Cefazolin versus Nafcillin for Methicillin-Sensitive Staphylococcus aureus Bloodstream Infection in a California Tertiary Medical Center.

Recent observational studies have suggested possible reductions in mortality in patients receiving cefazolin versus antistaphylococcal penicillins. We examined 90-day mortality in patients receiving cefazolin compared to nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infection (BSI). We identified persons with MSSA BSI admitted to San Francisco General Hospital from January 2008 to July 2013 through a hospital-wide infection surveillance system and confirmed 90-day mortality using U.S. national vital registries. We included persons receiving cefazolin or nafcillin as the predominant intravenous antimicrobial agent; all participants received inpatient Infectious Diseases service consultation. We estimated the association between receipt of cefazolin and 90-day risk of death by multivariate logistic regression, including a propensity score for receiving cefazolin as the second predictor. Of 230 MSSA BSI cases, 30 received nafcillin and 70 received cefazolin as the predominant antimicrobial; 10 died within 90 days, 5 from each group. Unadjusted analysis showed substantial but not statistically significant reduced odds of death in those receiving cefazolin (odds ratio, 0.38; 95% confidence interval [CI], 0.10 to 1.44). Multivariate analysis with propensity scores found a similar adjusted odds ratio (0.40; 95% CI, 0.09 to 1.74; P = 0.22). We found a large reduction in 90-day mortality in those receiving cefazolin compared to nafcillin for MSSA BSI, but this finding was not statistically significant. The magnitude of effect seen in this and other studies justifies further study.

Developing WHO guidelines with pragmatic, structured, evidence-based processes: A case study.

Many guidelines, including those produced by the World Health Organisation (WHO), have failed to adhere to rigorous methodological standards. Operational examples of guideline development processes may provide important lessons learned to improve the rigour and quality of future guidelines. To this end, this paper describes the process of developing WHO guidelines on prevention and care interventions for adults and adolescents living with HIV. Using a pragmatic, structured, evidence-based approach, we created an organising committee, identified topics, conducted systematic reviews, identified experts and distributed evidence summaries. Subsequently, 55 global HIV experts drafted and anonymously submitted guideline statements at the beginning of a conference. During the conference, participants voted on statements using scales evaluating appropriateness of the statements, strength of recommendation and level of evidence. After review of voting results, open discussion, re-voting and refinement of statements, a draft version of the guidelines was completed. A post-conference writing team refined the guidelines based on pre-determined guideline writing principles and incorporated external comments into a final document. Successes and challenges of the guideline development process were identified and are used to highlight current issues and debates in developing guidelines with a focus on implications for future guideline development at WHO.

Antiretroviral regimens for patients with HIV who fail first-line antiretroviral therapy.

BACKGROUND: Highly active antiretroviral therapy has reduced the morbidity and mortality of patients with HIV/AIDS. A common first-line ART regimen includes a non-nucleoside reverse transcriptase inhibitor (NNRTI) and two nucleoside reverse transcriptase inhibitors (NRTIs). If treatment failure occurs, a change to second-line therapy is necessary. OBJECTIVES: This meta-analysis aimed to assess the optimum antiretroviral regimen for patients with HIV who fail first-line therapy (ART-naive) with d4T+3TC+NVP; d4T+3TC+EFV; ZDV+3TC+NVP; and ZDV+3TC+EFV. SEARCH STRATEGY: Electronic databases and conference proceedings were searched with relevant search terms without limits to language. SELECTION CRITERIA: Randomised controlled trials of HIV-infected adult patients administered second-line ART after virologic failure of a first-line regimen were included. The primary outcome measure included the proportion of patients achieving undetectable plasma HIV RNA concentration (viral load). Secondary outcome measures included change in mean CD4 cell count, clinical resolution of symptoms, rate of adverse events, rate of change in therapy for failure, rate of change in therapy for toxicity, and mortality. DATA COLLECTION AND ANALYSIS: Two authors assessed each reference for inclusion and exclusion criteria established a priori. Data were abstracted independently using a standardised abstraction form. MAIN RESULTS: Twenty-one records were identified in total, 6 of which were duplicates. None of the records met inclusion criteria. AUTHORS' CONCLUSIONS: There is insufficient evidence to evaluate second-line therapies in patients with HIV who fail first-line treatment with d4T+3TC+NVP; d4T+3TC+EFV; ZDV+3TC+NVP; and ZDV+3TC+EFV. Current recommendations are based on available resources and results from individualised treatment decisions based on resistance testing and clinician choice.

Antiretroviral post-exposure prophylaxis (PEP) for occupational HIV exposure.

