results indicated that participants in the activational condition under all doses of alcohol, but particularly the highest dose of alcohol displayed poorer behavioral control (i.e., greater inhibitory failures) but self‐reported lower perceived impairment, when compared to participants in the inhibitory condition. Therefore, this study provides laboratory evidence that alcohol consumption in an active setting will lead to greater disinhibition and reduced perceptions of impairment of behavior. The findings highlight that perceived impairment varies with drinking settings and the results suggest potential avenues for harm reduction for individuals who are difficulty controlling their alcohol intake.
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Cetuximab in the first-line treatment of ras wild-type metastatic colorectal cancer with liver-limited disease
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Objectives: To evaluate the efficacy, safety and cost‐effectiveness of cetuximab for first‐line treatment of patients with wild‐type RAS metastatic colorectal cancer (MCRC) with liver‐limited disease. Methods: A Markov model was developed for RASwt mCRC patients and EGFR expression with liver‐limited disease who started treatment with cetuximab + chemotherapy or chemotherapy alone. The transition probabilities were populated according to the OS and PFS curves of a phase II head‐to‐head randomized controlled trial. The present study was conducted from a Brazilian public health system perspective and direct medical costs were obtained through micro‐costing and expert opinion. Incremental cost‐effectiveness ratio (ICER) was reported as R$ (BRL) per life year (LY) and budget impact analysis were conducted to assists the decision. One‐way sensitivity analysis was also conducted. A 20‐year time horizon was used. Future costs and health benefits were discounted at 5%. Results: The comparison results showed that the association of cetuximab + chemotherapy presented higher cost and greater effectiveness. ICER resulted in R$56,750 per life year gained (LYG). The budget impact analysis projects additional costs around R$ 41 million in the first year after the incorporation and R$ 326 million accumulated in 5 years. Results were sensitive to changes in percentage of patients undergoing curative resection, mean body surface area, outcomes discount rates, tested patients rates and market share. ConClusions: The addition of cetuximab to the standard chemotherapeutic treatment of RASwt mCRC patients with liver‐limited disease resulted in improved response rate and may increase the resectability rate of liver metastasis in this population. It's worth mentioning that this treatment is cost‐effective as the ICER (R$56,750/LYG) of the association of cetuximab and chemotherapy compared to chemotherapy alone results in acceptable levels that justify the higher costs due to significant clinical gains.
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Addressing the challenges in conducting international european multicenter trials in rare diseases: time for action?
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Purpose: International multicenter randomized controlled trials provide the highest quality evidence for safety and effectiveness assessments and have the theoretical advantage of permitting enrolment of many patients within a relatively short period. Methods: Epileptic encephalopathy with electrical status epilepticus in sleep (ESES), is a relatively rare childhood epilepsy syndrome which can lead to serious consequences in terms of poor cognitive outcome if untreated. Evidence on the most effective treatment in ESES is lacking and an institutional trial was designed to reflect existing medical practices. The international European multicenter randomized controlled trial of Steroids versus Clobazam Usage for Encephalopathy with ESES (RESCUE ESES) aims to compare the effects of treatment with corticosteroids and clobazam, for a period of 6 months, in 130 children with ESES aged 2‐12 years. Results: To ensure optimal trial conduct and coordination, several bureaucratic challenges had to be addressed. Trial initiation was delayed at many sites by the need to address heterogeneous procedures and requests by ethical committees and competent authorities working under different regulations, technical and cultural conditions. Although in clinical care all study drugs are readily available, the same drugs were not consistently for use in the trial and had to be imported by many study sites. Complying with regulatory requirements to import commercially available formulations from one EU country to another proved to be practically unfeasible in some instances. Approval of the study protocol and documents, and especially approval of the clinical trial agreements between the sponsor and the participating centers, was very time consuming. We strongly feel that simplification of regulations to conduct European non‐profit investigator‐driven trials is needed to encourage much needed comparative effectiveness research. Conclusion: The lessons learned in this trial are of considerable importance to all centers taking part in international multicenter studies.
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Superiority of the Split-dose PEG Regimen for Small-Bowel Capsule Endoscopy A Randomized Controlled Trial
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Goals: We aimed to evaluate the small‐bowel cleansing quality, the diagnostic yield (DY), the transit time, and the patients' tolerability, by comparing the 2 different polyethylene glycol (PEG) administration schedules. Background: The use of bowel purgatives before small‐bowel capsule endoscopy (SBCE) is recommended by the ESGE guidelines. Whether this regimen can be further refined by changing the timing of administration is unknown. Study: Fifty‐seven patients were prospectively enrolled and randomized into 2 groups: group 1 (G1, n=29) received 2 L of PEG in the day before SBCE (time between PEG and SBCE= 10 h); and group 2 (G2, n=28) received 1L of PEG in the day before SBCE and 1 L of PEG in the morning before SBCE (time between PEG and SBCE=4 h). The primary outcome measure was small‐bowel cleansing quality. Small‐bowel cleansing quality was evaluated according to a previously validated grading scale. Results: The entire and distal half small‐bowel cleansing scores were significantly higher among G2 (median score: 8 vs. 10 points, P=0.012; median score: 6 vs. 8 points, P=0.05, respectively). The DY did not differ significantly between groups. There were no significant differences in transit times between the 2 PEG regimens. Both schedules were well tolerated, showing no differences regarding symptoms while ingesting the preparation or after SBCE ingestion. Conclusions: Split‐dose PEG regimen for SBCE preparation improved the small‐bowel cleanliness, did not interfere with transit times and was equally well tolerated by the patients. No differenceswere observed regarding DY. ClinicalTrial.gov registration: NCT02396017.
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Mass drug administration strategies to control scabies in a highly endemic population
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Recently added to the World Health Organization list of neglected tropical diseases, scabies is an under‐recognised case of morbidity in many developing countries, due to secondary bacterial infection of the skin leading to septicaemia, kidney disease and potentially rheumatic heart disease. Countries of the Pacific region have a particularly high burden of scabies and its complications. Control of scabies based on treatment of individual cases is difficult due to frequent re‐infestation. We implemented a large‐scale intervention trial of Mass Drug Administration (MDA) for endemic scabies to ascertain the efficacy and safety of two alternative regimens (topical permethrin and oral ivermectin MDA) compared with current standard care. We identified 3 isolated island communities to which we randomly assigned one of the 3 treatment regimens. The study enrolled 2051 people: 803 participants in the standard care arm, 716 in the ivermectin arm and 532 in the permethrin arm. In each site, the proportion of the total island population enrolled was >85%. At baseline, scabies prevalence was found to be high in all arms, with the highest prevalence in the permethrin arm (41.7%) followed by 36.6% in the standard care arm and 32.1% in the ivermectin arm. A year after the intervention we observed a considerably greater reduction in scabies prevalence in the ivermectin arm with a prevalence of 1.9% corresponding to a relative risk reduction (RRR) of 94% (95% CI 83‐100). The prevalence of scabies was reduced in the 2 other arms, however with lower effect size: permethrin RRR 62% (95% CI 49‐75) and standard care RRR 49% (95% CI 37‐60). The prevalence of impetigo was also high at baseline, ranging from 20% to 24%. The effect of the intervention followed a similar trend to that of scabies, with greatest reduction in the ivermectin arm (RRR 67%, 95% CI 52‐83) compared to the permethrin arm (RRR 54%, 95% CI 35‐73) and the standard care arm (RRR 32%, 95% CI 14‐ 50). These results show that ivermectin MDA is a highly effective strategy for reducing community scabies prevalence and demonstrate the potential role of MDA in addressing a serious cause of illness in many developing countries.
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Effect of accurate heart outlining on radiation dose to the heart - the CONVERT Trial experience
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Purpose/Objective: RTOG 0617 has demonstrated that the percentage of heart receiving between 5 and 30 Gy is correlated with survival.This study investigated the accuracy of cardiac outlining carried out by individual clinicians and the subsequent effect on recorded cardiac dose. Materials and Methods: The CONVERT Trial is a multicentre phase III study which recruited 547 patients with limitedstage SCLC. Patients were randomised to receive once daily (66Gy in 33 fractions) or twice daily (45Gy in 30 fractions) radiotherapy concurrently with chemotherapy. The trial protocol specified that the heart and pericardial sac should be contoured. Outlining extended superiorly to the inferior aspect of the aortic arch and inferiorly to the apex of the heart. An atlas was provided which included heart contours. Each clinician completed a planning exercise which assessed patient selection, disease and organs at risk outlining, margin expansion and treatment plan. Centres were asked to anonymise and transfer data to the Mount Vernon Quality Assurance (QA) team which was reviewed using VODCA (Visualisation and Organisation of Data for Cancer Analysis), version 3.2.7. In this study, heart outline volumes provided by participating centres were compared to the gold standard heart volumes (in cm3) drawn according to the trial protocol for 28 patients. Results: one of the 28 cases delineated the heart according to protocol. The most common outlining discrepancy was that the cardiac outline was not countoured superiorly enough to the inferior aspect of the aortic arch (96.4% of cases). The average difference in volume between that provided by the centre and the gold standard was 85.1cm3 (range 5.6cm3 to 248.2cm3). In 100% of cases the heart was not outlined according to protocol and in 89.3% of cases the cardiac dose was underestimated (by 29.1%) as a result of deviation of the heart outline from the protocol. An increase in calculated cardiac dose was reported in 85.7% of cases in the experimental dose arm (range 0.98%‐90.5%) and in 92.9% of cases in the control arm (range 0.6%‐90.4%). Conclusions: In this study we have shown that in every case reviewed the heart was not delineated according to protocol. As a result the mean heart dose was underestimated by an average of 29.1%. In conclusion, this study highlights the importance of collecting radiotherapy plans to check heart coutours as part of a QA programme and to feed back deviations to investigators.
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Comparison of childhood size and dietary differences at age 4 years between three European countries
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Background/Objectives: Obesity in childhood is very common in Europe. It may be linked to diet, and intakes of protein and polyunsaturated fatty acids (PUFA) have been investigated. The study aims to investigate child size and dietary differences at the age of 4 years between three European countries and to assess dietary adequacy. Subjects/Methods: A total of 161 4‐year‐old children from Spain, Germany and Hungary, whose mothers participated in a pregnancy micronutrient supplementation trial, were included in this analysis. Child size was assessed by standardised anthropometry and diet calculated from parent‐completed food frequency questionnaires. Adequacy of the diet was evaluated using US guidelines. Results: The Spanish children had a higher mean body mass index (BMI) (16.4 + 1.5) compared with German (15.7 + 1.0) and Hungarian children (14.9 + 1.4, P < 0.01). In Spanish children, dietary intakes were higher in animal protein density, particularly from dairy foods, were little different in total protein density and slightly lower in n‐6 PUFA density compared with the intakes in the other groups. Dietary intakes of most children (% contribution to energy) were higher than those recommended for protein, saturated fat and added sugar. Conclusions: Spanish children had a higher mean BMI compared with German and Hungarian children. Diets taken by Spanish children may be more obesogenic than those taken by German or Hungarian children. In the present study, many children in all three countries were consuming diets that were high in protein, saturated fat and sugar. 2014 Macmillan Publishers Limited.
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Respiratory muscle trainings as a way of physical rehabilitation for old patients with complicated myocardial infarction
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Background: Physical exercises are well known to be an important part of comprehensive cardiac rehabilitation (CR), but many protocols of physical exercises are not applicable for the old patients for many reasons. Purpose: To study the possibility of respiratory muscles trainings (RMT) in old patients with myocardial infarction (MI) and heart failure (HF) as away of physical rehabilitation. Methods: 63 patients 84,3±5,2 years old with MI and NYHA II‐III HF were randomized to either an exercise training group (EG) (32pts) or to a control group (CG). The CG patients had standard CR according to the national guidelines The EG participated additionally in a RMT with gradual increase of inspire and expire resistance. At hospital stage, 10 to 12 trainings were held for 20 minutes twice a day with following trainings at home by themselves for 12 months. Peak oxygen consumption (VO2peak) during 6 minute walking test (6 MWT), maximal inspiratory mouth pressures (PI max) and heath related quality of life by SF‐36 were measured at baseline and in 12 months. Results: After 12 weeks there was significant increase in results of 6 MWT in EG (167,6±9,37 m in EG vs 168,2±9,12 m in CG at baseline, p>0,05; after 12 months 185±8,76m vs 179,3±8,85 m p<0,01), VO2peak in EG (5,96±1,84ml/kg/min in EG vs 5,99±1,91 ml/kg/min in CG at baseline, p>0,05; after 12 months 8,18±1,46 ml/kg/min vs 6,35±1,11 ml/kg/min, p<0,01) and PI‐max in EG (median PI max, 6,2 in both groups [25th‐75th percentile range 6,4‐6.8 in EG vs 25th‐75th percentile range 6,2‐6,8 in CG] at baseline, p=0,7), after 12 months EG median PI max, 6,9 in EG [25th‐75th percentile range6,8‐7,1] vs median PI max, 6,6 [25th‐75th percentile range 6,3‐6,3] in CG, p<0,01). Health‐related quality of life increased in both groups, but in EG patients' results in physical functioning, bodily pain, vitality, role emotional scales were significantly higher EG patients had significantly less hospitalizations because of HF progression (10,9% in EG vs 17,5% in CG) and pneumonias (14,1% vs 19.3%). There were 4 lethal outcomes in EG vs 7 in CG. Conclusion: RMT in old patients with MI and HF improves physical capacity maximal inspiratory mouth pressures, health‐related quality of life and decrease the number of hospitalizations because of HF progression and pneumonias during the first year after MI.
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HEMANGIOL STUDY: the first worldwide dose-effect study concerning propranolol in infantile hemangiomas
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Since 2008 propranolol has been used as first line treatment in infantile hemangiomas (IH). However, there is a need of large clinical trials because several problems remain unsolved: to demonstrate a dose and a duration effect by studying different dosages and different durations of treatment, to demonstrate statistically the efficacy of propranolol against placebo, to evaluate the safety by comparing the side effects between different arms, to determine the best monitoring procedure at initiation and during the course of the treatment, and to obtain an official worldwide approved treatment for the safety of patients and doctors by a protective legal framework (Marketing Authorization) in IH indication. For the first time in the field of IH, the EMA (European Medicines Agency) and FDA (US Food and Drug Administration) have together validated an original protocol of a phase 2/3 study enrolling 460 infants ‐ the HEMANGIOL study (NCT 01056341) ‐ involving 65 centers in the world. Patients are randomized to 5 arms: placebo, propranolol 1 mg/kg/day for 3 or 6 months, propranolol 3 mg/kg/day for 3 to 6 months. The principal criterion is based on photographic centralized assessment of complete or nearly complete resolution of IH at week 24. Close monitoring of various parameters is done, especially glycemia, blood pressure, heart rate and wheezing. The objective of this communication is to present the details of this protocol and what we will learn from this study.
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Efficacy of probiotics in irritable bowel syndrome: a meta-analysis of randomized, controlled trials
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PURPOSE: This study was designed to evaluate whether probiotics improve symptoms in patients with irritable bowel syndrome.METHODS: PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for studies that investigated the efficacy of probiotics in the management of irritable bowel syndrome. Clinical improvement was the key outcome of interest. Data were searched within the time period of 1966 through September 2007.RESULTS: Eight randomized, placebo‐controlled, clinical trials met our criteria and were included in the analysis. Pooling of eight trials for the outcome of clinical improvement yielded a significant relative risk of 1.22 (95 percent confidence interval, 1.07‐1.4; P = 0.0042).CONCLUSIONS: Probiotics may improve symptoms of irritable bowel syndrome and can be used as supplement to standard therapy.
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Effect of Cryotherapy Intervention on Pain among Hemodialysis Elderly Patients
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Background:Pain associated with arteriovenous (AV) fistula needle insertion is considered a major challenge for more than 57% of patients treated with hemodialysis. Further, pain is considered one of the leading causes of hemodialysis noncompliance to a therapeutic regimen. The aim of this study was to evaluate the effect of cryotherapy intervention on pain during arteriovenous fistula puncture among elderly patients undergoing hemodialysis. Research design: A quasi‐experimental pretest‐and‐posttest design was utilized. Setting: The study was conducted at the hemodialysis unit at the internal medicine department of Zagazig University Hospital and the hemodialysis unit at Al Ahrar hospital affiliated to the Ministry of Health. Subject: This study included 60 elderly patients. Tools: Two tools were used. Tool I: Structured Interview Questionnaire which consisted of part 1; demographic characteristics and part 2; Knowledge questionnaire regarding cryotherapy intervention among elderly patients undergoing hemodialysis. Tool II: Numerical Rating Pain scale. Results: There is a statistically significant difference in total mean knowledge score & total mean pain score among studied elderly patients pre and post‐intervention (P<0.001) Regarding pain, the total mean score of pain was 6.75+1.48 and decreased to 4.68+1.42 in the post‐intervention phase Conclusion: Post the cryotherapy intervention, the knowledge was improved and pain was decreased among the studied elderly patients. Recommendation: It is recommended to replicate this study using a randomized clinical trial design in order to confirm the findings and to provide a higher level of evidence of its findings. Hemodialysis units must involve cryotherapy intervention for managing needle puncture pain in the routine care for hemodialysis patients.
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Nursing effect of Nasoscopically assisted nasogastri tube and nasojejunal tube placement
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Objective: To investigate the nursing effect of nasoscopically assisted nasogastri tube and nasojejunal tube placement. Methods: 94 patients who need to place nasogastric tube and nasojejunal tube to establish enteral nutrition were randomly divided into two groups: the observation group (n=49) and control group (n=45). The patients in the observation group received nasogastric tube placement and jejunal nutrition tube placement, and the patients in the control group received general gastroscope and placed gastric tube and jejunal nutrition tube through mouth. Success rate of catheterization, catheter pain score, satisfaction score, vital signs, completion time of catheterization, and complication were collected. Results: the fluctuation of vital signs in control group was significantly higher than that in observation group. There was statistical significance between two groups in vital signs after intervention (P<0.05), mainly manifested in the heart rate, breathing and pulse pressure difference. On the other hand, there was no statistical significance between two groups in pulse oxygen after nursing intervention (P>0.05). The catheter pain score is obviously improved in the observation group compared with control group after intervention. The improvement score of satisfaction in the observation group was 91.47±7.65 points, and that in the control group was 83.64±5.24 points. The completion time of catheterization was improved in the observation group compared with control group. There was statistical significance between two groups in satisfaction score and completion time of catheterization (P<0.05). The rate of abdominal distention and diarrhea in the control group was higher than that in the observation group (P<0.05). Conclusion: Nasoscopically assisted nasogastri tube and nasojejunal tube placement has the advantages of simple and fast, short operation time, high success rate and few complications. It is the first choice of intubation method for enteral nutrition support treatment.
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Study of effect of add on L-Arginine therapy on working capacity and Fatigability in hypertensive patients in tertiary care center of rural hospital
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Background: Hypertension is the third most important risk factor for attributable burden of disease. The aim of present study was to examine the effects of oral L‐arginine supplementation on working capacity and fatigability as add on to standard antihypertensive therapy as L‐arginine may increase blood flow to myocardium and skeletal muscle Materials & Methods: This was a Randomized, open labeled clinical trial conducted in all patients with hypertension visiting the Medicine Out‐Patient Department (OPD) of Pravara Rural Hospital, Loni. 149 hypertensive patients were enrolled in study after satisfying inclusion and exclusion criteria and randomized in Intervention Group (n=74) and Control Group (n=75). The participants in the Intervention group received antihypertensive therapy along with add on L arginine oral supplementation for 14 days. The participants in the Control group received only standard antihypertensive therapy and had followed up similar to that of the participants of Intervention group. The questionnaire was prepared to observe the effect of L‐arginine on working capacity and Fatigability and responses of participants from both groups were recorded in pre‐structured proforma Results: In our study we found that add on L‐arginine supplementation at a dose of 3g/d (L‐arginine 5gm sachet) for 2 weeks in patients of hypertension resulted significant improvement in working capacity and significant reduction in fatigability in intervention group on first, second and third follow‐up visits compared to control group. Conclusion: L‐Arginine supplementation may be considered for short period as add on with standard antihypertensive therapy in patients of hypertension.
