Nevin Manimala

Eur J Prev Cardiol. 2021 Oct 25;28(13):1445-1451. doi: 10.1177/2047487320915342.

ABSTRACT

AIMS: Cumulative blood pressure (BP) is a measure that incorporates the severity and duration of BP exposure. The prognostic significance of cumulative BP in young adults for cardiovascular diseases (CVDs) in comparison to BP severity alone is, however, unclear.

METHODS AND RESULTS: We investigated 3667 Coronary Artery Risk Development in Young Adults participants who attended six visits over 15 years (year-0 (1985-1986), year-2, year-5, year-7, year-l0, and year-15 exams). Cumulative BP was calculated as the area under the curve (mmHg × years) from year 0 through year 15. Cox models assessed the association between cumulative BP (year 0 through year 15), current BP (year 15), and BP change (year 0 and year 15) and CVD outcomes. Mean (standard deviation) age at year 15 was 40.2 (3.6) years, 44.1% were men, and 44.1% were African-American. Over a median follow-up of 16 years, there were 47 heart failure (HF), 103 coronary heart disease (CHD), 71 stroke, and 191 CVD events. Cumulative systolic BP (SBP) was associated with HF (hazard ratio (HR) = 2.14 (1.58-2.90)), CHD (HR = 1.49 (1.19-1.87)), stroke (HR = 1.81 (1.38-2.37)), and CVD (HR = 1.73 (1.47-2.05)). For CVD, the C-statistic for SBP (year 15) was 0.69 (0.65-0.73) and change in C-statistic with the inclusion of SBP change and cumulative SBP was 0.60 (0.56-0.65) and 0.72 (0.69-0.76), respectively. For CVD, using year-15 SBP as a reference, the net reclassification index (NRI) for cumulative SBP was 0.40 (p < 0.0001) and the NRI for SBP change was 0.22 (p = 0.001).

CONCLUSIONS: Cumulative BP in young adults was associated with the subsequent risk of HF, CHD, stroke, and CVD. Cumulative BP provided incremental prognostic value and improved risk reclassification for CVD, when compared to single BP assessments or changes in BP.

PMID:34695218 | DOI:10.1177/2047487320915342

Bioinformatics. 2021 Oct 25;37(20):3514-3520. doi: 10.1093/bioinformatics/btab223.

ABSTRACT

MOTIVATION: Gene-environment interaction (GEI) studies are a general framework that can be used to identify genetic variants that modify the effects of environmental, physiological, lifestyle or treatment effects on complex traits. Moreover, accounting for GEIs can enhance our understanding of the genetic architecture of complex diseases and traits. However, commonly used statistical software programs for GEI studies are either not applicable to testing certain types of GEI hypotheses or have not been optimized for use in large samples.

RESULTS: Here, we develop a new software program, GEM (Gene-Environment interaction analysis in Millions of samples), which supports the inclusion of multiple GEI terms, adjustment for GEI covariates and robust inference, while allowing multi-threading to reduce computation time. GEM can conduct GEI tests as well as joint tests of genetic main and interaction effects for both continuous and binary phenotypes. Through simulations, we demonstrate that GEM scales to millions of samples while addressing limitations of existing software programs. We additionally conduct a gene-sex interaction analysis on waist-hip ratio in 352 768 unrelated individuals from the UK Biobank, identifying 24 novel loci in the joint test that have not previously been reported in combined or sex-specific analyses. Our results demonstrate that GEM can facilitate the next generation of large-scale GEI studies and help advance our understanding of the genetic architecture of complex diseases and traits.

AVAILABILITY AND IMPLEMENTATION: GEM is freely available as an open source project at https://github.com/large-scale-gxe-methods/GEM.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:34695175 | DOI:10.1093/bioinformatics/btab223

PLoS One. 2021 Oct 25;16(10):e0258764. doi: 10.1371/journal.pone.0258764. eCollection 2021.

ABSTRACT

BACKGROUND: Parents play a key role in providing nurturance and nurturing care to their child during the first 1000 days which is important for optimal child development. Various factors have been found to influence parenting but the contribution of these factors toward parental nurturance within the first 1000 days is not yet known in the South African context. This paper describes a protocol for a project that aims to develop a logic model of change for the determinants of parental nurturance in the first 1000 days in the South African context.