BACKGROUND: Populations such as healthcare workers (HCWs), injection drug users (IDUs), and people engaging in unprotected sex are all at risk of being infected with the human immunodeficiency virus (HIV). Animal models show that after initial exposure, HIV replicates within dendritic cells of the skin and mucosa before spreading through lymphatic vessels and developing into a systemic infection (CDC 2001). This delay in systemic spread leaves a "window of opportunity" for post-exposure prophylaxis (PEP) using antiretroviral drugs designed to block replication of HIV (CDC 2001). PEP aims to inhibit the replication of the initial inoculum of virus and thereby prevent establishment of chronic HIV infection. OBJECTIVES: To evaluate the effects of antiretroviral PEP post-occupational exposure to HIV. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AIDSearch, and the Database of Abstracts of Reviews of Effectiveness were searched from 1985 to January 2005 to identify controlled trials. There were no language restrictions. Because no controlled clinical trials were retrieved, the search was repeated on 31 May 2005 in MEDLINE, AIDSearch and EMBASE using a search strategy to identify analytic observational studies. Handsearches of the reference lists of all pertinent reviews and studies found were also undertaken. Experts in the field of HIV prevention were contacted. SELECTION CRITERIA: Types of studies: All controlled trials (including randomized clinical trials and controlled clinical trials). If no controlled trials were found, analytic studies (e.g. cohort and case-control studies) were considered. Descriptive studies (i.e. studies with no comparison groups) were excluded. Types of participants included:HCWs exposed to any known or potentially HIV contaminated product;anyone exposed to a needlestick contaminated by known or potentially HIV-infected blood or other bodily fluid in an occupational setting; andanyone exposed through the mucous membranes to an HIV-infected or potentially infected substance in occupational setting.Excluded: Sex workers (PEP post-sexual exposure is addressed in another Cochrane review (Martín 2005)). Types of interventions: Any intervention that administered single or combinations of antiretrovirals as PEP to people exposed to HIV through percutaneous injuries and/or occupational mucous membrane exposures when the HIV status of the source patient was positive or unknown. Studies comparing two types of PEP regimens were considered, as were studies comparing PEP with no intervention. Types of outcome measures:Incidence of HIV infection in those given PEP versus those given placebo or a different PEP regimen; Adherence to PEP; Complications of PEPTypes of outcome measures: Incidence of HIV infection in those given PEP versus those given placebo or a different PEP regimen; Adherence to PEP; Complications of PEP DATA COLLECTION AND ANALYSIS: Data concerning outcomes, details of the interventions, and other study characteristics were extracted by two independent authors (TY and JA) using a standardized data extraction form (Table 04). A third author (GK) resolved disagreements. The following information was gathered from each included study: location of study, date, publication status, demographics (e.g. age, gender, occupation, risk behavior, etc.) of participants/exposure modality, form of PEP used, duration of use, and outcomes. Odds ratios with a 95% confidence interval (CI) were used as the measure of effect. A meta-analysis was performed for adverse events where two-drug regimens were compared with three-drug regimens. Due to overlap between Puro 2000 and Puro 2005, the former was not included in the combined analysis. MAIN RESULTS: Effect of PEP on HIV seroconversionNo randomized controlled trials were identified. Only one case-control study was included. HIV transmission was significantly associated with deep injury (OR 15, 95% CI 6.0 to 41), visible blood on the device (OR 6.2, 95% CI 2.2 to 21), procedures involving a needle placed in the source patient's blood vessel (OR 4.3, 95% CI 1.7 to 12), and terminal illness in the source patient (OR 5.6, 95% CI 2.0 to 16). After controlling for these risk factors, no differences were detected in the rates at which cases and controls were offered post-exposure prophylaxis with zidovudine. However, cases had significantly lower odds of having taken zidovudine after exposure compared to controls (OR 0.19, 95%CI 0.06 to 0.52). No studies were found that evaluated the effect of two or more antiretroviral drugs for occupational PEP. Adherence to and complications with PEPEight reports from observational comparative studies confirmed findings that adverse events were higher with a three-drug regimen, especially one containing indinavir. However, discontinuation rates were not significantly different. AUTHORS' CONCLUSIONS: The use of occupational PEP is based on limited direct evidence of effect. However, it is highly unlikely that a definitive placebo-controlled trial will ever be conducted, and, therefore, on the basis of results from a single case-control study, a four-week regimen of PEP should be initiated as soon as possible after exposure, depending on the risk of seroconversion. There is no direct evidence to support the use of multi-drug antiretroviral regimens following occupational exposure to HIV. However, due to the success of combination therapies in treating HIV-infected individuals, a combination of antiretroviral drugs should be used for PEP. Healthcare workers should be counseled about expected adverse events and the strategies for managing these. They should also be advised that PEP is not 100% effective in preventing HIV seroconversion. A randomized controlled clinical trial is neither ethical nor practical. Due to the low risk of HIV seroconversion, a very large sample size would be required to have enough power to show an effect. More rigorous evaluation of adverse events, especially in the developing world, are required. Seeing that current practice is partly based on results from individual primary animal studies, we recommend a formal systematic review of all relevant animal studies.

