ImportanceThere are limited efficacious treatments for Alzheimer disease.ObjectiveTo assess efficacy and adverse events of donanemab, an antibody designed to clear brain amyloid plaque.Design, Setting, and ParticipantsMulticenter (277 medical research centers/hospitals in 8 countries), randomized, double-blind, placebo-controlled, 18-month phase 3 trial that enrolled 1736 participants with early symptomatic Alzheimer disease (mild cognitive impairment/mild dementia) with amyloid and low/medium or high tau pathology based on positron emission tomography imaging from June 2020 to November 2021 (last patient visit for primary outcome in April 2023).InterventionsParticipants were randomized in a 1:1 ratio to receive donanemab (n = 860) or placebo (n = 876) intravenously every 4 weeks for 72 weeks. Participants in the donanemab group were switched to receive placebo in a blinded manner if dose completion criteria were met.Main Outcomes and MeasuresThe primary outcome was change in integrated Alzheimer Disease Rating Scale (iADRS) score from baseline to 76 weeks (range, 0-144; lower scores indicate greater impairment). There were 24 gated outcomes (primary, secondary, and exploratory), including the secondary outcome of change in the sum of boxes of the Clinical Dementia Rating Scale (CDR-SB) score (range, 0-18; higher scores indicate greater impairment). Statistical testing allocated α of .04 to testing low/medium tau population outcomes, with the remainder (.01) for combined population outcomes.ResultsAmong 1736 randomized participants (mean age, 73.0 years; 996 [57.4%] women; 1182 [68.1%] with low/medium tau pathology and 552 [31.8%] with high tau pathology), 1320 (76%) completed the trial. Of the 24 gated outcomes, 23 were statistically significant. The least-squares mean (LSM) change in iADRS score at 76 weeks was −6.02 (95% CI, −7.01 to −5.03) in the donanemab group and −9.27 (95% CI, −10.23 to −8.31) in the placebo group (difference, 3.25 [95% CI, 1.88-4.62]; P < .001) in the low/medium tau population and −10.2 (95% CI, −11.22 to −9.16) with donanemab and −13.1 (95% CI, −14.10 to −12.13) with placebo (difference, 2.92 [95% CI, 1.51-4.33]; P < .001) in the combined population. LSM change in CDR-SB score at 76 weeks was 1.20 (95% CI, 1.00-1.41) with donanemab and 1.88 (95% CI, 1.68-2.08) with placebo (difference, −0.67 [95% CI, −0.95 to −0.40]; P < .001) in the low/medium tau population and 1.72 (95% CI, 1.53-1.91) with donanemab and 2.42 (95% CI, 2.24-2.60) with placebo (difference, −0.7 [95% CI, −0.95 to −0.45]; P < .001) in the combined population. Amyloid-related imaging abnormalities of edema or effusion occurred in 205 participants (24.0%; 52 symptomatic) in the donanemab group and 18 (2.1%; 0 symptomatic during study) in the placebo group and infusion-related reactions occurred in 74 participants (8.7%) with donanemab and 4 (0.5%) with placebo. Three deaths in the donanemab group and 1 in the placebo group were considered treatment related.Conclusions and RelevanceAmong participants with early symptomatic Alzheimer disease and amyloid and tau pathology, donanemab significantly slowed clinical progression at 76 weeks in those with low/medium tau and in the combined low/medium and high tau pathology population.Trial RegistrationClinicalTrials.gov Identifier: NCT04437511
First case of COVID-19 was reported in Wuhan, China in December 2019. As of now, May 2021, a total of 164,189,004 people were infected, and 3,401,990 deaths have occurred caused by SARS-CoV-2. As SARS-CoV-2 virus cell entry mainly depends on the ACE2 and TMPRSS2 proteins, the presence of high expression levels of both ACE2 and TMPRSS2 in testes highlights the possible vulnerability of men to the virus. Other RNA viruses frequently induce orchitis and result in male infertility. This review evaluates the decline in male fertility and a total of 48 original articles were included for the analysis. We investigated the effects of COVID-19 on male reproductive health and male fertility. There is a strong association between the high number of ACE2 receptors in the testes and the COVID-19 viral loads. SARS-CoV-2 infection negatively affects the male reproductive tract. Human biological tissues, including body fluids and excretions, tissues, and organs showed positive results tests for SARS-CoV-2. A disruption in the balance of male reproductive system hormones is also observed. Male gonads may be potentially vulnerable to SARS-CoV-2 infection, suggesting caution to follow-up and evaluate infected men that have plans to conceive. Further studies are required to determine if this impairment is temporary or permanent, elucidate SARS-CoV-2’s entrance strategies into the testis and how it can affect the semen quality and quantity. We recommend a post-infection follow-up, especially in male patients of reproductive age already having fertility issues.
