Tag: nevin manimala

Alzheimers Res Ther. 2022 Sep 23;14(1):138. doi: 10.1186/s13195-022-01079-4.

ABSTRACT

BACKGROUND: Early detection of individuals at risk for Alzheimer’s disease (AD) is highly important. Amyloid accumulation is an early pathological AD event, but the genetic association with known AD risk variants beyond the APOE4 effect is largely unknown. We investigated the association between different AD polygenic risk scores (PRS) and amyloid accumulation in the Flemish Prevent AD Cohort KU Leuven (F-PACK).

METHODS: We calculated PRS with and without the APOE region in 90 cognitively healthy F-PACK participants (baseline age 67.8 (52-80) years, 41 APOE4 carriers), with baseline and follow-up amyloid-PET (time interval 6.1 (3.4-10.9) years). Individuals were genotyped using Illumina GSA and imputed. PRS were calculated using three p-value thresholds (pT) for variant inclusion: 5 × 10^-8, 1 × 10^-5, and 0.1, based on the stage 1 summary statistics from Kunkle et al. (Nat Genet 51:414-30, 2019). Linear regression models determined if these PRS predicted amyloid accumulation.

RESULTS: A score based on PRS excluding the APOE region at pT = 5 × 10^-8 plus the weighted sum of the two major APOE variants (rs429358 and rs7412) was significantly associated with amyloid accumulation (p = 0.0126). The two major APOE variants were also significantly associated with amyloid accumulation (p = 0.0496). The other PRS were not significant.

CONCLUSIONS: Specific PRS are associated with amyloid accumulation in the asymptomatic phase of AD.

PMID:36151568 | DOI:10.1186/s13195-022-01079-4

Cardiovasc Diabetol. 2022 Sep 23;21(1):194. doi: 10.1186/s12933-022-01619-0.

ABSTRACT

BACKGROUND: Sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of kidney and heart failure events independent of glycemic effects. We assessed whether initiation of the SGLT2 inhibitor canagliflozin guided by multivariable predicted risk based on clinical characteristics and novel biomarkers is more efficient to prevent clinical outcomes compared to a strategy guided by HbA1c or urinary-albumin-creatinine ratio (UACR) alone.

METHODS: We performed a post-hoc analysis of the CANVAS trial including 3713 patients with available biomarker measurements. We compared the number of composite kidney (defined as a sustained 40% decline in eGFR, chronic dialysis, kidney transplantation, or kidney death) and composite heart failure outcomes (defined as heart failure hospitalization or cardiovascular (CV) death) prevented per 1000 patients treated for 5 years when canagliflozin was initiated in patients according to HbA1c ≥ 7.5%, UACR, or multivariable risk models consisting of: (1) clinical characteristics, or (2) clinical characteristics and novel biomarkers. Differences in the rates of events prevented between strategies were tested by Chi²-statistic.

RESULTS: After a median follow-up of 6.1 years, 144 kidney events were recorded. The final clinical model included age, previous history of CV disease, systolic blood pressure, UACR, hemoglobin, body weight, albumin, estimated glomerular filtration rate, and randomized treatment assignment. The combined biomarkers model included all clinical characteristics, tumor necrosis factor receptor-1, kidney injury molecule-1, matrix metallopeptidase-7 and interleukin-6. Treating all patients with HbA1c ≥ 7.5% (n = 2809) would prevent 33.0 (95% CI 18.8 to 43.3 ) kidney events at a rate of 9.6 (95% CI 5.5 to 12.6) events prevented per 1000 patients treated for 5 years. The corresponding rates were 5.8 (95% CI 3.4 to 7.9), 16.6 (95% CI 9.5 to 22.0) (P < 0.001 versus HbA1c or UACR approach), and 17.5 (95% CI 10.0 to 23.0) (P < 0.001 versus HbA1c or UACR approach; P = 0.54 versus clinical model). Findings were similar for the heart failure outcome.

