Recurrence after hospitalization for acute coronary syndrome among HIV-infected and HIV-uninfected individuals.

OBJECTIVES: We evaluated the association of HIV infection and immunodeficiency with acute coronary syndrome (ACS) recurrence, and with all-cause mortality as a secondary outcome, after hospitalization for ACS among HIV-infected and HIV-uninfected individuals. METHODS: We conducted a retrospective cohort study within Kaiser Permanente Northern California of HIV-infected and HIV-uninfected adults discharged after ACS hospitalization [types: ST-elevation myocardial infarction (STEMI), non-STEMI, or unstable angina] during 1996-2010. We compared the outcomes of ACS recurrence and all-cause mortality within 3 years, both overall by HIV status and stratified by recent CD4 count, with HIV-uninfected individuals as the reference group. Hazard ratios (HRs) were obtained from Cox regression models with adjustment for age, sex, race/ethnicity, year, ACS type, smoking, and cardiovascular risk factors. RESULTS: Among 226 HIV-infected and 86 321 HIV-uninfected individuals with ACS, HIV-infected individuals had a similar risk of ACS recurrence compared with HIV-uninfected individuals [HR 1.08; 95% confidence interval (CI) 0.76-1.54]. HIV infection was independently associated with all-cause mortality after ACS hospitalization overall (HR 2.52; 95% CI 1.81-3.52). In CD4-stratified models, post-ACS mortality was higher for HIV-infected individuals with CD4 counts of 201-499 cells/µL (HR 2.64; 95% CI 1.66-4.20) and < 200 cells/µL (HR 5.41; 95% CI 3.14-9.34), but not those with CD4 counts ≥ 500 cells/µL (HR 0.67; 95% CI 0.22-2.08), compared with HIV-uninfected individuals (P trend < 0.001). CONCLUSIONS: HIV infection and immunodeficiency were not associated with recurrence of ACS after hospitalization. All-cause mortality was higher among HIV-infected compared with HIV-uninfected individuals, but there was no excess mortality risk among HIV-infected individuals with high CD4 counts.

Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation.

Immune abnormalities have been described in some individuals with autism spectrum disorders (ASDs) as well as their family members. However, few studies have directly investigated the role of prenatal cytokine and chemokine profiles on neurodevelopmental outcomes in humans. In the current study, we characterized mid-gestational serum profiles of 22 cytokines and chemokines in mothers of children with ASD (N=415), developmental delay (DD) without ASD (N=188), and general population (GP) controls (N=428) using a bead-based multiplex technology. The ASD group was further divided into those with intellectual disabilities (developmental/cognitive and adaptive composite score<70) (ASD+ID, N=184) and those without (composite score⩾70) (ASD-noID, N=201). Levels of cytokines and chemokines were compared between groups using multivariate logistic regression analyses, adjusting for maternal age, ethnicity, birth country and weight, as well as infant gender, birth year and birth month. Mothers of children with ASD+ID had significantly elevated mid-gestational levels of numerous cytokines and chemokines, such as granulocyte macrophage colony-stimulating factor, interferon-γ, interleukin-1α (IL-1α) and IL-6, compared with mothers of children with either ASD-noID, those with DD, or GP controls. Conversely, mothers of children with either ASD-noID or with DD had significantly lower levels of the chemokines IL-8 and monocyte chemotactic protein-1 compared with mothers of GP controls. This observed immunologic distinction between mothers of children with ASD+ID from mothers of children with ASD-noID or DD suggests that the intellectual disability associated with ASD might be etiologically distinct from DD without ASD. These findings contribute to the ongoing efforts toward identification of early biological markers specific to subphenotypes of ASD.

Maternal mid-pregnancy C-reactive protein and risk of autism spectrum disorders: the early markers for autism study.

Maternal pregnancy levels of the inflammatory marker C-reactive protein (CRP) has been previously associated with autism spectrum disorder (ASD) in the offspring. We conducted a population-based nested case-control study with 500 children with ASD, 235 with developmental delay (DD) and 580 general population (GP) controls to further investigate whether elevated CRP during pregnancy increases the risk of ASD. Maternal CRP concentration was measured in archived serum collected during 15-19 weeks of pregnancy and genome-wide single-nucleotide polymorphism (SNP) data were generated. The levels of CRP were compared between ASD vs GP and DD vs GP. The genetic associations with CRP were assessed via linear regression. Maternal CRP levels in mid-pregnancy were lower in mothers of ASD compared with controls. The maternal CRP levels in the upper third and fourth quartiles were associated with a 45 and 44% decreased risk of ASD, respectively. Two SNPs at the CRP locus showed strong association with CRP levels but they were not associated with ASD. No difference was found between maternal CRP levels of DD and controls. The reasons for the lower levels of CRP in mothers of ASD are not known with certainty but may be related to alterations in the immune response to infectious agents. The biological mechanisms underlying this association remain to be clarified.

