Tag: statistics

Anal Chim Acta. 2021 Apr 15;1154:338327. doi: 10.1016/j.aca.2021.338327. Epub 2021 Feb 17.

ABSTRACT

Mercury (Hg) stable isotope signatures are widely used to understand Hg cycling in the environment. Sample preparation methods for determining Hg isotope ratios by CV-MC-ICP-MS vary widely among laboratory facilities and sample types. Here, we present a novel and rapid method for preparing solid samples prior to determining Hg isotope composition. We use a direct Hg analyzer (that measures total Hg) for sample combustion, amalgamation and analysis. During the thermal release of Hg from the amalgamator and following detection, the analyte gas enters a trapping solution consisting of 10% HCl/BrCl (5:1, vol/vol). We find Hg blank values are less than 1% of the Hg introduced during sample analysis, Hg detection is not altered by modifying the system, and more than 90% of the introduced Hg is recovered in the trapping solution. Hg isotope results are statistically indistinguishable from accepted values for previously published certified reference materials and uncertainty of 2σ (0.05-0.12‰) is similar to the solution standard RM8610 (2σ = 0.09‰). This new method allows for solid sample preparation for Hg isotope analysis in under 15 min. It has the additional advantage of minimizing use of sample mass during simultaneous detection and preparation.

PMID:33736793 | DOI:10.1016/j.aca.2021.338327

Anal Chim Acta. 2021 Apr 15;1154:338331. doi: 10.1016/j.aca.2021.338331. Epub 2021 Feb 17.

ABSTRACT

The diffusion of small, charged molecules incorporated in an anisotropic polyelectrolyte multilayer (PEM) was tracked in three dimensions by combining single-molecule fluorescence localization (to characterize lateral diffusion) with Förster resonance energy transfer (FRET) between diffusing molecules and the supporting surface (to measure diffusion in the surface-normal direction). Analysis of the surface-normal diffusion required model-based statistical analysis to account for the inherently noisy FRET signal. Combining these distinct single-molecule methods, which are inherently sensitive to different length-scales, permitted simultaneous characterization of severely anisotropic diffusion, which was more than three orders of magnitude slower in the surface-normal direction. We hypothesize that the anomalously slow surface-normal diffusion was related to the periodic distribution of charge in the PEM, which created electrostatic barriers. The motion was strongly subdiffusive, with anomalous temporal scaling exponents in lateral and normal directions, suggesting a connection to the transient, random fractal conformation of polymer chains in the film’s matrix.

PMID:33736806 | DOI:10.1016/j.aca.2021.338331

J Am Coll Cardiol. 2021 Mar 23;77(11):1381-1392. doi: 10.1016/j.jacc.2021.01.033.

ABSTRACT

BACKGROUND: Investigators have hypothesized that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert diuretic effects that contribute to their ability to reduce serious heart failure events, and this action is particularly important in patients with fluid retention.

OBJECTIVES: This study sought to evaluate the effects of the SGLT2 inhibitor empagliflozin on symptoms, health status, and major heart failure outcomes in patients with and without recent volume overload.

METHODS: This double-blind randomized trial compared the effects of empagliflozin and placebo in 3,730 patients with heart failure and a reduced ejection fraction, with or without diabetes. Approximately 40% of the patients had volume overload in the 4 weeks before study enrollment.

RESULTS: Patients with recent volume overload were more likely to have been hospitalized for heart failure and to have received an intravenous diuretic agent in an outpatient setting in the previous 12 months, and to experience a heart failure event following randomization, even though they were more likely to be treated with high doses of a loop diuretic agent as an outpatient (all p < 0.001). When compared with placebo, empagliflozin reduced the composite risk of cardiovascular death or hospitalization for heart failure, decreased total hospitalizations for heart failure, and improved health status and functional class. Yet despite the predisposition of patients with recent volume overload to fluid retention, the magnitude of these benefits (even after 1 month of treatment) was not more marked in patients with recent volume overload (interaction p values > 0.05). Changes in body weight, hematocrit, and natriuretic peptides (each potentially indicative of a diuretic action of SGLT2 inhibitors) did not track each other closely in their time course or in individual patients.

CONCLUSIONS: Taken together, study findings do not support a dominant role of diuresis in mediating the physiological changes or clinical benefits of SGLT2 inhibitors on the course of heart failure in patients with a reduced ejection fraction. (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977).

PMID:33736819 | DOI:10.1016/j.jacc.2021.01.033

J Am Coll Cardiol. 2021 Mar 23;77(11):1397-1407. doi: 10.1016/j.jacc.2021.01.044.

