Biomedical subjects

Donald R Hoover

Publications and source records attributed to Donald R Hoover.

34 records · Page 2Linked to original sources

PubMed2004

Subject allocation and study curtailment for fixed event comparative Poisson trials.

Comparative Poisson trials of prophylactic interventions, such as vaccines, can be lengthy and costly. We evaluate two easily implemented approaches to reduce numbers of disease cases and person years of follow up (N(u+t)) for comparative Poisson trials with fixed numbers of cases (T); (i) altering k the portion of N(u+t) allocated to treatment and (ii) curtailed stopping before T cases if numbers of cases in the treatment or control group indicate that H(0) has already been rejected or will not be rejected at T cases. Normal and arcsine approximations as well as discrete exact tests are evaluated. For studies not stopped early, allocating about 1/(1+\sqrt r_a) of person years to treatment roughly minimizes T needed for given size and power (where r(a) is the alternative hypothesized relative disease incidence in treated subjects used to power the study). This reduces T moderately vs equal allocation (k=0.5) by 2-3 cases in our examples with exact tests. However, the common practice of allocating k=0.5 of the person years to treatment may be the overall best strategy to minimize N(u+t) for studies that are not stopped early. For studies analysed by exact test and planned with a one-sided alpha ranging from 0.005 to 0.025, beta from 0.1 to 0.2 and r(a) from 0.2 to 0.5, curtailed stopping reduces both the number of disease cases and N(u+t) by 6-40 per cent depending on true treatment benefit. With curtailed stopping, allocating k=0.5 person years to treatment approximately minimizes the numbers of cases and person years under most conditions, although k as large as 0.6 often performs comparably well. If a specific localized k is selected to minimize disease cases for a study analysed by exact test, the study may be underpowered should the final allocation deviate even slightly from that k when it is conducted.

Chemoprevention↗

PubMed2004

Total lymphocyte count, hemoglobin, and delayed-type hypersensitivity as predictors of death and AIDS illness in HIV-1-infected women receiving highly active antiretroviral therapy.

BACKGROUND: Total lymphocyte count (TLC) and hemoglobin level have been suggested as useful and inexpensive parameters to indicate need for HAART in settings in which CD4 cell counts are unavailable. If delayed-type hypersensitivity (DTH) response predicts clinical response in persons using highly active antiretroviral therapy (HAART), it may also prove useful in resource-poor settings. OBJECTIVE: To examine whether TLC, hemoglobin, and DTH response observed prior to initiation of HAART predict post-HAART clinical response. DESIGN: Prospective cohort study. PARTICIPANTS: 873 women in the Women's Interagency HIV Study. MEASUREMENTS: TLC, hemoglobin, CD4 cell counts, and DTH testing using mumps, candida, and tetanus toxoid antigens, performed within 1 year prior to HAART initiation; death; self-report of initiation of HAART use and AIDS-defining illness (ADI). RESULTS: Three different multivariate analyses were performed: 2 models that excluded CD4 cell count and assessed TLC at either < 850 or < 1250 cells/microL, and 1 model that excluded TLC and included CD4 < 200 cells/microL. TLC < 850, TLC < 1250, CD4 < 200 cells/microL, anergy to DTH testing, hemoglobin < 10.6 g/dL, and a pre-HAART report of ADI were each consistently independently associated both with death and with incident ADI. Log likelihood chi2 values suggested similar power among the 3 models in predicting both death and incident ADI. CONCLUSIONS: Pre-HAART TLC, hemoglobin level, anergy to DTH testing, and clinical disease each independently predicted morbidity and death after HAART initiation. These findings support the use of TLC to guide decision-making for HAART initiation and suggest that further study of TLC, hemoglobin level, and DTH responses as an indication to provide HAART may be useful in resource-limited settings.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Hispanic ethnicity and post-traumatic stress disorder after a disaster: evidence from a general population survey after September 11, 2001.

