The cost-effectiveness of germline BRCA testing in metastatic prostate cancer followed by cascade testing of first-degree relatives of mutation carriers.

OBJECTIVES: Metastatic prostate cancer (mPCa) patients with BRCA mutations benefit from targeted treatments (e.g., olaparib). Additionally, family members of affected patients have increased risk of hereditary cancers and benefit from early detection and prevention. International guidelines recommend genetic testing in mPCa, however, the value for money of testing mPCa patients and cascade testing of blood-related family members has not been assessed. In this context we evaluated the cost-effectiveness of germline BRCA testing in mPCa patients followed by cascade testing of first-degree relatives (FDRs) of mutation carriers. METHODS: We conducted a cost-utility analysis of germline BRCA testing using two scenarios: 1) testing mPCa patients only; 2) testing mPCa patients and first-degree relatives (FDRs) of those who test positive. A semi-Markov multi-health-state transition model was constructed using a lifetime time horizon. The analyses were performed from an Australian payer perspective. Decision uncertainty was characterized using probabilistic analyses. RESULTS: Compared with no testing, BRCA testing in mPCa was associated with an incremental cost of AU$3,731 and a gain of 0.014 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio (ICER) of AU$265,942/QALY. Extending testing to FDRs of variant positive patients resulted in an ICER of AU$16,392/QALY. Probability of cost-effectiveness at a willingness-to-pay of AU$75,000/QALY was 0% in the standalone mPCa analysis and 100% in the cascade testing analysis. CONCLUSION: BRCA testing when performed as a standalone strategy in patients with mPCa may not be cost-effective but demonstrates significant value for money after the inclusion of cascade testing of FDRs of mutation carriers.

Improving equitable access to publicly funded bariatric surgery in Queensland, Australia.

BackgroundPeople living in regional Queensland, Australia, have less access to health care than their metropolitan neighbours; a gap that is wider if they are also of Aboriginal and Torres Strait Islander ethnicity. The Bariatric Surgery Initiative (BSI) aims to provide metabolic bariatric surgery as a public service accessible to all Queenslanders for patients with morbid obesity according to need, regardless of location or ethnicity.MethodsWe investigated the BSI's progress in closing the metro-regional gap by comparing the distribution of referrals for surgery with the geographic and ethnic spread of obesity across Queensland in 2017-2019.ResultsRegional Queensland is home to 59.8% of Queensland's individuals with obesity, whereas 40.2% live in metropolitan Brisbane. In contrast, 47.8% of referrals were from regional areas, with 52.2% received from Brisbane. We found that more patients from metropolitan than regional areas underwent metabolic bariatric surgery, probably due to a paucity of referrals from regional locations. Aboriginal and Torres Strait Islander peoples were able to access the service and all patients realised significant health benefits after surgery.ConclusionsThe BSI improved access to this service, and inequities in metro-regional access may depend on patient choice and healthcare provider awareness of the BSI.Trial registrationThis initiative was a quality improvement study focused on providing access to care rather than a clinical trial; as such it was not registered as a clinical trial.

The cost-effectiveness of germline BRCA testing-guided olaparib treatment in metastatic castration resistant prostate cancer.

BACKGROUND: Olaparib targets the DNA repair pathways and has revolutionized the management of metastatic castration resistant prostate cancer (mCRPC). Treatment with the drug should be guided by genetic testing; however, published economic evaluations did not consider olaparib and genetic testing as codependent technologies. This study aims to assess the cost-effectiveness of BRCA germline testing to inform olaparib treatment in mCRPC. METHODS: We conducted a cost-utility analysis of germline BRCA testing-guided olaparib treatment compared to standard care without testing from an Australian health payer perspective. The analysis applied a decision tree to indicate the germline testing or no testing strategy. A Markov multi-state transition approach was used for patients within each strategy. The model had a time horizon of 5 years. Costs and outcomes were discounted at an annual rate of 5 percent. Decision uncertainty was characterized using probabilistic and scenario analyses. RESULTS: Compared to standard care, BRCA testing-guided olaparib treatment was associated with an incremental cost of AU$7,841 and a gain of 0.06 quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) was AU$143,613 per QALY. The probability of BRCA testing-guided treatment being cost effective at a willingness-to-pay threshold of AU$100,000 per QALY was around 2 percent; however, the likelihood for cost-effectiveness increased to 66 percent if the price of olaparib was reduced by 30 percent. CONCLUSION: This is the first study to evaluate germline genetic testing and olaparib treatment as codependent technologies in mCRPC. Genetic testing-guided olaparib treatment may be cost-effective with significant discounts on olaparib pricing.

