Strategies for isoniazid preventive therapy in HIV-positive patients who consume alcohol.

WHO guidance to defer isoniazid preventive therapy (IPT) among those with regular alcohol use because of hepatotoxicity concerns may exclude many people living with HIV (PLWH) at high TB risk in these settings.To evaluate hepatotoxicity during TB preventive therapy (TPT) in PLWH who report alcohol use in Uganda over 10 years.We developed a Markov model of latent TB infection, isoniazid preventive therapy (IPT - a type of TPT), and TB disease using data from the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) study. We modeled several treatment scenarios, including no IPT, IPT with liver enzyme monitoring (AST/ALT) during treatment, and IPT with pre-screening using the tuberculin skin test (TST).The no IPT scenario had 230 TB deaths/100,000 population over 10 years, which is more than that seen in any IPT scenario. IPT, even with no monitoring, was preferred over no IPT when population TB disease incidence was >50 in 100,000.For PLWH who report alcohol use in high TB burden settings, IPT should be offered, ideally with regular AST/ALT monitoring. However, even if regular monitoring is not possible, IPT is still preferable to no IPT in almost every modeled scenario..

Prevalence of, and factors associated with, alcohol use disorder among young adults (aged 15-24 years) living with HIV/AIDS in low-income and middle-income countries: protocol for a systematic review.

INTRODUCTION: Alcohol use is a global driver of HIV infection and disease progression, mediated through risky behaviour and poor antiretroviral adherence. Most studies about the burden of alcohol use among people living with HIV (PLWH)/AIDS have been done in adult populations, but less is known about young people with HIV, especially in low-income and middle-income countries (LMICs), despite the high level of alcohol use in these settings. The aim of this review is to collate evidence on the prevalence of, and factors associated with, alcohol use disorder (AUD) among young adults (aged 15-24 years) living with HIV/AIDS in LMICs. METHODS AND ANALYSIS: Two experienced librarians will conduct an independent article search in PubMed, PsycINFO, Embase and Web of Science databases, using relevant Medical Subject Headings terms and Boolean operators ('AND', 'OR'). We will include English-language articles that were published in peer-reviewed journals from 1 January 2000, to 25 July 2022, that documented the prevalence of AUD among young people (15-24 years) living with HIV in LMICs. We shall exclude systematic review articles and qualitative studies. Two independent reviewers will screen the articles for eligibility and data will be extracted onto a preset Excel spreadsheet. Data analysis will be done using Stata V.14.0. Heterogeneity will be assessed by use of the I2 statistic and data will be pooled in meta-analyses where appropriate. Publication bias will be assessed using the funnel plot. ETHICS AND DISSEMINATION: Ethical approval is not needed as this systematic review will be based on published studies. Findings from this study will be disseminated via submission for publication in a peer-reviewed journal, at conference presentations, and made available to health professionals, scientists and policy makers. Our data set can be made available on request. REGISTRATION DETAILS: PROSPERO, CRD42022308955.

Microbiology of community-acquired bacterial pneumonia in persons with and at risk for human immunodeficiency virus type 1 infection. Implications for rational empiric antibiotic therapy.

BACKGROUND: Bacterial pneumonia is a very common cause of morbidity and mortality among persons with human immunodeficiency virus; however, the microbiologic characteristics (including antibiotic resistance) of bacterial pathogens causing community-acquired pneumonia in this population have not been well characterized or correlated with potentially predictive clinical presentation characteristics. METHODS: We conducted a retrospective cohort study of all adults known to have or to be at high risk for human immunodeficiency virus infection and hospitalized at San Francisco (Calif) General Hospital from May 1990 through April 1991, with a hospital discharge diagnosis of community-acquired bacterial pneumonia and for whom a medical records review confirmed that this diagnosis met a uniform case definition. RESULTS: Two hundred sixteen eligible patients had one or more hospital admissions meeting the case definition. One or more etiologic pathogens were definitively identified in 75% of cases, with Streptococcus pneumoniae, Haemophilus species, Staphylococcus aureus, and gram-negative bacilli most frequently identified. In patients who had a bacteriologic diagnosis made, 18.6%, 6.8%, and 4.3% had pneumonia caused by pathogens resistant to ampicillin sodium, cefuroxime sodium, or trimethoprim-sulfamethoxazole, respectively. One hundred percent of pathogens isolated were susceptible to ceftazidime. Anemia and use of antibacterial medication at the time of hospital admission were the only independent predictors of ampicillin and cefuroxime resistance. CONCLUSION: Nearly one fifth of human immunodeficiency virus-associated community-acquired bacterial pneumonias requiring hospitalization were caused by ampicillin-resistant pathogens, and presenting clinical characteristics did not consistently define a subset of patients at lower risk for resistance. In the absence of a diagnostic sputum Gram's stain and pending definitive microbiologic diagnosis, initial empiric therapy should be with a second- or third-generation cephalosporin or possibly trimethoprim-sulfamethoxazole.

Tuberculosis prophylaxis in the homeless. A trial to improve adherence to referral.

