Real-World Outcomes and Prognostic Factors Among Patients with Advanced Non-Small Cell Lung Cancer and High PD-L1 Expression Treated with Immune Checkpoint Inhibitors as First-Line Therapy.

Background: Immune checkpoint inhibitors (ICIs) are standard-of-care for patients with advanced non-small cell lung cancer (aNSCLC) and programmed cell death-ligand 1 (PD-L1) expression ≥50%. Methods: A retrospective cohort study was conducted using the US de-identified electronic health record-derived Flatiron Health aNSCLC database (January 1, 2018, to July 31, 2021) among patients with PD-L1 ≥50% initiating first-line ICIs with or without chemotherapy. A clinical trial-like sub-cohort was also identified with Eastern Cooperative Oncology Group performance status 0-1, adequate organ function, and no brain metastases or other primary cancers. Kaplan-Meier methods were used to estimate time to treatment discontinuation, time to next treatment, progression-free survival and overall survival (OS) by ICI regimen (ICI+chemotherapy, ICI monotherapy) and PD-L1 expression (50-69%, 70-89%, 90-100%). Cox proportional hazard models were used to examine associations between ICI regimen, PD-L1 level, and OS, adjusting for baseline demographic and clinical variables. Results: A total of 2631 patients with aNSCLC initiating ICI+chemotherapy (n = 992) or ICI monotherapy (n = 1639) were included; median (Q1, Q3) age was 71 (63-78) years and 51.6% were male. The trial-like sub-cohort (n = 1029) generally had better outcomes vs. the overall cohort. Patients receiving ICI+chemotherapy generally had longer median OS vs. ICI monotherapy. Multivariable analyses showed no association between ICI regimen and OS among patients with PD-L1 70-89% (hazard ratio [HR]: 0.90, 95% confidence interval [CI]: 0.73-1.09) or 90-100% (HR: 0.91, 95% CI: 0.77-1.08), but patients with PD-L1 50-69% receiving ICI+chemotherapy had longer OS (HR: 0.80, 95% CI: 0.64-0.99). Conclusion: Outcomes in real-world clinical trial-like patients with aNSCLC approached those reported in pivotal ICI trials in high PD-L1 expressers. ICI monotherapy offers a potential alternative in patients with PD-L1 ≥70% while avoiding potential chemotherapy toxicity exposure; the benefits are less clear in patients with PD-L1 50-69%. Future studies should confirm these findings.

Real-World Cost of Nasal Polyps Surgery and Risk of Major Complications in the United States: A Descriptive Retrospective Database Analysis.

Background: Endoscopic nasal polyp (NP) surgery is a treatment option for patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Previous studies report NP surgery costs of $8000-13,000 and risk of major complications of NP surgery of ~0.1-1%. Limited contemporary data for costs and complications associated with NP surgery in US clinical practice are available. Methods: IQVIA PharMetrics Plus claims data were used to identify patients with NP surgery in 2019 with ≥3 years continuous baseline health-plan enrollment prior to index date (date of first eligible NP surgery) and ≥30 days continuous enrollment after index (follow-up). In this descriptive analysis, total costs of NP surgery were estimated as all medical costs on the index date (or during the entire hospital stay for patients who received surgery in the inpatient setting). Total medical costs (all-cause) were estimated for all medical services occurring from the index date to the index date +9 or +29 days (10-day and 30-day). Major complication was defined as cerebrospinal fluid (CSF) leak, orbital injury, or major hemorrhage within 30 days of index. Results: Of 6311 patients, median age was 46 years (interquartile range: 34-56); 59.7% were male; 88.2% had no NP surgery in the prior 3 years; 63.7% had allergic rhinitis, and 37.1% had asthma. Mean (SD) total medical cost of surgery was $14,697 (11,679) and mean (SD) 10-day total medical cost was $15,401 (11,968). Major complications occurred in 102 (1.7%) patients. Total medical costs and 10-day costs were higher in patients with major complications than those without ($23,605 [19,264] vs $15,251 [11,741]). Conclusion: In this descriptive analysis, NP surgery costs and rates of major surgical complications were updated using recent real-world data in the US. Results indicated that NP surgery complication rates were numerically higher than previously reported.

Machine learning models for identifying predictors of clinical outcomes with first-line immune checkpoint inhibitor therapy in advanced non-small cell lung cancer.