Increased female autosomal burden of rare copy number variants in human populations and in autism families.

Autosomal genetic variation is presumed equivalent in males and females and makes a major contribution to disease risk. We set out to identify whether maternal copy number variants (CNVs) contribute to autism spectrum disorders (ASDs). Surprisingly, we observed a higher autosomal burden of large, rare CNVs in females in the population, reflected in, but not unique to, ASD families. Meta-analysis across control data sets confirms female excess in CNV number (P=2.1 × 10(-5)) and gene content (P=4.1 × 10(-3)). We additionally observed CNV enrichment in ASD mothers compared with control mothers (P=0.03). We speculate that tolerance for CNV burden contributes to decreased female fetal loss in the population and that ASD-specific maternal CNV burden may contribute to high sibling recurrence. These data emphasize the need for study of familial CNV risk factors in ASDs and the requirement of sex-matched comparisons.

Trends in annual incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection in HIV-infected and HIV-uninfected patients.

We describe trends in incidence rates of methicillin-resistant Staphylococcus aureus (MRSA) in HIV-infected and HIV-uninfected patients enrolled in a large northern California Health Plan, and the ratio of MRSA to methicillin-susceptible S. aureus (MSSA) case counts. Between 1995 and 2010, 1549 MRSA infections were diagnosed in 14060 HIV-infected patients (11·0%) compared to 89546 MRSA infections in 6597396 HIV-uninfected patients (1·4%) (P = 0·00). A steady rise in MRSA infection rates began in 1995 in HIV-uninfected patients, peaking at 396·5 infections/100000 person-years in 2007. A more rapid rise in MRSA infection rates occurred in the HIV-infected group after 2000, peaking at 3592·8 infections/100000 in 2005. A declining trend in MRSA rates may have begun in 2008-2009. Comparing the ratio of MRSA to MSSA case counts, we observed that HIV-infected patients shouldered a greater burden of MRSA infection during most years of study follow-up compared to HIV-uninfected patients.

Serum uric acid and risk of multiple sclerosis.

Because of evidence implicating oxidative stress in multiple sclerosis pathogenesis, it has been postulated that high levels of urate, a potent antioxidant, could reduce risk or favorably influence disease progression. We conducted a prospective study to determine whether serum urate levels contribute to prediction of multiple sclerosis risk. Analyses included 31 cases with blood collected a median of 1.9 years before multiple sclerosis onset from the Nurses' Health Study and Nurses' Health Study II cohorts, and 42 cases with collection a median of 14.5 years before onset from the Kaiser Permanente Northern California health plan cohort. Relative risks were estimated by unconditional logistic regression, including 26 controls in the Nurses' cohorts and 130 controls in the Kaiser cohort. In analyses including only cases in the Nurses' cohorts where blood was collected shortly before onset, there was a trend toward a lower risk of multiple sclerosis among individuals with higher serum urate, but the association was not significant (multivariable relative risk 0.52, 95% CI 0.22, 1.20, p value 0.13). In contrast, there was no evidence of a decline in risk with increasing serum urate in the Kaiser cohort where there was a longer period of time between blood collection and onset (multivariable relative risk 1.36, 95% CI 0.87, 2.14, p value 0.18). The results of this study suggest that serum urate is not a strong predictor of MS risk. This lack of association is consistent with the interpretation that the lower urate levels among multiple sclerosis cases are a consequence rather than a cause of the disease.

A prospective study of Chlamydia pneumoniae infection and risk of MS in two US cohorts.

BACKGROUND: Chlamydia pneumoniae (Cpn) has been proposed as a possible etiologic agent in multiple sclerosis (MS). However, previous studies were cross-sectional and could not assess whether Cpn infection preceded the onset of MS. METHODS: The authors conducted a prospective nested case-control study among 3 million US Army personnel and 121,466 members of the Kaiser Permanente Medical Care Program (KPMCP) cohort. Serum samples collected prior to onset of MS symptoms were available for 83 MS cases in the Army and 46 in the KPMCP cohort. Two controls were matched to each case on age, sex, and date of blood collection. Microimmunofluorescence was used to measure serum immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody titers to Cpn; IgG titers > or 1:16 were considered positive for past Cpn infection. RESULTS: Seropositivity for Cpn was not significantly associated with risk of MS in either cohort (Army: OR = 1.0; 95% CI 0.6, 1.8; KPMCP: OR = 1.5; 95% CI 0.7, 3.1) or in the pooled analysis (OR = 1.2; 95% CI 0.8, 1.9). Serum levels of anti-Cpn IgG antibody were also not associated with an increased risk of MS in the Army (OR for a fourfold difference in antibody titers = 0.9; 95% CI 0.7, 1.2) or in the pooled analysis (OR = 1.2; 95% CI 0.9, 1.4), but a significant increase in risk was seen in the KPMCP cohort (OR = 1.7; 95% CI 1.2, 2.5). The difference between these results in the Army and the KPMCP cohort was significant (p = 0.01). CONCLUSIONS: Neither Cpn seropositivity nor serum anti-Cpn IgG antibody titers predicted risk of developing MS. However, due to the heterogeneity of results between cohorts, we cannot exclude the possibility that infection with Cpn may modify the risk of MS.

