Tag: pubmed

Mult Scler. 2022 Jun 23:13524585221100401. doi: 10.1177/13524585221100401. Online ahead of print.

ABSTRACT

Randomised controlled trials (RCTs) play an important role in multiple sclerosis (MS) research, ensuring that new interventions are safe and efficacious before their introduction into clinical practice. Trials have been evolving to improve the robustness of their designs and the efficiency of their conduct. Advances in digital and mobile technologies in recent years have facilitated this process and the first RCTs with decentralised elements became possible. Decentralised clinical trials (DCTs) are conducted remotely, enabling participation of a more heterogeneous population who can participate in research activities from different locations and at their convenience. DCTs also rely on digital and mobile technologies which allows for more flexible and frequent assessments. While hospitals quickly adapted to e-health and telehealth assessments during the COVID-19 pandemic, the conduct of conventional RCTs was profoundly disrupted. In this paper, we review the existing evidence and gaps in knowledge in the design and conduct of DCTs in MS.

PMID:35735014 | DOI:10.1177/13524585221100401

Stroke. 2022 Jun 23:101161STROKEAHA121038659. doi: 10.1161/STROKEAHA.121.038659. Online ahead of print.

ABSTRACT

BACKGROUND: Millions of women worldwide use exogenous hormones as oral contraceptives or hormone replacement therapy. Still, time-dependent and long-term consequences of exogenous hormones on stroke risk remains unclear.

METHODS: We examined the association between self-reported oral contraceptive and hormone replacement therapy use and stroke risk in 257 194 women from the UK Biobank, born between 1939 and 1970. Outcomes included any type of stroke, ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Exposures were analyzed as time-varying variables in Cox regression models.

RESULTS: During first year of oral contraceptive use, an increased event rate of any stroke was observed (hazard ratio [HR], 2.49 [95% CI, 1.44-4.30]), while the hazards were found to be comparable during remaining years of use (HR, 1.00 [95% CI, 0.86-1.14]), compared with nonusers. Similarly, first year of hormone replacement therapy use was associated with higher hazard rates of any stroke (HR, 2.12 [95% CI, 1.66-2.70]), as well as cause-specific stroke, including ischemic stroke (HR, 1.93 [95% CI, 1.05-3.57]) and subarachnoid hemorrhage (HR, 2.17 [95% CI, 1.25-3.78]), which remained increased for any stroke during remaining years of use (HR, 1.18 [95% CI, 1.05-1.31]), and after discontinuation (HR, 1.16 [95% CI, 1.02-1.32]).

CONCLUSIONS: Oral contraceptive use and hormone replacement therapy were associated with an increased risk of stroke, especially during the first year of use, possibly due to immediate changes in hemostatic balance. This study provides new insights on the effects of hormone exposure on stroke risk and provide evidence of not only an overall risk but also a pronounced effects seen in the beginning of treatment.

PMID:35735009 | DOI:10.1161/STROKEAHA.121.038659

Circulation. 2022 Jun 23:101161CIRCULATIONAHA121058389. doi: 10.1161/CIRCULATIONAHA.121.058389. Online ahead of print.

ABSTRACT

BACKGROUND: Genome-wide association studies have identified many genetic loci that are robustly associated with coronary artery disease (CAD). However, the underlying biological mechanisms are still unknown for most of these loci, hindering the progress to medical translation. Evidence suggests that the genetic influence on CAD susceptibility may act partly through vascular smooth muscle cells (VSMCs).

METHODS: We undertook genotyping, RNA sequencing, and cell behavior assays on a large bank of VSMCs (n>1499). Expression quantitative trait locus and splicing quantitative trait locus analyses were performed to identify genes with an expression that was influenced by CAD-associated variants. To identify candidate causal genes for CAD, we ascertained colocalizations of VSMC expression quantitative trait locus signals with CAD association signals by performing causal variants identification in associated regions analysis and the summary data-based mendelian randomization test. Druggability analysis was then performed on the candidate causal genes. CAD risk variants were tested for associations with VSMC proliferation, migration, and apoptosis. Collective effects of multiple CAD-associated variants on VSMC behavior were estimated by polygenic scores.