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Detecting bacterial sepsis among allogeneic hct recipients with population-specific bedside tools
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Background: Diagnosing sepsis among allogeneic hematopoietic cell transplant (aHCT) recipients remains challenging. Existing criteria, for use in hospitalized patients, have limited predictive accuracy among aHCT recipients and their use may lead to missed events or antibiotic overuse. We developed bedside bacterial sepsis prediction tools (criteria and decision tree [DT]) for aHCT recipients and compared them against Systemic Inflammatory Response Syndrome (SIRS), quick Sequential Organ Failure Assessment (qSOFA) and National Early Warning Score (NEWS) criteria. Methods: Adult aHCT recipients transplanted between September 2010‐2019 with ≥ 1 potential infection (PI) within 100 days post‐transplantation were randomly assigned to model/validation (7/3) cohorts. Tools included demographic and clinical factors and were built against a bacterial sepsis endpoint (gram‐negative, Staphylococcus aureus, or Streptococcus species bacteremia). The tools were developed using best subset selection with rare event logistic regression (criteria) and classification tree (DT) algorithms. Criteria scores were estimated using a beta/10 integer weighting approach and tool predictive performances were compared against existing criteria. Results: Between September 2010‐2019, 1571 recipients with ≥ 1 PI contributed 7755 PIs and 238 sepsis events. The DT model included 7 terminal nodes based on 3 predictors: temperature, respiratory rate (RR), and sex. The criteria model contained 10 categories with 4 predictors: RR, temperature, pulse, and diastolic blood pressure (Figure 1). Our criteria and DT had AUCs of 71.1% (95% Confidence Interval (CI): 64.3, 77.9%) and 70.0% (CI: 63.7, 76.2%). SIRS had the highest AUC of existing criteria ‐ 64.7% (CI: 57.1, 71.9%). Our criteria had the highest net benefit (for probabilities < 10%) and, at a 7+ cut‐point, had a sensitivity of 73.8% (CI: 61.5‐84.0%) and specificity of 55.0% (CI: 52.9, 57.1%) (Figure 2). Conclusion: We developed aHCT recipient‐specific bedside bacterial sepsis prediction tools with higher AUCs than existing criteria. Tools targeted to high‐risk populations may lead to fewer missed sepsis events and, in turn, reduce sepsis related mortality among this high‐risk population. (Figure Presented).
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Effects of risedronate versus menopausal hormone therapy on bone mineral density in postmenopausal Korean women with hip fracture: a randomized, open-label trial
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Objective: Both bisphosphonates and menopausal hormone therapy (MHT)are indicated for osteoporosis. The purpose of this study is to compare the effects of risedronate (RISE)and MHT on bone mineral density (BMD)after hip fracture surgery in postmenopausal Korean women. Subjects and Methods: A total of 223 participants were randomly received RISE 35 mg weekly (n = 114)or percutaneous 17β‐estradiol gel (0.1%, 1.5 gm/day)plus oral micronized progesterone (100 mg/day)daily (n = 109)with calcium supplement for four years. Activity of daily living (ADL)was evaluated by Kyo's classification modified by Park. BMD was measured using dual‐energy X‐ray absorptiometry every year and serum levels of N‐telopeptide of type I collagen (NTx)was examined every six months. Data are expressed with mean ± SD. Time trends and group differences at each time point were analyzed using a Generalized Estimating Equation. Results: At baseline, there were significant differences in body mass index (BMI, Kg/m2; 23.2 ± 3.7 versus 22.1 ± 3.6)and activity of daily living (ADL)between the RISE and MHT groups and the drop‐out rates were 53.5% and 67.0%, respectively. Within‐group analysis revealed that BMD at lumbar spine showed a significant time trend of increase in both groups with significant increase from one year of treatment on. Mean increase at four years was 10.53% in the RISE group and 7.49% in the MHT group. After adjustment for baseline BMI and ADL, between‐group analysis demonstrated no differences at each time point and in time trend between the two groups. In contrast, BMD at total hip showed no significant change in the two groups. NTx decreased significantly after six months of treatment on in both RISE and MHT groups, but no difference was found between two groups. Conclusions: The effects on BMD and bone resorption marker are comparable between RISE and MHT after hip fracture surgery in postmenopausal women.
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Early response evaluation in radiation therapy driven larynx organ preservation
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Long‐term laryngectomy‐free (LFS), tumour‐specific (TSS) and overall survival (OS) is achieved by non‐surgical larynx preservation (LP) only in a proportion of patients with locally advanced laryngeal or hypopharyngeal cancer. A score facilitating decision‐making after 1 cycle induction chemotherapy (IC‐1) may improve LFS and TSS. The German multicenter randomized phase II larynx organ preservation (LOP) trial DeLOS‐II was carried out to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy‐free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC). The DeLOS‐II trial met its primary objective of 24 months LFS >35% in arm B. Cetuximab given concomitantly over 16 weeks during IC þ RT achieved 24 months LFS in 41 patients (46.6%, 80% CI 39.8% to 53.4%), whereas 40 patients in A had 24 month laryngectomy free survival (47.1%, 80% CI 40.1% to 54.0%) and demonstrated similarly improved outcome (p=0.925 for A versus B). Early response to IC‐1 with TPF ± cetuximab was assessed in 52 patients as subgroup of the DeLOS‐II‐trial using endoscopic tumour staging for selecting total laryngectomy for non‐responders with endoscopic tumour surface shrinkage <30% versus induction chemotherapy plus radiotherapy (IC + RT) for responders. Computed tomography (CT)‐based volumetry was used to assess volumes of primary tumour, neck nodes and their sum; maximum and mean standardised uptake value (SUVmax, SUVmean) were measured by 18F‐FDG‐PET/CT. Baseline and residual values after IC‐1 were calculated and correlated with LFS, TSS and OS. After IC‐1, 39/52 patients (75%) were early responders. Early response predicted complete response to IC + RT (p = 8.48 × 10‐9). Early laryngectomised non‐responders and responders with endoscopic tumour surface shrinkage > 70% had best OS. Significant independent predictors for LFS in responders are number of CT‐staged suspect positive neck nodes (N+), residual primary tumour volume, residual total tumour volume and the ratio of residual SUVmax and SUVmean (resSUVmax/resSUVmean). Our LFS‐score combines >2N+, residual primary tumour volume > 20%, residual total tumour volume > 5.6 mL and resSUVmax/resSUVmean > 1.51 weighted by their hazard ratio (12, 6, 5 and 4); LFS‐score ≤ 16 predicts increased LFS, OS and TSS (p < 0.05). LFS‐score ≤ 16 identifies in responders to IC‐1 the patients with maximum benefit of non‐surgical LP achieving long‐term LFS. Even more importantly, a LFS‐score > 16 defines patients unsuitable for LP applying the TPF/TP IC + RT protocol. List: Dietz A, G Wichmann, T Kuhnt, L. Pfreundner, R Hagen, M Scheich, O Kölbl, M G Hautmann, J Strutz, F Schreiber, U Bockmühl, V Schilling, P Feyer, M deWit, G Maschmeyer, M Jungehülsing, U Schroeder, B Wollenberg, C Sittel, M Münter, T Lenarz, J P Klussmann, O Guntinas‐Lichius, C Rudack, H T Eich, T Foerg, S Preyer, M Westhofen, H J Welkoborsky, D Esser, D Thurnher, S Remmert, H Sudhoff, M Görner, J Bünzel, V Budach, S Held, M Knödler, F Lordick, S Wiegand, K Vogel, A Boehm, M Flentje & U Keilholz, German Larynx Organ Preservation Study Group; DeLOS: Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy–final results of the larynx organ preservation trial DeLOS‐II; Annals of Oncology 0: 1‐10, 2018; Published online 23 August 2018 Wichmann G, Krüger A, Boehm A, Kolb M, Hofer M, Fischer M, Müller S, Purz S, Stumpp P, Sabri O, Dietz A, Kluge R. Induction chemotherapy followed by radiotherapy for larynx preservation in advanced laryngeal and hypopharyngeal cancer: Outcome prediction after one cycle induction chemotherapy by a score based on clinical evaluation, computed tomography‐based volumetry and 18F‐FDG‐PET/CT. Eur J Cancer. 2017 Feb;72:144‐155.
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Ras antagonists correct hyperfiltration in DKD stage 1
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INTRODUCTION AND AIMS: An ACE inhibitor or an angiotensin receptor blocker is not recommended for the primary prevention of diabetic kidney disease (DKD) in patients with diabetes who have normal blood pressure, normal urinary albumin‐tocreatinine ratio (<30 mg/g), and normal estimated glomerular filtration rate. Stage 1 DKD is characterized by hyperfiltration with elevated GFR. Aim: estimate the possibility of RAS antagonists to prevent progression to stage 2 DKD in patients with hyperfiltration in DKD 1 stage. METHODS: 62 patients with DKD 1 stage and hyperfiltration were enrolled in 22 months randomized prospective open‐label study in parallel groups: 31 for treatment with RAS antagonists either ACEI or ARB once a day at bedtime minimal dosage and 31‐control group. Inclusion criteria: normal ambulatory BP and urine albumin‐creatinine ratio. GFR by clearance probe or renoscintigraphy with 99mTc‐DTPA is above 120 ml/min/m2. RAS antagonists were titrated for 2 following months to target blood pressure 115‐125mmHg. Progression to stage 2 DKD were documented either by elevated BP above 140mmHg or urinary ACR>30 mg/g. RESULTS: 59 (30+29) patients ended the trial. In 12 months treatment with RAS antagonists progression to stage 2 DKD were observed in 6 patients while 15 in control group (P<0.05, Fisher criteria 0.009, v2=3,36 ≥=0.6). GFR decreased from 12863 ml/min/m2 to 11664 ml/min/m2 (P>0.05) with RAS antagonists treatment and from 12763 ml/min/m2 to 10466 ml/min/m2 in control group (P<0.05) CONCLUSIONS: RAS antagonists might normalize hyperfiltration and prevent progression DKD stage 1 to stage 2.
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Consumption of galacto-oligosaccharides increases iron absorption from a micronutrient powder containing ferrous fumarate and sodium iron EDTA: a stable-isotope study in Kenyan infants
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Background: Whether consumption of prebiotics increases iron absorption in infants is unclear. Objective: We set out to determine whether prebiotic consumption affects iron absorption from a micronutrient powder (MNP) containing a mixture of ferrous fumarate and sodium iron EDTA (FeFum+ NaFeEDTA) in Kenyan infants. Design: Infants (n = 50; aged 6‐14 mo) consumed maize porridge that was fortified with an MNP containing FeFum+NaFeEDTA and 7.5 g galacto‐oligosaccharides (GOSs) (Fe+GOS group, n = 22) or the same MNP without GOSs (Fe group, n = 28) each day for 3 wk. Then, on 2 consecutive days, we fed all infants isotopically labeled maize porridge and MNP test meals containing 5 mg Fe as <sup>57</sup>FeFum+Na<sup>58</sup> FeEDTA or ferrous sulfate (<sup>54</sup>FeSO<inf>4</inf>). Iron absorption was measured as the erythrocyte incorporation of stable isotopes. Iron markers, fecal pH, and bacterial groups were assessed at baseline and 3 wk. Comparisons within and between groups were done with the use of mixed‐effects models. Results: There was a significant group‐by‐compound interaction on iron absorption (P = 0.011). The median percentages of fractional iron absorption from FeFum+NaFeEDTA and from FeSO<inf>4</inf> in the Fe group were 11.6% (IQR: 6.9‐19.9%) and 20.3% (IQR: 14.2‐25.7%), respectively, (P, 0.001) and, in the Fe+GOS group, were 18.8% (IQR: 8.3‐37.5%) and 25.5% (IQR: 15.1‐37.8%), respectively (P = 0.124). Between groups, iron absorption was greater from the FeFum+NaFeEDTA (P = 0.047) in the Fe+GOS group but not from the FeSO<inf>4</inf> (P = 0.653). The relative iron bioavailability from FeFum+NaFeEDTA compared with FeSO<inf>4</inf> was higher in the Fe+GOS group than in the Fe group (88% compared with 63%; P = 0.006). There was a significant time‐by‐group interaction on Bifidobacterium spp. (P = 0.008) and Lactobacillus/Pediococcus/Leuconostoc spp. (P = 0.018); Lactobacillus/Pediococcus/Leuconostoc spp. decreased in the Fe group (P = 0.013), and there was a nonsignificant trend toward higher Bifidobacterium spp. in the Fe+GOS group (P = 0.099). At 3 wk, iron absorption was negatively correlated with fecal pH (P, 0.001) and positively correlated with Lactobacillus/Pediococcus/ Leuconostoc spp. (P = 0.001). Conclusion: GOS consumption by infants increased iron absorption by 62% from an MNP containing FeFum+NaFeEDTA, thereby possibly reflecting greater colonic iron absorption. This trial was registered at clinicaltrials.gov as NCT02666417. Copyright © 2017 American Society for Nutrition.
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Comparison of antiarrhythmic drugs clinical effect during early post procedural period after atrial fibrillation ablation
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Background: Catheter pulmonary veins isolation (PVI) is one of the recommended standard treatment options for paroxysmal atrial fibrillation refractory to medical management. However, due to acute inflammatory changes, the early post‐procedural period is commonly complicated by atrial tachycardia recurrences. Early recurrence significance in predicting late recurrences, as well as the choice of antiarrhythmic drugs and it's effect in the early post‐procedural period, are still under debate. Purpose: Our aim was to compare clinical effects of AAD during the early postprocedural period of atrial fibrillation ablation based on a rate of pharmacological cardioversions (PC) and electrical cardioversions (EC). Methods: Our prospective open, randomized study included 243 patients who underwent PVI ablation. 142 (58%) were males, mean age (56.09±10.14 years) with an average time since diagnosis 4.48±2.6 years. For detection of atrial tachycardias, we used EKG, Holter monitor, symptoms diary and 112 patients (pts) had an implantable loop recorder for constant monitoring. All pts were subdivided into 4 groups: 61 pts were started on Verapamil, 62 pts ‐ propafenone, 60 pts ‐ sotalol and 60 pts were monitored without any AAD (control group). All pts were followed for 12 months. Results: In the first 3 moths after ablation in all groups there were 11.52±10.91 pharmacological cardioversions and 0.839±1.44 electrical cardioversions. When compared between the groups of AAD there was found to be a significant decrease in the number of PC in Propafenone group compared with Verapamil group (8.92±9.37 vs 13.24±10.77, p=0.013); and there was a trend in reduction of PC in Propafenone group compared with Sotalol group (8.92±9.37 vs 11.62±12.02, p=0.123). Propafenone group was associated with significant reduction of EC compared with Verapamil group (0.40±1.03 vs 1.016±1.74, p=0.024) as well as there was a significant reduction in EC in Propafenone group compared with Sotalol group (0.40±1.03 vs 1.033±1.52, p=0,0096). Comparison of EC and MC in the each AAD group with the control group is shown in the Figure below. Conclusions: In the early postprocedural period in between the group analysis Propafenone was shown to be associated with significant reduction in EC comparing with both Verapamil and Sotalol and a significant reduction in PC comparing with Verapamil as well as a trend in reduction in PC comparing with Sotalol. When compared with control group, Propafenone was associated with significant reduction in EC but no significant difference in PC. (Figure Presented).
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The Effect of Dietary Fibre Source on Satiety and Bowel Function
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Research suggests that a diet rich in fibre is strongly correlated with improvement in bowel functioning and satiety induction(1). Despite the considerable variety of fibre‐rich foods available, it is alarming that a significant number of individuals' intake is considerably lower than the recommended level recently advised by SACN (30 g/day)(2). However, as dietary fibre comes from various sources with somewhat varying chemical composition, this study aimed to investigate the effect of fibre source by examining three types, namely, psyllium husk, flaxseed, and chia seeds in equal amounts on bowel function and satiety. Within a pre‐post repeated measure design, 18 participants were randomly assigned into three groups. Each group was provided with a different fibre source for consumption (5 g of fibre) in its natural form; daily for seven consecutive days. All participants were required to complete an evaluation questionnaire for two weeks where satiety index and parameters of bowel functioning were assessed. Parameters of bowel functions were weekly bowel movement, Bristol stool scale score, and bowel function index (taking into account; ease of defecation, bowel evacuation and perceived constipation)(3). During week 1, participants were asked to maintain their normal diet (baseline) and during week 2, participants were asked to consume the provided fibre source with breakfast (treatment). Analysis of Variance for the change to the baseline followed by Tukey test for multiple comparisons was performed using SPSS version 19. A statistically significant difference (P < 0·05) in Bristol stool scale score was found, indicating that psyllium husk was more effective than flaxseed whereas chia seed was not significantly different from psyllium husk. Overall, positive trends suggested that all three fibres led to improvement in bowel function and satiety; however psyllium husk presented the greatest mean change for the majority of parameters measured. (Table Presented) These findings suggest that fibre intake has a positive effect on satiety and bowel function, reinforcing the importance of fibre intake, whilst appreciating that not all fibres work the same on bowel functioning. Additionally, the findings also highlight the rapid effects of fibre on bowel movement (within seven days clinically positive outcomes were experienced by several participants).
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Analysis of the efficacy of oca in primary biliary cirrhosis by varying patient disease severity across three randomized double-blind, placebo-controlled clinical trials
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Background and aim: Obeticholic acid (OCA), a selective and potent farnesoid X receptor (FXR) agonist, produced significant liver biochemistry improvements, including alkaline phosphatase (ALP) and total bilirubin (bili) in 3 randomized, double‐blind (DB) placebo (PBO)‐controlled trials in primary biliary cirrhosis (PBC). This pooled analysis from the 3 trials evaluates efficacy of OCA across a range of disease severity based on baseline (BL) ALP tertile and total bili. (≤ULN/>ULN). Material and methods: Key inclusion criteria: ALP 1.5 to 10x ULN and conjugated bili ≤2x ULN for the two 3 month trials and ALP ≥1.67x ULN or total bili >ULN but <2x ULN for the 12 month trial. Data were pooled based on end of DB treatment (EOT). Treatment arms were PBO (n=134) and ≤OCA 10 mg (n=201). Endpoints were LS mean (SE) change from BL to EOT for ALP and percent of patients achieving a composite endpoint (ALP <1.67 ULN, total bili ≤ULN and ALP decrease ≥15%), shown to be correlated with long‐term survival in PBC. Safety and tolerability by disease severity were also assessed. Results: Significant differences for OCA compared with PBO for both efficacy endpoints were achieved irrespective of PBC disease severity. The magnitude of ALP reduction was proportional to ALP tertile suggesting improved response even in more advanced patients (Figure). The percentage of OCA patients achieving the composite endpoint was inversely proportional to BL tertile (68% low, 54% mid, and 19% upper) and total bili (49%≤ULN, 17%>ULN). Similar results were observed when subgroups were analyzed by OCA monotherapy or OCA plus UDCA. Pruritus was the most common adverse event. The incidence of pruritus for OCA ≤10 mg was similar for the low and mid tertiles and slightly higher in patients with more severe disease. Conclusions: These data demonstrate efficacy of OCA across a range of PBC severity and confirm ALP and total bili both as continuous and categorical variables predictive of clinical outcomes. This integrated analysis demonstrates robust response with OCA irrespective of BL ALP or total bili. Across the ranges of disease severity, OCA was safe and well‐tolerated. These data are clinically relevant given that PBC is a chronic and progressive disease, and demonstrate that even in patients with more advanced disease, OCA improves parameters shown to correlate with improved clinical outcomes and reduced risk. (Figure Presented).
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Evaluation of the effect of tamsulosin and tadalafil in relieving BPH related symptoms: a randomized double blind placebo controlled cross-over study
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Introduction: In BPH, ED and LUTS are correlated and treated with PDEI alone or in combination with an Alfa‐blocker. But current scientific evidence is insufficient to predict patient profile that would respond preferably to either of drugs. This was a randomized double blind placebo controlled cross‐over study evaluating the effect of Tadalafil and Tamsulosin on BPH‐LUTS. Methods‐Men ≥45 years of age, having IPSS ≥8 were included. Patients received a placebo lead‐in period for two weeks, followed by drug A (Tadalafil 10mg OD) or drug B (Tamsulosin0.4mg OD) for six weeks; and then crossed over for another six weeks after a placebo washout of 4 weeks. The randomized sequences were either AB or BA. IPSS scores, uroflow parameters and IIEF score were recorded. Appropriate statistical tests were applied. Results‐36 patients out of 40 completed the study. Demographic and baseline characteristics were comparable. No significant placebo effect observed. The effect of Tadalafil and Tamsulosin were significant on total IPSS score and quality of life (p<0.05). There was no significant difference between the drugs for the extent of effect. Significant period effect was observed (p<0.05) but there was no sequence effect (p>0.05) Half of the non‐responders to either of drugs responded when the drug was changed to other. Tadalafil showed good improvement in EF than Tamsulosin. Conclusion‐Both Tadalafil and Tamsulosin equally improved LUTS with better improvement in ED with Tadalafil. Patients who did not respond to Tadalafil showed improvement with Tamsulosin and vice‐a‐versa.
