Exploring the impact of HIV infection and antiretroviral therapy on placenta morphology.

INTRODUCTION: Women living with HIV experience more adverse birth outcomes; the mechanisms are not fully understood. We examined placenta morphology and associations with birth outcomes in a Canadian cohort of women living with HIV (HIV+) on antiretroviral therapy (ART) from conception and HIV-uninfected (HIV-) women. METHODS: Term placentas from 94 women (40 HIV-, 54 HIV+) were studied. Trimmed placenta weight was collected. Placenta digital photos were used to compute morphometric parameters. Regression models investigated associations between log-transformed placenta parameters and birth outcomes. RESULTS: We observed a trend towards lower placenta weight and smaller placenta area in the HIV+ group, both of which were significantly associated with small for gestational age births. HIV+ serostatus was associated with 6-fold (95%CI 2-20) greater odds of having placenta area in the lowest quartile (<236 cm2). Cord marginality (distance from the edge) was significantly lower in the HIV+ group (p = 0.004), with 35% of placenta having an abnormal (marginal or velamentous) cord insertion vs. 12.5% in the HIV- group (p = 0.01). Velamentous cord insertion was seen in 13% of placentas in the HIV+ vs. 0% in HIV- group (p = 0.02). A significant correlation between cord marginality and placenta thickness was observed in the HIV- group, with a more marginal cord being associated with a thicker placenta. This correlation was not observed in the HIV+ group. HIV+ placentas exposed to protease inhibitors were significantly less circular compared to the HIV- group (p = 0.03). CONCLUSION: Our data suggest that HIV/ART exposure affects placenta morphology and is associated with higher rates of abnormal cord insertion.

Interferon beta-1a for patients with moderate to severe acute respiratory distress syndrome: a systematic review and meta-analysis of randomized trials.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a life-threatening disease characterized by respiratory failure with rapidly progressing inflammation. Currently, no effective pharmacological treatment for ARDS is available. OBJECTIVES: We conducted this systematic review and meta­ analysis to examine the use of interferon beta-1a in patients with ARDS. METHODS: Data sources included the following databases: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. We retained trials from 1996 to February 25, 2020 that comparatively examined the use of interferon beta-1a in patients with ARDS. Two reviewers identified eligible studies, independently extracted study data, and assessed the risk of bias. The authors evaluated the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: We included 2 trials (n = 392 patients). No significant differences in 28-day hospital mortality (risk ratio [RR], 0.59; 95% CI, 0.13-2.67; P = 0.49; very low certainty) and the number of ventilator-free days (mean difference, 4.85 days; 95% CI, -3.25 to 12.93; P = 0.24, very low certainty) were observed in patients treated with interferon beta-1a compared with those not receiving this drug. Interferon beta-1a also had no significant impact on the risk of adverse events (RR, 0.98%; 95% CI, 0.94-1.03; P = 0.47; low certainty). CONCLUSIONS: The use of interferon beta-1a does not appear to improve mortality or reduce the number of ventilator-free days and adverse events in patients with ARDS. This review is based on 2 small studies reporting a limited number of events, which raises questions regarding the true effects of interferon beta-1a. The analysis of 1 study revealed increased mortality with the concomitant use of corticosteroids and interferon beta-1a, suggesting a need for careful consideration of this drug-drug interaction.

COVID-19 coronavirus research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine.

OBJECTIVES/BACKGROUND AND OBJECTIVES: Prior epidemics of high-mortality human coronaviruses, such as the acute respiratory syndrome coronavirus (SARS-CoV or SARS-1) in 2003, have driven the characterization of compounds that could be possibly active against the currently emerging novel coronavirus SARS-CoV-2 (COVID-19). Presently, no approved treatment or prophylaxis is available for COVID-19. We comment on the existing COVID-19 research methodologies in general and the published reporting. Given the media attention and claims of effectiveness, we chose chloroquine and hydroxychloroquine, in combination with azithromycin, as an area of COVID-19 research to examine. METHODS/STUDY DESIGN AND SETTING: MEDLINE and EMBASE electronic databases were searched from 2019 to present (April 3rd, 2020) using a mix of keywords such as COVID-19 and chloroquine and hydroxychloroquine. We also searched the largest clinical medicine preprint repository, medRxiv.org. RESULTS: We found 6 studies, 3 randomized control trials and 3 observational studies, focusing on chloroquine and hydroxychloroquine (with azithromycin). We critically appraised the evidence. CONCLUSION: We found that the COVID-19 research methodology is very poor in the area of chloroquine/hydroxychloroquine research. In screening the literature, we observed the same across COVID-19 research in relation to potential treatments. The reporting is very poor and sparse, and patient-important outcomes needed to discern decision-making priorities are not reported. We do understand the barriers to perform rigorous research in health care settings overwhelmed by a novel deadly disease. However, this emergency pandemic situation does not transform flawed methods and data into credible results. The adequately powered, comparative, and robust clinical research that is needed for optimal evidence-informed decision-making remains absent in COVID-19.

Clinical evaluation of sealants and preventive resin restorations in a group of environmentally homogeneous children.

PURPOSE: Pit and fissure sealants reduce occlusal caries when proper patient selection and application techniques are followed. To increase retention rate of sealants over time, good adaptation and deep sealant penetration are important. Studies remain inconclusive, however, as to determining if the bur preparation of pits and fissures would increase the adaptation and penetration thus improving sealant retention. The aim of this study was to assess if tooth preparation prior to sealant application improves sealant retention. METHODS: In this prospective cohort study, 43 children and adolescents from 4 Hutterites colonies were, for 3 years, bussed to the University of Manitoba pediatric dental clinic, Winnipeg, Manitoba, Canada, for comprehensive dental care including sealant placement using standard procedures. These came from a community with homogeneous social economical status, dietary habits, fluoride intake, and lifestyles. The decision of tooth preparation prior to sealant application was made ad hoc. Of 122 treated permanent posterior teeth, 54 had been treated as preventive resin restorations (PRRs, type A or B) and 68 were nonprepared sealants. RESULTS: After 1 year, teeth prepared (type B PRRs) and restored with flowable composite resins had significantly (P<.01) lower retention rates (27% vs 63%) than did teeth with nonprepared sealants or typeA PRRs. Teeth prepared (type B PRRs) were also significantly (P<.001) more likely to have caries on follow-up examination (50% vs 11%) than were teeth with nonprepared sealants or type A PRRs. CONCLUSIONS: These results suggest that preventive resin type B restorations restored with flowable composites are not helpful in terms of retention or caries reduction.