Comorbidity and survival in HIV-infected men in the San Francisco Men's Health Survey.

The course of disease associated with infection with the human immunodeficiency virus varies widely. Some patients deteriorate rapidly, while others live for years, even after an illness that defines the acquired immunodeficiency syndrome (AIDS). In this study, comorbidity, or the presence of concurrent health problems, was investigated prospectively as a possible co-factor for different rates of decline in 395 homosexual/bisexual men in the San Francisco Men's Health Study (SFMHS) who were infected with the human immunodeficiency virus (HIV). Comorbidity data obtained from baseline interviews included both chronic and infectious diseases as well as depression. Smoking, alcohol, and drug use were also examined. The most prevalent comorbid conditions were sexually transmitted diseases (90%) and hepatitis B infection (76%). Most chronic and acute concurrent health conditions were not significant discrete predictors of survival to AIDS or death after controlling for immune status and markers of disease progression. Significantly, other risk factors (e.g., depression and smoking) were found to be associated with more rapid progression. Men with symptoms of depression had a higher risk of progression of AIDS diagnosis; the relative hazard (RH) was 1.4 (95% confidence interval [CI], 1.00-2.08); smoking was associated with higher risk of death (RH, 1.6; 95% CI, 1.20-2.17). Older age was marginally associated with poorer survival to death. No associations were found between survival and alcohol and drug use.

Imbalance in an older population: an epidemiological analysis.

Difficulties with balance are associated with limitations in activities of daily living. There is little information, however, about the epidemiology of imbalance. Imbalance, defined as the inability to maintain a full-tandem stand for 10 seconds, was assessed as part of an interview with 2,018 residents of Marin County, California, age 55 and older. The likelihood of imbalance was greater in women, those aged 85 and older, and those with less than 12 years of education. It was also associated with specific chronic conditions, including a history of hypertension, stroke, or cataracts. Even after adjusting for these conditions, imbalance was associated with reduced lower-body strength as well as poor short-term memory, hip pain, vision problems, abstention from alcohol, and current cigarette smoking. With those aged 85 and older representing the fastest growing age group in developed nations, imbalance may become a major health problem.

The likelihood of returning to work after breast cancer.

OBJECTIVE: This is an examination of factors associated with returning to work after the diagnosis of breast cancer. METHODS: Three months after being diagnosed with breast cancer, 296 employed women from the Detroit metropolitan area (52 black and 244 white women) were interviewed. These women were part of a larger cohort of 1,011 breast cancer patients ages 40 to 84 interviewed for the study "Health and Functioning in Women with Breast Cancer". RESULTS: Although most employed women returned to work within three months of the diagnosis of breast cancer, black women were twice as likely as white women to be on medical leave three months after diagnosis (OR = 1.94; 95% CI 1.04 to 3.62). Being on leave was found to be associated with the need for assistance with transportation, limitations in upper-body strength, and employment in jobs requiring physical activity. After adjusting for these factors, the racial difference was reduced and no longer statistically significant (OR = 1.34; 95% CI 0.67, 2.70). CONCLUSION: Breast cancer rehabilitation programs should not only address the patient's physical capacity but also the daily demands she is likely to face once she leaves the hospital and returns to work.

Limitations in upper-body strength associated with breast cancer: a comparison of black and white women.

We examined differences in reported upper-body limitations between black and white breast cancer cases and controls aged 40 to 84 years at 3 and 12 months after diagnosis in the Detroit metropolitan area (n = 954 cases and 1000 controls at 3 months; n = 879 cases and 909 controls at 12 months). At 3 months black cases were more likely than white cases to report limitations in upper-body strength (30.4 versus 19.8%). No difference was found between black and white controls (8.0 versus 9.4%). At 12 months, the proportion of white patients with upper-body limitation returned to the same level as white controls. Black patients with limitations, however, did not return to the same level as black controls. Stage of disease was strongly associated with upper-body limitations, especially for black women. Race and stage differences in upper-body limitation could not be explained by differences in breast cancer treatment, financial adequacy, education, marital status, or comorbidity. Recommendations are made for more comprehensive studies of rehabilitation.