Universal screening of Tanzanian HIV-infected adult inpatients with the serum cryptococcal antigen to improve diagnosis and reduce mortality: an operational study

Cryptococcal meningitis is a leading cause of death among HIV-infected individuals in sub-Saharan Africa. Recent developments include the availability of intravenous fluconazole, cryptococcal antigen assays and new data to support fluconazole pre-emptive treatment. In this study, we describe the impact of screening HIV-positive adult inpatients with serum cryptococcal antigen (CRAG) at a Tanzanian referral hospital. All adults admitted to the medical ward of Bugando Medical Centre are counseled and tested for HIV. In this prospective cohort study, we consecutively enrolled HIV-positive patients admitted between September 2009 and January 2010. All patients were interviewed, examined and screened with serum CRAG. Patients with positive serum CRAG or signs of meningitis underwent lumbar puncture. Patients were managed according to standard World Health Organization treatment guidelines. Discharge diagnoses and in-hospital mortality were recorded.\ud Of 333 HIV-infected adults enrolled in our study, 15 (4.4%) had confirmed cryptococcal meningitis and 10 of these 15 (66%) died. All patients with cryptococcal meningitis had at least two of four classic symptoms and signs of meningitis: fever, headache, neck stiffness and altered mental status. Cryptococcal meningitis accounted for a quarter of all in-hospital deaths. Despite screening of all HIV-positive adult inpatients with the serum CRAG at the time of admission and prompt treatment with high-dose intravenous fluconazole in those with confirmed cryptococcal meningitis, the in-hospital mortality rate remained unacceptably high. Improved strategies for earlier diagnosis and treatment of HIV, implementation of fluconazole pre-emptive treatment for high-risk patients and acquisition of better resources for treatment of cryptococcal meningitis are needed

A comparison of meningococcal carriage by pregnancy status

Neisseria meningitidis is the second leading cause of invasive meningitis. A prerequisite for infection is colonization of the nasopharynx, and asymptomatic carrier rates are widely reported in the range of 10-15%. Recent reports have indicated an increased likelihood that a pediatric admission for Neisseria meningitidis will have a mother who is pregnant in the home. We hypothesized that this association may relate to immunologic changes in pregnancy leading to higher carrier rates

Urinary phthalate metabolite concentrations and blood glucose levels during pregnancy

Purpose: To examine associations between phthalate metabolite urinary concentrations during early pregnancy and blood glucose levels obtained at the time of screening for gestational diabetes mellitus (GDM). Methods: Upon initiation of prenatal care, women with a mean gestational age of 12.8 weeks were recruited for a study of environmental chemical exposures (n = 110) and provided a spot urinary specimen. Blood glucose concentrations (mg/dl) were obtained from the electronic medical record for those patients who did not experience a pregnancy loss and did not transfer care to another facility prior to glucose screening (n = 72). Urinary concentrations of nine phthalate metabolites and creatinine were measured at the US Centers for Disease Control and Prevention. Associations between tertiles of phthalate metabolites concentrations and blood glucose levels were estimated using linear regression. Results: Compared to pregnant women in the lowest concentration tertile, women with the highest urinary concentrations (≥ 3 rd tertile) of mono-iso-butyl phthalate (tertile: ≥ 15.3 μg/l, β = -18.3, 95% CI: -35.4, -1.2) and monobenzyl phthalate (tertile: ≥ 30.3 μg/l, β = -17.3, 95% CI: -34.1, -0.4) had lower blood glucose levels at the time of GDM screening after adjustment for urinary creatinine and demographic covariates. Conclusion: Because maternal glucose levels increase during pregnancy to provide adequate nutrition for fetal growth and development, these findings may have implications for fetal health. However, given the limitations of our study, findings should be interpreted cautiously

Is bisphenol-A exposure during pregnancy associated with blood glucose levels or diagnosis of gestational diabetes?

Recent epidemiological studies indicate bisphenol A (BPA), an estrogenic chemical used in production of epoxy, polycarbonate, and plastic may increase risk of insulin resistance and type 2 diabetes. Exposure to BPA during pregnancy may contribute to development of gestational diabetes mellitus (GDM), a precursor to type 2 diabetes in women. This pilot study examined the association between BPA exposure, fasting blood glucose levels (FBG), and GDM diagnosis during pregnancy. Banked urine samples from 22 cases of GDM and 72 controls were analyzed for total (free BPA + conjugates) urinary BPA concentrations (μg/L). FBG levels (mg/dl) were obtained from 1-h 50-g glucose tolerance tests (GTT) that women underwent for routine GDM screening (mean gestational age = 26.6 weeks, SD = 3.8). Those with an initial screening value ≥ 135 mg/dl underwent 3-h 100 g oral GTT. GDM diagnoses were made when the initial screening value was ≥ 200 mg/dl or when values at ≥ 2 time points exceeded 3-h oral GTT thresholds. Among controls, median FBG levels (mg/dL) did not differ across exposure tertiles, defined according to the distribution of total specific-gravity-adjusted urinary BPA concentrations. Logistic regression models controlling for race/ethnicity did not provide evidence of association between BPA exposure and case status across increasing tertiles of BPA exposure (number of GDM cases/controls in tertile1: 13/24; in tertile 2: 6/24; in tertile 3: 3/24). Findings do not support a relationship between total urinary BPA concentrations and altered glucose metabolism during pregnancy. However, due to study limitations, findings need to be interpreted with caution