Health outcomes of patients with type 2 diabetes following bariatric surgery: Results from a publicly funded initiative.

OBJECTIVE: Bariatric surgery is an effective treatment for type 2 diabetes and morbid obesity. This paper analyses the clinical and patient-reported outcomes of patients treated through the Bariatric Surgery Initiative, a health system collaboration providing bariatric surgery as a state-wide public service in Queensland, Australia. RESEARCH DESIGN AND METHODS: A longitudinal prospective cohort study was undertaken. Eligible patients had type 2 diabetes and morbid obesity (BMI ≥ 35 kg/m2). Following referral by specialist outpatient clinics, 212 patients underwent Roux-en-Y gastric bypass or sleeve gastrectomy. Outcomes were tracked for a follow-up of 12-months and included body weight, BMI, HbA1c, comorbidities, health-related quality of life, eating behaviour, and patient satisfaction. RESULTS: Following surgery, patients' average body weight decreased by 23.6%. Average HbA1c improved by 24.4% and 48.8% of patients were able to discontinue diabetes-related treatment. The incidence of hypertension, non-alcoholic steatohepatitis, and renal impairment decreased by 37.1%, 66.4%, and 62.3%, respectively. Patients' emotional eating scores, uncontrolled eating and cognitive restraint improved by 32.5%, 20.7%, and 6.9%, respectively. Quality of life increased by 18.8% and patients' overall satisfaction with the treatment remained above 97.5% throughout the recovery period. CONCLUSIONS: This study confirmed previous work demonstrating the efficacy of publicly funded bariatric surgery in treating obesity, type 2 diabetes and related comorbidities, and improving patients' quality of life and eating behaviour. Despite the short follow-up period, the results bode well for future weight maintenance in this cohort.

A review of the cost-effectiveness of genetic testing for germline variants in familial cancer.

BACKGROUND: Targeted germline testing is recommended for those with or at risk of breast, ovarian, or colorectal cancer. The affordability of genetic sequencing has improved over the past decade, therefore the cost-effectiveness of testing for these cancers is worthy of reassessment. OBJECTIVE: To systematically review economic evaluations on cost-effectiveness of germline testing in breast, ovarian, or colorectal cancer. METHODS: A search of PubMed and Embase databases for cost-effectiveness studies on germline testing in breast, ovarian, or colorectal cancer, published between 1999 and May 2022. Synthesis of methodology, cost-effectiveness, and reporting (CHEERS checklist) was performed. RESULTS: The incremental cost-effectiveness ratios (ICERs; in 2021-adjusted US$) for germline testing versus the standard care option in hereditary breast or ovarian cancer (HBOC) across target settings were as follows: (1) population-wide testing: 344-2.5 million/QALY; (2) women with high-risk: dominant = 78,118/QALY, 8,337-59,708/LYG; (3) existing breast or ovarian cancer: 3,012-72,566/QALY, 39,835/LYG; and (4) metastatic breast cancer: 158,630/QALY. Likewise, ICERs of germline testing for colorectal cancer across settings were: (1) population-wide testing: 132,200/QALY, 1.1 million/LYG; (2) people with high-risk: 32,322-76,750/QALY, dominant = 353/LYG; and (3) patients with existing colorectal cancer: dominant = 54,122/QALY, 98,790-6.3 million/LYG. Key areas of underreporting were the inclusion of a health economic analysis plan (100% of HBOC and colorectal studies), engagement of patients and stakeholders (95.4% of HBOC, 100% of colorectal studies) and measurement of outcomes (18.2% HBOC, 38.9% of colorectal studies). CONCLUSION: Germline testing for HBOC was likely to be cost-effective across most settings, except when used as a co-dependent technology with the PARP inhibitor, olaparib in metastatic breast cancer. In colorectal cancer studies, testing was cost-effective in those with high-risk, but inconclusive in other settings. Cost-effectiveness was sensitive to the prevalence of tested variants, cost of testing, uptake, and benefits of prophylactic measures. Policy advice on germline testing should emphasize the importance of these factors in their recommendations.