CONCLUSION: Initiation of canagliflozin based on an estimated risk-based approach prevented more kidney and heart failure outcomes compared to a strategy based on HbA1c or UACR alone. There was no apparent gain from adding novel biomarkers to the clinical risk model. These findings support the use of risk-based assessment using clinical markers to guide initiation of SGLT2 inhibitors in patients with type 2 diabetes.

PMID:36151557 | DOI:10.1186/s12933-022-01619-0

BMC Public Health. 2022 Sep 24;22(1):1813. doi: 10.1186/s12889-022-14195-5.

ABSTRACT

BACKGROUND: Caring for children with disabilities has both immediate and long-term economic costs that affect the well-being of children, parents, and society. The purpose of this study was to investigate the impact of child disability on parental employment and labour income by examining differences by parental gender, disability severity, and child age.

METHODS: The study included children with disabilities born between 2004 to 2011 and their mothers (n = 139,189) and fathers (n = 134,457). Longitudinal data on employment, working hours and labour income was obtained from Statistics Norway, specifically the National Education Database, the Central Population Register and the Event History Database. A quasi-experimental difference-in-differences model was used to examine differences in employment, working hours and labour income.

RESULTS: The results showed that caring for children with disabilities has a negative effect on mothers’ labour market participation, working hours and labour income. The more severe a child’s condition is, the more likely the mother was to work and earn less, or to stop working entirely. Additionally, the differences in labour market participation and income between mothers of children with and without disabilities increased as their children reached school age. Labour market participation, working hours, and labour income for fathers of children with less severe disabilities is comparable to those of fathers of children without disabilities. Caring for children with more severe disabilities reduces fathers’ labour income but has no effect on their working hours or labour market participation.

CONCLUSION: Policymakers and child welfare stakeholders should evaluate policy options and provide the necessary welfare support particularly to mothers caring for children with a more severe disability.

PMID:36151541 | DOI:10.1186/s12889-022-14195-5

Cardiovasc Diabetol. 2022 Sep 23;21(1):192. doi: 10.1186/s12933-022-01613-6.

ABSTRACT

BACKGROUND: Glucokinase activators (GKAs) are an emerging class of glucose lowering drugs that activate the glucose-sensing enzyme glucokinase (GK). Pending formal cardiovascular outcome trials, we applied two-sample Mendelian randomisation (MR) to investigate the impact of GK activation on risk of cardiovascular diseases.

METHODS: We used independent genetic variants in or around the glucokinase gene meanwhile associated with HbA_1c at genome-wide significance (P < 5 × 10^-8) in the Meta-Analyses of Glucose and Insulin-related traits Consortium study (N = 146,806; European ancestry) as instrumental variables (IVs) to mimic the effects of GK activation. We assessed the association between genetically proxied GK activation and the risk of coronary artery disease (CAD; 122,733 cases and 424,528 controls), peripheral arterial disease (PAD; 7098 cases and 206,541 controls), stroke (40,585 cases and 406,111 controls) and heart failure (HF; 47,309 cases and 930,014 controls), using genome-wide association study summary statistics of these outcomes in Europeans. We compared the effect estimates of genetically proxied GK activation with estimates of genetically proxied lower HbA_1c on the same outcomes. We repeated our MR analyses in East Asians as validation.

RESULTS: Genetically proxied GK activation was associated with reduced risk of CAD (OR 0.38 per 1% lower HbA_1c, 95% CI 0.29-0.51, P = 8.77 × 10^-11) and HF (OR 0.54 per 1% lower HbA_1c, 95% CI 0.41-0.73, P = 3.55 × 10^-5). The genetically proxied protective effects of GKA on CAD and HF exceeded those due to non-targeted HbA_1c lowering. There was no causal relationship between genetically proxied GK activation and risk of PAD or stroke. The estimates in sensitivity analyses and in East Asians were generally consistent.

CONCLUSIONS: GKAs may protect against CAD and HF which needs confirmation by long-term clinical trials.

