Biomedical subjects

Martin L Lee

Publications and source records attributed to Martin L Lee.

18 recordsLinked to original sources

PubMed2006

A population-based, cross-sectional comparison of lipid-related indexes for symptoms of atherosclerotic disease.

Current lipid guidelines recommend that therapy be targeted primarily at low-density lipoprotein (LDL) cholesterol, and that other lipid indexes may be used as secondary or supplementary targets. Emerging data have suggested that measures such as non-high-density lipoprotein (HDL) cholesterol, apolipoprotein-B, or the total/HDL cholesterol ratio may be more predictive of cardiovascular risk than LDL cholesterol. We conducted a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey to directly compare the strengths of the associations among various lipid-related indexes and clinical features consistent with atherosclerotic disease. From approximately 9,500 data sets in the overall analysis, the apolipoprotein-B/HDL cholesterol ratio emerged as the strongest correlate (odds ratio 1.177 per 1 mg/dl increment, 95% confidence interval 1.063 to 1.302, p <0.01), followed by the total or non-HDL cholesterol/HDL cholesterol ratio (odds ratio for each 1.070 per 1 mg/dl increment, 95% confidence interval 1.024 to 1.118, p <0.01), followed by the triglyceride/HDL cholesterol ratio (odds ratio 1.033 per 1 mg/dl increment, 95% confidence interval 1.011 to 1.056, p <0.01). Neither LDL cholesterol nor the LDL/HDL cholesterol ratio correlated significantly. Parallel analyses comparing tertile extremes and analyses in subgroups determined by gender, age, and body mass index revealed similar findings. The LDL/HDL cholesterol ratio was only significant for lean patients. In conclusion, these observations add to the published data suggesting that LDL cholesterol may not be the best target of lipid-lowering treatment strategies.

Apolipoproteins B↗

PubMed2006

Impacts of evidence-based quality improvement on depression in primary care: a randomized experiment.

CONTEXT: Previous studies testing continuous quality improvement (CQI) for depression showed no effects. Methods for practices to self-improve depression care performance are needed. We assessed the impacts of evidence-based quality improvement (EBQI), a modification of CQI, as carried out by 2 different health care systems, and collected qualitative data on the design and implementation process. OBJECTIVE: Evaluate impacts of EBQI on practice-wide depression care and outcomes. DESIGN: Practice-level randomized experiment comparing EBQI with usual care. SETTING: Six Kaiser Permanente of Northern California and 3 Veterans Administration primary care practices randomly assigned to EBQI teams (6 practices) or usual care (3 practices). Practices included 245 primary care clinicians and 250,000 patients. INTERVENTION: Researchers assisted system senior leaders to identify priorities for EBQI teams; initiated the manual-based EBQI process; and provided references and tools. EVALUATION PARTICIPANTS: Five hundred and sixty-seven representative patients with major depression. MAIN OUTCOME MEASURES: Appropriate treatment, depression, functional status, and satisfaction. RESULTS: Depressed patients in EBQI practices showed a trend toward more appropriate treatment compared with those in usual care (46.0% vs 39.9% at 6 months, P = .07), but no significant improvement in 12-month depression symptom outcomes (27.0% vs 36.1% poor depression outcome, P = .18). Social functioning improved significantly (mean score 65.0 vs 56.8 at 12 months, P = .02); physical functioning did not. CONCLUSION: Evidence-based quality improvement had perceptible, but modest, effects on practice performance for patients with depression. The modest improvements, along with qualitative data, identify potential future directions for improving CQI research and practice.

Adult↗

PubMed2006

Effects of testosterone supplementation on skeletal muscle fiber hypertrophy and satellite cells in community-dwelling older men.