PURPOSE: To assess ethnic differences in the risk of post-traumatic stress disorder (PTSD) after a disaster, and to assess the factors that may explain these differences. METHODS: We used data from a representative survey of the New York City metropolitan area (n=2,616) conducted 6 months after September 11, 2001. Linear models were fit to assess differences in the prevalence of PTSD between different groups of Hispanics and non-Hispanics and to evaluate potential explanatory variables. RESULTS: Hispanics of Dominican or Puerto Rican origin (14.3% and 13.2%, respectively) were more likely than other Hispanics (6.1%) and non-Hispanics (5.2%) to report symptoms consistent with probable PTSD after the September 11 terrorist attacks. Dominicans and Puerto Ricans were more likely than persons of other races/ethnicities to have lower incomes, be younger, have lower social support, have had greater exposure to the September 11 attacks, and to have experienced a peri-event panic attack upon hearing of the September 11 attacks; these variables accounted for 60% to 74% of the observed higher prevalence of probable PTSD in these groups. CONCLUSION: Socio-economic position, event exposures, social support, and peri-event emotional reactions may help explain differences in PTSD risk after disaster between Hispanic subgroups and non-Hispanics.

Adult↗

PubMed2004

Characteristics of community dwelling elderly not vaccinated for pneumococcus in 1998 and 2001.

BACKGROUND: We estimate proportions and numbers of elderly (>65 years old) not vaccinated for pneumococcus in 1998 and 2001 by ethnic group, socioeconomic status, health history, and access and use of health care. METHODS: Self-reported lifetime pneumococcal vaccination and participant characteristics were obtained from 10,624 community dwelling elderly in the 1998 and 2001 National Health Interview Surveys (NHIS). Robust descriptive and inferential statistical analyses were fit. Outcome. Non-receipt of pneumococcal vaccination. RESULTS: In 2001, about 13 million (or 45% of all) community dwelling elderly were unvaccinated against pneumococcus, including 11.5 million who saw a doctor at least once, 4 million who received an influenza vaccination and 2.3 million who were hospitalized, during the previous year. In 1998 and 2001 non-US born, Hispanic, African-American, and Medicaid recipient elderly were disproportionately un-vaccinated, with about 65% of each group not vaccinated in 2001. CONCLUSIONS: In 2001, lifetime pneumonia vaccination of community dwelling elderly (55%) was below the goal (60%) for Healthy People 2000. While there has been important progress in improving overall vaccination rates, much more needs to be done to attain national goals and reduce large, persistent racial/ethnic and socioeconomic disparities. Lack of a usual source of healthcare and lower frequency of physician visits were among the factors associated with non-vaccination. However, most unvaccinated individuals had seen a physician in the last year, and many had received influenza vaccination or been hospitalized, suggesting the need for more consistent implementation and monitoring of guidelines for routine pneumococcal vaccination in healthcare settings.

Aged↗

PubMed2004

Mental illness and length of inpatient stay for medicaid recipients with AIDS.

OBJECTIVE: To examine the associations between comorbid mental illness and length of hospital stays (LOS) among Medicaid beneficiaries with AIDS. DATA SOURCE AND COLLECTION/STUDY SETTING: Merged 1992-1998 Medicaid claims and AIDS surveillance data obtained from the State of New Jersey for adults with >or=1 inpatient stay after an AIDS diagnosis from 1992 to 1996. STUDY DESIGN: Observational study of 6,247 AIDS patients with 24,975 inpatient visits. Severe mental illness (SMI) and other less severe mental illness (OMI) diagnoses at visits were ascertained from ICD-9 Codes. About 4 percent of visits had an SMI diagnosis; 5 percent had an OMI diagnosis; 43 percent did not have a mental illness diagnosis, but were patients who had been identified as having an SMI or OMI history; and 48 percent were from patients with no identified history of mental illness. PRINCIPAL FINDINGS: The overall mean hospital LOS was 12.7 days. After adjusting for measures of HIV disease severity and health care access in multivariate models, patients presenting with primary and secondary severe mental illness (SMI) diagnoses had approximately 32 percent and approximately 11 percent longer LOS, respectively, than did similar patients without a mental illness history (p<0.001 for each). But in these adjusted models of length of stay: (1) diagnosis of OMI was not related to LOS, and (2) in the absence of a mental illness diagnosed at the visit, an identified history of either SMI or OMI was also not related to LOS. In adjusted models of time to readmission for a new visit, current diagnosis of SMI or OMI and in the absences of a current diagnosis, history of SMI or OMI all tended to be associated with quicker readmission. CONCLUSIONS: This study finds greater (adjusted) LOS for AIDS patients diagnosed with severe mental illness (but not for those diagnosed with less severe mental comorbidity) at a visit. The effect of acute severe mental illness on hospitalization time may be comparable to that of an acute AIDS opportunistic illness. While previous research raises concerns that mental illness increases LOS by interfering with treatment of HIV conditions, the associations here may simply indicate that extra time is needed to treat severe mental illnesses or arrange for discharge of afflicted patients.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Short postexposure prophylaxis in newborn babies to reduce mother-to-child transmission of HIV-1: NVAZ randomised clinical trial.

