Nevin Manimala

Int J Artif Organs. 2022 Sep 23:3913988221126728. doi: 10.1177/03913988221126728. Online ahead of print.

ABSTRACT

BACKGROUND: Hyperlactatemia is a common complication in critically ill patients with high morbidity and mortality. Hyperlactatemia patients who require continuous renal replacement therapy (CRRT) constitute a subgroup with increased mortality risk. The clinical significance of serum lactate in these patients was not well understood and clearance of lactate using CRRT shown no survival benefits. The aim of this study is to investigate the incidence and non-lactate risk factors for ICU mortality in hyperlactatemia patients who underwent CRRT.

METHOD: Hyperlactatemia patients with a serum lactate level >2 μmol/L who underwent CRRT between January, 2014 and May, 2021 were retrospectively investigated. Demographic characteristics and clinical data were collected from the electronic medical record system. The primary endpoint was predictors for ICU mortality which were identified by using multivariate logistic regression analysis.

RESULTS: A total of 178 eligible patients were finally included with a mean age of 56.6 ± 17.9 years and a median APACHE II score of 18 (IQR (14-22)). The multivariate regression results showed that male gender (OR 0.55 (95%CI 0.27-1.12), p = 0.1), mechanical ventilation (OR 2.60 (95%CI 1.27-5.34), p = 0.008), history of hypertension (OR 2.40 (95%CI 1.12-5.14), p = 0.02), SOFA score (OR 1.16 (95%CI 1.05-1.28), p = 0.002), AST (OR 1.0005 (95%CI 0.99-1.001), p = 0.08), and PT (OR 1.08 (95%CI 0.99-1.17), p = 0.06) were independently associated with ICU mortality. After adjusting for age, illness severity (APACHE II score), and serum lactate level, the statistical significances of SOFA score (OR 1.16 (95%CI 1.04-1.29), p = 0.005), hypertension (OR 2.25 (95%CI 1.02-4.95), p = 0.04), and mechanical ventilation (OR 2.54 (95%CI 1.22-5.25), p = 0.01) were not affected. The overall ICU mortality was 58.4% (104/178).

CONCLUSION: The hyperlactatemia patients who underwent CRRT were at increased ICU mortality. Gender, AST, PT, SOFA score, history of hypertension, and mechanical ventilation were independent predictors for ICU mortality. Future studies with prospectively design, large sample size, and subgroup analyses are warranted to validate these findings.

PMID:36151706 | DOI:10.1177/03913988221126728

J Adv Nurs. 2022 Sep 23. doi: 10.1111/jan.15446. Online ahead of print.

ABSTRACT

AIMS: To assess the impact of community-level characteristics on the role of magnet designation in relation to hospital value-based purchasing quality scores, as health disparities associated with geographical location could confound hospitals’ ability to meet outcome metrics.

DESIGN: This cross-sectional study was carried out between October 2021 and March 2022 using data from 2016 to 2021.

METHODS: Propensity score analysis was used to match hospital and community-level characteristics, implementing nearest neighbour matching to adjust for pre-treatment differences between magnet and non-magnet hospitals to account for multi-level differences. Secondary data were obtained from all operational acute-care facilities in the United States that participated in the Centers for Medicare and Medicaid Services’ hospital value-based purchasing (HVBP) program. Dependent variables were the four value-based purchasing domains that comprise the Total Performance Score (TPS; Clinical Care, Person and Community Engagement, Safety, and Efficiency and Cost Reduction).

RESULTS: Magnet hospitals had increased odds for better scores in the HVBP domains of Clinical Care and Person and Community Engagement, and decreased odds for having better Safety. However, no statistically significant difference was found for the Efficiency domain or the TPS.

CONCLUSION: Measuring performance equitably across organizations of various sizes serving diverse communities remains a key factor in ensuring distributive justice. Analysing the TPS components can identify complex influences of community-level characteristics not evident at the composite level. More research is needed where community and nurse-level factors may indirectly affect patient safety.

IMPACT: This study’s findings on the role of community contexts can inform policymakers designing value-based care programs and healthcare management administrators deliberating on magnet certification investments across diverse community settings.

NO PATIENT OR PUBLIC CONTRIBUTION: For this study of US hospitals’ organizational performance, we did not engage members of the patient population nor the general public. However, the multi-disciplinary research team does include diverse perspectives.

PMID:36151700 | DOI:10.1111/jan.15446

Anat Rec (Hoboken). 2022 Sep 23. doi: 10.1002/ar.25067. Online ahead of print.

ABSTRACT

The geographic ranges in which species live is a function of many factors underlying ecological and evolutionary contingencies. Observing the geographic range of an individual species provides valuable information about these historical contingencies for a lineage, determining the distribution of many distantly related species in tandem provides information about large-scale constraints on evolutionary and ecological processes generally. We present a linear regression method that allows for the discrimination of various hypothetical biogeographical models for determining which landscape distributional pattern best matches data from the fossil record. The linear regression models used in the discrimination rely on geodesic distances between sampling sites (typically geologic formations) as the independent variable and three possible dependent variables: Dice/Sorensen similarity; Euclidean distance; and phylogenetic community dissimilarity. Both the similarity and distance measures are useful for full-community analyses without evolutionary information, whereas the phylogenetic community dissimilarity requires phylogenetic data. Importantly, the discrimination method uses linear regression residual error to provide relative measures of support for each biogeographical model tested, not absolute answers or p-values. When applied to a recently published dataset of Campanian pollen, we find evidence that supports two plant communities separated by a transitional zone of unknown size. A similar case study of ceratopsid dinosaurs using phylogenetic community dissimilarity provided no evidence of a biogeographical pattern, but this case study suffers from a lack of data to accurately discriminate and/or too much temporal mixing. Future research aiming to reconstruct the distribution of organisms across a landscape has a statistical-based method for determining what biogeographic distributional model best matches the available data.

PMID:36151605 | DOI:10.1002/ar.25067

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