Mannose-binding lectin gene 2 variant DD (rs 5030737) is associated with susceptibility to COVID-19 infection in the urban population of Patna City (India).

The study aimed to measure plasma levels of Mannose-Binding Lectin (MBL) and MBL-associated serine protease-2 (MASP-2) and their polymorphisms in COVID-19 patients and controls to detect association. As MBL is a protein of immunological importance, it may contribute to the first-line host defence against SARS-CoV-2. MBL initiates the lectin pathway of complement activation with help of MASP-1 and MASP-2. Hence, appropriate serum levels of MBL and MASPs are crucial in getting protection from the disease. The polymorphisms of MBL and MASP genes affect their plasma levels, impacting their protective function and thus may manifest susceptibility, extreme variability in the clinical symptoms and progression of COVID-19 disease. The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively.The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively. Our results indicate that median serum levels of MBL and MASP-2 were significantly low in diseased cases but attained normal levels on recovery. Only genotype DD was found to be associated with COVID-19 cases in the urban population of Patna city.

Molecular identification and genetic characterization of Theileria and Anaplasma infection in sheep and goat of North Gujarat, India.

Hemoprotozoal diseases are significant health concerns in small ruminants. The present study was conducted to identify and characterize the species of Theileria and Anaplasma in sheep and goats located in different districts of North Gujarat, India. A total of 226 (Banaskantha = 175, Patan = 26, and Bhuj = 25) blood samples were collected from sheep (n = 78) and goats (n = 148), and 46 ticks were collected and identified from sheep and goats. PCR assays were carried out using genus and species-specific primers for Theileria targeting 18S rRNA locus and for Anaplasma targeting the msp5 gene. Overall, 37.2% sheep (29/78) and 10.8% of goats (16/148) were positive for Theileria by PCR, whereas 15.4% of sheep (12/78) and 25.7% goats (38/148) were positive for Anaplasma infection. Moreover, mixed infection was found in 4.4% (10/226) of sheep and goats by PCR. Sanger sequencing of Theileria and Anaplasma positives revealed a high similarity to T. ovis and A. ovis using NCBI blast, respectively. Phylogenetic analyses revealed that the Anaplasma spp. DNA sequences belonged to the A. ovis group and closely associated with the A. ovis nucleotide sequence strain Haibei isolated in China from sheep (GQ483471). The phylogenetic analysis based on the SSU rRNA locus revealed that the Theileria ovis DNA sequences belonged to the T. ovis group and closely related to MW440586 isolated in Kerala, India, from a goat. The majority of ticks (91.3%) were identified as Hyalomma. In conclusion, Theileria ovis and Anaplasma ovis were commonly identified species in sheep and goats and transmitted mainly by Hyalomma ticks in North Gujarat, India, which is important baseline data for future research and control strategies. This is the first report on Theileria and Anaplasma co-infections in sheep and goats from North Gujarat, India.

Right of association and new business entry: country-level evidence from the market sector.

Labor market institutions (LMIs) could enable new firm entry by lowering burdens to attracting and retaining human capital or restrict new firm entry by increasing concerns of additional demands on ventures facing liabilities of newness and smallness. In this study, we focus on the LMI of the right of association, and whether its relationship with new business entry depends on the vertical ordering of bargaining (represented in the centralization of collective bargaining) or the horizontal synchronization of wage-setting (represented in the coordination of wage-setting). In a panel of 44 countries covering the period 2005-2019, we find that the right of association in the market sector is positively associated with new business entry; however, with increasing centralization of collective bargaining, the association becomes negative. Coordination of wage-setting does not significantly affect the relationship between the right of association and new business entry. The results are robust to accounting for both serial correlation and cross-sectional correlation in the panel regressions and carry implications for policymakers regarding the effects of LMIs on new business creation.

Waste to energy: a decision-making process for technology selection through characterization of waste, considering energy and emission in the city of Ahmedabad, India.

