Category: Statistics

JAMA Netw Open. 2023 Oct 2;6(10):e2339584. doi: 10.1001/jamanetworkopen.2023.39584.

ABSTRACT

IMPORTANCE: Black women in the United States have higher breast cancer (BC) mortality rates than White women. The combined role of multiple factors, including body mass index (BMI), age, and tumor subtype, remains unclear.

OBJECTIVE: To assess the association of race and ethnicity with survival among clinical trial participants with early-stage BC (eBC) according to tumor subtype, age, and BMI.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed survival data, as of November 12, 2021, from participants enrolled between 1997 and 2010 in 4 randomized adjuvant chemotherapy trials: Cancer and Leukemia Group B (CALGB) 9741, 49907, and 40101 as well as North Central Cancer Treatment Group (NCCTG) N9831, legacy groups of the Alliance of Clinical Trials in Oncology. Median follow-up was 9.8 years.

EXPOSURES: Non-Hispanic Black and Hispanic participants were compared with non-Hispanic White participants within subgroups of subtype (hormone receptor positive [HR+]/ERBB2 [formerly HER2] negative [ERBB2-], ERBB2+, and HR-/ERBB2-), age (<50, 50 to <65, and ≥65 years), and BMI (<18.5, 18.5 to <25.0, 25.0 to <30.0, and ≥30.0).

MAIN OUTCOMES AND MEASURES: Recurrence-free survival (RFS) and overall survival (OS).

RESULTS: Of 9479 participants, 436 (4.4%) were Hispanic, 871 (8.8%) non-Hispanic Black, and 7889 (79.5%) non-Hispanic White. The median (range) age was 52 (19.0-89.7) years. Among participants with HR+/ERBB2- tumors, non-Hispanic Black individuals had worse RFS (hazard ratio [HR], 1.49; 95% CI, 1.04-2.12; 5-year RFS, 88.5% vs 93.2%) than non-Hispanic White individuals, although the global test for association of race and ethnicity with RFS was not significant within any tumor subtype. There were no OS differences by race and ethnicity in any subtype. Race and ethnicity were associated with OS in young participants (age <50 years; global P = .008); young non-Hispanic Black participants (HR, 1.34; 95% CI, 1.04-1.71; 5-year OS, 86.6% vs 92.0%) and Hispanic participants (HR, 1.62; 95% CI, 1.16-2.29; 5-year OS, 86.2% vs 92.0%) had worse OS than young non-Hispanic White participants. Race and ethnicity were associated with RFS in participants with BMIs of 25 to less than 30, with non-Hispanic Black participants having worse RFS (HR, 1.81; 95% CI, 1.23-2.68; 5-year RFS, 83.2% vs 87.3%) than non-Hispanic White participants.

CONCLUSIONS AND RELEVANCE: In this cohort study, racial and ethnic survival disparities were identified in patients with eBC receiving standardized initial care, and potentially at-risk subgroups, for whom focused interventions may improve outcomes, were found.

PMID:37878313 | DOI:10.1001/jamanetworkopen.2023.39584

JAMA Netw Open. 2023 Oct 2;6(10):e2339723. doi: 10.1001/jamanetworkopen.2023.39723.

ABSTRACT

IMPORTANCE: Prior studies suggested that metformin may be associated with reduced dementia incidence, but associations may be confounded by disease severity and prescribing trends. Cessation of metformin therapy in people with diabetes typically occurs due to signs of kidney dysfunction but sometimes is due to less serious adverse effects associated with metformin.

OBJECTIVE: To investigate the association of terminating metformin treatment for reasons unrelated to kidney dysfunction with dementia incidence.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted at Kaiser Permanente Northern California, a large integrated health care delivery system, among a cohort of metformin users born prior to 1955 without history of diagnosed kidney disease at metformin initiation. Dementia follow-up began with the implementation of electronic health records in 1996 and continued to 2020. Data were analyzed from November 2021 through September 2023.

EXPOSURES: A total of 12 220 early terminators, individuals who stopped metformin with normal estimated glomerular filtration rate (eGFR), were compared with routine metformin users, who had not yet terminated metformin treatment or had terminated (with or without restarting) after their first abnormal eGFR measurement. Early terminators were matched with routine users of the same age and gender who had diabetes for the same duration.