Luminous Infrared Galaxies with the Submillimeter Array: I. Survey Overview and the Central Gas to Dust Ratio

We present new data obtained with the Submillimeter Array for a sample of fourteen nearby luminous and ultraluminous infrared galaxies. The galaxies were selected to have luminosity distances D < 200 Mpc and far-infrared luminosities log(L_FIR) > 11.4. The galaxies were observed with spatial resolutions of order 1 kpc in the CO J=3-2, CO J=2-1, 13CO J=2-1, and HCO+ J=4-3 lines as well as the continuum at 880 microns and 1.3 mm. We have combined our CO and continuum data to measure an average gas-to-dust mass ratio of 120 +/- 28 (rms deviation 109) in the central regions of these galaxies, very similar to the value of 150 determined for the Milky Way. This similarity is interesting given the more intense heating from the starburst and possibly accretion activity in the luminous infrared galaxies compared to the Milky Way. We find that the peak H_2 surface density correlates with the far-infrared luminosity, which suggests that galaxies with higher gas surface densities inside the central kiloparsec have a higher star formation rate. The lack of a significant correlation between total H_2 mass and far-infrared luminosity in our sample suggests that the increased star formation rate is due to the increased availability of molecular gas as fuel for star formation in the central regions. In contrast to previous analyses by other authors, we do not find a significant correlation between central gas surface density and the star formation efficiency, as trace by the ratio of far-infrared luminosity to nuclear gas mass. Our data show that it is the star formation rate, not the star formation efficiency, that increases with increasing central gas surface density in these galaxies.Comment: 66 pages, 39 figures, aastex preprint format; to be published in ApJ Supplements. Version of paper with full resolution figures available at http://www.physics.mcmaster.ca/~wilson/www_xfer/ULIRGS_publi

Oesophageal varices, schistosomiasis, and mortality among patients admitted with haematemesis in Mwanza, Tanzania: a prospective cohort study.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a common cause of hospital admissions worldwide. Aetiologies vary by sociodemographics and geography. Retrospective studies of endoscopies in much of Africa have documented oesophageal varices as a leading cause of UGIB. Prospective studies describing outcomes and associations with clinical factors are lacking. METHODS: We conducted a prospective cohort study at a referral hospital in Mwanza, Tanzania where schistosomiasis is endemic. Adults admitted with haematemesis underwent laboratory workup, schistosomiasis antigen testing and elective endoscopy, and were followed for two months for death or re-bleeding. We assessed predictors of endoscopic findings using logistic regression models, and determined prediction rules that maximised sensitivity and positive predictive value (PPV). RESULTS: Of 124 enrolled patients, 13 died within two months (10%); active schistosomiasis prevalence was 48%. 64/91(70%) patients had oesophageal varices. We found strong associations between varices and numerous demographic or clinical findings, permitting construction of simple, high-fidelity prediction rules for oesophageal varices applicable even in rural settings. Portal vein diameter ≥ 13 mm or water sourced from the lake yielded sensitivity, specificity, PPV and NPV >90% for oesophageal varices; presence of splenomegaly or water sourced from the lake maintained sensitivity and PPV >90%. CONCLUSIONS: Our results guide identification of patients, via ultrasound and clinical examination, likely to have varices for whom referral for endoscopy may be life-saving. Furthermore, they support empiric anti-schistosome treatment for patients with UGIB in schistosome-endemic regions. These interventions have potential to reduce UGIB-related morbidity and mortality in Africa

Assessing urinary phenol and paraben mixtures in pregnant women with and without gestational diabetes mellitus: a case-control study

