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..

Low body mass index and latent tuberculous infection: a systematic review and meta-analysis.

BACKGROUND: The well-documented association between underweight and increased incidence of active tuberculosis (TB) has not been extended to incidence or prevalence of latent tuberculous infection (LTBI). DESIGN: After identifying studies that reported a categorical measure of body mass index (BMI) and used the tuberculin skin test (TST) or QuantiFERON®-TB Gold In-Tube (QFT) to measure LTBI, a maximum likelihood random-effects model was used to examine the pooled association between LTBI and low BMI (<18.5 kg/m2), compared with 1) normal BMI (18.5-25 kg/m2) and 2) a complementary group of all others, i.e., non-underweight subjects (BMI 18.5 kg/m2). RESULTS: Among studies using TST, the odds ratios (ORs) showed a slight, non-statistically significant decrease in the odds of TST positivity in underweight persons compared with both groups (non-underweight, OR 0.88, 95%CI 0.73-1.05; normal weight, OR 0.96, 95%CI 0.77-1.20). Among studies using QFT, the OR suggested slightly decreased, yet non-significant, odds of QFT positivity in underweight compared with non-underweight subjects (OR 0.92, 95%CI 0.68-1.26), and significantly decreased odds of QFT positivity in underweight compared with normal weight subjects (OR 0.84, 95%CI 0.73-0.98). CONCLUSION: These results suggest that underweight persons are not at an increased risk of LTBI. Screening this population for LTBI would not increase the yield of identified LTBI.

Eighteen- to 30-year-olds more likely to link to hepatitis C virus care: an opportunity to decrease transmission.

Hepatitis C virus (HCV) infection incidence among 18- to 30-year-olds is increasing and guidelines recommend treatment of active injection drug users to limit transmission. We aimed to : measure linkage to HCV care among 18- to 30-year-olds and identify factors associated with linkage; compare linkage among 18- to 30-year-olds to that of patients >30 years. We used the electronic medical record at an urban safety net hospital to create a retrospective cohort with reactive HCV antibody between 2005 and 2010. We report seroprevalence and demographics of seropositive patients, and used multivariable logistic regression to identify factors associated with linkage to HCV care. We defined linkage as having evidence of HCV RNA testing after reactive antibody. Thirty two thousand four hundred and eighteen individuals were tested, including 8873 between 18 and 30 years. The seropositivity rate among those ages 18-30 was 10%. In multivariate analysis, among those 18-30, diagnosis location (Outpatient vs Inpatient/ED) (OR 1.78, 95% CI 1.28-2.49) and number of visits after diagnosis (OR 5.30, 95% CI 3.91-7.19) were associated with higher odds of linking to care. When we compared linkage in patients ages 18-30 to that among those older than 30, patients in the 18-30 years age group were more likely to link to HCV care than those in the older cohort even when controlling for gender, ethnicity, socioeconomic status, birthplace, diagnosis location and duration of follow-up. Eighteen- to 30-year-olds are more likely to link to HCV care than their older counterparts. During the interferon-free treatment era, there is an opportunity to prevent further HCV transmission in this population.

Clinical impact of treatment timing for chronic hepatitis C infection: a decision model.

