Evaluation of Endpoints Used in Clinical Trials on Adenomyosis - A Systematic Review.

Adenomyosis lacks approved pharmacological treatment even after decades of its identification. We performed this study to review the status of clinical research on adenomyosis for finding an effective drug therapy and to identify the most common endpoints used in adenomyosis trials. A systematic search was performed in the PubMed and Clinicaltrials.gov registries to identify interventional trials for analysis without any time and language restrictions. Our search revealed that barely 15 drugs have been assessed for the management of adenomyosis from 2001 to 2021. Among these, LNG-IUS was found to be the most evaluated drug, followed by dienogest. In these trials, the most commonly assessed endpoints included VAS, NPRS for pain, haemoglobin and PBAC for menstrual bleeding, uterine volume, and serum estradiol. There appears to be a need for developing a comprehensive score that takes into consideration all disease symptoms as well as incorporates some objective elements to evaluate the disease.

Safety and Efficacy of Saroglitazar in Nonalcoholic Fatty Liver Patients With Diabetic Dyslipidemia-A Prospective, Interventional, Pilot Study.

BACKGROUND: Saroglitazar-a unique dual peroxisome proliferator-activated receptor agonist was approved marketing authorization in India in 2013 for diabetic dyslipidemia. Postmarketing studies have additionally shown improvement in liver parameters in diabetic dyslipidemia patients with nonalcoholic fatty liver disease (NAFLD) who received saroglitazar. AIM: The aim of this study was to evaluate the effect of saroglitazar on liver function test, liver fibrosis score by FibroScan, lipid profiles, HbA1c in NAFLD patients with diabetic dyslipidemia in southern India. METHODOLOGY: A prospective, interventional, pilot study was performed to study the safety and efficacy of saroglitazar in NAFLD patients having type 2 diabetes mellitus. About 97 patients were screened, of which 85 patients were involved in the study based on the inclusion criteria. The clinical parameters and liver stiffness were measured at the baseline and also after 12 weeks of treatment with administration of saroglitazar 4 mg once daily. The change in the parameters at the baseline and after the end of the treatment was measured and was subjected to statistical analysis using SPSS software. RESULTS: The recruited patients received saroglitazar and were followed up for a period of 12 weeks. The clinical parameters such as fasting blood sugar, postprandial blood sugar, HbA1c, total cholesterol, triglycerides, SGPT, and liver stiffness showed significant difference after 12 weeks of treatment when compared with the baseline values. No adverse drug reaction was reported in patients receiving saroglitazar during the study. CONCLUSION: Saroglitazar was found to show significant improvement in liver parameters in NAFLD patients with a significant reduction in liver fibrosis and triglycerides level.

Evaluation of pharmacological interventions in the management of adenomyosis: a systematic review.

PURPOSE: Medical management of adenomyosis largely revolves around symptom management, with very few drugs having received regulatory approval for the disease. However, the level of evidence supporting the use of pharmacological interventions is low, making it difficult to establish their efficacy in the treatment of adenomyosis. Hence, the aim of our systematic review is to identify the strength of evidence currently available and evaluate the effectiveness of different medical interventions in the management of adenomyosis. METHODS: The search was performed in MEDLINE, Embase, Cochrane Library, CENTRAL and ClinicalTrials.gov. Articles published between 1 January 2010 and 30 November 2020 were considered. Randomized controlled trials and observational studies that assessed the efficacy of medical interventions in patients with adenomyosis were included. The quality of the data was analyzed using RevMan 5.3 software. RESULTS: LNG-IUS (levonorgestrel intrauterine system), dienogest and gonadotropin-releasing hormone (GnRH) analogues were effective in reducing pain, uterine volume and menstrual bleeding. However, these data were largely obtained in the non-trial setting and were fraught with issues that included patient selection, short duration of therapy, small sample size, and limited long-term safety and effectiveness data. CONCLUSIONS: Although LNG-IUS, dienogest and GnRH analogues have better evidence for effectiveness in adenomyosis, the need of the hour is to thoroughly evaluate other novel molecules for adenomyosis using well-designed randomized controlled trials.

Toward a science of delivering aid with dignity: Experimental evidence and local forecasts from Kenya.

How can governments and nonprofits design aid programs that afford dignity and facilitate beneficial outcomes for recipients? We conceptualize dignity as a state that manifests when the stigma associated with receiving aid is countered and recipients are empowered, both in culturally resonant ways. Yet materials from the largest cash transfer programs in Africa predominantly characterize recipients as needy and vulnerable. Three studies examined the causal effects of alternative aid narratives on cash transfer recipients and donors. In study 1, residents of low-income settlements in Nairobi, Kenya (N = 565) received cash-based aid accompanied by a randomly assigned narrative: the default deficit-focused "Poverty Alleviation" narrative, an "Individual Empowerment" narrative, or a "Community Empowerment" narrative. They then chose whether to spend time building business skills or watching leisure videos. Both empowerment narratives improved self-efficacy and anticipated social mobility, but only the "Community Empowerment" narrative significantly motivated recipients' choice to build skills and reduced stigma. Given the diverse settings in which aid is delivered, how can organizations quickly identify effective narratives in a context? We asked recipients to predict which narrative would best motivate skill-building in their community. In study 2, this "local forecasting" methodology outperformed participant evaluations and experimental pilots in accurately ranking treatments. Finally, study 3 confirmed that the narrative most effective for recipients did not undermine donors' willingness to contribute to the program. Together these studies show that responding to recipients' psychological and sociocultural realities in the design of aid can afford recipients dignity and help realize aid's potential.

