Multimorbidity, Social Engagement, and Age-Related Cognitive Decline in Older Adults from the Rancho Bernardo Study of Healthy Aging.

Background: Multimorbidity is associated with increased rate of cognitive decline with age. It is unknown whether social engagement, which is associated with reduced risk of dementia, modifies associations between multimorbidity and cognitive decline. Objective: To examine the associations of multimorbidity with longitudinal cognitive test performance among community-dwelling older adults, and to determine whether associations differed by levels of social engagement. Methods: We used data from the Rancho Bernardo Study of Healthy Aging, a community-based prospective cohort study. Starting in 1992-1996, participants completed a battery of cognitive function tests at up to 6 study visits over 23.7 (mean = 7.2) years. Multimorbidity was defined as≥2 of 14 chronic diseases. Social engagement was assessed using items based on the Berkman-Syme Social Network Index. Multivariable linear mixed-effects models were used to test associations of multimorbidity and cognitive performance trajectories. Effect measure modification by social engagement was evaluated. Results: Among 1,381 participants (mean age = 74.5 years; 60.8% women; 98.8% non-Hispanic White), 37.1% had multimorbidity and 35.1% had low social engagement. Multimorbidity was associated with faster declines in Mini-Mental State Examination (MMSE; ß= -0.20; 95% CI -0.35, -0.04), Trail-Making Test Part B (ß= 10.02; 95% CI 5.77, 14.27), and Category Fluency (ß= -0.42; 95% CI -0.72, -0.13) after adjustment for socio-demographic and health-related characteristics. Multimorbidity was associated with faster declines in MMSE among those with low compared to medium and high social engagement (p-interaction < 0.01). Conclusions: Multimorbidity was associated with faster declines in cognition among community-dwelling older adults. Higher social engagement may mitigate multimorbidity-associated cognitive decline.

The Association of Epigenetic Age Acceleration and Multimorbidity at Age 90 in the Women's Health Initiative.

BACKGROUND: Epigenetic age acceleration (EAA), a measure of accelerated biological aging, has been associated with an increased risk of several age-related chronic conditions. This is the first study to prospectively examine the relationship between EAA and both multimorbidity count and a weighted multimorbidity score among long-lived postmenopausal women. METHODS: We included 1 951 women from the Women's Health Initiative who could have survived to age 90. EAA was estimated using the Horvath pan-tissue, Hannum, PhenoAge, and GrimAge "clocks." Twelve chronic conditions were included in the multimorbidity count. The multimorbidity score was weighted for each morbidity's relationship with mortality in the study population. Using mixed-effects Poisson and linear regression models that included baseline covariates associated with both EAA and multimorbidity, we estimated relative risks (RRs) and 95% confidence intervals (CIs) for the relationships between each EAA measure at the study baseline with both multimorbidity count and weighted multimorbidity score at age 90, respectively. RESULTS: For every one standard deviation increase in AgeAccelPheno, the rate of multimorbidity accumulation increased 6% (RR = 1.06; 95% CI = 1.01-1.12; p = .025) and the multimorbidity score by 7% (RR = 1.07; 95% CI = 1.01-1.13; p = .014) for women who survived to age 90. The results for a one standard deviation increase in AgeAccelHorvath, AgeAccelHannum, and AgeAccelGrim with multimorbidity accumulation and score were weaker compared to AgeAccelPheno, and the latter 2 did not reach statistical significance. CONCLUSION: AgeAccelPheno and AgeAccelHannum may predict multimorbidity count and score at age 90 in older women and, thus, may be useful as a biomarker predictor of multimorbidity burden in the last decades of life.

Analysis of Epigenetic Age Acceleration and Healthy Longevity Among Older US Women.