RESULTS: Approximately 60% of the known CAD-associated variants showed statistically significant expression quantitative trait locus or splicing quantitative trait locus effects in VSMCs. Colocalization analyses identified 84 genes with expression quantitative trait locus signals that significantly colocalized with CAD association signals, identifying them as candidate causal genes. Druggability analysis indicated that 38 of the candidate causal genes were druggable, and 13 had evidence of drug-gene interactions. Of the CAD-associated variants tested, 139 showed suggestive associations with VSMC proliferation, migration, or apoptosis. A polygenic score model explained up to 5.94% of variation in several VSMC behavior parameters, consistent with polygenic influences on VSMC behavior.

CONCLUSIONS: This comprehensive analysis shows that a large percentage of CAD loci can modulate gene expression in VSMCs and influence VSMC behavior. Several candidate causal genes identified are likely to be druggable and thus represent potential therapeutic targets.

PMID:35735005 | DOI:10.1161/CIRCULATIONAHA.121.058389

J Biochem Mol Toxicol. 2022 Jun 23:e23154. doi: 10.1002/jbt.23154. Online ahead of print.

ABSTRACT

Statins are widely used lipid-lowering drugs that cause many side effects. Withaferin-A (WA), popularly known as Ashwagandha, an ancient Indian medicinal herb, is extracted from Withania somnifera. Anti-atherosclerotic effect of WA has been reported. However, the mechanism remains unknown. Hence, we planned this study to investigate the WA mechanism in anti-atherosclerosis in a rat model. High cholesterol diet (HCD) was fed to induce atherosclerosis in Sprague-Dawley male rats. Five groups (N = 6 rats/group) were fed with normal diet, HCD, WA (10 mg/kg bw)+HCD, lovastatin (LS: 10 mg/kg bw)+HCD, WA (10 mg/kg bw) respectively for 90 days. Statistical analysis was done by GraphPad Prism (version 8.0.1) using one-way analysis of variance (ANOVA) followed by post hoc Duncan’s test with a significance level (p < 0.05). The groups were compared for lipid profiles, oxidative stress, lipid peroxidation, inflammatory mediators, apoptotic markers, and histopathological changes in the liver and aorta. Treatment with HCD increased lipid profiles, inflammatory mediators, cytokines, and lipid peroxidation. WA as well as LS treatments significantly decreased these parameters restored the antioxidant status, and reduced lipid peroxidation (p < 0.05). Histopathological studies revealed that WA and LS reduced the hepatic fat and aortic plaque. WA reduced apoptosis via augmentation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway; increased B-cell lymphoma 2 and inhibited Bcl-2 associated X-protein proapoptotic proteins; TNF receptor superfamily member 6, Bim, caspase-3, and -9; demonstrated significant hypolipidemic and anti-inflammatory properties against HCD induced atherosclerosis in rats through regulation of inflammatory mediators and apoptosis via the PI3K/AKT signaling pathway.

PMID:35734936 | DOI:10.1002/jbt.23154

J Intellect Disabil Res. 2022 Jun 23. doi: 10.1111/jir.12959. Online ahead of print.

ABSTRACT

BACKGROUND: Low muscle quality index (MQI) is a potential risk of developing functional impairments in older people. However, considering that individuals with Down syndrome (DS) present with a faster decline in biological aging, an investigation on MQI in individuals with DS is necessary. The aims of this present cross-sectional study were to compare (1) MQI between adolescents with and without DS and (2) evaluate laboratory versus field-based estimates of MQI.

METHODS: Fifty-six adolescents were recruited and separated into two groups: DS (n = 30, 13 boys and 17 girls; age: 12.38 ± 3.07 years) and a control (non-DS; n = 26, 9 boys and 17 girls; age: 12.46 ± 2.88 years). Laboratory MQI was derived from the ratio of grip strength to arm muscle mass (in kg) measured by dual-energy X-ray absorptiometry (DXA). Field-based MQI was quantified from the ratio of hand grip strength (HGS) to body mass index (BMI). For statistical analyses, a two-way ANOVA was conducted for group comparisons, and a Pearson correlation was used to test the association between field MQI and laboratory MQI.

