A secondary data analysis of qualitative study of individualized treatment regimen for North Indians living with human immunodeficiency virus-1

The follow-up of fifty-seven patients were conducted after a confirmation genotyping test. The secondary data analysis was done on the data available to observe the correlation between the CD4 counts and viral loads (One of the markers of clinical outcome) of the individual North Indian patients infected with HIV-1 Subtype C. The drug resistance mutations in individual patient were analysed through the drug resistance database, Stanford University, USA. The data of resistance associated with drugs, CD4 counts, viral loads of the individual patient was compiled and statistically analysed for drug resistance pattern profiles using Microsoft Excel 2016 and SPSS Version 22. The normality of data was checked by Shapiro-Wilk test (p<0.05). The study starting and endpoint data on CD4 counts, viral loads and drug resistance patterns associated with multiple first-line ART was available for 24 north Indian patients. The starting and study endpoint data on CD4 counts and drug resistance patterns associated with multiple first- line ART was available for 33 North Indian patients. The study indicative that the recommendation of policy to provide a tailor-made individualized regimen to each patient under AIDS control program.

Effect of Psychobiotics on Psychometric Tests and Inflammatory Markers in Major Depressive Disorder: Meta-Analysis of Randomized Controlled Trials with Meta-Regression

Probiotics were shown to act positively on gut–brain axis signaling. We aimed to assess the effect of the administration of a new class of probiotics—psychobiotics—using data from individual psychometric scales, markers of the immune system and neuroactive metabolites. Medical databases were searched from database inception until 22 April 2021 for randomized clinical trials in clinically proven Major Depressive Disorder (MDD) patients treated with either probiotics or placebo reporting any psychometric score (PROSPERO registration number: CRD42021253024). Ten studies with 705 randomized participants and 603 analyzed were included. The mean age of individuals was 38.43 ± 12.1 years, predominantly women (n = 461, 76.45). The mean study duration was 48.8 ± 12.3 (range = 28–62) days. The dosage ranged between 1 × 109 to 2 × 1010 colony forming units (CFU)/day. We found that probiotics might alleviate symptoms of MDD; endpoint data (pooled scores): SMD = −0.292, 95%CI = −0.577 to −0.007, p < 0.044; change scores (BDI): SMD = −0.482, 95%CI = −0.854 to –0.109, p < 0.011; DM = −4.848, 95%CI = −8.559 to −1.137, p < 0.01. The therapy tended to be more effective with time of psychobiotic supplementation (coefficient = −0.12, SE = 0.06, Z = −1.84, p = 0.06) and in men (% of females: coefficient = 0.1, SE = 0.06, Z = 1.78, p = 0.07). Psychobiotics have great potential in the treatment of MDD. However, no specific strain/strains, dosage or duration of treatment can currently be recommended.

Impact of Intraprocedural Pressor Use on Catheter Ablation for Ventricular Tachycardia

Background: Ventricular tachycardia (VT) remains a leading cause of morbidity and sudden death. Improvements in catheter ablation have significantly advanced this option as a treatment method for refractory VT. Despite advances, use and impact of inotrope and vasodepressor medicines as part of intraprodcedural management during VT ablation have been understudied. Methods: We conducted a exploratory, retrospective analysis of consecutive patients undergoing VT ablation. Patient, intra and peri-procedural data, focusing on pressor use and hemodynamics through ablation, and procedural endpoint data were collected. Results: From 2014-2017, 149 patients underwent VT ablation of which 67% exhibited cardiomyopathy (53% ischemic). Most procedures (71%) were conducted under general anesthesia. In those with cardiomyopathy, steady-state use of dobutamine and dopamine was more common though substantial use of phenylephrine was noted. In adjusted analyses, (1) dobutamine was associated with increased procedure time (402.5±18.8 vs 347.2±14.0 min, p = 0.03), (2) dopamine was associated with increased number of distinct VTs (2.8 vs. 2.2, p<0.001) while both dopamine and dobutamined resulted in increased intra-procedural cardioversions (1.3 vs. 0.6, p<0.001 and 1.34 vs. 0.66, p=0.001, respectively) and (3) dobutamine dose exhibited a linear correlation with post-ablation length of stay. Conclusions: In this exploratory work, we sought to understand effects of hemodynamic drug use on short-term, procedural outcomes of VT ablation. Salient findings include: (1) arrhythmogenic nature of inotropes resulting in an increase in intraprocedural cardioversions, (2) greater propensity for induction of non-clinical VTs with use of intraprocedural dopamine and (3) substantial use of phenylephrine in those with underlying cardiomyopathy.

