Lower serum osteocalcin concentrations in patients with type 2 diabetes and relationships with vascular risk factors among patients with coronary artery disease.

BACKGROUND: Lower serum concentrations of the osteoblast-derived protein, osteocalcin, have been associated with poorer glycemic control, insulin resistance and atherosclerosis, and with the development of type 2 diabetes (T2DM). METHODS: This study compares concentrations of two physiological forms of osteocalcin, carboxylated (cOCN) and uncarboxylated (unOCN), between participants with T2DM (n = 20) and age-, gender- and body mass index (BMI)-matched participants without T2DM (n = 40) among patients with coronary artery disease (CAD), and it explores relationships between osteocalcin concentrations and cardiovascular risk factors. RESULTS: Concentrations of unOCN (2.71 ±â€¯1.86 vs. 4.70 ±â€¯2.03 ng/mL; t = -3.635, p = 0.001) and cOCN (8.70 ±â€¯2.27 vs. 10.77 ±â€¯3.69 ng/mL; t = -2.30, p = 0.025) were lower in participants with T2DM. In participants without T2DM, concentrations of cOCN were associated with fitness (VO2Peak rho = 0.317, p = 0.047) and lower body fat (rho = -0.324, p = 0.041). In participants with T2DM, lower unOCN was associated with HbA1c (rho = -0.516, p = 0.020). Higher body mass was associated with higher unOCN (rho = 0.423, p = 0.009) in participants without T2DM, but with lower concentrations of both unOCN (rho = -0.590, p = 0.006) and cOCN (rho = -0.632, p = 0.003) in participants with T2DM. CONCLUSION: In patients with CAD, lower osteocalcin concentrations were related to type 2 diabetes, and to adverse fitness, metabolic and obesity profiles.

A prospective study examining the influence of cardiac rehabilitation on the sedentary time of highly sedentary, physically inactive patients.

OBJECTIVES: Prolonged sedentary time is recognized as a distinct health risk, and mortality risks are expected to be greatest for individuals with low exercise levels. It is unknown whether participation in exercise-based cardiac rehabilitation (CR) programs influences sedentary behaviour particularly among those patients expected to be at greatest mortality risk. This study examined the influence of CR participation on sedentary behaviour and identified the proportion and characteristics (socio-demographic and clinical) of patients who do not meet exercise recommendations and have prolonged sedentary times. METHODS: A prospective study was conducted among patients of an exercise-based CR program and assessments performed at baseline and 3 months. Physical activity and sedentary behaviour information were collected by self-report, and convergent validity was examined on an accelerometer-wearing subsample. RESULTS: Of 468 CR patients approached, 130 participants were recruited with an average sedentary time of 8hours/day. Sedentary behaviour remained consistent at follow-up (relative change= -2.4%, P=0.07) notwithstanding a greater proportion meeting exercise recommendations (relative change= 57.4%). 19.2% of participants were classified to have prolonged sedentary time and not meet exercise recommendations at baseline. No significant differences were found between the characteristics of high-risk individuals and lower risk subgroups. Findings were consistent among the accelerometer-derived subgroup and the overall sample despite poor to moderate convergent validity. CONCLUSIONS: These results suggest that the exercise-focus of CR may not reduce sedentary behaviours. Future studies are needed to determine whether sedentary behaviour-specific reduction strategies are more effective than traditional exercise-based strategies and lead to meaningful improvements in clinical outcomes.

Depressive symptoms predict non-completion of a structured exercise intervention for people with Type 2 diabetes.

AIM: To quantify the impact of depressive symptoms on completion of exercise-based rehabilitation for Type 2 diabetes management. METHODS: Depressive symptoms were assessed using the Center for Epidemiological Studies Depression scale in a prospective cohort of consecutive patients with Type 2 diabetes entering a 6-month hybrid (home- and clinic-based) exercise rehabilitation programme. Attendance at exercise sessions was monitored and programme completion/non-completion was ascertained. RESULTS: Of the programme participants (n=624, mean age 55.6±10.5 years, 47% male), 26.8% endorsed significant depressive symptoms (depression score ≥16) and 68.1% completed the intervention, attending 54.6±30.0% of supervised exercise sessions. Baseline depressive symptoms (depression scale score ≥16) increased the risk of non-completion [hazard ratio 1.49 (95% CI 1.10-2.03); P = 0.010], and predicted fewer sessions attended (ß=-2.1, P= 0.002) in adjusted models. A depression score threshold of ≥10 (48.4% of participants) predicted non-completion [hazard ratio 1.60 (95% CI 1.19-2.17); P= 0.002) with optimum accuracy. Non-completions resulting from lack of interest (18.9 vs. 11.0%; P= 0.026) and medical complications (14.6 vs. 6.6%; P= 0.006) were more common among participants with depression scores ≥10. Greater hazard ratios for depression scores ≥10 were observed in subgroups not currently using insulin [hazard ratio 1.70 (95% CI 1.24-2.33); P= 0.001), or an antidepressant [hazard ratio 1.83 (95% CI 1.32-2.54); P<0.001]. CONCLUSIONS: Depressive symptoms were highly prevalent among participants with Type 2 diabetes entering exercise-based rehabilitation, and even mild depressive symptoms posed a significant barrier to completion. Depression screening may help target additional supports to facilitate completion of exercise interventions for people with Type 2 diabetes.

