Category: Nevin Manimala

Neurol Res. 2023 Jan 24:1-9. doi: 10.1080/01616412.2022.2158640. Online ahead of print.

ABSTRACT

BACKGROUND: Observational studies showed renal function had associations with Alzheimer’s disease (AD), Parkinson’s disease (PD), Lewy body dementia (LBD) and multiple sclerosis (MS). However, it is unknown whether these associations are causal.

METHODS: We use a two-sample Mendelian randomization (MR) analysis to investigate causal relationships between renal function and 6 neurodegenerative diseases (NDDs): AD (including familial AD), PD, LBD, frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and MS. Blood urea nitrogen (BUN), chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) were used to measure renal function. The inverse-variance weighted (IVW) was the predominant estimation method. The results were further validated using sensitivity analysis (i.e. MR Egger regression, Cochran Q statistic of IVW, and leave-one-out method).

RESULTS: There was no indication of any causative relationship of BUN, CKD, or eGFR with AD, familial AD, PD, LBD, FTD and ALS (all P values >0.05). The IVW analysis demonstrated a causal relationship between eGFR and MS [odds ratio (OR), 4.89; 95% confidence interval (CI), 1.43 to 16.71; P = 0.01] that was not verified in the MR-Egger and weighted median (all P values >0.05). However, no causal association of MS with BUN (OR, 0.91; 95% CI, 0.40-2.07; P = 0.82) and CKD (OR,1.04; 95% CI, 0.88-1.23; P = 0.66) was found. There was no single SNP that affects the overall trend.

CONCLUSIONS: Our study showed that reduced eGFR was related to MS. The value of this study is that it provides a direction for further research on the relationship between reduced eGFR and MS.

PMID:36692889 | DOI:10.1080/01616412.2022.2158640

JAMA Netw Open. 2023 Jan 3;6(1):e2252109. doi: 10.1001/jamanetworkopen.2022.52109.

ABSTRACT

IMPORTANCE: Workplace bullying is associated with mental disorders and suicidality in civilians, but few studies have examined associations of bullying with these outcomes among military personnel.

OBJECTIVE: To evaluate associations of being bullied or hazed during deployment with major depressive disorder (MDD), intermittent explosive disorder, posttraumatic stress disorder (PTSD), suicidal ideation, and substance use disorder (SUD).

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) New Soldier Study (NSS; April 1, 2011, to November 30, 2012) and wave 1 of the STARRS Longitudinal Study (STARRS-LS1; September 1, 2016, to April 30, 2018). A computerized survey administered at 3 US Army installations (NSS) and a web/telephone survey (STARRS-LS1) were used to collect data. Data were analyzed from October 11, 2021, to October 28, 2022. The STARRS-LS1 recruited a probability sample of active-duty soldiers and veterans who had participated in Army STARRS baseline surveys while on active duty (weighted response rate, 35.6%). Respondents whose baseline was the NSS and who had deployed to a combat theater at least once were eligible for this study.

EXPOSURES: Being bullied or hazed during a combat deployment.

MAIN OUTCOMES AND MEASURES: The primary outcomes were MDD, intermittent explosive disorder, PTSD, and suicidal ideation in the 12 months before STARRS-LS1 and SUD in the 30 days before STARRS-LS1, assessed with items from the Composite International Diagnostic Interview Screening Scales, PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and Columbia-Suicide Severity Rating Scale. Logistic regression was used to estimate associations of bullying or hazing exposure with the outcomes.

RESULTS: The 1463 participants were predominantly male (weighted percentage [SE], 90.4% [0.9%]) and had a mean (SE) age of 21.1 (0.1) years at baseline. At STARRS-LS1, 188 respondents (weighted percentage [SE], 12.2% [1.1%]) reported bullying or hazing during deployment. Weighted outcome prevalences were 18.7% (1.3%) for MDD, 5.2% (0.9%) for intermittent explosive disorder, 21.8% (1.5%) for PTSD, 14.2% (1.2%) for suicidal ideation, and 8.7% (1.0%) for SUD. In models that adjusted for baseline sociodemographic and clinical characteristics and other potential traumas, exposure to bullying or hazing was significantly associated with MDD (adjusted odds ratio [aOR], 2.92; 95% CI, 1.74-4.88), intermittent explosive disorder (aOR, 2.59; 95% CI, 1.20-5.59), PTSD (aOR, 1.86; 95% CI, 1.23-2.83), suicidal ideation (aOR, 1.91; 95% CI, 1.17-3.13), and SUD (aOR, 2.06; 95% CI, 1.15-3.70).