Stavudine, lamivudine and nevirapine combination therapy for treatment of HIV infection and AIDS in adults.

BACKGROUND: A favourable regimen for people infected with HIV/AIDS is one that provides optimal efficacy, durability of antiretroviral activity, tolerability, and has low adverse effects and drug-drug interactions. The combination of the non-nucleoside reverse transcriptase inhibitor nevirapine (NVP), and two nucleoside reverse transcriptase inhibitors, stavudine (d4T) and lamivudine (3TC), is widely used as first-line therapy, especially in low-resource countries. Analysis of the efficacy, durability and tolerability of the regimen is thus important to clinicians, consumers and policy-makers living in both rich and poor countries. OBJECTIVES: To examine the efficacy of the stavudine, lamivudine and nevirapine regimen for the treatment of HIV infection and AIDS in adults. SEARCH STRATEGY: We used the comprehensive search strategy developed specifically by the Cochrane HIV/AIDS Review Group to identify HIV/AIDS randomised controlled trials, and searched the following electronic databases: MEDLINE (searched July 2004); Embase (searched October 2004); and CENTRAL (July 2004). This search was supplemented with a search of AIDSearch (April 2005) to identify relevant conference abstracts, as well as searching reference lists of all eligible articles. The search was not limited by language or publication status. SELECTION CRITERIA: Randomised controlled trials of the stavudine, lamivudine and nevirapine regimen, compared with any other regimens for treating HIV/AIDS, in antiretroviral treatment-naive or antiretroviral treatment-experienced adults. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality of the trials and extracted data. MAIN RESULTS: Our search resulted in 1,148 records, of which two studies described trials that met our inclusion criteria. One trial was a small single-centre Australian trial of 70 antiretroviral-naive participants, while the other trial was a large, multicentre trial, conducted in 14 countries, of 1,216 antiretroviral-naive participants. In both trials over 60% of participants were male. As the therapeutic combinations compared in both trials were not identical, it was not possible to conduct a meta-analysis to increase the power of the results. The main findings, therefore, are from the much larger trial, which was of a high quality. This trial found that there was no statistically significant difference in the efficacy (measured by treatment failure) between nevirapine and efavirenz (EFZ), when used in combination with 3TC and d4T (RR = 1.16; 95%CI: 0.95, 1.41). There was no statistically significant difference between once daily or twice-daily dosing of NVP, when used in combination with 3TC and d4T (RR = 1.00; 95%CI: 0.83; 1.21). It also showed that, compared with NVP plus EFZ, 3TC and d4T, a once-daily dosing of NVP, in combination with 3TC and d4T, performs better in averting treatment failure (RR = 0.82; 95%CI: 0.67, 1.00) than does twice-daily dosing of NVP with 3TC and d4T (RR = 0.82; 95%CI: 0.69; 0.97). Frequency of toxicity was higher in participants receiving NVP, compared with EFZ. AUTHORS' CONCLUSIONS: The combination of nevirapine, 3TC and d4T is as efficacious as a combination of efavirenz, 3TC and d4T. Once-daily NVP with twice-daily 3TC and d4T is as efficacious as twice-daily NVP, 3TC and d4T. However, toxicity may be increased in the once-daily NVP regime. Additional trials of sufficient duration are required to provide better evidence for the use of this combination as a first line therapy. Ideally, trials should use standardised assessment measures especially with respect to measuring viral load, so that results can be compared and combined in meta-analyses.

A meta-analysis of the effect of high weight on asthma.

BACKGROUND: Prevalence rates for both overweight and asthma have been increasing among children in developed countries over the past two decades. Some recent studies have postulated a causal relation between these but have lacked power to form a definitive conclusion. AIM: To estimate the effect of high body weight in childhood on the future risk of asthma. METHODS: Medline search (1966 to October 2004), supplemented by manual search of reference lists and grey literature. Cohort studies that examined high body weight at birth or during childhood and future outcome of asthma were included. Data from each study were extracted on exposure status, clinical outcome, and study characteristics. RESULTS: A total of 402 studies were initially identified, of which 12 met the inclusion criteria. The combined results from four studies that examined the effect of high body weight during middle childhood on the outcome of subsequent asthma showed a 50% increase in relative risk (RR 1.5, 95% CI 1.2 to 1.8). The combined results from nine studies that examined the effect of high birth weight on subsequent asthma had a pooled RR of 1.2 (95% CI 1.1 to 1.3). There was consistency among the results in sensitivity analyses examining studies containing only estimates of odds ratios, studies containing only the outcome of physician diagnosis of asthma, and studies including all definitions of high body weight. CONCLUSIONS: Children with high body weight, either at birth or later in childhood, are at increased risk for future asthma. Potential biological mechanisms include diet, gastro-oesophageal reflux, mechanical effects of obesity, atopy, and hormonal influences. Further research might elucidate the causal pathway, which could improve our understanding of the pathophysiology of asthma and perhaps lead to knowledge of potential preventive interventions.

