Renal replacement therapy could be initiated in patients with severe AKI, regardless of age and critical condition

A clinical decision report using: Meersch M, Küllmar M, Schmidt C, et al. Long-Term Clinical Outcomes after Early Initiation of RRT in Critically Ill Patients with AKI. J Am Soc Nephrol. Mar 2018;29(3):1011-1019. https://doi.org/10.1681/asn.2017060694 for a critically ill elderly patient with severe acute kidney injury

Seasonality of COVID-19 incidence in the United States

BackgroundThe surges of Coronavirus Disease 2019 (COVID-19) appeared to follow a repeating pattern of COVID-19 outbreaks regardless of social distancing, mask mandates, and vaccination campaigns.ObjectivesThis study aimed to investigate the seasonality of COVID-19 incidence in the United States of America (USA), and to delineate the dominant frequencies of the periodic patterns of the disease.MethodsWe characterized periodicity in COVID-19 incidences over the first three full seasonal years (March 2020 to March 2023) of the COVID-19 pandemic in the USA. We utilized a spectral analysis approach to find the naturally occurring dominant frequencies of oscillation in the incidence data using a Fast Fourier Transform (FFT) algorithm.ResultsOur study revealed four dominant peaks in the periodogram: the two most dominant peaks show a period of oscillation of 366 days and 146.4 days, while two smaller peaks indicate periods of 183 days and 122 days. The period of 366 days indicates that there is a single COVID-19 outbreak that occurs approximately once every year, which correlates with the dominant outbreak in the early/mid-winter months. The period of 146.4 days indicates approximately 3 peaks per year and matches well with each of the 3 annual outbreaks per year.ConclusionOur study revealed the predictable seasonality of COVID-19 outbreaks, which will guide public health preventative efforts to control future outbreaks. However, the methods used in this study cannot predict the amplitudes of the incidences in each outbreak: a multifactorial problem that involves complex environmental, social, and viral strain variables

Maternal and perinatal outcomes and pharmacological management of Covid-19 infection in pregnancy: a systematic review protocol

Over 4.2 million confirmed cases and more than 285,000 deaths, COVID-19 pandemic continues to harm significant number of people worldwide. Several studies have reported the impact of COVID-19 in general population; however, there is scarcity of information related to pharmacological management and maternal and perinatal outcomes during the pandemic. Altered physiological, anatomical, and immunological response during pregnancy makes it more susceptible to infections. Furthermore, during pregnancy, a woman undergoes multiple interactions with the health care system that increases her chance of getting infected; therefore, managing pregnant population presents a unique challenge. This systematic review seeks to answer the following questions in relation to COVID-19: What are the different clinical characteristics presented in maternal and perinatal population? What are the different maternal and perinatal outcome measures reported? What are the distinct therapeutic interventions reported to treat COVID-19? Is it safe to use "medications" used in the treatment of COVID-19 during antenatal, perinatal, postnatal, and breastfeeding? The search will follow a comprehensive, sequential three step search strategy. Several databases relevant to COVID-19 and its impact on pregnancy including Medline, CINAHL, and LitCovid will be searched from the inception of the disease until the completion of data collection. The quality of this search strategy will be assessed using Peer Review of Electronic Search Strategies Evidence-Based Checklist (PRESS EBC). An eligibility form will be developed for a transparent screening and inclusion/exclusion of studies. All studies will be sent to RefWorks, and abstraction will be independently performed by two researchers. Risk of bias will be assessed using Cochrane Risk of Bias tool for randomized controlled trials, Newcastle-Ottawa Quality Assessment Scale for non-randomized studies, and for case reports, Murad et al. tool will be used. Decision to conduct meta-analysis will be based on several factors including homogeneity and outcome measures reported; otherwise, a narrative synthesis will be deemed appropriate. This systematic review will summarize the existing data on effect of COVID-19 on maternal and perinatal population. Furthermore, to the best of our knowledge, this is the first systematic review addressing therapeutic management and safety of medicines to treat COVID-19 during pregnancy and breastfeeding. This systematic review has been registered and published with Prospero ( CRD42020172773 )

Maternal Mortality Ratio and Universal Access to Reproductive Health Care in the State of Qatar between 1990 and 2012: A PEARL Study Analysis

Study Aim: The Millennium Development Goal (MDG)- 5 mandates a three quarters reduction in Maternal Mortality Ratio (MMR) and provision of universal access to reproductive health by 2015. Our study aims to analyze Qatar’s performance in achieving MDG 5 between 1990 and 2012.Study Design: A National Prospective cohort-studyData Source: Qatar Perinatal Registry (Q-Peri-Reg) for 2011 and 2012 dataMethods: National data on total deliveries, total births (live and stillbirths) and maternal mortality (during pregnancy to day 42 post-delivery) was collected from all public and private maternity units in Qatar (1st January 2011- December, 31st 2012) and compared with historical maternal mortality data (1990-2010) ascertained from the database of maternity and neonatal units of Women’s Hospital, annual reports of Hamad Medical Corporation and international reports. For inter country comparison, country data was extracted from World Health Statistics 2011(WHO).Results: The country wide live births were 20583 during 2011 and 22,225 during 2012 with two maternal deaths duringeach year giving an MMR of 9.85/100,000 and 8.99/100,000 live births respectively which was more than three quarters decline from an MMR of 49/100,000 in 1990. During 2011, 74.22% deliveries were normal vaginal (n 15076) and 25.78% (n 5238) by Caesarean section. 99.45 % of deliveries were attended by a trained birth attendant in a maternity facility while 0.55 % (n = 114) took place out of hospital. 100% of mothers had made at least one antenatal visit and 100% of live births were examined by a pediatrician and entered in national birth register. Qatar’s 2011 and 2012 MMR is significantly lower than the current global MMR of 260/100,000 and Eastern Mediterranean Region MMR of 320/100,000.Conclusion: Qatar has achieved its target MDG 5 well before 2015. Qatar’s 2011 and 2012 MMR is comparable to most high income countries. Qatar’s reproductive health system, with its universal access for all, provides a unique model to study the correlates and associations of maternal survival which can form the basis of global health systems improvement strategies