Immune checkpoint inhibitors (ICIs) are standard-of-care as first-line (1L) therapy for advanced non-small cell lung cancer (aNSCLC) without actionable oncogenic driver mutations. While clinical trials demonstrated benefits of ICIs over chemotherapy, variation in outcomes across patients has been observed and trial populations may not be representative of clinical practice. Predictive models can help understand heterogeneity of treatment effects, identify predictors of meaningful clinical outcomes, and may inform treatment decisions. We applied machine learning (ML)-based survival models to a real-world cohort of patients with aNSCLC who received 1L ICI therapy extracted from a US-based electronic health record database. Model performance was evaluated using metrics including concordance index (c-index), and we used explainability techniques to identify significant predictors of overall survival (OS) and progression-free survival (PFS). The ML model achieved c-indices of 0.672 and 0.612 for OS and PFS, respectively, and Kaplan-Meier survival curves showed significant differences between low- and high-risk groups for OS and PFS (both log-rank test p < 0.0001). Identified predictors were mostly consistent with the published literature and/or clinical expectations and largely overlapped for OS and PFS; Eastern Cooperative Oncology Group performance status, programmed cell death-ligand 1 expression levels, and serum albumin were among the top 5 predictors for both outcomes. Prospective and independent data set evaluation is required to confirm these results.

Characterizing the Shifting Real-World Treatment Landscape by PD-L1 Testing Status and Expression Level in Advanced Non-Small Cell Lung Cancer.

INTRODUCTION: Contemporary real-world data on advanced non-small cell lung cancer (aNSCLC) treatment patterns across programmed cell death-ligand 1 (PD-L1) expression levels and testing status are limited. METHODS: A retrospective cohort was selected of adults newly diagnosed with aNSCLC between January 1, 2018, and July 31, 2021, who initiated first-line treatments, which were described by PD-L1 status and expression levels (≥ 50%, 1-49%, < 1%). Treatment received before and after PD-L1 test results were described for patients initiating first-line treatment before PD-L1 results. For patients who initiated chemotherapy alone before PD-L1 results, the probability of receiving immune checkpoint inhibitors (ICIs) after PD-L1 results was estimated by PD-L1 level and associated factors were explored. RESULTS: Among 12,202 patients with aNSCLC initiating first-line treatment [54.7% male, mean (standard deviation) age 69.2 (9.4) years], the most common therapies were ICI-based regimens across PD-L1 levels, and chemotherapy alone among PD-L1-untested patients. Use of chemotherapy alone decreased between 2018 and 2019 and stabilized thereafter, accounting for 21-29% of first-line treatments across PD-L1 levels and 48% of untested patients in 2021. Of 1468 patients initiating first-line treatment before PD-L1 results, treatments remained unchanged in most patients after PD-L1 results. Among patients initiating chemotherapy alone before PD-L1 results, the probability of receiving ICIs within 45 days after test results was 40.5% [95% confidence interval (CI) 31.6-48.3%], 28.6% (95% CI 20.3-36.0%), and 22.9% (95% CI 16.9-28.4%) at PD-L1 ≥ 50%, 1-49%, and < 1%, respectively. CONCLUSION: While ICI-based regimens accounted for most first-line treatments across PD-L1 levels, chemotherapy alone was initiated in > 20% of patients tested for PD-L1 and 48% of untested patients in 2021. Patients who initiated chemotherapy alone had a low probability of receiving ICIs after PD-L1 test results. These results highlight the need for understanding the role and timing of PD-L1 test results for informing treatment decisions for patients with aNSCLC.

Hedgehog pathway inhibitor real-world treatment patterns in patients with basal cell carcinoma: a claims-based analysis.

Aims: To examine real-world treatment patterns for Hedgehog pathway inhibitors (HHIs) for the treatment of advanced basal cell carcinoma. Patients & methods: HHI initiators between January 2013 and June 2019 were identified from IBM MarketScan® claims data. Time to treatment discontinuation and reinitiation were estimated using Kaplan-Meier methods using a 60-day grace period. Results: Among 526 patients with basal cell carcinoma who initiated an HHI, median time to first discontinuation was 144 days, and risk of discontinuation by 12 months was 88.0%. Probability of reinitiation within 12 months was 19.7%, and median time to second discontinuation was 118 days. Conclusion: HHI discontinuation was common and reinitiation uncommon in clinical practice. Future research should evaluate persistence with recently approved therapies.