Recent advances in the treatment of hepatitis C virus (HCV) infection have led to the availability of both highly efficacious interferon-containing and interferon-sparing regimens. However, the use of such therapies faces restrictions due to high costs. For patients who are medically eligible to receive interferon, the choice between the two will likely be impacted by preferences surrounding interferon, severity of disease, coverage policies and out-of-pocket costs. We developed a decision model to quantify the trade-offs between immediate, interferon-containing therapy and delayed, interferon-free therapy for patients with chronic, genotype 1 HCV infection. We projected the quality-adjusted life expectancy stratified by the presence or absence of cirrhosis for four strategies: (i) no treatment; (ii) immediate, one-time treatment with an interferon-containing regimen; (iii) immediate treatment as above with the opportunity for retreatment in patients who fail to achieve sustained virologic response with interferon-free therapy in 1 year; and (iv) delayed therapy with interferon-free therapy in 1 year. When compared to one-time immediate treatment with the interferon-containing regimen, delayed treatment with the interferon-free regimen in 1 year resulted in longer life expectancy, with a 0.2 quality-adjusted life year (QALY) increase in noncirrhotic patients, and a 1.1 QALY increase in patients with cirrhosis. This superiority in health benefits was lost when wait time for interferon-free therapy was greater than 3-3.2 years. In this modelling analysis, interferon-free therapy resulted in superior health benefits compared to immediate therapy with interferon until wait time exceeded 3-3.2 years. Such data can inform decision-making regarding treatment initiation for HCV as healthcare financing evolves.

The impact of HIV/HCV co-infection on health care utilization and disability: results of the ACTG Longitudinal Linked Randomized Trials (ALLRT) Cohort.

HIV/hepatitis C virus (HCV) co-infection places a growing burden on the HIV/AIDS care delivery system. Evidence-based estimates of health services utilization among HIV/HCV co-infected patients can inform efficient planning. We analyzed data from the ACTG Longitudinal Linked Randomized Trials (ALLRT) cohort to estimate resource utilization and disability among HIV/HCV co-infected patients and compare them to rates seen in HIV mono-infected patients. The analysis included HIV-infected subjects enrolled in the ALLRT cohort between 2000 and 2007 who had at least one CD4 count measured and completed at least one resource utilization data collection form (N = 3143). Primary outcomes included the relative risk of hospital nights, emergency department (ED) visits, and disability days for HIV/HCV co-infected vs HIV mono-infected subjects. When controlling for age, sex, race, history of AIDS-defining events, current CD4 count and current HIV RNA, the relative risk of hospitalization, ED visits, and disability days for subjects with HIV/HCV co-infection compared to those with HIV mono-infection were 1.8 (95% CI: 1.3-2.5), 1.7 (95% CI: 1.4-2.1), and 1.6 (95% CI: 1.3-1.9) respectively. Programs serving HIV/HCV co-infected patients can expect approximately 70% higher rates of utilization than expected from a similar cohort of HIV mono-infected patients.

New York State pharmacists' attitudes toward needle and syringe sales to injection drug users before implementation of syringe deregulation.

In May 2000, New York State passed legislation permitting the sale, purchase, and possession of up to 10 needles and syringes without a prescription. The law is intended to reduce the transmission of human immunodeficiency virus (HIV) and hepatitis among injection drug users (IDUs), their sexual partners, and their children. To obtain baseline information about the attitudes and likely practices of New York State pharmacists, we distributed a self-administered questionnaire to attendees of the state pharmacy association meeting in June 2000. Of 48 usable responses, 19% were from New York City and the rest from New York State. Of the 48, 42% were unaware of the new law before the day of the survey, and 60% were somewhat or very willing to sell needles and syringes to an IDU. Of those who were not willing to sell to an IDU, 82% cited familiarity of the customer as a very important consideration in their decision making. Those who were not willing to sell to an IDU were more concerned about the detrimental impact of syringe sales on the community, were less likely to be aware of the new law, and were more likely to be concerned about legal liability for syringe sales. Over 80% of all pharmacists believed that syringe sales to IDUs are an important preventive health measure. The majority also favored learning more about the law. Compared to other state surveys of pharmacists, these preliminary data show a similar level of interest in becoming involved with syringe availability programs.

New York City pharmacists' attitudes toward sale of needles/syringes to injection drug users before implementation of law expanding syringe access.

