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Biomedical subjects

N M Graham

Publications and source records attributed to N M Graham.

At least 73 records · Page 4Linked to original sources
PubMed1994

Beta 2-microglobulin and other early predictors of human immunodeficiency virus type 1-related wasting.

The objective of this study was to determine whether beta 2-microglobulin, neopterin, nutritional status, clinical status, immunosuppression, and hematologic status are predictors of human immunodeficiency virus (HIV)-related wasting and wasting syndrome. In addition, we aimed to determine which factors are early predictors and which are late predictors of wasting. For this cohort study of HIV-1-seropositive men seen semiannually from 1984 to 1991, a nested case-control design was used to analyze the predictive value of independent variables collected at baseline (first study visit for the seropositive cohort, first seropositive visit for seroconverters), 12 to 18 months prior, 6 to 12 months prior, and less than 6 months prior to the time at which case patients and control subjects were identified. Data on beta 2-microglobulin, neopterin, educational status, and diet were only available at baseline. A total of 41 case patients and 161 control subjects (n = 202) were identified. These were homosexual/bisexual men who were either HIV-seropositive on entering the study (n = 177) or who seroconverted during the study period (n = 25). Case patients were defined as men who had lost more than 10% of their baseline weight or who had a clinical diagnosis of wasting syndrome using the 1987 Centers for Disease Control definition. Control subjects had less than 5% weight loss from baseline or no weight loss at all. Four control subjects were matched to each case patient (where possible) by age and duration of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Drug smoking, Pneumocystis carinii pneumonia, and immunosuppression increase risk of bacterial pneumonia in human immunodeficiency virus-seropositive injection drug users.

To examine the risk factors for the first episode of bacterial pneumonia among human immunodeficiency virus (HIV)-seropositive injection drug users (IDUs), medical record review was performed on IDUs participating in a cohort study from January 1988 to June 30, 1992. HIV-seropositive IDUs with a first episode of bacterial pneumonia (n = 40) were matched with up to five HIV-seropositive control subjects without bacterial pneumonia (n = 197) by date of entry (+/- 3 mo) and length of follow-up. Odds ratios (OR) were estimated using conditional logistic regression. The incidence of bacterial pneumonia was 1.93 in 100 person-years in HIV seropositive and 0.45 in 100 person-years in HIV seronegative subjects (relative incidence = 4.3; 95% CI 2.4 to 7.5). In univariate analyses, CD4 lymphocyte count < 200 cells/microliters previous episode of Pneumocystis carinii pneumonia (PCP), age between 30 and 40 yr and smoking illicit drugs (marijuana, cocaine, or crack) were associated with bacterial pneumonia. Cigarette smoking was associated with an increased odds of bacterial pneumonia (OR = 2.0), but this was not statistically significant because it was nearly universal in this cohort. In multivariate analysis, CD4 < 200 cells/microliters (OR = 6.75, 95% CI 2.13 to 21.42) and smoking illicit drugs (OR = 2.24, 95% CI 1.03 to 4.89) remained significantly associated with bacterial pneumonia. The odds ratio for cigarette smoking in the final model remained at 2.08 but was still not significant (95% CI 0.49 to 8.70). Smoking illicit drugs had the strongest effect on risk of bacterial pneumonia among HIV-seropositive IDUs with a previous history of PCP (OR = 22.94; 95% CI 2.18 to 241.10).

AIDS-Related Opportunistic Infections↗
PubMed1994

Epidemiology and pharmacoeconomic issues relating to acute respiratory tract infections and acute uncomplicated infections of the urinary tract.

Respiratory and urinary tract bacterial infections are among the most frequently encountered conditions in clinical medicine. Driven by the increasing incidence of antimicrobial resistance and treatment failures in these conditions, newer, and unfortunately more costly, alternatives are constantly being sought. As expenditures on healthcare are currently under greater levels of scrutiny than ever before, the economic aspects of drug therapy have become an important area of inquiry. Cost-effective drug therapy depends on several factors, of which initial drug cost is only one. Clearly, drug efficacy, duration of therapy and dose regimen, diagnostic strategies, route of drug administration, microbial drug resistance and patient compliance all directly impact on cost-effectiveness evaluations. However, to avoid merely shifting costs, true evaluation of cost-benefit must take indirect economic factors such as loss of patient (and parental) income, loss of productivity, opportunity costs, and patient discomfort/suffering into account. In this article, these issues are discussed and illustrated using common respiratory and urinary tract bacterial infections as a model.

