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Biomedical subjects

James Young

Publications and source records attributed to James Young.

32 records · Page 2Linked to original sources
PubMed2003

Meta-analysis of randomized controlled trials of simplified versus continued protease inhibitor-based antiretroviral therapy in HIV-1-infected patients.

OBJECTIVE: To evaluate the efficacy and safety of simplified maintenance therapy (SMT) compared with continued protease inhibitor (PI) therapy. DESIGN: Meta-analysis of nine randomized controlled trials in which 833 patients were switched to SMT (abacavir, efavirenz or nevirapine) and 616 continued PI, assessing virologic failure (primary outcome), discontinuation of therapy for reasons other than virologic failure, CD4 cell count, total plasma cholesterol and triglycerides. RESULTS: The risk ratio for virologic failure for SMT compared to continued PI was 1.06 [95% confidence interval (CI) 0.58-1.92; test for homogeneity P = 0.01] for SMT, 2.56, (95% CI, 1.17-5.64) for abacavir, 0.83 (95% CI, 0.36-1.91) for efavirenz and 0.54 (95% CI, 0.29-1.02) for nevirapine. The risk ratio for premature discontinuation of therapy with SMT was 0.61 (95% CI, 0.48-0.77; test for homogeneity P < 0.10). The difference in absolute mean cholesterol for SMT compared to continued PI was -0.15 mmol/l, (95% CI, -0.40 to 0.09; test for homogeneity P < 0.01) for SMT, -0.51 mmol/l (95% CI, -0.70 to -0.33) for abacavir, 0.22 mmol/l (95% CI, 0 to 0.43) for efavirenz and -0.19 mmol/l (95% CI, -0.48 to 0.09) for nevirapine. CONCLUSIONS: Current evidence suggests that SMT with abacavir rather than continued PI increases the risk of virologic failure, this increased risk may be confined to patients with prior mono or dual therapy with reverse transcriptase inhibitors. There is not enough evidence on whether SMT with efavirenz and nevirapine influences the risk of virologic failure. SMT with any of the three drugs reduces the risk of discontinuation of therapy, and SMT with abacavir reduces plasma cholesterol.

Adult↗
PubMed2003

Hormone replacement therapy is associated with improved survival in women with advanced heart failure.

OBJECTIVES: We sought to determine whether hormone replacement therapy (HRT) is associated with an improved prognosis in women with advanced heart failure (HF) and systolic dysfunction. BACKGROUND: There are about two million postmenopausal women in the U.S. with HF. However, limited data are available to assess the effects of HRT on survival in this large group of patients. METHODS: A retrospective analysis of women age 50 years and over entered into the Beta-Blocker Evaluation of Survival Trial (BEST) was conducted using Cox regression analysis comparing survival in HRT users and non-users after correcting for baseline variables known to predict survival in women with HF and systolic dysfunction. RESULTS: In 493 women age 50 years and older, HRT was associated with a significant reduction in mortality-21% mortality in HRT users and 34% in non-users (p = 0.025). Multivariate analysis demonstrated a hazard ratio for mortality of 0.6 (95% confidence interval = 0.36 to 0.97) (p = 0.039) for HRT users. The benefits of HRT were noted only in women with a nonischemic etiology of HF (n = 237). CONCLUSIONS: Hormone replacement therapy is associated with a marked improvement in survival in postmenopausal women with advanced HF. A prospective, randomized trial of HRT should be performed in this large group of patients.

Aged↗
PubMed2003

Prevalence of unsafe sexual behavior among HIV-infected individuals: the Swiss HIV Cohort Study.