Antifungal interventions for the primary prevention of cryptococcal disease in adults with HIV.

BACKGROUND: Cryptococcal disease is an opportunistic infection that causes significant morbidity and mortality in adults with HIV. Primary prophylaxis with antifungal interventions may decrease cryptococcal disease incidence and associated mortality. OBJECTIVES: To assess the efficacy of antifungal interventions for the primary prevention of cryptococcal disease in adults with HIV. SEARCH STRATEGY: We searched the following databases: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), ClinicalTrials.gov, Database of Abstracts of Reviews of Effectiveness (DARE), Latin American and Caribbean Literature on the Health Sciences (LILACS), and the Cochrane Controlled Trials Register (CCTR). We reviewed abstracts from the following relevant conferences: International AIDS Conference, International AIDS Society Conference on HIV Pathogenesis and Treatment, and Conference on Retroviruses and Opportunistic Infections. We searched reference lists for all primary and other pertinent articles identified. We attempted to contact experts in the field, particularly primary authors of included studies, to better ensure completeness of included studies. We also approached pharmaceutical companies for any available and relevant unpublished data. The time period searched was from 1980 to August 2004. We placed no language restrictions on the search. Key words used include: meningitis, cryptococcal, cryptococcus, cryptococcosis, acquired immunodeficiency syndrome, human immunodeficiency virus, prophylaxis, chemoprevention, antifungal agents, and the Cochrane screen for randomized controlled trials. SELECTION CRITERIA: Randomized controlled trials using antifungal interventions for the primary prevention of cryptococcal disease in adults with HIV were selected. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and quality. Trial authors, experts, and pharmaceutical companies were contacted for additional and/or missing information. Data were abstracted by two reviewers. Data were pooled, where appropriate, to yield summary estimates. MAIN RESULTS: Five studies (N=1316) were identified. All study patients had CD4 cell counts <300 cells/microl, and the majority of patients had CD4 cell counts <150 cells/microl. When all five studies are analyzed as a single group (N=1316), the incidence of cryptococcal disease was decreased in those taking primary prophylaxis (RR 0.21, 95% CI 0.09, 0.46) compared to those taking placebo. However, there was no significant difference in overall mortality observed (RR 1.01, 95% CI 0.71, 1.44). When the three studies using itraconazole as the intervention were analyzed together (N=798), the incidence of cryptococcal disease was decreased in those taking itraconazole for primary prophylaxis (RR 0.12, 95% CI 0.03, 0.51) compared to those taking placebo; however, there was no significant difference in overall mortality (RR 1.12, 95% CI 0.70, 1.80). When the two studies using fluconazole as the intervention were analyzed together (N=518), the incidence of cryptococcal disease was decreased in those taking fluconazole for primary prophylaxis (RR 0.25, 95% CI 0.07, 0.87) compared to those taking placebo; however, there was no significant difference in overall mortality (RR 0.59, 95% CI 0.14, 2.62). AUTHORS' CONCLUSIONS: Antifungal primary prophylaxis with either itraconazole or fluconazole is effective in reducing the incidence of cryptococcal disease in adults with advanced HIV disease. However, neither of these interventions has a clear effect on overall mortality. Further research is needed to better understand these interventions and the populations in which they may be most effective.

Three- or four- versus two-drug antiretroviral maintenance regimens for HIV infection.

