Estimating the impact of stimulant use on initiation of buprenorphine and extended-release naltrexone in two clinical trials and real-world populations.

BACKGROUND: Co-use of stimulants and opioids is rapidly increasing. Randomized clinical trials (RCTs) have established the efficacy of medications for opioid use disorder (MOUD), but stimulant use may decrease the likelihood of initiating MOUD treatment. Furthermore, trial participants may not represent "real-world" populations who would benefit from treatment. METHODS: We conducted a two-stage analysis. First, associations between stimulant use (time-varying urine drug screens for cocaine, methamphetamine, or amphetamines) and initiation of buprenorphine or extended-release naltrexone (XR-NTX) were estimated across two RCTs (CTN-0051 X:BOT and CTN-0067 CHOICES) using adjusted Cox regression models. Second, results were generalized to three target populations who would benefit from MOUD: Housed adults identifying the need for OUD treatment, as characterized by the National Survey on Drug Use and Health (NSDUH); adults entering OUD treatment, as characterized by Treatment Episodes Dataset (TEDS); and adults living in rural regions of the U.S. with high rates of injection drug use, as characterized by the Rural Opioids Initiative (ROI). Generalizability analyses adjusted for differences in demographic characteristics, substance use, housing status, and depression between RCT and target populations using inverse probability of selection weighting. RESULTS: Analyses included 673 clinical trial participants, 139 NSDUH respondents (weighted to represent 661,650 people), 71,751 TEDS treatment episodes, and 1,933 ROI participants. The majority were aged 30-49 years, male, and non-Hispanic White. In RCTs, stimulant use reduced the likelihood of MOUD initiation by 32% (adjusted HR [aHR] = 0.68, 95% CI 0.49-0.94, p = 0.019). Stimulant use associations were slightly attenuated and non-significant among housed adults needing treatment (25% reduction, aHR = 0.75, 0.48-1.18, p = 0.215) and adults entering OUD treatment (28% reduction, aHR = 0.72, 0.51-1.01, p = 0.061). The association was more pronounced, but still non-significant among rural people injecting drugs (39% reduction, aHR = 0.61, 0.35-1.06, p = 0.081). Stimulant use had a larger negative impact on XR-NTX initiation compared to buprenorphine, especially in the rural population (76% reduction, aHR = 0.24, 0.08-0.69, p = 0.008). CONCLUSIONS: Stimulant use is a barrier to buprenorphine or XR-NTX initiation in clinical trials and real-world populations that would benefit from OUD treatment. Interventions to address stimulant use among patients with OUD are urgently needed, especially among rural people injecting drugs, who already suffer from limited access to MOUD.

Combined effects of HIV and obesity on the gastrointestinal microbiome of young men who have sex with men.

OBJECTIVES: The prevalence of obesity is rising among people living with HIV, which may synergistically increase inflammation and the risk of associated diseases. Disruption of gut bacterial communities may be one of the key drivers of this inflammation; however, the combined effects of HIV and obesity on the microbiome have not been explored. METHODS: This study included 381 men who have sex with men. Thirty-nine were HIV-positive and obese (H+O+), 143 were HIV-positive and nonobese, 64 were HIV-negative and obese, and 135 were HIV-negative and nonobese. Microbiome composition was assessed by targeted sequencing of the V4 region of the 16S ribosomal RNA (rRNA) gene using rectal swab samples. Inverse probability of treatment-weighted marginal structural models were used to investigate differences in microbial composition between groups while controlling for numerous clinical and behavioural confounders. RESULTS: Significant variability in microbial composition was explained by the combination of HIV and obesity, over and above each condition alone (R2 for the marginal contribution of the H+/O+ group = 0.008; P = 0.001). H+O+ participants had the highest ratios of Prevotella to Bacteroides, a pro-inflammatory enterotype that has been described in HIV infection and obesity independently. H+O+ participants had lower levels of Bacteroides and Veillonella than all other groups, suggesting a synergistic effect of HIV and obesity on these genera. CONCLUSIONS: Our findings support the hypothesis that HIV and obesity act together to disrupt gut microbial communities, which may help explain higher levels of generalized inflammation among people living with both HIV and obesity.