MAIN OUTCOMES AND MEASURES: The outcome of interest was all-cause incident dementia. Follow-up for early terminators and their matched routine users was started at age of termination for the early terminator. Survival models adjusted for sociodemographic characteristics and comorbidities at the time of metformin termination (or matched age). Mediation models with HbA1c level and insulin usage 1 and 5 years after termination tested whether changes in blood glucose or insulin usage explained associations between early termination of metformin and dementia incidence.

RESULTS: The final analytic sample consisted of 12 220 early terminators (5640 women [46.2%]; mean [SD] age at start of first metformin prescription, 59.4 [9.0] years) and 29 126 routine users (13 582 women [46.6%]; mean [SD] age at start of first metformin prescription, 61.1 [8.9] years). Early terminators had 1.21 times the hazard of dementia diagnosis compared with routine users (hazard ratio, 1.21; 95% CI, 1.12 to 1.30). In mediation analysis, contributions to this association by changes in HbA1c level or insulin use ranged from no contribution (0.00 years; 95% CI, -0.02 to 0.02 years) for insulin use at 5 years after termination to 0.07 years (95% CI, 0.02 to 0.13 years) for HbA1c level at 1 year after termination, suggesting that the association was largely independent of changes in HbA1c level and insulin usage.

CONCLUSIONS AND RELEVANCE: In this study, terminating metformin treatment was associated with increased dementia incidence. This finding may have important implications for clinical treatment of adults with diabetes and provides additional evidence that metformin is associated with reduced dementia risk.

PMID:37878309 | DOI:10.1001/jamanetworkopen.2023.39723

J Integr Complement Med. 2023 Oct 25. doi: 10.1089/jicm.2023.0189. Online ahead of print.

ABSTRACT

Introduction: Endothelial dysfunction is the initial step in the pathogenesis of atherosclerosis; and it plays a central role in the development of cardiovascular diseases and many types of human diseases (diabetes, kidney failure, cancer, and viral infections). Strategies that are effective in protecting vascular endothelial function and retard or reversing endothelial dysfunction in the early stage appear to be potential in the prevention of vascular, cardiac, and many human diseases. Several studies have been carried out on the effects of yoga on endothelial function, but the results of these studies have not been synthesized. This study aimed at conducting a systematic review and meta-analysis to determine the effectiveness of yoga on endothelial function. Methods: A systematic review and meta-analysis of studies that assessed the effect of yoga practice on vascular endothelial function was done as per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, Scopus, Google Scholar, and Cochrane controlled register of trials (CENTRAL) were searched from inception to August 2022. The search strategy was constructed around yoga-based techniques and endothelial function. All the yoga-based interventional studies on endothelial function or dysfunction were included in this review. A narrative synthesis and descriptive analysis were done due to the diverse methodology of selected studies. We carried out a formal meta-analysis of controlled trials that assessed the effect of yoga on flow-mediated dilatation (FMD), a measure of endothelial function. Results: A total of 18 studies were included for review involving 1043 participants. Yoga training showed improved endothelial function in 12 studies, whereas 6 studies did not find any statistically robust effect. Meta-analysis (n = 395 participants, 6-studies, 7 comparisons) showed an increase in brachial FMD by yoga practice (mean difference = -1.23%; 95% confidence interval -2.23 to -0.23; p = 0.02). The heterogeneity between the studies was 43% (Tau² = 0.70, χ² = 10.49). The risk of bias was low to moderate in these studies. No adverse effects were reported. Conclusions: Yoga practice improved endothelial function. Yoga could be a safe and potential integrative medicine to improve endothelial function. However, as the statistical heterogeneity, that is, variation in the FMD among the studies was moderate, large clinical trials are necessary for its clinical recommendations.

PMID:37878297 | DOI:10.1089/jicm.2023.0189

Metab Syndr Relat Disord. 2023 Oct 25. doi: 10.1089/met.2023.0127. Online ahead of print.