Importance: Accelerated biological aging is associated with decreased physical capability and cognitive functioning, which are associated with increased risk of morbidity and mortality. Objective: We investigated associations between epigenetic age acceleration (EAA), a biomarker associated with aging, and healthy longevity among older women. Design, Setting, and Participants: This cohort study was a secondary analysis of participants in the Women's Health Initiative (WHI) who were eligible to survive to age 90 years by September 30, 2020. Participants were located in multiple centers. This study was restricted to women with genome-wide DNA methylation data, generated from baseline blood samples within 3 WHI ancillary studies. Median (IQR) follow-up times from baseline were 21.6 (19.6-22.9) years and 21.4 (19.8-22.7) years for women who survived to age 90 years with and without intact mobility, respectively, and 13.2 (8.8-16.7) for women who did not survive to age 90 years. Data were analyzed from December 2020 to July 2021. Exposures: EAA was estimated using 4 established "clocks": Horvath pantissue, Hannum, Pheno, and Grim. Main Outcomes and Measures: Using multinomial logistic regression, odds ratios (ORs) and 95% CIs were estimated for 3 healthy longevity outcomes for each clock: survival to age 90 years with intact mobility, survival to age 90 years without intact mobility, and no survival to age 90 years. Results: Among 1813 women, there were 464 women (mean [SD] age at baseline, 71.6 [3.5] years) who survived to age 90 years with intact mobility and cognitive functioning, 420 women (mean [SD] age at baseline, 71.3 [3.2] years) who survived to age 90 years without intact mobility and cognitive functioning, and 929 women (mean [SD] age at baseline, 70.2 [3.4] years) who did not survive to age 90 years. Women who survived to age 90 years with intact mobility and cognitive function were healthier at baseline compared with women who survived without those outcomes or who did not survive to age 90 years (eg, 143 women [30.8%] vs 101 women [24.0%] and 202 women [21.7%] with 0 chronic conditions). The odds of surviving to age 90 years with intact mobility were lower for every 1 SD increase in EAA compared with those who did not survive to age 90 years as measured by AgeAccelHorvath (OR, 0.82; 95% CI, 0.69-0.96; P = .01), AgeAccelHannum (OR, 0.67; 95% CI, 0.56-0.80; P < .001), AgeAccelPheno (OR, 0.60; 95% CI, 0.51-0.72; P < .001), and AgeAccelGrim (OR, 0.68; 95% CI, 0.55-0.84; P < .001). ORs were similar for women who survived to age 90 years with intact mobility and cognitive function (eg, AgeAccelHorvath: OR per 1 SD increase in EAA, 0.83; 95% CI, 0.71-0.98; P = .03) compared with women who did not survive to age 90 years. Conclusions and Relevance: These findings suggest that EAA may be a valid biomarker associated with healthy longevity among older women and may be used for risk stratification and risk estimation of future functional and cognitive aging. Outcomes suggest that future studies may focus on the potential for public health interventions to counteract EAA and its association with poor health outcomes to lower disease burden while increasing longevity.

Markers of kidney function, genetic variation related to cognitive function, and cognitive performance in the UK Biobank.

BACKGROUND: Chronic kidney disease has been linked to worse cognition. However, this association may be dependent on the marker of kidney function used, and studies assessing modification by genetics are lacking. This study examined associations between multiple measures of kidney function and assessed effect modification by a polygenic score for general cognitive function. METHODS: In this cross-sectional study of up to 341,208 European ancestry participants from the UK Biobank study, we examined associations between albuminuria and estimated glomerular filtration rate based on creatinine (eGFRcre) or cystatin C (eGFRcys) with cognitive performance on tests of verbal-numeric reasoning, reaction time and visual memory. Adjustment for confounding factors was performed using multivariate regression and propensity-score matching. Interaction between kidney function markers and a polygenic risk score for general cognitive function was also assessed. RESULTS: Albuminuria was associated with worse performance on tasks of verbal-numeric reasoning (ß(points) = -0.09, p < 0.001), reaction time (ß(milliseconds) = 7.06, p < 0.001) and visual memory (ß(log errors) = 0.013, p = 0.01). A polygenic score for cognitive function modified the association between albuminuria and verbal-numeric reasoning with significantly lower scores in those with albuminuria and a lower polygenic score (p = 0.009). Compared to participants with eGFRcre ≥ 60 ml/min, those with eGFRcre < 60 ml/min had lower verbal-numeric reasoning scores and slower mean reaction times (verbal numeric reasoning ß = -0.11, p < 0.001 and reaction time ß = 6.08, p < 0.001 for eGFRcre < 60 vs eGFRcre ≥ 60). Associations were stronger using cystatin C-based eGFR than creatinine-based eGFR (verbal numeric reasoning ß = -0.21, p < 0.001 and reaction time ß = 11.21, p < 0.001 for eGFRcys < 60 vs eGFRcys ≥ 60). CONCLUSIONS: Increased urine albumin is associated with worse cognition, but this may depend on genetic risk. Cystatin C-based eGFR may better predict cognitive performance than creatinine-based estimates.