RESULTS: Adolescents with DS displayed lower field (P = 0.001), laboratory MQI estimates (P = 0.001) and HGS (P = 0.001) as compared non-DS. Also, there was a strong correlation effect between field MQI and laboratory MQI estimates (P < 0.001, R = 0.81).

CONCLUSION: Adolescents with DS have lower field and laboratory MQI compared with adolescents without DS. Simpler field MQI might be used in daily clinical practice, with special attention to those with DS.

PMID:35734961 | DOI:10.1111/jir.12959

Haematologica. 2022 Jun 23. doi: 10.3324/haematol.2022.280660. Online ahead of print.

ABSTRACT

Not available.

PMID:35734925 | DOI:10.3324/haematol.2022.280660

Dtsch Arztebl Int. 2022 Aug 22;(Forthcoming):arztebl.m2022.0229. doi: 10.3238/arztebl.m2022.0229. Online ahead of print.

ABSTRACT

BACKGROUND: 40 000 to 60 000 people develop malignant pleural effusion (MPE) in Germany each year. The most common causes are lung cancer and breast cancer. Patients with pleural carcinomatosis have a median survival time of four months.

METHODS: We investigated the current health services situation regarding treatment with indwelling pleural catheters (IPC) versus talc pleurodesis (TP) in Germany based on registry data from the Federal Statistical Office, the Pleural Tumor Registry of the German Society for Thoracic Surgery, and the IPC registry of the ewimed GmbH company. In addition, we conducted a selective literature review on IPC and TP.

RESULTS: The symptoms of dyspnea and thoracic pressure determine the need for therapy in MPE. Both TP and IPC are effective treatment options for MPE. Both therapeutic procedures are considered equally effective with respect to the relief of dyspnea, post-interventional quality of life, and complication rates. TP yields a higher rate of successful pleurodesis than IPC (relative risk: 1.56; 95% confidence interval: [1.26; 1.92]; p < 0.0001), while patients who receive an IPC stay in the hospital for a shorter time than those who undergo TP (a difference of slightly more than two days). The survival of patients with MPE is not affected by which of the two local therapeutic procedures is chosen.

CONCLUSION: The indication for either IPC or TP needs to be determined individually for each patient on the basis of his or her general condition, symptoms, clinical situation (“trapped lung”), and prognosis.

PMID:35734918 | DOI:10.3238/arztebl.m2022.0229

Dtsch Arztebl Int. 2022 Sep 5;(Forthcoming):arztebl.m2022.0235. doi: 10.3238/arztebl.m2022.0235. Online ahead of print.

ABSTRACT

BACKGROUND: Studies from Denmark and the USA have shown that the outcome of treatment of peripheral arterial occlusive disease (PAOD) varies as a function of the size and certification status of the treating hospital. It is not yet known whether this holds for Germany as well.

METHODS: We studied all hospitalizations for PAOD of stage IIb or higher (in Fontaine’s classification) using DRG statistics from the German Federal Statistical Office. The treating hospitals were classified by size and certification status. For each hospitalization, the patient’s PAOD stage, age, sex, and comorbidities were recorded. Independent variables predicting different endpoints of treatment were identified by univariate and multivariate logistic regression.

RESULTS: 29% of the 558 785 hospitalizations included in our analysis were in hospitals with certified vascular centers. In a multivariate analysis, hospitalization in a certified hospital was associated with a lower rate of major amputation (odds ratio [OR] 0.95; 95% confidence interval [0.92; 0.98], p = 0.003) and a higher rate of minor amputation (OR 1.04 [1.01; 1.06], p = 0.004), with no difference in mortality (OR 0.99 [0.96; 1.03], p = 0.791). Patients who were treated in larger hospitals had more extensive comorbidity, stayed longer in the hospital, and had higher amputation rates and a higher mortality.

CONCLUSION: Being treated for PAOD in a certified hospital is associated with fewer major amputations and more minor amputations. This may be due to greater utilization of treatments aimed at preserving limb function.

PMID:35734915 | DOI:10.3238/arztebl.m2022.0235

Thyroid. 2022 Jun 23. doi: 10.1089/thy.2022.0243. Online ahead of print.