OBJECTIVE: In this study, we determined the effects of graded doses of testosterone on muscle fiber cross-sectional area (CSA) and satellite cell number and replication in older men. PARTICIPANTS: Healthy men, 60-75 yr old, received a long-acting GnRH agonist to suppress endogenous testosterone production and 25, 50, 125, 300, or 600 mg testosterone enanthate im weekly for 20 wk. METHODS: Immunohistochemistry, light and confocal microscopy, and electron microscopy were used to perform fiber typing and quantitate myonuclear and satellite cell number in vastus lateralis biopsies, obtained before and after 20 wk of treatment. RESULTS: Testosterone administration in older men was associated with dose-dependent increases in CSA of both types I and II fibers. Satellite cell number increased dose dependently at the three highest doses (3% at baseline vs. 6.2, 9.2, and 13.0% at 125, 300, and 600 mg doses, P < 0.05). Testosterone administration was associated with an increase in the number of proliferating cell nuclear antigen+ satellite cells (1.8% at baseline vs. 3.9, 7.5, and 13% at 125, 300, and 600 mg doses, P < 0.005). The expression of activated Notch, examined only in the 300-mg group (baseline, 2.3 vs. 9.0% after treatment, P < 0.005), increased in satellite cells after testosterone treatment. The expression of myogenin (baseline, 6.2 vs. 20.7% after treatment, P < 0.005), examined only in the 300-mg group, increased significantly in muscle fiber nuclei after testosterone treatment, but Numb expression did not change. CONCLUSIONS: Older men respond to graded doses of testosterone with a dose-dependent increase in muscle fiber CSA and satellite cell number. Testosterone-induced skeletal muscle hypertrophy in older men is associated with increased satellite cell replication and activation.

Aged↗

PubMed2006

Measuring the quality of colorectal cancer screening: the importance of follow-up.

PURPOSE: As evidence mounts for effectiveness, an increasing proportion of the United States population undergoes colorectal cancer screening. However, relatively little is known about rates of follow-up after abnormal results from initial screening tests. This study examines patterns of colorectal cancer screening and follow-up within the nation's largest integrated health care system: the Veterans Health Administration. METHODS: We obtained information about patients who received colorectal cancer screening in the Veterans Health Administration from an existing quality improvement program and from the Veterans Health Administration's electronic medical record. Linking these data, we analyzed receipt of screening and follow-up testing after a positive fecal occult blood test. RESULTS: A total of 39,870 patients met criteria for colorectal cancer screening; of these 61 percent were screened. Screening was more likely in patients aged 70 to 80 years than in those younger or older. Female gender (relative risk, 0.92; 95 percent confidence interval, 0.9-0.95), Black race (relative risk, 0.92; 95 percent confidence interval, 0.89-0.96), lower income, and infrequent primary care visits were associated with lower likelihood of screening. Of those patients with a positive fecal occult blood test (n = 313), 59 percent received a follow-up barium enema or colonoscopy. Patient-level factors did not predict receipt of a follow-up test. CONCLUSIONS: The Veterans Health Administration rates for colorectal cancer screening are significantly higher than the national average. However, 41 percent of patients with positive fecal occult blood tests failed to receive follow-up testing. Efforts to measure the quality of colorectal cancer screening programs should focus on the entire diagnostic process.

Aged↗

PubMed2006

Drug insight: Testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging.

Several regulatory concerns have hindered development of androgens as anabolic therapies, despite unequivocal evidence that testosterone supplementation increases muscle mass and strength in men; it induces hypertrophy of type I and II muscle fibers, and increases myonuclear and satellite cell number. Androgens promote differentiation of mesenchymal multipotent cells into the myogenic lineage and inhibit their adipogenic differentiation, by facilitating association of androgen receptors with beta-catenin and activating T-cell factor 4. Meta-analyses indicate that testosterone supplementation increases fat-free mass and muscle strength in HIV-positive men with weight loss, glucocorticoid-treated men, and older men with low or low-normal testosterone levels. The effects of testosterone on physical function and outcomes important to patients have not, however, been studied. In older men, increased hematocrit and increased risk of prostate biopsy and detection of prostate events are the most frequent, testosterone-related adverse events. Concerns about long-term risks have restrained enthusiasm for testosterone use as anabolic therapy. Selective androgen-receptor modulators that are preferentially anabolic and that spare the prostate hold promise as anabolic therapies. We need more studies to determine whether testosterone or selective androgen-receptor modulators can induce meaningful improvements in physical function and patient-important outcomes in patients with physical dysfunction associated with chronic illness or aging.