Municipal solid waste (MSW) disposal has become major issue for the city of Ahmedabad, India. Development, concentrated population and economic growth have led to a substantial increase of MSW generation. Therefore, the objective of the study was to characterize MSW for selection of waste processing technology. To provide a solution for sustainable processing and for safe disposal of fresh MSW, Abellon Clean Energy Ltd joined forces with Ahmedabad Municipal Corporation (AMC) under Public-Private Partnership (PPP) to establish a 14.9MW advanced controlled combustion-based waste to energy (WTE) generation facility to process and dispose 1000 tons/day of fresh MSW. For waste characterization, samples (n=201) were collected from the Pirana waste dumping site using quadrate sampling method. A yearly weighted average Low Heating Value (LHV) of 9.85/kg and ash content 25.12% for unsegregated MSW makes controlled combustion with electricity generation an eligible technology. After combustion, the waste volume is reduced by 75%. The 14.9MW WTE facility replaces 417 t coal/day, reducing greenhouse gas (GHG) emissions of 300.38 tCO2eq/day through coal replacement, while avoiding 735.24 t CO2eq/day on account of landfill emissions from MSW dumping. Waste to energy is the fastest solution to reduce waste volume by generating electricity through reduction of GHG.

Saroglitazar, a PPAR-α/γ Agonist, for Treatment of NAFLD: A Randomized Controlled Double-Blind Phase 2 Trial.

BACKGROUND AND AIMS: NAFLD is characterized by insulin resistance and dysregulated lipid and glucose metabolism. Saroglitazar, a dual peroxisome proliferator activated receptor-α/γ agonist, improves insulin sensitivity, and lipid and glycemic parameters. Saroglitazar improved NASH histology in animal studies. In this randomized controlled clinical trial, we evaluated the efficacy and safety of saroglitazar in patients with NAFLD/NASH. APPROACH AND RESULTS: A total of 106 patients with NAFLD/NASH with alanine aminotransferase (ALT) ≥ 50 U/L at baseline and body mass index ≥25 kg/m2 were randomized in a 1:1:1:1 ratio to receive placebo or saroglitazar 1 mg, 2 mg, or 4 mg for 16 weeks. The primary efficacy endpoint was percentage change from baseline in ALT levels at week 16. Liver fat content (LFC) was assessed by MRI proton density fat fraction. The least-squares mean percent change from baseline in ALT at week 16 was -25.5% (5.8), -27.7% (5.9), and -45.8% (5.7), with saroglitazar 1 mg, 2 mg, and 4 mg, respectively, versus 3.4% (5.6) in placebo (P < 0.001 for all). Compared with placebo, saroglitazar 4 mg improved LFC (4.1% [5.9] vs. -19.7% [5.6]), adiponectin (-0.3 µg/mL [0.3] vs. 1.3 µg/mL [0.3]), homeostatic model assessment-insulin resistance (-1.3 [1.8] vs. -6.3 [1.7]), and triglycerides (-5.3 mg/dL [10.7] vs. -68.7 mg/dL [10.3]) (P < 0.05 for all). Saroglitazar 4 mg also improved lipoprotein particle composition and size and reduced lipotoxic lipid species. Saroglitazar was well-tolerated. A mean weight gain of 1.5 kg was observed with saroglitazar 4 mg versus 0.3 kg with placebo (P = 0.27). CONCLUSIONS: Saroglitazar 4 mg significantly improved ALT, LFC, insulin resistance, and atherogenic dyslipidemia in participants with NAFLD/NASH. (ClinicalTrials.gov identifier: NCT03061721.).

Estimated size of the clinical medical imaging physics workforce in the United States.

There is no current authoritative accounting of the number of clinical imaging physicists practicing in the United States. Information about the workforce is needed to inform future efforts to secure training pathways and opportunities. In this study, the AAPM Diagnostic Demand and Supply Projection Working Group collected lists of medical physicists from several state registration and licensure programs and the Conference of Radiation Control Program Directors (CRCPD) registry. By cross-referencing individuals among these lists, we were able to estimate the current imaging physics workforce in the United States by extrapolating based on population. The imaging physics workforce in the United States in 2019 consisted of approximately 1794 physicists supporting diagnostic X-ray (1073 board-certified) and 934 physicists supporting nuclear medicine (460 board-certified), with a number of individuals practicing in both subfields. There were an estimated 235 physicists supporting nuclear medicine exclusively (150 board-certified). The estimated total workforce, accounting for overlap, was 2029 medical physicists. These estimates are in approximate agreement with other published studies of segments of the workforce.

Impact of the COVID-19 pandemic on the hours lost by self-employed racial minorities: evidence from Brazil.