ABSTRACT

BACKGROUND: Thyroid dysfunction has been observed among some patients with COVID-19. It is unclear whether SARS-CoV-2 infection (or its severity) leads to the development of thyroid dysfunction, or vice versa. In this study, we examined the bi-directional causal relationship between host genetic liability to three COVID-19 phenotypes (including SARS-CoV-2 infection, hospitalized and severe COVID-19) and three thyroid dysfunction traits [including hyperthyroidism, hypothyroidism, and autoimmune thyroid disease (AITD)] and three continuous traits of thyroid hormones [including thyroid-stimulating hormone (TSH) and free thyroxine (FT4) within reference range, and TSH in full range].

METHODS: Summary statistics from the largest available meta-analyses of human genome-wide association studies were retrieved for the following variables: SARS-CoV-2 infection (n=1,348,701), COVID-19 hospitalization (n=1,557,411), severe COVID-19 (n=1,059,456), hyperthyroidism (n=51,823), hypothyroidism (n=53,423), AITD (n=755,406), TSH within reference range (n=54,288), FT4 within reference range (n=49,269), and TSH in full range (n=119,715). Using a two-sample Mendelian randomization (MR) approach, the inverse-variance weighted (IVW) method was adopted as the main MR analysis. Weighted median, contamination mixture, MR-Egger, and MR-PRESSO methods were applied as sensitivity analyses.

RESULTS: Host genetic susceptibility to SARS-CoV-2 infection was causally associated with hypothyroidism in the main IVW analysis (per doubling in prevalence of SARS-CoV-2 infection, Odds Ratio (OR)=1.335; 95% CI: 1.167-1.526; p=2.4×10-5, surpassing the Bonferroni multiple-testing threshold). Similar causal estimates were observed in the sensitivity analyses (weighted median: OR=1.296; 95% CI: 1.066-1.575; p=9×10-3; contamination mixture: OR=1.356; 95% CI: 1.095-1.818; p=0.013; MR-Egger: OR=1.712; 95% CI: 1.202-2.439; p=2.92×10-3, and MR-PRESSO: OR=1.335; 95% CI: 1.156-1.542; p=5.73×10-4). Host genetic liability to hospitalized or severe COVID-19 was not associated with thyroid dysfunction or thyroid hormone levels. In the reverse direction, there was no evidence to suggest that genetic predisposition to thyroid dysfunction or genetically determined thyroid hormone levels altered the risk of the COVID-19 outcomes.

CONCLUSIONS: This bi-directional MR study supports that host response to SARS-CoV-2 viral infection plays a role in the causal association with increased risk of hypothyroidism. Long-term follow-up studies are needed to confirm the expected increased hypothyroidism risk.

PMID:35734897 | DOI:10.1089/thy.2022.0243

Psychiatr Serv. 2022 Jun 23:appips202100651. doi: 10.1176/appi.ps.202100651. Online ahead of print.

ABSTRACT

OBJECTIVE: A 3-year study explores employment outcomes of certified peer specialists (CPSs). Analyses reported here identified relationships between demographic, clinical, work history, and geographic characteristics and employment status and current employment in peer services jobs versus other jobs.

METHODS: The study recruited adults who recently became a CPS, regardless of current employment status, in four states. Online survey data were collected from March to October 2020 and included demographic information, health status and diagnoses, mental health service use, motivations for becoming certified, employment history, and job characteristics, including job satisfaction. Descriptive statistics and logistic regression models were used to compare groups.

RESULTS: Of 681 respondents, 591 provided data on current employment and were included. Participants who received Social Security Disability Insurance or Supplemental Security Income, veterans, those who used outpatient counseling or therapy, and those who did not disclose their mental health status in the workplace were less likely to report current employment. Lack of disclosure and higher local unemployment rates contributed to a lower likelihood of working in peer services jobs, whereas individuals reporting depressive disorders were more likely to hold such jobs. Compared with those in other jobs, those in peer services jobs reported longer job tenure, and a larger proportion received employee benefits. Job satisfaction was significantly higher among those with peer services jobs.

CONCLUSIONS: Workers with a CPS credential had higher employment rates, compared with adults with psychiatric disabilities, and the quality of peer specialist jobs was equal to or higher than the quality of other jobs held by study participants.

PMID:35734863 | DOI:10.1176/appi.ps.202100651