Aging↗

PubMed2006

Determinants of contraceptive availability at medical facilities in the Department of Veterans Affairs.

OBJECTIVE: To describe the variation in provision of hormonal and intrauterine contraception among Veterans Affairs (VA) facilities. DESIGN: Key informant, cross-sectional survey of 166 VA medical facilities. Data from public use data sets and VA administrative databases were linked to facility data to further characterize their contextual environments. PARTICIPANTS: All VA hospital-based and affiliated community-based outpatient clinics delivering services to at least 400 unique women during fiscal year 2000. MEASUREMENTS: Onsite availability of hormonal contraceptive prescription and intrauterine device (IUD) placement. RESULTS: Ninety-seven percent of facilities offered onsite prescription and management of hormonal contraception whereas 63% offered placement of IUDs. After adjusting for facility caseload of reproductive-aged women, 3 organizational factors were independently associated with onsite IUD placement: (1) onsite gynecologist (adjusted odds ratio [OR], 20.35; 95% confidence interval [CI], 7.02 to 58.74; P<.001); (2) hospital-based in contrast to community-based practice (adjusted OR, 5.49; 95% CI, 1.16 to 26.10; P=.03); and (3) availability of a clinician providing women's health training to other clinicians (adjusted OR, 3.40; 95% CI 1.19 to 9.76; P=.02). CONCLUSIONS: VA's provision of hormonal and intrauterine contraception is in accordance with community standards, although onsite availability is not universal. Although contraception is a crucial component of a woman's health maintenance, her ability to obtain certain contraceptives from the facility where she obtains her primary care is largely influenced by the availability of a gynecologist. Further research is needed to determine how fragmentation of women's care into reproductive and nonreproductive services impacts access to contraception and the incidence of unintended pregnancy.

Adult↗

PubMed2005

Pharmacokinetics of a testosterone gel in healthy postmenopausal women.

BACKGROUND: The paucity of pharmacokinetic data on androgen formulations in women has hindered clinical trials of testosterone supplementation in women. OBJECTIVE: The objective of this study was to determine the time course and profile of serum testosterone concentrations during treatment with different doses of testosterone gel in postmenopausal women and assess whether estrogen treatment affects the pharmacokinetics of testosterone gel. METHODS: Postmenopausal women with total testosterone levels less than 33 ng/dl after baseline 24-h sampling were treated with 4.4, 8.8, or 13.2 mg testosterone gel daily for 7 d each in random order, with a 7-d washout period between doses. We studied 13 women who had not received estrogen therapy (group I) and 13 who had received stable estrogen therapy for 3 months or more (group II). Total and free testosterone concentrations were measured for 48 h on the seventh day of each dose administration. RESULTS: Twenty-six women were randomized; of these, 24 were evaluable, 13 in group I and 11 in group II. The average steady-state concentrations (Cav) of serum total and free testosterone increased with increasing testosterone dose and were highly correlated with the dose (dose effect, P < 0.00001), but were not affected by estrogen therapy (P = 0.43). In both groups, the 4.4-mg dose increased Cav total and free testosterone into the mid- to high-normal range, whereas 8.8- and 13.2-mg doses raised total (Cav: 22.3, 51.6, 80.3, and 92.0 ng/dl in group I; 22.7, 59.8, 82.0, and 114.3 ng/dl in group II at 0, 4.4, 8.8, and 13. 2 mg, respectively) and free testosterone (5.9, 8.4, 11.5,12.8 pg/ml in group I and 5.0,7.6,11.1,10.8 in group II, respectively, at the various doses) above the physiological range. The area under the curve, maximum and minimum concentrations, and the change in Cav for total and free testosterone were dose related and significantly higher during administration of the 13.2-mg dose than during the 0- or 4.4-mg dose; estrogen therapy had no significant effect on these measures. Serum estradiol, LH, FSH, and SHBG levels did not change significantly at any dose. Testosterone gel was well tolerated. CONCLUSIONS: Administration of testosterone gel to postmenopausal women raised total and free testosterone concentrations in proportion to the administered dose without affecting estradiol levels. A 4.4-mg dose raised testosterone levels into the mid- to high-normal range. Previous estrogen therapy had no significant effect on testosterone pharmacokinetics over this short duration.