Biomarkers of kidney function and cognitive ability: A Mendelian randomization study.

BACKGROUND: Estimated glomerular filtration rate (eGFR), albuminuria and serum uric acid (SUA) are markers of kidney function that have been associated with cognitive ability. However, whether these associations are causal is unclear. METHODS: We performed one-sample Mendelian randomization (MR) to estimate the effects of kidney function markers on cognitive performance using data from the UK Biobank. Polygenic scores for SUA, urine albumin to creatinine ratio (ACR), estimated glomerular filtration rate based on serum creatinine (eGFRcre) and serum cystatin C (eGFRcys) were used as instrumental variables, and cognitive function outcomes included tests of verbal-numeric reasoning, reaction time, visual memory, and numeric memory. RESULTS: We found no evidence of a causal effect of genetically determined SUA, eGFRcre or eGFRcys on cognitive function outcomes. There was no association between a polygenic score for ACR and verbal-numeric reasoning or numeric memory. However, there was suggestive evidence of a relationship between genetically increased ACR and slower reaction time and worse visual memory. ACR was no longer significantly associated with visual memory in analyses using an unweighted polygenic score and in analyses stratified by sex and age category. Pleiotropy adjusted estimates were directionally consistent with those of the principal analysis but overlapped with the null. CONCLUSIONS: This MR study does not support causal effects of SUA, eGFRcre or eGFRcys on cognitive performance. Genetically increased ACR was associated with slower processing speed and visual memory, but results need confirmation in independent samples.

Markers of Kidney Function and Longitudinal Cognitive Ability Among Older Community-Dwelling Adults: The Rancho Bernardo Study.

BACKGROUND: Reduced kidney function has been associated with cognitive decline. Most studies have examined a single marker of kidney function and have limited duration of follow-up. OBJECTIVE: This study evaluated associations between markers of kidney function (urine albumin, estimated glomerular filtration rate [eGFR], and hyperuricemia) with cognitive performance over time. METHODS: This is a longitudinal study of 1,634 community-dwelling adults (mean age = 71.7 years), with kidney function markers and cognitive ability measured at baseline (1992-1996) and at up to five additional time points with a maximum of 23.4 years (mean = 8.1 years) of follow-up. Associations between kidney function and cognitive performance were assessed using linear mixed effects models. Testing for interaction by sex was conducted. RESULTS: Albuminuria (urine albumin-to-creatinine ratio [ACR]≥30 mg/g) was associated with steeper annual declines in global cognitive function (MMSE, ß= -0.12, p = 0.003), executive function (Trails B, ß= 4.50, p < 0.0001) and episodic memory (Buschke total recall, ß= -0.62, p = 0.02) scores in men. Results were similar when cognitive test scores were regressed on latent trajectory classes of ACR. In men, hyperuricemia (serum uric acid [SUA]≥6.8 mg/dl for men and SUA≥6.0 mg/dl for women) was associated with lower baseline MMSE (ß= -0.70, p = 0.009) scores but not with MMSE change over time. No such associations were detected in women. There were no significant associations between eGFR and cognitive performance for either sex. CONCLUSION: In older men, albuminuria is an independent predictor of subsequent cognitive decline. More investigations are needed to explain the observed sex differences and the potential relationship between hyperuricemia and poorer global cognition.

Prevalence and correlates of obstructive lung disease among people who inject drugs, San Diego, California.