BACKGROUND: In sub-Saharan Africa, most women present late for delivery with unknown HIV status, which limits the use of intrapartum nevirapine to prevent mother-to-child transmission of HIV. We aimed to determine whether post-exposure prophylaxis of nevirapine plus zidovudine given to babies only reduced transmission of HIV more than did a regimen of nevirapine alone. METHODS: We randomly assigned 1119 babies of Malawian women with HIV-1 who presented late (ie, within 2 h of expected delivery) to either nevirapine alone or nevirapine and zidovudine. Both drugs were given immediately after birth: one dose of nevirapine (2 mg/kg weight) was given as a single dose; babies in the nevirapine plus zidovudine group also received zidovudine twice daily for 1 week (4 mg/kg weight). Infant HIV infection was determined at birth and at 6-8 weeks. Primary outcome was HIV infection in babies at 6-8 weeks in those not infected at birth. Analysis was by intention to treat. FINDINGS: The overall rate of mother-to-child transmission at 6-8 weeks was 15.3% in 484 babies who received nevirapine and zidovudine and 20.9% in 468 babies who received nevirapine only (p=0.03). At 6-8 weeks, in babies who were HIV negative at birth, 34 (7.7%) babies who had nevirapine and zidovudine and 51 (12.1%) who received nevirapine only were infected (p=0.03)-a protective efficacy of 36%. This finding remained after controlling for maternal viral load and other factors at baseline. Adverse events were mild and of similar frequency in the two groups. INTERPRETATION: Postexposure prophylaxis can offer protection against HIV infection to babies of women who missed opportunities to be counselled and tested before or during pregnancy. The nevirapine and zidovudine regimen is safe and easy to implement.

Anti-HIV Agents↗

PubMed2003

Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection.

With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients.

Administration, Oral↗

PubMed2003

Psychological distress and progression to AIDS in a cohort of injection drug users.

OBJECTIVE: We investigated whether distress was independently associated with more rapid progression to AIDS among HIV-infected injection drug users (IDUs). DESIGN: A cohort study of IDUs in Baltimore followed from 1988 through 1999. A total of 451 IDUs met the eligibility criteria of being HIV-seropositive but AIDS-free at baseline. METHODS: We used Cox proportional hazards models to investigate progression to AIDS within 2 years of baseline, controlling for CD4 lymphocyte count, HIV-1 viral load, and oral thrush. RESULTS: Of the 451 participants, 76.3% were male and 95.8% were African-American; the median age at enrollment was 34 years. The cumulative incidence of AIDS within 2 years of baseline was 7.1%. In multiple regression analysis, distress was associated with more rapid time to AIDS (adjusted relative hazard [RH] = 2.39; 95% CI: 1.16-4.90). The strongest association was observed among IDUs with the lowest (<200 x 10 /L) CD4 counts (adjusted RH = 4.94; 95% CI: 1.30-18.77). CONCLUSIONS: Psychological distress was independently associated with shorter time to AIDS among HIV-infected IDUs, especially among those with the lowest CD4 cell counts, but was not predictive of mortality in this cohort. Further study of the effects of psychological distress on AIDS progression within this population is warranted.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Multivariate estimation of cumulative incidence, prevalence, and morbidity time of a disease when death is likely.

Competing risk of death from other causes before developing the outcome of interest is a common phenomenon in clinical settings. In a previous article, we developed the "sandwiching method" as one approach to estimate disease incidence and morbidity time for populations at a high risk of death from other causes. In addition to its computational simplicity, the sandwiching method is also relatively assumption free. This article extends the original sandwiching method to incorporate patient characteristics into the estimation by using Cox's proportional hazards model. Data from the Johns Hopkins Hospital AIDS service were used to illustrate this extended method. The importance of estimates was discussed in the context of planning health care needs.

AIDS-Related Opportunistic Infections↗

PubMed2003

Reproducibility of immunological tests used to assess multiple chemical sensitivity syndrome.