This study examined patterns of discontinuation and reinitiation of Hedgehog pathway inhibitors (HHIs) such as vismodegib or sonidegib for patients with basal cell carcinoma, the most common form of skin cancer. Initiation of HHI treatment was identified from prescriptions filled by patients with commercial insurance or Medicare who had basal cell carcinoma. Discontinuation was defined as a gap of more than 60 days without treatment, after drug supply had run out. Among the 526 patients identified, one-half had discontinued HHI treatment within about 5 months and 88% had discontinued treatment within 1 year. Fewer than 20% of patients restarted treatment. Discontinuations are common but restarting treatment is uncommon among patients with basal cell carcinoma treated with HHIs.

Real-World Treatment Patterns After CD19-Directed CAR T Cell Therapy Among Patients with Diffuse Large B Cell Lymphoma.

INTRODUCTION: CD19-directed chimeric antigen receptor T cells (CAR T) are approved for treatment of adults with relapsed/refractory diffuse large B cell lymphoma (DLBCL) following at least two lines of therapy. METHODS: This study describes real-world treatment patterns after CAR T in adults with DLBCL. It includes adults diagnosed with DLBCL in IBM MarketScan Commercial and Medicare Supplemental healthcare claims databases administered CAR T between 2017 and 2019 (index event) and at least 6 months of continuous health plan enrollment pre-index. Kaplan-Meier methods were used to estimate risk and time to first subsequent treatment after CAR T, as a proxy for CAR T failure. RESULTS: Among 129 patients meeting study criteria, most (123; 95.4%) were hospitalized during CAR T therapy. Median length of stay was 17 (25th-75th percentile, 13-22) days. Estimated 6-month risk of subsequent treatment was 36.2% (95% confidence interval [CI] 27.1-45.8%). During median follow-up of 195 (25th-75th percentile, 102-362) days, median time to the first line of therapy after CAR T, accounting for censoring, was 378 days (95% CI 226, not reached). Among 48 patients who received another therapy after CAR T, 58.3% received immunotherapy, 50.0% radiation therapy, 25.0% chemotherapy, 25.0% targeted therapy, and 12.5% hematopoietic stem cell transplant. CONCLUSIONS: Among real-world patients with DLBCL treated with CAR T, the risk of not achieving a durable response is considerable; additional, effective options for DLBCL salvage treatment are needed.

Epidemiology of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in the United States and Western Europe: population-level projections for 2020-2025.

Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) treatments have been rapidly evolving for patients treated in later lines of therapy (LoT). Country-specific cancer registry data for the US and Western Europe (WE) were combined with physician survey results to project the incidence, prevalence, and number of DLBCL and FL patients eligible for and treated by LoT between 2020 and 2025. The total number of incidents and prevalent cases of DLBCL and FL is expected to increase between 2020 and 2025 in the US and WE. 56% and 53% of the third line plus (3L+) eligible DLBCL patients and 60% and 55% of eligible FL patients initiated treatment in the US and WE, respectively. Further research is warranted to understand the reasons behind the high proportion of treatment eligible patients who do not initiate treatment, and potential differences between countries, especially in the 3L + settings.

Trends in real-world biomarker testing and overall survival in US patients with advanced non-small-cell lung cancer.

Background: Trends/outcomes associated with National Comprehensive Cancer Network (NCCN)-recommended biomarker testing to guide advanced non-small-cell lung cancer (aNSCLC) treatment were assessed. Methods: Patients initiating first-line aNSCLC treatment were included using a nationwide electronic health record-derived database (1/1/2015-10/31/2021). Trends in pre-first-line biomarker testing (PD-L1, major genomic aberrations), factors associated with testing and associations between testing and outcomes were assessed. Results: PD-L1/genomic aberration testing rates increased from 33% (2016) to 81% (2018), then plateaued. Certain clinical and demographic factors were associated with a greater likelihood of PD-L1 testing. Patients tested for PD-L1 or genomic aberrations had longer overall survival (OS). Conclusion: Biomarker testing may be associated with improved OS in aNSCLC, though not all patients had equal access to testing.