METHOD: This study will apply a mixed methods approach with a sequential design within an intervention mapping framework. The study will occur in two phases. The first phase will identify the problem, which will be done via a scoping review, a policy review and a needs assessment for parents and stakeholders. This phase will recruit approximately 35 participants (20 parents and 15 stakeholders) for the qualitative component and then approximately 398 participants for the quantitative component. Data will be collected via semi-structured interviews and with questionnaires (Home Observation for Measurement of the Environment Inventory, the Depression and Anxiety Scale, and the Multidimensional Perceived Social Support Scale). Data will be thematically analysed, and the Statistical Package for Social Science (SPSS) will be used to determine descriptive statistics, both of which will inform the development of the model in phase 2. The second phase will be the development of a logic model of change for determinants for parental nurturance in the first thousand days. This phase will consist of one stage- a consensus workshop which will be attended by approximately 20 participants (5 parents, 5 pregnant woman/new mothers, and 10 stakeholders). The data collected in this stage will be thematically analysed and will contribute to the refinement of the model.

DISCUSSION: The first thousand days (FTD) is a period in which rapid growth occurs in all domains of development. If children do not receive sensitive and responsive care in an environment that is conducive for their optimal development, children may not reach their full developmental potential.

PMID:34695150 | DOI:10.1371/journal.pone.0258764

PLoS One. 2021 Oct 25;16(10):e0258827. doi: 10.1371/journal.pone.0258827. eCollection 2021.

ABSTRACT

BACKGROUND: Mental health problems follow a distinct socio-economic gradient and contribute to the health inequalities. The study aims to analyse the socio-economic and demographic factors of self-reported mental health complaints (stress, depressiveness, overtiredness, suicidal thoughts) among employed adult population in Estonia.

METHODS: Data on 4041 employed respondents (2064 men and 1977 women) aged 20-64 years from nationally representative health surveys from years 2016 and 2018 in Estonia were used for the study. Dependent variables included self-reported stress, depressiveness, overtiredness, and suicidal thoughts. Descriptive statistics and both log-binomial and Poisson regression analysis were used to describe the socio-economic and demographic variations in these mental health complaints.

RESULTS: More than half of the respondents had either stress, depressiveness, overtiredness or suicidal thoughts with 25% reporting two or more of mental health complaints. Lower personal income was associated with higher rates of all mental health complaints (stress, depressiveness, overtiredness, and suicidal thoughts) among employed adults in Estonia. Additionally, lower education was associated with higher prevalence of depressiveness and lower job skills predicted higher prevalence of suicidal thoughts. Higher prevalence ratios for depressiveness and overtiredness were found for women compared to men whereas Estonians had higher prevalence ratios for stress and suicidal thoughts compared to non-Estonians. All mental health complaints were more frequently reported at younger ages (compared to 50-64-year olds) and by not married or cohabiting respondents.

CONCLUSION: High prevalence of mental health complaints and their socio-economic and demographic patterning refer to considerable inequalities in mental health among employed adults. Policy actions targeting especially younger adults and those with financial difficulties are needed to address these early manifestations of mental health problems.

PMID:34695142 | DOI:10.1371/journal.pone.0258827

PLoS One. 2021 Oct 25;16(10):e0257942. doi: 10.1371/journal.pone.0257942. eCollection 2021.

ABSTRACT

INTRODUCTION: Depression is a commonly overwhelming problem among patients with epilepsy which compromises their quality of life especially in developing countries. Previously limited studies were conducted using Becks Depression Inventory tool in Ethiopia. The aim of this study’s objective was to determine the prevalence of depression and associated factors among patients with epilepsy.

METHODS: Institution based cross-sectional study was employed at the University of Gondar Comprehensive Specialized Hospital from March 01-30, 2019.A total of 370 participants were selected using an interview administered structured questionnaire. Hospital Anxiety and Depression Scale was used to assess the prevalence of depression.Multivariable logistic regression analysis was done to investigate potential predictors and variables with a P-value of < 0.05 and a 95% confidence interval were considered statistically significant.

RESULTS: A total of 370 study participants participated with a response rate of 92%. From the total respondents 37% experienced depression. Perceived stigma (AOR = 3.89, CI: 2.27, 6.68), educational status (AOR = 0.48, CI: 0.25, 0.92), residence (AOR = 0.5, CI: 0.28, 0.89), frequency of seizure (AOR = 2.07, CI: 1.01, 4.23) and social support (AOR = 2.73, CI: 1.41-5.31) were significantly associated with depression status.