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The effect of light load resistance exercise and whey protein supplementation on muscle protein synthesis and amino-acid transporters in elderly
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In this study we tested how light load resistance exercise (LL RE) affects skeletal muscle protein synthesis (FSR) and amino‐acid transporter (AAT) protein expression as a way to counteract anabolic resistance and age related loss of muscle mass. Untrained healthy men (age: +65 yrs) were subjected to 13 hours supine rest. After 21/2 hours of rest, unilateral LL RE was conducted: 10 times 36 reps of knee‐extensions at 15% 1RM. Hereafter, the subjects were randomized to oral intake of Placebo (4g maltodextrin/hour) (n=10), Pro‐C (4g whey protein/hour) (n=10) or Pro‐2 (28g whey protein at 0 hours and 12g whey protein at 7 hours post exercise) (n=10). Quadriceps muscle biopsies were taken at 0, 3, 7 and 10 hours post exercise from both resting and exercised leg. Myofibrillar‐FSR and membrane protein expression of select AATs were analyzed from the biopsies. LL RE increased myofibrillar‐FSR compared to the resting leg in all groups. An increase in AAT protein expression was only observed when LL RE was followed by whey protein intake. Specifically, Pro‐C increased LAT1, PAT1 and a tendency towards increased SNAT2 protein expression, Pro‐2 only increased PAT1 protein expression. We conclude that myofibrillar‐FSR increased in response to LL RE, irrespective of feeding in older adults. AAT protein expression only increased when LL RE was combined with whey protein intake.
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IgA nephropathy presenting as a rapidly progressive glomerulonephritis in an elderly woman
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LEARNING OBJECTIVE 1: Recognize the clinical and pathologic features of IgA nephropathy that portend a poorer prognosis and thus require aggressive management CASE: An 81‐year‐old woman presented to an outside provider with 3 months of post‐prandial abdominal pain and bloating. Her symptoms were not relieved with a proton‐pump inhibitor so she underwent upper endoscopy that was reportedly unremarkable. When seen in an outside hospital emergency department for acute worsening of her abdominal pain now associated with increased abdominal girth, the patient had an abdominal CT. This was notable for large volume ascites. The patient denied fevers, chills, cough, diarrhea, dysuria, hematuria and rash. She reported chronic, bilateral knee pain but no new joint pains. She was admitted to the outside hospital for workup of new onset ascites. After several days the patient signed out against medical advice and presented to our hospital for further management. Past medical history was significant for knee osteoarthritis, herpes zoster and bereavement disorder. Home medications were pantoprazole, diazepam and corticosteroid knee injections. There was no family history of autoimmune, renal or hepatic disease. The patient lives at home with her daughter, is independent in activities of daily living and denied tobacco, alcohol or illicit drug use. On physical exam at our hospital, vital signs were notable for a blood pressure of 172/102. She was in no acute distress. Abdomen was distended, firm and mildly tender to palpation diffusely. Legs were massively edematous. Labs were most notable for creatinine that rose from 1.3 mg/dL to 4.5 mg/dL over 12 days. Spot urine protein/creatinine was 9602 mg/g. Ascitic fluid was negative for SBP and malignant cells. ANA 1:640, ANCA negative. HIV, Hepatitis B/C all negative. Renal biopsy showed: proliferative, necrotizing glomerulonephritis, consistent with IgA nephropathy, severe, acute; tubular atrophy and interstitial fibrosis, mild; interstitial edema and inflammation, moderate. Prior to leaving the outside hospital, the patient had received 2 days of pulse‐dose methylprednisolone after her renal biopsy results came back. She received a third dose of methylprednisolone at our hospital and cyclophosphamide on the recommendation of our nephrology consultant. We gave IV loop diuretics for her massive volume overload but the patient required initiation of hemodialysis via a tunneled catheter. Further doses of cyclophosphamide were held due to development of anemia and thrombocytopenia, as well as infectious complications including gram‐negative sepsis. A long, tapering course of prednisone was continued. The patient has not required hemodialysis for approximately 3 months. DISCUSSION: IgA nephropathy is believed to be the most common cause of primary glomerulonephritis worldwide. It occurs most commonly in the second and third decades of life and among males more often than females. The typical presentation is painless, macroscopic hematuria (40‐50 % of patients), frequently temporally associated with an upper respiratory tract infection. Thirty to forty percent of patients present with microscopic hematuria with or without proteinuria. Much less commonly (<10 %), patients present with nephrotic syndrome or acute kidney injury associated with a rapidly progressive glomerulonephritis. Essential to the diagnosis of this condition is renal biopsy and the identification of glomerular IgA deposits on immunofluorescence microscopy. Several clinical features have been associated with a poor prognosis in studies of IgA nephropathy patients. These include sustained hypertension, persistent proteinuria >1 g/day, impaired renal function at time of diagnosis, and nephrotic syndrome. The Oxford classification is a histologic scoring system, validated in diverse cohorts, that incorporates findings on renal biopsy that are also associated with adverse outcomes independent of clinical features. The cornerstone of management in nearly all patients with IgA nephropathy is treatment of hypertension and/or proteinuria by ACE inhibition or angiotensin receptor blockade. Corticosteroids demonstrated some efficacy for preservation of renal function and improvement in proteinuria among patients with more significant proteinuria and normal baseline renal function in a randomized controlled trial. Immunosuppression with corticosteroids and cyclophosphamide is often used to manage rapidly progressive glomerulonephritis with cellular crescents seen on renal biopsy, based on observational data, but randomized controlled trial data is lacking. Our patient presented with a number of poor prognostic factors, mostly significantly the rapid progression of her condition, massive proteinuria and crescents on renal biopsy. Consequently, we aggressively managed the patient with steroids and a cytotoxic agent given the acuity and fulminant nature of her presentation.
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Health literacy predicts change in physical activity self-efficacy among sedentary Latinas
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Health literacy (HL) is associated with preventive health behaviors. Self‐efficacy is a predictor of health behavior, including physical activity (PA); however, causal pathways between HL and self‐efficacy for PA are unknown, especially among Latinas who are at risk for chronic disease. To explore this potential relationship, secondary analyses were conducted on data [Shortened Test of Functional Health Literacy in Adults (STOFHLA), PA self‐efficacy, and socio‐demographics] from a 6‐month, randomized controlled trial of a print‐based PA intervention (n = 89 Spanish‐speaking Latinas). Linear regression models revealed associations between HL and baseline self‐efficacy in addition to changes in self‐efficacy at 6‐months. After controlling for significant covariates, higher HL scores were associated with lower baseline PA self‐efficacy. Regardless of treatment assignment, higher HL scores at baseline predicted greater changes in PA self‐efficacy at 6‐months. HL may contribute to Latinas' improved PA self‐efficacy, though further research is warranted.
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Increased catheter stability with robotic assisted navigation during pulmonary vein isolation, does it matter? Novel cardiac MR findings
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Introduction: Durable pulmonary vein lesions is integral in minimizing pulmonary vein reconnection and subsequent post‐ablation recurrences.Catheter stability, tissue contact force and RF duration are determinants of lesion formation and may be operatordependent. Remote robotic assisted navigation systems permit accurate titration of contact force while maintaining a stable catheter position. Objectives: We sought to compare lesions imaged on cardiac MR created by standard versus robotic assisted catheter ablation by quantifying the amount of tissue injury with delayed enhancement (DE) and tissue edema with T2‐weighted enhancement (T2) on cardiac MR. Methods: Thirty PAF patients (mean age 54±15.4 years, twenty male) undergoing their first left atrial ablation were randomized to either robotic assisted navigation (Sensei® X Robotic Catheter System, Hansen Medical, Inc) or standard navigation. Pre and 24 hours post procedure scans were performed. Following successful electrical isolation, 60 pairs of PVs (30 right, 30left) were imaged with DE and T2 imaging sequences. Percentages (%) of circumferential DE and T2 around the PV antrum was quantified 1. DE and T2 rings (DE&T2) were then overlayed to assess the combined total % encirclement. Ratios of DE/(T2&DE) was calculated to assess the proportion of tissue injury. Results: Robotic ablation (Sensei® X Robotic Catheter System, Hansen Medical, Inc)resulted in a greater circumferential lesion extent as assessed by DE and T2. Higher % encirclement of DE and T2 means around the pulmonary vein antrum were seen in the robotic assisted procedures In both groups, areas of T2 enhancement (edema) not only overlapped with areas of DE but also filled in gaps between areas of DE resulting in increased circumferential enhancement. Combination of T2 and DE conferred a higher % encirclement in the robotic series (94%) versus standard navigation (83%) achieving a statistical significance (p=0.04). A higher mean ratio of DE over (T2+DE) of 0.76±0.18 versus 0.63±0.30 in the robotic arm suggests greater injury. Mean energy delivered was 85.2kJ versus 82.6kJ in the robotic versus standard navigation groups. Conclusion: In comparison to manual ablation, robotic LA ablation achieves more tissue injury and a greater degree of PV antral encirclement. This may be a function of improved stability and contact force information.
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Variations of responders rates according to response critera used in a Randomized Controlled Trial (RCT) in knee osteoarthritis (OA)
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Background: Results of clinical trials in OA are usually reported as group comparisons of the mean (± standard deviation, sd) in score of the selected outcome. It might be more clinically relevant to show the results at a patient level, using a response criterion. Several response criteria are available: OARSI/OMERACT modified set of responder criteria [1], the Patient Acceptable Symptom State (PASS) [2] and the Minimum Clinically Important Improvement (MCII) [3]. Objectives: To assess differences in responder rates using various response criteria in a RCT in knee OA. Methods: Data were extracted from a prospective, multicentre, double‐blind RCT comparing two hyaluronans over 24 weeks (F60027‐Structovial and Hylan G‐F 20‐Synvisc) according to a non inferiority design. The main outcome was the Lequesne index score (LFI). The secondary outcome was global pain on a Visual Analog Scale (VAS). 236 patients were available in the main analysis (per protocol analysis, PP). Demographic and knee OA characteristics were identical to those usually reported in knee OA trials. Since no value of the PASS is validated for the LFI yet, the results on pain VAS were used to classify patients as responders or not using OMERACT/OARSI modified criteria, PASS and MCII (using absolute value or % of improvement). Results are reported as mean (sd) and number (%). Results: Table 1 below shows the response rates according to the different criteria. Rates of responders varied considerably: from 60 to 80% in each group and from 63% to 78% in the overall population (both treatment groups can be merged since non‐inferiority was proven). The most liberal definition seems to be MCII (absolute), while the strictest appears to be PASS. Conclusions: Reporting clinical trial results at a patient level using response rates might be meaningful in knee OA. However this study clearly demonstrate that results significantly vary according to the response criterion used which is likely to lead to “positive” or “negative” results accordingly. More work is needed to help assessing the most clinically relevant response definition in knee OA. Acknowledgement: This work was possible thanks to a grant from Pierre Fabre Labs.{table presented}.
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The PROPER study: interim analysis of a Pan-European real-world study of SB5 adalimumab biosimilar after transition from reference adalimumab in patients with Crohn's disease
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Background: SB5, a biosimilar to reference adalimumab (ADL), received EU marketing authorisation in August, 2017, based on preclinical and clinical phase I and III studies that demonstrated bioequivalence and comparable efficacy, safety and immunogenicity profiles to ADL. The real‐world study 'PROPER' is designed to provide insights into outcomes of the transition from reference to SB5 outside the controlled, randomised, clinical trial setting. Under an umbrella design, 1000 patients with immune‐mediated inflammatory disease have been enrolled at centres in Belgium, Germany, Ireland, Italy, Spain and the UK. Methods: Eligible patients had been transitioned to SB5 as part of routine treatment following a minimum of, 16 weeks' treatment with ADL. Data were captured from patient charts retrospectively for, 24 weeks prior to and prospectively and/or retrospectively for, 48 weeks after SB5 initiation. This interim analysis of the Crohn's disease cohort reports outcome measures including clinical characteristics, disease activity, persistence on SB5, clinical management and safety for patients enrolled at, 32 specialist sites and followed up to the data extract date of October, 5th, 2021. Results: Of the, 462 patients included in this interim analysis, the majority were enrolled in Germany (n=127), Spain (n=118) and Italy (n=79); Belgium, Ireland and UK enrolled, 56, 46 and, 36 patients, respectively. At time of data extract, 416 patients had completed, 48 weeks of follow‐up and, 15 had withdrawn from the study. The most common reasons driving transition were physician decision, or a mandate from the health authority or payer. At baseline, the majority of patients were in remission or had mild disease as determined by Harvey Bradshaw Index (HBI), and were in remission or stable according to physician opinion. Most patients transitioned to the same SB5 regimen as they had received for ADL (Table 1). Twenty‐four patients reported, 27 serious adverse events (SAE), of which, 4 (anal fistula [n=1], perianal abscesses [n=2] and subileus [n=1]) were considered by the study physician to be related to SB5 administration. Conclusion: No meaningful change in HBI or SB5 dosing regimen was observed from baseline to Week, 48 after transition from ADL. The number of patients experiencing a treatment‐related SAE was low, and no new safety concerns were detected. Thus, transition from ADL to SB5 was generally safe and effective in patients with Crohn's disease over, 48 weeks of follow‐up. (Figure Presented).
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Effect of tactile?kinesthetic stimulation on growth, neurobehavior and development among preterm neonates
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Background: Preterm neonates are at risk of delayed growth and development. Hence, early tactile?kinesthetic stimulation (TKS) is required to improve their growth and development. Objective: To evaluate the effect of TKS on growth, neurobehavior and development among preterm neonates. Method: An interventional study was conducted from August 2015 to July 2017 in the neonatal unit of Dr. Cipto Mangunkusumo Hospital. Preterm neonates were recruited via random sampling and divided into two groups (the intervention group and control group). TKS was performed for 15 min, three times a day, for 10 days. The anthropometric measurements, neurobehavior (Dubowitz score) and development (Capute Scale score) of neonates in both groups were assessed. Results: There were 126 preterm neonates (n = 63 in each group). During the 10‐day TKS period, the intervention group had a significant increment in weight and length compared to the control group (p < 0.05) at 11?14 days, at term and 3 months. Moreover, increased tone, reflexes, and improvement in behavior based on the Dubowitz score were observed during monitoring. However, the result did not differ significantly (p > 0.05). There was no significant difference in terms of cognitive and language development in both groups (Developmental Quotient of Clinical Linguistic Adaptive Milestone Scale, Developmental Quotient of Clinical Adaptive Test and Full Scale Developmental Quotient scores, p > 0.05). Conclusion: TKS was significantly effective in promoting growth, particularly weight and length, among preterm neonates. However, it did not significantly influence neurobehavior and development at 3 months of chronological age.
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The development of a stress test for assessing the metabolic state of articular cartilage
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Purpose: Clinically, the inability to assess the overall condition of cartilage prevents detection of the early changes that predate symptoms and also negatively impact clinicians’ ability to define an appropriate physical activity regimen with optimal loading intensity and duration for the patients’ clinical state. Most prior studies evaluate cartilage under static loading conditions, whereas assessing the in vivo cartilage response to load would provide a more physiologic and meaningful assessment of the status of cartilage health. A potential clinical assessment can be made using a stimulus‐response framework that applies quantitative graded biomechanical stimuli to the joint with responses determined by measurement of specific disease‐related markers, such as a serum biomarker of cartilage turnover (cartilage oligomeric matrix protein, COMP). Prior stimulus response frameworks have utilized a flat walking loading paradigm which does not isolate a stress to a particular joint and has resulting in a biomarker response that is non‐specific to a joint. We have developed an innovative mechanical stimulus protocol using a medial/laterally tilted treadmill allowing up to 10º of angulation while walking. The objective of the present study was to assess the difference in biomarker (COMP) response to an angular tilt paradigm in individuals with and without knee OA and across risk factors for knee OA (age, sex and BMI) and radiographic severity of knee OA. Methods: Subjects: The study had IRB approval (IRB#STU00204429). Individuals with normal knees (i.e. without a history of knee pain, or prior surgery completed a specific treadmill walking session (n=10, mean age 24.2+/‐ 4.2, 6 males, 4 females) were compared to individuals with knee OA (n=10, mean age 65.9+/‐9.4, 5 males 5 females). A custom fabricated treadmill in our laboratory that allows up to 10° lateral angular tilt walking and regular flat walking was utilized for this study. Walking protocol: For each study session subjects walked 30 minutes flat on a treadmill at a self‐selected speed (which is the equivalent of a rating of 13‐14, ‘somewhat hard’ on the Borg Scale of perceived exertion) and 30 minutes of lateral angular tilt walking in which the treadmill is tilted at a 10‐degree angle The order in which they do each of the walking protocols was randomized. The direction of angulation was randomized to the left in individuals in control subjects and towards the side with the higher knee pain in individuals with knee OA. Biomechanical Assessment: Functional three‐dimensional motion analysis will be performed using an eight‐camera system (Motion Analysis Corporation, Santa Rosa, CA) during all bouts of walking. Serum biomarker assessment: Five milliliter blood samples were drawn via an IV peripheral line every 15 and 30 mins during the walking sessions and for up to 60 mins post‐walking. The concentration of COMP was determined using a commercially available assay according to the manufacturer’s protocol. Pain assessment: Pain every 15 minutes of walking was assessed using the Numeric Pain Rating Scale (NPRS). Radiographic assessment: OA subjects had radiographs performed at baseline that were scored using Kellgren‐Lawrence (K‐L) criteria. Statistical analysis: Significant differences in serum COMP concentration were measured with significance set at p<0.05. Results: All subjects were able to complete the walking protocol with no significant increase in knee pain. We firstly investigated the effect of tilt walking on joint kinematics throughout the lower extremity. When comparing across joints, we found that in normal knees the effect size for change in kinematics was highest in the frontal plane of the lower knee (Cohen’s d=0.82). Specifically the lower knee joint had the highest change in adduction angulation compared to other joints in the lower extremity. Closer examination of this change, specifically in individuals with medial knee OA found that the lower knee, developed an adduction angulation throughout the entire stance phase (p<0.0001) and also during the swing phase (p<0.002). At peak initial contact, there was 122.3% increase in knee adduction angle of the lower knee compared to when walking flat, and at mid‐stance there was a 57.9% increase. There was also a moderate positive relationship between change in knee adduction angle during initial contact and serum COMP concentration (r=0.43, p=0.042).Individuals with knee OA had a significantly higher percentage change in COMP concentration after 30 minutes of tilt‐walking than those without knee OA (p=0.02). Individuals in the non‐OA group had a 22.3% increase in serum COMP concentration with tilt‐walking, compared to 9.7% increase when walking on a flat treadmill (p=0.048). However, participants with OA had a 44.2% increase in serum COMP concentration compared to a 3.7% increase (p=0.002), when walking on a tilted or flat treadmill, respectively. Similarly, the serum concentrations of MMP‐13 increased in response to 30 minutes of tilt walking (p=0.002) but not flat walking, in the OA group. There was a significant correlation between the percentage change in serum COMP and MMP‐13 concentration in the OA group with tilt‐walking (r=0.67, p=0.042). When evaluating participants with knee OA we further assessed the COMP biomarker response in individuals with certain risk factors for knee OA i.e. age sex and BMI. We found that individuals with knee OA, who were female, above the age of 60, and who had a BMI>30 had a significantly higher COMP response at 30 minutes of tilt walking (p<0.05). In addition, individuals who had K‐L grades 1‐3 radiographic knee OA had a significantly higher COMP response to tilt walking compared to individuals with K‐L grade 4 knee OA. The latter is unsurprising since individuals with grade 4 knee OA have less cartilage than those with less severe knee OA, potentially leading to a lower COMP response. Conclusions: This study is the first to evaluate the stress response to a novel angular tilting paradigm comparing subjects with knee OA and those with normal knees. Lateral angular tilt walking of 10° does appear to place a safe biomechanical stress that did not exacerbate subject pain. Our data suggests that this stress is able to cause a significant change in a biomarker associated with cartilage tissue turnover, COMP in individuals with and without knee joint disease. The differential response across individuals with and without knee OA and severity of radiographic disease was able to be elucidated from the response to the biomechanical stimulus in as little as 30 minutes. In addition, in those with knee OA, there was a significantly larger response in individuals with known risk factors for OA progression (older age, female sex and higher BMI) [Formula presented]
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Levonorgestrel release rates measured through analysis of two-rod contraceptive explants
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Objective: The objective was to characterize and compare in vivo rates of levonorgestrel (LNG) release from Sino‐implant (II) and Jadelle® contraceptive implants. Study design: We sampled 48 Sino‐implant (II) and 49 Jadelle® explant sets for residual LNG content from participants treated for up to 51 months in a randomized contraceptive efficacy trial in the Dominican Republic (DR). Additional Sino‐implant (II) explants were obtained from 8 women who became pregnant in the DR trial and 10 who contributed 3 to 5 years of use in a cohort study in China. Baseline LNG loads were estimated from five unused implant sets per device type. Release profiles were estimated using mixture models that captured initial burst fractions and compared with efficacy and pharmacokinetics data from the DR trial. Results: Estimated baseline LNG loads for Sino‐implant (II) and Jadelle® were 142.8 mg and 150.5 mg, respectively (vs. the labeled 150 mg). There was an initial burst release of drug (5.6% and 7.9%, respectively) followed by an exponential decrease in LNG content evident for each device. Release rates were significantly lower for Sino‐implant (II) throughout the treatment period, with estimated rates after 3 years of 24.2 mcg/day and 29.0 mcg/day for Sino‐implant (II) and Jadelle®, respectively. The estimated Sino‐implant (II) rate after 3 years was similar to the predicted rate after 5 years (23.6 mcg/day) for Jadelle® (rate ratio: 1.03; 95% confidence interval: 0.92–1.13). Conclusions: Sino‐implant (II) LNG release rates were significantly lower than Jadelle® with Sino‐implant (II) rates through year 3 comparable to Jadelle® rates through year 5. These results reinforce the 3‐year duration of action for which Sino‐implant (II) was prequalified by the World Health Organization. Implications: This analysis confirms the WHO prequalification of Sino‐implant (II) for 3 years of use and supports different durations of action for Jadelle® and Sino‐implant (II). It provides additional evidence that this approach can complement efficacy trials in determining duration of action of hormonal contraceptives in general.