CONCLUSIONS AND RELEVANCE: In this cohort study of combat-deployed soldiers, reports of being bullied or hazed during deployment were associated with mental disorders and suicidal thoughts. Recognition of these associations may inform efforts to prevent and address mental health problems among service members.

PMID:36692883 | DOI:10.1001/jamanetworkopen.2022.52109

JAMA Netw Open. 2023 Jan 3;6(1):e2252371. doi: 10.1001/jamanetworkopen.2022.52371.

ABSTRACT

IMPORTANCE: There are limited data about how lifestyle factors are associated with breast cancer prognosis among Black or African American women because most of the evidence is based on studies of White breast cancer survivors.

OBJECTIVE: To examine the association of prediagnostic cigarette smoking and alcohol consumption with all-cause mortality and breast cancer-specific mortality in a cohort of Black breast cancer survivors.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included 1926 Black or African American breast cancer survivors who received a diagnosis from June 6, 2005, to May 21, 2019, identified in 10 counties in New Jersey through rapid case ascertainment by the New Jersey State Cancer Registry. Statistical analysis was conducted from January 1, 2021, to August 1, 2022.

EXPOSURES: Information on prediagnostic cigarette smoking, alcohol consumption, and additional covariates was collected during in-person interviews. The covariates examined included smoking status at the time of breast cancer diagnosis (currently smoking at the time of breast cancer diagnosis, formerly smoking, or never smoking), smoking duration (number of years smoking), smoking intensity (cigarettes smoked per day), number of pack-years of smoking, and regular alcohol consumption the year before diagnosis (categorized as nondrinkers, ≤3 drinks per week, or >3 drinks per week).

MAIN OUTCOMES AND MEASURES: Primary outcomes included breast cancer-specific mortality and all-cause mortality.

RESULTS: Among the 1926 women in the study, the mean (SD) age at breast cancer diagnosis was 54.4 (10.8) years. During 13 464 person-years of follow-up (median follow-up, 6.7 years [range, 0.5-16.0 years]), there were 337 deaths, of which 187 (55.5%) were breast cancer related. Compared with never smokers, current smokers at the time of breast cancer diagnosis had a 52% increased risk for all-cause mortality (hazard ratio [HR], 1.52; 95% CI, 1.15-2.02), which was most pronounced for those with 10 or more pack-years of smoking (HR, 1.84; 95% CI, 1.34-2.53). Similar findings were observed for breast cancer-specific mortality (current smokers vs never smokers: HR, 1.27; 95% CI, 0.87-1.85), although they were not statistically significant. There was no statistically significant association between alcohol consumption and all-cause mortality (>3 drinks per week vs nondrinkers: HR, 1.05; 95% CI, 0.73-1.51) or breast cancer-specific mortality (>3 drinks per week vs nondrinkers: HR, 1.06; 95% CI, 0.67-1.67).

CONCLUSIONS AND RELEVANCE: This population-based cohort study of Black breast cancer survivors suggests that current smoking at the time of diagnosis was associated with an increased risk of all-cause mortality, particularly among women with greater pack-years of smoking.

PMID:36692882 | DOI:10.1001/jamanetworkopen.2022.52371

JAMA Netw Open. 2023 Jan 3;6(1):e2252378. doi: 10.1001/jamanetworkopen.2022.52378.

ABSTRACT

IMPORTANCE: Direct costs of substance use disorders (SUDs) in the United States are incurred primarily among the working-age population. Quantifying the medical cost of SUDs in the employer-sponsored insurance (ESI) population can improve understanding of how SUDs are affecting workplaces and inform decision-making on the value of prevention strategies.

OBJECTIVE: To estimate the annual attributable medical cost of SUDs in the ESI population from the health care payer perspective.

DESIGN, SETTING, AND PARTICIPANTS: In this economic evaluation, Merative MarketScan 2018 databases were weighted to represent the non-Medicare eligible ESI population. Regression and mathematical modeling of medical expenditures controlled for insurance enrollee demographic, clinical, and insurance factors to compare enrollees with and without an SUD diagnosis to identify the annual attributable medical cost of SUDs. Data analysis was conducted from January to March 2022.

EXPOSURES: International Statistical Classification of Diseases, Tenth Revision, Clinical Modification SUD diagnoses on inpatient or outpatient medical records according to Clinical Classifications Software categories (alcohol-, cannabis-, hallucinogen-, inhalant-, opioid-, sedative-, stimulant-, and other substance-related disorders).

