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Nevin Manimala Statistics

The Contribution of Known Familial Cardiovascular Disease Genes to Sudden Cardiac Death in Patients Undergoing Hemodialysis

Cardiorenal Med. 2021;11(4):174-183. doi: 10.1159/000517123. Epub 2021 Aug 10.

ABSTRACT

INTRODUCTION: Patients with chronic kidney disease experience high rates of cardiovascular mortality and morbidity. When kidney disease progresses to the need for dialysis, sudden cardiac death (SCD) accounts for 25-35% of all cardiovascular deaths. The objective was to determine if rare genetic variants known to be associated with cardiovascular death in the general population are associated with SCD in patients undergoing hemodialysis.

METHODS: We performed a case-control study comparing 126 (37 African American [AfAn] and 89 European ancestry [EA]) SCD subjects and 107 controls (34 AfAn and 73 EA), matched for age, sex, self-reported race, dialysis duration (<2, 2-5 and >5 years), and the presence or absence of diabetes mellitus. To target the coding regions of genes previously reported to be associated with 15 inherited cardiac conditions (ICCs), we used the TruSight Cardio Kit (Illumina, San Diego, CA, USA) to capture the genetic regions of interest. In all, the kit targets 572-kb regions that include the protein-coding regions and 40-bp 5′ and 3′ end-flanking regions of 174 genes associated with the 15 ICCs. Using the sequence data, burden tests were conducted to identify genes with an increased number of variants among SCD cases compared to matched controls.

RESULTS: Eleven genes were associated with SCD, but after correction for multiple testing, none of the 174 genes were identified as having more variants in the SCD cases than the matched controls, including previously identified genes. Secondary burden tests grouping variants based on diseases and gene function did not produce statistically significant associations.

DISCUSSION/CONCLUSIONS: We found no associations between genes known to be associated with ICCs and SCD in our sample of patients undergoing hemodialysis. This suggests that genetic causes are unlikely to be a major pathogenic factor in SCD in hemodialysis patients, although our sample size limits definitive conclusions.

PMID:34433165 | DOI:10.1159/000517123

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Nevin Manimala Statistics

Major Adverse Renal and Cardiovascular Events following Intra-Arterial Contrast Media Administration in Hospitalized Patients with Comorbid Conditions

Cardiorenal Med. 2021;11(4):193-199. doi: 10.1159/000517884. Epub 2021 Aug 12.

ABSTRACT

INTRODUCTION: Several clinical studies and meta-analyses have demonstrated lower incidence of adverse renal and cardiovascular outcomes associated with the use of iso-osmolar contrast media (IOCM) than low-osmolar contrast media (LOCM) in patients with variable risk profiles undergoing intra-arterial interventional procedures. However, the association of contrast-type and major adverse renal and cardiovascular events (MARCE) has not been studied via comprehensive and robust real-world data analyses in patients with comorbid conditions considered at risk for post-procedural acute kidney injury (AKI). The objective of this study was therefore to retrospectively assess the MARCE rates comparing IOCM with LOCM in at-risk patients receiving iodinated intra-arterial contrast media using a real-world inpatient data source.

METHODS: Patients who underwent a diagnostic or treatment procedure with intra-arterial IOCM or LOCM administration were identified using the Premier Healthcare Database. Patient subgroups including those with diabetes, heart failure, chronic kidney disease (CKD) stages 1-4, CKD 3-4, or diagnosis of chronic total occlusion (CTO) were formed. Subgroups with combinations of diabetes and CKD 3-4 with and without CTO were also investigated. We compared the primary endpoint of MARCE (composite of AKI, AKI requiring dialysis, acute myocardial infarction, stroke/transient ischemic attack, stent occlusion/thrombosis, or death) after IOCM versus LOCM administration via adjusted multivariable regression analyses.

RESULTS: A total of 536,013 inpatient visits met the primary inclusion and exclusion criteria (IOCM = 133,192; LOCM = 402,821). After multivariable modeling, the use of IOCM was associated with a significantly lower incidence of MARCE than LOCM in patients with CKD 1-4, CKD 3-4, diabetes, or heart failure, with greatest absolute risk reduction (ARR) of 2.4% (p < 0.0001) in CKD 3-4 patients (relative risk reduction [RRR] = 13.8%, number needed to treat [NNT] = 43). Additionally, ARR associated with IOCM increased to 3.5% (p < 0.0001) in patients with combined comorbidities of diabetes and CKD 3-4 (RRR = 19.1%, NNT = 29). Statistically significant risk reduction was also found for the use of IOCM among patients who underwent revascularization for CTO (ARR = 1.6% [p < 0.0001], RRR = 22.3%, NNT = 62).