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Bioequivalence study of tolvaptan orally disintegrating tablets in healthy adult male volunteers
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Bioequivalence of orally disintegrating (OD) toivaptan tablets to conventional ones at 15 and 30 mg was evaluated in an open‐label, three‐period, three‐way crossover trial. Total 84 healthy adult male volunteers were divided into two cohorts and randomized to three groups: Conventional tablet (CT) first, OD tablet with water (ODT+W) first, and OD tablet without water (ODT‐W) first. 90% confidence intervals (CIs) for geometric mean ratios (GMRs) of AUC, and Cmax of toivaptan for 15 mg of ODT‐W to those for 15 mg of CT were log (0.95)‐log (1.06) and log (1.07)‐log (1.23), respectively. Those for the GMRs of the AUC, and Craax of toivaptan for 15 mg of ODT+W to those for 15 mg of CT were log (0.94)‐log (1.05) and log (0.89)‐log (1.02), respectively. Those for the GMRs of the AUC, and Cmax of toivaptan for 30 mg of ODT‐W to those for 30 mg of CT were log (0.97)‐log (1.06) and log (1.04)‐log (1.17), respectively. Those for the GMRs of the AUC, and Craax of toivaptan for 30 mg of ODT+W to those for 30 mg of CT were log (0.95)‐log (1.05) and log (0.94)‐log (1.06), respectively. These results were within the range of log (0.80)‐log (1.25) specified for bioequivalence, indicating that the two formulations were bioequivalent. All observed adverse events were mild and resolved spontaneously. There were no consistent trends indicating clinical concerns in clinical laboratory tests, vital signs, body weight, or 12‐lead electrocardiogram.
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Aspirin in combination with clopidogrel in the treatment of acute myocardial infarction patients undergoing percutaneous coronary intervention
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Objective: To investigate the clinical effect of aspirin combined with clopidogrel on acute myocardial infarction after percutaneous coronary intervention (PCI). Methods: One hundred thirty two patients with acute myocardial infarction who were admitted to the hospital between December 2016 and December 2017 were divided into a control group and an observation group according to random number table, 66 each group. Both groups were given emergency PCI and symptomatic treatment. The control group was given aspirin on the basis of conventional treatment before and after operation, while the observation group was given clopidogrel treatment on the basis of the treatment the same as the control group. The treatment lasted for 4 months. The clinical efficacy of the two groups was analyzed, and the cardiac function indicator, coagulation indicator and occurrence of adverse reactions were compared before and after treatment. Results: There was no thrombosis at the infarct site in coronary angiography after treatment in both groups. The efficacy in the observation group and control group were 89.4% and 81.8%, respectively; there was no significant difference between the two groups. The incidence of re‐thrombosis in the two groups was 1.5% and 12.1% respectively, which was significantly lower in the observation group than in the control group (P<0.05). The cardiac function indicator of both groups improved after treatment, especially the observation group (P<0.05). There was no significant difference in prothrombin time (PT), activated partial thromboplastin time (APTT), prothrombin activity (PA) and platelet aggregation rate (PAR) in the two groups before treatment (P>0.05). There was also no significant difference in PT and PA before and after treatment (P>0.05). The APTT and PAR were significantly different after treatment (P<0.05), and the PAR of the observation group was significantly higher than that of the control group (P<0.05). The incidence of adverse reactions in the observation group was 7.58%, which was not significantly different with that of the control group (12.12%) (P<0.05). Conclusion: Aspirin combined with clopidogrel can effectively reduce the occurrence of re‐thrombosis after PCI and improve the recovery of cardiac function after acute operation, moreover the safety is high. It has important clinical application values.
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Integrated versus referred management of cardiovascular disease (CVD) risk factors for HIV-positive patients on antiretroviral therapy in Swaziland
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Objectives/aims: Even though cardiovascular diseaserisk factors (CVDRF) are prevalent among people living with HIV (PLHIV), the optimal clinical management strategy for patients with both HIV and CVDRFin resource‐limited settings is unknown. In some contexts, care for both conditions is conveniently integratedin the HIV clinic, while in others, PLHIV are referredto specialist clinics for management of their CVDRF.We compared integrated versus referred strategies forpatients with HIV and CVDRF at a large urban hospital in Swaziland, exploring linkage to and retentionin CVDRF care, and HIV and CVDRF‐related healthoutcomes.Methods: PLHIV were screened for CVDRF if they wereon antiretroviral therapy for =1 year, were =40 yearsold, had no history of CVD and were not pregnant oracutely ill. CVDRF screening included measurement ofresting blood pressure (BP) to screen for hypertension,glycated haemoglobin (HbA1c) to screen for diabetesmellitus and total cholesterol to screen for hyperlipidaemia. Tobacco smoking was assessed via self‐reportand 10‐year CVD risk via WHO/ISH risk stratifcation.Patients with hypertension and/or >10% 10‐year CVDrisk were randomized 1:1 to receive CVDRF management at the HIV clinic (INTEGRATED arm) or outpatient clinic (REFERRED arm) for 6 months. Theprimary study outcome was a composite measure oflinkage to CVDRF care, retention in both CVDRF andHIV management, medication initiation, and changesin systolic BP, HbA1c and total cholesterol.Results: 240 participants were enrolled. One‐quarterhad hypertension and/or >10% 10‐year CVD risk.Linkage to CVDRF care within 1 month was similar (85% in the INTEGRATED arm and 84% in theREFERRED arm). Retention in HIV care was 98% inboth arms. A higher proportion of eligible participantswith hypertension initiated BP medication in the INTEGRATED arm (72%) than in the REFERRED arm(53%). There was a statistically signifcant mean reduction in systolic BP (‐15 mmHg) at 6 months in bothstudy arms, but no differences between arms. Amongindividuals with diabetes mellitus, there was a statistically signifcant mean HbA1c reduction of‐0.68%(CI‐1.26,‐0.10) and‐1.37% (CI‐2.51,‐0.24) in theINTEGRATED and REFERRED arms, respectively,but no differences between arms. Among participantswith hyperlipidaemia, a statistically signifcant meanreduction in total cholesterol of‐0.91 mmol/l (CI‐1.76,‐0.65) was observed only in the REFERRED arm.Conclusions: Among participants with both HIV andCVDRF, linkage to CVDRF care was high regardlessof the management strategy assigned. Marked improvements in systolic BP and HbA1c were noted in botharms while improvement in total cholesterol was seenonly in the REFERRED arm. Substantial improvementsin BP and diabetes mellitus control were achieved irrespective of management strategy, suggesting that management for these comorbidities can be effectively integrated in the HIV clinic.
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Updated efficacy data and MRD analysis according to risk status in newly diagnosed myeloma patients treated with carfilzomib + lenalidomide or cyclophosphamide (FORTE trial)
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Background: Carf plus Len‐Dex (KRd) or Cyclo‐Dex (KCd) is effective in NDMM. Treatment of high‐risk pts is an unmet medical need. Methods: NDMM pts ≤65 yrs were randomized (1:1:1; stratification ISS and age) to ARM A: 4 28‐day induction cycles with KCd (Carf: 20/36 mg/m2 IV days 1,2,8,9,15,16; Cyclo: 300 mg/m2 days 1,8,15; Dex: 20 mg days 1,2,8,9,15,16) followed by MEL200‐ ASCT and consolidation with 4 KCd; ARM B: 4 28‐day cycles with KRd (Carf: 20/36 mg/m2 IV days 1,2,8,9,15,16; Len: 25 mg days 1‐21; Dex: 20 mg days 1,2,8,9,15,16) followed by MEL200‐ASCT and 4 KRd; ARM C: 12 KRd cycles. Primary endpoint was VGPR rate with KRd vs KCd induction. For this analysis, the 2 KRd arms were pooled (2:1), as treatment was the same until that point. Enrollment was completed in March, 2017; data cut‐off was November 30, 2017. Results: 474 pts were randomized (KRd, n = 315; KCd, n = 159). Pts characteristics were well balanced: 49% of KRd pts vs 49% of KCd pts had ISS Stage 2‐3 at baseline, 31% vs 35% had high‐risk chromosomal abnormalities [del17 and/or t(4;14) and/or t(14;16) by FISH], 68% vs 74% had Revised ISS Stage 2‐3. Rates of sCR/CR (14% vs 3%; P = 0.0004), ≥nCR (33% vs 21%; P = 0.0106) and ≥VGPR (75% vs 60%; P = 0.0017) were significantly higher with KRd vs KCd. The advantage of KRd was consistent in all subgroups; ≥VGPR, ≥nCR in high‐risk pts treated with KRd were comparable to the overall population. MRD evaluation (8 color second generation flow cytometry, sensitivity 10 ) was available in a subset of pts: 144 KRd and 56 KCd. Rate of MRD negativity in evaluable pts was 56% with KRd vs 29% with KCd (P = 0.008). MRD negativity in high‐risk pts treated with KRd was comparable to the overall population (Table). Treatment was well tolerated, as previously shown (Gay F ASCO 2017). Conclusions: KRd induction significantly improved sCR/CR, ≥nCR, ≥VGPR rates and MRD negativity vs KCd with similar efficacy in high‐risk pts. (Table Presented) .
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Childhood eye injuries in New Zealand: a 10-year national review of incidence, aetiology and visual outcomes
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Purpose: To evaluate the incidence, demographics, aetiology, and visual outcomes of 0‐17‐year‐old children in New Zealand sustaining traumatic eye injuries. Methods: New Zealand Accident Compensation Corporation (ACC) data were analysed to identify all children presenting to any registered New Zealand health provider with eye injuries in the decade spanning 2006‐2015. ACC national data were correlated with Auckland (regional) eye‐injury data and a randomised sample of 125 patients were selected for additional analysis. Clinical notes were reviewed providing data on visual outcomes, protective eyewear use, surgical intervention, and follow‐up. Population incidence, aetiology, demographics and location of injury were calculated from the national and regional sample data. Results: From 2006‐2015 there was a total of 83,869 eye injuries recorded nationally in 0‐17year‐old children. The incidence of eye injury was 6.8/ 10,000/year. Patients were predominantly male, 70.8%(95%CI=68.9‐72.7%), and NZ‐European ethnicity 47.8%(95%CI=45.7‐49.9%). The rate of injury was highest in patients aged 10‐14y 35.9%(95% CI=33.9‐37.9%). Mechanism of injury was 'struck by object' in 49.6%(95%CI=47.5‐51.7%). Eye injury occurred most commonly at home 49.4%(95% CI=47.2‐51.5%), and at school in 17.6%(95% CI=11.8‐25.2%). Permanent disability, with final visual acuity worse than 6/12, was noted in 22.4% (95%CI=15.9‐30.5%). Enucleation was required in 2.4%(n=3). Protective eyewear use was reported in 3%. Conclusions: Childhood eye injury is a common, preventable cause of potentially severe permanent disability. Male children aged 10‐14y are in the highest risk category. A significant proportion of injuries occur at school and protective eyewear use is reportedly low. The promotion of appropriate childhood injury prevention strategies is an important public health message.
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Effects of intraoperative single bolus fentanyl administration and remifentanil infusion on postoperative nausea and vomiting
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Background: Although the use of postoperative opioids is a well‐known risk factor for postoperative nausea and vomiting (PONV), few studies have been performed on the effects of intraoperative opioids on PONV. We examined the effects of a single bolus administration of fentanyl during anesthesia induction and the intraoperative infusion of remifentanil on PONV. Methods: Two hundred and fifty women, aged 20 to 65 years and scheduled for thyroidectomy, were allocated to a control group (Group C), a single bolus administration of fentanyl 2 μg/kg during anesthesia induction (Group F), or 2 ng/ ml of effect‐site concentration‐controlled intraoperative infusion of remifentanil (Group R) groups. Anesthesia was maintained with sevoflurane and 50% N2O. The incidence and severity of PONV and use of rescue antiemetics were recorded at 2, 6, and 24 h postoperatively. Results: Group F showed higher incidences of nausea (60/82, 73% vs. 38/77, 49%; P = 0.008), vomiting (40/82, 49% vs. 23/77 30%; P = 0.041) and the use of rescue antiemetics (47/82, 57% vs. 29/77, 38%; P = 0.044) compared with Group C at postoperative 24 h. However, there were no significant differences in the incidence of PONV between Groups C and R. The overall incidences of PONV for postoperative 24 h were 49%, 73%, and 59% in Groups C, F, and R, respectively (P = 0.008). Conclusions: A single bolus administration of fentanyl 2 μg/kg during anesthesia induction increases the incidence of PONV, but intraoperative remifentanil infusion with 2 ng/ml effect‐site concentration did not affect the incidence of PONV.
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Long-term safety and efficacy of recombinant factor VIII Fc fusion protein (rFVIIIFc) in subjects with haemophilia A
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Introduction: The safety, efficacy and prolonged half‐life of recombinant factor VIII Fc fusion protein (rFVIIIFc) in previously treated patients with severe haemophilia A was demonstrated in the phase 3 A‐LONG and Kids A‐LONG studies. Here, we report interim safety and efficacy data from the rFVIIIFc extension study, ASPIRE (ClinicalTrials.gov #NCT01454739). Methods: Eligible subjects could enrol in ASPIRE upon completing A‐LONG or Kids A‐LONG. There were four treatment groups: individualized prophylaxis; weekly prophylaxis; modified prophylaxis (for subjects in whom optimal treatment could not be achieved with individualized or weekly prophylaxis); and episodic treatment. The primary endpoint was development of inhibitors. Results: A total of 150 A‐LONG subjects and 61 Kids A‐LONG subjects enrolled in ASPIRE. As of the interim data cut (6 January 2014), the median time on study was 80.9 (A‐LONG) and 23.9 (Kids A‐LONG) weeks. The majority of subjects (A‐LONG, 92.0%; Kids A‐LONG, 57.4%) had >100 cumulative rFVIIIFc exposure days. No inhibitors were observed. Adverse events were generally consistent with those expected in the general haemophilia A population. Median annualized bleeding rates (ABRs) were low with individualized [A‐LONG: 0.66; Kids A‐LONG: 0.00 (<6 years old), 1.54 (6 to <12 years old)], weekly (A‐LONG: 2.03) and modified (A‐LONG: 1.97) prophylaxis. There was no change in prophylactic infusion frequency or total weekly prophylactic dose in the majority of subjects from A‐LONG and Kids A‐LONG. Conclusion: Interim data from ASPIRE confirm the long‐term safety of rFVIIIFc and the maintenance of a low ABR with extended‐interval prophylactic dosing in patients with severe haemophilia A.
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EFFECTS OF TARGETED NURSING INTERVENTIONS ON CANCER-INDUCED FATIGUE AND MENTAL HEALTH IN CHEMOTHERAPY PATIENTS WITH LEUKEMIA
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Background: The phenomenon of cancer‐induced fatigue is one of the research hotspots at this stage in the field of foreign tumors, but the understanding and attention of this symptom in china leukemia field is not enough, which is not conducive to the provision of high‐quality care for leukemia patients. Aims: To investigate the implementation method of targeted nursing intervention program and its application value in the care of chemotherapy patients with leukemia. Methods: The 100 leukemia chemotherapy patients admitted to our hospital from January to December 2021 were randomly divided into a control group and an observation group of 50 cases each, and the observation group implemented routine nursing intervention and the control group targeted nursing intervention. Before and after nursing interventions, the Cancer Fatigue Scale (CFS) was used to evaluate the state of cancer‐induced fatigue, and the Hamilton Depression Scale (HAMD) and the Hamilton Anxiety Scale (HAMA) were used to evaluate the state of mental health. Results: After the intervention, the CFS scale score of patients in the control group was lower than that in the observation group (P≤0.05), and the HAMD score and HAMA score were lower than those in the observation group (P≤0.05). Summary/Conclusion: The implementation of targeted nursing interventions in the clinical care of chemotherapy patients with leukemia can effectively improve the patient's cancer‐induced fatigue state and negative psychology.
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Vonoprazan based triple and high dose dual therapies are effective in the primary eradication of h.pylori infection- an interim analysis
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Background and Aim: We compared between vonoprazan based triple therapy with amoxicillin and clarithromycin of 7 days (V‐STT‐1), vonoprazan based triple therapy of 14 days (V‐STT‐2) and vonoprazan based dual therapy with high dose amoxicillin (V‐HDDT) for 14 days for eradication of H pylori. Methods: This is a prospective, randomized open label comparative study. All patients recruited at endoscopy who has proven H pylori infection were randomized into 3 treatment groups comprising of; V‐STT‐1: Vonoprazan 20mg b.i.d + Amoxicillin 1g b.i.d + Clarithromycin 500mg b.i.d for 1 week; V‐STT‐2: Vonoprazan 20mg b.i.d + Amoxicillin 1g b.i.d + Clarithromycin 500mg b.i.d for 2 weeks; and V‐HDDT : Vonoprazan 20mg b.i.d + Amoxcillin 1g t.i.d for 2 weeks. Follow up on successful eradication using either C13‐UBT or endoscopic biopsies were done after 4 weeks post treatment. Results: In this interim analysis, 200 patients were recruited. The mean age was 49.6 (±16.4) years and 55.0% were males. 12.5% of them were active smokers and 8.5% were active drinkers. The eradication rates in the intention to treat (ITT) and per protocol (PP) analysis were similar in all 3 groups. The results are shown in Table 1. There were no major side effects, however bitter taste was the most common minor side effect seen in V‐STT‐1 (29.4%) and V‐STT‐2 (32.8%) while none were seen in V‐HDDT group. Conclusion: Vonoprazan based therapy (both triple and dual) is shown to be safe and efficacious in eradicating H pylori. V‐HDDT appears to have fewer side effects.