PMID:36151532 | DOI:10.1186/s12933-022-01613-6

Rhinology. 2022 Sep 23. doi: 10.4193/Rhin22.141. Online ahead of print.

NO ABSTRACT

PMID:36150154 | DOI:10.4193/Rhin22.141

Rhinology. 2022 Sep 23. doi: 10.4193/Rhin22.157. Online ahead of print.

ABSTRACT

INTRODUCTION: Compensatory inferior turbinate hypertrophy is a common accompanying manifestation in patients with nasal obstruction due to deviated nasal septum (DNS). The grounds for inferior turbinate reduction (ITR) in this population are still not well established. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of septoplasty with ITR versus septoplasty alone.

METHODS: Computerised search in Medline, Embase, and CENTRAL was performed. Eligible for inclusion were randomised controlled trials (RCTs) comparing septoplasty to septoplasty with unilateral, contralateral, ITR in adults with DNS. Primary outcomes were health-related quality of life and nasal patency. The secondary outcome was the occurrence of adverse events. Standardised mean differences (SMD) and odds ratios (OR) with 95% confidence intervals were calculated.

RESULTS: Twelve RCTs that enrolled 775 participants were found eligible. Data were reported at follow-up periods ranging from 1 month to 48 months. The pooled effect estimate showed a statistically significant improvement with unilateral, contralateral, ITR in Nasal Obstruction Symptom Evaluation scale (NOSE) scores. The rate of adverse events was significantly higher with ITR.

CONCLUSIONS: Unilateral reduction of the hypertrophied contralateral inferior turbinate during septoplasty resulted in better subjective relief of nasal obstruction in adults with DNS than septoplasty alone. However, caution is warranted since only few well-designed RCTs were identified.

PMID:36150153 | DOI:10.4193/Rhin22.157

Biostatistics. 2022 Sep 23:kxac040. doi: 10.1093/biostatistics/kxac040. Online ahead of print.

ABSTRACT

For randomized clinical trials where a single, primary, binary endpoint would require unfeasibly large sample sizes, composite endpoints (CEs) are widely chosen as the primary endpoint. Despite being commonly used, CEs entail challenges in designing and interpreting results. Given that the components may be of different relevance and have different effect sizes, the choice of components must be made carefully. Especially, sample size calculations for composite binary endpoints depend not only on the anticipated effect sizes and event probabilities of the composite components but also on the correlation between them. However, information on the correlation between endpoints is usually not reported in the literature which can be an obstacle for designing future sound trials. We consider two-arm randomized controlled trials with a primary composite binary endpoint and an endpoint that consists only of the clinically more important component of the CE. We propose a trial design that allows an adaptive modification of the primary endpoint based on blinded information obtained at an interim analysis. Especially, we consider a decision rule to select between a CE and its most relevant component as primary endpoint. The decision rule chooses the endpoint with the lower estimated required sample size. Additionally, the sample size is reassessed using the estimated event probabilities and correlation, and the expected effect sizes of the composite components. We investigate the statistical power and significance level under the proposed design through simulations. We show that the adaptive design is equally or more powerful than designs without adaptive modification on the primary endpoint. Besides, the targeted power is achieved even if the correlation is misspecified at the planning stage while maintaining the type 1 error. All the computations are implemented in R and illustrated by means of a peritoneal dialysis trial.

PMID:36150142 | DOI:10.1093/biostatistics/kxac040

J Marital Fam Ther. 2022 Sep 23. doi: 10.1111/jmft.12611. Online ahead of print.

ABSTRACT

Examining associations between therapists’ perceptions of therapy sessions and client-reported outcomes in naturalistic settings (real-life therapy settings) can provide valuable guidance for the assessment, treatment, and monitoring of clients. This study included data of 1334 sessions from 127 clients (86 individual and 41 couple cases) and 15 therapists, collected at a therapy training center. Clients reported their personal functioning and individual symptoms before each session. Therapists rated clients’ participation, receptivity, session progress, goal progress, and therapeutic alliance at the end of each therapy session. Multilevel Structural Equation Modeling analyses revealed that therapist-rated client participation and goal progress predicted better personal functioning, beyond clients’ previous personal functioning scores. In contrast, none of therapist-rated session variables predicted clients’ individual symptoms, beyond previous symptom scores. Power analyses suggested sufficient statistical power to detect small effect sizes. Findings of the current study have clinical implications for treatment planning and progress monitoring.

