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We studied all-cause mortality during the COVID-19 pandemic in 19 Indian states (population 1.27 billion). Excess mortality was calculated by comparison with years 2015 to 2019. The known COVID-19 deaths reported for a state were assumed to be accurate, unless excess mortality data suggested a higher toll. Data from one state were excluded due to anomalies. In several regions, fewer deaths were reported in 2020 than expected. Areas in Andhra Pradesh, Delhi, Haryana, Karnataka, Madhya Pradesh, Tamil Nadu, and West Bengal saw spikes in mortality in Spring 2021. The pandemic-related mortality through August 31, 2021, in 18 Indian states was estimated to be 198.7 per 100,000 population (range 146.1–263.8 per 100,000). If these rates apply nationally, then 2.69 million people (range 1.98 to 3.57 million) may have perished in India as a result of the pandemic by August 31, 2021.

Point-of-care (POC) testing for Toxoplasma infection has the potential to revolutionize diagnosis and management of toxoplasmosis, especially in high-risk populations in areas with significant environmental contamination and poor health infrastructure precluding appropriate follow-up and preventing access to medical care. Toxoplasmosis is a significant public health challenge in Morocco, with a relatively heavy burden of infection and, to this point, minimal investment nationally to address this infection. Herein, we analyse the performance of a novel, low-cost rapid test using fingerstick-derived whole blood from 632 women (82 of whom were pregnant) from slums, educational centres, and from nomad groups across different geographical regions (i.e. oceanic, mountainous) of Morocco. The POC test was highly sensitive and specific from all settings. In the first group of 283 women, sera were tested by Platelia ELISA IgG and IgM along with fingerstick whole blood test. Then a matrix study with 349 women was performed in which fingerstick – POC test results and serum obtained by venipuncture contemporaneously were compared. These results show high POC test performance (Sensitivity: 96.4% [IC95 90.6–98.9%]; Specificity: 99.6% [IC95 97.3–99.9%]) and high prevalence of Toxoplasma infection among women living in rural and mountainous areas, and in urban areas with lower educational levels. The high performance of POC test confirms that it can reduce the need for venipuncture and clinical infrastructure in a low-resource setting. It can be used to efficiently perform seroprevalence determinations in large group settings across a range of demographics, and potentially expands healthcare access, thereby preventing human suffering.

We studied sources of variation between countries in per-capita mortality from COVID-19 (caused by the SARS-CoV-2 virus). Potential predictors of per-capita coronavirus-related mortality in 200 countries by May 9, 2020 were examined, including age, gender, obesity prevalence, temperature, urbanization, smoking, duration of the outbreak, lockdowns, viral testing, contact-tracing policies, and public mask-wearing norms and policies. Multivariable linear regression analysis was performed. In univariate analysis, the prevalence of smoking, per-capita gross domestic product, urbanization, and colder average country temperature were positively associated with coronavirus-related mortality. In a multivariable analysis of 196 countries, the duration of the outbreak in the country, and the proportion of the population aged 60 years or older were positively associated with per-capita mortality, whereas duration of mask-wearing by the public was negatively associated with mortality (all P < 0.001). Obesity and less stringent international travel restrictions were independently associated with mortality in a model which controlled for testing policy. Viral testing policies and levels were not associated with mortality. Internal lockdown was associated with a nonsignificant 2.4% reduction in mortality each week (P = 0.83). The association of contact-tracing policy with mortality was not statistically significant (P = 0.06). In countries with cultural norms or government policies supporting public mask-wearing, per-capita coronavirus mortality increased on average by just 16.2% each week, as compared with 61.9% each week in remaining countries. Societal norms and government policies supporting the wearing of masks by the public, as well as international travel controls, are independently associated with lower per-capita mortality from COVID-19.