Addressing Systemic Causes of Physician Burnout: Improving Joy in Work

Healthcare provider burnout has been shown to result in lower staff engagement levels and reduced work satisfaction, which correlates with lower patient experience scores, lower productivity, and increased workplace accidents. By making work engaging and restoring joy, healthcare leadership can reframe barriers to reduce burnout. This paper presents the results of an organizational system-wide intervention designed to rethink the approach to lowering burnout by improving joy in work to address provider well-being at the Guthrie healthcare system. System wide and targeted area strategies were used to create change over a 1-year interval of intervention. After endpoint data was collected, eight power items had positive change for this healthcare system. Scheduling and recognition emerged as system wide areas in need of reform.

Which psychotherapy is effective in panic disorder? And which delivery formats are supported by the evidence? Study protocol for two systematic reviews and network meta-analyses

IntroductionPanic disorder is among the most prevalent anxiety diseases. Although psychotherapy is recommended as first-line treatment for panic disorder, little is known about the relative efficacy of different types of psychotherapies. Moreover, there is little evidence concerning the effectiveness of different formats of major psychotherapeutic types, such as cognitive–behavioural therapy (CBT). In this protocol, we present an overarching project consisting of two systematic reviews and network meta-analyses (NMA) to shed light on which psychotherapy (NMA-1), and specifically, which CBT delivery format (NMA-2) should be considered most effective for adults suffering from panic disorder with or without agoraphobia.Methods and analysesStarting from a common pool of data, we will conduct two systematic reviews and NMA of randomised controlled trials examining panic disorder. A comprehensive search will be performed in electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Register of Controlled Trials—CENTRAL from database inception to 1 January 2021 to identify relevant studies. A systematic approach to searching, screening, reviewing and data extraction will be applied. Titles, abstract and—whenever necessary—full texts will be examined independently by at least two reviewers. The quality of the included studies will be assessed using the revised Cochrane risk of bias tool V.2. The primary efficacy outcome will be anxiety symptoms at study endpoint. The primary acceptability outcome will be all-cause discontinuation, as measured by the proportion of patients who had discontinued treatment for any reason at endpoint. Data will be pooled using a random-effects model. Pairwise and NMA will be conducted.Ethics and disseminationNo ethical approval is necessary for these two studies, as there will be no collection of primary data. The results will be disseminated through peer-reviewed publications and presentations at national and international conferences and meetings.

Lessons from the CONSCIOUS-1 Study

After years of research on treatment of aneurysmal subarachnoid hemorrhage (aSAH), including randomized clinical trials, few treatments have been shown to be efficacious. Nevertheless, reductions in morbidity and mortality have occurred over the last decades. Reasons for the improved outcomes remain unclear. One randomized clinical trial that has been examined in detail with these questions in mind is Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1). This was a phase-2 trial testing the effect of clazosentan on angiographic vasospasm (aVSP) in patients with aSAH. Clazosentan decreased moderate to severe aVSP. There was no statistically significant effect on the extended Glasgow outcome score (GOS), although the study was not powered for this endpoint. Data from the approximately 400 patients in the study were detailed, rigorously collected and documented and were generously made available to one investigator. Post-hoc analyses were conducted which have expanded our knowledge of the management of aSAH. We review those analyses here.

