I-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations.

INTRODUCTION: The COVID-19 pandemic brought an urgent need to discover novel effective therapeutics for patients hospitalised with severe COVID-19. The Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis (ISPY COVID-19 trial) was designed and implemented in early 2020 to evaluate investigational agents rapidly and simultaneously on a phase 2 adaptive platform. This manuscript outlines the design, rationale, implementation and challenges of the ISPY COVID-19 trial during the first phase of trial activity from April 2020 until December 2021. METHODS AND ANALYSIS: The ISPY COVID-19 Trial is a multicentre open-label phase 2 platform trial in the USA designed to evaluate therapeutics that may have a large effect on improving outcomes from severe COVID-19. The ISPY COVID-19 Trial network includes academic and community hospitals with significant geographical diversity across the country. Enrolled patients are randomised to receive one of up to four investigational agents or a control and are evaluated for a family of two primary outcomes-time to recovery and mortality. The statistical design uses a Bayesian model with 'stopping' and 'graduation' criteria designed to efficiently discard ineffective therapies and graduate promising agents for definitive efficacy trials. Each investigational agent arm enrols to a maximum of 125 patients per arm and is compared with concurrent controls. As of December 2021, 11 investigational agent arms had been activated, and 8 arms were complete. Enrolment and adaptation of the trial design are ongoing. ETHICS AND DISSEMINATION: ISPY COVID-19 operates under a central institutional review board via Wake Forest School of Medicine IRB00066805. Data generated from this trial will be reported in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT04488081.

Geriatric Physiology and the Frailty Syndrome.

Understanding geriatric physiology is critical for successful perioperative management of older surgical patients. The frailty syndrome is evolving as an important, potentially modifiable process capturing a patient's biologic age and is more predictive of adverse perioperative outcomes than chronologic age. Use of frailty in risk stratification and perioperative decision-making allows providers to effectively diagnose, risk stratify, and treat patients in the perioperative setting. Further study is needed to develop a universal definition of frailty, to identify comprehensive yet feasible screening tools that allow for accurate detection of frailty in the perioperative setting, and to refine treatment programs for frail surgical patients.

Palliative Care Interventions for Surgical Patients: A Systematic Review.

IMPORTANCE: Inpatient palliative care improves symptom management and patient satisfaction with care and reduces hospital costs in seriously ill patients. However, the role of palliative care in the treatment of patients undergoing surgery (surgical patients) remains poorly defined. OBJECTIVE: To characterize the content, design, and results of interventions to improve access to palliative care or the quality of palliative care for surgical patients. EVIDENCE REVIEW: This systematic review was conducted according to PRIMSA guidelines. Articles were identified through searches of PubMed, PsycINFO, EMBASE, and CINAHL as well as manual review of references. Eligible articles included experimental, quasi-experimental, and observational studies published in English from January 1, 1994, through October 31, 2014, in which patient outcomes of palliative care interventions for adult surgical patients were reported. Data on the study setting, design, intervention, participants, and results were extracted from the final study set and analyzed from December 22, 2014, to February 7, 2015. FINDINGS: A total of 3838 abstracts were identified and screened by 2 reviewers, 77 articles were reviewed in full text, and 25 articles (22 unique interventions involving 8575 unique patients) met the study criteria. Interrater agreement was good (κ = 0.78). Nine single-institution retrospective cohort studies, 7 single-institution prospective cohort studies, 7 single-institution randomized clinical studies, and 2 multicenter randomized clinical studies were included. Nineteen of the 23 single-site studies were performed at academic hospitals. Given the heterogeneity of study methods and measures, meta-analysis was not possible. Preoperative decision-making interventions were associated with decreased mortality in 4 studies. Three studies reported improved quality of communication; 4, improved symptom management; and 7, decreased use of health care resources and decreased cost. However, many studies were small, performed in academic settings, and methodologically flawed and did not measure clinically meaningful outcomes. CONCLUSIONS AND RELEVANCE: The sparse evidence regarding interventions to introduce or improve palliative care for surgical patients is further limited by methodologic flaws. Rigorous evaluations of standardized palliative care interventions measuring meaningful patient outcomes are needed.