Purpose: The Surviving Sepsis Campaign guidelines recommend 30 mL/kg of fluids within 3 hours (30by3) of sepsis-induced hypoperfusion, but a national mandate released an allowance for dosing based on ideal instead of actual body weight (IBW/ABW) for obese patients. This study aims to determine the dose-effect of 30by3 for patients with severe sepsis or septic shock (SS/SS) with respect to body mass index (BMI) categories and secondarily, examine the clinical impact of IBW vs. ABW-based dosing. Methods: Retrospective cohort study of adults (≥18 years; n = 1,032) with SS/SS presenting to an urban, tertiary-care emergency department. Models include MEDS score, antibiotic timing, lactate, renal and heart failure, among others. Results: The cohort was 10.2% underweight and 28.7% obese. Overall mortality was 17.1% with 20.4% shock mortality. An exponential increase in mortality was observed for each 5 mL/kg under 30by3 for underweight ( p = 0.02), but not obese patients. ABW vs IBW-30by3 dosing was reached in 80.0 vs 52.4% (underweight), 56.4 vs 56.9% (normal/overweight), and 23.3 vs 46.0% (obese). Across all BMI categories, there was increased mortality for not reaching ABW-based 30by3 dosing (OR 1.78, 95% CI 1.18-2.69) with no significant impact for IBW (OR 1.28, 95% CI 0.87 -1.91). The increased mortality for failing to reach ABW-dosed 30by3 remained for underweight patients ABW (OR 5.82, 95% CI 1.32-25.57) but not obese patients. Longer ICU stays were observed for not reaching 30by3 based on ABW (β = 2.40, 95% CI 0.84-3.95) and IBW dosing (β = 1.58, 95% CI 0.07-3.08) overall. This effect remained for obese and underweight (except IBW dosing) patients. Conclusions: An exponential, dose-effect increase in mortality was observed for underweight patients not receiving 30by3. Therefore, the mortality impact of under-dosing may be amplified using ABW for underweight patients. Fluid dosing did not impact mortality for obese patients, but we caution against deviation from guidelines without further studies.

BackgroundOutdoor environmental variables, such as cold temperatures and low wind speed, have been correlated with incidence and mortality from Covid-19 (caused by the SARS-CoV-2 virus). However, as Covid-19 predominantly spreads indoors, the degree to which outdoor environmental variables might directly cause disease spread is unclear.MethodsWorld regions were considered to have reliable data if the excess mortality did not greatly exceed reported Covid-19 mortality. The relative risk of Covid-19 mortality for 142 regions as a function of median weekly temperature and wind speed was determined. For instance, Covid-19 mortality following warm weeks in a country was compared with mortality following cold weeks in the same country.ResultsCovid-19 mortality increases with cooling from 20 C to close to freezing (0 to 4 C, pConclusionThe steep decline in Covid-19 mortality with warming in the range from freezing to room temperature may relate to window opening and less indoor crowding when it is comfortable outside. Below freezing, all windows are closed, and further cooling increases stack ventilation (secondary to indoor-outdoor temperature differences) and thereby tends to decrease Covid-19 mortality. Opening windows and other tools for improving indoor ventilation may decrease the spread of Covid-19.

Background As both testing for SARS Cov-2 and death registrations are incomplete or not yet available in many countries, the full impact of the Covid-19 pandemic is currently unknown in many world regions. Methods We studied the Covid-19 and all-cause mortality in 18 Indian states (combined population of 1.26 billion) with available all-cause mortality data during the pandemic for the entire state or for large cities: Gujarat, Karnataka, Kerala, Maharashtra, Tamil Nadu, West Bengal, Delhi, Madhya Pradesh, Andhra Pradesh, Telangana, Assam, Bihar, Odisha, Haryana, Rajasthan, Himachal Pradesh, Punjab, and Uttar Pradesh. Excess mortality was calculated by comparison with available data from years 2015-2019. The known Covid-19 deaths reported by the Johns Hopkins University Center for Systems Science and Engineering for a state were assumed to be accurate, unless excess mortality data suggested a higher toll during the pandemic. Data from Uttar Pradesh were not included in the final model due to anomalies. Results In several regions, fewer deaths were registered in 2020 than expected. The excess mortality in Mumbai (in Maharashtra) in 2020 was 137.0 / 100K. Areas in Tamil Nadu, Kolkata (in West Bengal), Delhi, Madhya Pradesh, Karnataka, Haryana, and Andhra Pradesh saw spikes in mortality in the spring of 2021. Conclusions The pandemic-related mortality through June 30, 2021 in 17 Indian states was estimated to be 132.9 to 194.4 per 100,000 population. If these rates apply to India as a whole, then between 1.80 to 2.63 million people may have perished in India as a result of the Covid-19 pandemic by June 30, 2021. This per-capita mortality rate is similar to that in the United States and many other regions.