BACKGROUND: Adherence to tuberculosis evaluation is poor in a high-risk population such as the homeless. OBJECTIVE: To test two interventions aimed at improving adherence to tuberculosis evaluation and to identify predictors of adherence. METHODS: We conducted a randomized clinical trial in shelters and food lines in the inner city of San Francisco, Calif. We randomized 244 eligible subjects infected with tuberculosis to (1) peer health adviser (assistance by a peer [n = 83]), (2) monetary incentive ($5 payment [n = 82]), or (3) usual care (referral slips and bus tokens only [n = 79]). The primary outcome of the study was adherence to a first follow-up appointment at the tuberculosis clinic, where subjects were evaluated for active tuberculosis and the need for isoniazid prophylaxis. RESULTS: Of the subjects assigned to a monetary incentive, 69 (84%) completed their first follow-up appointment, compared with 62 subjects (75%) assigned to a peer health adviser and 42 subjects (53%) assigned to usual care. Adherence was higher in the monetary incentive and peer health adviser groups than in the usual care group (P < .001 and P = .004, respectively). Patients not using intravenous drugs and patients 50 years of age or older were more likely to adhere to a first follow-up appointment (odds ratios [95% confidence intervals], 2.5 [1.3 to 5.0] and 3.3 [1.2 to 8.8], respectively). Among the 173 tuberculosis-infected subjects who completed their appointment, isoniazid therapy was started for 72 individuals, and three cases of active tuberculosis were identified. CONCLUSION: A monetary incentive or a peer health adviser is effective in improving adherence to a first follow-up appointment in homeless individuals infected with tuberculosis. A monetary incentive appears to be superior. Intravenous drug users and young individuals are at high risk for poor adherence to referral.

Adherence to isoniazid prophylaxis in the homeless: a randomized controlled trial.

OBJECTIVES: To test 2 interventions to improve adherence to isoniazid preventive therapy for tuberculosis in homeless adults. We compared (1) biweekly directly observed preventive therapy using a $5 monetary incentive and (2) biweekly directly observed preventive therapy using a peer health adviser, with (3) usual care at the tuberculosis clinic. METHODS: Randomized controlled trial in tuberculosis-infected homeless adults. Outcomes were completion of 6 months of isoniazid treatment and number of months of isoniazid dispensed. RESULTS: A total of 118 subjects were randomized to the 3 arms of the study. Completion in the monetary incentive arm was significantly better than in the peer health adviser arm (P = .01) and the usual care arm (P = .04), by log-rank test. Overall, 19 subjects (44%) in the monetary incentive arm completed preventive therapy compared with 7 (19%) in the peer health adviser arm (P = .02) and 10 (26%) in the usual care arm (P = .11). The median number of months of isoniazid dispensed was 5 in the monetary incentive arm vs 2 months in the peer health adviser arm (P = .005) and 2 months in the usual care arm (P = .04). In multivariate analysis, independent predictors of completion were being in the monetary incentive arm (odds ratio, 2.57; 95% CI, 1.11-5.94) and residence in a hotel or other stable housing at entry into the study vs residence on the street or in a shelter at entry (odds ratio, 2.33; 95% CI, 1.00-5.47). CONCLUSIONS: A $5 biweekly cash incentive improved adherence to tuberculosis preventive therapy compared with a peer intervention or usual care. Living in a hotel or apartment at the start of treatment also predicted the completion of therapy.

Release of immunoassayable prostaglandin E by the human ischemic kidney.

Immunoassayable prostaglandin E concentration in renal venous plasma was measured in eight patients with renovascular hypertension. Two subjects with bilateral renal artery stenosis had similar concentrations from both renal veins. The six subjects with unilateral artery stenosis had greater concentration on the stenotic side in each case, suggesting that the human ischemic kidney produces increased amounts of prostaglandins.

Loss of Rb expression in an ACTH-secreting pituitary carcinoma.

Little is known about the molecular mechanisms of tumor progression in the pituitary. However, animal studies suggest that the Rb gene may be involved in the development of pituitary carcinoma. Pathologic examination of a pituitary tumor that included both benign and malignant components provided insight into this mechanism. Both benign and malignant tumors were immunoreactive for ACTH. The benign adenoma showed strong nuclear immunoreactivity for Rb, however, both the adjacent sellar carcinoma and its metastases were Rb-negative. This study suggests that loss of Rb may in some cases be important in the progression of pituitary adenoma to carcinoma.

Cost efficient sampling design for quality control of a birth defects registry.

Quality control studies of registries are frequently conducted. We employed a cost effective sampling scheme for assessing the quality of case identification and abstracting in one birth defects registry. The general sampling method was a stratified two-stage design, and the optimal sample size for each stratum was chosen to minimize cost, which was defined as time for data collection. The resulting sample sizes depended on the variability in the number of abstracts between and within data collection facilities, and the amount of time needed to complete each data collection step. The most time effective scheme was to visit several facilities each for a short period of time rather than fewer facilities for a longer period of time. Cost efficient sampling strategies, such as the method used here, can be applied to ensure precision in registry quality control analyses and other public health studies.

Can the poor adhere? Incentives for adherence to TB prevention in homeless adults.

