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Biomedical subjects

G W Rutherford

Publications and source records attributed to G W Rutherford.

At least 19 recordsLinked to original sources

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.

Acquired Immunodeficiency Syndrome↗

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.

Adolescent↗

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.

AIDS-Related Opportunistic Infections↗

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.

Acquired Immunodeficiency Syndrome↗

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)

Anti-HIV Agents↗

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.

Academic Medical Centers↗

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.

Adult↗

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.

California↗

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.

Adult↗

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.

Adolescent↗

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.

Adolescent↗

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.

Acquired Immunodeficiency Syndrome↗

Drug-resistant Mycobacterium tuberculosis in California, 1991 to 1992.

To determine the proportion and distribution of drug-resistant Mycobacterium tuberculosis in California, we surveyed all California counties for drug-susceptibility test results for initial isolates from tuberculosis cases counted during the first quarters of 1991 and 1992. Overall, drug-susceptibility test results were not available for 17% of isolates. Among isolates with available test results, the proportion with resistance to isoniazid averaged 8.7%, and the proportion with resistance to at least 2 drugs, multidrug resistance, averaged 5.9% during these two quarters. The proportion of isolates with drug resistance did not change substantially during these time periods. The proportion with combined isoniazid and rifampin resistance remained stable at about 1.1%. Among persons whose isolates were tested for drug resistance, those with a known previous diagnosis of tuberculosis (relative risk [RR] = 2.6; 95% confidence interval [CI], 1.6 to 4.3; P < .01) and persons who were foreign born (RR = 1.7; 95% CI, 1.1 to 2.7; P = .014) were more likely to have isoniazid-resistant organisms. These statewide data suggest that the initial tuberculosis treatment regimen in California should include 4 antituberculosis drugs, as recommended by the American Thoracic Society and the Centers for Disease Control and Prevention for areas with a prevalence of isoniazid resistance of 4% or greater. The lack of test results for 1 in 6 patients with tuberculosis suggests the need for improved physician and laboratorian education to implement the recommendations that drug susceptibility be tested on all initial isolates.

Adolescent↗

Lyme disease in northwestern coastal California.

To determine the incidence of physician-diagnosed Lyme disease in an endemic area of California, an active surveillance program was implemented in Lake, Mendocino, Sonoma, and southern Humboldt counties. More than 200 medical care providers were called monthly for their list of suspected cases of Lyme disease. Pertinent information was abstracted from the medical record of each patient. Of 153 cases of possible early Lyme disease ascertained from July 1991 to December 1992, 37% consisted of physician-diagnosed erythema migrans. Only 58% of erythema migrans rashes were at least 5 cm in diameter. An additional 43 patients had suspicious rashes not classified as erythema migrans. Of 166 patients with possible late-stage Lyme disease, 31% had specific clinical symptoms and 75% had a positive serologic test. With an incident case defined as physician-diagnosed erythema migrans of at least 5 cm in diameter, the annual incidence of Lyme disease in northwestern coastal California according to active surveillance only was 5.5 per 100,000. The rate of Lyme disease in California is substantially lower than that in the Atlantic northeastern United States. Many suspected cases of Lyme disease in this endemic area do not meet surveillance criteria, which are intentionally restrictive. Although some of the illnesses not meeting surveillance criteria may be due to infection with Borrelia burgdorferi, it appears that Lyme disease is being overdiagnosed in this area.

Adolescent↗