BACKGROUND: Combination antiretroviral therapy administered to HIV-infected individuals has been shown to decrease viral replication, improve immunologic function and delay the progression of HIV infection. However, because patient adherence to complicated combination-therapy antiretroviral regimens is difficult and because of concerns regarding the cumulative toxicity of antiretroviral drugs, regimens that utilize fewer antiretroviral agents are desirable. OBJECTIVES: To compare the use three- or four- versus two-drug antiretroviral maintenance regimens following successful initial therapy for HIV infection. SEARCH STRATEGY: The following electronic databases were searched for relevant randomized trials or reviews: 1. MEDLINE for the years 1982-May 2003 using the search terms human immunodeficiency virus, antiretroviral therapy, maintenance therapy, zidovudine, lamivudine, indinavir, stavudine, saquinivir, nelfinavir, didanosine, zalcitabine, ritonovir, AIDS, anti-HIV agents, HIV infection and HIV seropositivity. 2. AIDSLINE for the years 1982- May 2003 using the search terms antiretroviral therapy, maintenance therapy, zidovudine, lamivudine, indinavir, stavudine, saquinivir, nelfinavir, didanosine, zalcitabine, ritonovir, anti-HIV agents. 3. The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness and the Cochrane Clinical Trials Register in the Cochrane Library, through May 2003. 4. AIDSTRIALS, a specialist registry of current and completed trials maintained by the U.S. National Library of Medicine through May 2003. The abstracts of relevant conferences, including the International Conferences on AIDS, the Conference on Retroviruses and Opportunistic Infections, the Infectious Disease Society of America annual meeting and the Interscience Conference on Antimicrobial Agents and Chemotherapy, as indexed by AIDSLINE, were also reviewed. Reference lists of all review articles and primary articles identified were also searched. SELECTION CRITERIA: Randomized controlled trials in which HIV-infected adults who had successfully completed initial three- or four-drug antiretroviral therapy were randomized to maintenance therapy with three or four drugs or maintenance therapy with two drugs. Successful initial therapy was defined by a plasma viral load of less than 500 copies/ml. DATA COLLECTION AND ANALYSIS: Two reviewers assessed eligibility and trial quality. Attempts were made to contact the authors of the included abstract. Data on the number of patients experiencing loss of viral suppression were abstracted by two reviewers. The data were pooled, where appropriate, to yield odds ratios, using random effects models. MAIN RESULTS: Four trials were identified including three published studies and one abstract. Compared to three- or four-drug maintenance therapy, maintenance therapies including fewer drugs were associated with a higher risk of virologic failure (loss of HIV suppression to non-detectable levels). Combining the results of all four studies yielded an odds ratio of 5.55 (95% confidence interval, 3.14 - 9.80). Similar results were obtained when the one abstract was excluded (odds ratio, 5.48; 95% confidence interval, 2.82 - 10.65). Performing subgroup analyses of studies using similar induction and maintenance regimens gave similar results. Maintenance regimens of zidovudine and lamivudine compared to maintenance regimens with zidovudine, lamivudine and indinavir, were associated with significantly higher rates of virologic failure (odds ratio, 4.57; 95% confidence interval, 1.80 - 11.58). Similarly, maintenance regimens that discontinued one or more protease inhibitor after including them in induction therapy were also associated with a significantly higher risk of virologic failure (odds ratio, 6.15; 95% confidence interval, 3.40 -11.10). REVIEWER'S CONCLUSIONS: Although it is desirable to reduce the number of antiretroviral drugs given in combination therapy for reasons of compliance and toxicity, maintenance regimens with fewer drugs are associated with significantly increased resistance and risk of loss of viral suppression. Successful initial therapy, as evidenced by suppression of viral load, should not be modified in the maintenance phase unless clinically necessary.

Three- or four- versus two-drug antiretroviral maintenance regimens for HIV infection.

BACKGROUND: Combination antiretroviral therapy administered to HIV-infected individuals has been shown to improve immunologic function and delay the progression of HIV infection. However, because patient adherence to complicated combination-therapy antiretroviral regimens is difficult and because of concerns regarding cumulative toxicity of antiretroviral drugs, regimens that utilize fewer antiretroviral agents are desirable. OBJECTIVES: To compare the use three- or four- versus two-drug antiretroviral maintenance regimens following successful induction therapy for HIV infection. SEARCH STRATEGY: The following electronic databases were searched for relevant randomized trials or reviews: 1. MEDLINE for the years 1982-1999 using the search terms human immunodeficiency virus, antiretroviral therapy, maintenance therapy, zidovudine, lamivudine, indinavir, stavudine, saquinivir, nelfinavir, didanosine, zalcitabine, ritonovir, AIDS, anti-HIV agents, HIV infection and HIV seropositivity 2. AIDSLINE for the years 1982-1999 using the search terms antiretroviral therapy, maintenance therapy, zidovudine, lamidvudine, indinavir, stavudine, saquinivir, nelfinavir, didanosine, zalcitabine, ritonovir, anti-HIV agents 3. The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness and the Cochrane Clinical Trials Register in the Cochrane Library, Issue 2, 1999. 4. The specialist register of trials maintained by the Cochrane Collaborative Review Group on HIV Infection and AIDS 5. AIDSTRIALS, a specialist registry of current and completed trials maintained by the U.S. National Library of Medicine The abstracts of relevant conferences, including the International Conferences on AIDS, the Conference on Retroviruses and Opportunistic Infections, the Infectious Disease Society of America annual meeting and the Interscience Conference on Antimicrobial Agents and Chemotherapy, as indexed by AIDSLINE, were also reviewed. All reference lists of all review articles and primary articles identified were searched. SELECTION CRITERIA: Randomized controlled trials in which HIV-infected adults who had successfully completed three- or four-drug antiretroviral induction therapy were randomized to maintenance therapy with three or four drugs or maintenance therapy with two drugs. Successful induction therapy was defined by a plasma viral load of less than 500 copies/ml. DATA COLLECTION AND ANALYSIS: Two reviewers assessed eligibility and trial quality. Attempts were made to contact the authors of the included abstract. Data on the number of patients experiencing loss of viral suppression were abstracted by two reviewers. The data were pooled, where appropriate, to yield odds ratios, using random effects models. MAIN RESULTS: Four trials were identified including three published studies and one abstract. Compared to three- or four-drug maintenance therapy, maintenance therapies including fewer drugs were associated with a higher risk of virologic failure (loss of HIV suppression to non-detectable levels). Combining the results of all four studies yielded an odds ratio of 5.55 (95% confidence interval, 3.14 - 9.80). Similar results were obtained when the one abstract was excluded (odds ratio, 5.48; 95% confidence interval, 2.82 - 10.65). Performing subgroup analyses of studies using the same induction and maintenance regimens gave similar results. Maintenance regimens of zidovudine and lamivudine compared to maintenance regimens with zidovuine, lamivudine and indinavir, were associated with significantly higher rates of virologic failure (odds ratio, 4.57; 95% confidence interval, 1.80 - 11.58). Similarly, maintenance regimens that discontinued one or more protease inhibitor after including them in induction therapy were also associated with a significantly higher risk of virologic failure (odds ratio, 6.15; 95% confidence interval, 3.40 -11.10). (ABSTRACT TRUNCATED)