Drawing on minority enclave theory and resilience theory in entrepreneurship, we test whether, with the onset of the COVID-19 pandemic, the self-employed lost more hours than the employed and whether traditionally disadvantaged self-employed racial minorities faced harsher penalties in the form of reduced hours of work. Though spatially concentrated ethnic minority colocations could improve business outcomes in the non-crisis period, with the pandemic affecting all the members in the enclave, the very dependencies in minority enclaves could be a liability. Using a large-scale survey during the COVID-19 pandemic conducted by the Brazilian government, we draw on a one-to-one nearest neighbor matched pair sample of 19,626 employed (public or private sector) and self-employed individuals, and control for industry-sector-interview-location fixed effects. The results show that self-employed people, compared to employed, reported a greater loss of hours. At the sample level, black self-employed people on aggregate lost 9,051 hours per month, and mixed race self-employed people on aggregate lost 27,880 hours per month. The disproportionate loss of work hours by the self-employed from racial minority groups during the COVID-19 pandemic in a developing country context calls for a closer examination and assessment of the long-term impact of COVID-19 on racial minorities.

The Association Between Participation in Mahatma Gandhi National Rural Employment Guarantee Program and Smoking in India.

BACKGROUND: This paper examines whether participating in Mahatma Gandhi National Rural Employment Guarantee Program (NREGA) is associated with the likelihood of smoking among program participants in India. METHODS: We use two-stage residual inclusion (2SRI) estimation method and two waves of India Human Development Surveys completed before (2005) and after (2012) NREGA implementation. RESULTS: The likelihood of smoking increased with NREGA participation. For every 10% increase in NREGA income, the likelihood of smoking bidis (but not cigarettes) increased by 0.88 percentage point. A bidi, a stick of unprocessed tobacco wrapped in temburini leaves, is a significantly cheaper alternative to cigarettes. Nonparticipants who had a comparable increase in income between the two India Human Development Survey waves did not show an increase in likelihood of smoking. The heterogeneity in NREGA treatment effect shows that smoking tendency is not influenced by caste/religion or literacy. CONCLUSIONS: NREGA, as the largest workfare program, most certainly has had a significantly positive influence on the rural poor in India. The findings highlight its small but meaningful influence of a negative health behavior, greater likelihood of uptake of smoking bidis/hookah among program participants. IMPLICATIONS: Existing studies have found mixed evidence of an exogenous increase in income among low-income adults and its impact on smoking. No studies to date have tested the influence of workfare programs in rural areas of developing countries, where unemployment rates are higher and a substantial share of population in those areas is poor. Based on participation in employment guarantee programs as a proxy for exogenous increase in guaranteed income among rural population in India, we find that participants in the program were more likely to smoke bidis/hookah but not cigarettes.

Global Trigger Tool: Proficient Adverse Drug Reaction Autodetection Method in Critical Care Patient Units.

BACKGROUND: Emergency department (ED) being the most crucial part of hospital, where adverse drug reactions (ADRs) often go undetected. Trigger tools are proficient ADR detection methods, which have only been applied for retrospective surveillance. We did a prospective analysis to further refine the trigger tool application in healthcare settings. OBJECTIVE: To estimate the prevalence of ADRs and prospectively evaluate the importance of using trigger tools for their detection. MATERIALS AND METHODS: A prospective study was conducted in the ED for the presence of triggers in patient records to monitor and report ADRs by applying the Institute for Healthcare Improvement (IHI) trigger tool methodology. RESULTS: Four hundred sixty-three medical records were analyzed randomly using 51 trigger tools, where triggers were found in 181 (39.09%) and ADRs in 62 (13.39%) patients. The prevalence of ADR was 13.39%. According to the World Health Organization (WHO)-Uppsala Monitoring Centre (UMC) causality scale, 47 (75.8%) were classified as probable and 15 (24.2%) as possible, wherein 39 (62.9%) were predictable and 8 (12.9%) were definitely preventable. Most common triggers were abrupt medication stoppage (34.98%), antiemetic use (25.91%), and time in ED >6 hours (17.49%). The positive predictive values (PPVs) of triggers such as international normalized ratio (INR) > 4 (p = 0.0384), vitamin K administration (p = 0.002), steroid use (p = 0.0001), abrupt medication stoppage (p = 0.0077), transfusion of blood or blood products (p = 0.004), and rash (p = 0.0042) showed statistically significant results, which make the event detection process more structured when these triggers are positive. Presence of five or more triggers has statistically significant chances of developing an ADR (p < 0.05). CONCLUSION: Trigger tool could be a viable method to identify ADRs when compared to the traditional ADR identification methods, but there is insufficient data on IHI tool and its use to identify ADRs in the general outpatient setting. Healthcare providers may benefit from better trigger tools to help them detect ADRs. HOW TO CITE THIS ARTICLE: Pandya AD, Patel K, Rana D, Gupta SD, Malhotra SD, Patel P. Global Trigger Tool: Proficient Adverse Drug Reaction Autodetection Method in Critical Care Patient Units. Indian J Crit Care Med 2020;24(3):172-178.