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

The Short-term Effects of Fine Airborne Particulate Matter and Climate on COVID-19 Disease Dynamics

Background: Despite more than 60% of the United States population being fully vaccinated, COVID-19 cases continue to spike in a temporal pattern. These patterns in COVID-19 incidence and mortality may be linked to short-term changes in environmental factors. Methods: Nationwide, county-wise measurements for COVID-19 cases and deaths, fine-airborne particulate matter (PM2.5), and maximum temperature were obtained from March 20, 2020 to March 20, 2021. Multivariate Linear Regression was used to analyze the association between environmental factors and COVID-19 incidence and mortality rates in each season. Negative Binomial Regression was used to analyze daily fluctuations of COVID-19 cases and deaths with those of environmental factors in New York, NY. Results: In Spring 2020, a 1 µg/m3increase in average county PM2.5 concentration was associated with a 15.7% increase in incidence rate and a 9.3% increase in death rate. In Summer 2020, a 1 K increase in maximum temperature was associated with a 11.5% increase in incidence rate, but a 1.7% decrease in incidence rate in Fall 2020. For each 1 µg/m3and 1 K increase in daily PM2.5 concentration and maximum daily temperature in New York, NY, daily COVID-19 cases increase by 5.2% and decrease by 2.3%, respectively. Discussion: The effect of PM2.5 concentration and maximum temperature on COVID-19 incidence and mortality rates varied greatly between different seasons. The temporality of COVID-19 could be linked to the seasonality of these effects. Furthermore, the significant association of daily measurements of environmental factors with COVID-19 cases and deaths warrants further analysis across multiple counties

The primary unfolded protein response transducer endoplasmic reticulum-to-nucleus signaling 1 is downregulated in livers of human nonalcoholic steatohepatitis patients

Background: The Unfolded Protein Response (UPR) is an elegant signaling pathway from the Endoplasmic Reticulum (ER) to protect cells from stress caused by accumulation of unfolded or misfolded proteins in the ER lumen. ER-to-Nucleus Signaling 1 (IRE1, also called ERN1), an ER-localized protein kinase and endoribonuclease (RNase), is the most conserved transducer of the UPR signaling pathway. In this study, we investigated expression levels of IRE1 in the livers of human non-alcoholic steatohepatitis (NASH) patients. Methods: We analyzed the expression profiles of the primary UPR transducer IRE1 in the livers of human NASH patients based on the microarray gene expression datasets obtained from public domain. Results: Our analyses indicated that expression levels of IRE1 were decreased in the livers of human obese patients with NASH, compared to those of obese patients without NASH. Conclusions: Our analysis result is consistent with the role of IRE1-mediated UPR in preserving cellular homeostasis and functions and in protecting organisms from injuries. This study provides important information in regard to the activation and functional involvement of the UPR signaling pathway in human NASH

The links of fine airborne particulate matter exposure to occurrence of cardiovascular and metabolic diseases in Michigan, USA.

Air pollutants, particularly airborne particulate matter with aerodynamic diameter < 2.5μm (PM2.5), have been linked to the increase in mortality and morbidity associated with cardiovascular and metabolic diseases. In this study, we investigated the dose-risk relationships between PM2.5 concentrations and occurrences of cardiovascular and metabolic diseases as well as the confounding socioeconomic factors in Michigan, USA, where PM2.5 levels are generally considered acceptable. Multivariate linear regression analyses were performed to investigate the relationship between health outcome and annual ground-level PM2.5 concentrations of 82 counties in Michigan. The analyses revelated significant linear dose-response associations between PM2.5 concentrations and cardiovascular disease (CVD) hospitalization. A 10 μg/m3 increase in PM2.5 exposure was found to be associated with a 3.0% increase in total CVD, 0.45% increase in Stroke, and a 0.3% increase in Hypertension hospitalization rates in Medicare beneficiaries. While the hospitalization rates of Total Stroke, Hemorrhagic Stroke, and Hypertension in urbanized counties were significantly higher than those of rural counties, the death rates of coronary heart disease and ischemic stroke in urbanized counties were significantly lower than those of rural counties. These results were correlated with the facts that PM2.5 levels in urbanized counties were significantly higher than that in rural counties and that the percentage of the population with health insurance and the median household income in rural counties were significantly lower. While obesity prevalence showed evidence of a weak positive correlation (ρ = 0.20, p-value = 0.078) with PM2.5 levels, there was no significant dose-response association between county diabetes prevalence rates and PM2.5 exposure in Michigan. In summary, this study revealed strong dose-response associations between PM2.5 concentrations and CVD incidence in Michigan, USA. The socioeconomic factors, such as access to healthcare resources and median household income, represent important confounding factors that could override the impact of PM2.5 exposure on CVD mortality