Whether persons with multiple chemical sensitivity syndrome (MCS) have immunological abnormalities is unknown. To assess the reliability of selected immunological tests that have been hypothesized to be associated with MCS, replicate blood samples from 19 healthy volunteers, 15 persons diagnosed with MCS, and 11 persons diagnosed with autoimmune disease were analyzed in five laboratories for expression of four T-cell surface activation markers (CD25, CD26, CD38, and HLA-DR) and in four laboratories for autoantibodies (to smooth muscle, thyroid antigens, and myelin). For T-cell activation markers, the intralaboratory reproducibility was very good, with 90% of the replicates analyzed in the same laboratory differing by < or = 3%. Interlaboratory differences were statistically significant for all T-cell subsets except CD4+ cells, ranging from minor to eightfold for CD25+ subsets. Within laboratories, the date of analysis was significantly associated with the values for all cellular activation markers. Although reproducibility of autoantibodies could not be precisely assessed due to the rarity of abnormal results, there were inconsistencies across laboratories. The effect of shipping on all measurements, while sometimes statistically significant, was very small. These results support the reliability of fresh and shipped samples for detecting large (but perhaps not small) differences between groups of donors in the T-cell subsets tested. When comparing markers that are not well standardized, it may be important to distribute samples from different study groups evenly over time.

Antigens, Differentiation, T-Lymphocyte↗

PubMed2002

Heat-denatured human immunodeficiency virus type 1 protein 24 antigen: prognostic value in adults with early-stage disease.

CD4(+) lymphocyte count and human immunodeficiency virus (HIV) type 1 RNA level are useful for determining when to initiate antiretroviral therapy but are not used widely in developing countries due to the high cost. Heat-denatured protein 24 (p24) antigen is an inexpensive assay that predicts disease progression among persons with advanced disease but has not been assessed among persons with early-stage disease. Plasma levels of heat-denatured p24 antigen were quantified in baseline study-visit specimens obtained from injection drug users enrolled in a longitudinal cohort study of HIV-1 infection. Of the 494 study participants (median initial CD4(+) lymphocyte count, 518 lymphocytes/mm(3)), 90 (18%) progressed to acquired immunodeficiency syndrome within 5 years. p24 antigen level correlated with both CD4(+) lymphocyte count (r=-0.34; P<.0001) and HIV-1 RNA level (r=0.55; P<.0001). p24 antigen level >5 pg/mL predicted disease progression, comparable with that of cutoff CD4(+) lymphocyte count <350 lymphocytes/mm(3) and HIV-1 RNA level >30,000 copies/mL. Heat-denatured p24 antigen level predicted subsequent clinical disease progression in early-stage HIV-1 infection and correlated with both CD4(+) lymphocyte count and HIV-1 RNA level.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Clinical trials of behavioural interventions with heterogeneous teaching subgroup effects.

Behaviour modification is often delivered to teaching subgroups. For example, experimental and control smoking cessation programmes may be given to 15 classes (subgroups) with 10 (otherwise independent) individuals. We present general statistical tests and power estimates to compare continuous outcomes from two interventions in settings where the magnitude of teaching subgroup heterogeneity, number of subgroups and subgroup size can differ between intervention arms. An application is made to data from a trial to reduce disease-transmitting sexual behaviour. The statistical impact of teaching subgroup heterogeneity effect increases as the (a) number of participants in a subgroup increases, and (b) ratio of 'averaged experimental and control subgroup effect variance' to study subject variance increases. If plausible levels of subgroup teaching effect heterogeneity are ignored, the true sizes of tests with nominal 0.05 two-sided type I errors range from 0.055 to 0.47, while when planning studies, estimated sample sizes are only 11.1-95.2 per cent of the true requirements.

Behavior Therapy↗

PubMed2002

Protection against persistence of hepatitis C.

BACKGROUND: Neither previous hepatitis C virus (HCV) infection nor vaccination with HCV-derived antigens protects against reinfection. However, HCV infection and vaccination in chimpanzees has been shown to reduce the magnitude and duration of viraemia with re-challenge. We aimed to establish whether similar immunity could be achieved in man. METHODS: From a study of injecting drug users, we identified 164 people who had no evidence of previous HCV infection and 98 individuals who had been previously, but were not currently, infected with HCV. We compared the incidence and persistence of HCV viraemia in these two groups over four consecutive 6-month periods. FINDINGS: Of participants without previous infection, the incidence of HCV infection was 21% (35/164). By contrast, people previously infected were half as likely to develop new viraemia (12% [12/98]), even after accounting for risk behaviour (hazard ratio, 0.45; 95% CI 0.23-0.88). Furthermore, in HIV-1-negative people, those previously infected were 12 times less likely than people infected for the first time to develop persistent infection (odds ratio 0.05, 95% CI 0.01-0.30), and median peak HCV RNA concentration was two logs lower. HCV persisted in six of six HIV-1-positive people, even in one man who had previously cleared HCV infection when he was HIV-1 negative. INTERPRETATION: There is an alarming frequency of HCV infection and persistence among injecting drug users. Our data suggest that immunity against viral persistence can be acquired, and that vaccines should be tested to reduce the burden of HCV-related liver disease.