Administration, Topical↗

PubMed2005

Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials.

BACKGROUND: We performed a meta-analysis of randomized clinical trials to determine the risks of adverse events associated with testosterone replacement in older men. METHODS: The MEDLINE database was searched from 1966 to April 2004, using testosterone as the indexing term; limits included human, male, > or =45 years old, and randomized controlled trial. Of the 417 studies thus identified, 19 met the inclusion criteria: testosterone replacement for at least 90 days, men > or =45 years old with low or low-normal testosterone level, randomized controlled trial, and medically stable men. Odds ratios (ORs) were pooled using a random effects model, assuming heterogeneous results across studies, and were weighted for sample size. RESULTS: In the 19 studies that met eligibility criteria, 651 men were treated with testosterone and 433 with placebo. The combined rate of all prostate events was significantly greater in testosterone-treated men than in placebo-treated men (OR = 1.78, 95% confidence interval [CI], 1.07-2.95). Rates of prostate cancer, prostate-specific antigen (PSA) >4 ng/ml, and prostate biopsies were numerically higher in the testosterone group than in the placebo group, although differences between the groups were not individually statistically significant. Testosterone-treated men were nearly four times as likely to have hematocrit >50% as placebo-treated men (OR = 3.69, 95% CI, 1.82-7.51). The frequency of cardiovascular events, sleep apnea or death was not significantly different between the two groups. CONCLUSIONS: Testosterone replacement in older men was associated with a significantly higher risk of detection of prostate events and of hematocrit >50% than was placebo; hematocrit increase was the most frequent adverse event associated with testosterone replacement. These data reaffirm the need to monitor hematocrit, PSA, and digital examination of the prostate during testosterone replacement in older men.

Aged↗

PubMed2005

Persistent elevation of high mobility group box-1 protein (HMGB1) in patients with severe sepsis and septic shock.

OBJECTIVE: To study the systemic release and kinetics of high mobility group box-1 protein (HMGB1) in relation to clinical features in a population of patients with severe sepsis or septic shock and to compare these with the kinetics of the cytokines interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-alpha. DESIGN: Prospective study of two cohorts of patients. SETTING: Intensive care unit and infectious disease clinic at Karolinska University Hospital Huddinge. PATIENTS: Twenty-six patients with severe sepsis, 33 patients with septic shock, and a reference group of five patients with sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixty-four patients were included, ten of whom died within 28 days. Cytokine levels were measured at five time points during the first week after admission and were correlated to Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment scores. Two HMGB1 assays were used. Both demonstrated delayed kinetics for HMGB1 with high levels on inclusion that remained high throughout the study period. Serum concentration at 144 hrs, the last sampling point, was 300 times higher, 34,000 +/- 76,000 pg/mL (mean +/- sd), than any of the other cytokines. This study, however, found no predictable correlation between serum levels of HMGB1 and severity of infection. We did quite unexpectedly find significantly lower levels of HMGB1 in nonsurvivors compared with survivors as measured by our main assay, but the other showed no difference between the two groups. Levels of interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-alpha correlated significantly with severity of disease, and all were significantly higher in patients with septic shock compared with those with severe sepsis. Neither of these comparisons showed significant correlations for HMGB1. CONCLUSIONS: This is the first prospective study assessing the release over time of HMGB1 in a population of patients with sepsis, severe sepsis, or septic shock. Levels remained high in the majority of patients up to 1 wk after admittance, indicating that the cytokine indeed is a downstream and late mediator of inflammation. Further studies are required to fully define the relationship of HMGB1 to severity of disease.

Biomarkers↗

PubMed2004

Delta-4-androstene-3,17-dione binds androgen receptor, promotes myogenesis in vitro, and increases serum testosterone levels, fat-free mass, and muscle strength in hypogonadal men.