ABSTRACT

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) and sodium glucose co-transporter 2 inhibitors favorably influence the clinical course of patients with heart failure and reduced ejection fraction.

OBJECTIVES: This study sought to study the mutual influence of empagliflozin and MRAs in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).

METHODS: Secondary analysis that compared the effects of empagliflozin versus placebo in 3,730 patients with heart failure and a reduced ejection fraction, of whom 71% used MRAs at randomization.

RESULTS: The effects of empagliflozin on the primary endpoint, on most efficacy endpoints, and on safety were similar in patients receiving or not receiving an MRA (interaction p > 0.20). For cardiovascular death, the hazard ratios for the effect of empagliflozin versus placebo were 0.82 (95% confidence interval [CI]: 0.65 to 1.05) in MRA users and 1.19 (95% CI: 0.82 to 1.71) in MRA nonusers (interaction p = 0.10); a similar pattern was seen for all-cause mortality (interaction p = 0.098). Among MRA nonusers at baseline, patients in the empagliflozin group were 35% less likely than those in the placebo group to initiate treatment with an MRA following randomization (hazard ratio: 0.65; 95% CI: 0.49 to 0.85). Among MRA users at baseline, patients in the empagliflozin group were 22% less likely than those in the placebo group to discontinue treatment with an MRA following randomization (hazard ratio: 0.78; 95% CI: 0.64 to 0.96). Severe hyperkalemia was less common in the empagliflozin group.

CONCLUSIONS: In EMPEROR-Reduced, the use of MRAs did not influence the effect of empagliflozin to reduce adverse heart failure and renal outcomes. Treatment with empagliflozin was associated with less discontinuation of MRAs. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977).

PMID:33736821 | DOI:10.1016/j.jacc.2021.01.044

Cardiol Young. 2021 Mar 19:1-8. doi: 10.1017/S1047951121000858. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate outcomes in patients with Turner Syndrome, especially those with cardiac conditions, compared to those without Turner syndrome.

DESIGN: Retrospective cohort study utilising hospitalisation data from 2006 to 2012. Conditional logistic regression models are used to analyse outcomes of interest: all-cause mortality, increased length of stay, and discharge to home.

PARTICIPANTS: We identified 2978 women with Turner syndrome, matched to 11,912 controls by primary diagnosis.

RESULTS: Patients with Turner syndrome were more likely to experience inpatient mortality (odds ratio 1.44, 95% confidence interval 1.02-2.02, p = 0.04) and increased length of stay (OR 1.31, CI 1.18-1.46, p = 0.03) than primary diagnosis matched controls, after adjusting for age, race, insurance status, and Charlson comorbidity index. Patients with Turner syndrome were 32% less likely to be discharged to home (OR 0.68, CI 0.60-0.78, p < 0.001). When restricting the sample of patients to those admitted with a cardiac diagnosis, the likelihood of mortality (OR 3.10, CI 1.27-7.57, p = 0.01) and prolonged length of stay (OR 1.42, CI 1.03-1.95, p = 0.03) further increased, while the likelihood of discharge to home further decreased (OR 0.55, CI 0.38-0.80, p = 0.001) in Turner syndrome compared to primary diagnosis matched controls. Specifically, patients with congenital heart disease were more likely to have prolonged length of stay (OR: 1.53, CI 1.18-2.00, p = 0.002), but not increased mortality or decreased discharge to home.

CONCLUSIONS: Hospitalised women with Turner syndrome carry a higher risk of adverse outcomes even when presenting otherwise similarly as controls, an important consideration for those treating them in these settings.

PMID:33736722 | DOI:10.1017/S1047951121000858

Epidemiol Psychiatr Sci. 2021 Mar 19;30:e24. doi: 10.1017/S2045796021000081.

ABSTRACT

AIMS: There is a lack of mental health promotion and treatment services targeting HIV-positive men who have sex with men (HIVMSM) in China. The aim of this study was to evaluate the mental health promotion efficacy of an online intervention that combined Three Good Things (TGT) with electronic social networking (TGT-SN) and an intervention that used TGT only (TGT-only), compared with a control group.

METHODS: We conducted a randomised controlled trial among HIVMSM in Chengdu, China. The participants were randomly assigned to the TGT-SN, TGT-only, and control groups. The participants in the TGT-SN group were divided into five social network groups and asked to post brief messages to the group about three good things that they had experienced and for which they felt grateful. The participants in the TGT-only group were only required to write down their three good things daily without sharing them with others. The control group received information about mental health promotion once a week for a month. The primary outcome was probable depression. Secondary outcomes were anxiety, positive and negative affect, gratitude, happiness and social support. These outcomes were assessed at baseline, 1, 3, 6 and 12 months after the intervention. Repeated-measures analyses were conducted using generalised estimation equations. The study was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-13003252).