Molecular diagnostics play a critical role in precision medicine. Treatment guidelines from the National Comprehensive Cancer Network (NCCN) recommend that patients newly diagnosed with advanced non-small-cell lung cancer (aNSCLC) undergo molecular testing for PD-L1 and genomic aberrations to guide treatment choices. Based on the results of such biomarker testing, physicians can select optimal treatments for individual patients. The aim of this study was to describe the latest trends and disparities in real-world biomarker testing with a focus on PD-L1 and to explore the impact of biomarker testing on outcomes in first-line treatment of aNSCLC in the United States. Patients initiating first-line aNSCLC treatment were identified in the Flatiron Health database (1/1/2015­10/31/2021; N = 30,631). Annual trends in pre-first-line biomarker testing (PD-L1, major genomic aberrations), demographic and clinical factors associated with PD-L1 testing, and associations between PD-L1 and/or ≥1 genomic aberration testing and outcomes (e.g., overall survival [OS], time-to-next treatment [TTNT]) were assessed. Biomarker testing in patients receiving first-line treatment for aNSCLC increased between 2015 and 2017 and plateaued between 2018 and 2021. By 2021, approximately 20% of patients did not receive PD-L1 testing before first-line treatment and not all patients had equal access to testing. Both PD-L1 and genomic aberration testing were associated with improved OS and TTNT. This is likely due to enhanced treatment decisions leading to optimal treatment selection. Future research is warranted to understand interventions to improve biomarker testing and reduce disparities between different patient populations to improve treatment outcomes.

Breast Cancer Risk Factors and Circulating Anti-Müllerian Hormone Concentration in Healthy Premenopausal Women.

CONTEXT: We previously reported that anti-Müllerian hormone (AMH), a marker of ovarian reserve, is positively associated with breast cancer risk, consistent with other studies. OBJECTIVE: This study assessed whether risk factors for breast cancer are correlates of AMH concentration. METHODS: This cross-sectional study included 3831 healthy premenopausal women (aged 21-57, 87% aged 35-49) from 10 cohort studies among the general population. RESULTS: Adjusting for age and cohort, AMH positively associated with age at menarche (P < 0.0001) and parity (P = 0.0008) and inversely associated with hysterectomy/partial oophorectomy (P = 0.0008). Compared with women of normal weight, AMH was lower (relative geometric mean difference 27%, P < 0.0001) among women who were obese. Current oral contraceptive (OC) use and current/former smoking were associated with lower AMH concentration than never use (40% and 12% lower, respectively, P < 0.0001). We observed higher AMH concentrations among women who had had a benign breast biopsy (15% higher, P = 0.03), a surrogate for benign breast disease, an association that has not been reported. In analyses stratified by age (<40 vs ≥40), associations of AMH with body mass index and OCs were similar in younger and older women, while associations with the other factors (menarche, parity, hysterectomy/partial oophorectomy, smoking, and benign breast biopsy) were limited to women ≥40 (P-interaction < 0.05). CONCLUSION: This is the largest study of AMH and breast cancer risk factors among women from the general population (not presenting with infertility), and it suggests that most associations are limited to women over 40, who are approaching menopause and whose AMH concentration is declining.

Necessity of personal sampling for exposure assessment on specific constituents of PM2.5: Results of a panel study in Shanghai, China.

Many epidemiological studies have evaluated the health risks of ambient fine particulate matter (PM2.5). However, few studies have investigated the potential exposure misclassification caused by using ambient PM2.5 concentrations as proxy for individual exposure to PM2.5 in regions with high-level of air pollution. This study aimed to compare the differences between personal and ambient PM2.5 constituent concentrations, and to predict the personal exposure of sixteen PM2.5 constituents. We collected 141 72-h personal exposure filter samples from a panel of 36 healthy non-smoking college students in Shanghai, China. We then used the liner mixed effects models to predict personal constituent-specific exposure using ambient observations and several possible influencing factors including time-activity patterns, temporal variables, and meteorological conditions. The final model of each component was further evaluated by determination coefficient (R2) and root mean square error (RMSE) from leave-one-out-cross-validation (LOOCV). We observed ambient concentrations were higher than personal concentrations for all PM2.5 components except for Mn, Fe, Ca, and V. Especially, ambient NH4+, As, and NO3- concentrations were 3.65, 5.65 and 7.33-fold higher than their corresponding personal concentrations, respectively. The ambient level was the strongest predictor of their corresponding personal PM2.5 components with the highest marginal R2 (RM2: 0.081 ~ 0.901), meteorological conditions (RM2: 0.000 ~ 0.357), time-activity pattern (RM2: 0.000 ~ 0.083) and temporal indicators (RM2: 0.031 ~ 0.562) were also important predictors. Our final models predicted at least 50% of the variance of all personal PM2.5 constituents and even over 90% for K, Pb, and SO42-. LOOCV analysis showed that R2 and RMSE ranged from 0.251 to 0.907 and 0.000 to 0.092 µg/m3, respectively. Our results showed that ambient concentration of most PM2.5 constituents along with time-activity patterns, temporal variables, and meteorological conditions, could adequately predict personal exposure concentration. Prediction models of individual PM2.5 constituent may help to improve the accuracy of exposure measurement in future epidemiological studies.