Anti-Bacterial Agents↗
PubMed1994

Impact of immunosuppression on health care use by men in the Multicenter AIDS Cohort Study (MACS).

The effects of human immunodeficiency virus type 1 (HIV-1) serostatus, AIDS, and level of immunosuppression on health service use were examined in the Multicenter AIDS Cohort Study. Data on self-reported hospitalizations, outpatient medical services (non-emergency room) and emergency room care during the preceding 6 months were collected for 3,447 homosexual/bisexual men returning for their 14th and/or 15th semiannual visits in Chicago, Baltimore, Los Angeles, and Pittsburgh. AIDS-free seropositive men with CD4+ cells < 200/microliters were more likely to be hospitalized [odds ratio (OR) = 2.3, 95% confidence limits (CL) = 1.4, 3.8] and use outpatient medical care (OR = 7.9, 95% CL = 4.9, 12.6), compared with seronegative men. Increased outpatient care was initiated at the earliest stages of HIV-1 infection, even when CD4+ cells were > 500/microliter. Dramatic increases in outpatient care for each level of immunosuppression were observed. HIV-1-related symptoms were associated with increased hospitalizations (OR = 4.8, 95% CL = 3.2, 7.3), use of outpatient medical services (OR = 3.3, 95% CL = 1.9, 5.6), and emergency room care (OR = 3.1, 95% CL = 2.1, 4.6). Persons with AIDS and < or = 50 CD4+ cells/microliter most likely to be hospitalized (OR = 8.1; 95% CL = 4.4, 14.9). No significant difference (p > 0.05) in emergency room use was observed according to HIV-1 serostatus, AIDS, or immunosuppression, after adjusting for insurance and clinical symptoms. To the extent that CD4+ cell counts are used as one of the criteria for an AIDS diagnosis and such a diagnosis broadens available benefits to persons with HIV disease, the pattern of health care services described here will be important for health care providers and planners.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Initiation of antiretroviral therapy in HIV infection: a review of interstudy consistencies.

A number of clinical trials have explored the optimal dosage for antiretroviral therapy and, in various ways, the optimal time, in terms of stage of human immunodeficiency virus (HIV) disease, at which treatment should begin. Some studies have shown that treatment with zidovudine results in a delay in progression to more advanced stages of HIV disease, and that the benefits are more durable among persons who started zidovudine with higher CD4+ cell counts. Efficacy is preserved and toxicity is reduced when zidovudine is used at dosages lower than those originally recommended. The Concorde study found that administration of zidovudine to asymptomatic persons was associated with increases in CD4+ cell counts and improvement in delaying disease progression at 55 weeks, but found no correlation between time of initiation of therapy and either longer-term delay in onset of symptomatic disease or ultimate survival. The analysis of these results, however, is complicated because of premature crossover of study participants from deferred treatment to immediate treatment. The consensus of the discussants of these studies is that antiretroviral treatment should be initiated by the time the CD4+ cell count has fallen to 200-500 cells/mm3. Although recognizing that, in general, viral infections call for treatment, the panelists were divided in their opinions about treatment of asymptomatic patients with CD4+ cell counts > 500/mm3.

Cohort Studies↗
PubMed1993

Bacterial pneumonia in adult populations with human immunodeficiency virus (HIV) infection.