RESULTS: Between June 2013 and May 2015, 404 participants were enrolled and randomly assigned to either the TGT-SN (n = 129), TGT-only (n = 139) or control group (n = 136). The main effects of TGT-SN (adjusted odds ratio (aOR) = 0.75, 95% CI 0.52-1.09; p = 0.131) and TGT-only (aOR = 0.83, 95% CI 0.57-1.21; p = 0.332) in reducing depression were statistically non-significant. The participants of the TGT-SN group showed significantly lower anxiety symptoms (aOR = 0.62, 95% CI 0.43-0.89; p = 0.009) and negative affect (β = -1.62, 95% CI 2.98 to -0.26; p = 0.019) over time compared with those of the control group. No significant main effect was found for any secondary outcomes for the TGT-only group.

CONCLUSIONS: The novel intervention combining the TGT exercise with electronic social networking was found effective in reducing anxiety and negative affect among HIVMSM.

PMID:33736740 | DOI:10.1017/S2045796021000081

BJPsych Open. 2021 Mar 19;7(2):e68. doi: 10.1192/bjo.2021.30.

ABSTRACT

BACKGROUND: For people in mental health crisis, acute day units (ADUs) provide daily structured sessions and peer support in non-residential settings, often as an addition or alternative to crisis resolution teams (CRTs). There is little recent evidence about outcomes for those using ADUs, particularly compared with those receiving CRT care alone.

AIMS: We aimed to investigate readmission rates, satisfaction and well-being outcomes for people using ADUs and CRTs.

METHOD: We conducted a cohort study comparing readmission to acute mental healthcare during a 6-month period for ADU and CRT participants. Secondary outcomes included satisfaction (Client Satisfaction Questionnaire), well-being (Short Warwick-Edinburgh Mental Well-being Scale) and depression (Center for Epidemiologic Studies Depression Scale).

RESULTS: We recruited 744 participants (ADU: n = 431, 58%; CRT: n = 312, 42%) across four National Health Service trusts/health regions. There was no statistically significant overall difference in readmissions: 21% of ADU participants and 23% of CRT participants were readmitted over 6 months (adjusted hazard ratio 0.78, 95% CI 0.54-1.14). However, readmission results varied substantially by setting. At follow-up, ADU participants had significantly higher Client Satisfaction Questionnaire scores (2.5, 95% CI 1.4-3.5, P < 0.001) and well-being scores (1.3, 95% CI 0.4-2.1, P = 0.004), and lower depression scores (-1.7, 95% CI -2.7 to -0.8, P < 0.001), than CRT participants.

CONCLUSIONS: Patients who accessed ADUs demonstrated better outcomes for satisfaction, well-being and depression, and no significant differences in risk of readmission, compared with those who only used CRTs. Given the positive outcomes for patients, and the fact that ADUs are inconsistently provided in the National Health Service, their value and place in the acute care pathway needs further consideration and research.

PMID:33736743 | DOI:10.1192/bjo.2021.30

Int J Health Geogr. 2021 Mar 18;20(1):13. doi: 10.1186/s12942-021-00267-z.

ABSTRACT

BACKGROUND: Cancer epidemiology studies require sufficient power to assess spatial relationships between exposures and cancer incidence accurately. However, methods for power calculations of spatial statistics are complicated and underdeveloped, and therefore underutilized by investigators. The spatial relative risk function, a cluster detection technique that detects spatial clusters of point-level data for two groups (e.g., cancer cases and controls, two exposure groups), is a commonly used spatial statistic but does not have a readily available power calculation for study design.

RESULTS: We developed sparrpowR as an open-source R package to estimate the statistical power of the spatial relative risk function. sparrpowR generates simulated data applying user-defined parameters (e.g., sample size, locations) to detect spatial clusters with high statistical power. We present applications of sparrpowR that perform a power calculation for a study designed to detect a spatial cluster of incident cancer in relation to a point source of numerous environmental emissions. The conducted power calculations demonstrate the functionality and utility of sparrpowR to calculate the local power for spatial cluster detection.

CONCLUSIONS: sparrpowR improves the current capacity of investigators to calculate the statistical power of spatial clusters, which assists in designing more efficient studies. This newly developed R package addresses a critically underdeveloped gap in cancer epidemiology by estimating statistical power for a common spatial cluster detection technique.

