Alcohol consumption patterns and HIV viral suppression among persons receiving HIV care in Florida: an observational study.

BACKGROUND: Alcohol consumption has been associated with poor antiretroviral therapy (ART) adherence but less is known about its relationship to HIV viral suppression, or whether certain drinking patterns have a stronger association than others. The objectives of this study were to determine the association of different patterns of alcohol consumption to HIV viral suppression and ART adherence, and to determine whether any associations of alcohol with HIV viral suppression were mediated by poor ART adherence. METHODS: This observational study used baseline data from 619 HIV+ participants, recruited across 8 clinical and community settings across Florida as part of the Florida Cohort from 2014 to 2016. Alcohol consumption was measured by self-report, and grouped into four categories: heavy drinking (>7/week for women or >14 drinks/week for men); binge, but not heavy drinking (≥4 or >5 drinks/occasion for women and men, respectively), low level drinking (neither heavy nor binge), and abstinence. Serum HIV RNA measurements were obtained from statewide HIV surveillance data, and durable viral suppression was defined as achieving HIV viral suppression (<200 copies/ml) at every assessment in the past 12 months. RESULTS: The majority of the 619 participants were male (63%) and aged 45 or greater (65%). The proportion of participants with heavy, binge, low-level drinking and abstinence was 9, 25, 37 and 30%, respectively. Optimal ART adherence (≥95%) was reported by 68%, and 60% achieved durable viral suppression. In multivariable analysis controlling for demographic factors, drug use, and homelessness, heavy drinking (compared to abstinence) was associated with increased odds of failing to achieve durable viral suppression (OR 2.16, 95% CI 1.08-4.32) whereas binge drinking alone was not significantly associated with this outcome (OR 1.04, 95% CI 0.64-1.70). Both heavy drinking and binge drinking were significantly associated with suboptimal ART adherence. Mediation analyses suggested that only a small proportion of the relationship between heavy drinking and suboptimal viral suppression was due to poor ART adherence. CONCLUSIONS: Exceeding weekly recommended levels of alcohol consumption (heavy drinking) was significantly associated with poor HIV viral suppression and ART non-adherence, while binge drinking was associated with suboptimal ART adherence in this sample. Clinicians should attempt to address heavy drinking in their patients with HIV.

The impact of a school-based water supply and treatment, hygiene, and sanitation programme on pupil diarrhoea: a cluster-randomized trial.

The impact of improved water, sanitation, and hygiene (WASH) access on mitigating illness is well documented, although impact of school-based WASH on school-aged children has not been rigorously explored. We conducted a cluster-randomized trial in Nyanza Province, Kenya to assess the impact of a school-based WASH intervention on diarrhoeal disease in primary-school pupils. Two study populations were used: schools with a nearby dry season water source and those without. Pupils attending 'water-available' schools that received hygiene promotion and water treatment (HP&WT) and sanitation improvements showed no difference in period prevalence or duration of illness compared to pupils attending control schools. Those pupils in schools that received only the HP&WT showed similar results. Pupils in 'water-scarce' schools that received a water-supply improvement, HP&WT and sanitation showed a reduction in diarrhoea incidence and days of illness. Our study revealed mixed results on the impact of improvements to school WASH improvements on pupil diarrhoea.

Synthesis of evidence from epidemiological studies with interval-censored exposure due to grouping.

We describe a method for assessing dose-response effects from a series of case-control and cohort studies in which the exposure information is interval censored. The interval censoring of the exposure variable is dealt with through the use of retrospective models in which the exposure is treated as a multinomial response and disease status as a binary covariate. Polychotomous logistic regression models are adopted in which the dose-response relationship between exposure and disease may be modeled in a discrete or continuous fashion. Partial conditioning is possible to eliminate some of the nuisance parameters. The methods are applied to the motivating study of the relationship between chorionic villus sampling and the occurrence of terminal transverse limb reduction.

Marginal structural models and causal inference in epidemiology.

In observational studies with exposures or treatments that vary over time, standard approaches for adjustment of confounding are biased when there exist time-dependent confounders that are also affected by previous treatment. This paper introduces marginal structural models, a new class of causal models that allow for improved adjustment of confounding in those situations. The parameters of a marginal structural model can be consistently estimated using a new class of estimators, the inverse-probability-of-treatment weighted estimators.

Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men.