Effect of caudal bupivacaine alone and with adjuvant fentanyl and nalbuphine to minimize the catheter-related bladder discomfort after tubeless percutaneous nephrolithotomy: A prospective randomized study.

BACKGROUND AND AIMS: Catheter-related bladder discomfort (CRBD) is a major cause of postoperative morbidity following urological procedures. The aim of this study was to compare the effect of caudal bupivacaine alone and with adjuvant fentanyl and nalbuphine to minimize the severity of CRBD after tubeless percutaneous nephrolithotomy (PCNL). MATERIAL AND METHODS: A randomized prospective study was conducted on one hundred thirty-two (American society of Anaesthesiologist physical status I to II) patients who presented for tubeless PCNL under general anesthesia. Patients were randomly divided into four groups control (C), bupivacaine (B), bupivacaine-fentanyl (BF), and bupivacaine-nalbuphine (BN) by using computer-generated codes. All patients received local infiltration at the procedure site while Groups B, BF, and BN received caudal epidural block (CEB) under ultrasound guidance after conclusion of the procedure. Groups B, BF, and BN received bupivacaine alone, bupivacaine-fentanyl, and bupivacaine-nalbuphine, respectively, for CEB. Patients were monitored 24 h for CRBD scale, visual analogue score (VAS), and duration of analgesia at 30 min, 1, 2, 4, 6, 12, 18, and 24 h intervals. The analgesics were supplemented if the CRBD score was >2 and VAS was ≥4. Student t-test, analysis of variance, and Chi-square test were applied for quantitative, within group occurrence, and qualitative analysis respectively. RESULTS: The CRBD scores were considerably lower in the Groups BF and BN as compared to Groups C and B during the first four hours. The duration of analgesia was significantly prolonged in Group BN (475 ± 47 min) versus BF (320 ± 68 min) versus B (104 ± 40 min) versus C (26 ± 14 min). CONCLUSIONS: The severity of CRBD can be reduced with CEB. The effect of CEB can be prolonged with the addition of opioid.

Real-time Feedback in Pay-for-Performance: Does More Information Lead to Improvement?

BACKGROUND: Pay-for-performance (P4P) has been used expansively to improve quality of care delivered by physicians. However, to what extent P4P works through the provision of information versus financial incentives is poorly understood. OBJECTIVE: To determine whether an increase in information feedback without changes to financial incentives resulted in improved physician performance within an existing P4P program. INTERVENTION/EXPOSURE: Implementation of a new registry enabling real-time feedback to physicians on quality measure performance. DESIGN: Observational, predictive piecewise model at the physician-measure level to examine whether registry introduction associated with performance changes. We used detailed physician quality measure data 3 years prior to registry implementation (2010-2012) and 2 years after implementation (2014-2015). We also linked physician-level data including age, gender, and board certification; group-level data including registry click rates; and patient panel data including chronic conditions. PARTICIPANTS: Four hundred thirty-four physicians continuously affiliated with Advocate from 2010 to 2015. MAIN MEASURES: Physician performance on ten quality metrics. KEY RESULTS: We found no consistent pattern of improvement associated with the availability of real-time information across ten measures. Relative to predicted performance without the registry, average performance increased for two measures (childhood immunization status-rotavirus (p < 0.001) and diabetes care-medical attention for nephropathy (p = 0.024)) and decreased for three measures (childhood immunization status-influenza (p < 0.001) and diabetes care-HbA1c testing (p < 0.001) and poor HbA1c control (p < 0.001)). Results were consistent for subgroup analysis on those most able to improve, i.e., physicians in the bottom tertile of performance prior to registry introduction. Physicians who improved most were in groups that accessed the registry more than those who improved least (8.0 vs 10.0 times per week, p = 0.010). CONCLUSIONS: More frequent provision of information, provided in real-time, was insufficient to improve physician performance in an existing P4P program with high baseline performance. Results suggest that electronic registries may not themselves drive performance improvement. Future work should consider testing information feedback enhancements with financial incentives.