Surveillance for incident HIV infection: new technology and new opportunities.

Although surveillance for HIV infection has traditionally focused on the incidence of AIDS and the prevalence of HIV, new diagnostic technologies that allow the estimation of incident HIV infection have become available. Number and distribution of new cases of HIV infection, rather than old cases, are the data most relevant to guide rational application of HIV prevention programs. Historically, incident HIV infection has been measured in longitudinal cohort studies, diagnosed clinically or since 1993 by detection of seroconverting patients (during the window period before appearance of HIV antibody) who are viremic as measured by p24 antigen or RNA-PCR. The sensitive-less sensitive EIA test (or serologic testing algorithm for recent HIV seroconversion [STAHRS]) has now made the serologic diagnosis of incident HIV infection in individual patients as well as the estimation of HIV incidence in populations possible. Examples of the public health application of this are studies of HIV incidence in anonymous test site attendees, sexually transmitted disease clinic patients, and in-treatment injection drug users in San Francisco. These sorts of studies allow us not only to measure incidence cross-sectionally but also facilitate surveillance for HIV subtypes and primary antiretroviral resistance, targeting early antiretroviral therapy and partner notification, and understanding who is "failing" prevention. Having an HIV surveillance system that focuses on incident rather than prevalent infection should be our long-term goal.

Medicaid managed care and public health data.

In summary, there are a number of ways in which state public health data can be of value in the design of Medicaid managed care plans. At the level of the purchaser, such as a state Medicaid agency, public health data can assist in decision-making around pricing policy and can be useful in prioritizing interventions for those conditions that most severely affect the covered population. Quality assurance standards such as the HEDIS clinical performance measures can be used to define a baseline of prevention-oriented services or, by adding additional customized data points, to emphasize a particular service. From the standpoint of the managed care plan, public health data can be useful in understanding the needs of a community it serves or would like to serve and in estimating the prevalence of various conditions in that community that will influence the premium it will charge. Thus, there are multiple routes through which public health goals and priorities can be incorporated into managed care and can leverage the power of managed care to improve the public's health.

Research in the Veterans Health Administration: the report of the Research Realignment Advisory Committee.

In 1995 the Under Secretary for Health of the Department of Veterans Affairs constituted the Research Realignment Advisory Committee and charged it with reviewing the VA's research program. After meeting in 1995 and 1996, the committee identified 12 findings, which fall into four broad categories: allocation of research resources among VA research programs, acquisition and protection of resources, stability and maintenance of infrastructure, and outreach and communications. The most far-reaching recommendation was to establish designated research areas so that VA research could be focused more sharply on the specific needs of veterans while maintaining a research base for relatively less common conditions and needs integral to the VA's mission. The second major issue was that research funding should be increased (because it had fallen in inflation-adjusted dollars while the cost of doing research continued to rise). The third major area dealt with operational issues about how research was administered in the newly created system of geographically defined "veterans integrated service networks" and at the medical centers and how research monies flowed to medical centers. The final major area had to do with career development, for the committee considered the recruitment and retention of outstanding junior investigators to be a core function of VA research. The committee's recommendations, some of which have already been implemented, form the basis for strengthening the VA's research enterprise and for fully integrating it within the new structure of health care delivery in the VA.

