Association between SARS-CoV-2 infection during pregnancy and postpartum depressive and anxiety symptoms: finding from the International Registry of Coronavirus Exposure in Pregnancy (IRCEP) study

Archives of Women's Mental Health - While there has been concern over the perinatal mental health implications of the COVID-19 outbreak, evidence on the risk of postpartum depression and...     

A 7-deaza-adenosine analog is a potent and selective inhibitor of hepatitis C virus replication with excellent pharmacokinetic properties

Improved treatments for chronic hepatitis C virus (HCV) infection are needed due to the suboptimal response rates and deleterious side effects associated with current treatment options. The triphosphates of 2'-C-methyl-adenosine and 2'-C-methyl-guanosine were previously shown to be potent inhibitors of the HCV RNA-dependent RNA polymerase (RdRp) that is responsible for the replication of viral RNA in cells. Here we demonstrate that the inclusion of a 7-deaza modification in a series of purine nucleoside triphosphates results in an increase in inhibitory potency against the HCV RdRp and improved pharmacokinetic properties. Notably, incorporation of the 7-deaza modification into 2'-C-methyl-adenosine results in an inhibitor with a 20-fold-increased potency as the 5'-triphosphate in HCV RdRp assays while maintaining the inhibitory potency of the nucleoside in the bicistronic HCV replicon and with reduced cellular toxicity. In contrast, while 7-deaza-2'-C-methyl-GTP also displays enhanced inhibitory potency in enzyme assays, due to poor cellular penetration and/or metabolism, the nucleoside does not inhibit replication of a bicistronic HCV replicon in cell culture. 7-Deaza-2'-C-methyl-adenosine displays promising in vivo pharmacokinetics in three animal species, as well as an acute oral lethal dose in excess of 2,000 mg/kg of body weight in mice. Taken together, these data demonstrate that 7-deaza-2'-C-methyl-adenosine is an attractive candidate for further investigation as a potential treatment for HCV infection.     

Why saying what you mean matters: An analysis of trauma team communication

Background

We hypothesized that team communication with unmatched grammatical form and communicative intent (mixed mode communication) would correlate with worse trauma teamwork.

Use of erythropoietin in heart failure management

OBJECTIVE: To review the use of erythropoietin for anemia in heart failure (HF). DATA SOURCES: Peer-reviewed articles in MEDLINE (1966-June 2004) were identified and citations from available articles were reviewed using the search terms anemia, erythropoietin, and heart failure. DATA SYNTHESIS: Anemia worsens HF prognosis. Clinical studies in patients with New York Heart Association Class III/IV HF who had hemoglobin <12 mg/dL and were refractory to maximal medical management showed that erythropoietin improves symptoms. Larger scale studies with mortality endpoints are required to confirm the benefits. CONCLUSIONS: In selected patients with severe, chronic HF, erythropoietin may be considered for functional improvement. However, routine use of this treatment strategy is not recommended until more data are available.     

The Interplay of Socioeconomic Status,Distance to Center,and Interdonor Service Area Travel on Kidney Transplant Access and Outcomes

Background and objectives: Variation in kidney transplant access across the United States may motivate relocation of patients with ability to travel to better-supplied areas.Design, setting, participants, & measurements: We examined national transplant registry and U.S. Census data for kidney transplant candidates listed in 1999 to 2009 with a reported residential zip code (n = 203,267). Cox''s regression was used to assess associations of socioeconomic status (SES), distance from residence to transplant center, and relocation to a different donation service area (DSA) with transplant access and outcomes.Results: Patients in the highest SES quartile had increased access to transplant compared with those with lowest SES, driven strongly by 76% higher likelihood of living donor transplantation (adjusted hazard ratio [aHR] 1.76, 95% confidence interval [CI] 1.70 to 1.83). Waitlist death was reduced in high compared with low SES candidates (aHR 0.86, 95% CI 0.84 to 0.89). High SES patients also experienced lower mortality after living and deceased donor transplant. Patients living farther from the transplant center had reduced access to deceased donor transplant and increased risk of post-transplant death. Inter-DSA travel was associated with a dramatic increase in deceased donor transplant access (HR 1.94, 95% CI 1.88 to 2.00) and was predicted by high SES, white race, and longer deceased-donor allograft waiting time in initial DSA.Conclusions: Ongoing disparities exist in kidney transplantation access and outcomes on the basis of geography and SES despite near-universal insurance coverage under Medicare. Inter-DSA travel improves access and is more common among high SES candidates.It has been nearly a decade since the Department of Health and Human Services issued the Final Rule regarding the operations of the Organ Procurement and Transplantation Network (OPTN), which directs the transplant community to reduce disparity in access to transplantation, to allocate organs over as wide of a geographic area possible, and to ensure that organs are allocated on the basis of medical necessity (1). Reflecting such directives, the kidney allocation algorithm has been adjusted to reduce the importance of HLA matching to improve access to transplantation for racial and ethnic minorities (2). However, with the exception of the recent revisions to the heart transplant allocation system (3), there have been no successful revisions to the current geographic boundaries of organ allocation.Current deceased donor allocation policy is based on a system in which kidneys are initially offered to transplant centers in the local geographic area of recovery (donation service area [DSA]) before sharing within 1 of 11 geographic United Network for Organ Sharing (UNOS) regions, which each include ≥1 DSAs. As a result of substantial differences in the ratio of organs recovered to waiting candidates, there is dramatic variation in average waiting times across the UNOS regions, ranging from <2 years to nearly 7 years (4–7).The role of socioeconomic status (SES) in determining access to transplantation services is complex because SES affects care throughout the transplant process (8,9). Patients with low SES often delay seeking medical care and lack access to specialty services, leading to delays in transplant referral, evaluation, and listing (10,11). Despite near-universal eligibility for Medicare coverage on the basis of ESRD provisions, insurance status continues to influence outcome and access to transplantation. For example, kidney transplant candidates with Medicare-only health insurance were recently shown to have a 78% lower likelihood of being pre-emptively listed for transplant compared with privately insured patients, thereby increasing waiting list morbidity and reducing post-transplant graft survival (12). Conversely, patients with college (odds ratio 1.20, P < 0.001) or postgraduate education (odd ratio 1.65, P < 0.001) were significantly more likely to be listed before dialysis.The study presented here examined the associations of SES, distance from an individual''s residence to the transplant center (quantified as travel time), and choosing to travel to a different DSA with kidney transplant access and outcomes in the United States. Specifically, we examined the differential effects of these sociodemographic factors among listed candidates and recipients of live and deceased donor organs. We sought to understand the potential contributions of SES, geographic differences in place of residence, and individual relocation behaviors to current disparities in transplant access and outcomes.