CONCLUSION: Intra-arterial administration using IOCM in at-risk patients is associated with lower rates of MARCE than the use of LOCM. This difference is especially apparent in patients with a combination of CKD 3-4 and diabetes and in patients with CTO, providing real-world data validation with meaningful NNT in favor of IOCM.

PMID:34433166 | DOI:10.1159/000517884

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Nevin Manimala Statistics

Rapid and improved identification of drinking water bacteria using the Drinking Water Library, a dedicated MALDI-TOF MS database

Water Res. 2021 Aug 12;203:117543. doi: 10.1016/j.watres.2021.117543. Online ahead of print.

ABSTRACT

According to the European Directives (UE) 2020/2184 and 2009/54/EC, which establishes the sanitary criteria for water intended for human consumption in Europe, water suitable for human consumption must be free of the bacterial indicators Escherichia coli, Clostridium perfringens and Enterococcus spp. Drinking water is also monitored for heterotrophic bacteria, which are not a human health risk, but can serve as an index of bacteriological water quality. Therefore, a rapid, accurate, and cost-effective method for the identification of these colonies would improve our understanding of the culturable bacteria of drinking water and facilitate the task of water management by treatment facilities. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is potentially such a method, although most of the currently available mass spectral libraries have been developed in a clinical setting and have limited environmental applicability. In this work, a MALDI-TOF MS drinking water library (DWL) was defined and developed by targeting bacteria present in water intended for human consumption. This database, made up of 319 different bacterial strains, can contribute to the routine microbiological control of either treated drinking water or mineral bottled water carried out by water treatment and distribution operators, offering a faster identification rate compared to a clinical sample-based library. The DWL, made up of 96 bacterial genera, 44 of which are not represented in the MALDI-TOF MS bacterial Bruker Daltonics (BDAL) database, was found to significantly improve the identification of bacteria present in drinking water.

PMID:34433109 | DOI:10.1016/j.watres.2021.117543

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Nevin Manimala Statistics

Mental imagery-based episodic simulation amplifies motivation and behavioural engagement in planned reward activities

Behav Res Ther. 2021 Aug 15;145:103947. doi: 10.1016/j.brat.2021.103947. Online ahead of print.

ABSTRACT

Preliminary evidence suggests mental imagery-based episodic simulation of planned reward activities may amplify motivation and promote greater behavioural engagement, particularly for activities with high motivational barriers (Renner, Murphy, Ji, Manly, & Holmes, 2019). This study conducted a conceptual replication and extension of Renner et al. (2019). N = 81 first-year university students self-selected and scheduled two reward activities (one hedonic, one mastery) for the following week before being randomly allocated to either an Imagery-Experiential elaboration condition (n = 27), a Verbal-Reasoning elaboration condition (n = 28), or a Scheduling-only Control condition (n = 26). Following the lab session, all participants received standardized daily prompts to complete daily activity diaries online for seven days. The Imagery-Experiential condition reported greater increases in anticipatory pleasure (state mood), anticipated pleasure, and self-reported motivation compared to the Scheduling-only Control condition, and greater increases in anticipatory pleasure (state mood), but not anticipated pleasure or motivation, relative to the Verbal-Reasoning condition. Consistent with Renner et al. (2019), the Imagery-Experiential condition, but not the Verbal-Reasoning condition, reported more frequent engagement in high motivational barrier activities than the Scheduling-only Control condition. Exploratory mediational analyses suggested that mental imagery may exert unique motivational impacts via its impact on anticipatory pleasure (state mood), although indirect effects were only observed for self-reported motivation change in the lab, with real world behavioural effects falling short of statistical significance.

PMID:34433114 | DOI:10.1016/j.brat.2021.103947

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Nevin Manimala Statistics

Prophylactic Muscle Flaps in Primary Vascular Procedures of the Groin

Ann Vasc Surg. 2021 Aug 22:S0890-5096(21)00527-6. doi: 10.1016/j.avsg.2021.05.049. Online ahead of print.

ABSTRACT

INTRODUCTION: Complications following vascular procedures involving the groin can lead to significant morbidity. Achieving stable soft tissue coverage over sites of revascularization can help mitigate complications. Prior evidence supports the use of muscle flaps in reoperative groins and in high risk patient populations to reduce postoperative complications. Data regarding the use of prophylactic muscle flap coverage of the groin is lacking. Therefore, the purpose of this study is to evaluate the effect of immediate prophylactic muscle flap coverage of vascular wounds involving the groin.