MAIN OUTCOMES AND MEASURES: Annual SUD medical cost in the ESI population overall and by substance type (eg, alcohol). Number of enrollees with an SUD diagnosis and the annual mean cost per affected enrollee of SUD diagnosis (any and by substance type) are also reported.

RESULTS: Among 162 million ESI enrollees, 2.3 million (1.4%) had an SUD diagnosis in 2018. The regression analysis sample included 210 225 individuals with an SUD diagnosis (121 357 [57.7%] male individuals; 68 325 [32.5%] aged 25-44 years) and 1 049 539 individuals with no SUD diagnosis. The mean annual medical cost attributable to SUD diagnosis per affected enrollee was $15 640 (95% CI, $15 340-$15 940), and the total annual medical cost in the ESI population was $35.3 billion (2018 USD). Alcohol use disorder ($10.2 billion) and opioid use disorder ($7.3 billion) were the most costly.

CONCLUSIONS AND RELEVANCE: In this economic evaluation of medical expenditures in the ESI population, the per-person and total medical costs of SUDs were substantial. Strategies to support employees and their health insurance dependents to prevent and treat SUDs can be considered in terms of potentially offsetting the existing high medical cost of SUDs. Medical expenditures for SUDs represent the minimum direct cost that employers and health insurers face because not all people with SUDs have a diagnosis, and costs related to absenteeism, presenteeism, job retention, and mortality are not addressed.

PMID:36692881 | DOI:10.1001/jamanetworkopen.2022.52378

JAMA Netw Open. 2023 Jan 3;6(1):e2252387. doi: 10.1001/jamanetworkopen.2022.52387.

ABSTRACT

IMPORTANCE: Previous research has suggested an association of kidney function with risk of Alzheimer disease (AD) or other dementias and dementia-related blood biomarkers, but a distinct association remains unclear.

OBJECTIVE: To evaluate the association of kidney function with risk of diagnosis of incident AD or dementia within 17 years and with the blood biomarkers neurofilament light (NfL), phosphorylated tau181 (p-tau181), and glial fibrillary acidic protein (GFAP).

DESIGN, SETTING, AND PARTICIPANTS: In this prospective, population-based cohort study and nested case-control study, 9940 participants in Germany were enrolled between 2000 and 2002 by their general practitioners and followed up for up to 17 years. Participants were included if information on dementia status and creatinine/cystatin C measurements were available. A subsample of participants additionally had measurements of NfL, p-tau181, and GFAP obtained from blood samples. Statistical analysis was performed from January 3 to November 25, 2022.

EXPOSURES: Impaired kidney function, based on estimated glomerular filtration rate less than 60 mL/min/1.73 m2 according to the 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C equation.

MAIN OUTCOMES AND MEASURES: All-cause dementia, AD, and vascular dementia diagnosis, as well as log-transformed levels of NfL, p-tau181, and GFAP in blood.

RESULTS: Of 6256 participants (3402 women [54.4%]; mean [SD] age at baseline, 61.7 [6.6] years), 510 received an all-cause dementia diagnosis within 17 years of baseline. The dementia-related blood biomarker nested case-control sample included 766 participants. After adjusting for age and sex, impaired kidney function at baseline was not associated with a higher risk of all-cause dementia (hazard ratio [HR], 0.95; 95% CI, 0.69-1.29), AD (HR, 0.94; 95% CI, 0.55-1.63), or vascular dementia diagnosis (HR, 1.06; 95% CI, 0.65-1.70) within 17 years. In the cross-sectional analysis, after adjusting for age and sex, impaired kidney function was significantly associated with NfL and p-tau181 levels in blood (NfL: β = 0.47 and P < .001; p-tau181: β = 0.21 and P = .003). After adjusting for age and sex, significant associations with GFAP levels were evident only among men (men: β = 0.31 and P = .006; women: β = -0.12 and P = .11).

CONCLUSIONS AND RELEVANCE: In this population-based study of community-dwelling adults, reduced kidney function was associated with increased levels of dementia-related blood biomarkers but not increased dementia risk. Kidney function might influence the accuracy of dementia-related blood biomarkers and should be considered in clinical translation.

PMID:36692879 | DOI:10.1001/jamanetworkopen.2022.52387

Eur J Neurol. 2023 Jan 24. doi: 10.1111/ene.15702. Online ahead of print.

