ETHICAL ISSUES IN RANDOMIZED CONTROL TRIALS: A REVIEW

Randomized Control Trials (RCTs) are scientific experiments that are used to investigate the effectiveness of various interventions in the field of Medicine and public health. As a result of complexity of the process, even the competent individuals are not able to understand the process of randomization with anticipated consequences associated with it. There is rise in trend of research and conduct of RCTs in developing countries; hence, there is a need to review all ethical issues confronted by the researchers during conduct of such trials. An Online literature search was carried out in April 2015 to May 2015 from Google Scholar, BioMed Central Ethics and PubMed using the key term “Trials”, “Randomized Control Trials”, “Ethical issues” and various synonymous terms from the titles of the articles. This resulted in 25 articles. Following, which these articles were scrolled down, and all articles with ethical issues encountered with different type of trials, were included. Avoiding the duplication of issues, 13 articles were finally selected for review. From the review narrates that ethical issues of patient autonomy, informed consent, therapeutic misconceptions, state of equipoise for individuals, clinicians and researchers, controversies between placebo and active control orthodoxies, design biases, role of gate keepers, benefit verses risk assessment and protection of vulnerable groups are the important ethical issues highlighted by various researchers. There can be issues related to some surgeries, early cessation of RCTs due to some apparent benefits and conduct of trials in third world countries. It is imperative that institutional review boards should consider all such issues during ethical assessment of such trials. Keywords:Benefit verses risk assessment Institutional review board (IRB), Randomized Control Trials (RCTs), vulnerable groups

CARDIOVASCULAR IMPLICATIONS OF CUMULATIVE RADIOIODINE DOSES IN PATIENTS WITH DIFFERENTIATED THYROID CANCER AND TYPE 2 DIABETES MELLITUS, BIHAR, INDIA: A RETROSPECTIVE STUDY.

Background: The study aims to investigate the cardiovascular effects associated with cumulative doses of radioiodine therapy in people diagnosed with differentiated thyroid cancer (DTC) and comorbid Type 2 diabetes mellitus, with a focus on elucidating potential risks and outcomes for this patient population.  Methods: A retrospective cohort study was conducted, enrolling 75 female participants categorized into DTC/−T2DM (Category I) and DTC/+T2DM (Category II). Data on demographic characteristics, radioiodine therapy, cardiovascular outcomes, and clinical parameters were collected from medical records. Statistical analyses were accomplished using SPSS software ver. 18.  Results: Patients with DTC and without T2DM (DTC/−T2DM) exhibited higher average age (60 ± 6.3 years) and BMI (28.5 kg/m²) compared to patients with both DTC and T2DM (55 ± 5.2 years, 25.1 kg/m²). Patients with both DTC and T2DM received higher cumulative doses of radioiodine (200 mCi ± 25) over a longer duration (14 months) compared to patients with DTC and without T2DM (180 mCi ± 20, 12 months). The prevalence of hypertension, arrhythmias, and myocardial infarctions was higher in patients with DTC and without T2DM than in patients with both DTC and T2DM. Statistical analysis revealed significant variations in hypertension incidence (p < 0.001) and myocardial infarction occurrence (p = 0.03) between the groups. Multivariate regression analysis showed an independent association of T2DM with a higher risk of hypertension (p < 0.001) and myocardial infarction (p = 0.015) among DTC patients.  Conclusion: The study highlights the importance of considering cardiovascular risks associated with radioiodine therapy in DTC patients, particularly those with T2DM. Personalized treatment strategies balancing cancer management and cardiovascular risk mitigation are crucial for optimizing patient outcomes.  Recommendations: Clinicians should adopt a multidisciplinary approach integrating endocrinology, oncology, and cardiology to optimize the management of DTC patients with T2DM

A CASE-CONTROL PERSPECTIVE STUDY ON EXPLORING DIASTOLIC DYSFUNCTION IN ASYMPTOMATIC TYPE 2 DIABETES MELLITUS PATIENTS WITH PRESERVED SYSTOLIC FUNCTION, BIHAR, INDIA.