Recurrent bacterial pneumonia was recently added to the definition of the acquired immunodeficiency syndrome (AIDS), based on the observation that bacterial pneumonia rates have been increased in human immunodeficiency virus (HIV)-infected persons and are indicative of immunosuppression in this population. Nonetheless, risk factors for bacterial pneumonia among HIV-infected persons remain largely uninvestigated. Identification of risk factors that may be associated with bacterial pneumonia can guide development of future interventions and further clarify target groups for such interventions. From a methodological viewpoint, diagnostic algorithms need to be further standardized to provide comparable estimates of disease incidence. Epidemiologic studies will also need to address the effectiveness of chemoprophylaxis and vaccine interventions in HIV-infected populations. Since clinical trials will not be feasible for testing efficacy of interventions that are already recommended, observational data will be critically important in guiding clinical practice.

AIDS-Related Opportunistic Infections↗
PubMed1993

Dietary micronutrient intake and risk of progression to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus type 1 (HIV-1)-infected homosexual men.

The authors sought to determine if different levels of dietary intake of micronutrients are associated with the progression of human immunodeficiency virus type 1 (HIV-1) infection to acquired immunodeficiency syndrome (AIDS). A total of 281 HIV-1 seropositive homosexual/bisexual men were seen semiannually since 1984 at the Baltimore/Washington, DC site of the Multicenter AIDS Cohort Study. Participants completed a self-administered semiquantitative food frequency questionnaire at baseline. Levels of daily micronutrient intake at baseline were examined in relation to subsequent progression to AIDS (1987 Centers for Disease Control definition; n = 108) during a median follow-up period of 6.8 years. For each nutrient, the authors used a Cox proportional hazards model to adjust for age, presence of symptoms, CD4+ lymphocyte count, energy intake, use of antiretrovirals, and use of Pneumocystis carinii pneumonia prophylaxis. The highest levels of total intake (from food and supplements) of vitamins C and B1 and niacin were associated with a significantly decreased progression rate to AIDS: vitamin C (relative hazard (RH) = 0.55, 95% confidence interval (CI) 0.34-0.91), vitamin B1 (RH = 0.60, 95% CI 0.36-0.98), and niacin (RH = 0.52, 95% CI 0.31-0.86). The relation between total vitamin A intake and progression to AIDS appeared to be U-shaped; the lowest and highest quartiles of intake did most poorly, while the middle two quartiles were associated with significantly slower progression to AIDS (RH = 0.55, 95% CI 0.35-0.88). Increased intake of zinc was monotonically and significantly associated with an increased risk of progression to AIDS (for highest vs. lowest quartiles, RH = 2.06, 95% CI 1.16-3.64). In a final multinutrient model, vitamin A, niacin, and zinc remained significantly associated with progression to AIDS, while vitamin C was only marginally significant.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Increased mortality associated with vitamin A deficiency during human immunodeficiency virus type 1 infection.

OBJECTIVE: To determine whether plasma vitamin A levels are associated with immunologic status and clinical outcome during human immunodeficiency virus type 1 (HIV-1) infection. PATIENTS AND METHODS: Analysis of vitamin A levels, CD4 T cells, complete blood cell count, and serologic markers for liver disease in a random subsample of 179 subjects from a cohort of more than 2000 intravenous drug users with longitudinal follow-up to determine survival. RESULTS: Mean (+/- SE) follow-up time was 22.8 +/- 1.1 months, and 15 subjects died during follow-up. More than 15% of the HIV-1-seropositive individuals had plasma vitamin A levels less than 1.05 mumol/L, a level consistent with vitamin A deficiency. The HIV-1-seropositive individuals had lower mean plasma vitamin A levels than HIV-1-seronegative individuals (P < .001). Vitamin A deficiency was associated with lower CD4 levels among both seronegative individuals (P < .05) and seropositive individuals (P < .05). In the HIV-seropositive participants, vitamin A deficiency was associated with increased mortality (relative risk = 6.3; 95% confidence interval, 2.1 to 18.6). CONCLUSION: Vitamin A deficiency may be common during HIV-1 infection, and vitamin A deficiency is associated with decreased circulating CD4 T cells and increased mortality. Vitamin A is an essential micronutrient for normal immune function, and vitamin A deficiency seems to be an important risk factor for disease progression during HIV-1 infection.

Adult↗
PubMed1993

Clinical factors associated with weight loss related to infection with human immunodeficiency virus type 1 in the Multicenter AIDS Cohort Study.