A Bayesian Analysis of Prenatal Maternal Factors Predicting Nonadherence to Infant HIV Medication in South Africa.

While efforts to prevent mother-to-child transmission of HIV been successful in some districts in South Africa, rates remain unacceptably high in others. This study utilized Bayesian logistic regression to examine maternal-level predictors of adherence to infant nevirapine prophylaxis, including intimate partner violence, maternal adherence, HIV serostatus disclosure reaction, recency of HIV diagnosis, and depression. Women (N = 303) were assessed during pregnancy and 6 weeks postpartum. Maternal adherence to antiretroviral therapy during pregnancy predicted an 80% reduction in the odds of infant nonadherence [OR 0.20, 95% posterior credible interval (.11, .38)], and maternal prenatal depression predicted an increase [OR 1.04, 95% PCI (1.01, 1.08)]. Results suggest that in rural South Africa, failure to provide medication to infants may arise from shared risk factors with maternal nonadherence. Intervening to increase maternal adherence and reduce depression may improve adherence to infant prophylaxis and ultimately reduce vertical transmission rates.

Minimizing photobleaching during confocal microscopy of fluorescent probes bound to chromatin: role of anoxia and photon flux.

Exposure to light can destroy the ability of a molecule to fluoresce. Such photobleaching limits the use of fluorescence and confocal microscopy in biological studies. Loss of fluorescence decreases the signal-to-noise ratio and so image resolution; it also prevents the acquisition of meaningful data late during repeated scanning (e.g. when collecting three-dimensional images). The aim of this work was to investigate the role of oxygen in the photobleaching of fluorophores bound to DNA in fixed cells, and to explore whether anoxia could minimize such bleaching. Anoxia significantly reduced bleaching rates and changed the order of reaction of both propidium iodide (an intercalator) and chromomycin A3 (a minor-groove binder) bound to DNA; it afforded the greatest protection at low photon fluxes. However, it had no effect on the bleaching of the green fluorescent protein (GFP) covalently attached to a histone and so bound to DNA, probably because the protein shielded the chromophore from oxygen. Bleaching of all three fluorophores depended on photon flux. Practical ways of minimizing bleaching were examined, and examples of three-dimensional images of DNA marked by propidium and GFP (collected under standard and optimized conditions) are presented.

Breast implants and cancer: causation, delayed detection, and survival.

Concern for many women with breast implants has been focused on three topics: cancer (both breast and other cancers), delayed detection of breast cancer, and increased breast cancer recurrence or decreased length of survival. In this study, a qualitative review of the literature on these subjects was conducted, coupled with a meta-analysis of the risk for breast cancer or other cancers (excluding that of the breast). Researchers have consistently found no persuasive evidence of a causal association between breast implants and any type of cancer. The meta-analysis results obtained by combining the epidemiology studies support the overall conclusion that breast implants do not pose any additional risk for breast cancer (relative risk, 0.72; 95% confidence interval, 0.61 to 0.85) or for other cancers (relative risk, 1.03; 95% confidence interval, 0.87 to 1.24). This analysis suggests that breast implants may confer a protective effect against breast cancer. Women with implants should be reassured by the consistency of scientific studies which have uniformly determined that, compared with women without implants, they are not at increased risk for cancer, are not diagnosed with later-stage breast malignancies, are not at increased risk for breast cancer recurrence, and do not have a decreased length of survival.

The prevalence of breast implants among women in the United States.

Estimates of the number of women with breast implants have varied from less than one million to over three million. Most of these appear to be extrapolations from either industry production figures or reports of surgical procedures. In late 1989 under contract to the Dow Corning Corporation, Market Facts, Inc. conducted a mail survey of 40,000 households selected to be representative of the population of the United States. They received responses from 70.7%. Based upon the data collected, 8.08 per 1,000 women in the United States reported ever having had some type of breast implant. Approximately 60% of the procedures had been done for cosmetic reasons. Most of the women were White (94.6%) and rates were highest in the South or West. Although younger women were more likely to have had implants for augmentation and older women for reconstruction presumptively following breast cancer surgery, the largest prevalences for either of the two procedures were in the 45 to 54 year old age group. Breast implant prevalence also increased in direct proportion to household income with the largest increases being related to cosmetic augmentation. Based upon the data collected in this survey, the total number of women in the United States in late 1989 who had ever had breast implants was estimated to be 815,700 (95% confidence interval: 715,757-924,729).