Previous studies of Delta 4-androstene-3,17-dione (4-androstenedione) administration in men have not demonstrated sustained increments in testosterone levels, fat-free mass (FFM), and muscle strength, and failure to demonstrate androstenedione's androgenic/anabolic effects has stifled efforts to regulate its sales. To determine whether 4-androstenedione has androgenic/anabolic properties, we evaluated its association with androgen receptor (AR) and its effects on myogenesis in vitro. Additionally, we studied the effects of a high dose of 4-androstenedione on testosterone levels, FFM, and muscle strength in hypogonadal men. We determined the dissociation constant (K(d)) for 4-androstenedione using fluorescence anisotropy measurement of competitive displacement of fluorescent androgen from AR ligand-binding domain. AR nuclear translocation and myogenic activity of androstenedione were evaluated in mesenchymal, pluripotent C3H10T1/2 cells, in which androgens stimulate myogenesis through an AR pathway. We determined effects of a high dose of androstenedione (500 mg thrice daily) given for 12 wk on FFM, muscle strength, and hormone levels in nine healthy, hypogonadal men. 4-Androstenedione competitively displaced fluorescent androgen from AR ligand-binding domain with a lower affinity than dihydrotestosterone (K(d), 648 +/- 21 and 10 +/- 0.4 nm, respectively). In C3H10T1/2 cells, 4-androstenedione caused nuclear translocation of AR and stimulated myogenesis, as indicated by a dose-dependent increase in myosin heavy chain II+ myotube area and up-regulation of MyoD protein. Stimulatory effects of 4-androstenedione on myosin heavy chain II+ myotubes and myogenic determination factor expression were attenuated by bicalutamide, an AR antagonist. Administration of 1500 mg 4-androstenedione daily to hypogonadal men significantly increased serum androstenedione, total and free testosterone, estradiol, and estrone levels and suppressed SHBG and high-density lipoprotein cholesterol levels. 4-androstenedione administration was associated with significant gains in FFM (+1.7 +/- 0.5 kg; P = 0.012) and muscle strength in bench press (+4.3 +/- 3.1 kg; P = 0.006) and leg press exercises (+18.8 +/- 17.3 kg; P = 0.045). 4-androstenedione is an androgen that binds AR, induces AR nuclear translocation, and promotes myogenesis in vitro, with substantially lower potency than dihydrotestosterone. 4-androstenedione administration in high doses to hypogonadal men increases testosterone levels, FFM, and muscle strength, although at the dose tested, the anabolic effects in hypogonadal men are likely because of its conversion to testosterone.

3T3 Cells↗

PubMed2004

Immune responses and antibody decay after immunization of adolescents and adults with an acellular pertussis vaccine: the APERT Study.

As part of a prospective acellular pertussis (ACP) vaccine efficacy trial, 5 serum samples were obtained, over an 18-month period, from 101 ACP-vaccine recipients and 99 control subjects, to assess ACP antibody response and decay. Immunoglobulin (Ig) G and IgA antibodies to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae 2/3 (FIM) were measured by enzyme-linked immunosorbant assay, and titers of agglutinin were determined. Of the subjects, 16%-19% had preimmunization values of antibodies to PT that were above the assay's limit of quantitation (LOQ); in contrast, 36%-63% of the subjects had preimmunization values of antibodies to FHA, PRN, or FIM that were above the LOQ. Substantial increases in titers of IgG and IgA antibodies to the 3 ACP antigens (PT, FHA, and PRN) were observed. Over the 18-months, the percent decay in IgG and IgA antibodies ranged from 56% to 73% and from 57% to 70%, respectively; the IgG antibody response and decay suggests that geometric mean titers likely remain above the LOQ for 2-9 years and above the threshold of detection for 4-13 years. These findings support the use of ACP booster immunizations for adolescents and adults, to provide sustained levels of antibody.

Adolescent↗

PubMed2004

Lipid screening in HIV-infected veterans.