Prior studies have identified the associations between environmental phenol and paraben exposures and increased risk of gestational diabetes mellitus (GDM), but no study addressed these exposures as mixtures. As methods have emerged to better assess exposures to multiple chemicals, our study aimed to apply Bayesian kernel machine regression (BKMR) to evaluate the association between phenol and paraben mixtures and GDM. This study included 64 GDM cases and 237 obstetric patient controls from the University of Oklahoma Medical Center. Mid-pregnancy spot urine samples were collected to quantify concentrations of bisphenol A (BPA), benzophenone-3, triclosan, 2,4-dichlorophenol, 2,5-dichlorophenol, butylparaben, methylparaben, and propylparaben. Multivariable logistic regression was used to evaluate the associations between individual chemical biomarkers and GDM while controlling for confounding. We used probit implementation of BKMR with hierarchical variable selection to estimate the mean difference in GDM probability for each component of the phenol and paraben mixtures while controlling for the correlation among the chemical biomarkers. When analyzing individual chemicals using logistic regression, benzophenone-3 was positively associated with GDM [adjusted odds ratio (aOR) per interquartile range (IQR) = 1.54, 95% confidence interval (CI) 1.15, 2.08], while BPA was negatively associated with GDM (aOR 0.61, 95% CI 0.37, 0.99). In probit-BKMR analysis, an increase in z-score transformed log urinary concentrations of benzophenone-3 from the 10th to 90th percentile was associated with an increase in the estimated difference in the probability of GDM (0.67, 95% Credible Interval 0.04, 1.30), holding other chemicals fixed at their medians. No associations were identified between other chemical biomarkers and GDM in the BKMR analyses. We observed that the association of BPA and GDM was attenuated when accounting for correlated phenols and parabens, suggesting the importance of addressing chemical mixtures in perinatal environmental exposure studies. Additional prospective investigations will increase the understanding of the relationship between benzophenone-3 exposure and GDM development

Urinary total arsenic and arsenic methylation capacity in pregnancy and gestational diabetes mellitus: A case-control study

Previous studies suggest arsenic exposure may increase the risk of gestational diabetes mellitus (GDM). However, prior assessments of total arsenic concentrations have not distinguished between toxic and nontoxic species. Our study aimed to investigate the relationships between inorganic arsenic exposure, arsenic methylation capacity, and GDM. Sixty-four cases of GDM and 237 controls were analyzed for urinary concentrations of inorganic arsenic species and their metabolites (arsenite (As3), arsenate (As5), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)), and organic forms of arsenic. Inorganic arsenic exposure was defined as the sum of inorganic and methylated arsenic species (iSumAs). Methylation capacity indices were calculated as the percentage of inorganic arsenic species [iAs% = (As3 + As5)/iSumAs, MMA% = MMA/iSumAs, and DMA% = DMA/iSumAs]. Multivariable logistic regression was performed to evaluate the association between inorganic arsenic exposure, methylation capacity indices, and GDM. We did not observe evidence of a positive association between iSumAs and GDM. However, women with GDM had an increased odds of inefficient methylation capacity when comparing the highest and lowest tertiles of iAs% (adjusted odds ratio (aOR) = 1.48, 95% CI 0.58–3.77) and MMA% (aOR = 1.95 (95% CI 0.81–4.70) and a reduced odds of efficient methylation capacity as indicated by DMA% (aOR = 0.62 (95% CI 0.25–1.52), though the confidence intervals included the null value. While the observed associations with arsenic methylation indices were imprecise and warrant cautious interpretation, the direction and magnitude of the relative measures reflected a pattern of lower detoxification of inorganic arsenic exposures among women with GDM

Dietary vitamin D and calcium intake and mammographic density in postmenopausal women

Dietary intake of vitamin D and calcium may be related to risk of breast cancer, possibly by affecting mammographic density. However, the few studies that have evaluated the association between these nutrients and mammographic density in postmenopausal women have had inconsistent results

Antiretroviral Therapy, Renal Function among HIV-Infected Tanzanian, Adults, HIV/AIDS, .

Data regarding the outcomes of HIV-infected adults with baseline renal dysfunction who start antiretroviral therapy are conflicting. We followed up a previously-published cohort of HIV-infected adult outpatients in northwest Tanzania who had high prevalence of renal dysfunction at the time of starting antiretroviral therapy (between November 2009 and February 2010). Patients had serum creatinine, proteinuria, microalbuminuria, and CD4(+) T-cell count measured at the time of antiretroviral therapy initiation and at follow-up. We used the adjusted Cockroft-Gault equation to calculate estimated glomerular filtration rates (eGFRs). In this cohort of 171 adults who had taken antiretroviral therapy for a median of two years, the prevalence of renal dysfunction (eGFR <90 mL/min/1.73 m(2)) decreased from 131/171 (76.6%) at the time of ART initiation to 50/171 (29.2%) at the time of follow-up (p<0.001). Moderate dysfunction (eGFR<60 mL/min/1.73 m(2)) decreased from 21.1% at antiretroviral therapy initiation to 1.1% at follow-up (p<0.001), as did the prevalence of microalbuminuria (72% to 44%, p<0.001). Use of tenofovir was not associated with renal dysfunction at follow-up. Mild and moderate renal dysfunction were common in this cohort of HIV-infected adults initiating antiretroviral therapy, and both significantly improved after a median follow-up time of 2 years. Our work supports the renal safety of antiretroviral therapy in African adults with mild-moderate renal dysfunction, suggesting that these regimens do not lead to renal damage in the majority of patients and that they may even improve renal function in patients with mild to moderate renal dysfunction