Breast, ovarian, prostate, and colorectal cancers are among the top causes of cancer related deaths. A substantial proportion of people with these cancers have inherited mutations. The identification of these gene abnormalities could provide people with opportunities to utilize preventive risk reduction surgeries or undertake frequent routine testing for these cancers. However, genetic testing requires healthcare resources and money. Previous reviews on the cost-effectiveness of genetic testing in familial cancers have concluded that targeted screening i.e., selective assessment of people at high-risk could justify the costs of testing. Our evaluation of economic studies in breast and ovarian cancer, however, suggests that genetic testing is cost-effective across a wide variety of situations starting from the screening of all healthy women above 30 years to the testing of women with existing breast or ovarian cancer. Testing in metastatic breast cancer to inform treatment with Olaparib, a drug known to selectively improve survival in people with genetic mutations, was the sole exception where testing was not cost-effective. Contrary to findings for breast or ovarian cancer, testing for colorectal cancer was cost-effective in people with high-risk i.e., family history but inconclusive in other situations. Evidence on the cost-effectiveness of testing in prostate cancer is lacking and as a result we were not able to provide advice in this cancer group.

Profiles of vocalization change in children with autism receiving early intervention.

Children with autism spectrum disorder (ASD) commonly present with comorbid language impairment, negatively impacting their learning and participation across settings. Addressing these needs requires a detailed understanding of their communication trajectories. In this study, we used the language environment and analysis (LENA) system to examine possible changes in children's (a) vocalizations and (b) ratio of speech to nonspeech vocalizations over a 10-month period. Data for 23 children with ASD (17M, 6F; ages 32-67 months) were analyzed, including monthly 3-hr in-class recordings and standardized measures of language, cognition, and ASD characteristics. Using hierarchical generalized linear models, we found significant time-trends for child vocalizations (P ≤ 0.001) and the vocalization ratio (P = 0.02), reflecting a waxing and waning pattern. Children with higher expressive language scores (Mullen scales of early learning, Vineland adaptive behavior scales - 2nd Ed.) and nonverbal cognition (Mullen scales of early learning), and fewer ASD characteristics (social communication questionnaire) demonstrated greater increases in the vocalization ratio over time (P values 0.04-0.01). Children with greater language and cognition difficulties were the most vocal, but produced a higher proportion of nonspeech vocalizations. The results demonstrate that significant fluctuations, as opposed to linear increases, may be observed in children with ASD receiving intervention, highlighting the value of assessment at multiple time-points. In addition, the findings highlight the need to consider both the quantity (vocalization counts) and quality (ratio of speech to nonspeech vocalizations) when interpreting LENA data, with the latter appearing to provide a more robust measure of communication. Autism Research 2019, 12: 830-842. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY ABSTRACT: In this study, we examined possible changes in speech and nonspeech vocalizations in 23 children with autism attending a comprehensive early intervention program over a 10-month period. Contrary to our expectation, we observed a waxing and waning pattern of change in children's vocalizations over time, rather than a steady increase. We also found evidence to suggest that looking at the quality of children's vocalizations (i.e., the ratio of speech to nonspeech vocalizations) provides a more accurate picture of children's development than simply looking at the quantity (i.e., how frequently they vocalize).

Variation in Functional Status After Hip Fracture: Facility and Regional Influence on Mobility and Self-Care.