Burden of hereditary transthyretin amyloidosis on quality of life.

INTRODUCTION: Hereditary transthyretin (hATTR) amyloidosis is a progressive, degenerative disease, with peripheral neuropathy, cardiomyopathy, and other clinical manifestations. In this study we examine the impact of hATTR amyloidosis on quality of life (QOL). METHODS: Neuropathy-specific QOL, measured with the Norfolk QOL-Diabetic Neuropathy questionnaire, was compared between patients with hATTR amyloidosis and patients with type 2 diabetes, whereas generic QOL, measured with the 36-item Short Form Health Survey version 2 (SF-36v2), was compared between patients with hATTR amyloidosis, the general population, and patients with chronic diseases. RESULTS: Neuropathy-specific QOL for patients with hATTR amyloidosis was nearly equivalent to that of patients with type 2 diabetes with diabetic neuropathy accompanied by a history of ulceration, gangrene, or amputation. Generic QOL was worse than that seen in the general population, with physical functioning worse than that for patients with multiple sclerosis and congestive heart failure. DISCUSSION: Patients with hATTR amyloidosis show significant burden on QOL, particularly in physical functioning. Muscle Nerve 60: 169-175, 2019.

Establishing a Multicentre Trauma Registry in India: An Evaluation of Data Completeness.

BACKGROUND: The completeness of a trauma registry's data is essential for its valid use. This study aimed to evaluate the extent of missing data in a new multicentre trauma registry in India and to assess the association between data completeness and potential predictors of missing data, particularly mortality. METHODS: The proportion of missing data for variables among all adults was determined from data collected from 19 April 2016 to 30 April 2017. In-hospital physiological data were defined as missing if any of initial systolic blood pressure, heart rate, respiratory rate, or Glasgow Coma Scale were missing. Univariable logistic regression and multivariable logistic regression, using manual stepwise selection, were used to investigate the association between mortality (and other potential predictors) and missing physiological data. RESULTS: Data on the 4466 trauma patients in the registry were analysed. Out of 59 variables, most (n = 51; 86.4%) were missing less than 20% of observations. There were 808 (18.1%) patients missing at least one of the first in-hospital physiological observations. Hospital death was associated with missing in-hospital physiological data (adjusted OR 1.4; 95% CI 1.02-2.01; p = 0.04). Other significant associations with missing data were: patient arrival time out of hours, hospital of care, 'other' place of injury, and specific injury mechanisms. Assault/homicide injury intent and occurrence of chest X-ray were associated with not missing any of first in-hospital physiological variables. CONCLUSION: Most variables were well collected. Hospital death, a proxy for more severe injury, was associated with missing first in-hospital physiological observations. This remains an important limitation for trauma registries.

Assessment of the in vitro cytochrome P450 (CYP) inhibition potential of ZYTP1, a novel poly (ADP-ribose) polymerase inhibitor.

ZYTP1 is a novel Poly (ADP-ribose) polymerase protein inhibitor being developed for cancer indications. The focus of the work was to determine if ZYTP1 had a perpetrator role in the in vitro inhibition of cytochrome P450 (CYP) enzymes to aid dosing decisions during the clinical development of ZYTP1. ZYTP1 IC50 for CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4/5 was determined using human liver microsomes and LC-MS/MS detection. CYP3A4/5 IC50 of depropylated metabolite of ZYTP1 was also determined. Time dependent inhibition of CYP3A4/5 by ZYTP1 was also assessed using substrates, testosterone and midazolam. The mean IC50 values of ZYTP1 were >100 µM for CYP1A2, 2B6 and 2D6, while 56.1, 24.5, 39.5 and 23.3-58.7 µM for CYP2C8, 2C9, 2C19 and 3A4/5, respectively. The CYP3A4/5 IC50 of depropylated metabolite was 11.95-24.51 µM. Time dependent CYP3A4/5 inhibition was noted for testosterone and midazolam with IC50 shift of 10.9- and 39.9-fold, respectively. With midazolam, the kinact and KI values of ZYTP1 were 0.075 min-1 and 4.47 µM for the CYP3A4/5 time dependent inhibition, respectively. Because of potent inhibition of CYP3A4/5, drugs that undergo metabolism via CYP3A4/5 pathway should be avoided during ZYTP1 therapy.