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Muscle histopathology and functional data in a large cohort of patients with Becker muscular dystrophy
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Age of onset, clinical presentation and rate of disease progression in Becker Muscular Dystrophy (BMD) patients display wide variability. At our Center we are currently performing a randomised, double‐blind, placebo‐controlled study to evaluate the histological effects, the safety and tolerability, and the efficacy of Givinostat in BMD patients. Ambulant adult male patients with a molecular diagnosis of BMD and a screening 6 minutes walking test (6MWT) between 200 and 450 meters were recruited. All patients underwent other functional tests (4‐stair climb, 10 meters walk/run test, rise from floor, motor function measure MFM, muscle strength) and biceps open muscle biopsy before the randomization visit. The enrolment phase of the study has been closed and we have collected histological specimens from 45 patients, with an average age of 38 years and a mean disease duration of 23 years. Similarly to the wide clinical variability of BMD patients in our cohort, muscle biopsies also showed marked histological variability, ranging from an almost normal morphology to a severe dystrophic pattern with a marked fibroadipose replacement. The correlation analysis between histological parameters and clinical outcomes showed that in BMD patients the percentage of muscle fiber area (MFA) positively correlated with most of the clinical outcomes, while the percentage of adipose and fibrous replacement showed a negative correlation (Figure 1). The in‐depth statistical analysis allowed to divide our cohort of BMD patients into three clusters (mild, moderate and severe), according to the clinical and histological features. The severe cluster is characterized by significant increase of both connective (56.26%) and adipose tissue (8%) with a consequent marked reduction of MFA (26.23%). The moderate and mild clusters had 34.44% and 17.83% fibrotic tissue respectively, and no fatty infiltration was detected. In these two clusters, the residual MFA were 64.37% and 80.93% respectively. Marked tissue replacement caused a deterioration of muscle contractile function, which may explain the worst functional performances in more severe patients. Our results underline the importance of the choice of appropriate functional tests to monitor the state of disease progression. At present, this work has collected one of the largest cohorts of ambulant BMD patients, providing relevant information about muscle alterations and allowing significant correlations between them and functional data.
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Short term treatment of achalasia by dark chocolate
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Background: Pneumatic dilatation or myotomy for achalasia are usually efficient. Pharmacological treatment (Ca channel blockers or nitrates) is usually minimally helpful and accompanied by side effects. Aim: To test the efficacy of dark chocolate (containing flavonol ‐ a nitric oxide donor) in improving achalasia symptoms and esophageal physiology. Methods: Consecutive naive patients diagnosed as suffering from primary achalasia (diagnosed by gastroscopy and/or barium meal plus manometry). All patients were randomized into 2 groups ‐ treatment arm used dark chocolate, 75% cacao solids and compared to placebo arm ‐ patients using “white” chocolate. All underwent repeat manometry 15 minutes after chewing and melting 21gr of chocolate to test the immediate effects of the chocolate on esophageal function. All patients were discharges with dark chocolate for a period of 2 weeks and were instructed to chew and melt 7gr of chocolate 3 times a day, 15 minutes before each meal. All patients filled a daily symptom diary and health related quality of life questionnaire (HRQL). Results: 27 patients were recruited for the study. 4 omitted because of subsequent refusal. 19 agreed to undergo 2 manometries before and after chocolate consumption (10 study group, 9 controls) all patients were followed by symptom and HRQL questionnaires. No significant changes in LES pressure before and after treatment were observed for each group and no significant differences between the 2 groups (+6.8 mm Hg vs. ‐1.38 mm Hg). Esophageal body pressures declined more in the study group, however, not statistically significant. After 2 weeks of treatment, statistically significant changes were observed in the sense of food limitation, solid food dysphagia and regurgitations (P < 0.01). No significant changes were observed for liquid dysphagia, vomiting, nausea, chest pain and heartburn. Discussion: In this small pilot study, chocolate was able to modify some symptoms related to dysphagia, however, it did not show efficacy in changing physiological parameters.
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Ureteric stenting versus non-stenting following uncomplicated ureteroscopic lithotripsy: a prospective randomized trial
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Introduction & Objectives: There is no consensus about whether a double‐J ureteric stent (DJ‐US) should be placed following uncomplicated ureteroscopy for stone retrieval. This study aimed to compare three groups of patients who underwent uncomplicated ureteroscopic lithotripsy (URSL) and to evaluate whether stents could be eliminated after the procedure. Materials & Methods: A total of 105 patients underwent uncomplicated URSL for ureteric stones were prospectively randomized into three groups: Group 1 (34 patients) with DJ‐US, Group 2 (35 patients) with DJ‐US on extraction string, and Group 3 (36 patients) with no DJ‐US after the procedure. The outcomes measured were; postoperative Visual Analog Score (VAS) for flank pain and dysuria score, urgency, frequency, suprapubic pain, hematuria and analgesia requirement. In addition, operative time, re‐hospitalization, and return to normal physical activity. Results: Mean operative time was significantly longer in Groups 1 and 2 compared to Group 3 [mean time ± SD, 22.2 ± 9.1 min, 20.2 ± 6 min, 15.1 ± 7.1 min respectively, p<0.0001]. The results of the VAS for flank pain and dysuria scores, urgency, frequency, hematuria, and suprapubic pain showed a significant difference at all time points of follow‐up, with significantly higher in Groups 1 and 2 compared to Group 3. Further analysis showed that measured outcomes, and analgesia need for Groups 1 and 2 were similar, at all time points except at week 1 and 1 month where Group 2 patient's had less symptoms. Conclusions: DJ‐US placement appear to be unnecessary in procedures considered uncomplicated by operating urologists at the time of surgery. The advantages of DJ‐US with extraction string over DJ‐US only include earlier and easy removal with earlier relief of symptoms, and less analgesia requirements.
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Compliance with preventive measures before and during home quarantine among a Tunisian cohort of COVID-19 patients
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Introduction: Until now, there is no specific treatment to beat the COVID‐19 disease. Regarding the scarcity of vaccines, compliance with collective and individual preventive measures remain the most important weapon against this new disease in developed countries. Objectives: To assess compliance with collective and individual preventive measures among COVID‐19 patients before and during home quarantine in the governorate of Sousse. Methods: A prospective longitudinal study of three months was led among a cohort of 375 patients with COVID‐19 isolated at home. Participants were randomly selected from the new declared cases in the governorate of Sousse during November 2020. Data were collected using a pre‐established and pre‐tested questionnaire administered during phone calls interviews with trained medical doctors. The frequency of the compliance with hygiene measures was evaluated using a five item scale with the following possible responses: (“do not remember”; “never”;“sometimes”; “often” and “all the time”). Results: A total of 375 participants were included. The median age of participants was 40.0 (IQR: 29.75‐54.25) years. Females represented 60% of them. Among participants, 359 (95.7%) consider that social distancing is an efficient collective preventive action. Before the COVID‐19 infection episode, this measure was not easy to respect for 121 (32.3%) participants. Besides, compliance all the time with mask wearing, coughing into the elbow and hand hygiene were reported by 49.1%, 41.9% and 58.9% of participants respectively. Otherwise, during the confinement, 95 (25.4%) participants declared not respecting the quarantine and 111 (29.6%) participants transmitted the infection to their family members. Conclusion: The current national awareness compaign should be reinforced in Tunisia in order to enhance compliance with collective and individual preventive measures. Use of social media, involving leaders and enforcing the law may increase people's adherence to hygiene rules.
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Pembrolizumab (pembro) plus lenvatinib (len) for first-line treatment of patients (pts) with advanced melanoma: phase III LEAP-003 study
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Background: Pembro, a PD‐1 inhibitor, has shown effective antitumor activity, durable responses, and survival benefit in pts with advanced melanoma. Len‐a potent inhibitor of VEGF receptors 1‐3, FGF receptors 1‐4, PDGF receptor a, RET, and KIT‐ plus a PD‐1 inhibitor showed superior antitumor efficacy to either agent alone in a murine tumor model. Len +pembro showed antitumor activity and was well tolerated in pts with advanced melanoma in the phase Ib/II KEYNOTE‐146 trial. LEAP‐003 will compare the efficacy and safety of pembro6len in advanced melanoma (NCT03820986). Trial design: Eligibility criteria include ≥18 y, histologically/cytologically confirmed unresectable untreated stage III‐IV melanoma, documented BRAFV600 status, ECOG performance status 0/1, toxicity resolution from most recent therapy, and provision of baseline tumor sample. Prior first‐line standard of care targeted therapy allowed only if pt has BRAFV600‐mutant disease. Prior targeted therapy or immunotherapy (as adjuvant/ neoadjuvant) allowed if relapse did not occur during treatment or≤6mo after discontinuation. Pts will be randomized 1:1 to pembro 200 mg every 3 weeks (Q3W) IV plus len 20 mg or placebo QD PO. Randomization will be stratified by BRAF status (mutant/WT), prior adjuvant therapy (PD‐1 inhibitor, yes/no), geographic region (China, yes/no). Pembro will continue for up to °2 y; len or placebo may continue beyond 2 y in cases of clinical benefit, until progression, unacceptable toxicity, or investigator/ pt decision. Response will be assessed per RECIST v1.1 Q9W until wk 54, Q12W until wk 102, and Q24Wthereafter. Pts with a CR can discontinue treatment after ≥24 wk of pembro and≥2 pembro doses after initial CR. Eligible pts can continue treatment beyond initial RECIST‐defined PD. AEs will be assessed for ≤90 d and graded per NCI CTCAE v4.0. Survival follow‐up will be Q12W. Primary end points are PFS by blinded independent central review (BICR) per modified RECIST v1.1 (max target lesions: 10; 5 per organ) and OS. Secondary end points are ORR and DOR (by BICR per modified RECIST v1.1), safety, and pt‐reported health outcomes. Exploratory biomarker and PK analyses of len plus pembro are planned.
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The Effects of Emotional Intelligence Trainings in Methamphetamine Users under Methadone Maintenance Treatments in Qazvin
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Introduction: Considering that substance users are characterized by lower emotional intelligence than other individuals in a society, this study is conducted aimed at determining the effectiveness of trainings on the emotional intelligence of methamphetamine users who receive methadone maintenance treatments. Materials and Methods: This study was conducted through a randomized clinical trial that included the pretest‐posttest control group design. In this regard, 70 methamphetamine users who received methadone maintenance treatments in drops in a Center (DIC, Qazvin, Iran) and scored higher than 80 in the Wechsler intelligence scale were selected. The users were divided randomly into an intervention group and a control group. The two groups took the Bar‐On emotional quotient inventory test. The intervention group attended 4 sessions of emotional intelligence training that took 90 minutes per week. In contrast, the control group did not undergo any intervention. Three months after the last training session, the Bar‐On emotional quotient inventory was repeated for the members of the two groups. Results: The program for offering trainings in emotional intelligence could comparatively increase the emotional intelligence score of the intervention group by a significant manner (P=0.03). However, the program did not contribute to the reduction of the methamphetamine use (P=0.13). Conclusion: Offering trainings in emotional intelligence to methamphetamine users could increase their emotional intelligence, but further studies and more effective methods will be required to reduce the methamphetamine use.
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Heterogeneity of neuroendocrine differentiation in prostate adenocarcinoma: a study on whole-mount radical prostatectomy specimens
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Background: Neuroendocrine differentiation (NED) has been recognized in prostatic adenocarcinomas, in addition to small cell neuroendocrine carcinomas and carcinoid tumors of the prostate. NED has been shown to increase in high‐grade and high‐stage prostate cancers. However, the prognostic value of NED in prostate adenocarcinoma is not well understood due to conflicting results in reported studies. Genomic and transcriptomic studies have suggested that there is intra‐tumor heterogeneity of neuroendocrine differentiation in prostatic adenocarcinoma. We hypothesize that the heterogeneous nature of NED may contribute to the difficulty in predicting outcomes in morphologically similar prostate cancer specimens. Design: Thirty‐six radical prostatectomy cases with a diagnosis of prostatic adenocarcinoma were chosen from our archival specimens, including 18 patients who developed recurrent cancer after curative surgery, and 18 patients whose cancers did not recur during matched follow up times. NED was evaluated by performing immunohistochemistry (IHC) for Chromogranin A (CgA). 10 cancer areas are randomly selected on each whole mount section, and the CgA IHC staining intensity in these areas was graded as 0‐5. Results: Significant intra‐tumoral heterogeneity of CgA staining intensity was observed, as illustrated in Figure 1A. The cumulative CgA scores from 10 areas were higher in specimens from patients whose cancers relapsed, as compared with specimens from patients whose cancers did not recur. Mean cumulative CgA score is 18.72 ± 2.78 in the relapsed group and 8.28 ± 1.44 in the remission group. (Figure 1B and C) Conclusions: This study reveals that intra‐tumor heterogeneity of NED exists in prostate adenocarcinoma and influences the precise evaluation of NED in clinical samples. Though the data is not conclusive, we do observe a lower level of NED in patients with remission compared to patients with relapsed cancer by thorough evaluation of NED in prostate whole mount sections. This study potentially provides guidance to clinical usage of NED in prostate adenocarcinoma. (Figure Presented).
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PUREAIR protocol: randomized controlled trial of intensive pulmonary rehabilitation versus standard care in patients undergoing surgical resection for lung cancer
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Background: Non‐small cell lung cancer is the most common type of lung cancer. Surgery is proven to be the most effective treatment in early stages, despite its potential impact on quality of life. Pulmonary rehabilitation, either before or after surgery, is associated with reduced morbidity related symptoms and improved exercise capacity, lung function and quality of life. Methods: We describe the study protocol for the open‐label randomized controlled trial we are conducting on patients affected by primary lung cancer (stages I‐II) eligible for surgical treatment. The control group receives standard care consisting in one educational session before surgery and early inpatient postoperative physiotherapy. The treatment group receives, in addition to standard care, intensive rehabilitation involving 14 preoperative sessions (6 outpatient and 8 home‐based) and 39 postoperative sessions (15 outpatient and 24 home‐based) with aerobic, resistance and respiratory training, as well as scar massage and group bodyweight exercise training. Assessments are performed at baseline, the day before surgery and one month and six months after surgery. The main outcome is the long‐term exercise capacity measured with the Six‐Minute Walk Test; short‐term exercise capacity, lung function, postoperative morbidity, length of hospital stay, quality of life (Short Form 12), mood disturbances (Hospital Anxiety and Depression Scale) and pain (Numeric Rating Scale) are also recorded and analysed. Patient compliance and treatment‐related side effects are also collected. Statistical analyses will be performed according to the intention‐to‐treat approach. T‐test for independent samples will be used for continuous variables after assessment of normality of distribution. Chi‐square test will be used for categorical variables. Expecting a 10% dropout rate, assuming alpha of 5% and power of 80%, we planned to enrol 140 patients to demonstrate a statistically significant difference of 25m at Six‐Minute Walk Test. Discussion: Pulmonary Resection and Intensive Rehabilitation study (PuReAIR) will contribute significantly in investigating the effects of perioperative rehabilitation on exercise capacity, symptoms, lung function and long‐term outcomes in surgically treated lung cancer patients. This study protocol will facilitate interpretation of future results and wide application of evidence‐based practice. Trial registration: ClinicalTrials.gov Registry n. NCT02405273[31.03.2015]. Copyright © 2017 The Author(s).
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A comprehensive education program for carers of persons with dementia: a randomized crossover trial
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Background: In a preliminary study, carers occasionally showed either depression or positive emotions in daily caregiving [1] and their burdens may increase continuously as dementia progresses [1]. However, a comprehensive education program (CEP) can help carers by enabling an objectively self‐evaluation of t stress and caregiving environments and coping with dementia. A CEP was designed to enhance carer coping skills to handle progressive dementia. It comprises medical, care‐related, psychological, and social welfare domains, plus interactive exercises. A controlled crossover trial prioritized ethical considerations and benefit to all participants. CEP efficacy on carers was verified. Methods: In a controlled crossover trial, 54 carers were allocated randomly to CEP group (intervention group) and self‐study group (control group) for the first trial period. Each group had 27 participants. After a one‐month carryover period, participants in an intervention group were switched to the control group and vice versa for the second trial period. We measured dementia symptoms, caregiving stressors, care coping skills, cognitive caregiving appraisal, depression scale, and burnout at the beginning and the end of each trial period. Results: Forty‐one carers in the intervention condition showed positive behavioral changes (less depression and burnout, and better care coping skills and caregiving appraisal). Regarding coping strategy, “having opportunities away from caregiving”, “use of informal support” and “caregiving fulfillment” increased in the CEP group, but decreased in the self‐study group, with significant differences of p=0.048, p=0.049 and p=0.047, respectively. Conclusions: CEP may help carers improve caregiving environments, enhance awareness of self‐emotion by education in better coping skills, and enabling the share of experiences with other carers.
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Decreased glucagon levels and decreased insulin secretion after sitagliptin versus mitiglinide administration with similar glycemic levels following an oral glucose load: a randomized crossover pharmaceutical mechanistic study
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Aims: Both sitagliptin (SIT) and mitiglinide (MIT) can lower postprandial hyperglycemia. The purpose of this study was to examine differences in insulin and glucagon secretion after SIT or MIT administration when similar levels of plasma glucose (PG) were achieved for both agents following an oral glucose load. Patients and methods: We directly compared the effects of these two agents in 16 type‐2 diabetic patients (M/F = 10/6, age 66 ± 3 years old, HbA1c 6.6 ± 0.5 %). Patients received SIT (50 mg qd for 1 week and 100 mg qd for an additional week) or MIT (10 mg tid for 2 weeks). After 2 weeks, patients crossed over to the other treatment. 75‐g oral glucose tolerance tests were conducted before the study and after interventions. Results: The area under the curve (AUC) up to 180 min for the PG response was similar for both agents. While basal insulin secretion rates (ISR) were similar, incremental AUC of ISR was significantly lower in the SIT treatment (522 ± 108 vs 702 ± 288 pmol/min min, p < 0.01), although the difference between the SIT and MIT treatments in the Matsuda index—which reflects insulin sensitivity—remained nonsignificant. Glucose‐stimulated insulin secretion was similarly increased by the MIT and SIT treatments. Suppression of the AUC for glucagon was observed in the SIT treatment, while MIT treatment failed to suppress the glucagon concentration (−432 ± 2322 vs MIT 1116 ± 2520 pg/ml min, p < 0.05). The basal proinsulin/insulin ratio was lower in the SIT treatment (0.23 ± 0.04 vs MIT 0.26 ± 0.36, p < 0.05). Conclusions: Although either SIT or MIT can be employed to reduce postprandial hyperglycemia, SIT induces changes in hormonal profiles that are more favorable to islet functions than MIT does.
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The preventive effect of methotrexate on uveitis onset in JIA depends on uveitis risk factors
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Background/Purpose: Uveitis is the most common extra‐articular manifestation of juvenile idiopathic arthritis (JIA), often entirely asymptomatic but could be sight‐threatening. The main predictors of uveitis in JIA are oligoarticular (OA) subtype, ANA‐positivity and younger age at the JIA onset. Methotrexate (MTX) has been able to decrease the incidence of uveitis in JIA up to 2 times [1]. Objectives:To evaluate the possibility of MTX to prevent the onset of uveitis in different JIA subgroups according to the main uveitis risk factors. Methods: The clinical charts of all consecutive patients who had received a stable management for at least 2 years with or without MTX were reviewed. Patients who were given systemic medications other than MTX (except NSAID) were excluded. Patients with systemic arthritis, rheumatoid factor‐positive arthritis, or enthesitis‐related arthritis were also excluded. In each patient, the al least 2‐year follow‐up period after first visit was examined to establish whether uveitis had occurred. MTX was administered in the subcutaneous injections in the dosage 15 mg/m<sup>2</sup>/week. Results: A total of 281 patients with a median disease duration of 3.8 year were included. One hundred and ninety one patients (68%) were treated with MTX compare to 33.9% in previous study [1]. During the at least 2‐year follow‐up, 64 patients (22.8%) developed uveitis, a median of 1.6 year after the disease onset. The frequency of uveitis was lower in MTX‐treated than in MTX‐untreated patients (11.5% vs 46.7%, respectively, OR=6.7 (95%CI:3.7‐12.3), p= 0.0000001). In previous study the frequency of uveitis was 10.5 in MTX‐treated vs 20.2 in MTX‐untreated patients [1]. Survival analysis confirmed that patients treated with MTX had a lower probability of developing uveitis (HR=4.35, p=0.000001). The results of preventive effect of MTX in different JIA subgroups, according to the main uveitis risk factors are shown in the table 1. Conclusion: Conclusions:MTX therapy may differently prevent the onset of uveitis in children with JIA depends on uveitis risk factors. Further randomized controlled trial required to confirmation our results. (Table Presented).