Background Early antibiotics are fundamental to sepsis management. Second-dose antibiotic delays were associated with increased mortality in a recent study. Study objectives include: 1) determine factors associated with delays in second-dose antibiotic administration; 2) evaluate if delays influence clinical outcomes. Methods ED-treated adults (≥18 years; n = 1075) with severe sepsis or septic shock receiving ≥2 doses of intravenous antibiotics were assessed, retrospectively, for second-dose antibiotic delays (dose time > 25% of recommended interval). Predictors of delay and impact on outcomes were determined, controlling for MEDS score, 30 mL/kg fluids and antibiotics within three hours of sepsis onset, lactate, and renal failure, among others. Results In total, 335 (31.2%) patients had delayed second-dose antibiotics. A total of 1864 second-dose antibiotics were included, with 354 (19.0%) delays identified by interval (delayed/total doses): 6-h (36/67) = 53.7%; 8-h (165/544) = 30.3%; 12-h (114/436) = 26.1%; 24-h (21/190) = 8.2%; 48-h (0/16) = 0%. In-hospital mortality in the timely group was 15.5% (shock-17.6%) and 13.7% in the delayed group (shock-16.9%). Increased odds of delay were observed for ED boarding (OR 2.54, 95% 1.81–3.55), shorter dosing intervals (6/8-h- OR 2.99, 95% CI 1.95–4.57; 12-h- OR 2.46, 95% CI 1.72–3.51), receiving 30 mL/kg fluids by three hours (OR 1.42, 95% CI 1.06–1.90), and renal failure (OR 2.57, 95% CI 1.50–4.39). Delays were not associated with increased mortality (OR 0.87, 95% CI 0.58–1.29) or other outcomes. Conclusions Factors associated with delayed second-dose antibiotics include ED boarding, antibiotics requiring more frequent dosing, receiving 30 mL/kg fluid, and renal failure. Delays in second-dose administration were not associated with mortality or other outcomes.

PurposeTo determine sources of variation between countries in per-capita mortality from COVID-19 (caused by the SARS-CoV-2 virus).MethodsPotential predictors of per-capita coronavirus-related mortality in 200 countries by May 9, 2020 were examined, including age, sex, obesity prevalence, temperature, urbanization, smoking, duration of infection, lockdowns, viral testing, contact tracing policies, and public mask-wearing norms and policies. Multivariable linear regression analysis was performed.ResultsIn univariate analyses, the prevalence of smoking, per-capita gross domestic product, urbanization, and colder average country temperature were positively associated with coronavirus-related mortality. In a multivariable analysis of 196 countries, the duration of infection in the country, and the proportion of the population 60 years of age or older were positively associated with per-capita mortality, while duration of mask-wearing by the public was negatively associated with mortality (all pConclusionsSocietal norms and government policies supporting the wearing of masks by the public, as well as international travel controls, are independently associated with lower per-capita mortality from COVID-19.

Supplemental Material, BMI_Supplement_10.26.2020 for The Effect of Body Mass Index and Weight-Adjusted Fluid Dosing on Mortality in Sepsis by Michael A. Ward, Hani I. Kuttab, Joseph D. Lykins V, Kristen Wroblewski, Michelle D. Hughes, Eric P. Keast, Jason A. Kopec, Erron M. Rourke and John Purakal in Journal of Intensive Care Medicine