Patterns and trends of adult height in India in 2005-2006.

Differences in height by wealth, education, caste, geography, and birth years are examined for men and women born between 1961 and 1981 in India using data from the 2005-2006 Indian National Family Health Survey. There is a positive association between socioeconomic position (SEP) and height with lower SEP individuals being shorter. Height varies across the 29 Indian states even after accounting for individual differences in SEP, with substantial variation in height remaining at the neighborhood and state levels. Among men, height appears to have modestly increased for all birth cohorts as compared to the 1961-1965 cohort, with smaller increases for the most recent cohorts. For women, height across birth cohorts has shown little increase. These results suggest that inequalities in several health outcomes for low SEP adults may be reflected in inequalities in height, which can be used to represent long-term health at the population level. Shorter stature and slower growth among some groups may indicate that they did not experience the improvements that were assumed to have occurred across the population. This study presents a comprehensive, empirical description of mean height differences and the underlying variation among adults in India across diverse socioeconomic, demographic, and geographically oriented groups as well as birth cohorts.

Do burdens of underweight and overweight coexist among lower socioeconomic groups in India?

BACKGROUND: The coexistence of underweight and overweight in rapidly developing economies is well recognized. However, less is known about the socioeconomic patterning of underweight and overweight as economies move through the epidemiologic transition. OBJECTIVE: The objective was to assess whether burdens of underweight and overweight coexist among lower socioeconomic groups in India. DESIGN: Repeated cross-sectional analyses were conducted in nationally representative samples of 76,514 and 80,054 women aged 15-49 y drawn from the 1998-1999 and 2005-2006 Indian National Family Health Survey, respectively. Body mass index (in kg/m(2)) was used to measure weight status. We also calculated a ratio of the number of underweight women (<18.5) divided by the number of overweight women (>24.9). Indicators of socioeconomic status (SES) included wealth and education. RESULTS: Although the ratio of underweight to overweight women decreased from 3.3 in 1998-1999 to 2.2 in 2005-2006, there were still considerably more underweight women than overweight women. It was only in the top wealth quintile and in groups with higher education that there was a slight excess of overweight women as compared with underweight women. There was a strong positive relation between SES and body mass index at both time points and across urban and rural areas. A positive relation between SES and body mass index was also observed for men in 2005-2006. CONCLUSIONS: The distribution of underweight and overweight in India remains socially segregated. Despite rapid economic growth, India has yet to experience a situation in which underweight and overweight coexist in the low-SES groups.

Patterns and distribution of HIV among adult men and women in India.

BACKGROUND: While the estimated prevalence of HIV in India experienced a downward revision in 2007, the patterning and distribution of HIV in the population remains unclear. We examined the individual and state-level socioeconomic patterning of individual HIV status among adult men and women in India as well as the patterning of other individual demographic and behavioral determinants of HIV status. METHODOLOGY/PRINCIPAL FINDINGS: We conducted logistic regression models accounting for the survey design using nationally representative, cross-sectional data on 100,030 women and men from the 2005-2006 India National Family Health survey which, for the first time, provided objective assessments of HIV seroprevalence. Although there was a weak relationship between household wealth and risk of being HIV-positive, there was a clear negative relationship between individual education attainment and risk of being HIV-positive among both men and women. A 1000 Rupee change in the per capita net state domestic product was associated with a 4% and 5% increase in the risk for positive HIV status among men and women, respectively. State-level income inequality was associated with increased risk of HIV for men. Marital status and selected sexual behavior indicators were significant predictors of HIV status among women whereas the age effect was the most dominant predictor of HIV infection among men. CONCLUSIONS/SIGNIFICANCE: Although the prevalence of HIV in India is low, the lack of strong wealth patterning in the risk of HIV suggests a more generalized distribution of HIV risk than some of India's high-risk group HIV prevention policies have assumed. The positive association between state economic development and individual risk for HIV is intriguing and requires further scrutiny.