P1637UK KIDNEY ALLOCATION SCHEME: APPROPRIATE MATCHING BUT RESOURCE IMPLICATIONS

Background and Aims UK NHSBT kidney matching scheme changed in September 2019, aiming to better match graft and patient survival through stratification of donors and recipients into risk quartiles. We present data on two years of transplants aiming to highlight discrepancies between our unit and the model on which the scheme is based, and the potential implications on service provision of its’ introduction. Method We reviewed all deceased donor transplants in our centre in 2015 and 2016. Recipients and donors were re-classified into the risk index quartiles and endpoint data included inpatient days in first year, 1 year eGFR, survival, imaging, and infection episodes. Comparisons were made with NHSBT literature. Results 196 deceased donor transplants were performed. Distribution of D1-4 kidneys to R1-4 recipients in our cohort did not reflect those presented in the allocation scheme models, with our population skewed toward higher risk R4 category (73.4%), including 55 D4R4 (83% of D4 kidneys), see Figure 1. 2.0% had an age difference between donor and recipient of &gt;25years, and 12.8% 15-25 years, compared with the NHSBT proposed targets of 8% and 20% respectively. Within the R4 group, recipients receiving a D4 graft were associated with a higher rate of DGF (41.7%, vs 23.2% D1-D3 grafts, p=0.009), longer index admission (median 11 days vs 8 days, p=0.038) and more readmissions within the first post-operative year (median 18 vs 11 days, p = 0.005) – Figure 2. D4 grafts demonstrated lower mean eGFR at one year (35.7, vs. 54.8 ml/min, p&lt;0.001), Figure 3. R4 recipients experienced graft loss more frequently (HR 3.4 vs R1-3 (95%CI 0.8-13.9, p=0.12). One-year survival in R4 cohort was 97.8% (four deaths), and 93.8% at 4 years; R1-3 cohort had 100% survival to 4 years; there was no significant impact on R4 patient survival with D4 kidneys vs. D1-D3. Day ward attendances, bacteraemia, and CT imaging events did not differ by R or D category; D4 was associated with higher rates of transplant ultrasound (5.6 vs R1-3 4.25, p=0.009), and R4 with higher rates of urinary tract infection (3.6 vs R1-3 1.5, p=0.03). Conclusion Firstly, our transplant population is weighted to higher risk R4 recipients; secondly, intended principals of the allocation scheme are already largely being observed. Thirdly, our data does suggest that increasing R4D4 transplants will have a significant impact on transplant centres, with resource burden primarily within the first year. But despite poorer graft function, patient survival appears to be equivalent and improved matching may in the longer term reduce need for re-implantation as the scheme intends.

A phase III randomized, double-blind placebo controlled study of armodafinil (Nuvigil) to reduce cancer-related fatigue in patients with high-grade glioma (Alliance A221101).

12007 Background: Up to 96% of patients with high grade glioma (HGG) report moderate to severe fatigue. Armodafinil, the R-enantiomer of modafinil, is a psychostimulant with low potential for abuse that has shown potential for improving severe fatigue in HGG patients. Methods: In this phase III double blinded placebo-controlled study, adults with HGG and moderate to severe fatigue, > 4 weeks after completing radiotherapy, were randomized to receive armodafinil daily (150 mg or 250 mg) or placebo for a total of 8 weeks. The primary outcome was efficacy in treating severe fatigue. Secondary outcomes included evaluation of tolerability, neurocognitive function, and quality of life. Patients were evaluated at baseline, 4 and 8 weeks. Results: A total of 328 patients were enrolled between 6/3/13-3/1/19. There were 103 (150 mg arm), 97 (250 mg arm) and 97 (placebo arm) evaluable patients with primary endpoint data available. The median age was 60 years (20-85) with a median Brief Fatigue Inventory (BFI) worst fatigue score of 8 (6-10). 60.3% were male, 80.5% received concomitant chemotherapy, and 39.7% were on corticosteroids. The global fatigue score at end of weeks 4 and 8 were lower than at baseline (p<0.0001) and in the 250 mg arm than placebo (p=0.0356) and was higher for corticosteroid users than non-users (p=0.0002). There was no statistically significant difference for clinically meaningful improvement in BFI usual fatigue score from baseline to end of week 8 between the three arms (p=0.9601). Patients reported an improvement in concentration at week 4 from baseline on the 150 mg arm(P=0.0311). There was no statistically significant difference on neurocognitive tests from baseline to end of week 4 (p>0.05) or week 8 (p>0.05) between arms. More patients reported insomnia on the 250 mg arm (p=0.0083). Conclusions: There is no meaningful benefit of the use of armodafinil to reduce moderate to severe fatigue in patients with HGG. In certain cases there may be benefit of armodafinil 150 mg to aid concentration without the risk of insomnia.Support: UG1CA189823;U10CA180868 (NRG). Clinical trial information: NCT01781468 .