Sexual contact is the major mode of HIV transmission. Increased sexual risk taking has been described in HIV-infected individuals receiving potent antiretroviral therapy. A new questionnaire on sexual behavior was introduced into the Swiss HIV Cohort Study on April 1, 2000. We evaluated sexual behavior in all individuals who completed the questionnaire for the first time within 1 year after its introduction. Our primary hypothesis was that self-reported unsafe sexual behavior would be more prevalent among individuals with optimal viral suppression. On April 1, 2000, 4948 individuals were registered in the study, and 4723 (95%) completed the questionnaire. Of these individuals, 12% reported unsafe sex, 78% received antiretroviral therapy, and 25% had optimal viral suppression (HIV RNA level always <50 copies/mL during the preceding 12 months). During the preceding 6 months, 55% of individuals had stable and 19% had occasional partners, and 6% had both types of partners. Sexual intercourse was reported by 82% of individuals with stable and 87% of individuals with occasional partners, and of those reporting sexual intercourse in each group, 76% and 86%, respectively, said that they always used condoms. After adjustment for covariates, reported unsafe sex was not associated with optimal viral suppression (odds ratio, 1.04; 95% confidence interval, 0.81-1.33) or antiretroviral therapy (odds ratio, 0.83; 95% confidence interval, 0.65-1.07), but it was associated with gender, age, ethnicity, HIV transmission group, HIV status of partner, having occasional partners, and living alone. There is no evidence that self-reported unsafe sexual behavior is more prevalent among HIV-infected individuals with optimal viral suppression. However, unsafe sex is associated with other factors.

Adult↗
PubMed2003

Prevention of Heart Failure in Patients in the Heart Outcomes Prevention Evaluation (HOPE) Study.

BACKGROUND: Previous trials in the prevention of heart failure have been restricted to patients with low ejection fraction or hypertension. We assessed an angiotensin-converting enzyme (ACE) inhibitor, ramipril, to prevent the development of heart failure in high-risk patients without known low ejection fraction or heart failure. METHODS AND RESULTS: We randomly assigned 9297 patients to receive double-blind ramipril (10 mg daily) or matching placebo for 4.5 years. Death attributable to heart failure, hospitalization for heart failure, initiation of open-label ACE inhibitor for heart failure, or development of typical signs or symptoms of heart failure developed in 951 patients and was associated with a 4.01-fold increase in the risk of death (P<0.0001). The rate of developing heart failure was significantly increased with coronary disease (risk ratio, 2.17), microalbuminuria (1.82), left ventricular hypertrophy (1.47), increasing age (by decade, 1.37), and diabetes (1.36). Ramipril reduced new-onset heart failure rate from 11.5% to 9.0% (relative risk, 0.77; 95% CI, 0.68 to 0.87; P<0.0001). Ramipril consistently reduced heart failure rate both in those with (relative risk, 0.87) and those without an interim myocardial infarction (relative risk, 0.78). Ramipril also reduced the heart failure rate more in patients with baseline systolic pressure above the median (139 mm Hg) (relative risk, 0.67) compared with those below the median (relative risk, 0.91; P=0.024 for interaction of group by treatment). CONCLUSION: Ramipril significantly reduces the rate of development of heart failure in patients at high risk of cardiovascular events.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Early constriction or expansion of the external elastic membrane area determines the late remodeling response and cumulative lumen loss in transplant vasculopathy: an intravascular ultrasound study with 4-year follow-up.

BACKGROUND: Early constriction of the external elastic membrane (EEM) area has been observed after cardiac transplantation. The aim of this study was to compare the late disease process of transplant vasculopathy between coronary segments with early constrictive and expansive remodeling. METHODS: Serial intravascular ultrasound data obtained annually for 4 years after transplantation in 38 transplant recipients was available. In 135 matched segments from 59 coronary arteries ultrasound images were digitized at 1-mm intervals. Mean values of the external elastic membrane (EEM), lumen and intimal areas were calculated. On the basis of a decrease or increase in EEM area within the first year after transplantation, we defined segments with early constrictive remodeling (CR, n = 71) or early expansive remodeling (ER, n = 64). RESULTS: Annual changes in intimal area were similar between segments with early CR and ER throughout the follow-up period. However, during the second and third year, annual increases in EEM area were greater in segments with early CR than in segments with early ER (second year: 1.5 +/- 2.7 vs 0.6 +/- 2.8 mm(2), p = 0.052; third year: 1.3 +/- 2.5 vs -0.03 +/- 2.6 mm(2), p = 0.003). Despite this late expansion, segments with early CR showed a cumulative decrease in the EEM area and a greater lumen loss than segments with early ER (-2.5 +/- 3.4 vs -0.6 +/- 2.6 mm(2), p < 0.001). CONCLUSIONS: In transplant vasculopathy, the late remodeling response was different between segments with early constrictive and expansive remodeling, despite similar intimal thickening. Early constriction caused an overall decrease in EEM area and greater loss of lumen during follow-up.