Background Pregnancy is an immunocompromised state and, for this reason, a pregnant woman is at a higher risk of getting infected as compared with a healthy individual. There is limited data available regarding the impact of COVD-19 on pregnancy; however, the case of miscarriage due to placental infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in second trimester has already been reported. Methods We searched for all published articles in PubMed, Science Direct, Cochrane, Scopus, and Embase. The literature search produced 167 relevant publications; 67 manuscripts were further excluded because they did not satisfy our inclusion criteria. Out of the remaining 100 articles, 78 were excluded after full text screening. Therefore, a total of 22 articles were eligible for review in our study. Results Overall, these 22 studies included a total of 7,034 participants: 2,689 (38.23%) SARS-CoV-2 positive pregnant women, of which 2,578 (95.87%) were laboratory confirmed and 111 (4.13%) were clinically diagnosed. Among the positive patients, there were 174 (6.47%) cases of abortion, of them 168 (96.55%) were spontaneous abortions and 6 (3.45%) were missed. Most patients either reported mild symptoms of fever, cough, fatigue, and anosmia or they presented asymptomatic. Conclusion Additional investigation and rigorous research are warranted to confirm placental pathology mechanisms concerning COVID-19 to protect maternal and fetal health.
Lavras, from 1999Lavras, from to 2013. From 60 fetuses studied, 30 (50%) had microscopic lesions. From these, eight had lesions consistent with bacterial agents and three had lesions suggestive of viral agents. In the bacterial abortions, one fetus presented lesions compatible with leptospirosis, characterized by jaundice, cholestasis, lymphoplasmacytic intersticial nephritis, and tubular nephrosis. Seven fetuses had purulent pneumonia or bronchopneumonia and one of them had also fibrinous pleuritis and peritonitis; two of them presented positive immunostaining for Brucella abortus. One of the three fetuses with lesions of viral infection revealed positive imunostaining for bovine herpesvirus. The results showed that abortions of bacterial and viral origin occur in the Region of this study and prophylactic measures should be adopted on the farms. This study also demonstrates that immunohistochemistry associated with histopathology is a useful and viable tool for the diagnosis, especially when microbiological and/or serological tests are not available.
Stimulant medications including illegal use of Methamphetamine (MA) continues to rise in adolescents and young adults. This study aims to examine mortality trends because of the stimulant overdose in this age group (15 to 34 years). Methods:Age-adjusted mortality data, including 95% confidence intervals and standard errors, were extracted using publicly available multiple causes of death files from the United States Centers for Disease Control Wideranging ONline Data for Epidemiologic Research (WONDER). The data was filtered using International Classification of Disease (ICD-10) codes: F15.0 (Mental and behavioral disorders because of use of other stimulants, acute intoxication), F15.1 (Mental and behavioral disorders because of use of other stimulants, harmful use), T43.6 (Psychostimulants with abuse potential). The trends analysis for 1999 to 2019 was conducted using Joinpoint regression statistical software. Results:The mortality rate has been consistently increasing in the last decade across all races and ethnicities in adolescents and young adults. Non-Hispanic White population had the highest mortality rates (7.6 per 100,000 in 2019) compared with non-Hispanic Black (3.08 per 100,000 in 2019) and Hispanic population (3.33 per 100,000 in 2019). But the annual percent change in mortality was shown to be highest in non-Hispanic Black population (34.3% between 2009 and 2019). Conclusion:The increase in overall mortality rate because of stimulants use reflects the increase of MA use in this age group. The difference in the rate of change shows worsening racial inequality. Public health policies should be implemented to include evidence-based strategies to prevent MA misuse or overdose.
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