Background: Asymptomatic individuals with Type 2 Diabetes Mellitus (T2DM) often exhibit diastolic dysfunction, a precursor to symptomatic heart failure (HF), despite preserved systolic function. The study aims to investigate the incidence and severity of diastolic dysfunction (DD) in this population and its association with diabetes duration, glycemic control, and cardiovascular risk factors.   Methods: A case-control prospective study was carried out enrolling 82 participants: 55 with T2DM and 27 non-diabetic individuals. Echocardiographic evaluations were performed to assess diastolic function parameters. Statistical analysis was conducted using SPSS version 24.  Results: The study revealed a high incidence of diastolic dysfunction, with 54.9% of participants affected, ranging from mild to severe impairment. Individuals with T2DM exhibited a significantly higher incidence of diastolic dysfunction compared to non-diabetic participants (p < 0.05). Diabetes status independently contributed to impaired diastolic function, with a positive correlation observed between diabetes duration and severity of dysfunction (r = 0.42, p < 0.01). Subgroup analysis hinted at a trend towards significance between poorly controlled diabetes and increased diastolic dysfunction prevalence (p = 0.08). Uncontrolled hypertension was associated with heightened diastolic dysfunction severity.  Conclusion: Asymptomatic individuals with T2DM and preserved systolic function demonstrate a substantial burden of diastolic dysfunction, which is independently associated with diabetes status and duration. Early detection and management of diabetes, glycemic control, and blood pressure are crucial in mitigating the risk of diastolic dysfunction and improving cardiovascular outcomes in this population.  Recommendations: Clinicians should emphasize early screening for diastolic dysfunction in asymptomatic individuals with T2DM, particularly focusing on glycemic control and blood pressure management. Future research should explore targeted interventions aimed at preserving diastolic function and reducing cardiovascular morbidity and mortality in this high-risk population. Diastolic dysfunction (DD

Pregnancy Characteristics and Delivery Outcomes of Individual Mother Hospitalized at Jalalabad, Kyrgyzstan

Background: Maternal morbidity is a silent struggle, echoing the untold stories of resilience and strength in the face of adversity. Women of childbearing age are faced with extreme uncertainties; hence the purpose of this study was to analyze fertility trend and maternal complications including the possible high-risk factors connected to maternal morbidity. Maternal morbidity could be prevented through early detection, including the period preceding pregnancy.  Methods and methodology: This is a retrospective cross-sectional study using data from hospital database describes trends of fertility and with immediate post-delivery maternal complication. The data was collected just from month January in 2023 from a Regional Maternity Hospital in Jalalabad, Kyrgyzstan. Total of 260 sample were drawn from the data base for the study.  Objective: The study intended to find the different pregnancy characteristics and the outcomes of delivery of Individual mother who were Hospitalized at Jalalabad, Kyrgyzstan. We settled for this topic because it is one of the significant causes of death among reproductive age group women around the world.  Result: Among 260 delivery cases, majority 56.2% of them were from age group 21 - 25 years. Majority of them have more than one child and 22.7% cases had more than 3 children. Common complications associated during pregnancy were anemia (17.3%) & Pre-eclampsia (16.1%) whereas most common postpartum complication was PPH associated with atony (17.3%). Obesity (10%) and Pre-existing hypertension (9.6%) were the most common comorbidity associated with pregnancy.  Conclusion: The research population appears to have high fertility trends. The main causes of obstetric complications were anemia, hypertension, and postpartum hemorrhage. Two prevalent comorbidities linked to pregnancy were obesity and underlying hypertension. To reduce pregnancy-related problems, it is imperative that interventions be implemented that support early ANC attendance, lower obesity, increase access to blood pressure monitoring, and provide family planning information and services.&nbsp

Interaction-driven breakdown of dynamical localization in a kicked quantum gas

Quantum interference can terminate energy growth in a continually kicked system, via a single-particle ergodicity-breaking mechanism known as dynamical localization. The effect of many-body interactions on dynamically localized states, while important to a fundamental understanding of quantum decoherence, has remained unexplored despite a quarter-century of experimental studies. We report the experimental realization of a tunably-interacting kicked quantum rotor ensemble using a Bose-Einstein condensate in a pulsed optical lattice. We observe signatures of a prethermal localized plateau, followed for interacting samples by interaction-induced anomalous diffusion with an exponent near one half. Echo-type time reversal experiments establish the role of interactions in destroying reversibility. These results quantitatively elucidate the dynamical transition to many-body quantum chaos, advance our understanding of quantum anomalous diffusion, and delimit some possibilities for protecting quantum information in interacting driven systems.Comment: 17 pages including supp inf

Burden of 375 diseases and injuries, risk-attributable burden of 88 risk factors, and healthy life expectancy in 204 countries and territories, including 660 subnational locations, 1990–2023: a systematic analysis for the Global Burden of Disease Study 2023

Background: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. Methods: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010–23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. Findings: Total numbers of global DALYs grew 6·1% (95% UI 4·0–8·1), from 2·64 billion (2·46–2·86) in 2010 to 2·80 billion (2·57–3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0–14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31–1·61) global DALYs in 2010, increasing to 1·80 billion (1·63–2·03) in 2023, alongside a concurrent 4·1% (1·9–6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176–209] DALYs), stroke (157 million [141–172]), and diabetes (90·2 million [75·2–107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0–107·5]), depressive disorders (26·3% [11·6–42·9]), and diabetes (14·9% [7·5–25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837–917) in 2010 to 681 million (642–736) in 2023, and a 25·8% (22·6–28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7–61·0) for diarrhoeal diseases, 42·9% (38·0–48·0) for HIV/AIDS, and 42·2% (23·6–56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6–22·0) and 24·8% (7·4–36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7–19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18–1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation—with high SBP accounting for 8·4% (6·9–10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories—behavioural, metabolic, and environmental and occupational—risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8–37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0–11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023—eg, declining by 54·4% (38·7–65·3) for unsafe sanitation, 50·5% (33·3–63·1) for unsafe water source, and 45·2% (25·6–72·0) for no access to handwashing facility, and by 44·9% (37·3–53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [–2·7 to 15·6]; non-significant). Interpretation: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors—eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG—including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic—the complex interaction of multiple health risks, social determinants, and systemic challenges—will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity

Global, regional, and national prevalence of adult overweight and obesity, 1990–2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021

Background: Overweight and obesity is a global epidemic. Forecasting future trajectories of the epidemic is crucial for providing an evidence base for policy change. In this study, we examine the historical trends of the global, regional, and national prevalence of adult overweight and obesity from 1990 to 2021 and forecast the future trajectories to 2050. Methods: Leveraging established methodology from the Global Burden of Diseases, Injuries, and Risk Factors Study, we estimated the prevalence of overweight and obesity among individuals aged 25 years and older by age and sex for 204 countries and territories from 1990 to 2050. Retrospective and current prevalence trends were derived based on both self-reported and measured anthropometric data extracted from 1350 unique sources, which include survey microdata and reports, as well as published literature. Specific adjustment was applied to correct for self-report bias. Spatiotemporal Gaussian process regression models were used to synthesise data, leveraging both spatial and temporal correlation in epidemiological trends, to optimise the comparability of results across time and geographies. To generate forecast estimates, we used forecasts of the Socio-demographic Index and temporal correlation patterns presented as annualised rate of change to inform future trajectories. We considered a reference scenario assuming the continuation of historical trends. Findings: Rates of overweight and obesity increased at the global and regional levels, and in all nations, between 1990 and 2021. In 2021, an estimated 1·00 billion (95% uncertainty interval [UI] 0·989–1·01) adult males and 1·11 billion (1·10–1·12) adult females had overweight and obesity. China had the largest population of adults with overweight and obesity (402 million [397–407] individuals), followed by India (180 million [167–194]) and the USA (172 million [169–174]). The highest age-standardised prevalence of overweight and obesity was observed in countries in Oceania and north Africa and the Middle East, with many of these countries reporting prevalence of more than 80% in adults. Compared with 1990, the global prevalence of obesity had increased by 155·1% (149·8–160·3) in males and 104·9% (95% UI 100·9–108·8) in females. The most rapid rise in obesity prevalence was observed in the north Africa and the Middle East super-region, where age-standardised prevalence rates in males more than tripled and in females more than doubled. Assuming the continuation of historical trends, by 2050, we forecast that the total number of adults living with overweight and obesity will reach 3·80 billion (95% UI 3·39–4·04), over half of the likely global adult population at that time. While China, India, and the USA will continue to constitute a large proportion of the global population with overweight and obesity, the number in the sub-Saharan Africa super-region is forecasted to increase by 254·8% (234·4–269·5). In Nigeria specifically, the number of adults with overweight and obesity is forecasted to rise to 141 million (121–162) by 2050, making it the country with the fourth-largest population with overweight and obesity. Interpretation: No country to date has successfully curbed the rising rates of adult overweight and obesity. Without immediate and effective intervention, overweight and obesity will continue to increase globally. Particularly in Asia and Africa, driven by growing populations, the number of individuals with overweight and obesity is forecast to rise substantially. These regions will face a considerable increase in obesity-related disease burden. Merely acknowledging obesity as a global health issue would be negligent on the part of global health and public health practitioners; more aggressive and targeted measures are required to address this crisis, as obesity is one of the foremost avertible risks to health now and in the future and poses an unparalleled threat of premature disease and death at local, national, and global levels. Funding: Bill & Melinda Gates Foundation

Driving Fast and Slow: Dynamics of Periodically Modulated Quantum Gases

Driven degenerate quantum gases are flexible platforms that allow for rich investigationsof quantum dynamics. Certain gases, such as Bose-Einstein condensates of 7Li, also afford the ability to tune interactions and thus study quantum many-body phenomena. In this thesis, I present three experiments which explore dynamic and thermodynamic quantum behavior using both periodic driving and interaction control. The experiments span a range of frequencies from Hz to MHz, and elucidate fundamental phenomena of localization and energy transfer. I will first describe an experiment which introduces interactions to the quantum kicked rotor, a prototypical quantum chaotic system, and observe the role interactions play in localization. I will then show how using the same system with altered symmetries can create a probe for previously unobserved dynamical signatures of Anderson localization. Finally, switching to a completely different regime, I’ll outline how a slowly driven quantum gas can be used to realize a novel quantum thermodynamic engine