ABSTRACT

BACKGROUND: It has been suggested that trimethylamine N-oxide (TMAO) is related to Parkinson’s disease (PD) in observational studies. However, the direction of this association is inconsistent. An exploratory Mendelian randomisation study was conducted to investigate whether TMAO and its precursors have a causal relationship with PD.

METHODS: We obtained summary statistics for single nucleotide polymorphisms related to circulating levels of TMAO, betaine, carnitine, choline, and the corresponding data for the risk, age at onset, and progression of PD from the genome-wide association studies. Inverse variance weighting was used as the primary method for effect estimation. The false discovery rate (FDR) was applied to the correction of multiple testing. The P-value of association < 0.05 but above the FDR-corrected threshold was deemed suggestive evidence of a possible association. A range of robust MR methods were used for sensitivity analysis.

RESULTS: We observed suggestive evidence of inverse causal effect of TMAO on motor fluctuations (OR=0.851, 95%CI (0.731,0.990), P=0.037) and carnitine on insomnia (OR=0.817, 95%CI (0.700,0.954), P=0.010), and positive causal effect of betaine on Hoehn-Yahr stage (OR=1.397, 95%CI (1.112,1.756), P=0.004), Unified Parkinson’s Disease Rating Scale (UPDRS) III score (β=0.138, 95%CI (0.051,0.225), P=0.002), motor fluctuations (OR=1.236, 95%CI (1.011,1.511), P=0.039), and choline on UPDRS IV (β=0.106, 95%CI (0.026,0.185), P=0.009) and modified Schwab and England Activities of Daily Living Scale score (β=0.806, 95%CI (0.127,1.484), P=0.020).

CONCLUSIONS: Our findings provide suggestive evidence that TMAO and its precursors have a causal effect on the progression of PD. Further investigation of the underlying mechanisms is required.

PMID:36692876 | DOI:10.1111/ene.15702

Eur J Neurol. 2023 Jan 24. doi: 10.1111/ene.15703. Online ahead of print.

ABSTRACT

BACKGROUND: Performance Validity Tests (PVTs) are used in neuropsychological assessments to detect patterns of performance suggesting that the broader evaluation may be an invalid reflection of an individual’s abilities. Data on Functional motor disorder (FMD) are currently poor and conflicting.

OBJECTIVES: We aimed to examine the rate of failure at three different PVTs of non-litigant, non-compensation seeking FMD patients, and we compared their performance to that of healthy controls and controls asked to simulate malingering (healthy simulators).

METHODS: We enrolled 29 non-litigant, non-compensation seeking patients with a clinical diagnosis of FMD, 29 healthy controls and 29 healthy simulators. Three PVTs, the Coin in the Hand Test (CIH), the Rey 15-item Test (REY) and the Finger Tapping Test (FTT), were employed.

RESULTS: FMD Patients showed low rates of failure at the CIH and REY tests (7% and 10%, respectively) and slightly higher at the FTT (15%, n=26) test, which implies a motor task. Their performance was statistically comparable to that of healthy controls but statistically different from that of healthy simulators (p<0.001). 93% of FMD patients, 7% of healthy simulators, and 100% of healthy controls passed at least two of the three tests.

CONCLUSIONS: PVT performance of non-litigant, non-compensation seeking patients with FMD ranged from 7 to 15%. Patient’s performance was comparable to controls and significantly differed from that of simulators. This simple battery of three PVTs could be of practical utility and routinely used in clinical practice.

PMID:36692870 | DOI:10.1111/ene.15703

Eur J Neurol. 2023 Jan 24. doi: 10.1111/ene.15697. Online ahead of print.

ABSTRACT

BACKGROUND: Although cognitive impairment (CI) is frequent in multiple sclerosis (MS) patients, only few studies (and with conflicting results) evaluated early predictors of CI in the long-term. We aimed at determining associations between early clinical/neuroradiological variables with reference to CI after 20 years of MS.

METHODS: We investigated in 170 MS patients the relationship between clinical/MRI data at diagnosis and cognitive status after almost 20 years from MS onset. Among others, number/volume of both white matter lesions (WML) and cortical lesions (CL) were evaluated at diagnosis and after 2 years. All MS patients were followed over time and underwent a comprehensive neuropsychological assessment at the end of study. Advanced statistical methods (unsupervised cluster analysis and random forest model) were conducted.