Standard methods for survival analysis, such as the time-dependent Cox model, may produce biased effect estimates when there exist time-dependent confounders that are themselves affected by previous treatment or exposure. Marginal structural models are a new class of causal models the parameters of which are estimated through inverse-probability-of-treatment weighting; these models allow for appropriate adjustment for confounding. We describe the marginal structural Cox proportional hazards model and use it to estimate the causal effect of zidovudine on the survival of human immunodeficiency virus-positive men participating in the Multicenter AIDS Cohort Study. In this study, CD4 lymphocyte count is both a time-dependent confounder of the causal effect of zidovudine on survival and is affected by past zidovudine treatment. The crude mortality rate ratio (95% confidence interval) for zidovudine was 3.6 (3.0-4.3), which reflects the presence of confounding. After controlling for baseline CD4 count and other baseline covariates using standard methods, the mortality rate ratio decreased to 2.3 (1.9-2.8). Using a marginal structural Cox model to control further for time-dependent confounding due to CD4 count and other time-dependent covariates, the mortality rate ratio was 0.7 (95% conservative confidence interval = 0.6-1.0). We compare marginal structural models with previously proposed causal methods.

A meta-analysis of case-control and cohort studies with interval-censored exposure data: application to chorionic villus sampling.

Chorionic villus sampling (CVS) is a valued method of prenatal diagnosis that is often preferred over amniocentesis because it can be performed earlier, but which has also raised concern over a possible association with increased risk of terminal transverse limb deficiency (TTLD). We present and apply a meta-analytic method for estimating a combined dose-response effect from a series of case-control and cohort studies in which the exposure variable is interval-censored. Assuming coarsening at random for the interval-censoring, and calling upon the familiar result of Cornfield to pool case-control and cohort information on the association between a rare binary outcome and a multilevel exposure variable, we form a likelihood-based model to assess the effect of gestational age at the time of CVS on the presence or absence of a rare birth defect. Effect estimates are computed with a variant of the EM algorithm termed the method of weights, which enables the use of standard weighted regression software. Our findings suggest that CVS exposure at early gestational age leads to an increased risk of TTLD.

Adverse effects of chorionic villus sampling: a meta-analysis.

Meta-analysis is a popular tool for combining evidence from several related studies. The technique is usually used to combine randomized clinical trials, case-control studies or prospective studies where each study has its own exposed and unexposed groups. By including separate 'study effects' (either fixed or random), one can combine information about differences between control and exposed groups, while still allowing for study heterogeneity. In this paper, we extend existing methods to combine studies of disparate designs, where some studies do not include concurrent controls. We apply the methods to a meta-analysis of the association of prenatal testing via chorionic villus sampling with the occurrence of terminal transverse limb defects.

Comparison of culture and the antigenemia assay for detection of cytomegalovirus in blood specimens submitted to a reference laboratory.

We compared the antigenemia assay (AA) with tandem shell vial cultures (SVCs) and tube cultures (TCs) for detection of cytomegalovirus (CMV) in 343 blood specimens. For 249 specimens, the AA was performed in duplicate with two different commercially available monoclonal antibody reagents (Biotest Diagnostic Corporation and Argene Biosoft). Specimens considered true positives were positive in either culture system or both AAs. Only specimens which were negative in both cultures and positive in a single AA were tested retrospectively with a CMV PCR assay. CMV recovery rates were also calculated to determine if increased specimen age resulted in decreased positivity. CMV recovery rates for the AA and the combination of both cultures were 20.0 and 5.0% at 3 to 18 h, 20.2 and 14.0% at 18 to 35 h, 12.5 and 7.8% at 36 to 52 h, and 18.8 and 6.3% at 64 to 75 h, respectively. The sensitivities and specificities of the Biotest AA, the Argene AA, SVC, and TC were 84.4 and 100.0, 100.0 and 99.6, 44.4 and 100.0, and 46.0 and 100.0%, respectively. The AA was significantly more sensitive than either culture method alone and was also more sensitive than the two culture methods used in tandem (the tandem culture sensitivity was 63.5%); the Argene AA identified more positives than the Biotest AA.

Simultaneous rapid culture for four respiratory viruses in the same cell monolayer using a differential multicolored fluorescent confirmatory stain.

A simultaneous rapid culture for influenza virus types A and B, parainfluenza virus, and respiratory syncytial virus was developed in a 96-well plate format with a culture-confirmatory stain using multiple fluorescent tags. Performance characteristics were comparable to those of standard and/or single rapid-culture methods as shown by parallel testing of 590 fresh clinical specimens and retrospective testing of 190 previously positive frozen specimens. The quadruple culture required less specimen volume than separate cultures, was significantly quicker than standard tube culture, was less labor intensive than separate cultures, and was less expensive than the other methods.

Bone mass and subtle abnormalities in ovulatory function in healthy women.