In May 2000, New York State passed legislation permitting the sale, purchase, and possession of up to 10 needles and syringes (hereafter "syringes") without a prescription, intended to reduce blood-borne pathogen transmission among injection drug users (IDUs). To obtain baseline data on pharmacists' attitudes and practices related to human immunodeficiency virus (HIV) prevention and IDUs, a telephone survey was administered to 130 pharmacists systematically selected in New York City. Less than half of pharmacists were aware of the new law; 49.6% were willing to or supported providing nonprescription sales of syringes to IDUs. Pharmacists in support tended to be less likely to consider customer appearance "very important." Managing and supervising pharmacists were more likely than staff pharmacists to support syringe sales to IDUs. Managing and supervising pharmacists who stocked packs of 10 syringes and personal sharps disposal containers, pharmacists who supported syringe exchange in the pharmacy, and pharmacists who were willing to sell syringes to diabetics without a prescription were more likely to support syringe sales to IDUs. Syringe disposal was a prominent concern among all pharmacists. Those not in support of syringe sales to IDUs tended to be more likely to believe the practice would increase drug use. These data suggest the need for initiatives to address concerns about syringe disposal and tailored continuing education classes for pharmacists on HIV and viral hepatitis prevention among IDUs.

Physician resource use and willingness to participate in assisted suicide.

OBJECTIVE: To explore the relationship between general internists' tendency to conserve medical resources and their willingness to participate in physician-assisted suicide (PAS). DESIGN AND PARTICIPANTS: Survey of a random sample of general internists in 6 urban areas of the United States. MEASUREMENTS: We assessed the physicians' use of medical resources by constructing a scale based on 6 hypothetical clinical scenarios in which respondents were given a choice between resource-intensive and resource-conserving options. We then presented a scenario of a competent terminally ill patient with breast cancer making stable and persistent requests for PAS. RESULTS: Sixty-seven (33%) of the 206 respondents indicated that they would participate in the suicide of the depicted patient. In a multivariate model, physicians who were more conservative with resources were 6.4 times more likely than their resource-intensive counterparts to prescribe the requested drugs (P = .02); minority physicians were less willing than whites to participate in PAS (odds ratio, 0.34; P = .03). Physicians' number of years in practice, location, sex, reported percentage of fee-for-service patients, and self-reported strength and direction of financial incentives in the respondents' practices were not associated with willingness to prescribe drugs for PAS. CONCLUSIONS: Most general internists, especially minority physicians, are personally reluctant to participate in PAS. While the characteristics of their practices do not affect PAS, physicians who tend to practice resource-conserving medicine are significantly more likely than their resource-intensive counterparts to provide a lethal prescription at the request of a terminally ill patient.

Pharmacoeconomics: state of the art in 1997.

Economic evaluation of pharmaceutical products, or pharmacoeconomics, is a rapidly growing area of research. Pharmacoeconomic evaluation is important in helping clinicians and managers make choices about new pharmaceutical products and in helping patients obtain access to new medications. Over the last few years, the scientific rigor of this field has increased greatly. At the same time, new types of analysis, based on prospective data collection, have been developed. This article reviews the basic concept of pharmacoeconomics, the types of data available for economic evaluation, and the "state of the art" in pharmacoeconomics as reported in the medical literature.

Evaluation of quality of life for diverse patient populations.

Quality of life is used increasingly as a primary and secondary endpoint of clinical investigations of new therapies. Quality of life information may be especially useful for the assessment of cancer treatments, where increases in survival may be accompanied by detrimental side effects. The recognition of the importance of quality of life has led to the recent proliferation of cancer specific quality of life instruments. As more is understood about the heterogeneity of patient populations, however, we must assess how culturally defined factors may impact patient quality of life and its assessment. Quality of life instruments are diverse, ranging from those focusing on objective measures of functionality to those assessing subjective measures of patient preferences for their current health state. These instruments have been developed for use in the general population and for disease-specific populations. Assessment of the appropriateness of potential quality of life instruments in specific clinical settings, in addition to understanding the cultural diversity of the clinical population being studied, will guide the researcher in the choice of an appropriate quality of life instrument for cancer clinical trials.