BACKGROUND: Recent reports show substantial geographic variation in postacute health care spending. Little is known about variation in functional outcomes after postacute rehabilitation for patients with hip fracture. We examined variation in mobility and self-care after hip fracture rehabilitation across inpatient rehabilitation facilities (IRFs), hospital referral regions (HRRs) and states. METHODS: Retrospective cohort study using data from the Centers for Medicare and Medicaid Services (CMS) from 2006 to 2009. Study sample included 149,258 records from patients 66 years and older at 1,166 IRFs located within 292 HRRs and across 50 states. Hip fracture cases were defined by CMS impairment group codes (08.11, 08.12). Hierarchical generalized linear models were used to assess discharge mobility and self-care functional status, adjusting for individual patient characteristics and the random effect of IRFs, HRRs, and states. RESULTS: Variation in discharge mobility status as assessed by the intraclass correlation percentage (ICC%) was 8.8% across IRFs, 4.0% across HRRs, and 1.8% across states. For self-care, the ICCs were 10.2% across IRFs, 4.8% across HRRs, and 2.4% across states. The range of discharge mobility scores (maximum functional status rating to minimum functional status rating) showed a 9.6-point difference for IRFs, 6.5 for regions, and 2.6 for states. Range of discharge self-care scores were 13.1 for IRFs, 6.8 for HRRs, and 3.4 for states. CONCLUSION: Variation in functional status following postacute hip fracture rehabilitation appears to occur primarily at the level of facilities rather than geographic location.

Geographic and facility variation in inpatient stroke rehabilitation: multilevel analysis of functional status.

OBJECTIVE: To examine geographic and facility variation in cognitive and motor functional outcomes after postacute inpatient rehabilitation in patients with stroke. DESIGN: Retrospective cohort design using Centers for Medicare and Medicaid Services (CMS) claims files. Records from 1209 rehabilitation facilities in 298 hospital referral regions (HRRs) were examined. Patient records were analyzed using linear mixed models. Multilevel models were used to calculate the variation in outcomes attributable to facilities and geographic regions. SETTING: Inpatient rehabilitation units and facilities. PARTICIPANTS: Patients (N=145,460) with stroke discharged from inpatient rehabilitation from 2006 through 2009. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Cognitive and motor functional status at discharge measured by items in the CMS Inpatient Rehabilitation Facility-Patient Assessment Instrument. RESULTS: Variation profiles indicated that 19.1% of rehabilitation facilities were significantly below the mean functional status rating (mean ± SD, 81.58±22.30), with 221 facilities (18.3%) above the mean. Total discharge functional status ratings varied by 3.57 points across regions. Across facilities, functional status values varied by 29.2 points, with a 9.1-point difference between the top and bottom deciles. Variation in discharge motor function attributable to HRR was reduced by 82% after controlling for cluster effects at the facility level. CONCLUSIONS: Our findings suggest that variation in motor and cognitive function at discharge after postacute rehabilitation in patients with stroke is accounted for more by facility than geographic location.

Relationship between urinary bisphenol A levels and prediabetes among subjects free of diabetes.

Bisphenol A (BPA) is a high volume production chemical used in the manufacture of polycarbonate plastics and epoxy resins. Recent experimental studies have suggested that BPA affects glucose metabolism through diverse mechanisms including insulin resistance, pancreatic ß-cell dysfunction, adipogenesis, inflammation and oxidative stress. Prediabetes is a stage earlier in the hyperglycemia continuum associated with increased future risk of developing diabetes. Therefore, we examined the association between BPA exposure and prediabetes among subjects free of diabetes. We examined the association between urinary BPA levels and prediabetes in 3,516 subjects from the National Health and Nutritional Examination Survey 2003-2008. Urinary BPA levels were examined in tertiles. Prediabetes was defined as fasting glucose concentration 100-125 mg/dL or 2-h glucose concentration of 140-199 mg/dL or an A1C value of 5.7-6.4 %. Overall, we observed a positive association between higher levels of urinary BPA and prediabetes, independent of potential confounders including body mass index, alcohol intake, blood pressure and serum cholesterol levels. Compared to tertile 1 (referent), the multivariate-adjusted odds ratio (95 % confidence interval) of prediabetes associated with tertile 3 of BPA was 1.34 (1.03-1.73), p-trend = 0.02. In subgroup analysis, this association was stronger among women and obese subjects. Higher urinary BPA levels are found to be associated with prediabetes independent of traditional diabetes risk factors. Future prospective studies are needed to confirm or disprove this finding.