BACKGROUND: Pulmonary tissue damage leading to obstructive lung disease (OLD) could result from intravenous administration of insoluble particles found in illicit drugs. This study described the prevalence and identified correlates of OLD among people who inject drugs (PWID). METHODS: In 2012-2016, a community-based cohort of PWID who had injected within the past month were enrolled in a study to assess HIV, hepatitis C virus (HCV) andMycobacterium tuberculosis (Mtb) infections and their related risk factors. Data were obtained through face-to-face interviews, serological testing and spirometry. Baseline data were used for a cross-sectional analysis of the prevalence and correlates of OLD, defined as FEV1/FVC < 0.7. Univariate and multivariable logistic regression were used to identify factors associated with OLD. RESULTS: Among 516 participants who had complete spirometry and interview results, the mean age was 43.3 years, 73.6 % were male, 9.5 % were Black, 91.1 % smoked cigarettes and 18.2 % had OLD. Few (9.6 %) PWID with OLD reported a previous diagnosis of COPD although many (44.7 %) reported related symptoms. Black race (AOR = 2.66, 95 %CI: 1.37, 5.17), pack-years smoked (AOR = 1.06/5 years, 95 %CI: 1.01, 1.12), and duration of injection drug use (AOR = 1.13, 95 %CI: 1.01, 1.27) were independently associated with OLD after controlling for age. CONCLUSIONS: The prevalence of OLD was high in this cohort and associated with Black race and cigarette smoking-known risk factors. In addition, OLD prevalence increased with greater duration of injection drug use, suggesting a link between cumulative exposure to injected insoluble particles and OLD. Further examination of these adulterants and lung pathology are needed.

Racial/Ethnic Disparities in Physical Function Before and After Total Knee Arthroplasty Among Women in the United States.

Importance: Although racial/ethnic differences in functional outcomes after total knee arthroplasty (TKA) exist, whether such differences are associated with differences in presurgical physical function (PF) has not been thoroughly investigated. Objective: To examine trajectories of PF by race/ethnicity before and after TKA among older women. Design, Setting, and Participants: This cohort study was conducted among the prospective Women's Health Initiative with linked Medicare claims data. A total of 10 325 community-dwelling women throughout the United States with Medicare fee-for-service underwent primary TKA between October 1, 1993, and December 31, 2014, and were followed up through March 31, 2017. Exposures: Race/ethnicity comparisons between Hispanic or Latina women, non-Hispanic black or African American women, and non-Hispanic white women (hereafter referred to as Hispanic, black, and white women, respectively). Main Outcomes and Measures: Physical functioning scale scores and self-reported activity limitations with walking 1 block, walking several blocks, and climbing 1 flight of stairs were measured by the RAND 36-Item Health Survey during the decade before and after TKA, with a median of 9 PF measurements collected per participant over time. Results: In total, 9528 white women (mean [SD] age at surgery, 74.6 [5.5] years), 622 black women (mean [SD] age at surgery, 73.1 [5.3] years), and 175 Hispanic women (mean [SD] age at surgery, 73.1 [5.2] years) underwent TKA. During the decade prior to TKA, black women had lower PF scores than white women (mean difference, -5.8 [95% CI, -8.0 to -3.6]) and higher odds of experiencing difficulty walking a single block (5 years before TKA: odds ratio, 1.86 [95% CI, 1.57-2.21]), walking multiple blocks (odds ratio, 2.14 [95% CI, 1.83-2.50]), and climbing 1 flight of stairs (odds ratio, 1.81 [95% CI, 1.55-2.12]). After TKA, black women continued to have lower PF scores throughout the decade (mean difference 1 year after TKA, -7.8 [95% CI, -10.8 to -4.9]). After adjusting for preoperative PF scores, PF scores after TKA were attenuated (mean difference 1 year after TKA, -3.0 [95% CI, -5.3 to -0.7]), with no statistically significant differences in long-term follow-up. Hispanic women had similar PF scores to white women during the pre-TKA and post-TKA periods. Conclusions and Relevance: This study suggests that black women had significantly poorer PF than white women during the decades before and after TKA. Poorer PF after surgery was associated with poorer preoperative PF. Reducing disparities in post-TKA functional outcomes should target maintenance of function preoperatively in the early stages of arthritic disease and/or reduction of delays to receiving TKA once need arises.

Association of Race and Major Adverse Cardiac Events (MACE): The Atherosclerosis Risk in Communities (ARIC) Cohort.