Adult↗

PubMed2002

Power for T-test comparisons of unbalanced cluster exposure studies.

Studies of individuals sampled in unbalanced clusters have become common in health services and epidemiological research, but available tools for power/sample size estimation and optimal design are currently limited. This paper presents and illustrates power estimation formulas for t-test comparisons of effect of an exposure at the cluster level on continuous outcomes in unbalanced studies with unequal numbers of clusters and/or unequal numbers of subjects per cluster in each exposure arm. Iterative application of these power formulas obtains minimal sample size needed and/or minimal detectable difference. SAS subroutines to implement these algorithms are given in the Appendices. When feasible, power is optimized by having the same number of clusters in each arm k(A) = k(B) and (irrespective of numbers of clusters in each arm) the same total number of subjects in each arm n(A)k(A) = n(B)k(B). Cost beneficial upper limits for numbers of subjects per cluster may be approximately (5/rho) - 5 or less where rho is the intraclass correlation. The methods presented here for simple cluster designs may be extended to some settings involving complex hierarchical weighted cluster samples.

Cluster Analysis↗

PubMed2002

Three surveys of HIV-1 prevalence and risk factors among men working at a sugar estate in Malawi.

BACKGROUND: HIV-1 surveys in defined populations identify underlying risks and trends useful to mount interventions. GOAL: The goal of the study was to determine HIV-1 prevalence and risk factors among men working at a Malawian sugar estate. STUDY DESIGN: Three independent surveys were conducted in 1994, 1997, and 1998. Procedures included obtaining informed consent, interviewing, and drawing blood for HIV and syphilis testing. Analyses determined prevalence of HIV and associated risk factors. RESULTS: HIV prevalence was 24.3% in 1994 (n = 1691), 22.8% in 1997 (n = 615), and 20.9% in 1998 (n = 1354; P < 0.03). From 1994 to 1998, the percentage of subjects with a history of sexually transmitted disease (STD) decreased from 43.6% to 29.5% (P < 0.0001), accompanied by a substantial rise in STDs confirmed by physical examination (from 7.5% to 16.8%; P < 0.0001) and by laboratory testing for syphilis (from 6.5% to 10.4%; P < 0.0001). The percentage with multiple sex partners declined (from 62.0% to 35.2%; P < 0.0001), and condom use rose (from 10.9% to 18.9%; P < 0.0001). STDs were significantly associated with prevalent HIV infection each year. CONCLUSIONS: The prevalence of HIV has remained relatively stable and high in this cohort.

Adult↗

PubMed2002

Medical expenditures during the last year of life: findings from the 1992-1996 Medicare current beneficiary survey.

OBJECTIVE: To compare medical expenditures for the elderly (65 years old) over the last year of life with those for nonterminal years. DATA SOURCE: From the 1992-1996 Medicare Current Beneficiary Survey (MCBS) data from about ten thousand elderly persons each year. STUDY DESIGN: Medical expenditures for the last year of life and nonterminal years by source of payment and type of care were estimated using robust covariance linear model approaches applied to MCBS data. DATA COLLECTION: The MCBS is a panel survey of a complex weighted multilevel random sample of Medicare beneficiaries. A structured questionnaire is administered at four-month intervals to collect all medical costs by payer and service. Medicare costs are validated by claims records. PRINCIPAL FINDINGS: From 1992 to 1996, mean annual medical expenditures (1996 dollars) for persons aged 65 and older were $37,581 during the last year of life versus $7,365 for nonterminal years. Mean total last-year-of-life expenditures did not differ greatly by age at death. However, non-Medicare last-year-of-life expenditures were higher and Medicare last-year-of-life expenditures were lower for those dying at older ages. Last-year-of-life expenses constituted 22 percent of all medical, 26 percent of Medicare, 18 percent of all non-Medicare expenditures, and 25 percent of Medicaid expenditures. CONCLUSIONS: While health services delivered near the end of life will continue to consume large portions of medical dollars, the portion paid by non-Medicare sources will likely rise as the population ages. Policies promoting improved allocation of resources for end-of-life care may not affect non-Medicare expenditures, which disproportionately support chronic and custodial care.

Aged↗