Breast cancer risk prediction in women aged 35-50 years: impact of including sex hormone concentrations in the Gail model.

BACKGROUND: Models that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening. Premenopausal concentrations of circulating anti-Müllerian hormone (AMH), a biomarker of ovarian reserve, and testosterone have been positively associated with breast cancer risk in prospective studies. We assessed whether adding AMH and/or testosterone to the Gail model improves its prediction performance for women aged 35-50. METHODS: In a nested case-control study including ten prospective cohorts (1762 invasive cases/1890 matched controls) with pre-diagnostic serum/plasma samples, we estimated relative risks (RR) for the biomarkers and Gail risk factors using conditional logistic regression and random-effects meta-analysis. Absolute risk models were developed using these RR estimates, attributable risk fractions calculated using the distributions of the risk factors in the cases from the consortium, and population-based incidence and mortality rates. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory accuracy of the models with and without biomarkers. RESULTS: The AUC for invasive breast cancer including only the Gail risk factor variables was 55.3 (95% CI 53.4, 57.1). The AUC increased moderately with the addition of AMH (AUC 57.6, 95% CI 55.7, 59.5), testosterone (AUC 56.2, 95% CI 54.4, 58.1), or both (AUC 58.1, 95% CI 56.2, 59.9). The largest AUC improvement (4.0) was among women without a family history of breast cancer. CONCLUSIONS: AMH and testosterone moderately increase the discriminatory accuracy of the Gail model among women aged 35-50. We observed the largest AUC increase for women without a family history of breast cancer, the group that would benefit most from improved risk prediction because early screening is already recommended for women with a family history.

Circulating anti-Müllerian hormone and breast cancer risk: A study in ten prospective cohorts.

A strong positive association has been observed between circulating anti-Müllerian hormone (AMH), a biomarker of ovarian reserve, and breast cancer risk in three prospective studies. Confirming this association is important because of the paucity of biomarkers of breast cancer risk in premenopausal women. We conducted a consortium study including ten prospective cohorts that had collected blood from premenopausal women. A nested case-control design was implemented within each cohort. A total of 2,835 invasive (80%) and in situ (20%) breast cancer cases were individually matched to controls (n = 3,122) on age at blood donation. AMH was measured using a high sensitivity enzyme-linked immunoabsorbent assay. Conditional logistic regression was applied to the aggregated dataset. There was a statistically significant trend of increasing breast cancer risk with increasing AMH concentration (ptrend across quartiles <0.0001) after adjusting for breast cancer risk factors. The odds ratio (OR) for breast cancer in the top vs. bottom quartile of AMH was 1.60 (95% CI = 1.31-1.94). Though the test for interaction was not statistically significant (pinteraction = 0.15), the trend was statistically significant only for tumors positive for both estrogen receptor (ER) and progesterone receptor (PR): ER+/PR+: ORQ4-Q1 = 1.96, 95% CI = 1.46-2.64, ptrend <0.0001; ER+/PR-: ORQ4-Q1 = 0.82, 95% CI = 0.40-1.68, ptrend = 0.51; ER-/PR+: ORQ4-Q1 = 3.23, 95% CI = 0.48-21.9, ptrend = 0.26; ER-/PR-: ORQ4-Q1 = 1.15, 95% CI = 0.63-2.09, ptrend = 0.60. The association was observed for both pre- (ORQ4-Q1 = 1.35, 95% CI = 1.05-1.73) and post-menopausal (ORQ4-Q1 = 1.61, 95% CI = 1.03-2.53) breast cancer (pinteraction = 0.34). In this large consortium study, we confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs. bottom quartile of AMH.

Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer: A Nested Case-Control Study.

Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes other than the vitamin D receptor (VDR) gene and particularly have not examined the association with the retinoid X receptor alpha (RXRA) gene which may be a key vitamin D pathway gene. We conducted a nested case-control study of 734 cases and 1435 individually matched controls from a population-based prospective cohort study, the Northern Sweden Mammary Screening Cohort. Tag and functional SNPs were genotyped for the VDR, cytochrome p450 24A1 (CYP24A1), and RXRA genes. We also genotyped specific SNPs in four other genes related to vitamin D metabolism and signaling (GC/VDBP, CYP2R1, DHCR7, and CYP27B1). SNPs in the CYP2R1, DHCR7, and VDBP gene regions that were associated with circulating 25(OH)D concentration in GWAS were also associated with plasma 25(OH)D in our study (p-trend <0.005). After taking into account the false discovery rate, these SNPs were not significantly associated with breast cancer risk, nor were any of the other SNPs or haplotypes in VDR, RXRA, and CYP24A1. We observed no statistically significant associations between polymorphisms or haplotypes in key vitamin D-related genes and risk of breast cancer. These results, combined with the observation in this cohort and most other prospective studies of no association of circulating 25(OH)D with breast cancer risk, do not support an association between vitamin D and breast cancer risk.

A prospective study of arm circumference and risk of death in Bangladesh.

BACKGROUND: Epidemiological studies have observed protective effects of mid-upper arm circumference (MUAC) against all-cause mortality mostly in Western populations. However, evidence on cause-specific mortality is limited. METHODS: The sample included 19 575 adults from a population-based cohort study in rural Bangladesh, who were followed up for an average of 7.9 years for mortality. Cox proportional hazards regression was used to evaluate the effect of MUAC, as well as the joint effect of body mass index (BMI) and MUAC, on the risk of death from any cause, cancer and cardiovascular disease (CVD). RESULTS: During 154 664 person-years of follow-up, 744 deaths including 312 deaths due to CVD and 125 deaths due to cancer were observed. There was a linear inverse relationship of MUAC with total and CVD mortality. Each 1-cm increase in MUAC was associated a reduced risk of death from any cause [hazard ratio (HR) = 0.85; 95% confidence interval (C), 0.81-0.89) and CVD (HR = 0.87; 95% CI, 0.80-0.94), after controlling for potential confounders. No apparent relationship between MUAC and the risk of death from cancer was observed. Among individuals with a low BMI (<18.5 kg/m(2)), a MUAC less than 24 cm was associated with increased risk for all-cause (HR = 1.81; 95% CI, 1.52-2.17) and CVD mortality (HR = 1.45; 95% CI, 1.11-1.91). CONCLUSIONS: MUAC may play a critical role on all-cause and CVD mortality in lean Asians.

Association between arsenic exposure from drinking water and hematuria: results from the Health Effects of Arsenic Longitudinal Study.

Arsenic (As) exposure has been associated with both urologic malignancy and renal dysfunction; however, its association with hematuria is unknown. We evaluated the association between drinking water As exposure and hematuria in 7843 men enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). Cross-sectional analysis of baseline data was conducted with As exposure assessed in both well water and urinary As measurements, while hematuria was measured using urine dipstick. Prospective analyses with Cox proportional regression models were based on urinary As and dipstick measurements obtained biannually since baseline up to six years. At baseline, urinary As was significantly related to prevalence of hematuria (P-trend<0.01), with increasing quintiles of exposure corresponding with respective prevalence odds ratios of 1.00 (reference), 1.29 (95% CI: 1.04-1.59), 1.41 (95% CI: 1.15-1.74), 1.46 (95% CI: 1.19-1.79), and 1.56 (95% CI: 1.27-1.91). Compared to those with relatively little absolute urinary As change during follow-up (-10.40 to 41.17 µg/l), hazard ratios for hematuria were 0.99 (95% CI: 0.80-1.22) and 0.80 (95% CI: 0.65-0.99) for those whose urinary As decreased by >47.49 µg/l and 10.87 to 47.49 µg/l since last visit, respectively, and 1.17 (95% CI: 0.94-1.45) and 1.36 (95% CI: 1.10-1.66) for those with between-visit increases of 10.40 to 41.17 µg/l and >41.17 µg/l, respectively. These data indicate a positive association of As exposure with both prevalence and incidence of dipstick hematuria. This exposure effect appears modifiable by relatively short-term changes in drinking water As.