CONCLUSION: This study revealed that prevalence of depression among Epileptic patients was high. Perceived stigma, educational status, residence, frequency of seizure and social support were significantly associated with depression status. Thus, health care workers better to give more emphasis to patients with perceived stigma, higher number of seizure frequency and to those with poor level of social support.

PMID:34695130 | DOI:10.1371/journal.pone.0257942

PLoS Med. 2021 Oct 25;18(10):e1003844. doi: 10.1371/journal.pmed.1003844. Online ahead of print.

ABSTRACT

Florian Naudet and co-authors discuss strengthening requirements for sharing clinical trial data.

PMID:34695113 | DOI:10.1371/journal.pmed.1003844

PLoS Med. 2021 Oct 25;18(10):e1003837. doi: 10.1371/journal.pmed.1003837. Online ahead of print.

ABSTRACT

BACKGROUND: Through a multisectoral approach, the DREAMS Partnership aimed to reduce HIV incidence among adolescent girls and young women (AGYW) by 40% over 2 years in high-burden districts across sub-Saharan Africa. DREAMS promotes a combination package of evidence-based interventions to reduce individual, family, partner, and community-based drivers of young women’s heightened HIV risk. We evaluated the impact of DREAMS on HIV incidence among AGYW and young men in 2 settings.

METHODS AND FINDINGS: We directly estimated HIV incidence rates among open population-based cohorts participating in demographic and HIV serological surveys from 2006 to 2018 annually in uMkhanyakude (KwaZulu-Natal, South Africa) and over 6 rounds from 2010 to 2019 in Gem (Siaya, Kenya). We compared HIV incidence among AGYW aged 15 to 24 years before DREAMS and up to 3 years after DREAMS implementation began in 2016. We investigated the timing of any change in HIV incidence and whether the rate of any change accelerated during DREAMS implementation. Comparable analyses were also conducted for young men (20 to 29/34 years). In uMkhanyakude, between 5,000 and 6,000 AGYW were eligible for the serological survey each year, an average of 85% were contacted, and consent rates varied from 37% to 67%. During 26,395 person-years (py), HIV incidence was lower during DREAMS implementation (2016 to 2018) than in the previous 5-year period among 15- to 19-year-old females (4.5 new infections per 100 py as compared with 2.8; age-adjusted rate ratio (aRR) = 0.62, 95% confidence interval [CI] 0.48 to 0.82), and lower among 20- to 24-year-olds (7.1/100 py as compared with 5.8; aRR = 0.82, 95% CI 0.65 to 1.04). Declines preceded DREAMS introduction, beginning from 2012 to 2013 among the younger and 2014 for the older women, with no evidence of more rapid decline during DREAMS implementation. In Gem, between 8,515 and 11,428 AGYW were eligible each survey round, an average of 34% were contacted and offered an HIV test, and consent rates ranged from 84% to 99%. During 10,382 py, declines in HIV incidence among 15- to 19-year-olds began before DREAMS and did not change after DREAMS introduction. Among 20- to 24-year-olds in Gem, HIV incidence estimates were lower during DREAMS implementation (0.64/100 py) compared with the pre-DREAMS period (0.94/100 py), with no statistical evidence of a decline (aRR = 0.69, 95% CI 0.53 to 2.18). Among young men, declines in HIV incidence were greater than those observed among AGYW and also began prior to DREAMS investments. Study limitations include low study power in Kenya and the introduction of other interventions such as universal treatment for HIV during the study period.

CONCLUSIONS: Substantial declines in HIV incidence among AGYW were observed, but most began before DREAMS introduction and did not accelerate in the first 3 years of DREAMS implementation. Like the declines observed among young men, they are likely driven by earlier and ongoing investments in HIV testing and treatment. Longer-term implementation and evaluation are needed to assess the impact of such a complex HIV prevention intervention and to help accelerate reductions in HIV incidence among young women.

PMID:34695112 | DOI:10.1371/journal.pmed.1003837

PLoS Comput Biol. 2021 Oct 25;17(10):e1009524. doi: 10.1371/journal.pcbi.1009524. Online ahead of print.