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Assessment of renal toxicity in perampaneltreated subjects: pooled results from partial-onset seizure phase III clinical studies
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Objective: The objective is to report effects of perampanel, which is approved for adjunctive treatment of partial seizures, on renal laboratory parameters and effect of renal impairment on perampanel clearance. Methods: Phase III double‐blind studies included patients with refractory partial seizures, aged ≥12 years and receiving 1‐3 concomitant antiepileptic drugs (AEDs). Following 6‐week baseline, patients were randomized to 19 weeks of once‐daily treatment (6‐week titration/13‐week maintenance) with placebo or perampanel (2, 4, 8, or 12 mg). Renal laboratory parameters, measured at baseline and end‐of‐treatment, included blood urea nitrogen (BUN) and creatinine. Results were summarized through descriptive statistics, shift tables, and treatment‐emergent markedly abnormal values (increased National Cancer Institute grade from baseline and grade ≥2). Adverse events related to renal pa‐rameters were recorded. Population pharmacokinetic model using Phase III data evaluated the effect of renal impairment on perampanel clearance; the studies excluded patients with severe renal impairment and included only patients with normal and mildly to moderately impaired renal function. Results: Renal laboratory mean values (BUN, creatinine) were within normal ranges at baseline and end‐oftreatment for perampanel (n = 1,038) and placebo (n = 442) treated patients. Mean changes from baseline to end‐oftreatment were small, with no notable differences between treatment groups, no dose‐related trends, and no shifts of clinical concern. Three patients reported markedly abnormal high values for creatinine (n = 1, perampanel 2 mg; n = 1, perampanel 12 mg [resulted in discontinuation]; n = 1, placebo). Adverse events related to renal parameters occurred in 1.8% perampanel versus 1.1% placebo. In the pharmacokinetic model, perampanel median clearance was 27% lower in patients with mild renal impairment (creatinine clearance 50‐80 mL/min) compared with patients with normal renal function (creatinine clearance >80 mL/min). There was overlap in perampanel plasma concentration between mildly impaired and normal renal function groups. Conclusion: Perampanel 2, 4, 8, and 12 mg demonstrated no clinically important effects on renal function parameters, indicating low potential for renal toxicity. Considering the perampanel plasma concentration between patients with mildly impaired and normal renal function, no dosage adjustments are recommended. Support: Eisai Inc.
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Timing of influenza vaccination relative to maintenance infliximab infusion in inflammatory bowel disease patients does not impact immune response or safety of vaccine
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Background & Aims: In inflammatory bowel disease (IBD), immunosuppressive therapies such as infliximab (IFX) may suppress immune response to vaccines. The role of vaccine timing on immune response in IBD patients on IFX is unknown. The study aims were to evaluate immune responses and safety to the influenza vaccine in IBD patients on maintenance IFX. Methods: In this prospective, open‐label study, 137 adults and children with IBD (N= 115 Crohn's disease [CD], N=21 ulcerative colitis [UC], N=1 IBD‐unclassified) on maintenance IFX were randomly allocated to receive the influenza vaccine around time of IFX (N= 69) or midway between IFX infusions (N=68). Serum was collected for pre and post‐vaccine antibody titers (hemagglutination inhibition assay). Subjects were administered the 2012/ 2013 inactivated Fluviral® (GlaxoSmithKline, Canada) or Agriflu®, (Novartis, Canada) vaccine consisting of A/California/7/2009 (H1N1)‐pdm09‐like virus, A/Victoria/361/2011 (H3N2)‐like virus, and B/Wisconsin/1/2010‐like virus (B Yamagata lineage). The primary outcome was serologic protection (post‐vaccine titer ≥1:40) and the secondary outcome was immunogenic response (fourfold or greater increase between pre and post‐vaccine titers). Results are available for H1N1 and H3N2. Disease activity was measured by the Harvey Bradshaw Index (CD, clinically significant increase >3) and the Pediatric Ulcerative Colitis Activity Index (UC, clinically significant increase >20). Serum IL‐1 beta, IL‐6, IL‐8 and IFNgamma were measured by ELISA in a subset of subjects. Results: The proportion of subjects with serologic protection did not differ between subjects vaccinated around time of IFX compared to those vaccinated midway (H1N1: 67% vs 66%, respectively, P=1.0; H3N2 43% vs 49%, respectively, P=0.6). The proportion of subjects who mounted an immunogenic response also did not differ between subjects vaccinated around time of IFX compared to those vaccinated midway (H1N1: 28% vs 37%, respectively, P=0.3; H3N2 28% vs 23%, respectively, P=0.7). Adjustment for gender, age, diagnosis, past influenza vaccine history, concomitant immunosuppressant, and IFX dose per kilogram, frequency, and duration did not alter the lack of association between vaccine timing and immune responses. In each group, 50% had an adverse event; however, the majority were known local side effects of vaccine injection. No subject had a serious adverse event nor required additional medical attention. Overall, 6% had a clinically significant increase in disease activity; this did not differ between groups. Subjects who mounted serologic protection to H3N2 had significantly higher serum IL1beta and IL6 levels compared to those without serologic protection. Conclusions: For IBD patients on maintenance IFX, influenza vaccine timing relative to IFX does not impact immune response and the influenza vaccine is well‐tolerated.
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Comparison of the underwater treadmill, land-based treadmill, and exercise cycle on patient reported symptoms of knee osteoarthritis
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Purpose: To compare the effect of exercise modalities (underwater treadmill, land treadmill, and upright cycling) on patient reported symptoms of knee OA. Methods and Study Design: Subjects with knee pain and radiographic knee OA were randomized and prospectively assigned into 1 of 3 exercise groups: underwater treadmill (N = 20), land treadmill (N = 21), or upright cycle (N = 20). Subjects began an exercise progression over 3 weeks to achieve 30 minutes of moderate aerobic exercise (rating of perceived exertion 4‐6), followed by 40‐minute sessions, 3 days per week for 5 weeks. WOMAC, KOOS and SF 12 Health Surveys were completed at baseline and weekly. An intent‐to‐treat paradigm was utilized with pairwise comparisons of 3 groups via ANOVA and a Bonferroni correction to significance level (0.05 over 3 = 0.01667). Results: All groups improved WOMAC scores with no statistically significant differences between exercise groups. Baseline WOMAC and change in score (95% CI) at completion of exercise program was 74.8 to ‐46.4 (‐65.3 to ‐27.4) for the water treadmill; 60.2 to ‐1.2 (‐0.7 to ‐1.7) for the land treadmill; 71.9 to ‐0.3 (‐0.4 to ‐0.2) for the upright cycle. Using>than 25% improvement in WOMAC as a threshold for clinically significant change, 80% of water treadmill group improved (compared with 60% cycle and 62% land treadmill). Study completion rates for the underwater treadmill (80%) were greater than the land treadmill (60%) or cycle (65%). Conclusions: An 8‐week exercise program improved symptoms in patients with knee OA with no difference based on training device. The underwater treadmill group had the highest percentage of clinically significant change and study completion rates.
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Efficacy and safety of tocilizumab (TCZ) in patients with systemic juvenile idiopathic arthritis (SJIA): tender 52-week data
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Background: sJIA refractory to immunosuppressants including methotrexate and TNF‐α inhibitors can lead to severe disabilities. Excessive IL‐6 production has been implicated in the pathoetiology of sJIA. Aim: To determine the efficacy and safety of TCZ, an IL‐6 receptor inhibitor, in patients (pts) with sJIA treated for 52 weeks (wks) in the ongoing, 3‐part, 5‐year, phase 3 TENDER study. Methods: Pts (N=112) 2‐17 years with active sJIA for ≥6 months were randomized 2:1 to TCZ (8 mg/kg if body weight ≥30 kg; 12 mg/kg if <30 kg) or placebo every 2 wks for 12 wks in part 1; all pts received openlabel (OL) TCZ in part 2. Pts who escaped to OL TCZ in part 1 also entered part 2. Oral corticosteroid (CS) tapering was permitted at wks 6 and 8 in part 1 and in the OL extension in the presence of ACR70 response, ESR <20 mm/h, and absence of fever. Efficacy data included pts who reached wk 52 of TCZ treatment (n=88); safety data considered all pts (N=112). Results: Proportions of TCZ pts who achieved JIA ACR30 + absence of fever or JIA ACR70/90 increased to wk 52 (Table). Number of joints with active arthritis or with limitation of movement decreased from 19.8±15.7 and 19.8±15.6, respectively, to 3.0±7.0 and 7.5±11.7 at wk 52 (45% of pts had 0 active joints). CHAQ‐DI score improved from 1.7±0.9 to 0.7±0.8 at wk 52. Physician global assessment VAS and pt/parent global assessment VAS improved from 64.9±22.3 and 58.7±24.4, respectively, to 9.7±12.8 and 12.6±18.5 at wk 52. CS dose decreased from 0.30±0.20 mg/kg/d to 0.06±0.08 at wk 52; 48% discontinued CSs. 33 serious AEs (SAEs) occurred in 25 pts; 12 SAEs were considered related (remotely, possibly, or probably) to TCZ (rate: 0.23/pt year [PY] in part 1, 0.25/PY in part 2). 15 serious infections occurred; 6 (gastroenteritis, varicella, septic arthritis, otitis media, pharyngotonsillitis, upper respiratory tract infection) were considered related to TCZ; all resolved and none led to discontinuation. 12 pts withdrew (4, AEs; 4, insufficient response). One pt died of a suspected tension pneumothorax considered unrelated to treatment. Conclusions: TENDER 1‐year results demonstrate that TCZ is highly effective and generally well tolerated in pts with sJIA.
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Comparison of meperidine alone with meperidine plus dexmedetomidine for postoperative patient-controlled analgesia
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Objectives: To investigate if the addition of dexmedetomidine to meperidine in a patient‐controlled analgesia (PCA) device would reduce postoperative meperidine consumption when compared with meperidine alone. Methods: Forty patients scheduled for elective abdominal surgery under general anesthesia in Suleyman Demirel University Medical School, Isparta, Turkey between February and September 2006, were randomly allocated into 2 groups. Group I: meperidine 0.25 mg kg‐1 intravenous bolus and dexmedetomidine 0.5 mcg kg ‐1 in 50 ml of saline solution infusion before the end of surgery. Group II: meperidine 0.25 mg kg‐1 intravenous bolus and 50 ml of saline solution infusion. In the postanesthesia care unit (PACU) patients in both groups received intravenous meperidine 10 mg with 5‐minutes intervals until the patient's verbal pain score is lower than 2. Patients in both groups received PCA during the 24 hours after surgery (meperidine 5 mg + dexmedetomidine 10 mcg bolus for group I, meperidine 5 mg for group II). The verbal rating score of pain and meperidine requirement is recorded during PACU stay. Meperidine consumption with PCA is recorded until 24 hours postoperatively. Results: Verbal rating score of pain in the PACU was lower in group I than group II (p<0.05). Meperidine consumption was lower in group I than group II during the PACU stay and until 24 hours postoperatively (p<0.01). Conclusion: When compared with meperidine PCA, meperidine‐ dexmedetomidine PCA reduces postoperative meperidine consumption.
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TARGETED SAFETY ANALYSES of GUSELKUMAB: LONG-TERM RESULTS from RANDOMIZED CLINICAL TRIALS in PATIENTS with ACTIVE PSORIATIC ARTHRITIS and MODERATE to SEVERE PSORIASIS
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Background: Guselkumab (GUS) demonstrated efficacy and a favorable safety profile in active PsA in the Phase (Ph) 21 and Ph3 DISCOVER‐1&2 trials2,3 and in moderate‐to‐severe plaque psoriasis (PsO) in the Ph3 VOYAGE‐1&2 trials.4,5 Objectives: To assess long‐term safety of GUS across PsA/PsO trials. Methods: Using pooled safety data through 2 years (yrs) from PsA trials (N=1229; GUS 100 mg every 4/8 weeks [Q4W/Q8W])1‐3 and through 5 yrs from PsO trials (N=1721; GUS 100 mg Q8W),4,5 incidences of serious adverse events (SAEs); gastrointestinal (GI)‐related SAEs and other targeted AEs; including candidiasis, uveitis, and opportunistic infections (OIs) were evaluated. Incidence rates (IRs) were calculated as the number of events per 100 pt‐yrs (PY) of follow‐up with 95% CI. Patients (pts) with an IBD history were not excluded in PsA/PsO trials. Max exposure duration was W100 for PsA trials and W252 for PsO trials. Results: The PsA and PsO populations had comparable mean age and BMI. IRs of SAEs and GI‐related SAEs were generally similar between GUS‐and PBO‐treated pts during PBO‐controlled periods, and between PsA pts receiving GUS Q4W/Q8W for up to 2 yrs and PsO pts receiving GUS Q8W for up to 5 yrs (Table 1). IRs of other targeted AEs of interest were low. OIs did not occur in PsO pts and were infrequent in PsA pts (Table 1). Candidal infections were infrequent and non‐serious. Iridocyclitis was reported in 1 PBO‐and 1 GUS Q8W‐treated PsA pt. No exacerbations or new onset of IBD or active tuberculosis was reported in GUS‐treated PsA/PsO pts. Conclusion: IRs of SAEs; GI‐related SAEs; and AEs of interest including candid‐iasis, uveitis, and OIs were low, or no cases were reported. No new safety concerns were identifed with GUS treatment through 2 yrs and 5 yrs of follow‐up in the pooled PsA and PsO trials, respectively, supporting a durable and favorable GUS safety profile consistent between pts with active PsA and moderate‐to‐severe PsO.
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Addiction potential and its correlates among medical students
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Background: Drug dependency can be seen in all occupations, educational levels, and socioeconomic classes, and it is one of the most prevalent psychiatric disorders worldwide. The purpose of this study was to determine the addiction potential status and its correlates among medical students. Methods: In 2019, a total of 500 students were selected randomly from Shahroud University of Medical Sciences and asked to complete Addiction Potential Scale and Attitude to Addiction Questionnaires. Data were analyzed using ANOVA, Chi‐square, t‐test and Pearson correlation coefficient and linear regression model at the significant level of 0.05. Results: The mean score of addiction potential was 32.7±17.2. In the majority of the students (62.8%), the addiction potential status was low. Most of the students (66.8%) had used no tobacco or addictive substance. There was a significant relationship between addiction potentialwithgender, marital status, student's current place of residence, student's economic status, student's economic activity, along with education and semester (P≤0.05). In the regression model, 6 predictor factors of the knowledge and awareness of drugs, tendency to use drugs, field of study, history of drug use, alcohol and smoking history had significant relationships with potential addiction (P≤0.05). Conclusion: Given the relationship between potential addiction score and drug use tendency and noting that more than one‐third of students had moderate and high drug addiction, more attention to this issue and interventional measures can be effective in reducing the tendency to drug abuse, and control of drug abuse.
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Self-management training in chronic obstructive lung disease improves the quality of life
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OBJECTIVES: Management of chronic obstructive pulmonary disease (COPD) includes interventions such as improving skills in coping with the disease. We aimed to examine the effect of self‐management training on the quality of life and functional parameters in patients with moderate to severe COPD. MATERIALS AND METHODS: Sixty‐one consecutive patients with COPD were recruited in the study prospectively. The patients were randomized into two groups: self‐management training (n=31) and standard care (n=30). Each patient was evaluated by spirometry, COPD assessment test (CAT), St George’s respiratory questionnaire (SGRQ), hospital anxiety and depression scale (HADS), modified Brit‐ish Medical Research Council (mMRC) dyspnea scale, and short form‐36 (SF‐36). A team of physiotherapists, psychologists, pulmonary disease specialists, and dietitians provided self‐management training and biweekly counseling via phone. At the end of three months, both the groups were re‐evaluated using the same assessment parameters. RESULTS: We found no significant difference between the baseline demographic characteristics of the self‐management training and standard care groups. We observed a reduction in CAT (p<0.001), SGRQ impact (p=0.013), activity subscales (p<0.001) and the total scores (p=0.020), and HADS anxiety (p=0.012) and depression (p=0.014) scores in the self‐management training group after the education session. A significant increase in SF‐36 physical function score was also observed (p=0.008). No significant improvement in the functional parameters was observed in either group; however, the change in FEV1 was more pronounced in the self‐management training group than in the control group (p=0.017). The hospital readmissions and 1‐year survival rates were similar for both the groups after receiving education (p>0.05). CONCLUSION: Our results suggest that the self‐management training of the patients with COPD improves the quality of life and reduces the symptoms of depression and anxiety. Therefore, at the least, self‐management training should be done as the first step of pulmonary rehabilitation in patients with COPD who cannot access pulmonary rehabilitation facilities.
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First-line therapy of T-cell lymphoma: allogeneic or autologous transplantation for consolidation-final results of the aatt study
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Background: In patients (pts) with peripheral T‐cell lymphoma (PTCL) results of first‐line therapy remain poor; guidelines recommend consolidation with autologous transplantation (autoSCT) in transplanteligible pts. AATT (Autologous or AllogeneicTransplantation in T‐cell lymphoma) sought to improve first‐line therapy and compared alloSCT with autoSCT. Methods: This was a prospective randomized trial comparing autoSCT with alloSCT in younger pts (18‐60 yrs) with newly diagnosed PTCL who had achieved CR, PR, or SD after 4 courses of CHOEP and 1 course of DHAP. Pts were to receive BEAM followed by autoSCT or myeloablative conditioning (fludarabine, busulfan, cyclophosphamide) followed by alloSCT from a matched related or unrelated donor. Primary endpoint was 3‐year event‐free survival (EFS). The study was stopped prematurely after a pre‐planned interim analysis (JCO 33, 2015, suppl 8507a) Results: 103 pts randomized upfront to autoSCT (n = 54) or alloSCT (n = 49) formed the full analysis set. Median age was 50 years, 63% were male. 36 pts (35%) could not proceed to transplantation mostly due to early progression. Median observation time for EFS was 42 months. 3‐year EFS and overall survival (OS) did not significantly differ between alloSCT and autoSCT (EFS: 43% (95% CI29‐57%) vs. 38% (25‐52%), p = 0.58, OS: 57% (43‐71%) vs. 70% (57‐82%)(p = 0.41). Comparing pts who actually received autoSCT (n = 41) or alloSCT (n = 26) EFS, PFS, and OS also showed no significant difference. No patient relapsed but eight pts (31%) died of treatment‐related mortality (TRM) after alloSCT compared to 13 relapses (36%) but no TRM observed after autoSCT. Comparison of pts with aaIPI 2/3 vs. 0/1 showed significant differences for all endpoints. Conclusions: AlloSCT or autoSCT given to consolidate response in pts with PTCL showed no significant survival differences. While exerting a strong GvL‐effect alloSCT resulted in substantial TRM. For younger pts with PTCL autoSCT remains the preferred consolidation, in particular, because pts relapsing after autoSCT can be successfully salvaged with alloSCT.
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Clinical validation of cell-free circulating tumor DNA to detect therapy resistance and disease progression in metastatic colorectal cancer patients
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Introduction: DNA mutation analysis in individual patients paves the road towards personalized medicine, in which prognosis and therapy prediction are determined based on gene mutations. For example, it is known that RAS mutations are a negative predictor biomarker for response to therapeutic monoclonal antibodies directed against the epithelial growth factor receptor (EGFR) in metastasized colorectal cancer (mCRC) patients. Anti‐EGFR treatment is expensive and 80‐90% of the patients who do not benefit from anti‐EGFR therapy suffer from the negative side‐effects. Therefore, better prediction and monitoring of anti‐EGFR treatment response is necessary. Cell‐free circulating tumor DNA (ctDNA) derived from blood plasma is expected to improve stratification by early detection of therapy resistance and disease progression. Aim: The general aim of this study is to advance towards clinical implementation of ctDNA‐based tests as molecular biomarkers to improve disease management of mCRC patients. In particular, we investigate the added value of liquid biopsy mutation analysis for (1) assessment of primary and acquired resistance to anti‐EGFR treatment using a gene panel, compared to the conventional tissue analyses, and (2) for detection of disease progression, compared to conventional computed tomography (CT) imaging. Methods: CAIRO5 is a multicenter, randomized, phase 3 clinical trial of the Dutch Colorectal Cancer Group and includes patients with initially unresectable, liver‐only mCRC, as confirmed by a central panel of liver surgeons/radiologists. Liquid biopsies are longitudinally collected in cell‐save Streck tubes at baseline and during follow‐up, in parallel with the CT imaging (every 2 to 3 months). In ctDNA, RAS/RAF hotspot mutations are analyzed by droplet digital PCR (ddPCR), while a panel of 33 genes will be analyzed using ultrasensitive next generation sequencing approaches. Results: The nation‐wide multicenter logistics for longitudinal blood sample collection and plasma processing has been established, with participation of more than 55 Dutch hospitals. At present (November 2018), over 350 patients have been included from whom more than 850 blood samples were obtained. Based on tissue analyses, 59% of these patients harbors a RAS/RAF mutation (48% KRAS, 5% NRAS, 6% BRAF). Concordance between tissue biopsy and liquid biopsy was determined in a subset of patients and showed a >90% concordance for KRAS at codons 12, 13 or 61. In addition, radiologic evaluations of the CT images are collected and the lead time for recurrence will be compared with ctDNA analysis. Results of a first selection of patients will be presented. Conclusion: The liquid biopsy ctDNA and clinical data obtained in this study will provide the input for a health technology assessment yielding recommendations for clinical implementation of ctDNA applications.