Light pollution and insufficient sleep: Evidence from the United States.

OBJECTIVES: The objective of this study was to test whether light pollution is associated with lower or insufficient sleep. The American Medical Association recently issued a public notice cautioning against the effects of nighttime light on sleep quality and quantity. Light pollution, through the suprachiasmatic nucleus, disrupts circadian rhythm by reducing the secretion of melatonin, a sleep-inducing hormone. METHODS: I used 282 403 individual self-reports of sleep hours and insufficient sleep from the 2014 and 2016 metropolitan and micropolitan statistical area (MMSA) Behavioral Risk Factor Surveillance System (BRFSS) and the prevalence of insufficient sleep during 2014 in 2823 US counties from the County Health Rankings. The nighttime artificial light data are from the cloud-free Visible Infrared Imaging Radiometer Suite available from the National Oceanic and Atmospheric Administration in the US. RESULTS: At the MMSA level, for a 10-unit increase in nighttime light (nW/[cm2 sr]) the estimated decline in sleep was about 5.59 minutes per day and the odds of reporting insufficient sleep (<7 hours) increased by 13.77%. At the county-level, for a 10-unit increase in nighttime light, the prevalence of insufficient sleep increased by 2.19%. CONCLUSIONS: Although light pollution was negatively associated with sleep outcomes, the practical effect sizes were small. The small effects suggest that the effects at the population level are negligible, and the effect of nighttime light pollution is more idiosyncratic.

Dual PPARα/γ agonist saroglitazar improves liver histopathology and biochemistry in experimental NASH models.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common clinico-pathological conditions that affect millions of patients worldwide. In this study, the efficacy of saroglitazar, a novel PPARα/γ agonist, was assessed in models of NAFLD/NASH. METHODS & RESULTS: HepG2 cells treated with palmitic acid (PA;0.75 mM) showed decreased expression of various antioxidant biomarkers (SOD1, SOD2, glutathione peroxidase and catalase) and increased expression of inflammatory markers (TNFα, IL1ß and IL6). These effects were blocked by saroglitazar, pioglitazone and fenofibrate (all tested at 10µM concentration). Furthermore, these agents reversed PA-mediated changes in mitochondrial dysfunction, ATP production, NFkB phosphorylation and stellate cell activation in HepG2 and HepG2-LX2 Coculture studies. In mice with choline-deficient high-fat diet-induced NASH, saroglitazar reduced hepatic steatosis, inflammation, ballooning and prevented development of fibrosis. It also reduced serum alanine aminotransferase, aspartate aminotransferase and expression of inflammatory and fibrosis biomarkers. In this model, the reduction in the overall NAFLD activity score by saroglitazar (3 mg/kg) was significantly more prominent than pioglitazone (25 mg/kg) and fenofibrate (100 mg/kg). Pioglitazone and fenofibrate did not show any improvement in steatosis, but partially improved inflammation and liver function. Antifibrotic effect of saroglitazar (4 mg/kg) was also observed in carbon tetrachloride-induced fibrosis model. CONCLUSIONS: Saroglitazar, a dual PPARα/γ agonist with predominant PPARα activity, shows an overall improvement in NASH. The effects of saroglitazar appear better than pure PPARα agonist, fenofibrate and PPARγ agonist pioglitazone.

Preclinical evaluation of saroglitazar magnesium, a dual PPAR-α/γ agonist for treatment of dyslipidemia and metabolic disorders.