The relation between a number of potential risk factors and change in body mass index per semester was examined in a community-based cohort of 1,809 homosexual and bisexual men seropositive for human immunodeficiency virus type 1 (HIV-1). The men were followed semiannually for up to 6.5 years between 1984 and 1990. A total of 9,735 person-semesters of observations were available for analysis. A Markov-type autoregressive model, adjusting for previous body mass index, was used to predict the change in body mass index over each person-semester. Overall, the cohort was gaining weight. An asymptomatic participant 1.8 m in height whose CD4+ cell count was > 750/microliters gained a mean of 0.5 kg each person-semester. In bivariate autoregressive models, diarrhea, fever, oral thrush, acquired immunodeficiency syndrome (AIDS), and CD4+ lymphocyte counts of < 100 and 100-199 cells/microliters were all associated with a significant decrease in body mass index. A significant inverse association was also found between change in body mass index and lymphadenopathy and herpes zoster, but when the intercept coefficient was added, no overall decrease in body mass index was seen in these models. In a final multivariate model, diarrhea was less strongly associated with a change in body mass index (p = 0.057), although AIDS (p = 0.009), fever (p = 0.006), thrush (p = 0.002), and a CD4+ lymphocyte count of < 100 cells/microliters (p < 0.001) all remained independently associated with a decrease in body mass index. Lymphadenopathy and a CD4+ lymphocyte count of 100-199 cells/microliters were also significant covariates in the final model, but neither of the beta coefficients exceeded that of the intercept, indicating that they were not independently associated with a decrease in body mass index. These findings suggest that the importance of diarrhea as a cause of HIV-related weight loss may have been over-estimated in previous clinic-based studies. AIDS and nonspecific markers of progression (fever, thrush, and a CD4+ count of < 100 cells/microliters) were the best predictors of weight loss during a semester.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Dementia in AIDS patients: incidence and risk factors. Multicenter AIDS Cohort Study.

We determined incidence and future projections of dementia after AIDS onset in 492 homosexual men with AIDS in the Baltimore/Los Angeles sites of the Multicenter AIDS Cohort Study, 64 of whom developed dementia. We studied various risk factors for dementia, including demographic and clinical features, medical history, markers of immune status before AIDS, and zidovudine use. During the first 2 years after AIDS, HIV dementia developed at an annual rate of 7%. Overall, 15% of the cohort followed through death developed dementia. The median survival after dementia was 6.0 months. Using a proportional hazards model, risk factors for more rapid development of dementia were lower hemoglobin (relative hazard, 0.59 per additional 2 g/dl; p = 0.0005) and body mass index (relative hazard, 0.64 per additional 5 kg/m2; p = 0.05) 1 to 6 months before AIDS, more constitutional symptoms 7 to 12 months before AIDS (relative hazard, 1.68 per additional symptom, p = 0.005), and older age at AIDS onset (relative hazard, 1.60 per decade older; p = 0.009). In a multivariate model, pre-AIDS hemoglobin remained the most significant predictor of dementia. There were no significant risks defined from demographic characteristics, specific AIDS-defining illnesses, zidovudine use before AIDS, or CD4+ lymphocyte count before AIDS. We project that 12 months after the first AIDS diagnosis, 7.1% of survivors will have dementia. The observed association between anemia, low weight, constitutional symptoms, and dementia suggests a role for cytokines inducing both systemic and neurologic disease.

AIDS Dementia Complex↗
PubMed1993

The effect of prazosin on patients with symptoms of benign prostatic hypertrophy.

OBJECTIVE: To evaluate the effect of prazosin on the symptoms of benign prostatic hypertrophy for patients of general practitioners. SETTING AND PATIENTS: Eighty-two general practitioner patients from 317 who were identified as being eligible for inclusion in the trial. They were randomly allocated to receive either prazosin or placebo for the first 3 month arm then crossed-over for the second 3 months. RESULTS: Seventy-six patients completed the trial. An analogue scale of patient rating of symptoms showed a statistically significant decrease in symptoms for patients taking prazosin when compared with patients taking placebo, regardless of the order in which they had been administered. A total symptom score and an obstructive symptom score for benign prostatic hypertrophy showed a statistically significant difference between the two treatments at 4 weeks. A difference was still apparent at 8 and 12 weeks but it was not statistically significant. No difference was detected for irritative symptoms. CONCLUSION: Prazosin may have a limited place in the management of benign prostatic hypertrophy.

