Development of a composite indicator to prioritize districts for implementation of human immunodeficiency virus programmes in Maharashtra,India

A key recommendation of the National AIDS Control Programme‐IV of India was to develop new strategies for geo‐prioritization of the human immunodeficiency virus (HIV) epidemic. We conducted this study to categorize the districts in Maharashtra (India) based on a multidimensional framework for geo‐prioritization of services. Programmatic data on trends of HIV prevalence, coverage of marginalized populations and vulnerability factors were included. A composite indicator based on these was developed, and the cumulative score was calculated for each district. HIV prevalence among general population has declined steadily from 0.60% in 2007 to 0.33% in 2017. The programme coverage was stable but inadequate for men who have sex with men (MSM). The coverage for female sex workers (FSWs) was inadequate and reduced over time. Nine districts were categorized as high priority, 13 as moderate priority and 11 were classified as low‐priority districts based on burden and vulnerability for HIV. The high‐priority districts were Pune, Solapur and Yavatmal for FSW interventions and Pune, Thane and Latur for MSM interventions. This multidimensional indicator is based on existing programmatic data, dynamic and can be made state‐specific. It is useful to categorize and prioritize districts for allocation of resources and geo‐prioritization of services in resource limited settings.     

Enzobiotics—A Novel Therapy for the Elimination of Uremic Toxins in Patients with CKD (EETOX Study): A Multicenter Double-Blind Randomized Controlled Trial

Design, participants, setting, and measurements: Predialysis adult participants with chronic kidney disease (CKD) and mean estimated glomerular filtration rate (eGFR) <45 mL/min per 1.73 m²) were recruited in 2019 to a multicentric double-blinded randomized controlled trial of enzobiotic therapy (synbiotics and proteolytic enzymes) conducted over 12 weeks. The primary objective was to evaluate the efficacy and safety of enzobiotics in reducing the generation of p-cresol sulfate (PCS) and indoxyl sulfate (IS), stabilizing renal function, and improving quality of life (QoL), while the secondary objective was to evaluate the feasibility of the diagnostic prediction of IS and PCS from CKD parameters. Results: Of the 85 patients randomized (age 48.76 years, mean eGFR 23.24 mL/min per 1.73 m² in the placebo group; age 54.03 years, eGFR 28.93 mL/min per 1.73 m² in the enzobiotic group), 50 completed the study. The absolute mean value of PCS increased by 12% from 19 µg/mL (Day 0) to 21 µg/mL (Day90) for the placebo group, whereas it decreased by 31% from 23 µg/mL (Day 0) to 16 µg/mL (Day 90) for the enzobiotic group. For IS, the enzobiotic group showed a decrease (6.7%) from 11,668 to 10,888 ng/mL, whereas the placebo group showed an increase (8.8%) from 11,462 to 12,466 ng/mL (Day 90). Each patient improvement ratio for Day 90/Day 0 analysis showed that enzobiotics reduced PCS by 23% (0.77, p = 0.01). IS levels remained unchanged. In the placebo group, PCS increased by 27% (1.27, p = 0.14) and IS increased by 20% (1.20, p = 0.14). The proportion of individuals beyond the risk threshold for PCS (>20 µg/mL) was 53% for the placebo group and 32% for the enzobiotic group. The corresponding levels for IS risk (threshold >20,000 ng/mL) were 35% and 24% for the placebo and enzobiotic groups, respectively. In the placebo group, eGFR decreased by 7% (Day 90) but remained stable (1.00) in the enzobiotic group. QoL as assessed by the adversity ratio decreased significantly (p = 0.00), highlighting an improvement in the enzobiotic group compared to the placebo group. The predictive equations were as follows: PCS (Day 0 = −5.97 + 0.0453 PC + 2.987 UA − 1.310 Creat; IS (Day 0) = 756 + 1143 Creat + 436.0 Creat². Conclusion: Enzobiotics significantly reduced the PCS and IS, as well as improved the QoL.     

Gastric Ultrasound: POCUSing an Intolerant GUT!

How to cite this article: Kothekar AT, Joshi AV. Gastric Ultrasound: POCUSing an Intolerant GUT! Indian J Crit Care Med 2022;26(9):981–982.     

Immunotherapy Use Prior to Liver Transplant in Patients with Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide, and its incidence has increased rapidly in the United States over the past two decades. Liver transplant is considered curative, but is not always possible, and pre-transplant immunotherapy is of great interest as a modality for downstaging the tumor burden. We present a review of the literature on pre-liver transplant immunotherapy use in patients with HCC. Our literature search queried publications in Ovid MEDLINE, Ovid Embase, and Web of Science, and ultimately identified 24 original research publications to be included for analysis. We found that the role of PD-1 and PD-L1 in risk stratification for rejection is of special interest to researchers, and ongoing randomized clinical trials PLENTY and Dulect 2020-1 will provide insight into the role of PD-1 and PD-L1 in liver transplant management in the future. This literature search and the resulting review represents the most thorough collection, analysis, and presentation of the literature on the subject to date.     