1. Saroglitazar, a novel peroxisome proliferator-activated receptor (PPAR) agonist, regulates lipid and glucose metabolism. The objective of this report is to provide a preclinical evaluation (in vitro/in vivo) of ADME properties of saroglitazar. In vitro studies included determination of permeability, metabolic stability, plasma protein binding, CYP reaction phenotyping and CYP inhibitory liability. In vivo studies included oral bioavailability and pharmacokinetic assessment in mouse, rat and dog. The excretion of saroglitazar was determined in rats. Exploratory metabolism of saroglitazar was evaluated using in vitro and in vivo samples. 2. Saroglitazar was metabolically more stable in human liver microsomes as compared to rat and dog liver microsomes, highly protein bound (98-99.6%) with high Caco2 permeability (104 nm/s) with <2 efflux ratio. In vitro metabolism in rat, dog and human liver microsomes revealed three putative metabolites corresponding to di-hydroxylation, mono-oxygenation and dehydrogenation moieties. 3. Oral bioavailability was 100%, 72% and 47% in mouse, rat and dog, respectively. The intravenous clearance and volume of distribution of saroglitazar were 3.6, 8.5 and 6.9 mL/min/kg and 1.3, 4.8 and 1.8 L/kg for mouse, rat and dog, respectively. The elimination half-life of saroglitazar ranged between 6 and 15 h. Saroglitazar appeared to be eliminated via hepatobiliary route with negligible renal excretion.

Influence of acute and chronic kidney failure in rats on the disposition and pharmacokinetics of ZYAN1, a novel prolyl hydroxylase inhibitor, for the treatment of chronic kidney disease-induced anemia.

1. ZYAN1 is a prolyl hydroxylase inhibitor in clinical development for treatment of anemia associated with chronic kidney disease (CKD). We evaluated the effect of acute and chronic kidney impairment on the pharmacokinetics of ZYAN1 in rat models. 2. Cisplatin (2.5, 5 and 7.5 mg/kg) was used to induce acute kidney injury (AKI), and five-sixth and total nephrectomy was used to induce chronic kidney injury (CKI) in male Wistar rats. All groups received a single 15 mg/kg oral dose of ZYAN1. Blood/urine samples were analyzed for ZYAN1 to assess peak concentration (Cmax), area under the concentration-time curve (AUCinf), total body clearance (CL/F) and elimination half-life (T1/2). 3. Cmax and AUCinf were not significantly different in the various AKI groups or in five-sixth nephrectomized rats, as compared to control rats. Recovery of ZYAN1 in urine was reduced; the impact on the CL/F was minimal. There was a 2-fold increase in AUCinf with reduction in CL/F in total nephrectomized rats. T1/2 was longer for ZYAN1 in the severe AKI/five-sixth nephrectomy rats and total nephrectomy rats as compared to control rats. 4. Based on the rodent data it may be inferred that PK of ZYAN1 in CKD patients may be minimally affected.

Height-income association in developing countries: Evidence from 14 countries.

OBJECTIVES: The purpose of this study was to assess whether the height-income association is positive in developing countries, and whether income differences between shorter and taller individuals in developing countries are explained by differences in endowment (ie, taller individuals have a higher income than shorter individuals because of characteristics such as better social skills) or due to discrimination (ie, shorter individuals have a lower income despite having comparable characteristics). METHODS: Instrumental variable regression, Oaxaca-Blinder decomposition, quantile regression, and quantile decomposition analyses were applied to a sample of 45 108 respondents from 14 developing countries represented in the Research on Early Life and Aging Trends and Effects (RELATE) study. RESULTS: For a one-centimeter increase in country- and sex-adjusted median height, real income adjusted for purchasing power parity increased by 1.37%. The income differential between shorter and taller individuals was explained by discrimination and not by differences in endowments; however, the effect of discrimination decreased at higher values of country- and sex-adjusted height. CONCLUSIONS: Taller individuals in developing countries may realize higher income despite having characteristics similar to those of shorter individuals.

Using Behavioral Economics to Design Physician Incentives That Deliver High-Value Care.

Behavioral economics provides insights about the development of effective incentives for physicians to deliver high-value care. It suggests that the structure and delivery of incentives can shape behavior, as can thoughtful design of the decision-making environment. This article discusses several principles of behavioral economics, including inertia, loss aversion, choice overload, and relative social ranking. Whereas these principles have been applied to motivate personal health decisions, retirement planning, and savings behavior, they have been largely ignored in the design of physician incentive programs. Applying these principles to physician incentives can improve their effectiveness through better alignment with performance goals. Anecdotal examples of successful incentive programs that apply behavioral economics principles are provided, even as the authors recognize that its application to the design of physician incentives is largely untested, and many outstanding questions exist. Application and rigorous evaluation of infrastructure changes and incentives are needed to design payment systems that incentivize high-quality, cost-conscious care.