Bisphenol A and Metabolic Syndrome: Results from NHANES.

Background. Bisphenol A (BPA) is detected in the urine of >95% of US adults. Recent evidence from population-based studies suggests that BPA is associated with individual components for metabolic syndrome (MetS). However, no previous study has examined the direct association between BPA and MetS. Methods. We examined 2,104 participants from the National Health and Nutrition Examination Survey 2003-2008. The main outcome was the presence of MetS (n = 741). Results. Increasing levels of urinary BPA were positively associated with MetS, independent of confounders such as age, gender, race/ethnicity, smoking, alcohol intake, physical activity, and urinary creatinine. Compared to tertile 1 (referent), the multivariable adjusted odds ratio (95% confidence interval) of MetS in tertile 3 was 1.51 (1.07-2.12); P-trend was 0.02. Conclusions. Urinary BPA levels are positively associated with MetS, in a representative sample of US adults and independent of traditional risk factors for MetS. Future, prospective studies are needed to confirm our findings.

Urinary bisphenol a levels and measures of obesity: results from the national health and nutrition examination survey 2003-2008.

Bisphenol A (BPA) is a widely used chemical. We examined the association between urinary BPA levels and obesity in the National Health and Nutritional Examination Survey (NHANES) 2003-2008. The main outcome of interest was obesity defined as (1) body mass index (BMI) ≥ 30 Kg/m(2) and (2) waist circumference (WC) ≥ 102 cm in men and ≥ 88 cm in women. Urinary BPA levels were examined in quartiles. Overall, we observed a positive association between increasing levels of urinary BPA and both measures of obesity, independent of potential confounding factors including, smoking, alcohol consumption, and serum cholesterol levels. Compared to quartile 1 (referent), the multivariate-adjusted odds ratio (95% confidence interval) associated with quartile 4 for BMI-based obesity was 1.69 (1.30-2.20); P-trend < 0.0001 and for WC-based obesity was 1.59 (1.21-2.09); P-trend = 0.0009. This association between BPA and both measures of obesity was consistently present across gender and race-ethnic groups (all P-trend < 0.05). Elevated levels of urinary BPA are associated with measures of obesity independent of traditional risk factors. This association is consistently present across gender and race-ethnic groups. Future prospective studies are needed to confirm or disprove this finding.

Markers of Sleep-Disordered Breathing and Prediabetes in US Adults.

Background. Prediabetes is a preclinical stage in the hyperglycemia continuum where subjects are at increased risk of developing diabetes. Several studies reported a positive association between markers of sleep-disordered breathing (SDB) and diabetes. However, few studies investigated the relationship between SDB markers and prediabetes. Methods. We examined 5,685 participants ≥20 years from the National Health and Nutrition Examination Survey (NHANES) 2005-2008. The exposure of interest was SDB markers including sleep duration, snoring, snorting, and daytime sleepiness. The outcome was prediabetes (n = 2058), among subjects free of diabetes. Results. SDB markers were associated with prediabetes. Compared to those without any sleep disturbance, the multivariable odds ratio (OR) (95% confidence interval (CI)) of prediabetes among those with three or more SDB markers was 1.69 (1.28-2.22). In subgroup analyses, the association between SDB markers and prediabetes was stronger among women (OR (95% CI) = 2.09 (1.36-3.23) when compared to men (1.52 (1.00-2.35)) and was present among non-Hispanic whites (2.66 (1.92-3.69)) and Mexican Americans (1.99 (1.13-3.48)), but not among non-Hispanic blacks (1.10 (0.70-1.73)). Conclusion. SDB markers were associated with prediabetes. This association was stronger in women and was present mainly in non-Hispanic whites and Mexican Americans.

Bisphenol A and peripheral arterial disease: results from the NHANES.