BACKGROUND: Lipid screening is recommended for patients taking protease inhibitors (PIs). METHODS: We examined data from the Veterans Administration Immunology Case Registry to assess lipid screening among HIV-infected veterans who received PIs for at least 6 consecutive months during 1999 and 2001. We estimated crude and adjusted associations between lipid screening and patient characteristics (age, gender, HIV exposure, and race/ethnicity), comorbidities (AIDS, cardiovascular disease, diabetes, hypertension, smoking, and hyperlipidemia), and facility characteristics (urban location, case management, guidelines, and quality improvement programs). RESULTS: Among 4065 patients on PIs, clinicians screened 2395 (59%) for lipids within 6 months of initiating treatment. Adjusting for patient characteristics, comorbidities, facility traits, and clustering, lipid screening was more common among patients who were cared for in urban areas (relative risk [RR] = 1.3, confidence limits: 1.0-1.5), diabetic (RR = 1.2, confidence limits: 1.1-1.3), or previously hyperlipidemic (RR = 1.4, confidence limits: 1.3-1.5) and less common among patients with a history of intravenous drug use (IVDU) (RR = 0.90, confidence limits: 0.79-1.0) or unknown HIV risk (RR = 0.85, confidence limits: 0.75-0.95). CONCLUSIONS: Six in 10 patients taking PIs receive lipid screening within 6 months of PI use. Systemic interventions to improve overall HIV quality of care should also address lipid screening, particularly among patients with unknown or IVDU HIV risk and those cared for in nonurban areas.

Adolescent↗

PubMed2004

Variations in nurse practitioner use in Veterans Affairs primary care practices.

BACKGROUND: Increasingly, primary care practices include nurse practitioners (NPs) in their staffing mix to contain costs and expand primary care. To achieve these aims in U.S. Department of Veterans Affairs medical centers (VAMCs), national policy endorsed involvement of NPs as primary care (PC) providers. OBJECTIVES: To evaluate the degree to which VAMCs incorporated NPs into PC practices between 1996 and 1999, and to identify the internal and external practice environment features associated with NP use. STUDY DESIGN: We surveyed 131 PC directors of all VAMCs in 1996 and 1999 to ascertain the staffing and characteristics of the PC practice and parent organization (e.g., academic affiliation, level of physician staffing, use of managed care arrangements), and drew on previously published studies and HRSA State Health Workforce Profiles to characterize each practice's regional health care environment (e.g., geographic region, state NP practice laws, state managed care penetration). Using multivariate linear regression, we evaluate the contribution of these environmental and organizational factors on the number of NPs/10,000 PC patients in 1999, controlling for the rate of NP use in 1996. PRINCIPAL FINDINGS: From 1996-1999, NP use increased from 75 percent to 90 percent in VA PC practices. The mean number of NPs per practice increased by about 60 percent (2.0 versus 3.2; p<.001), while the rate of NPs/10,000 PC patients trended upward (2.2 versus 2.7; p=.09). Staffing of other primary care clinicians (e.g., physicians and physician assistants per practice) remained stable, while the NP-per-physician rate increased (0.2 versus 0.4; p<.001). After multivariate adjustment, greater reliance on managed-care-oriented provider education programs (p=.02), the presence of NP training programs (p=.05), and more specialty-trained physicians/10,000 PC patients (p=.09) were associated with greater NP involvement in primary care. CONCLUSIONS: Staffing models in VA PC practices have, in fact, changed, with NPs having a greater presence. However, we found substantial practice-based variations in their use, suggesting that more research is needed to better understand how they have been integrated into practice and what impact their involvement has had on the VA's ability to achieve its restructuring goals.

Hospitals, Veterans↗

PubMed2003

Testosterone dose-dependently increases maximal voluntary strength and leg power, but does not affect fatigability or specific tension.