RESULTS: CI patients showed at diagnosis higher focal cortical pathology compared to cognitively normal (p<0.001). Volumes of both WML and CL emerged as the MRI metrics most associated with long-term CI. Moreover, CL number (especially ≥3) was also strongly associated with long-term CI (≥3 CL: OR=3.7, 95% CI 1.8-7.5; p<0.001), more than WML number: the optimal cut-off of 3 CL (AUC=0.67, specificity=75%, sensitivity=55%) was estimated according to the risk of developing CI.

CONCLUSIONS: These results highlighted the importance of considering both white and grey matter focal damage since early MS stages. Given the low predictive value of WM lesion number and the poor clinical applicability of lesion volume estimation in the daily clinical context, the evaluation of CL number could represent a reliable prognostic marker of CI.

PMID:36692863 | DOI:10.1111/ene.15697

Health Promot J Austr. 2023 Feb;34(1):156-168. doi: 10.1002/hpja.649. Epub 2022 Aug 16.

ABSTRACT

ISSUE ADDRESSED: Men’s sheds (‘Sheds’) have been identified as inherently health promoting and as potential settings to engage ‘hard-to-reach’ men in more structured health promotion initiatives. However, little is known about the socio-demographic or health and wellbeing characteristics of Shed members (‘Shedders’) on which such initiatives might be based. This study captures a baseline cross-sectional analysis of Shedders (n = 384) who participated in ‘Sheds for Life’, a health promotion initiative tailored to Sheds.

METHODS: Objective health measures (body composition, blood pressure, blood lipids) captured via health screening as well as socio-demographic and health and wellbeing measures (physical activity, subjective wellbeing, mental health, social capital, cooking and diet) via questionnaires were assessed. Descriptive statistics were generated and differences between groups were determined via parametric and non-parametric testing. Bivariate analysis was used to determine associations and regression analysis then estimated various predictors on mental wellbeing, life satisfaction and loneliness.

RESULTS: Participants were mostly over 65 years (77.3%), retired (88.6%) with limited educational attainment (77%). The majority were in the ‘at-risk’ categories for objective health measures, with most being referred to their GP following health screening (79.6%). Older Shedders were also more likely to meet physical activity guidelines. Mental wellbeing was positively correlated with life satisfaction and increased social capital and these were also positively correlated with physical activity (P < .05).

CONCLUSIONS: Findings highlight the potential of Sheds in reaching a ‘hard-to-reach’ and ‘at-risk’ cohort of men. Despite a high prevalence of ‘at-risk’ objective health measures, participants report their health in positive terms. Future health promotion initiatives should capitalise on the inherent health-promoting properties of Sheds. SO WHAT?: Findings raise important implications for prioritising and designing health promotion initiatives in Shed settings.

PMID:36692862 | DOI:10.1002/hpja.649

J Nurs Res. 2023 Feb 1;31(1):e252. doi: 10.1097/jnr.0000000000000541.

ABSTRACT

BACKGROUND: Little is known regarding the effects of training programs on family caregivers of older persons with mild cognitive impairment because of the significant differences in outcome variables measured in the various studies in the literature.

PURPOSE: This study was designed to examine the effects of an outpatient-based caregiver training program on the preparedness, health-related quality of life, and depressive symptoms of participants responsible for caring for older persons with mild cognitive impairment.

METHODS: A randomized clinical trial was implemented. Of the 54 family caregiver participants who provided complete and valid data, 28 and 26 were assigned to the experimental and control groups, respectively. The experimental group participated in a researcher-developed training program that provided information on mild cognitive impairment, strategies for maintaining and promoting cognitive function in persons with mild cognitive impairment, managing their own and their care recipients’ healthcare, and managing their own emotional support and stress. Outcomes (caregiver preparedness, health-related quality of life, and depressive symptoms) were assessed before the start of the training program (baseline) and at 1, 3, and 6 months after completion of the program.

RESULTS: After controlling for baseline cognitive function of the care recipients and of caregiver preparedness, the experimental group was shown to be significantly less prepared than the control group at baseline (β = -1.41, p = .031) and better prepared than the control group at all three posttests (group differences: 1.3, 1.53, and 4.24, respectively), with the difference at the third posttest (6 months) reaching statistical significance (p = .008). No impact of the intervention on caregiver depressive symptoms or health-related quality of life was found at posttest.

CONCLUSIONS: The training intervention in this study was found to increase the perceived preparedness of the family caregiver participants to handle various aspects of providing care to persons with mild cognitive impairment. However, no changes were found in depressive symptoms or health-related quality of life.

PMID:36692834 | DOI:10.1097/jnr.0000000000000541