ABSTRACT

A key benefit of long-read nanopore sequencing technology is the ability to detect modified DNA bases, such as 5-methylcytosine. The lack of R/Bioconductor tools for the effective visualization of nanopore methylation profiles between samples from different experimental groups led us to develop the NanoMethViz R package. Our software can handle methylation output generated from a range of different methylation callers and manages large datasets using a compressed data format. To fully explore the methylation patterns in a dataset, NanoMethViz allows plotting of data at various resolutions. At the sample-level, we use dimensionality reduction to look at the relationships between methylation profiles in an unsupervised way. We visualize methylation profiles of classes of features such as genes or CpG islands by scaling them to relative positions and aggregating their profiles. At the finest resolution, we visualize methylation patterns across individual reads along the genome using the spaghetti plot and heatmaps, allowing users to explore particular genes or genomic regions of interest. In summary, our software makes the handling of methylation signal more convenient, expands upon the visualization options for nanopore data and works seamlessly with existing methylation analysis tools available in the Bioconductor project. Our software is available at https://bioconductor.org/packages/NanoMethViz.

PMID:34695109 | DOI:10.1371/journal.pcbi.1009524

PLoS Negl Trop Dis. 2021 Oct 25;15(10):e0009803. doi: 10.1371/journal.pntd.0009803. Online ahead of print.

ABSTRACT

World Health Organization goals against soil-transmitted helminthiases (STH) are pointing towards seeking their elimination as a public health problem: reducing to less than 2% the proportion of moderate and heavy infections. Some regions are reaching WHO goals, but transmission could rebound if strategies are discontinued without an epidemiological evaluation. For that, sensitive diagnostic methods to detect low intensity infections and localization of ongoing transmission are crucial. In this work, we estimated and compared the STH infection as obtained by different diagnostic methods in a low intensity setting. We conducted a cross-sectional study enrolling 792 participants from a district in Mozambique. Two stool samples from two consecutive days were collected from each participant. Samples were analysed by Telemann, Kato-Katz and qPCR for STH detection. We evaluated diagnostic sensitivity using a composite reference standard. By geostatistical methods, we estimated neighbourhood prevalence of at least one STH infection for each diagnostic method. We used environmental, demographical and socioeconomical indicators to account for any existing spatial heterogeneity in infection. qPCR was the most sensitive technique compared to composite reference standard: 92% (CI: 83%- 97%) for A. lumbricoides, 95% (CI: 88%- 98%) for T. trichiura and 95% (CI: 91%- 97%) for hookworm. qPCR also estimated the highest neighbourhood prevalences for at least one STH infection in a low intensity setting. While 10% of the neighbourhoods showed a prevalence above 20% when estimating with single Kato-Katz from one stool and Telemann from one stool, 86% of the neighbourhoods had a prevalence above 20% when estimating with qPCR. In low intensity settings, STH estimated prevalence of infection may be underestimated if based on Kato-Katz. qPCR diagnosis outperformed the microscopy methods. Thus, implementation of qPCR based predictive maps at STH control and elimination programmes would disclose hidden transmission and facilitate targeted interventions for transmission interruption.

PMID:34695108 | DOI:10.1371/journal.pntd.0009803

N Z Med J. 2021 Oct 22;134(1544):57-68.

ABSTRACT

AIMS: To determine the impact of perioperative sustained-release (SR) opioid use on total inpatient opioid consumption and longer-term outpatient dispensing for three months following elective total knee arthroplasty (TKA).

METHODS: Patients who underwent primary unilateral TKA between 1 January and 31 December 2018 at Counties Manukau Health were retrospectively identified. Participants were stratified into two groups by inpatient use or avoidance of strong SR opioids (OxyContin or M-Eslon). The primary outcome was the percentage of patients receiving prescriptions for opioid medications at thirty-day intervals for three months after discharge.

RESULTS: Two hundred and thirty-two patients were eligible for inclusion. The baseline demographics of both groups were similar. In the SR opioid use group, the majority (79%) received OxyContin. Overall, inpatient opioid use between postoperative days (POD) zero and three was lower in the SR opioid avoidance group, although this was not statistically significant (157.5 [IQR 110.0-220.0] vs 167.5mg OME [110.0-290.0], p=0.14). Outpatient postoperative opioid dispensing between 0-30 days was significantly greater in patients who received inpatient SR opioids (p=0.01). Dispensing of oxycodone was significantly higher in the SR opioid use group at one- and two- months (p=0.01 and 0.03 respectively).

CONCLUSION: The postoperative use of SR opioids is not routinely recommended following TKA. Their use is associated with greater overall inpatient opioid use, sustained opioid dispensing during and after the expected recovery period, and the potential for significant harm.

PMID:34695093