Ixazomib-dexamethasone (Ixa-Dex) vs physician’s choice (PC) in relapsed/refractory (RR) primary systemic AL amyloidosis (AL) patients (pts) by prior proteasome inhibitor (PI) exposure in the phase III TOURMALINE-AL1 trial.

8546 Background: The PI bortezomib is commonly used in first-line therapy of AL, but new therapies are needed that are tolerable in the context of multi-organ dysfunction and that, in RRAL, offer improved outcomes following prior bortezomib. Ixazomib is an oral PI, and in TOURMALINE-AL1, the first phase 3 trial conducted in RRAL, while the first primary endpoint of hematologic overall response rate (ORR) was not met, all clinically relevant time-to-event endpoint data favored Ixa-Dex vs PC (Dispenzieri et al, ASH 2019). Methods: RRAL pts with 1–2 prior therapies were randomized (1:1) to Ixa-Dex (n = 85) or PC (n = 83; Dex plus lenalidomide [n = 47], melphalan [n = 24], cyclophosphamide [n = 10], or thalidomide [n = 2]), stratified by cardiac stage, relapsed vs refractory disease, and prior PI exposure. The primary endpoints were hematologic ORR and 2-yr rate of vital organ deterioration or death. We report subgroup analyses of ORR and outcomes by prior PI exposure. Results: Of the 168 pts enrolled, 90 were PI-naïve and 78 PI-exposed (46 and 39 in the Ixa-Dex arm; 44 and 39 in the PC arm) per stratification; 28 and 27 pts in the Ixa-Dex and PC arms had received bortezomib in their last prior line. Hematologic ORR was 63% vs 50% for Ixa-Dex vs PC (odds ratio [OR] 1.71; 95% confidence interval [CI] 0.74–3.96) in PI-naïve pts, and 41% vs 51% (OR 0.66; 95% CI 0.27–1.62) in PI-exposed pts. For time-to-event outcomes (Table), hazard ratios (HRs) were 0.46–0.85 in favor of Ixa-Dex vs PC in both PI-naïve and PI-exposed pts. Conclusions: Hematologic ORR was higher with Ixa-Dex vs PC in PI-naïve pts but lower in PI-exposed pts (although not statistically significant), and long-term clinically relevant outcomes favored Ixa-Dex in both groups. Based on HRs, the magnitude of benefit appeared similar or greater in PI-naïve vs PI-exposed pts. Clinical trial information: NCT01659658 . [Table: see text]

Breakfast in the Classroom Initiative and Students’ Breakfast Consumption Behaviors: A Group Randomized Trial

Objectives. To identify the effect of a Breakfast in the Classroom (BIC) initiative on the foods and drinks students consume in the morning. Methods. Sixteen public schools in Philadelphia, Pennsylvania, that provide universal breakfast participated in a group randomized trial to examine the effects of BIC with complementary nutrition promotion between 2013 and 2016. Control schools (n = 8) offered breakfast in the cafeteria before school. Baseline data were collected from 1362 students in grades 4 to 6. Endpoint data were collected after 2.5 years. Students self-reported the foods and drinks they consumed in the morning. Results. At endpoint, there was no effect of the intervention on breakfast skipping. Nearly 30% of intervention students consumed breakfast foods or drinks from multiple locations, as compared with 21% of control students. A greater proportion of intervention students than control students consumed 100% juice, and a smaller proportion consumed sugar-sweetened beverages and foods high in saturated fat and added sugar. Conclusions. A BIC initiative led to improvements in the types of foods and drinks students consumed in the morning. However, the program did not reduce breakfast skipping and increased the number of locations where students ate.