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Effect of age on efficacy and safety of elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide (E/C/F/TAF) in virologically-suppressed, HIV-1-infected participants aged ≥65 years: pooled analysis of two Phase III trials
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Background: As the HIV population ages, analyzing safety and efficacy data for ARV agents in older adults living with HIV is increasingly important. TAF is a tenofovir prodrug associated with 90% lower tenofovir plasma levels and greater renal and bone safety than tenofovir disoproxil fumarate (TDF). We evaluated the efficacy and safety of E/C/F/TAF in individuals < and ≥65 years of age. Material and methods: In two international, multicenter, Phase III trials, ARV‐experienced participants with HIV RNA <50 copies/mL were randomized 2:1 to receive: (1) E/C/F/TAF for 48 weeks or continued current abacavir/lamivudine (ABC/3TC)‐based regimen for 24 weeks followed by a delayed switch to E/C/F/TAF for another 24 weeks (292 to 1823); or (2) E/C/F/TAF or continued TDF‐based regimen for 48 weeks (292 to 1826, all subjects were ≥60 years). This pooled analysis of the E/C/F/TAF arms evaluated efficacy (HIV‐1 RNA <50 copies/mL, FDA Snapshot analysis) and safety through Week 48 for participants categorized by age (< and ≥65 years). Randomization was not stratified by age. Results: A total of 293 participants were included in this analysis. Of the 74 participants ≥65 years, median age was 69 (range 65 to 80), 81% were male, 89% were White, median CD4 was 608 cells/mm3 compared to <65 years with a median age 51 years (range 25 to 64), 88% male, 85% White and median CD4 651 cells/mm3. Baseline regimens consisted of two NRTIs combined with an NNRTI 60% (175/ 293), INSTI 25% (73/293) or boosted PI 15% (45/293). At Week 48, HIV RNA <50 copies/mL was 89% in each age group. An HIV RNA ≥50 copies/mL was seen in 1 (0.5%) and 0 participants <65 and ≥65, respectively; no participant had virologic failure with resistance. Week 48 CD4 count was not significantly different between age groups. Adverse event (AE) profile was similar between both groups (Table 1). There were no discontinuations of E/C/F/TAF due to renal or bone AEs. Median change from baseline in eGFR was3.0 mL/min in the <65 subgroup compared to1.2 mL/min in the ≥65. Urine albumin: creatinine, urine beta‐2‐microglobulin:creatinine and urine retinol binding protein:creatinine ratios all improved more in the ≥65 than in younger participants. Conclusion: Through Week 48, rates of virologic suppression were high and similar between participants <65 and ≥65 years. AE, medication‐related discontinuation and tolerability were not significantly different between groups. Improved renal biomarkers were noted in those ≥65. The Week 48 efficacy and safety data support the switch to E/C/F/TAF in HIV‐infected, treatment‐experienced, HIV‐1 RNA suppressed people ≥65 years old.
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Characteristics and outcomes of patients with or without a bleeding event: results from the triple antiplatelets for reducing dependency in ischaemic stroke (TARDIS) trial
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Background and Aims: Intensive antiplatelet therapy following acute cerebral ischaemia was associated with increased bleeding in the TARDIS trial of intensive antiplatelet therapy. We compared the characteristics and outcomes of patients with or without bleeding events in the TARDIS trial. Method: TARDIS compared one month of intensive antiplatelet therapy with guideline in patients with acute non‐cardioembolic ischaemic stroke or transient ischaemic attack. Information on bleeding events and functional outcome by day 90 were assessed centrally blinded to treatment assignment. Outcomes were analysed using adjusted ordinal logistic regression and multiple regression. Results: Bleeding event data are available for 3072/3096 (99.2%) patients, of whom 444 (14.5%) suffered a bleed. Compared to the rest, patients with a bleed were more likely to: be female (43.0% vs. 36.0%, p=0.005); have presented with sensory loss (39.4% vs. 33.7%, p=0.019); have a higher pre‐morbid modified Rankin Scale score (>0: 19.8% vs. 15.2%, p=0.014) and have had a qualifying event of ischaemic stroke (73.0% vs. 71.5%, p=0.009). Patients with a bleed were also less likely to have been taking either aspirin (22.5% vs 27.1%, p=0.043) or combined aspirin and dipyridamole (1.4% vs. 3.0%, p=0.049) prior to their qualifying event. By day 90, patients with a bleed were more dependent (mRS, p=0.002), disabled (Barthel Index, p<0.001), cognitively impaired (t‐MMSE, p=0.027) and had a poorer quality of life (EQ‐5DHSUV, p=0.007) and mood (Zung depression scale, p=0.001). Conclusion: Patients with a bleeding event were more dependent at baseline and had a poorer outcome by day 90.
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Postprandial lipid responses after long-term intake of dairy products varying in fatty acid composition
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Background and objectives: Consumption of modified dairy products with a saturated fatty acid (SFA)‐reduced, monounsaturated fatty acid (MUFA)‐enriched content may have beneficial effects on the fasting cholesterol profile but their effects on metabolic perturbations during the postprandial state, a significant contributor to the pathogenesis of atherosclerosis, remain unknown. Specifically, it is important to consider the effects of sequential meals on postprandial metabolism, as this more accurately reflects Western dietary patterns. We investigated whether consumption of fatty acid (FA)‐modified dairy products altered postprandial metabolic responses, when compared to dairy foods with a FA composition typical of retail products (control). Methods: A 12‐week, randomised, crossover, double‐blinded controlled dietary intervention was conducted in fifty‐one adults at moderate CVD risk (RESET study; NCT02089035). Using a food‐exchange model, two iso‐energetic high‐fat (38% total energy (TE)), high‐dairy diets that contained milk, cheese and butter: control (dietary target: 19%TE SFA; 11%TE MUFA) and modified (16%TE SFA; 14%TE MUFA) were implemented. Before and after each intervention period, a sequential two‐meal, high‐fat postprandial investigation was performed. Using mixed models, changes from the baseline study visit in postprandial serum triacylglycerol, glucose, apolipoprotein B (apoB) and insulin responses were reported as incremental area under the curve (iAUC) for 0‐480min postprandially and following breakfast (0‐330min) and lunch meals (330‐480min), that were rich in control or modified dairy products. Results: A differential effect was observed for the apoB responses from 0‐480min and 0‐330min, with attenuations observed in iAUC following the modified diet (P<0.01 and P<0.0001, respectively). No differences were evident between diets for other outcome measures. Conclusions: Chronic consumption of FA‐modified dairy products decreased postprandial apoB responses, suggesting a potentially beneficial acute effect of these foods on TAG‐rich lipoproteins metabolism.
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Comparison of risk scoring systems for patients presenting with upper gastrointestinal bleeding: international multicentre prospective study
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Objective To compare the predictive accuracy and clinical utility of five risk scoring systems in the assessment of patients with upper gastrointestinal bleeding. Design International multicentre prospective study. Setting Six large hospitals in Europe, North America, Asia, and Oceania. Participants 3012 consecutive patients presenting over 12 months with upper gastrointestinal bleeding. Main outcom e measures Comparison of pre‐endoscopy scores (admission Rockall, AIMS65, and Glasgow Blatchford) and post‐endoscopy scores (full Rockall and PNED) for their ability to predict predefined clinical endpoints: a composite endpoint (transfusion, endoscopic treatment, interventional radiology, surgery, or 30 day mortality), endoscopic treatment, 30 day mortality, rebleeding, and length of hospital stay. Optimum score thresholds to identify low risk and high risk patients were determined. Results The Glasgow Blatchford score was best (area under the receiver operating characteristic curve (AUROC) 0.86) at predicting intervention or death compared with the full Rockall score (0.70), PNED score (0.69), admission Rockall score (0.66, and AIMS65 score (0.68) (all P<0.001). A Glasgow Blatchford score of =1 was the optimum threshold to predict survival without intervention (sensitivity 98.6%, specificity 34.6%). The Glasgow Blatchford score was better at predicting endoscopic treatment (AUROC 0.75) than the AIMS65 (0.62) and admission Rockall scores (0.61) (both P<0.001). A Glasgow Blatchford score of =7 was the optimum threshold to predict endoscopic treatment (sensitivity 80%, specificity 57%). The PNED (AUROC 0.77) and AIMS65 scores (0.77) were best at predicting mortality, with both superior to admission Rockall score (0.72) and Glasgow Blatchford score (0.64; P<0.001). Score thresholds of =4 for PNED, =2 for AIMS65, 4 for admission Rockall, and =5 for full Rockall were optimal at predicting death, with sensitivities of 65.8‐78.6% and specificities of 65.0‐65.3%. No score was helpful at predicting rebleeding or length of stay. Conclusions The Glasgow Blatchford score has high accuracy at predicting need for hospital based intervention or death. Scores of =1 appear the optimum threshold for directing patients to outpatient management. AUROCs of scores for the other endpoints are less than 0.80, therefore their clinical utility for these outcomes seems to be limited.
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Insufflation dependent simple and repeatable ring-shaped thread countertraction for safer colorectal endoscopic submucosal dissection: randomized prospective study
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Background/aims: There were several reports demonstrated the countertraction for safer endoscopic dissection (ESD). We developed more simple delivery and ease of use countertraction (see Figure), and conducted a prospective trial. Methods: Forty‐one patients were diagnosed with colorectal lateral spreading tumors (LSTs) over 20 mm. The patients were randomly allocated using the sealed‐envelope method; the conventional ESD group (CE) (n = 20) and the ring‐ shaped thread countertraction ESD group (RE) (n = 21). In both groups, dissection time (DTn) (min) was defined as only dissecting time of submucosal layer which was measured by nurse with stopwatch during ESD. The ellipsoid resected area (An) formula as follows: An (cm2) = π ± Sn/2 ± Ln/2 (π = 3.14) (n = 1‐41) (shorter axis (Sn) and longer axis (Ln)). The dissected area per minute during ESD (DAn) (cm2/min) = An/DTn (n = 1 ∼ 41). The primary outcome was dissected area per second during ESD (cm2/min). The secondary outcomes were the incidence of bleeding, perforation during ESD and 1‐7 days after ESD (approval 47) (Trial: UMIN000020160). Results and Discussion: The DAn in RE group 95% CI was 0.235(0.16‐0.36) (cm2/min) and 0.125(0.1‐0.18) (cm2/min) in CE group, significant difference (P = 0.003). The incidence of pin hole perforations during ESD were observed in 3 patients in CE group, but was not observed in the RE group, significant difference (P = 0.024). There was no significant difference in bleeding during and/or post ESD (P = 0.065). Conclusions: The ring‐shaped thread countertraction depending on insufflation is safety, effective and very simple method. (Figure Presented).
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Role of zinc supplementation in the outcome of repeated acute respiratory infections in Indian children: a randomized double blind placebo-controlled clinical trial
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This study was done to determine the role of zinc supplementation in the outcome of acute respiratory infections in Indian children. This prospective, double blind, randomized placebo‐controlled trial was conducted with children aged 6 months to 5 years having history of recurrent recent respiratory tract infections. After recruitment, they were randomized to receive 10 mg zinc sulfate or placebo once a day orally for 3 months and were followed monthly up‐to next 6 months. Serum zinc concentrations were estimated by colorimetry at the beginning and at the end of 3 months. Zinc supplementation didn’t reduce the frequency or duration of respiratory infections overall, but children with post‐treatment serum zinc concentrations > 70 mg/dl had significant better outcomes. Usefulness of zinc in improving outcome of ARI in children is an unsolved puzzle and more prospective studies correlating serum zinc concentrations periodically with frequency and duration of ARI in larger cohort are warranted.
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The use of ice pack for pain associated with arterial punctures
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Background: Arterial punctures for monitoring respiratory problems are one of the most painful procedures in hospitalized patients. The knowledge regarding non‐pharmacologic methods of pain management, including cold application is limited. Objective: This aim of this study was to determine if the application of ice pack before the procedure would decrease the pain perception of patients during the arterial puncture. Materials and Methods: This experimental study was undertaken among patients admitted to emergency ward in a public educational center affiliated to Ilam University of Medical Sciences, Ilam/Iran. Sixty‐one eligible subjects were randomly assigned to two groups. The treatment group (n=31) received ice pack before arterial puncture, whereas the control group (n=30) received no intervention for pain management. Pain immediately and 5 minute after the arterial puncture were scored on a visual analog scale (VAS) from 0 to 10. Results: The mean of pain score immediately after the arterial puncture were 3.12 (1.68) and 4.6 (1.56) for treatment and control group, respectively (p<0. 001). The mean pain score 5 minute after the punctures were 1.9 (1.51) for treatment group and 2.53 (1.85) for control group. This difference was not statistically significant. The mean of heart rate during the procedure were 75.45 (9.76) beats/min for the treatment subjects and 75.46 (9.36) beats/min for the control group (p>0.05). Patients with previous arterial puncture reported higher pain intensity. Conclusion: Cold pack is a simple, non‐invasive and inexpensive technique for pain management before the arterial puncture. However, there is a need for further research regarding this topic.
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Comparative study of efficacy of silodosin and tamsulosin in patients of lower ureteric calculi in a tertiary care hospital
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Objective: Recent studies have reported excellent result of MET (Medical Expulsive Therapy) with Silodosin for small distal ureteric calculi. This study was planned with an objective to compare the efficacy of Silodosin and Tamsulosin in terms of Stone Expulsion Rate (SER) and Time to Stone Expulsion (TSE). Materials and Method: We have conducted a comparative randomized trial (Study) in 60 patients. These patients were divided into two groups of 30 each. Group I were given Tab. Silodosin 8mg/day for 14 days and Group II were given Tamsulosin 0.4mg/day for 14 days. Follow up was done at weekly intervals for 4 weeks. Data collected was subjected to statistical analysis using Chi square test and student “T” Test. Results: We found that the number of patients who expelled ureteric stones in less time were (83.3%) in Group I and (70.3%) in Group II and was found to be statistically significant (p<0.05). Conclusion: Silodosin is more effective than Tamsulosin in Expulsion of smaller ureteric stones.
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QVA149 once daily is safe and well tolerated in patients with copd: the shine study
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Rationale QVA149 is a novel inhaled once‐daily, dual bronchodilator containing a fixed‐dose combination of the long‐acting β2‐agonist (LABA) indacaterol and the long‐acting muscarinic antagonist (LAMA) glycopyrronium (NVA237), in development for the maintenance treatment of COPD. This study evaluated the safety and tolerability of QVA149 in patients with COPD. Methods This 26‐week, multicenter, randomized, double‐blind, parallel‐group, placebo and active controlled study assessed the safety and tolerability of QVA149 (110/50μg) once daily compared to indacaterol (150μg), glycopyrronium (50μg), placebo (all delivered via the Breezhaler® device) and tiotropium (18μg; delivered via the Handihaler® device), in patients with moderate‐to‐severe COPD. Here we present the results of the safety profile of QVA149 in terms of adverse events (AEs), serious AEs (SAEs), adjudicated cerebro‐cardiovascular (CCVs) serious events and adjudicated deaths. Results Of the 2144 patients randomized, (QVA149 [n=475]; indacaterol [n=477]; glycopyrronium [n=475]; tiotropium [n=483]; placebo [n=234]), 89.1% completed the study. 75.4% were male; mean age: 63.9 years; mean post‐bronchodilator FEV1: 55.2% predicted. QVA149 had the smallest percentage of patients with any AEs (55.1%) compared to indacaterol (61.1%), glycopyrronium (61.3%), tiotropium (57.3%) and placebo (57.8%), with COPD worsening, nasopharyngitis and cough being the most frequent AEs. QVA149 had a total of 4.6% (22 patients) reported SAEs in comparison to 5.5% (26 patients) with indacaterol, 6.1% (29 patients) with glycopyrronium, 4.0% (19 patients) with tiotropium and 5.6% (13 patients) with placebo. There were no reported cases of any adjudicated serious CCV events with QVA149, whereas indacaterol, glycopyrronium, tiotropium and placebo adjudicated serious CCV events were reported in 1.3%, 1.5%, 0.8% and 0.4% of patients, respectively (Table). One adjudicated death was reported on QVA149 (colon cancer), compared to 3 for indacaterol, 2 for glycopyrronium, and 3 for tiotropium. No death was reported in the placebo arm. Conclusion QVA149 once daily was safe and well tolerated in patients with COPD. Treatment with combination of two bronchodilators in a single device did not increase the incidence or intensity of AEs compared to the monotherapies. Overall the AE and SAE profiles of QVA149 were similar to placebo. (Table Presented).
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Linagliptin improves glycaemic control in type 2 diabetes mellitus (T2DM) patients with increased cardiovascular (CV) risk
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Aims: Amongst other well‐established CV risk factors, T2DM duration and patient (pt) age are associated with increased CV risk. Research has shown reduced glycaemic treatment response with increasing disease duration and age. Hence, we determined the response to the DPP‐4 inhibitor linagliptin in pts with different T2DM durations and ages. Four randomised, double‐blind, placebo‐controlled, phase 3 trials examined the safety and efficacy of linagliptin as monotherapy, add‐on to metformin, add‐on to metformin/sulfonylurea (SU), and initial combination with pioglitazone in T2DM pts. Identical endpoints, study duration, linagliptin dosing, and a large cohort size (N = 2604) facilitated subgroup analyses using the pooled dataset. Given the need to evaluate new antidiabetic agents on backgrounds of other medications and Pt comorbidities, we analysed pooled Pt data to evaluate the effect of key Pt characteristics on the safety and efficacy of linagliptin. Methods: The primary efficacy outcome in all 4 studies was mean change from baseline in HbAIC at 24 weeks. The incidence of any adverse events (AEs) was recorded. Pts were categorised according to their T2DM duration (≥ 1,> 1‐5, and >5 years) and age (≤50,51‐64, 65‐74, and ≥75 years). Results: Mean (± SD) age, baseline BMI and HbAIC were 57.2± 10 yrs, 29.0±4.9kg/m2, and 8.2±0.8%, respectively. Pts were predominantly white (60%) and Asian (40%), with an equal gender distribution. T2DM duration was ≤ 1 year in 15% of pts, >1‐5 years in 31%, and >5 years in 55%. Age was ≤50 years in 24%, 51‐64 years in 51 %, 65‐74 years in 21 %, and ≥ 75 years in 3 %. Linagliptin treatment significantly reduced HbAIC in all groups with no significant differences based on T2DM duration and age. Mean change from baseline in HbAIC among pts with T2DM duration of ≤ 1 year was ‐0.77±1.05%, compared to similar reductions of ‐0.64 ± 0.89 % in pts with T2DM duration of >1‐5 years and ‐0.72±0.88% in pts with T2DM duration of >5 years. Mean change from baseline in HbAIC among pts aged ≤50 years was ‐0.60±0.93%, compared to similar reductions of ‐0.73 ± 0.91 % in pts aged 51‐64 years, ‐0.72±0.86% inptsaged 65‐74 years, and ‐0.77±0.96% in pts aged ≥75 years. Overall, the number of pts with serious AEs was low and comparable to placebo. The overall hypoglycaernic event rate with linagliptin was very low as monotherapy (<1.0%), add‐on to metformin (<1.0%), and initial combination with pioglitazone (1.2%). A higher hypoglycaemic event rate with linagliptin occurred in the study that used metformin and SU as background therapy; this was expected due to the combination with SU. Conclusions: Linagliptin treatment provided clinically meaningful HbAC reductions in T2DM pts with increased CV risk, such as long‐standing diabetes and older age with a safety profile comparable to placebo. In light of a previously reported promising CV safety profile, linagliptin can be considered as an attractive treatment alternative for T2DM pts with increased CV risk.