PMID:36150140 | DOI:10.1111/jmft.12611

Am J Med Genet A. 2022 Aug 12. doi: 10.1002/ajmg.a.62948. Online ahead of print.

ABSTRACT

Compared to the general population, individuals with Down syndrome (DS) are at a significantly increased risk to develop mental health conditions. This study sought to examine individuals with DS and co-existing mental health comorbidities at one DS specialty clinic. Retrospective chart review of medical records including demographics, genetic testing history, personal and familial mental health history, referrals for mental health indications, and recommendations was performed. Summary statistics, logistic regression, and log of odds were converted to odd ratios to assess associations and significance. The charts of 327 patients, average 19.4 years of age (1-70), were reviewed. Nearly half the participants (42.2%) had at least one diagnosis of a mental health condition. Those with a family history were significantly more likely to have a personal diagnosis of a mental health condition than those without a family history (p < 0.01). Moreover, those who completed referrals often received medical management recommendations (86%). This study highlights the prevalence of mental health comorbidities among individuals with DS, and the referral process for mental health conditions, at one DS specialty clinic. Further research is needed to investigate our family history findings, and to determine if these results are generalizable across other DS clinics.

PMID:36150133 | DOI:10.1002/ajmg.a.62948

Transbound Emerg Dis. 2022 Sep 23. doi: 10.1111/tbed.14709. Online ahead of print.

ABSTRACT

A long-term active epidemiological surveillance programme was conducted to determine seroprevalence to myxoma virus (MYXV), infection prevalence and spatiotemporal patterns and factors associated with MYXV circulation in wild rabbits (Oryctolagus cuniculus) in Spanish Mediterranean ecosystems. A total of 2,376 animals were sampled over four study periods: 2009-2012 (P1), 2012-2015 (P2), 2015-2018 (P3) and 2018-2021 (P4). Antibodies against MYXV were detected by a commercial indirect ELISA in 59.9% (1,424/2,376; 95%CI: 58.0-61.9) of wild rabbits. At least one seropositive animal was detected on 131 (96.3%) of 136 game estates sampled. MYXV infection was confirmed by PCR in 94 of 1,063 (8.8%; 95%CI: 7.3-10.7) wild rabbits. Circulation of the novel recombinant MYXV (ha-MYXV) was not found in wild rabbits analysed during P4. Five statistically significant spatiotemporal clusters of high MYXV seroprevalence were identified using a Bernoulli model: one in P2 and four in P3. A generalized linear mixed model (GLMM) analysis identified sampling season (autumn), age (adult and juvenile), outbreaks of myxomatosis in the month prior to sampling, mean annual temperature, humidity and seropositivity to rabbit haemorrhagic disease virus as factors potentially linked with MYXV seropositivity. GLMM analysis identified outbreaks of myxomatosis in the month prior to sampling, MYXV seropositivity and presence of lesions compatible with myxomatosis as factors associated with MYXV infection. The results indicate high exposure, widespread but non-homogeneous distribution, and endemic circulation of MYXV in wild rabbit populations in southern Spain during the last decade. Prevalence of antibodies against MYXV showed fluctuations both within the year and over the study periods, revealing variations in the immunity of wild rabbit populations in Mediterranean ecosystems that could increase the risk of MYXV re-emergence in immunologically naïve populations. The present study highlights the importance of long-term surveillance to better understand the epidemiology of MYXV in wild lagomorphs. This article is protected by copyright. All rights reserved.

PMID:36150087 | DOI:10.1111/tbed.14709