BACKGROUND: Bisphenol A (BPA) is a common chemical used in the manufacture of polycarbonate plastics and epoxy resins, and > 93% of U.S. adults have detectable levels of urinary BPA. Recent animal studies have suggested that BPA exposure may have a role in several mechanisms involved in the development of cardiovascular disease (CVD), including weight gain, insulin resistance, thyroid dysfunction, endothelial dysfunction, and oxidative stress. However, few human studies have examined the association between markers of BPA exposure and CVD. Peripheral arterial disease (PAD) is a subclinical measure of atherosclerotic vascular disease and a strong independent risk factor for CVD and mortality. OBJECTIVE: We examined the association between urinary BPA levels and PAD in a nationally representative sample of U.S. adults. METHODS: We analyzed data from 745 participants in the National Health and Nutritional Examination Survey 2003-2004. We estimated associations between urinary BPA levels (in tertiles) and PAD (ankle-brachial index < 0.9, n = 63) using logistic regression models adjusted for potential confounders (age, sex, race/ethnicity, education, smoking, body mass index, diabetes mellitus, hypertension, urinary creatinine, estimated glomerular filtration rate, and serum cholesterol levels). RESULTS: We observed a significant, positive association between increasing levels of urinary BPA and PAD before and after adjusting for confounders. The multivariable-adjusted odds ratio for PAD associated with the highest versus lowest tertile of urinary BPA was 2.69 (95% confidence interval: 1.02, 7.09; p-trend = 0.01). CONCLUSIONS: Urinary BPA levels were significantly associated with PAD, independent of traditional CVD risk factors.

Markers of Sleep Disordered Breathing and Diabetes Mellitus in a Multiethnic Sample of US Adults: Results from the National Health and Nutrition Examination Survey (2005-2008).

We examined gender and ethnic differences in the association between sleep disordered breathing (SDB) and diabetes among 6,522 participants aged ≥20 years from the National Health and Nutrition Examination Survey 2005-08. SDB severity was defined based on an additive summary score including sleep duration, snoring, snorting, and daytime sleepiness. We found that the summary SDB score was significantly associated with diabetes after adjusting for potential confounders in the whole population. Compared to those without any sleep disturbance, the multivariable odds ratio (OR) (95% confidence interval (CI)) of diabetes among those with ≥3 sleep disturbances was 2.04 (1.46-2.87). In sex-specific analyses, this association was significant only in women (OR (95% CI) = 3.68 (2.01-6.72)) but not in men (1.10 (0.59-2.04)), P-interaction = 0.01. However, there were no ethnic differences in this association, P-interaction = 0.7. In a nationally representative sample of US adults, SDB was independently associated with diabetes only in women, but not in men.

Urinary bisphenol A and hypertension in a multiethnic sample of US adults.

BACKGROUND: Bisphenol A (BPA) is a common chemical used in the manufacture of polycarbonate plastics and epoxy resins, with >93% of US adults having detectable BPA levels in urine. Recent animal studies have suggested that BPA exposure may have a role in several mechanisms involved in the development of hypertension, including weight gain, insulin resistance, thyroid dysfunction, endothelial dysfunction, and oxidative stress. However, no previous human study has examined the association between markers of BPA exposure and hypertension. METHODS: We examined urinary BPA levels in 1380 subjects from the National Health and Nutritional Examination Survey 2003-2004. Main outcome-of-interest was hypertension, defined as blood pressure-reducing medication use and/or blood pressures >140/90 mm of Hg (n = 580). RESULTS: We observed a positive association between increasing levels of urinary BPA and hypertension independent of confounding factors such as age, gender, race/ethnicity, smoking, body mass index (BMI), diabetes mellitus and total serum cholesterol levels. Compared to tertile 1 (referent), the multivariate-adjusted odds ratio (95% confidence interval) of hypertension associated with tertile 3 was 1.50 (1.12-2.00); P-trend = 0.007. The association was consistently present in subgroup analyses by race/ethnicity, smoking status, BMI, and diabetes mellitus. CONCLUSIONS: Urinary BPA levels are associated with hypertension, independent of traditional risk factors.

Relationship between body mass index and high cystatin levels among US adults.