SETTING: Community-based population of homeless adults living in San Francisco, California. OBJECTIVE: To compare the effect of cash and non-cash incentives on 1) adherence to treatment for latent tuberculosis infection, and 2) length of time needed to look for participants who missed their dose of medications. DESIGN: Prospective, randomized clinical trial comparing a 5 dollar cash or a 5 dollar non-cash incentive. All participants received directly observed preventive therapy and standardized follow-up per a predetermined protocol. Completion rates and amount of time needed to follow up participants was measured. RESULTS: Of the 119 participants, 102 (86%) completed therapy. There was no difference between the cash and non-cash arms. Completion was significantly higher among males (OR 5.65, 95%CI 1.36-23.40, P = 0.02) and persons in stable housing at study entry (OR 4.86, 95%CI 1.32-17.94, P = 0.02). No substance use or mental health measures were associated with completion. Participants in the cash arm needed significantly less follow-up to complete therapy compared to the non-cash arm (P = 0.03). In multivariate analysis, non-cash incentive, use of crack cocaine, and no prior preventive therapy were associated with more follow-up time. CONCLUSION: Simple, low cost incentives can be used to improve adherence to TB preventive therapy in indigent adults.

Quality control of birth defect registry data: a case study.

The California Birth Defects Monitoring Program maintains a population-based registry of children born with congenital malformations. Trained data collectors routinely visit hospitals and genetics centers to identify cases and abstract information. These data are provided to the public health, medical, and lay communities and are used for conducting prevalence and case-control studies. A stratified sample of each data collector's work for one data year was reevaluated to assess the quality of case ascertainment and record abstraction. The sample included data from 109 facilities (37 percent) and 729 abstracts (5 percent). There are three steps in data collection: case-finding, the process of identifying potential cases; culling, the process of reviewing the charts of potential cases to determine which are reportable; and abstracting, the process of recording information from the charts of reportable cases. The probability that a potential case is missed during casefinding is 7 percent for small facilities, 4 percent for medium facilities, and 1 percent for large facilities. The probability that a reportable case is mistakenly classified as not reportable during culling is 3 percent for small and medium facilities and 1 percent for large facilities. The probabilities of incorrectly abstracting selected diagnoses and demographic items are slightly higher (8 percent for small and medium facilities and 6 percent for large facilities) because these are more complex processes than are casefinding and culling. Finally, the overall probability of missing a case from the registry is 3 percent. Therefore, these data indicate that the information collected by this registry are both reliable and complete.

Overdosing among young injection drug users in San Francisco.

Heroin overdoses increased sharply in the US in the 1990s, but few studies have addressed overdose risk. We examined overdosing and injection-related risk behavior in young injection drug users (IDUs). We interviewed all consenting injectors under age 30 at needle exchanges and youth outreach sites in San Francisco. Their median age was 22, and their median number of years of injecting was 4. About 48% reported at least one overdose, with a median of two overdoses reported. Overdosing was associated with injecting "speedballs" (i.e. mixtures of heroin and cocaine), with borrowing syringes, and (with P-values of borderline statistical significance) with heroin injection and with gay or bisexual behavior. It was not associated with age, sex, years of injecting, or frequency of injecting. In multivariate analysis, only borrowing syringes and gay or bisexual behavior were independent statistically significant predictors, probably because gay and bisexual subjects were more likely to be heroin or "speedball" injectors. Most subjects (65%) reported that they had not received medical attention at time of last overdose. Risk of overdose in young injectors is acute and closely associated with HIV risk. HIV interventions should include overdose prevention. Emergency response protocols should minimize risk of arrest. Injectors and providers should be trained in overdose prevention, and developing overdose interventions should be a priority among drug educators.

Demystifying quality assurance.

At Methodist Hospital of Indiana, trustees participate as observers on certain medical staff committees. In addition to its educational and other advantages, the method has helped to increase understanding between trustees and medical staff members.

Hepatitis B virus infection and immunization status in a new generation of injection drug users in San Francisco.

Hepatitis B virus (HBV) infection is common among injection drug users (IDU). Younger IDU, however, may be less susceptible to infection due to the implementation of public health interventions, such as universal immunization programs and syringe exchange programs. To investigate the current epidemiology of HBV infection and control among a new generation of drug users in the United States, we conducted interviews and examined HBV serologic markers in a cross-section of street-recruited IDU under age 30 in San Francisco, CA. Of the 831 persons studied, 21% showed serologic evidence of current or past infection; 22% had isolated antibodies to hepatitis B surface antigen consistent with vaccine-mediated immunity; and 56% had no HBV markers. In multivariate analyses, HBV infection was associated with drug use behaviour in heterosexual males; sexual behaviour in males who have sex with males; and both drug use and sexual behaviour in females. Vaccine-mediated immunity was independently associated with female sex and younger age. In conclusion, HBV transmission persists among young IDU in San Francisco. Few young injectors show evidence of successful immunization and the majority remains susceptible to disease. Until the broad effects of universal vaccination are seen, targeted and innovative approaches to immunizing young IDU in the US are needed to prevent a substantial number of new HBV infections.