ULTRASTRUCTURAL BASIS OF BIOCHEMICAL EFFECTS IN A SERIES OF LETHAL ALLELES IN THE MOUSE : Neonatal and Developmental Studies

The fine structure of newborn and fetal mouse liver and of newborn kidney cells homozygous for any of three albino alleles known to have multiple biochemical effects was investigated. Electron microscope studies of mutant cells revealed dilation and vesiculation of the rough endoplasmic reticulum in parenchymal liver cells, as well as dilation and other anomalies of the Golgi apparatus. These abnormalities were observed in all newborn mutants but never in littermate controls. Although they were most pronounced in liver parenchymal cells, they were found also to a lesser degree in kidney cells, but they were absent altogether in other cell types of the mutant newborn. Homozygous fetuses showed similar anomalies in the liver at 19 days of gestational age. In one of the alleles studied, mutant liver parenchymal cells were found to be abnormal as early as the 18th day of gestation. There appears to be a striking parallelism between the biochemical defects and those of the cellular membranes in homozygous mutant newborn and fetuses. Although the specific nature of the mutational effect on membrane structure remains unknown, the results are compatible with the assumption that a mutationally caused defect in a membrane component interferes with a mechanism vital in the integration of morphological and biochemical differentiation

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

Modeling the Potential Impact of Missing Race and Ethnicity Data in Infectious Disease Surveillance Systems on Disparity Measures: Scenario Analysis of Different Imputation Strategies

BackgroundMonitoring progress toward population health equity goals requires developing robust disparity indicators. However, surveillance data gaps that result in undercounting racial and ethnic minority groups might influence the observed disparity measures. ObjectiveThis study aimed to assess the impact of missing race and ethnicity data in surveillance systems on disparity measures. MethodsWe explored variations in missing race and ethnicity information in reported annual chlamydia and gonorrhea diagnoses in the United States from 2007 to 2018 by state, year, reported sex, and infection. For diagnoses with incomplete demographic information in 2018, we estimated disparity measures (relative rate ratio and rate difference) with 5 imputation scenarios compared with the base case (no adjustments). The 5 scenarios used the racial and ethnic distribution of chlamydia or gonorrhea diagnoses in the same state, chlamydia or gonorrhea diagnoses in neighboring states, chlamydia or gonorrhea diagnoses within the geographic region, HIV diagnoses, and syphilis diagnoses. ResultsIn 2018, a total of 31.93% (560,551/1,755,510) of chlamydia and 22.11% (128,790/582,475) of gonorrhea diagnoses had missing race and ethnicity information. Missingness differed by infection type but not by reported sex. Missing race and ethnicity information varied widely across states and times (range across state-years: from 0.0% to 96.2%). The rate ratio remained similar in the imputation scenarios, although the rate difference differed nationally and in some states. ConclusionsWe found that missing race and ethnicity information affects measured disparities, which is important to consider when interpreting disparity metrics. Addressing missing information in surveillance systems requires system-level solutions, such as collecting more complete laboratory data, improving the linkage of data systems, and designing more efficient data collection procedures. As a short-term solution, local public health agencies can adapt these imputation scenarios to their aggregate data to adjust surveillance data for use in population indicators of health equity

Characterizing opioid agonist therapy uptake and factors associated with treatment retention among people with HIV in British Columbia, Canada

Accidental overdoses are now the leading cause of death among people with HIV (PWH) in British Columbia (BC). We examined the utilization and retention of opioid agonist therapy (OAT).Adult PWH (≥19 years) with ≥ 1 OAT dispensation in BC between 2008 and 2020 were included (n = 1,515). OAT treatment episodes were formed based on specific criteria for slow-release oral morphine (SROM), methadone, injectable OAT (iOAT), and buprenorphine/naloxone. Retention in treatment was defined as any episode lasting ≥ 12 months. Logistic regression with generalized estimating equations modeled retention-associated factors.There was a 56.6% decline in OAT retention over time. Buprenorphine treatment exhibited significantly lower odds of retention (OR: 0.58; 95% CI: 0.36–0.92) compared to methadone. Conversely, no significant change in retention odds was observed for SROM (0.72; 0.33–1.54) and iOAT (0.81; 0.31–2.12). Factors associated with increased odds of retention included a 10-year increase in age (1.69; 1.46–1.95), previous retention history (1.96; 1.40–2.73), achieving OAT therapeutic dose (8.22; 6.67–10.14), and suppressed HIV viral load (1.35; 1.10–1.67). Individuals with a lifetime HCV diagnosis receiving iOAT were more likely to retain (3.61; 1.20–10.83). Each additional year on OAT during the study period was associated with a 4% increase in the odds of retention.A significant proportion of PWH had a history of OAT prescribing but experienced low retention rates. Retention outcomes were more positive for SROM and iOAT. The association between OAT medication type and retention odds may be particularly influenced by HCV diagnosis. Optimal management of opioid use disorder among PWH, with an emphasis on attaining the therapeutic dose is crucial

Incidence of diabetes mellitus among people living with and without HIV in British Columbia, Canada between 2001 and 2013: a longitudinal population-based cohort study

Introduction People living with HIV (PLHIV) are increasingly at risk of age-related comorbidities such as diabetes mellitus (DM). While DM is associated with elevated mortality and morbidity, understanding of DM among PLHIV is limited. We assessed the incidence of DM among people living with and without HIV in British Columbia (BC), Canada, during 2001–2013.Methods We used longitudinal data from a population-based cohort study linking clinical data and administrative health data. We included PLHIV who were antiretroviral therapy (ART) naïve at baseline, and 1:5 age-sex-matched persons without HIV. All participants had ≥5 years of historic data pre-baseline and ≥1 year(s) of follow-up. DM was identified using the BC Ministry of Health’s definitions applied to hospitalisation, physician billing and drug dispensation datasets. Incident DM was identified using a 5-year run-in period. In addition to unadjusted incidence rates (IRs), we estimated adjusted incidence rate ratios (IRR) using Poisson regression and assessed annual trends in DM IRs per 1000 person years (PYs) between 2001 and 2013.Results A total of 129 PLHIV and 636 individuals without HIV developed DM over 17 529 PYs and 88,672 PYs, respectively. The unadjusted IRs of DM per 1000 PYs were 7.4 (95% CI 6.2 to 8.8) among PLHIV and 7.2 (95% CI 6.6 to 7.8) for individuals without HIV. After adjustment for confounding, HIV serostatus was not associated with DM incidence (adjusted IRR: 1.03, 95% CI 0.83 to 1.27). DM incidence did not increase over time among PLHIV (Kendall trend test: p=0.9369), but it increased among persons without HIV between 2001 and 2013 (p=0.0136).Conclusions After adjustment, HIV serostatus was not associated with incidence of DM, between 2001 and 2013. Future studies should investigate the impact of ART on mitigating the potential risk of DM among PLHIV

Isavuconazole in the Treatment of Chronic Forms of Coccidioidomycosis.

Coccidioidomycosis is a fungal infection with a range of clinical manifestations. Currently used antifungal agents exhibit variable efficacy and toxicity profiles that necessitate evaluation of additional therapeutic options. Improvement was observed in the majority of patients treated with isavuconazole, with clinical failures observed only in those with coccidioidal meningitis