METHODS: A retrospective cohort study was performed on all patients undergoing primary open vascular procedures involving the groin for occlusive, aneurysmal, or oncologic disease between 2014 and 2020 at a single institution where plastic surgery was involved in closure. Patient demographics, comorbidities, surgical details, and postoperative complications were compared between patients who had sartorius muscle flap coverage of the vascular repair versus layered closure alone.

RESULTS: A total of 133 consecutive groins were included in our analysis. A sartorius flap was used in 115 groins (86.5%) and a layered closure was used in 18 (13.5%). Wound breakdown was similar between groups (25.2% sartorius vs. 38.9% layered closure, p=0.26). However, the rate of reoperation was significantly higher in the layered closure group (50.0% vs. 12.2%, p<0.01). Among patients who experienced wound breakdown (N = 36), a larger proportion of layered closure patients required operative intervention (71.4% vs. 20.7%, p=0.02). Other rates of complications were not statistically different between groups.

CONCLUSIONS: In patients undergoing primary open vascular procedures involving the groin, patients who underwent prophylactic sartorius muscle flap closure had lower rates of reoperation. Although incisional breakdown was similar between the groups overall, the presence of a vascularized muscle flap overlying the vascular repair was associated with reduced need for reoperation and allowed more wounds to be managed with local wound care alone. Consideration should be given to this low morbidity local muscle flap in patients undergoing vascular procedures involving the groin.

PMID:34433093 | DOI:10.1016/j.avsg.2021.05.049

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Trajectories of and Disparities in HIV Prevalence among Black, White, and Hispanic/Latino High Risk Heterosexuals in 89 U.S. Metropolitan Statistical Areas, 1992-2013

Ann Epidemiol. 2021 Aug 22:S1047-2797(21)00265-9. doi: 10.1016/j.annepidem.2021.08.015. Online ahead of print.

ABSTRACT

Estimates of HIV prevalence, and how it changes over time, are needed to inform action (e.g., resource allocation) to improve HIV-related public health. However, creating adequate estimates of (diagnosed and undiagnosed) HIV prevalence is challenging due to biases in samples receiving HIV testing and due to difficulties enumerating key risk populations. To our knowledge, estimates of HIV prevalence among high risk heterosexuals in the United States produced for geographic areas smaller than the entire nation have to date been only for single years and/or for single cities (or other single geographic locations). The present study addresses these gaps by using multilevel modeling on multiple data series, in combination with previous estimates of HIV prevalence among heterosexuals from the extant literature, to produce annual estimates of HIV prevalence among high risk heterosexuals for each of 89 metropolitan statistical areas, from 1992-2013. It also produces estimates for these MSAs and years by racial/ethnic subgroup to allow for an examination of change over time in racial/ethnic disparities in HIV prevalence among high risk heterosexuals. The resulting estimates suggest that HIV prevalence among high risk heterosexuals has decreased steadily, on average, from 1992-2013. Examination of these estimates by racial/ethnic subgroup suggests that this trend is primarily due to decreases among Black and Hispanic/Latino high risk heterosexuals. HIV prevalence among white high risk heterosexuals remained steady over time at around 1 percent during the study period. Although HIV prevalence among Black and Hispanic/Latino high risk heterosexuals was much higher (approximately 3.5% and 3.3%, respectively) than that among whites in 1992, over time these differences decreased as HIV prevalence decreased over time among these subgroups. By 2013, HIV prevalence among Hispanic/Latino high risk heterosexuals was estimated to be very similar to that among white high risk heterosexuals (approximately 1 percent), with prevalence among Black high risk heterosexuals still estimated to be almost twice as high. It is likely that as HIV incidence has decreased among heterosexuals from 1992-2013, mortality due to all causes has remained disparately high among racial/ethnic minorities, thereby outpacing new HIV cases. Future research should aim to empirically examine this by comparing changes over time in estimated HIV incidence among heterosexuals to changes over time in mortality and causes of death among HIV-positive heterosexuals, by racial/ethnic subgroup.

PMID:34433105 | DOI:10.1016/j.annepidem.2021.08.015

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Long-lasting immune response to a mild course of PCR-confirmed SARS-CoV-2 infection: A cohort study

J Infect. 2021 Aug 22:S0163-4453(21)00419-9. doi: 10.1016/j.jinf.2021.08.030. Online ahead of print.