Post-infectious irritable bowel syndrome:Mechanistic insights into chronic disturbances following enteric infection

Irritable bowel syndrome(IBS)is a commonly encountered chronic functional gastrointestinal(GI)disorder.Approximately 10%of IBS patients can trace the onset of their symptoms to a previous a bout of infectious dysentery.The appearance of new IBS symptoms following an infectious event is defined as post-infectiousIBS.Indeed,with the World Health Organization estimating between 2 and 4 billion cases annually,infectious diarrheal disease represents an incredible international healthcare burden.Additionally,compounding evidence suggests many commonly encountered enteropathogens as unique triggers behind IBS symptom generation and underlying pathophysiological features.A growing body of work provides evidence supporting a role for pathogen-mediated modifications in the resident intestinal microbiota,epithelial barrier integrity,effector cell functions,and innate and adaptive immune features,all proposed physiological manifestations that can underlie GI abnormalities in IBS.Enteric pathogens must employ a vast array of machinery to evade host protective immune mechanisms,and illicit successful infections.Consequently,the impact of infectious events on host physiology can be multidimensional in terms of anatomical location,functional scope,and duration.This review offers a unique discussion of the mechanisms employed by many commonly encountered enteric pathogens that cause acute disease,but may also lead to the establishment of chronic GI dysfunction compatible with IBS.     

Least-cost targets and avoided fossil fuel capacity in India’s pursuit of renewable energy

India has set aggressive targets to install more than 400 GW of wind and solar electricity generation by 2030, with more than two-thirds of that capacity coming from solar. This paper examines the electricity and carbon mitigation costs to reliably operate India’s grid in 2030 for a variety of wind and solar targets (200 GW to 600 GW) and the most promising options for reducing these costs. We find that systems where solar photovoltaic comprises only 25 to 50% of the total renewable target have the lowest carbon mitigation costs in most scenarios. This result invites a reexamination of India’s proposed solar-majority targets. We also find that, compared to other regions and contrary to prevailing assumptions, meeting high renewable targets will avoid building very few new fossil fuel (coal and natural gas) power plants because of India’s specific weather patterns and need to meet peak electricity demand. However, building 600 GW of renewable capacity, with the majority being wind plants, reduces how often fossil fuel power plants run, and this amount of capacity can hold India’s 2030 emissions below 2018 levels for less than the social cost of carbon. With likely wind and solar cost declines and increases in coal energy costs, balanced or wind-majority high renewable energy systems (600 GW or ≈ 45% share by energy) could result in electricity costs similar to a fossil fuel-dominated system. As an alternative strategy for meeting peak electricity demand, battery storage can avert the need for new fossil fuel capacity but is cost effective only at low capital costs (≈ USD 150 per kWh).