Adolescent↗
PubMed2003

A comparative analysis of the results from 4 trials of beta-blocker therapy for heart failure: BEST, CIBIS-II, MERIT-HF, and COPERNICUS.

BACKGROUND: Recent large randomized, controlled trials (BEST [Beta-blocker Evaluation of Survival Trial], CIBIS-II [Cardiac Insufficiency Bisoprolol Trial II], COPERNICUS [Carvedilol Prospective Randomized Cumulative Survival Study], and MERIT-HF [Metoprolol Randomized Intervention Trial in Congestive Heart Failure]) have addressed the usefulness of beta-blockade in the treatment of advanced heart failure. CIBIS-II, COPERNICUS, and MERIT-HF have shown that beta-blocker treatment with bisoprolol, carvedilol, and metoprolol XL, respectively, reduce mortality in advanced heart failure patients, whereas BEST found a statistically nonsignificant trend toward reduced mortality with bucindolol. We conducted a post hoc analysis to determine whether the response to beta-blockade in BEST could be related to differences in the clinical and demographic characteristics of the study populations. We generated a sample from BEST to resemble the patient cohorts studied in CIBIS-II and MERIT-HF to find out whether the response to beta-blocker therapy was similar to that reported in the other trials. These findings are further compared with COPERNICUS, which entered patients with more severe heart failure. METHODS: To achieve conformity with the entry criteria for CIBIS-II and MERIT-HF, the BEST study population was adjusted to exclude patients with systolic blood pressure <100 mm Hg, heart rate <60 bpm, and age >80 years (exclusion criteria employed in those trials). The BEST comparison subgroup (BCG) was further modified to more closely reflect the racial demographics reported for patients enrolled in CIBIS-II and MERIT-HF. The association of beta-blocker therapy with overall survival and survival free of cardiac death, sudden cardiac death, and progressive pump failure in the BCG was assessed. RESULTS: In the BCG subgroup, bucindolol treatment was associated with significantly lower risk of death from all causes (hazard ratio (HR)=0.77 [95% CI=0.65, 0.92]), cardiovascular death (HR=0.71 [0.58, 0.86]), sudden death (HR=0.77 [0.59, 0.999]), and pump failure death (HR=0.64 [0.45, 0.91]). CONCLUSIONS: Although not excluding the possibility of differences resulting from chance alone or to different properties among beta-blockers, this study suggests the possibility that different heart failure population subgroups may have different responses to beta-blocker therapy.

Adolescent↗
PubMed2003

Facilitating heart transplant candidate evaluation throughout Ohio.

The Ohio Solid Organ Transplantation Consortium (OSOTC) has a mission to ensure equitable access to transplant services to those most likely to benefit, regardless of personal resources. Patients are selected according to criteria established by the OSOTC, which are delineated in the Ohio Department of Health rule, and consistent with national criteria. The University of Cincinnati's Institute for Health Policy and Health Services Research (IHPHSR) has implemented a secure internet-based system to replace the OSOTC's existing fax-based procedures. This system meets both the patient evaluation and basic research needs of the OSOTC.

Heart Transplantation↗
PubMed2002

Fatal child abuse-maltreatment syndrome. A retrospective study in Ontario, Canada, 1990-1995.