BACKGROUND AND AIMS: To evaluate the association of self-reported race with major adverse cardiac events (MACE) and modification of this association by paraoxonase gene (PON1, PON2, and PON3) single nucleotide polymorphisms (SNPs). METHODS: Included in this longitudinal study were 12,770 black or white participants from the Atherosclerosis Risk in Communities (ARIC) cohort who completed a baseline visit (1987-1989) with PON genotyping. Demographic, behavioral, and health information was obtained at baseline. MACE was defined as first occurrence of myocardial infarction, stroke, or CHD-related death through 2004. Cox proportional hazards regression was used to evaluate the association between race and MACE after adjustment for age, gender, and other demographic and cardiovascular risk factors such as diabetes and hypertension. Modification of the association between PON SNPs and MACE was also assessed. RESULTS: Blacks comprised 24.6% of the ARIC cohort; overall, 14.0% of participants developed MACE. Compared with whites, blacks had 1.24 times greater hazard of MACE (OR = 1.24,95%CI = 1.10,1.39) than whites after adjusting for age, gender, BMI, cigarette and alcohol use, educational and marital status, and aspirin use. This association became nonsignificant after further adjustment for high cholesterol, diabetes, and hypertension. None of the evaluated SNPs met the significance level (p < 0.001) after Bonferroni correction for multiple comparisons. CONCLUSIONS: No association between race and MACE was identified after adjusting for high cholesterol, diabetes, and hypertension, suggesting that comorbidities are major determinants of MACE; medical intervention with focus on lifestyle and health management could ameliorate the development of MACE. Further studies are needed to confirm this observation.

Rehabilitation After Total Knee Arthroplasty: Do Racial Disparities Exist?

BACKGROUND: Racial disparities in functional outcomes after total knee arthroplasty (TKA) exist. Whether differences in rehabilitation utilization contribute to these disparities remains to be investigated. METHODS: Among 8349 women enrolled in the prospective Women's Health Initiative cohort who underwent primary TKA between 2006 and 2013, rehabilitation utilization was determined through linked Medicare claims data. Postacute discharge destination (home, skilled nursing facility, and inpatient rehabilitation facility), facility length of stay, and number of home health physical therapy (HHPT) and outpatient physical therapy (OPPT) sessions were compared between racial groups. RESULTS: Non-Hispanic black women had worse physical function (median score, 65 vs 70) and higher likelihood of disability (13.2% vs 6.9%) than non-Hispanic white women before surgery. After TKA, black women were more likely to be discharged postacutely to an institutional facility (64.3% vs 54.5%) than white women, were more likely to receive HHPT services (52.6% vs 47.8%), and received more HHPT and OPPT sessions. After stratification by postacute discharge setting, the likelihood of receipt of HHPT or OPPT services was similar between racial groups. No significant difference in receipt of HHPT or OPPT services was found after use of propensity score weighting to balance health and medical characteristics indicating severity of need for physical therapy services. CONCLUSION: Rehabilitation utilization was generally comparable between black and white women who received TKA when accounting for need. There was no evidence of underutilization of post-TKA rehabilitation services, and thus disparities in post-TKA functional outcomes do not appear to be a result of inequitable receipt of rehabilitation care.

Indoor cannabis smoke and children's health.

Cannabis use is increasing and cannabis is typically consumed by smoking. This study explored how indoor secondhand cannabis smoke (SCS) was associated with child health. As part of a larger trial, air particle monitors were placed in 298 homes of families with at least one cigarette smoker and one child under 14 years old in San Diego County, California. Assessment included past 7-day indoor cigarette and cannabis use, the youngest child's exposure to cigarette smoke, and 5 smoke-related past-year child health outcomes: emergency department use for coughing/difficulty breathing; physician diagnosis of ear infection, bronchitis/bronchiolitis, asthma, or eczema/atopic dermatitis. An ordinal measure of adverse health outcomes (0, 1, or ≥2) was regressed on reported indoor cannabis smoking-the main measure of exposure (yes/no). Of 221 parents/guardians asked about cannabis use, 192 (86.9%) provided all required data, and 29 (15.1%) reported indoor cannabis smoking; reports were supported by air particle data. Homes without indoor smoking had lower average 7-day particle concentrations (1968 particles/0.01ft3) than homes with cannabis smoking only (3131 particles/0.01ft3), cigarette smoking only (3095 particles/0.01ft3), or both cigarette and cannabis smoking (6006 particles/0.01ft3). Odds of reporting a greater number of adverse health outcomes were 1.83 (95% CI = 0.89-3.80, p = 0.10) times higher for children of families with indoor cannabis smoking vs families without cannabis smoking, after controlling for exposure to cigarette smoke and other covariates. Our results do not indicate a statistically significant association. However, the magnitude of the (non-significant) association between indoor cannabis smoking and adverse health outcomes warrants more studies.