Globally, congenital toxoplasmosis remains a significant cause of morbidity and mortality, and outbreaks of infection with T. gondii represent a significant, emerging public health burden, especially in the developing world. This parasite is a threat to public health. Disease often is not recognized and is inadequately managed. Herein, we analyze the status of congenital toxoplasmosis in Morocco, Colombia, the United States, and France. We identify the unique challenges faced by each nation in the implementation of optimal approaches to congenital toxoplasmosis as a public health problem. We suggest that developed and developing countries use a multipronged approach, modeling their public health management protocols after those in France. We conclude that education, screening, appropriate treatment, and the development of novel modalities will be required to intervene successfully in caring for individuals with this infection. Gestational screening has been demonstrated to be cost-effective, morbidity-sparing, and life-saving. Recognition of the value and promise of public health interventions to prevent human suffering from this emerging infection will facilitate better patient and societal outcomes.

Objectives Rapid fluid resuscitation has become standard in sepsis care, despite "low-quality" evidence and absence of guidelines for populations "at risk" for volume overload. Our objectives include as follows: 1) identify predictors of reaching a 30 mL/kg crystalloid bolus within 3 hours of sepsis onset (30by3); 2) assess the impact of 30by3 and fluid dosing on clinical outcomes; 3) examine differences in perceived "at-risk" volume-sensitive populations, including end-stage renal disease, heart failure, obesity, advanced age, or with documentation of volume "overload" by bedside examination. Design Retrospective cohort study. All outcome analyses controlled for sex, end-stage renal disease, heart failure, sepsis severity (severe sepsis vs septic shock), obesity, Mortality in Emergency Department Sepsis score, and time to antibiotics. Setting Urban, tertiary care center between January 1, 2014, and May 31, 2017. Patients Emergency Department treated adults (age ≥18 yr; n = 1,032) with severe sepsis or septic shock. Interventions Administration of IV fluids by bolus. Measurements and main results In total, 509 patients received 30by3 (49.3%). Overall mortality was 17.1% (n = 176), with 20.4% mortality in the shock group. Patients who were elderly (odds ratio, 0.62; 95% CI, 0.46-0.83), male (odds ratio, 0.66; CI, 0.49-0.87), obese (odds ratio, 0.18; CI, 0.13-0.25), or with end-stage renal disease (odds ratio, 0.23; CI, 0.13-0.40), heart failure (odds ratio, 0.42; CI, 0.29-0.60), or documented volume "overload" (odds ratio, 0.30; CI, 0.20-0.45) were less likely to achieve 30by3. Failure to meet 30by3 had increased odds of mortality (odds ratio, 1.52; CI, 1.03-2.24), delayed hypotension (odds ratio, 1.42; CI, 1.02-1.99), and increased ICU stay (~2 d) (β = 2.0; CI, 0.5-3.6), without differential effects for "at-risk" groups. Higher fluid volumes administered by 3 hours correlated with decreased mortality, with a plateau effect between 35 and 45 mL/kg (p Conclusions Failure to reach 30by3 was associated with increased odds of in-hospital mortality, irrespective of comorbidities. Predictors of inadequate resuscitation can be identified, potentially leading to interventions to improve survival. These findings are retrospective and require future validation.

Twenty-two compounds belonging to several classes of polyamine analogs have been examined for their ability to inhibit the growth of the human malaria parasite Plasmodium falciparum in vitro and in vivo. Four lead compounds from the thiourea sub-series and one compound from the urea-based analogs were found to be potent inhibitors of both chloroquine-resistant (Dd2) and chloroquine-sensitive (3D7) strains of Plasmodium with IC50 values ranging from 150 to 460 nM. In addition, the compound RHW, N1,N7-bis (3-(cyclohexylmethylamino) propyl) heptane-1,7-diamine tetrabromide was found to inhibit Dd2 with an IC50 of 200 nM. When RHW was administered to P. yoelii-infected mice at 35 mg/kg for 4 days, it significantly reduced parasitemia. RHW was also assayed in combination with the ornithine decarboxylase inhibitor difluoromethylornithine, and the two drugs were found not to have synergistic antimalarial activity. Furthermore, these inhibitors led to decreased cellular spermidine and spermine levels in P. falciparum, suggesting that they exert their antimalarial activities by inhibition of spermidine synthase.