Child death due to repeated episodes of physical assault or neglect has been termed the child abuse-maltreatment syndrome (CAMS). We characterized the injuries in a series of fatally abused or maltreated child to delineate objective diagnostic criteria for the CAMS for use by clinicians and pathologists. All deaths (age <17 years) investigated by the Office of the Chief Coroner for Ontario, Canada during the time period 1990-1995 were reviewed. Cases of CAMS were defined as death due to lethal recent injury or malnutrition in the presence of significant old (healing or healed) injuries indicative of repeated episode of inflicted trauma. The nature and frequency of the various injuries was determined. The frequency of the shaken baby syndrome, and the types and frequency of ano-genital injuries were also studied. Twenty-one cases of fatal CAMS were found in the study period. Most cases had significant recent head injury with intra-cranial hemorrhage (71%). Other significant recent injuries commonly observed included blunt injuries of the skin and soft tissues (67%), blunt abdominal trauma with visceral injuries (14%), and fractures (18%). Eight cases (38%) fulfilled accepted criteria for the shaken baby syndrome. Many children with fatal head injuries had evidence of older head trauma (38% of all cases). A significant minority of cases had evidence of malnutrition due to neglect (10%) or ongoing ano-genital injuries (10%). Most cases of child homicides due to repeated episodes of abuse or maltreatment involve head trauma including shaken baby syndrome. Fractures of long bone and ribs, the classical markers of child abuse, were relatively infrequent compared with head injury. A proportion of cases had ano-genital injuries due to repeated sexual abuse or punitive maltreatment. All clinicians and pathologists must recognize the wide spectrum of injuries in child abuse to ultimate protect the victim or other children in an at-risk situation.

Child↗
PubMed2002

Usefulness of plasma vitamin B(6), B(12), folate, homocysteine, and creatinine in predicting outcomes in heart transplant recipients.

Atherothrombotic complications are frequently seen in patients undergoing heart transplantation. These patients have high plasma total homocysteine concentrations associated with lower folate and vitamin B(6) levels. The relation between these metabolic abnormalities and the development of vascular complications, however, remains unclear. Fasting plasma total homocysteine, folate, vitamin B(12), vitamin B(6), and creatinine were measured in 160 cardiac transplant recipients who were followed for a mean duration of 28 +/- 9 months after blood draw (mean 59 +/- 28 months after transplant). Cardiovascular events and causes of mortality were determined and Cox proportional-hazards regression analysis was used to identify the independent predictors for cardiovascular events and mortality. Twenty-five patients developed cardiovascular events and 17 died (11 cardiovascular deaths). Mean +/- SD total homocysteine value was 18.4 +/- 8.5 (range 4.3 to 63.5 micromol/L). Hyperhomocysteinemia (> or =15 micromol/L) was seen in 99 patients (62%). Levels were no different in patients with or without cardiovascular complications/death (16.8 +/- 6.2 vs 18.9 +/- 9 micromol/L, p = 0.4). However, vitamin B(6) deficiency was seen in 21% of recipients with and in 9% without cardiovascular complications/death (p = 0.05). The relative risk for cardiovascular events, including cardiovascular death, increased 2.7 times (confidence interval 1.2 to 5.9) for B(6) levels < or =20 nmol/L compared with those with normal B(6) levels (p = 0.02). Thus, hyperhomocysteinemia is common in transplant recipients but may have no causal role in the atherothrombotic vascular complications of transplantation. Deficiency of vitamin B(6), however, may predict adverse outcomes, suggesting a possible role for supplementation with this vitamin.

Adult↗
PubMed2002

The prognostic importance of different definitions of worsening renal function in congestive heart failure.

BACKGROUND: Worsening renal function in patients hospitalized for heart failure portends a poor prognosis. However, criteria used to define worsening renal function are arbitrary, and the implications of different definitions remain unclear. We therefore compared the prognostic importance of various definitions of worsening renal function in 1,002 patients hospitalized for congestive heart failure (CHF). METHODS AND RESULTS: The patient population was 49% female, aged 67 +/- 15 years. Twenty-three percent had a prior history of renal failure, 73% had known depressed ejection fraction, and 63% had known CHF. On admission to the hospital, 47% were receiving ACE inhibitors, 22% beta-blockers, 70% diuretics and 6% NAID's. 72% developed increased serum creatinine during the hospitalization, with 20% developing an increase of > or = 0.5 mg/dL. Worsening renal function predicted both in-hospital mortality and length of stay > 10 days. Even an increased creatinine of 0.1 mg/dL was associated with worse outcome. Sensitivity for death decreased from 92% to 65% as the threshold for increased creatinine was raised from 0.1 to 0.5 mg/dL, with specificity increasing from 28% to 81%. At a threshold of a 0.3 mg/dL increase, sensitivity was 81% and specificity was 62% for death and 64% and 65% for length of stay >10 days. Adding a requirement of final creatinine of > or = 1.5 mg/dL improved specificity. CONCLUSIONS: This analysis demonstrates that any detectable decrease in renal function is associated with increased mortality and prolonged hospital stay. This suggests that therapeutic interventions which improve renal function might be beneficial.