Association between anthropometric measures of obesity and subclinical atherosclerosis in Bangladesh.

BACKGROUND: Anthropometric measures such as waist-hip-ratio (WHR), waist-height-ratio (WHtR), waist circumference, Mid-upper arm circumference (MUAC), and upper thigh circumference, have been linked to the risk of cardiovascular disease (CVD). However, their relationships with subclinical atherosclerosis are unclear. Studies in normal-weight populations, especially in Asian countries where leanness is prevalent, are lacking. METHODS: We conducted a cross-sectional study to assess the associations of WHR, WHtR, waist circumference, hip circumference, body mass index (BMI), MUAC and upper thigh circumference with carotid intima-media thickness (cIMT) among 562 middle-aged participants free of CVD in rural Bangladesh. RESULTS: After adjusting for age and sex, WHR and waist circumference but not BMI showed a positive significant association with cIMT. In multivariate analysis, each standard deviation (SD) increase of WHR (0.08) or WHtR (0.07) was associated with an 8.96 µm (95% CI, 1.12-16.81) or 11.45 µm (95%CI, 0.86-22.04) difference in cIMT, respectively, after controlling for age, sex, BMI, smoking status, education level, and systolic blood pressure (SBP). The associations of WHR and WHtR with cIMT were independent of the influence of other anthropometric measures. The associations of other anthropometric measures and cIMT were not apparent. CONCLUSIONS: In our relatively lean, healthy Asian population, WHR and WHtR appear to be better predictors of early atherosclerosis than other common surrogates of adiposity.

Association between body mass index and cardiovascular disease mortality in east Asians and south Asians: pooled analysis of prospective data from the Asia Cohort Consortium.

OBJECTIVE: To evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians. DESIGN: Pooled analyses of 20 prospective cohorts in Asia, including data from 835,082 east Asians and 289,815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability. SETTING: General populations in east Asia (China, Taiwan, Singapore, Japan, and Korea) and south Asia (India and Bangladesh). PARTICIPANTS: 1,124,897 men and women (mean age 53.4 years at baseline). MAIN OUTCOME MEASURES: Risk of death from overall cardiovascular disease, coronary heart disease, stroke, and (in east Asians only) stroke subtypes. RESULTS: 49,184 cardiovascular deaths (40,791 in east Asians and 8393 in south Asians) were identified during a mean follow-up of 9.7 years. East Asians with a body mass index of 25 or above had a raised risk of death from overall cardiovascular disease, compared with the reference range of body mass index (values 22.5-24.9; hazard ratio 1.09 (95% confidence interval 1.03 to 1.15), 1.27 (1.20 to 1.35), 1.59 (1.43 to 1.76), 1.74 (1.47 to 2.06), and 1.97 (1.44 to 2.71) for body mass index ranges 25.0-27.4, 27.5-29.9, 30.0-32.4, 32.5-34.9, and 35.0-50.0, respectively). This association was similar for risk of death from coronary heart disease and ischaemic stroke; for haemorrhagic stroke, the risk of death was higher at body mass index values of 27.5 and above. Elevated risk of death from cardiovascular disease was also observed at lower categories of body mass index (hazard ratio 1.19 (95% confidence interval 1.02 to 1.39) and 2.16 (1.37 to 3.40) for body mass index ranges 15.0-17.4 and <15.0, respectively), compared with the reference range. In south Asians, the association between body mass index and mortality from cardiovascular disease was less pronounced than that in east Asians. South Asians had an increased risk of death observed for coronary heart disease only in individuals with a body mass index greater than 35 (hazard ratio 1.90, 95% confidence interval 1.15 to 3.12). CONCLUSIONS: Body mass index shows a U shaped association with death from overall cardiovascular disease among east Asians: increased risk of death from cardiovascular disease is observed at lower and higher ranges of body mass index. A high body mass index is a risk factor for mortality from overall cardiovascular disease and for specific diseases, including coronary heart disease, ischaemic stroke, and haemorrhagic stroke in east Asians. Higher body mass index is a weak risk factor for mortality from cardiovascular disease in south Asians.