Prevalence and correlates of hepatitis C virus infection among inmates entering the California correctional system.

To estimate the prevalence and predictors of hepatitis C virus (HCV) infection among inmates, a cross-sectional survey was conducted in 1994 among inmates entering six reception centers of the California Department of Corrections. Discarded serum samples were tested for antibodies to human immunodeficiency virus (HIV), HCV, hepatitis B core, and hepatitis B surface antigen (HBsAg). Of 4,513 inmates in this study, 87.0% were men and 13.0% were women. Among male inmates, 39.4% were anti-HCV-positive; by race/ethnicity, prevalences were highest among whites (49.1%). Among female inmates, 53.5% were anti-HCV-positive; the prevalence was highest among Latinas (69.7%). In addition, rates for HIV were 2.5% for men and 3.1% for women; and for HBsAg, 2.2% (men) and 1.2% (women). These data indicate that HCV infection is common among both men and women entering prison. The high seroprevalence of anti-HCV-positive inmates may reflect an increased prevalence of high-risk behaviors and should be of concern to the communities to which these inmates will be released.

Public health, communicable diseases, and managed care: Will managed care improve or weaken communicable disease control?

BACKGROUND: Several changes can be anticipated in the practice of communicable disease control as a result of the health care delivery system's transition from a predominantly fee-for-service system to a predominantly managed care system. These changes will clearly involve clinical services provided by public health agencies, such as immunizations and diagnosis and treatment of tuberculosis and sexually transmitted diseases, as well as those that do not involve direct patient care, such as public health surveillance, disease investigation, outbreak control, contact tracing, public health laboratory services, and health education. METHODS: In this paper I review the potential impact of managed care on each of these areas of communicable disease control and suggest strategies for minimizing adverse effects and maximizing potential areas of cooperation. RESULTS: Examples of successful strategies include California's Medi-Cal managed care expansion, which allows local public health agencies to bill managed care organizations for the sexually transmitted disease, immunization, and confidential HIV services they provide to managed care beneficiaries. A different strategy is illustrated by the Pacific Business Group on Health, an employer-based purchasing group, that uses purchasing power to standardize the clinical preventive services benefit across all plans with which it contracts and to promote immunization goals. CONCLUSION: This analysis and these examples suggest that the emergence of managed care as the predominant form of health care financing and delivery in the United States offers an important opportunity for public health.

Transmission of Mycobacterium tuberculosis in a California State Prison, 1991.

OBJECTIVES: An investigation was conducted to determine whether ongoing transmission of Mycobacterium tuberculosis was occurring in a California state prison. METHOD: Prison pharmacy records were used to identify cases of active tuberculosis (TB). RESULTS: Ten of the 18 cases of active TB treated at the facility during 1991 were diagnosed at the prison that same year (an incidence of 184 per 100,000). Three inmates were infectious for a total of 7 months while imprisoned. The prevalence of TB skin test-positivity among inmates was 30%, and the incidence of new infection attributable to incarceration was 5.9 per 100 inmates per year. CONCLUSIONS: Transmission of M. tuberculosis may be occurring in the California prison system.

Fatiguing illness among employees in three large state office buildings, California, 1993: was there an outbreak?

UNLABELLED: The objective was to determine if a cluster of chronic fatigue syndrome (CFS)-like illness had occurred among employees in two large state office buildings in northern California, and to identify risk factors for and features of fatiguing illness in this population. DESIGN: case-control study. POPULATION AND SETTING: Over 3300 current employees in two state office buildings and employees in a comparable "control" building. Information was collected on demographic and occupational variables, the occurrence of fatiguing illness for at least one month in the previous year, and the presence of 36 symptoms. A total of 3312 (82%) of 4035 employees returned questionnaires. Overall, 618 (18.7%) persons reported fatigue lasting at least one month; including 382 (11.5%) with fatigue of at least six months' duration and 75 (2.3%) with symptoms compatible with a CFS-like illness. Independent risk factors for fatigue lasting one month or longer were found to be Native American ethnicity (OR 2.4, CI 1.1,5.3), Hispanic ethnicity (OR 1.7, CI 1.3,2.3), female sex (OR 1.5, CI 1.2,1.9), gross household incomes of less than $50,000 (OR 1.3, CI 1.1,1.6), and less than a college education (OR 1.3, CI 1.1,1.6). Similar risks were observed for persons who reported fatigue lasting six months or longer. Female sex (OR 3.2, CI 1.7, 6.4) was the only independent risk factor found for those persons classified as having a CFS-like illness. Case prevalence rates for all three categories of fatigue, as determined by multivariate analysis, were not significantly different among buildings. Despite finding a substantial number of employees with fatiguing illness in the two state office buildings, the prevalence was not significantly different than that for a comparable control building. Previously unidentified risk factors for fatigue of at least one month and at least six months identified in this population included Hispanic ethnicity, not having completed college, and income below $50,000.