India emitted 3.2 billion metric tons of CO₂e in 2016, or 6% of annual global greenhouse gas emissions, placing it third only to China and the United States (1). One-third of these emissions were from coal-based electricity. At the same time, both per capita emissions and energy use remain well below global averages, suggesting a massive potential for growth of electricity generation and emissions (1). India’s primary energy demand is expected to double by 2040 compared to 2017 (2). Whether this energy comes from fossil or low-carbon sources will significantly affect the ability to limit average global temperature rise to below 2 °C.India is already pursuing significant technology-specific renewable energy targets—100 GW of solar and 60 GW of wind by 2022—and, in its Nationally Determined Contributions (NDC), committed to a 40% target for installed generation capacity from nonfossil fuel sources by 2030 (3). In 2019, in part to fulfill its NDC commitment, the Indian government proposed to install 440 GW of renewable energy capacity by 2030, with 300 GW of solar and 140 GW of wind capacity (4). Although costs of solar photovoltaic (PV) and wind technologies have declined significantly in recent years (5–7), the low cost of coal and integration costs associated with variable renewable energy (VRE) technologies like wind and solar may hinder India’s cost-effective transition to a decarbonized electricity system. This paper seeks to answer a number of questions that arise in the Indian context. What targets for wind and solar capacity have the lowest associated integration costs? Will these targets significantly offset the need to build fossil fuel generation capacity? What additional measures can we take to mitigate VRE integration costs?Merely comparing the levelized costs of VRE with the costs of conventional generation ignores additional cost drivers, which depend on the timing of VRE production and other conditions in the power system (8, 9). Quantifying these drivers requires models that choose lowest-cost generation capacity portfolios and simulate optimal system operation with detailed spatiotemporal data. Several prior studies address these system-level integration costs in a capacity expansion planning framework (10–16), often making decisions based on a limited sample of representative hours. Other studies explicitly estimate the relationship between long-run economic value (including integration costs) of VRE penetration levels (17, 18) but do not include VRE investment costs in their analysis. Few prior studies explore the impacts of high VRE penetration on India’s electricity system, and those that do either use the capacity expansion framework and do not evaluate the economic value of multiple VRE targets (4, 19, 20) or do not optimize capacity build around proposed VRE targets (21).Here we address this gap by estimating how different VRE targets affect the cost to reliably operate the Indian electricity system. To do so, we work with three interrelated models. First, using a spatially explicit model for VRE site selection, we identify the lowest levelized cost wind and solar sites to meet different VRE capacity targets, and study how the resource quality—and corresponding levelized cost—of selected sites changes with increasing VRE targets.Second, using a capacity investment model that accounts for VRE production patterns and optimal dispatch of hydropower and battery storage, we determine the capacity requirements and investment costs for coal, combined cycle gas turbines (CCGT), and combustion turbine (CT) peaker plants. Due to uncertainties in their future deployment (22), and because their current targets are relatively low (4), we did not consider new nuclear or hydro capacity in the main scenarios but include those in the sensitivity scenarios presented in SI Appendix, section 2. Third, we use a unit commitment and economic dispatch model to simulate hourly operation of the electricity system and estimate annual system operational costs. This model captures important technical constraints, including minimum operating levels, daily unit commitment for coal and natural gas plants, and energy limits on hydropower and battery storage. Rather than cooptimize VRE capacity, we compute the system-level economic value of a range of VRE targets by comparing the sum of the avoided new conventional capacity and energy generation costs to a no-VRE scenario. The net cost for a scenario is then the difference between the levelized cost of the VRE and the system-level economic value. Materials and Methods provides more detail on this process.Our results show that, despite greater levelized cost reduction forecasts for solar PV compared to wind technologies, VRE targets with greater amounts of wind have the lowest projected net carbon mitigation costs. This finding is robust to a range of scenarios, including low-cost solar and storage, and lower minimum generation levels for coal generators.We find that, although VRE production displaces energy production from conventional generators, it does very little to defer the need for capacity from those generators due to low correlation between VRE production and peak demand. Our findings suggest that VRE in India avoids far less conventional capacity than VRE in other regions in the world. These capacity requirements are slightly mitigated if India’s demand patterns evolve to more closely resemble demand in its major cities. Overall, we conclude that the importance of choosing the right VRE mix is significant when measured in terms of carbon mitigation costs: Whereas most solar-majority scenarios we examined lead to costs greater than or equal to estimates of the social cost of carbon (SCC), wind-majority mixes all cost far less than the SCC.     

Paramedic-Initiated Home Care Referrals and Use of Home Care and Emergency Medical Services

Objective: We examined the association between paramedic-initiated home care referrals and utilization of home care, 9-1-1, and Emergency Department (ED) services. Methods: This was a retrospective cohort study of individuals who received a paramedic-initiated home care referral after a 9-1-1 call between January 1, 2011 and December 31, 2012 in Toronto, Ontario, Canada. Home care, 9-1-1, and ED utilization were compared in the 6 months before and after home care referral. Nonparametric longitudinal regression was performed to assess changes in hours of home care service use and zero-inflated Poisson regression was performed to assess changes in the number of 9-1-1 calls and ambulance transports to ED. Results: During the 24-month study period, 2,382 individuals received a paramedic-initiated home care referral. After excluding individuals who died, were hospitalized, or were admitted to a nursing home, the final study cohort was 1,851. The proportion of the study population receiving home care services increased from 18.2% to 42.5% after referral, representing 450 additional people receiving services. In longitudinal regression analysis, there was an increase of 17.4 hours in total services per person in the six months after referral (95% CI: 1.7–33.1, p = 0.03). The mean number of 9-1-1 calls per person was 1.44 (SD 9.58) before home care referral and 1.20 (SD 7.04) after home care referral in the overall study cohort. This represented a 10% reduction in 9-1-1 calls (95% CI: 7–13%, p < 0.001) in Poisson regression analysis. The mean number of ambulance transports to ED per person was 0.91 (SD 8.90) before home care referral and 0.79 (SD 6.27) after home care referral, representing a 7% reduction (95% CI: 3–11%, p < 0.001) in Poisson regression analysis. When only the participants with complete paramedic and home care records were included in the analysis, the reductions in 9-1-1 calls and ambulance transports to ED were attenuated but remained statistically significant. Conclusions: Paramedic-initiated home care referrals in Toronto were associated with improved access to and use of home care services and may have been associated with reduced 9-1-1 calls and ambulance transports to ED.