Aged↗
PubMed1993

CD4+ lymphocyte response to zidovudine as a predictor of AIDS-free time and survival time.

It is unknown whether the early rise in CD4+ lymphocyte count seen in zidovudine-treated patients is associated with increased AIDS-free time and survival time. To determine the association of this and other changes in immunologic and hematologic markers with prognosis for time to AIDS and survival, we followed 747 AIDS-free patients from initiation of zidovudine therapy in the Multicenter AIDS Cohort Study (MACS). Participants were seen semiannually and had data collected on medication use, immunologic and hematologic variables, and clinical outcomes. AIDS was diagnosed in 216 participants and 165 died during the median follow-up period of 2.0 years. Duration of zidovudine use was categorized into 1-6 months (after 6 months of follow-up) and 7-12 months (12 months of follow-up). During the 6-month follow-up period in which zidovudine was first used, CD4+ lymphocyte levels rose by 17 cells/microliters compared with a mean decrease of 30 cells/microliters/6 months in untreated individuals (after adjusting for baseline CD4+ lymphocyte count). Baseline levels of CD4+ lymphocytes, platelets, and hemoglobin were significant predictors of AIDS and death. After 1-6 months with patients taking zidovudine and controlling for baseline (pretreatment) variables, change in markers after 6 months of follow-up and use of Pneumocystis carinii pneumonia prophylaxis and other antivirals, change in CD4+ lymphocyte count significantly predicted progression to AIDS [relative hazard (RH) = 0.71 for each 100 cell/microliters increase, p = 0.0001] and survival (RH = 0.78 per 100 cell/microliters increase; p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1993

Tuberculosis and HIV infection: epidemiology, pathogenesis, and clinical aspects.

Human immunodeficiency virus infection has profoundly affected the epidemiology, natural history, and clinical presentation of TB. It has also contributed in part to the recent epidemic of MDR-TB in the US and significantly reduced the sensitivity (but not the specificity) of the tuberculin skin test. Further research is needed to determine the optimal strategy for chemoprophylaxis in HIV-infected individuals, new methods of diagnosing TB infection and disease, and new drugs to control MDR-TB. Most importantly, however, further funding is necessary to improve compliance with therapy and chemoprophylaxis in order to regain control of this ancient scourge.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Effect of chronic substance abuse on the neuropsychological performance of intravenous drug users with a high prevalence of HIV-1 seropositivity.

Limited data are available on cognitive performance in populations of intravenous drug users during the early, asymptomatic stages of human immunodeficiency virus type 1 (HIV-1) infection. Between 1988 and 1990, 151 participants from the AIDS Link to Intravenous Experience (ALIVE) Study in Baltimore, Maryland, were evaluated neuropsychologically on a semiannual basis. This analysis focused on whether history of substance abuse influenced neuropsychological test performance. At baseline, 102 participants were HIV-1-seropositives who were free of acquired immunodeficiency syndrome and 49 participants were seronegative. Multivariate analyses, adjusting for correlation of repeated outcome measures, were conducted to determine predictors of neuropsychological functioning. Effects of the frequency of reported past use of marijuana, heroin, cocaine, barbiturates, and alcohol were not statistically associated with performance on the tests. Age and education were the most important predictors of test performance, and a significant practice effect was observed for most measures. After adjustment for age, education, the practice effect, and frequency of drug use, neuropsychological performance over time did not vary by HIV-1 serostatus. Overall, after acutely intoxicated individuals were excluded, neither frequency of drug and alcohol use nor HIV-1 seropositivity significantly influenced neuropsychological test performance over a 1-year period.