PMID:33736677 | DOI:10.1186/s12942-021-00267-z

Breast Cancer Res. 2021 Mar 18;23(1):34. doi: 10.1186/s13058-021-01410-1.

ABSTRACT

BACKGROUND: Among women diagnosed with invasive breast cancer, 30% have a prior diagnosis of benign breast disease (BBD). Thus, it is important to identify factors among BBD patients that elevate invasive cancer risk. In the general population, risk factors differ in their associations by clinical pathologic features; however, whether women with BBD show etiologic heterogeneity in the types of breast cancers they develop remains unknown.

METHODS: Using a nested case-control study of BBD and breast cancer risk conducted in a community healthcare plan (Kaiser Permanente Northwest), we assessed relationships of histologic features in BBD biopsies and patient characteristics with subsequent breast cancer risk and tested for heterogeneity of associations by estrogen receptor (ER) status, tumor grade, and size. The study included 514 invasive breast cancer cases (median follow-up of 9 years post-BBD diagnosis) and 514 matched controls, diagnosed with proliferative or non-proliferative BBD between 1971 and 2006, with follow-up through mid-2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using multivariable polytomous logistic regression models.

RESULTS: Breast cancers were predominantly ER-positive (86%), well or moderately differentiated (73%), small (74% < 20 mm), and stage I/II (91%). Compared to patients with non-proliferative BBD, proliferative BBD with atypia conferred increased risk for ER-positive cancer (OR = 5.48, 95% CI = 2.14-14.01) with only one ER-negative case, P-heterogeneity = 0.45. The presence of columnar cell lesions (CCLs) at BBD diagnosis was associated with a 1.5-fold increase in the risk of both ER-positive and ER-negative tumors, with a 2-fold increase (95% CI = 1.21-3.58) observed among postmenopausal women (56%), independent of proliferative BBD status with and without atypia. We did not identify statistically significant differences in risk factor associations by tumor grade or size.

CONCLUSION: Most tumors that developed after a BBD diagnosis in this cohort were highly treatable low-stage ER-positive tumors. CCL in BBD biopsies may be associated with moderately increased risk, independent of BBD histology, and irrespective of ER status.

PMID:33736682 | DOI:10.1186/s13058-021-01410-1

Mol Autism. 2021 Mar 18;12(1):24. doi: 10.1186/s13229-021-00429-7.

ABSTRACT

BACKGROUND: The Early Markers for Autism (EMA) study is a population-based case-control study designed to learn more about early biologic processes involved in ASD.

METHODS: Participants were drawn from Southern California births from 2000 to 2003 with archived prenatal and neonatal screening specimens. Across two phases, children with ASD (n = 629) and intellectual disability without ASD (ID, n = 230) were ascertained from the California Department of Developmental Services (DDS), with diagnoses confirmed according to DSM-IV-TR criteria based on expert clinical review of abstracted records. General population controls (GP, n = 599) were randomly sampled from birth certificate files and matched to ASD cases by sex, birth month and year after excluding individuals with DDS records. EMA has published over 20 papers examining immune markers, endogenous hormones, environmental chemicals, and genetic factors in association with ASD and ID. This review summarizes the results across these studies, as well as the EMA study design and future directions.

RESULTS: EMA enabled several key contributions to the literature, including the examination of biomarker levels in biospecimens prospectively collected during critical windows of neurodevelopment. Key findings from EMA include demonstration of elevated cytokine and chemokine levels in maternal mid-pregnancy serum samples in association with ASD, as well as aberrations in other immune marker levels; suggestions of increased odds of ASD with prenatal exposure to certain endocrine disrupting chemicals, though not in mixture analyses; and demonstration of maternal and fetal genetic influence on prenatal chemical, and maternal and neonatal immune marker and vitamin D levels. We also observed an overall lack of association with ASD and measured maternal and neonatal vitamin D, mercury, and brain-derived neurotrophic factor (BDNF) levels.

LIMITATIONS: Covariate and outcome data were limited to information in Vital Statistics and DDS records. As a study based in Southern California, generalizability for certain environmental exposures may be reduced.

CONCLUSIONS: Results across EMA studies support the importance of the prenatal and neonatal periods in ASD etiology, and provide evidence for the role of the maternal immune response during pregnancy. Future directions for EMA, and the field of ASD in general, include interrogation of mechanistic pathways and examination of combined effects of exposures.

PMID:33736683 | DOI:10.1186/s13229-021-00429-7