ABSTRACT

Genetic variants are predisposing factors to polycystic ovary syndrome (PCOS), a multifactorial condition that often gets triggered due to various environmental factors. The study investigates the association of the variants of genes that are involved in the steroidogenesis pathway or gonadotropin pathway with the risk of PCOS. Appropriate keywords for predetermined genes were used to search in PubMed, Google Scholar, Science Direct, and Central Cochrane Library up to January 11, 2023. PROSPERO (CRD42022275425). Inclusion criteria: (a) case-control study; (b) genotype or allelic data. Exclusion criteria were: (a) duplicate studies; (b) clinical trials, systematic reviews, meta-analysis or conference abstract, case reports; (c) other than the English language; (d) having insufficient data; e) genetic variants for which meta-analysis has been reported recently and does not have a scope of the update. Various genetic models were applied as per data availability. Overall 12 variants of 7 genes were selected for the analysis. Relevant data were extracted from 47 studies which include 10,584 PCOS subjects and 16,150 healthy controls. Meta-analysis indicates a significant association between TOX3 rs4784165 [ORs = 1.08, 95% CI (1.00-1.16)], HMGA2 rs2272046 [ORs = 2.73, 95% CI (1.97-3.78)], YAP1 rs1894116 [OR = 1.22, 95% CI (1.13-1.33)] and increased risk of PCOS. Whereas FSHR rs2268361 [ORs = 0.84, 95% CI (0.78-0.89)] is associated with decreased PCOS risk. When sensitivity analysis was carried out, the association became significant for CYP19 rs700519 and FSHR rs6165 under an additive model. In addition, C9Orf3 rs3802457 became significantly associated with decreased PCOS risk with the removal of one study. Insignificant association was observed for CYP19A (rs2470152), FSHR (rs2349415, rs6166), C9Orf3 (rs4385527), GnRH1 (rs6185) and risk of PCOS. Our findings suggest association of CYP19A (rs700519), TOX3 (rs4784165), HMGA2 (rs2272046), FSHR (rs6165, rs2268361), C9orf3 (rs3802457), and YAP1 (rs1894116) with risk for PCOS.

PMID:37878274 | DOI:10.1089/met.2023.0127

Med Lav. 2023 Oct 24;114(5):e2023042.

ABSTRACT

BACKGROUND: We aimed to investigate the contribution of serum IgG testing to the history of exposure in the diagnosis of fibrotic hypersensitivity pneumonitis.

METHODS: A single-center, retrospective, cross-sectional study including 63 patients pathologically diagnosed with fibrotic hypersensitivity pneumonitis in line with the guidelines of the American Thoracic Society. Descriptive statistics were presented and Kappa statistic was performed to evaluate the compatibility between panel and the history of exposure.

RESULTS: The median age was 63 (22-81) years and 34 (54%) were male. Forty-six patients (73%) had a positive history of exposure. Thirty-nine patients (61.9%) had a positive HP/Avian panel. The most common exposure agent was mold (34.9%), followed by parakeet (31.7%). The antibody detected the most was penicillium chrysogenum lgG (36.5%), followed by aspergillus fumigatus (31.8%). There was no compatibility between HP/Avian panel and history of exposure (kappa coefficient= 0.18, p= 0.14). When the exposure was only assessed based on the history, 4 (6.35%) patients were diagnosed as fibrotic hypersensitivity pneumonitis with low confidence, 6 (9.52%) with moderate confidence, 11 (17.46%) with high confidence and 42 (66.67%) with definite confidence; whereas 4 (6.35%) patients were diagnosed as fibrotic hypersensitivity pneumonitis with low confidence, 6 (9.52%) with moderate confidence, 9 (14.29%) patients with high confidence and 44 (69.84%) patients with definite confidence if exposure was evaluated with history and/or panel.

CONCLUSIONS: Serum specific precipitating antibody panel does not seem to provide additional value to the history of exposure in the diagnosis of fibrotic hypersensitivity pneumonitis.

PMID:37878260

Endocrine. 2023 Oct 25. doi: 10.1007/s12020-023-03570-w. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the association of body mass index (BMI) with risk of first cardiometabolic disease (FCMD), cardiometabolic multimorbidity (CMM) and death.

METHODS: 87,512 participants free of CMD were included from the Kailuan cohort, which was established during 2006-2007 and followed up until 2020. BMI was classified as underweight ( < 18.5 kg/m²), healthy weight (18.5-23.9 kg/m²), overweight (24.0-27.9 kg/m²), mildly obese (28.0-31.9 kg/m²), and severely obese ( ≥ 32.0 kg/m²). FCMD was defined as the first onset of diabetes, heart disease, or stroke, and CMM as the coexistence of at least two CMD. The hazard ratio (HR) and 95% confidence interval (95%CI) were estimated with multi-state models.