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Tramadol versus methadone for the management of acute opioid withdrawal: an add-on study
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Background: Opioid agonists such as methadone have been used widely in controlling opioid withdrawal symptoms. Tramadol, a partial opioid agonist, also has been prescribed to manage acute and chronic pain. We sought to compare the efficacy of tramadol and methadone in reducing the severity of opioid withdrawal symptoms. Methods: In a double blind clinical trial 70 opioid dependent patients who used daily opium equal to 15 mg methadone randomly were assigned in two groups. In one group, methadone was started at 15 mg/day while in the other group 450 mg/day tramadol was prescribed. Both drugs were tapered in a week and placebo was prescribed in the 2nd week. The severity of withdrawal symptoms were assessed five times by short opioid withdrawal scale (SOWS). Data were analyzed by Repeated Measures Analysis of Variance, Mann‐Whitney U, and Wilcoxon tests. Results: There were statistically significant differences between two groups in the severity of anxiety (P = 0.015), irritability (P = 0.044), palpitation (P = 0.018), agitation (P = 0.037), and dysphoria (P = 0.044) that all were more common in methadone group. Comparison of side effects revealed statistically significant differences in sweating (P = 0.003) and drowsiness (P = 0.019) between two groups that were more frequent in methadone group. Discussion: Tramadol was more efficacious in controlling opioid withdrawal symptoms with lower side effects.
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Meta-analysis of Randomized Controlled Trials in Quantitative Lung Ultrasound for Management of Volume Overload
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Volume overload is a leading risk factor for recurrent cardiovascular events and death in patients with heart failure, particularly those on hemodialysis with a high‐risk cardiovascular profile. Multiple studies have evaluated the effect of a lung ultrasound‐guided volume management strategy on outcomes in this population. While the majority of studies have demonstrated a trend toward decreased recurrent acute care utilization and repeated cardiovascular events, this effect has not been firmly established. We seek to aggregate this data to better understand trends. We performed a meta‐analysis of prospective, randomized, controlled trials with cardiovascular outcomes of a lung‐ultrasound guided volume management strategy versus usual care in patients with heart failure or those with chronic kidney failure on maintenance hemodialysis at high cardiovascular risk in the outpatient setting. 4 studies were included that met criteria represeting 800 patients. 3 studies were in patients with intact kidney function treated with loop diuretics for volume management and 1 study was in patients with chronic kidney failure requiring maintenance hemodialysis with ultrafiltration for volume management. 403 patients were in experimental groups and 397 in controls. A total of 113 events including 65 deaths occurred in the experimental groups and 155 events in the control groups including 74 deaths. Patients randomized to a lung ultrasound guided volume managmenet strategy were less likely to have cardiovascular events odds ratio 0.61 [95% confidence interval 0.45‐0.82]. Deaths were also numerically fewer among in the lung ultrasound group, although this effect was not statistically significant P = 0.40. Patients with heart failure or chronic kidney failure with high cardiovascular risk who were randomized to a lung ultrasound guided volume managmenet strategy had fewer cardiovascular events.
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Updated analyses from the CROWN study of first-line lorlatinib vs crizotinib in Asian patients with ALK-positive non-small cell lung cancer (NSCLC)
Abstract:
Background: Lorlatinib improved progression‐free survival (PFS) and demonstrated intracranial (IC) activity in patients with untreated advanced ALK+ non‐small cell lung cancer (NSCLC) in the phase III CROWN study (NCT03052608) of lorlatinib vs crizotinib. Here, we report updated results in the Asian subgroup from this study after 36 months of follow‐up. Methods: Patients were randomized 1:1 to receive lorlatinib 100 mg once daily or crizotinib 250 mg twice daily, stratified by presence of brain metastases (yes/no) and ethnicity (Asian/non‐Asian). The primary endpoint was PFS by based on blinded independent central review (BICR). Key secondary endpoints included objective response rate (ORR), intracranial ORR (IC ORR), IC time to progression (IC TTP), and safety. Endpoints were analyzed using unstratified analyses in the Asian subgroup. Results: In the Asian subgroup, 120 patients were randomized to lorlatinib (n=59) or crizotinib (n=61) arm. At data cutoff (Sep 20, 2021), median PFS by BICR was not reached with lorlatinib and 11.1 months with crizotinib (HR 0.40; 95% CI, 0.230‐0.710; Table). Both ORR and IC ORR were clinically improved with lorlatinib vs crizotinib. The HR of IC TTP with lorlatinib vs crizotinib was 0.03 (95% CI, 0.004‐0.200). All‐cause grade 3/4 treatment‐emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation were reported in 79.7% and 8.5% of patients with lorlatinib and 61.7% and 13.3% of patients with crizotinib, respectively. No new safety signals emerged. [Formula presented] Conclusions: Efficacy and safety results in the Asian subgroup were consistent with those in the overall population in the CROWN study. Our data support the use of lorlatinib as a first‐line treatment option in Asian patients with ALK+ NSCLC. Clinical trial identification: NCT03052608. Editorial acknowledgement: Editorial and medical writing support was provided by Ravi Subramanian of ClinicalThinking and was funded by Pfizer. Legal entity responsible for the study: Pfizer Inc. Funding: Pfizer Inc. Disclosure: Z. Qing: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, Sanofi. R.A. Soo: Financial Interests, Personal, Advisory Board: Amgen, Astra‐Zeneca, Bayer, BMS, Lily, Merck, Novartis, Pfizer, Roche, Takeda, Yuhan; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Other, Conference sponsorship: Taiho; Financial Interests, Institutional, Research Grant: Astra‐Zeneca, Boehringer Ingelheim. C.H. Chiu: Non‐Financial Interests, Personal, Invited Speaker: Taipei Veterans General Hospital; Non‐Financial Interests, Personal, Advisory Board: Taipei Veterans General Hospital; Non‐Financial Interests, Personal, Principal Investigator: Taipei Veterans General Hospital. H. Hayashi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Bristol Myers Squibb Co. Ltd, AstraZeneca K.K, Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K, Merck Biopharma Co. Ltd, MSD K.K., Novartis Pharmaceuticals K.K, Pfizer, Takeda Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K.; Financial Interests, Personal, Advisory Board: Bristol‐Myers Squibb Co. Ltd, Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K, Shanghai Haihe Biopharm, Pfizer, AstraZeneca K.K; Financial Interests, Institutional, Funding: AstraZeneca K.K., Astellas Pharma Inc., MSD K.K., Ono Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., grants, Pfizer Japan Inc., Bristol Myers Squibb Company, Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., Daiichi; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., and Ono Pharmaceutical Co. Ltd.; Non‐Financial Interests, Principal Investigator: Ono Pharmaceutical Co. Ltd. and Bristol Myers Squibb Co; Non‐Financial Interests, Member: West Japan Oncology Group, Japan Society of Medical Oncology. S. Teraoka: Financial Interests, Personal, Invited Speaker: AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Advisory Board: Pfizer R&D Japan G.K. D. Kim: Financial Interests, Invited Speaker: Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology, Taiwan Lung Cancer Society, Asian Thoracic Oncology Research Group; Other, Writing Engagements: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Chong Keun Dang, Daiichi Sankyo, GSK, Pfizer, MSD, Merck, Novartis, Roche, Takeda, Yuhan; Non‐Financial Interests, Advisory Board: Amgen, AstraZeneca, BMS/Ono Pharmaceuticals, Daiichi Sankyo, GSK, Janssen, Merck, MSD, Pfizer, SK Biopharm, Takeda; Other, Member of the Board of Directors: Asian Thoracic Oncology Research Group, Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology; Financial Interests, Institutional, Research Grant: Alpha Biopharma, Amgen, AstraZeneca/MedImmune, Boehringer Ingelheim, BMS, Bridge BioTherapeutics, Chong Keun Dang, Daiichi Sankyo, GSK, Hanmi, Janssen, Merck, Merus, Mirati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan; Other, Principal Investigator: Chong Keun Dang; Financial Interests, Advisory Role: Scientific advisor for Health insurance review and assessment service, Korea; Other, Travel Support: Amgen, Daiichi Sankyo, International Association for the Study of Lung Cancer, Asian Thoracic Oncology Research Group, Taiwan Lung Cancer Society. H. Zhan: Financial Interests, Personal, Full or part‐time Employment: Pfizer Inc. H. Zhao: Financial Interests, Personal, Full or part‐time Employment: Pfizer Inc. H. Li: Financial Interests, Personal, Full or part‐time Employment: Pfizer Inc. T.S.K. Mok: Financial Interests, Personal, Invited Speaker: AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo, Fishawack Facilitate, InMed Medical Communication, Lunit USA, Inc., Merck Serono, MSD, Roche, MD Health, Medscape/WebMD, PeerVoice, Permanyer SL, Prime Oncology, Research to Practice, Touch Medical Media, Sanofi‐Aventis, Takeda, PER, AstraZeneca, Hutchison Chi‐Med; Financial Interests, Personal, Advisory Board: AbbVie, Acea Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Blueprint Medicines, Berry Oncology, CStone Pharma, Daiichi Sankyo, Fishawack Facilitate, Eisai, Gritstone Oncology, Guardant Health, G1 Therapeutics, Hengrui, Ignyta, IQVIA, Incyte Corporation, Inivata, Janssen, Loxo Oncology, Qiming Dev., Lunit USA, Inc., Merck Serono, MSD, Roche, Mirati Therapeutics, MoreHealth, Novartis, OrigiMed, Puma Tech., Sanofi‐Aventis, Takeda, Virtus Medical, Yuhan, Curio Science; Financial Interests, Personal, Stocks/Shares: Sanomics Ltd., Hutchison Chi‐Med, Biolidics Ltd., Loxo Oncology, OrigiMed Co., Virtus Medical Group, Lunit USA, Inc., Aurora Tele‐Oncology; Financial Interests, Institutional, Funding, For clinical trials performed at CUHK: AstraZeneca, BMS, Merck Serono, MSD, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, XCovery, Takeda, G1 Therapeutics, Clovis Oncology; Non‐Financial Interests, Advisory Role: geneDecode, AstraZeneca; Non‐Financial Interests, Other, Invited Speaker: AstraZeneca; Non‐Financial Interests, Invited Speaker: Aurora Tele‐Oncology, Lunit USA, Inc., Sanomics Ltd.; Non‐Financial Interests, Leadership Role: American Society of Clinical Oncology (ASCO), Asian Thoracic Oncology Research Group (ATORG), Chinese Lung Cancer Research Foundation Limited (CLCRF), Chinese Society of Clinical Oncology (CSCO), Hong Kong Cancer Fund (HKCF), Hong Kong Cancer Therapy Society (HKCTS), St. Stephen’s College & Prep. School (Hong Kong); Non‐Financial Interests, Leadership Role, Term ended on 30 April 2019: International Association for the Study of Lung Cancer (IASLC). Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Takeda; Financial Interests, Invited Speaker: AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi, Yunhan, Eli Lilly; Non‐Financial Interests, Leadership Role: Chinese Thoracic Oncology Group (CTONG); Non‐Financial Interests, Other, WCLC 2020 Conference Chair: IASLC; Non‐Financial Interests, Leadership Role, Past President: Chinese Society of Clinical Oncology (CSCO). All other authors have declared no conflicts of interest.
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ISN World Congress of Nephrology (WCN) Abstracts
Abstract:
The proceedings contains 832 papers. The topics discussed include: POS‐001 Continuous Renal Replacement Therapy In Critical Patients With Acute Kidney Injury;POS‐002 ACUTE KIDNEY INJURY (AKI) IN RURAL WORKERS: SHOULD WE TALK ABOUT AGRICULTURAL NEPHROPATY INSTEAD OF MESOAMERICAN NEPHROPATY?;POS‐003 ACUTE KIDNEY INJURY IN CRITICALLY ILL PATIENTS WITH COVID‐19 EXPERIENCE OF A ICU BOLIVIAN CENTER REFERENCE;POS‐004 HYPOALBUMINEMIA AND ACUTE KIDNEY INJURY IN PATIENTS ADMITTED TO INTENSIVE CARE UNIT;POS‐005 ACUTE KIDNEY INJURY IN CRITICALLY ILL COVID‐19 PATIENTS ADMITTED AT A PRIVATE HOSPITAL;POS‐006 ACUTE KIDNEY INJURY AMONG CHILDREN WITH SICKLE CELL ANEMIA HOSPITALISED WITH VASO‐OCCLUSION IN UGANDA;POS‐007 MAGNITUDE AND ASSOCIATED RISK FACTORS OF NEONATAL ACUTE KIDNEY INJURY IN THE NEONATAL INTENSIVE CARE UNIT OF TIKUR ANBESSA SPECIALIZED HOSPITAL, ADDIS ABABA, ETHOPIA;POS‐008 AN UNUSUAL CASE OF TMA‐ASSOCIATED POLYOMAVIRUS BK NEPHROPATHY IN A NATIVE KIDNEY;POS‐009 PREVALENCE AND ETIOLOGIES OF ACUTE KIDNEY INJURY IN ELDERLY;POS‐010 THE HEART‐KIDNEY CROSS TALK IN CARDIAC INTENSIVE CARE UNIT;POS‐011 THE EFFECT IN RENAL FUNCTION AND VASCULAR DECONGESTION IN TYPE 1 CARDIORENAL SYNDROME TREATED WITH TWO STRATEGIES OF DIURETICS, A RANDOMIZED CLINICAL TRIAL;POS‐012 MINIMAL CHANGE DISEASE IN A PATIENT WITH CHRONIC EOSINOPHILIC PNEUMONIA AND ACUTE KIDNEY INJURY;POS‐013 FACTORS ASSOCIATED WITH ACUTE KIDNEY INJURY IN CRITICALLY ILL PATIENTS WITH COVID‐19;POS‐014 DOXAZOCINE‐INDUCED LUPUS NEPHROPATHY;POS‐015 BIOPSY PROVEN ACUTE TUBULAR NECROSIS: SPECTRUM AND PROGNOSIS;POS‐016 IDENTIFYING KIDNEY DYSFUNCTION IN THE COMMUNITY SETTING: THE ISN KIDNEY CARE NETWORK PROJECT;POS‐017 CAUSES OF ACUTE KIDNEY INJURY IN THE COMMUNITY SETTING: THE ISN KIDNEY CARE NETWORK PROJECT;POS‐018 TREATMENT OF ACUTE KIDNEY INJURY IN THE COMMUNITY SETTING: THE ISN KIDNEY CARE NETWORK PROJECT;POS‐028 OUTCOMES OF INTERMITTENT PERITONEAL DIALYSIS IN PAEDIATRIC POPULATION
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Is facilitated tucking by parents more effective than dextrose water (10%) in reducing full-term neonatal pain during the heel-lancing procedure: a randomized controlled trial
Abstract:
Neonates are exposed to pain as a result of routinely applied painful procedures which in many cases are poorly managed. There are numerous non‐pharmacologic interventions that could help manage procedural pain. There still a lack of evidence supporting the use of several non‐pharmacologic interventions, such as facilitated tucking by parents (FTP) for neonatal pain management. A randomized controlled three‐group experimental design was used to compare the effectiveness of oral dextrose water D10%W vs. FTP among neonates whose ages ranged from 24 to 48 hours. Three phases of (baseline, during, and after) heel stick procedures were videotaped. Pain responses were measured using a behavioral pain scale, as well as physiological pain responses (heart rate, respiratory rate, and oxygen saturation). A total of 135 neonates were included in the study. Both D10W and FTP groups were found to be effective in reducing behavioral scores (P=0.00). And physiological pain scores, including heart rate (P= 0.009), respiratory rate (P=0.01), and oxygen saturation (P=0.002) as compared to control group. However, immediately (20sec) after the procedure, the total pain score was significantly lower in dextrose group compared to the other two groups (m= 2.8, SD= 0.7). D10%W and FTP had pain‐relieving effects as compared to control in neonates who are 38‐40 ± 2 weeks of gestation and are undergoing heel stick procedure. However, an added advantage for D10%W, in these times, is reducing physical contact between neonate and parent during limited access of parent to NICUs units a s a result of COVID 19 transmission.
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A novel formulation of CT-P13 for subcutaneous administration: 30 week results from a part 2 of phase I/III randomized controlled trial in patients with rheumatoid arthritis
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Background: CT‐P13 subcutaneous (SC) formulation showed comparable efficacy and safety with CT‐P13 intravenous (IV) formulation in rheumatoid arthritis (RA)1 and Crohn's disease2 preliminary studies (Part 1). Objectives: The purpose of this study was to demonstrate non‐inferiority (NI) of efficacy and compare safety profiles of CT‐P13 SC to CT‐P13 IV in RA patients over 30 weeks of Part 2. Methods: In this randomized, controlled, double blinded, phase I/III study, RA patients received CT‐P13 IV 3 mg/kg at Weeks 0 and 2 and were randomized at Week 6 to receive CT‐P13 SC 120 mg every 2 weeks or CT‐P13 IV 3 mg/kg every 8 weeks. From Week 30, all patients received CT‐P13 SC 120 mg every 2 weeks. The primary efficacy endpoint, change of DAS28 (C‐reactive protein [CRP]) from baseline to Week 22, was analyzed by using an analysis of covariance (ANCOVA). Non‐inferiority is to be concluded if the lower bound of the 95% CI for the treatment difference in the change of DAS28 (CRP) from baseline to Week 22 is greater than the pre‐specified NI margin of ‐0.6. Results: A total of 362 patients were enrolled, of whom 348 were randomly assigned at Week 6 into 2 treatment arms in a 1:1 ratio (169 and 179 patients in SC 120 mg and IV 3 mg/kg arms, respectively). The mean change of DAS28 (CRP) from baseline to Week 22 was similar between the arms. The lower limit of two‐sided 95% CI (0.03) was greater than the pre‐specified NI margin (‐0.6) which indicated NI of SC 120 mg compared to IV 3 mg/kg (Table 1). Additional efficacy including ACR responses were similar between two treatment arms up to Week 22 with slightly higher response rate trend observed in SC 120 mg arm at Week 30 (Figure 1). The safety profiles which occurred after study drug administration at Week 6 in SC 120 mg arm were generally comparable to IV 3 mg/kg arm. All of injection site reactions were grade 1 or 2 in intensity. Majority of administration‐related reactions (ARRs) were grade 1 or 2 in intensity except 1 patient in IV 3 mg/kg arm who experienced grade 3 ARR and was withdrawn from the study due to this event (Table 2). (Figure Presented) Conclusion: The study demonstrated NI of efficacy for CT‐P13 SC to the CT‐P13 IV. Also, CT‐P13 SC showed similar efficacy and safety profiles to CT‐P13 IV up to Week 30. CT‐P13 SC could provide a favorable benefit to patients with an alternative convenient way of administration.
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Maternal and fetal outcomes of Asian pregnancies after bariatric surgery
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Introduction: Obesity is associated with high risk pregnancies including pregnancy‐induced hypertension (PIH), Pre‐Eclampsia (PE), Gestational Diabetes Mellitus (GDM), Intra uterine growth retardation (IUGR) and Macrosomia. Bariatric Surgery (BS ) is a widely accepted procedure to treat obesity. Aim: To report maternal and fetal outcomes following BS in morbidly obese Asian females. Method: We followed our female patients in their reproductive age who underwent BS like laparoscopic banding, sleeve gastrectomy or gastric bypass at our institute. Between 2010 and 2017, 19 pregnancies in 13 patients were reported. 1 pregnancy was after lap banding, 3 after gastric bypass and 15 after sleeve gastrectomy. Control group comprised of 19 randomly selected obese Asian women who delivered over the same time period. We compared both the groups for maternal and fetal complications. Results: We report fewer maternal and fetal complications. None of the Post BS patient had any GDM or PIH/PE in comparison to control group with 16%, 26% respectively. None of the mothers had any surgical or delivery related complications in both groups. Birth weights of those babies whose mothers underwent BS were lower than those for controls with none weighing more than 3.5kg. Eight babies with IUGR are reported in the BS group. None of the babies had birth defects in both groups. Conclusion: BS improved pregnancy outcomes favoring lower risk of maternal complications like PIH, PE, GDM. Fetal Complications like Macrosomia is higher among obese pregnant women while BS could potentially result in IUGR of fetus.
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