High cystatin C levels among patients without clinically recognized chronic kidney disease (CKD) may identify patients who are at preclinical stages of CKD. Higher body mass index (BMI) has been found to be associated with increased risk of CKD. However, the association between BMI and high cystatin C levels is not clear. The authors examined participants older than 20 years from the National Health and Nutrition Examination Survey 1999 to 2002 (N=2583, 50.2% women). BMI was categorized as <25 kg/m(2), 25-29.9 kg/m(2), and ≥30 kg/m(2) . Main outcome was high cystatin C (>1 mg/dL) among patients without clinically recognized CKD (estimated glomerular filtration rate <60 mL/min/1.73 m(2) or microalbuminuria). Higher BMI was positively associated with high cystatin C, independent of age, sex, race-ethnicity, education, smoking, alcohol intake, cholesterol, and C-reactive protein levels. Compared with patients with BMI <25 kg/m(2) (referent), the multivariable odds ratio (95% confidence interval) of high cystatin C was 2.53 (1.79-3.58) (P trend <.0001 among patients with BMI ≥30 kg/m(2)). The association between BMI and high cystatin C persisted in subgroup analyses by sex, race-ethnicity, and among those without diabetes or hypertension. Among US adults without clinically recognized CKD, higher BMI levels were independently associated with high cystatin C levels.

Relationship between urinary bisphenol A levels and diabetes mellitus.

BACKGROUND: Bisphenol A (BPA) is a widely used chemical in the manufacture of polycarbonate plastics and epoxy resins. Recent animal studies have suggested that BPA exposure may have a role in the development of weight gain, insulin resistance, pancreatic endocrine dysfunction, thyroid hormone disruption, and several other mechanisms involved in the development of diabetes. However, few human studies have examined the association between markers of BPA exposure and diabetes mellitus. METHODS: We examined the association between urinary BPA levels and diabetes mellitus in the National Health and Nutritional Examination Survey (NHANES) 2003-2008. Urinary BPA levels were examined in quartiles. The main outcome of interest was diabetes mellitus defined according the latest American Diabetes Association guidelines. RESULTS: Overall, we observed a positive association between increasing levels of urinary BPA and diabetes mellitus, independent of confounding factors such as age, gender, race/ethnicity, body mass index, and serum cholesterol levels. Compared to quartile 1 (referent), the multivariate-adjusted odds ratio (95% confidence interval) of diabetes associated with quartile 4 was 1.68 (1.22-2.30) (p-trend = 0.002). The association was present among normal-weight as well as overweight and obese subjects. CONCLUSIONS: Urinary BPA levels are found to be associated with diabetes mellitus independent of traditional diabetes risk factors. Future prospective studies are needed to confirm or disprove this finding.

Relationship between serum cystatin C and hypertension among US adults without clinically recognized chronic kidney disease.

Previous animal studies have suggested that mild reductions in renal function, even before the development of clinically recognized chronic kidney disease (CKD), are associated with hypertension. However, few studies have examined this hypothesis in humans. We therefore examined the association between serum cystatin C levels and hypertension among subjects without clinically recognized CKD in a large multiethnic sample of US adults. We examined the National Health and Nutrition Examination Survey 1999-2002 participants >20 years of age (n = 2583, 54.5% women) without clinically recognized CKD (defined as an estimated glomerular filtration rate <60 mL/min/1.73 m(2) or microalbuminuria). Serum cystatin C levels were categorized into quartiles (<0.76 mg/L, 0.76-0.86 mg/L, 0.87-0.97 mg/L, and >0.97 mg/L). Hypertension was defined as blood pressure (BP)-reducing medication use or having systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg. Higher serum cystatin C levels were found to be associated with hypertension in women, but not men. After adjusting for age, race-ethnicity, education, smoking, alcohol intake, body mass index, diabetes, total cholesterol and C-reactive protein, the odds ratio (95% confidence interval) of hypertension comparing quartile 4 of cystatin C to quartile 1 (referent) was 2.04 (1.13-3.69); P trend = .02 in women and 0.86 (0.53-1.41); P trend = .51 in men. In a representative sample of US adults, mild reductions in kidney function as measured by higher serum cystatin C levels among subjects without clinically recognized CKD are associated with hypertension in women, but not men.