Adult↗
PubMed1992

South Australian hypertension survey. General practitioner experiences with drug treatment.

OBJECTIVE: To investigate prescribing habits, educational approaches and perceived needs of general practitioners in the drug treatment of hypertension. DESIGN, SETTING AND PARTICIPANTS: Of 156 randomly selected South Australian general practitioners 132 responded to a questionnaire survey. MAIN FINDINGS: Diuretics are the most commonly chosen drug for the initial management of uncomplicated moderate hypertension. Equivalent patients aged 45, 60 and 75 years would be prescribed a diuretic as drug of first choice in 41%, 55% and 68% of cases respectively. Despite this, there are wide differences in the choice of initial therapy between individual practitioners. These differences can have a substantial cost impact, given that in Australia the cost of diuretic therapy for one month can be as low as $1.97 compared with $34.08 for standard angiotensin converting enzyme inhibitor therapy for one month. There was also a perceived need, and demand, for patient education materials to assist practitioners in the drug treatment of hypertension.

Adult↗
PubMed1992

The effects on survival of early treatment of human immunodeficiency virus infection.

BACKGROUND: Zidovudine has been shown to prolong survival in patients with the acquired immunodeficiency syndrome (AIDS) and, in persons with human immunodeficiency virus (HIV) infection but not AIDS, to delay the progression to AIDS. However, it is still uncertain whether treatment before the development of AIDS prolongs survival. METHODS: We analyzed data from a cohort of 2162 high-risk men who were already seropositive for HIV type 1 (HIV-1) and 406 men who seroconverted from October 1986 through April 1991. There were 306 deaths. The probabilities of death were compared among men at similar stages of disease who began zidovudine therapy before the diagnosis of AIDS and among those who did not. Relative risks of death were calculated for each of five initial disease states on the basis of CD4+ cell counts and clinical symptoms and signs appearing over follow-up periods of 6, 12, 18, and 24 months. Adjustments were also made for the use of prophylaxis against Pneumocystis carinii pneumonia (PCP). RESULTS: After we controlled for CD4+ cell count and symptoms, the use of zidovudine with or without PCP prophylaxis before the development of AIDS significantly reduced mortality in all follow-up periods. The relative risks of death were 0.43 (95 percent confidence interval, 0.23 to 0.78) at 6 months, 0.54 (95 percent confidence interval, 0.38 to 0.78) at 12 months, 0.59 (95 percent confidence interval, 0.44 to 0.79) at 18 months, and 0.67 (95 percent confidence interval, 0.52 to 0.86) at 24 months. After we adjusted for the effects of PCP prophylaxis, zidovudine alone significantly reduced mortality at 6, 12, and 18 months (relative risks, 0.45, 0.59, and 0.70, respectively), but not at 24 months (relative risk, 0.81). Among zidovudine users, those who also used PCP prophylaxis before the development of AIDS had significantly lower mortality at 18 and 24 months than those who did not (relative risks, 0.62 and 0.60, respectively). CONCLUSIONS: The results of this study support the hypothesis that in HIV-1 infection, early treatment with zidovudine and PCP prophylaxis improves survival in addition to slowing the progression to AIDS.

CD4-Positive T-Lymphocytes↗
PubMed1992

South Australian hypertension survey. General practitioner knowledge and reported management practices--a cause for concern?

OBJECTIVE: To survey South Australian general practitioners to investigate their knowledge and reported management of patients with hypertension. DESIGN, SETTING AND PARTICIPANTS: Of 156 randomly selected SA general practitioners 132 responded to a questionnaire survey. RESULTS: This survey showed substantial differences between general practitioners in their knowledge about hypertension and in their reported practices for diagnostic levels, investigations to be undertaken once diagnosis had been made, levels at which pharmaceutical treatment should be initiated, at which level treatment was regarded as having attained satisfactory control, and length of time for routine review. There was also a demand for materials to be provided to assist in the management of this important condition. CONCLUSIONS: There is a perceived need for better and more appropriate educational materials and a need for a different approach to try and reduce the reported variability in management of patients with hypertension by general practitioners.

Aged↗