Testosterone supplementation in men increases fat-free mass, but whether measures of muscle performance, such as maximal voluntary strength, power, fatigability, or specific tension, are improved has not been determined. Furthermore, the extent to which these measures of muscle performance are related to testosterone dose or circulating concentration is unknown. To examine the relationship between testosterone dose and muscle performance, 61 healthy, eugonadal young men (aged 18-35 yr) were randomized to 1 of 5 groups, each receiving a long-acting GnRH agonist to suppress endogenous testosterone production plus weekly injections of 25, 50, 125, 300, or 600 mg testosterone enanthate for 20 wk. These doses produced mean nadir testosterone concentrations of 253, 306, 542, 1345, and 2370 ng/dl, respectively. Maximal voluntary muscle strength and fatigability were determined by a seated leg press exercise. Leg power was measured using a validated leg power instrument. Specific tension was estimated by the ratio of one repetition maximum muscle strength to thigh muscle volume determined by magnetic resonance imaging. Testosterone administration was associated with a dose-dependent increase in leg press strength and leg power, but muscle fatigability did not change significantly during treatment. Changes in leg press strength were significantly correlated with total (r = 0.46; P = 0.0005) and free (r = 0.38; P = 0.006) testosterone as was leg power (total testosterone: r = 0.38; P = 0.007; free testosterone: r = 0.35; P = 0.015), but not muscle fatigability. Serum IGF-I concentrations were not significantly correlated with leg strength, power, or fatigability. Specific tension did not change significantly at any dose. We conclude that the effects of testosterone on muscle performance are specific; it increases maximal voluntary strength and leg power, but does not affect fatigability or specific tension. The changes in leg strength and power are dependent on testosterone dose and circulating testosterone concentrations and exhibit a log-linear relationship with serum total and free testosterone. Failure to observe a significant testosterone dose relationship with fatigability suggests that testosterone does not affect this component of muscle performance and that different components of muscle performance are regulated by different mechanisms.

Adolescent↗

PubMed2002

What patient population does visit-based sampling in primary care settings represent?

BACKGROUND: Evaluations of outpatient interventions often rely on consecutive sampling of clinic visitors, and assume that study results generalize to the population of patients cared for. OBJECTIVE: The representativeness of such visit-based sampling compared with the population of patients seen during the same year, in terms of sociodemographic and clinical characteristics of the user groups that visit-based sampling yielded were assessed. METHODS: One thousand five hundred forty-six continuing patients visiting the primary care firms in an urban VA medical center were consecutively sampled, and visit frequencies were compared for these patients with subsets of the patient population. Administrative and survey data was then used to describe the types of patients visit-based sampling most represented compared with the types of patients sampled less frequently. RESULTS: The average sampled patient visited the firms significantly more often than patients in the reference population (18.7 vs. 9.5). Sampled patients were significantly older (>55 years), in poorer health (higher prevalence of cancer, stroke, hypertension), less likely to smoke, and more likely to be single than the average patient visiting the firms (P<0.05). Adjusting for age and sickness, frequent visitors were more apt to have experienced continuity of care during the prior year, to prefer VA care, and to be unemployed. CONCLUSIONS: Consecutive visit-based sampling actually selected patients with a visit pattern more typical of the patient population visiting four or more times a year. Studies using sampling of consecutive visitors will typically under-represent low users of care and should account for the degree to which results may not generalize to the broader practice population.

Adult↗

PubMed2002

Measuring medication: do interviews agree with medical record and pharmacy data?

BACKGROUND: Medication measurement is crucial in assessing quality for chronic conditions yet agreement of alternate data sources remains uncertain. OBJECTIVES: To evaluate medication agreement between interviews, medical records, and pharmacy data; to assess data source contribution to attributing medication exposure; and to describe the impact of combining data sources on models that predict medication use. RESEARCH DESIGN: Prospective cohort study. SUBJECTS: Probability sample of HIV-infected participants in the HIV Cost and Services Utilization Study. MEASURES: Medications reported in 2267 interviews, 1936 medical records, and 457 pharmacy records were compared using crude agreement, kappa, and the proportion of average positive and negative agreement. The percent of medications reported in each source alone was used to assess their relative contribution to attributing exposure status. We performed weighted logistic regression in alternate data sources. RESULTS: Kappa varied from 0.38 for nucleoside reverse transcriptase inhibitors to 0.70 for protease inhibitors, when comparing drug classes in interview versus medical record, interview versus pharmacy data, and medical record versus pharmacy data. The percentage of medications reported in medical records was greater than that reported in interviews or pharmacy data. Pharmacy data contributed little to the attribution of medication exposure. Adding medication data to interview data did not appreciably change analytic models predicting medication use. CONCLUSIONS: For specific medications, agreement between alternative data sources is fair to substantial, but is lower for key drug classes. Relying on one data source may lead to misclassification of drug exposure status, but combining data sources does not change the results of analytic models predicting appropriate medication use.