RESULTS: 20,577 participants developed FCMD, 2232 developed CMM afterwards, and 10,191 died. Individuals with higher BMI was more likely to develop FCMD and CMM. Compared with healthy weight, the HR (95%CI) of severe obesity for transition from health to FCMD and from FCMD to CMM was 3.12 (2.91, 3.34) and 1.92 (1.60, 2.31), respectively. On the other hand, underweight was consistently associated with higher mortality risk regardless of initial status, whereas severe obesity was only related to increased risk for transition from health to death (HR: 1.36; 95%CI: 1.17, 1.56) but not for transition from FCMD (HR: 0.70; 95%CI: 0.57, 0.87) or CMM (HR: 0.80; 95%CI: 0.54, 1.19) to death.

CONCLUSION: Our findings highlighted the importance of maintaining healthy weight for primary and secondary prevention of CMD and reflected the demand for more accurate measurement and comprehensive management of obesity for CMD patients.

PMID:37878230 | DOI:10.1007/s12020-023-03570-w

Environ Geochem Health. 2023 Oct 25. doi: 10.1007/s10653-023-01776-5. Online ahead of print.

ABSTRACT

The concentration and bioaccessibility of potentially toxic metals, including As, Cd, Cr, Cu, Mn, Ni, Pb and Zn, were determined in surface soil samples from a mining community (Kenyasi) and a non-mining community (Sunyani) in Ghana, to investigate the contribution of mining activities to the environmental burden of potentially toxic metals. The study found significant differences in metal concentrations (p < 0.05) in As, Cd, Cu, Mn, Ni, and Zn, but no significant difference (p > 0.05) in Pb and Cr between the two communities. The study found a moderate correlation between pH and metal concentrations in the mining community and a moderate positive correlation with As, Cd, Cr, Cu, Ni, and Zn in the non-mining community. The distribution pattern revealed elevated levels of toxic metals in the southeastern corridor of the mining community, which is close to a gold mine. Most heavy metals were concentrated in the commercial community’s southern zone, with more residents and private elementary schools. Metal bioaccessibility was variable, and except for Cu and Zn, the mean bioaccessibility was less than 50% for a given metal. Contamination factor, geoaccumulation index, and soil enrichment factor suggested very high contamination of Cd, and a considerable to moderate contamination of As, Ni, Zn, and Cu at both the mining and non-mining communities. The above observations and the pollution and risk indices employed in this study confirmed that the mining community was more polluted (PLI = 2.145) than the non-mining community (PLI = 1.372). The total metal hazard (HI) exceeded thresholds by three and four times at non-mining and mining sites. Regular monitoring is necessary, especially in the mining community, to prevent soil metal accumulation.

PMID:37878226 | DOI:10.1007/s10653-023-01776-5

Int Ophthalmol. 2023 Oct 25. doi: 10.1007/s10792-023-02790-3. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the optical coherence tomography angiogram changes in non-active severe thyroid-related ophthalmopathy patients after cosmetic bone decompression.

METHODS: Eighteen patients (25 eyes) with severe not active not compressive (NANC) TED who were candidates for decompression surgery for cosmetic reasons were included in this study, and a 3 × 3 mm macular scan was used to measure vessel density and RNFL thickness. Whole macular vessel density in its superficial, deep and choriocapillaris layers was evaluated. The following data were extracted for each of layers: superior and inferior hemispheres, fovea, parafoveal vessel density, its superior and inferior hemispheres, and temporal, superior, nasal and inferior quadrant.

RESULTS: The mean RPC increased postoperatively, which was statistically significant in small vessels of peripapillary area (p-value = 0.045). The mean RNFL thickness decreased after surgery and it was statistically significant in the peripapillary (p-value = 0.032) and Inferior-Hemifield area (p-value = 0.036). The choriocapillaris changes were significant in Superior-Hemifield (p-value = 0.031) and Fovea (p-value = 0.03).

CONCLUSION: Thyroid-associated orbitopathy patients have a tendency to decrease vascular density and correlated with disease activity more than stage of orbitopathy. There was not a strong and even discrepant result in linkage of RNFL thickness and other optic nerve function tests and TED patient status and it is needed to do studies with more epidemiologic power and same methodology of study to be more comparable.