Folic acid supplement use and the risk of gestational hypertension and preeclampsia.

BACKGROUND: Hypertensive disorders of pregnancy are among the leading causes of maternal morbidity and mortality. Studies suggest that the use of folic acid may lower the risk of hypertensive disorders in pregnant women. AIM: The aim of this study was to assess the effects of timing and duration of folic acid-containing supplement use on the risk for gestational hypertension and preeclampsia. METHODS: Exposures and outcomes data were obtained through interviews and review of participant's medical records from the MotherToBaby cohort studies across the United States and Canada. Demographics, medical history, lifestyle factors, substance use, and fetal sex were assessed as potential confounders. Unadjusted and adjusted risks for gestational hypertension and preeclampsia were examined using odds ratios and 95% confidence intervals. FINDINGS: 3247 women were included in the study. Compared to non-supplement use, early and late supplement use were not significantly associated with the development of gestational hypertension or preeclampsia. The odds of developing gestational hypertension and preeclampsia were significantly reduced as the duration of folic acid-containing supplement use increased. CONCLUSION: Findings from this study suggest that the use of folic acid-containing supplements may mitigate the risk for gestational hypertension and preeclampsia.

Individual and community factors contributing to anemia among women in rural Baja California, Mexico.

INTRODUCTION: Anemia is a public health concern among women in rural Baja California, Mexico. The purpose of this study was to identify the individual and community factors contributing to the disproportionately high prevalence of anemia among women in this region. METHODS: A cross-sectional study of 118 women (15-49 years) was performed in a rural colonia (small settlement) in Baja California, Mexico in 2012. Participants completed a survey comprised of demographic, socioeconomic, health, and dietary questions and provided a capillary blood sample. A portable HemoCue was used to measure hemoglobin and diagnose anemia. Anemic participants provided a venous blood sample for laboratory testing to elucidate the etiology of anemia. Anemic participants received vitamin supplements and nutritional counseling. Assessments of six local tiendas (community grocery stores) were performed to ascertain the types of food available for purchase within the community. RESULTS: Prevalence of anemia was 22% among women; laboratory tests revealed iron deficiency was the primary etiology in 80.8% of anemia cases. Other causes of anemia in women included vitamin B-12 deficiency (11.5%) and combined iron and vitamin B-12 deficiency (7.7%). Women from low SES households and women enrolled in the government assistance program Prospera were significantly more likely to be anemic (OR = 3.48, 95% CI 1.35-8.98 and OR = 2.49, 95% CI 1.02-6.09, respectively). Vitamin supplementation was significantly more common among non-anemic women (OR = 0.12, 95% CI 0.02-0.94). Dietary assessments showed limited consumption of iron absorption enhancing foods such as fruits and vegetables. Assessments of local tiendas revealed at least one type of meat and citrus fruit available for purchase at each store; however, leafy green vegetables were only available for purchase at one store. CONCLUSION: All cases of anemia were due to nutritional deficiencies. While vitamin supplementation is a temporary solution, improved individual nutrition knowledge and community access to iron absorption enhancing foods, particularly produce, is needed. Promoting government assistance programs like Prospera and implementing additional programs designed to improve nutrition and health literacy, in conjunction with ensuring access to nutritious foods, might reduce the high prevalence nutritional anemia within the community.

Risk of gestational hypertension and preeclampsia in women who discontinued or continued antidepressant medication use during pregnancy.

PURPOSE: This study aimed to examine the association between discontinued and continued use of antidepressants and risk for gestational hypertension (GH) and preeclampsia (PE). METHODS: Data from the MotherToBaby pregnancy studies from 2004 to 2014 were analyzed to compare women who discontinued antidepressant use ˂20 weeks of gestation (discontinuers) and women who continued antidepressant use ≥20 weeks of gestation (continuers) to non-users for risk of GH (blood pressure ≥140/90 mmHg on two or more occasions at ≥20 weeks of gestation) and PE (GH with proteinuria). Maternal data, including exposures and study outcomes, were collected through multiple phone interviews. Medical records were used to validate outcomes. Odds ratios (ORs) and 95 % confidence intervals were estimated using logistic regression. Risk for GH and PE were also assessed within antidepressant drug classes. RESULTS: Data from 3471 women were analyzed. Continuers were significantly at risk for GH (adjusted odds ratios (aOR) 1.83; 95 % CI 1.05, 3.21) after adjustment. Analyses by drug class showed that continued use of serotonin-norepinephrine reuptake inhibitors (SNRI) increased risk for GH; however, of the 21 women who continued to use SNRI, only 3 developed GH. Continuers who used two or more antidepressant drug classes had increased risk for PE. Selective serotonin reuptake inhibitors or other antidepressant use was not associated with increased risk for GH or PE. No significant associations with PE or GH were found for discontinuers. CONCLUSIONS: Results suggest that women who continued to use antidepressants in the second half of pregnancy are at risk for GH and PE. No significant association was found among discontinuers.