Dupilumab in the Treatment of Moderate to Severe Asthma: An Evidence-Based Review.

BACKGROUND: Asthma affects millions of patients across the globe and also accounts for numerous mortalities every year. The current pharmacologic approach to the treatment of asthma includes the use of glucocorticoids and beta-agonists mainly. However, these conventional therapies have poor controllability of moderate-to-severe asthma and also produce several side effects on their long-term use. These limitations had led to the development of biologics targeting the mediators involved in T helper 2-inflammation associated with the pathogenesis of asthma such as interleukin (IL) 4, IL-5, and IL-13. dupilumab, a fully human monoclonal antibody, an IL-4 receptor alpha-antagonist targeting IL-13 and IL-4 has a potential role in treatment of moderate-to-severe asthma and was approved by the Food and Drug Administration on October 19, 2018. The dual-antagonistic action of dupilumab on IL-4 and IL-13 receptors renders it more efficient in asthma treatment. OBJECTIVES: To review the efficacy and safety profile of dupilumab in the treatment of moderate-to-severe asthma. METHODS: Systematic search was performed via PubMed, Cochrane library, Embase, and ClinicalTrials.gov using the key words dupilumab, moderate-to-severe asthma, interleukin, IL-13, IL-4, and monoclonal antibody. Randomized controlled trials that compared between placebo and dupilumab in patients with uncontrolled asthma were included and observational studies were excluded in this review. RESULTS: The review of selected literature reveals that addition of dupilumab to conventional therapy improves forced expiratory volume in 1 second and reduces the risk of severe asthma exacerbations in patients. No significant differences in incidence of adverse drug reactions/adverse drug events were observed between dupilumab and placebo groups except higher rates of injection site reactions in the dupilumab group. CONCLUSIONS: Concomitant use of dupilumab with long-acting beta agonists used in combination with inhaled corticosteroids, improves clinical outcomes and quality of life in patients with moderate to severe asthma. Although dupilumab has a promising role in treatment of patients with asthma, it is still in the emerging stage for its acceptance globally. Ongoing studies will help to determine dupilumab's long-term efficacy and safety for its future extensive use.

Tight near-total corrosive strictures of the proximal esophagus with concomitant involvement of the hypopharynx: Flexible endoscopic management using a novel technique.

AIM: To investigate the role of a novel minimally invasive endoscopic technique in the management of tight near-total corrosive strictures of the proximal esophagus involving the hypopharynx. METHODS: Two patients with near-total corrosive strictures of the proximal esophagus involving the hypopharynx were managed with the novel endoscopic technique. The technique involved passing a 0.025-inch flexible guide-wire across the stricture, and stricture dilatation, using 10F coaxial diathermy and balloon dilators, followed by electro-incision of the proximal aspect of the residual eccentric stricture by means of a novel approach using a wire-guided sphincterotome. RESULTS: Both patients were successfully managed on an outpatient department basis with the complete relief of symptoms and resolution of strictures on endoscopy and an esophagogram. No adverse events were seen during or after the procedure. There was no recurrence of symptoms at a follow-up of over a year in both cases. There was a significant improvement in the body mass index of both patients after the procedure. CONCLUSION: We report a novel flexible endoscopic technique for the management of complex hypopharyngo-esophageal strictures. In experienced hands, the procedure is relatively simple, safe and effective with a durable response.

Measuring self-efficacy, executive function, and temporal discounting in Kenya.

Developing countries have low adherence to medical regimens like water chlorination or antenatal and postnatal care, contributing to high infant and child mortality rates. We hypothesize that high levels of stress affect adherence through temporal discounting, self-efficacy, and executive control. Measurement of these constructs in developing countries requires adaptation of existing measures. In the current study, we adapt psychological scales and behavioral tasks, measuring each of these three constructs, for use among adults in Kenya. We translated and back-translated each measure to Kiswahili and conducted cognitive interviewing to establish cultural acceptability, refined existing behavioral tasks, and developed new ones. Then, in a laboratory session lasting 3 h, participants (N=511) completed the adapted psychological inventories and behavioral tasks. We report the psychometric properties of these measures. We find relatively low reliability and poor correlational evidence between psychological scales and behavioral tasks measuring the same construct, highlighting the challenges of adapting measures across cultures, and suggesting that assays within the same domain may tap distinct underlying processes.