PMID:37878198 | DOI:10.1007/s10792-023-02790-3

Infection. 2023 Oct 25. doi: 10.1007/s15010-023-02108-6. Online ahead of print.

ABSTRACT

OBJECTIVE: Carbapenem-resistant Enterobacteriaceae (CRE) pose a significant threat to human health and have emerged as a major public health concern. We aimed to compare the efficacy and the safety of ceftazidime-avibactam (CAZ-AVI) and polymyxin in the treatment of CRE infections.

METHODS: A systematic review and meta-analysis was performed by searching the databases of EMBASE, PubMed, and the Cochrane Library. Published studies on the use of CAZ-AVI and polymyxin in the treatment of CRE infections were collected from the inception of the database until March 2023. Two investigators independently screened the literature according to the inclusion and exclusion criteria, evaluated the methodological quality of the included studies and extracted the data. The meta-analysis was performed using RevMan 5.4 software.

RESULTS: Ten articles with 833 patients were included (CAZ-AVI 325 patients vs Polymyxin 508 patients). Compared with the patients who received polymyxin-based therapy, the patients who received CAZ-AVI therapy had significantly lower 30-days mortality (RR = 0.49; 95% CI 0.01-2.34; I² = 22%; P < 0.00001), higher clinical cure rate (RR = 2.70; 95% CI 1.67-4.38; I² = 40%; P < 0.00001), and higher microbial clearance rate (RR = 2.70; 95% CI 2.09-3.49; I² = 0%; P < 0.00001). However, there was no statistically difference in the incidence of acute kidney injury between patients who received CAZ-AVI and polymyxin therapy (RR = 1.38; 95% CI 0.69-2.77; I² = 22%; P = 0.36). In addition, among patients with CRE bloodstream infection, those who received CAZ-AVI therapy had significantly lower mortality than those who received polymyxin therapy (RR = 0.44; 95% CI 0.27-0.69, I² = 26%, P < 0.00004).

CONCLUSIONS: Compared to polymyxin, CAZ-AVI demonstrated superior clinical efficacy in the treatment of CRE infections, suggesting that CAZ-AVI may be a superior option for CRE infections.

PMID:37878197 | DOI:10.1007/s15010-023-02108-6

Environ Sci Pollut Res Int. 2023 Oct 25. doi: 10.1007/s11356-023-30316-y. Online ahead of print.

ABSTRACT

Persistent organic pollutants (POPs) are compounds that are recalcitrant and ubiquitous that bioaccumulate in human milk (HM) and can impact infant growth and development. We explore the association between POP concentration in HM at 2-50 days postpartum and infant growth and development trajectory throughout the first year of life. A cohort of 68 healthy adult Brazilian women and their infants were followed from 28 to 35 gestational weeks to 12 months postpartum. HM samples were collected between 2 and 50 days postpartum, and POP concentrations were analyzed using gas chromatography with mass spectrometry. Concentrations of POPs >limit of quantification (LOQ) were defined as presence, and concentrations ≤LOQ as an absence. Growth z-scores were analyzed according to WHO growth charts and infant development scores according to Age & Stages Questionnaires at 1 (n = 66), 6 (n = 50), and 12 months (n = 45). Linear mixed effects (LME) models were used to investigate the association of POPs in HM with infant growth and development. Benjamini-Hochberg (BH) correction for multiple testing was performed to reduce the false discovery ratio. P < 0.1 was considered for models with the interaction between POPs and time/sex. After BH correction, adjusted LME models with time interaction showed (1) a positive association between the presence of β hexachlorocyclohexane and an increase in head circumference-for-age z-score (β = 0.003, P = 0.095); (2) negative associations between total POPs (β = -0.000002, P = 0.10), total organochlorine pesticides (β = -0.000002, P = 0.10), and dichlorodiphenyldichloroethylene concentrations in HM (β = -0.000002, P = 0.10) and fine motor scores. No statistical difference between the sexes was observed. Postnatal exposure to organochlorine pesticides in HM shows a positive association with the trajectory of head circumference-for-age z-score and a negative association with the trajectories of fine motor skills scores. Future studies on POP variation in HM at different postpartum times and their effect on infant growth and development should be encouraged.

PMID:37878172 | DOI:10.1007/s11356-023-30316-y