A meta-analysis of breast implants and connective tissue disease.

Case reports have raised questions about an increased risk of connective tissue diseases (CTDs) among women with breast implants. From the reviews of more than 2,600 manuscripts, abstracts, and dissertations, this meta-analysis included 13 epidemiology studies that provided a relative risk (RR) estimate for the possible association between breast implants and CTDs. The meta-analysis summary RR was 0.76 for CTD in general (95% confidence interval [CI]: 0.55, 1.04; homogeneity p-value = 0.073) and was 0.98 for scleroderma (95% CI: 0.57, 1.64; homogeneity p = 0.006). Irrespective of which studies were aggregated in this meta-analysis, there was no significant increased risk for scleroderma, rheumatoid arthritis, or CTD in general. Conclusions from this study are consistent with the most recent review by the British Medical Devices Agency that found no scientific evidence to date of an increased risk of CTD associated with silicone gel breast implants.

The prevalence of women with breast implants in the United States--1989.

Most estimates of the number of women with breast implants appear to be extrapolations of industry or clinical data. While both provide valuable information, the former about the total number of devices ever produced or sold and the latter about the cumulative number of surgeries performed, neither can be used to directly estimate the prevalence of women with silicone gel or saline implants. In 1989, Market Facts, Inc., conducted a mail survey of 40,000 households chosen as representative of the population of the United States and received responses from 70.7%. Overall, the prevalence was 8.08 per 1,000 women with about 60% of the devices reportedly implanted for cosmetic reasons. The procedure was more common among Whites of the higher socio-economic classes. Based upon the results of this survey, the total number of US women in 1989 with breast implants was estimated to be 815,700 (95% confidence interval: 715,757-924,729).

The breast implant controversy.

The breast implant issue is a "bad news/good news" story. For many women with implants, the controversy has caused a fair degree of anxiety which may or may not be resolved as further information becomes available. It has also taken its toll on Dow Corning. Whole lines of medical products have been eliminated or are being phase out. The development of new medical applications has been terminated. As a consequence, employees have lost their jobs. What the effect will be on the biomedical industry as a whole remains to be seen (11). While silicones have been an important component in various medical devices, it is likely that other materials can be used as replacements. However, suppliers of non-silicone materials are also reevaluating their role in this market. For example, Du Pont, the nation's largest chemical company, has determined that the unpredictable and excessive costs of doing business with manufacturers of implantable medical devices no longer justifies the unrestricted sale of standard raw materials into this industry. Other companies are quietly following suit. On the up side, it is possible that the research being driven by this controversy will result in a greater understanding of the immunologic implications of xenobiotics, of the importance of nonbiased observations, of the need for ready access to valid data sets, and of the opportunity for valid scientific information to guide legal decisions. Only time will tell.

An update of mortality among chemical workers potentially exposed to the herbicide 2,4-dichlorophenoxyacetic acid and its derivatives.

Four years of additional mortality follow-up through 1986 are reported for a previously studied cohort of 878 chemical workers who were potentially exposed to 2,4-dichlorophenoxyacetic acid (2,4-D) and its derivatives between 1945 and 1983. Observed mortality was compared with expected levels based on death rates of the US population and of 36,804 "unexposed" workers from the same manufacturing location. Non-Hodgkin's lymphoma (NHL) was a particular focus of the study because of a suggested association with 2,4-D exposure in some case-control studies. For the total observation period, the standardized mortality ratios for all causes and for malignant neoplasms were 92 and 91, respectively. Analyses using the internal comparison group yielded virtually identical results. The initial study had found two deaths from NHL, both of which occurred under circumstances (ie, short latency and modest exposure) which made it less plausible that they were related to 2,4-D exposure. No new deaths from NHL were observed in the extended follow-up period and mortality for this cause showed a nonstatistically significant excess (standardized mortality ratio, 196; 95% confidence interval 24 to 708) for the total observation period. Analyses by production area, and by two different measures of exposure, combined with two different approaches to account for latency, did not show patterns suggestive of a causal relationship between exposure to 2,4-D or its derivatives and any particular cause of death.