Antiretroviral Therapy, Highly Active↗

PubMed2002

Use of general medical services by VA patients with psychiatric disorders.

OBJECTIVE: Patients with psychiatric disorders, particularly those with severe mental illnesses, have high rates of undetected and untreated medical problems and substantially elevated mortality rates due to medical illness. The authors sought to develop a better understanding of the demographic, medical, and psychiatric characteristics of this population to inform efforts to improve the medical care of these persons. METHODS: Using Department of Veterans Affairs (VA) databases, the authors examined use of medical services by 175,653 patients who were treated in Southern California and Nevada during fiscal year 2000. Multivariate regression models were used to examine factors affecting receipt of any medical care and the number of medical visits. RESULTS: Patients with psychiatric diagnoses had fewer medical visits than other VA patients; the largest differences were seen for patients with severe mental illnesses. Patients who were younger and male had few visits. Patients with diabetes or hypertension who had been diagnosed as having schizophrenia, bipolar disorder, or an anxiety disorder had substantially fewer visits than those who did not have these psychiatric diagnoses. Patients older than 50 years were less likely to have any medical care if they had a diagnosis of a substance use, depressive, bipolar, or anxiety disorder or posttraumatic stress disorder. CONCLUSIONS: Use of medical care varies by psychiatric diagnosis. Young adults with schizophrenia and posttraumatic stress disorder and adults of all ages with bipolar disorder have an especially high risk of not receiving general medical services. Interventions to improve medical care may need to be tailored to the population being targeted.

Diabetes Mellitus↗

PubMed1992

Prophylactic intravenous administration of standard immune globulin as compared with core-lipopolysaccharide immune globulin in patients at high risk of postsurgical infection.

BACKGROUND: Infections and their sequelae are a major cause of death among patients admitted to the surgical intensive care unit (ICU). Studies of passive immunotherapy with standard intravenous immune globulin and hyperimmune globulin directed against gram-negative core lipopolysaccharide to prevent gram-negative infections and their serious systemic complications have had equivocal results in such patients. METHODS: We performed a double-blind study to assess the efficacy of standard immune globulin and core-lipopolysaccharide hyperimmune globulin in preventing infections in surgical patients at high risk. The patients received standard immune globulin (400 mg per kilogram of body weight), hyperimmune globulin (400 mg per kilogram), or placebo (25 percent albumin, 8 ml per kilogram) weekly, for a maximum of four doses while in the ICU. RESULTS: A total of 352 patients were enrolled, and 329 could be evaluated. The number of patients in whom infections developed was significantly lower in the group receiving standard immune globulin than in the placebo group (36 of 109 vs. 53 of 112 patients, P = 0.03), as was the incidence of pneumonia (15 vs. 30 cases, P = 0.04), especially pneumonia due to gram-negative bacteria (5 vs. 16 cases, P = 0.02). The number of days spent in the ICU and the total days spent in the hospital were lower in the standard immune globulin group (medians of 2 and 7.5 days fewer; P = 0.02 and 0.06, respectively). In contrast, the hyperimmune globulin had no detectable prophylactic effect on infections (50 of 108 patients, with 25 cases of pneumonia). The rate of systemic infections and shock was similar in the three study groups, and hospital mortality did not differ significantly among them. CONCLUSIONS: Intravenous immune globulin given prophylactically to selected high-risk patients in the surgical ICU can reduce the incidence of infection. Core-lipopolysaccharide hyperimmune globulin is not effective in preventing gram-negative infections and their systemic complications.

Bacteremia↗