Women with occasional anovulatory or short luteal phase menstrual cycles have been reported to lose bone mineral density (BMD) at a greatly accelerated rate compared to women without such abnormalities. To investigate this association, we performed a longitudinal study of BMD in a group of healthy premenopausal women enrolled in a comprehensive study of ovulatory function. Subjects had collected daily urine samples that were analyzed for estrone and progesterone metabolites by enzyme-linked immunoassay. The 53 participants collected urine for an average of 4.1 cycles. Computer algorithms identified 7 (13.2%) women with luteal phase abnormalities (> 1 anovulatory cycle or cycle with luteal phase length < or = 10 days) and 17 (32.1%) women with other menstrual abnormalities. Areal BMD (grams per cm2) was measured at the lumbar spine, hip, and whole body using dual energy x-ray absorptiometry; BMD was measured 2-3 times over an average observation period of 17.5 months. At baseline, women with luteal abnormalities had mean BMD similar to those of the 29 women with no abnormal cycles: lumbar spine, 1.06 vs. 1.09 g/cm2; total hip, 0.95 vs. 0.94 g/cm2; whole body, 1.15 vs. 1.11 g/cm2 (P > 0.10; adjusted for age and weight at baseline, parity, physical activity level, and calcium intake). When compared at follow-up to women with no abnormal cycles, women with luteal abnormalities tended to gain BMD at the spine and hip (P > 0.10). On whole body measurement, women with luteal abnormalities tended to lose BMD compared to women with no abnormal cycles (-1.1%/yr vs. 0%/yr; P = 0.08); however, the magnitude of loss was not unusual for women in this age range and was within the coefficient of variation for replicate measurements. Neither mean luteal phase length, percent time in luteal phase, nor average daily excretion of progesterone metabolites was associated with baseline BMD or percent annual change in BMD at any measurement site. Thus, we did not confirm a relationship between luteal abnormalities and accelerated bone loss in this population of healthy premenopausal women.

Rapid culture for influenza virus, types A and B, in 96-well plates.

BACKGROUND: Rapid diagnosis and typing of influenza virus are important for patient treatment and management during seasonal outbreaks. Centrifugation-enhanced rapid culture has been reported to be useful as an adjunct to traditional tube culture for rapid diagnosis of influenza virus. OBJECTIVES: We compared rapid culture in 96-well plates against standard tube culture for recovery of influenza virus, types A and B. We also tested two different cell types, MDCK and RMK, to determine if the use of multiple cell lines increases the sensitivity of rapid culture. STUDY DESIGN: The rapid method was initially evaluated by retrospective culture of previously positive frozen specimens. It was then compared to standard culture for recovery of influenza virus by parallel testing of fresh respiratory specimens. RESULTS: Of 32 previously positive frozen specimens, 28 were positive upon repeat culture. Rapid culture recovered 25 (89.3%) and standard culture recovered 23 (82.1%). All positives were type A. Of 722 fresh specimens cultured in parallel, 76 (10.5%) were positive for influenza virus: 43 for type A and 33 for type B. For type A, rapid culture recovered 42 of 43 (97.7%) and tube culture recovered 39 (90.7%). For type B, rapid culture recovered 33 of 33 (100%) and tube culture recovered 24 (72.7%). In the rapid system, the MDCK cell line was positive for 40 of 42 type A positives (95.2%) and the RMK was positive for 41 (97.6%). The MDCK line was positive for 32 of the 33 type B isolates (97.0%) and the RMK cells were positive for all 33 (100%). CONCLUSIONS: Rapid culture substantially reduced total test time and was more sensitive than tube culture. Duplicate cell lines did not significantly increase test sensitivity.

Simultaneous culture for adenovirus, cytomegalovirus, and herpes simplex virus in same shell vial by using three-color fluorescence.

A simultaneous triple culture for adenovirus, cytomegalovirus, and herpes simplex virus, using three different fluorochromes for virus detection and differentiation in the same shell vial, was developed. In evaluations the triple culture performed comparably to separate cultures, required less specimen volume, and was less expensive to perform.

Simultaneous detection of and differentiation between herpes simplex and varicella-zoster viruses with two fluorescent probes in the same test system.

Specimens from skin lesions were examined simultaneously for herpes simplex virus (HSV) and varicella-zoster virus (VZV) by direct specimen testing and shell vial culture in single-test systems. For direct testing, cells in a single specimen well were stained with a combination direct-indirect immunofluorescence stain by using two fluorescent tags. A total of 203 fresh specimens were tested in parallel. Of these, 100 specimens contained too few cells for the direct VZV comparison and 91 contained too few cells for the HSV comparison. After these specimens were eliminated, the sensitivities and specificities, respectively, of the dual direct test were 86.1 and 97.3% for HSV compared with single culture and 92.2 and 100% for VZV compared with single direct testing. Shell vial monolayers in the combined cultures were stained for both viruses by the same method. A total of 305 fresh specimens were cultured in parallel by dual- and single-culture methods. The sensitivities and specificities, respectively, of the combined culture compared with separate cultures were 100 and 98.4% for HSV and 87.9 and 99.2% for VZV. The combined methods gave a performance comparable to those of single tests, required less specimen volume, and were less costly to perform.