Effect of Depression on Risky Drinking and Response to a Screening, Brief Intervention, and Referral to Treatment Intervention.

We assessed alcohol consumption and depression in 234 American Indian/Alaska Native women (aged 18-45 years) in Southern California. Women were randomized to intervention or assessment alone and followed for 6 months (2011-2013). Depression was associated with risk factors for alcohol-exposed pregnancy (AEP). Both treatment groups reduced drinking (P < .001). Depressed, but not nondepressed, women reduced drinking in response to SBIRT above the reduction in response to assessment alone. Screening for depression may assist in allocating women to specific AEP prevention interventions.

Associations of military divorce with mental, behavioral, and physical health outcomes.

BACKGROUND: Divorce has been linked with poor physical and mental health outcomes among civilians. Given the unique stressors experienced by U.S. service members, including lengthy and/or multiple deployments, this study aimed to examine the associations of recent divorce on health and military outcomes among a cohort of U.S. service members. METHODS: Millennium Cohort participants from the first enrollment panel, married at baseline (2001-2003), and married or divorced at follow-up (2004-2006), (N = 29,314). Those divorced were compared to those who remained married for mental, behavioral, physical health, and military outcomes using logistic regression models. RESULTS: Compared to those who remained married, recently divorced participants were significantly more likely to screen positive for new-onset posttraumatic stress disorder, depression, smoking initiation, binge drinking, alcohol-related problems, and experience moderate weight gain. However, they were also more likely be in the highest 15(th) percentile of physical functioning, and be able to deploy within the subsequent 3-year period after divorce. CONCLUSIONS: Recent divorce among military members was associated with adverse mental health outcomes and risky behaviors, but was also associated with higher odds of subsequent deployment. Attention should be given to those recently divorced regarding mental health and substance abuse treatment and prevention strategies.

Frequency and geographic distribution of gyrA and gyrB mutations associated with fluoroquinolone resistance in clinical Mycobacterium tuberculosis isolates: a systematic review.

BACKGROUND: The detection of mutations in the gyrA and gyrB genes in the Mycobacterium tuberculosis genome that have been demonstrated to confer phenotypic resistance to fluoroquinolones is the most promising technology for rapid diagnosis of fluoroquinolone resistance. METHODS: In order to characterize the diversity and frequency of gyrA and gyrB mutations and to describe the global distribution of these mutations, we conducted a systematic review, from May 1996 to April 2013, of all published studies evaluating Mycobacterium tuberculosis mutations associated with resistance to fluoroquinolones. The overall goal of the study was to determine the potential utility and reliability of these mutations as diagnostic markers to detect phenotypic fluoroquinolone resistance in Mycobacterium tuberculosis and to describe their geographic distribution. RESULTS: Forty-six studies, covering four continents and 18 countries, provided mutation data for 3,846 unique clinical isolates with phenotypic resistance profiles to fluoroquinolones. The gyrA mutations occurring most frequently in fluoroquinolone-resistant isolates, ranged from 21-32% for D94G and 13-20% for A90V, by drug. Eighty seven percent of all strains that were phenotypically resistant to moxifloxacin and 83% of ofloxacin resistant isolates contained mutations in gyrA. Additionally we found that 83% and 80% of moxifloxacin and ofloxacin resistant strains respectively, were observed to have mutations in the gyrA codons interrogated by the existing MTBDRsl line probe assay. In China and Russia, 83% and 84% of fluoroquinolone resistant strains respectively, were observed to have gyrA mutations in the gene regions covered by the MTBDRsl assay. CONCLUSIONS: Molecular diagnostics, specifically the Genotype MTBDRsl assay, focusing on codons 88-94 should have moderate to high sensitivity in most countries. While we did observe geographic differences in the frequencies of single gyrA mutations across countries, molecular diagnostics based on detection of all gyrA mutations demonstrated to confer resistance should have broad and global utility.