NO ABSTRACT

PMID:34433071 | DOI:10.1016/j.jinf.2021.08.030

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Evaluating the impact of age on immune checkpoint therapy biomarkers

Cell Rep. 2021 Aug 24;36(8):109599. doi: 10.1016/j.celrep.2021.109599.

ABSTRACT

Both tumors and aging alter the immune landscape of tissues. These interactions may play an important role in tumor progression among elderly patients and may suggest considerations for patient care. We leverage large-scale genomic and clinical databases to perform comprehensive comparative analysis of molecular and cellular markers of immune checkpoint blockade (ICB) response with patient age. These analyses demonstrate that aging is associated with increased tumor mutational burden, increased expression and decreased promoter methylation of immune checkpoint genes, and increased interferon gamma signaling in older patients in many cancer types studied, all of which are expected to promote ICB efficacy. Concurrently, we observe age-related alterations that might be expected to reduce ICB efficacy, such as decreases in T cell receptor diversity. Altogether, these changes suggest the capacity for robust ICB response in many older patients, which may warrant large-scale prospective study on ICB therapies among patients of advanced age.

PMID:34433020 | DOI:10.1016/j.celrep.2021.109599

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Nevin Manimala Statistics

P-sort: an open-source software for cerebellar neurophysiology

J Neurophysiol. 2021 Aug 25. doi: 10.1152/jn.00172.2021. Online ahead of print.

ABSTRACT

Analysis of electrophysiological data from Purkinje cells (P-cells) of the cerebellum presents unique challenges to spike sorting. Complex spikes have waveforms that vary significantly from one event to the next, raising the problem of misidentification. Even when complex spikes are detected correctly, the simple spikes may belong to a different P-cell, raising the danger of misattribution. To address these identification and attribution problems, we wrote an open-source, semi-automated software called P-sort, and then tested it by analyzing data from P-cells recorded in three species: marmosets, macaques, and mice. Like other sorting software, P-sort relies on nonlinear dimensionality reduction to cluster spikes. However, it also uses the statistical relationship between simple and complex spikes to merge disparate clusters and split a single cluster. In comparison with expert manual curation, occasionally P-sort identified significantly more complex spikes, as well as prevented misattribution of clusters. Three existing automatic sorters performed less well, particularly for identification of complex spikes. To improve development of analysis tools for the cerebellum, we provide labeled data for 313 recording sessions, as well as statistical characteristics of waveforms and firing patterns of P-cells in three species.

PMID:34432996 | DOI:10.1152/jn.00172.2021

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Nevin Manimala Statistics

Inequalities in immunization coverage in Indonesia: a multilevel analysis

Rural Remote Health. 2021 Aug;21(3):6348. doi: 10.22605/RRH6348. Epub 2021 Aug 25.

ABSTRACT

INTRODUCTION: Immunization is one of the most cost-effective methods for reducing mortality and morbidity rates in children. Children being fully vaccinated helps prevent diseases that would have great societal costs otherwise. Incomplete vaccination poses public health risks and challenges. This study examines the issue of incomplete vaccination in Indonesia. The objectives were to quantify the association between child level, parent level and community level determinants and child immunization coverage in Indonesia.

METHODS: Data were from the 2017 Indonesian Demographic Health Survey; this study included 4753 children aged 12-24 months. The survey implemented multistage random sampling. The data were examined using descriptive statistics and multilevel logistic regression analysis.

RESULTS: The survey found that in Indonesia, country-wide, 58.22% of children were fully vaccinated. A multilevel logistic regression model after adjusting for household wealth and proportion of public healthcare centers (PHCs) showed that children of first birth order had significantly lower likelihood of being fully immunized than children of second order and higher. The parent level factors, such as age of mother at delivery, mother’s education, father’s occupation, antenatal care (ANC) and region, significantly influenced the completeness of child immunization. At the community level, the presence of a PHC significantly improved immunization coverage.

CONCLUSION: The findings indicate that there is a wide range of inequality in immunization throughout the region due to socioeconomic and demographic factors. Findings revealed that complete immunization status was significantly associated with birth order, age of mother at delivery, mother’s education, father’s occupation, ANC, region, and proportion of PHCs. This study emphasizes the need to increase healthcare centers in each community with the objective to reduce disparities in maternal and child health services.

PMID:34432982 | DOI:10.22605/RRH6348