Aged↗
PubMed2002

Needle anatomy changes with increasing tree age in Douglas-fir.

Morphological differences between old-growth trees and saplings of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) may extend to differences in needle anatomy. We used microscopy with image analysis to compare and quantify anatomical parameters in cross sections of previous-year needles of old-growth Douglas-fir trees and saplings at the Wind River Canopy Crane site in Washington and at three sites in the Cascade Mountains of Oregon. We also compared needle anatomy across a chronosequence of 10-, 20-, 40- and 450-year-old Douglas-fir trees from the Wind River site. Anatomy differed significantly between needles of old-growth trees and saplings at all sites, suggesting a developmental change in needle anatomy with increasing tree age. Compared with needles of old-growth trees, needles of saplings were longer and had proportionately smaller vascular cylinders, larger resin canals and few hypodermal cells. Astrosclereids, which sequester lignin in their secondary cell walls and occupy space otherwise filled by photosynthetic cells, were scarce in needles of saplings but abundant in needles of old-growth trees. Needles of old-growth trees had an average of 11% less photosynthetic mesophyll area than needles of saplings. The percentage of non-photosynthetic area in needles increased significantly with increasing tree age from the chronosequence of 10-, 20-, 40- and 450-year-old trees at the Wind River site. This reduction in photosynthetic area may contribute to decreased growth rates in old trees.

Microscopy, Electron, Scanning↗
PubMed2002

Improving the care of patients dying of heart failure.

Patients with heart failure have special palliative care needs, but palliative measures for treating the symptoms of end-stage heart failure have been largely ignored. A formal disease-management program for heart failure should include palliative care.

Decision Making↗
PubMedDate not supplied

Effect of amoxicillin-clavulanate in clinically diagnosed acute rhinosinusitis: a placebo-controlled, double-blind, randomized trial in general practice.

BACKGROUND: Acute rhinosinusitis is one of the most common reasons for prescribing antibiotics in primary care. However, it is not clear whether antibiotics improve the outcome for patients with clinically diagnosed acute rhinosinusitis. We evaluated the effect of a combination product of amoxicillin-potassium clavulanate on adults with acute rhinosinusitis that was clinically diagnosed in a general practice setting. METHODS: We conducted a randomized, placebo-controlled, double-blind trial with 252 adults recruited at 24 general practices and 2 outpatient clinics. Each patient had a history of purulent nasal discharge and maxillary or frontal pain for at least 48 hours. Patients were given amoxicillin, 875 mg, and clavulanic acid, 125 mg, or placebo twice daily for 6 days. Main outcome measures were time to cure (primary outcome), number of days during which rhinosinusitis restricted activities at home or work, and frequency of adverse effects (secondary outcomes). RESULTS: The adjusted hazard ratio for the effect of amoxicillin-clavulanate was 0.99 (95% confidence interval [CI], 0.68-1.45) on time to cure and 1.28 (95% CI, 0.80-2.05) in the prespecified subgroup of patients with a positive rhinoscopy result. At 7 days the mean difference between amoxicillin-clavulanate and placebo was -0.29 (95% CI, -0.93 to 0.34) in the number of days with restrictions due to rhinosinusitis and -0.60 (95% CI, -1.41 to 0.21) in patients with a positive rhinoscopy result. At 7 days patients who took amoxicillin-clavulanate were more likely to have diarrhea (odds ratio, 3.89; 95% CI, 2.09-7.25). CONCLUSIONS: Adult patients in general practice with clinically diagnosed acute rhinosinusitis experience no advantage with antibiotic treatment with amoxicillin-clavulanate and are more likely to experience adverse effects.

Acute Disease↗