Preventing alcohol-exposed pregnancy among an American Indian/Alaska Native population: effect of a screening, brief intervention, and referral to treatment intervention.

BACKGROUND: Fetal alcohol spectrum disorders are the result of alcohol-exposed pregnancies (AEP) and believed to be the leading known cause of developmental disabilities in the United States. Our objective was to determine whether a culturally targeted Screening, Brief Intervention, and Referral to Treatment (SBIRT) intervention may reduce risky drinking and vulnerability to AEP among American Indian/Alaska Native (AIAN) women in Southern California. METHODS: Southern California AIAN women of childbearing age who completed a survey including questions regarding alcohol consumption and contraceptive use were randomized into intervention or treatment as usual groups where the former group completed an online SBIRT intervention, and were followed up at 1, 3, and 6 months postintervention. RESULTS: Of 263 women recruited and 247 with follow-up data, one-third were at high risk of having an AEP at baseline. Both treatment groups decreased self-reported risky drinking behavior (drinks per week, p < 0.001; frequency of heavy episodic [binge] drinking episodes per 2 weeks, p = 0.017 and risk of AEP p < 0.001 at 6 months postintervention) in the follow-up period. There was no difference between treatment groups. Baseline factors associated with decreased risk of an AEP at follow-up included the perception that other women in their peer group consumed a greater number of drinks per week, having reported a greater number of binge episodes in the past 2 weeks, and depression/impaired functionality. CONCLUSIONS: Participation in assessment alone may have been sufficient to encourage behavioral change even without the web-based SBIRT intervention. Randomization to the SBIRT did not result in a significantly different change in risky drinking behaviors. The importance of perception of other women's drinking and one's own depression/functionality may have implications for future interventions.

The impact of deployment experience and prior healthcare utilization on enrollment in a large military cohort study.

BACKGROUND: Longitudinal cohort studies are highly valued in epidemiologic research for their ability to establish exposure-disease associations through known temporal sequences. A major challenge in cohort studies is recruiting individuals representative of the targeted sample population to ensure the generalizability of the study's findings. METHODS: We evaluated nearly 350,000 invited subjects (from 2004-2008) of the Millennium Cohort Study, a prospective cohort study of the health of US military personnel, for factors prior to invitation associated with study enrollment. Multivariable logistic regression was utilized, adjusting for demographic and other confounders, to determine the associations between both deployment experience and prior healthcare utilization with enrollment into the study. RESULTS: Study enrollment was significantly greater among those who deployed prior to and/or during the enrollment cycles or had at least one outpatient visit in the 12 months prior to invitation. Mental disorders and hospitalization for more than two days within the past year were associated with reduced odds of enrollment. CONCLUSIONS: These findings suggest differential enrollment by deployment experience and health status, and may help guide recruitment efforts in future studies.

Association of phosphodiesterase 4 polymorphism (rs702553) with blood pressure in the African American Study of Kidney Disease and Hypertension Genomics Study.

Hypertension is a risk factor for diseases such as stroke, heart and kidney disease. Phosphodiesterase (PDE) enzymes play a significant role in regulating inflammation and there is some association between increased inflammatory cell mediators and development of hypertension. Previous research has shown the single nucleotide polymorphism (rs702553) on the PDE4D gene to be associated with stroke and carotid atherosclerosis. This research analyzed the association of rs702553 with baseline mean arterial blood pressure (MAP) in a subset of the African American Study of Kidney Disease and Hypertension Cohort. Data analysis identified baseline diuretic use as an interaction term in the association between this polymorphism and MAP. Compared with participants with AA/AT genotypes, those with a TT genotype at rs702553 had significantly lower baseline MAP among study participants on a diuretic (P=0.02). To our knowledge, the influence of rs702553 on final PDE4D gene expression has not yet been studied. Additional clinical and in-vitro studies are needed to better understand the biological mechanisms from gene expression to enzyme translation that affect blood pressure.