Risk factors for injuries from in-line skating and the effectiveness of safety gear.

BACKGROUND: Of the estimated 22.5 million people participating in in-line skating in the United States in 1995, about 100,000 were sufficiently injured so as to require emergency department care. We investigated the effectiveness of wrist guards, elbow pads, knee pads, and helmets in preventing skating injuries. METHODS: We used data from the 91 hospital emergency departments participating in the National Electronic Injury Surveillance System, a national probability sample of randomly selected hospitals with 24-hour emergency departments. Injured in-line skaters who sought medical attention between December 1992 and July 1993 were interviewed by telephone. We conducted a case-control study of skaters who injured their wrists, elbows, knees, or heads as compared with skaters with injuries to other parts of their bodies. RESULTS: Of 206 eligible injured subjects, 161 (78 percent) were interviewed. Wrist injuries were the most common (32 percent); 25 percent of all injuries were wrist fractures. Seven percent of injured skaters wore all the types of safety gear; 46 percent wore none. Forty-five percent wore knee pads, 33 percent wrist guards, 28 percent elbow pads, and 20 percent helmets. The odds ratio for wrist injury, adjusted for age and sex, for those who did not wear wrist guards, as compared with those who did, was 10.4 (95 percent confidence interval, 2.9 to 36.9). The odds ratio for elbow injury, adjusted for the number of lessons skaters had had and whether or not they performed trick skating, was 9.5 (95 percent confidence interval, 2.6 to 34.4) for those who did not wear elbow pads. Non-use of knee pads was associated with a nonsignificant increase in the risk of knee injury (crude odds ratio, 2.2; 95 percent confidence interval, 0.7 to 7.2). The effectiveness of helmets could not be assessed. CONCLUSIONS: Wrist guards and elbow pads are effective in protecting in-line skaters against injuries.

An outbreak of cholera from food served on an international aircraft.

In February 1992, an outbreak of cholera occurred among persons who had flown on a commercial airline flight from South America to Los Angeles. This study was conducted to determine the magnitude and the cause of the outbreak. Passengers were interviewed and laboratory specimens were collected to determine the magnitude of the outbreak. A case-control study was performed to determine the vehicle of infection. Seventy-five of the 336 passengers in the United States had cholera; 10 were hospitalized and one died. Cold seafood salad, served between Lima, Peru and Los Angeles, California was the vehicle of infection (odds ratio, 11.6; 95% confidence interval, 3.3-44.5). This was the largest airline-associated outbreak of cholera ever reported and demonstrates the potential for airline-associated spread of cholera from epidemic areas to other parts of the world. Physicians should obtain a travel history and consider cholera in patients with diarrhoea who have travelled from cholera-affected countries. This outbreak also highlights the risks associated with eating cold foods prepared in cholera-affected countries.

Human immunodeficiency virus disease in California. Effects of the 1993 expanded case definition of the acquired immunodeficiency syndrome.

On January 1, 1993, the case definition of the acquired immunodeficiency syndrome (AIDS) in adults and adolescents used for monitoring the AIDS epidemic in California was expanded to include persons infected with the human immunodeficiency virus (HIV) with CD4 T-lymphocyte counts of less than 200 x 10(6) per liter (< 200 per mm3), pulmonary tuberculosis, recurrent pneumonia, or invasive cervical cancer. To assess the implications of this revision on AIDS case reporting in California, we compared cases reported through the end of 1994 based on 1 or more of the 4 new AIDS-defining conditions added in 1993 to cases reported based on pre-1993 AIDS-defining opportunistic infections and cancers. The 4 new conditions included in the 1993 expanded AIDS case definition accounted for a 23% increase in cumulative AIDS cases reported in California by the end of 1993, a 170% increase in the number of cases reported during 1993, and an 88% increase in the number of patients with AIDS living at the end of 1993. The number of cases reported in 1993 (19,629) was 124% more than that reported in 1992 (8,780) and 69% more than that reported in 1994 (11,587). The proportion of cases among women, injection-drug users, and African Americans also increased as a result of this change in the case definition. The expansion of the case definition may have resulted in a peak or plateau in the AIDS incidence in California because of reporting earlier in the HIV disease progression. The expanded case definition has enhanced the usefulness of AIDS surveillance data for targeting secondary prevention efforts, but more behavioral and HIV serosurveys are still needed to adequately target primary HIV prevention efforts.