A phase II exercise randomized controlled trial for patients with acute myeloid leukemia undergoing induction chemotherapy.

Curative treatment for acute myeloid leukemia (AML) involves induction chemotherapy (IC) which is associated with bed rest and toxicities, leading to worsening quality of life (QOL), fatigue, and fitness. Exercise during IC may ameliorate declines but has not been rigorously tested. We examined the efficacy of supervised exercise during IC on QOL, fatigue, and fitness. Eighty-three inpatients age 18-80 scheduled to receive IC for newly diagnosed or relapsed AML were randomized 2:1 (exercise intervention:control group). Study measures were completed at baseline, post-IC, and following the first cycle of consolidation. The intervention consisted of a supervised mixed-modality, moderate-intensity exercise program (4-5 days per week, 30-60min per session) throughout admission. Recruitment was good (56%), retention excellent (96%), and adherence was 54%. Global QOL improved similarly in both groups from baseline to post-IC (between-group difference 3.0 points, p=0.62). Fatigue improved in the exercise group from baseline to post-IC (potentially clinically important between-group difference of 3.6 points, p=0.23). Aerobic fitness, lower body strength, and grip strength improved in the exercise group (between-group differences p=0.005, p<0.001, p=0.03, respectively). Supervised exercise for patients with AML undergoing IC is feasible, safe, and appears effective at improving fitness and possibly fatigue. A larger trial is warranted.

Regional cerebral arterial transit time hemodynamics correlate with vascular risk factors and cognitive function in men with coronary artery disease.

BACKGROUND AND PURPOSE: Arterial transit time is the time needed for blood to travel from large arteries to capillaries, as estimated from arterial spin-labeling MR imaging. The purpose of this study was to determine whether vascular risk factors and cognitive performance are related to regional differences in cerebral arterial transit time in patients with coronary artery disease who are at risk for cognitive decline. MATERIALS AND METHODS: Arterial transit time was estimated from multiple postlabel delay pseudocontinuous arterial spin-labeling images obtained from 29 men with coronary artery disease. Tests of memory, attention, processing speed, and executive function were administered. Principal component analysis was used to create separate models of cognition and vascular risk, which were related to brain regions through voxelwise analyses of arterial transit time maps. RESULTS: Principal component analysis identified 2 components of vascular risk: 1) "pressor" (age, systolic blood pressure, and pulse pressure) and 2) "obesity" (body fat percentage and body mass index). Obesity was inversely related to arterial transit time in the posterior cingulate, precuneus, lateral occipital cortices, middle temporal gyrus, and frontal pole (P corrected < .05), whereas pressor was not significant. Cognitive scores were factored into a single component. Poor performance was inversely related to precuneus arterial transit time (P corrected < .05). The average arterial transit time in regions identified by obesity was associated with poorer cognitive function (r(2) = 0.21, t = -2.65, P = .01). CONCLUSIONS: Altered cerebral hemodynamics, notably in nodal structures of the default mode network, may be one way that vascular risk factors impact cognition in patients with coronary artery disease.

Quality of life and psychosocial measures influenced by exercise modality in patients with coronary artery disease.

BACKGROUND: The optimal approach to prescribing resistance training (RT) combined with aerobic training (AT) for psychosocial and health-related quality of life (HRQOL) is unclear. AIM: To compare the effects of AT combined with RT (1 versus 3 sets) versus AT alone on HRQOL and psychosocial outcomes. DESIGN: Subjects (N.=72) were randomized to AT (5 d∙wk-1) or AT (3 d∙wk-1) with either 1 set (AT/RT1) or 3 sets (AT/RT3) of RT performed 2 d∙wk-1. SETTING: Outpatient Cardiac Rehabilitation Program. POPULATION: Subjects with coronary artery disease. METHODS: HRQOL and psychosocial parameters were assessed before and after 29 weeks of training by questionnaire. RESULTS: Fifty-three subjects (mean±SD age 60.6±10.6 years) completed training. There was a group effect for change in self-efficacy of lower body physical activity tasks (P=0.03) with significantly greater improvement for AT/RT3 than AT alone (17.5±16.6% vs. 3.2±12.8% respectively, p=0.04). Lower body self-efficacy improved for AT/RT1 (15.5±13.8%, p<0.001) but not for AT alone (P=0.2). Self-efficacy for upper body tasks improved with AT/RT3 (18.2±19.9%, P=0.003) and AT/RT1 training (12.6±15.8%, P=0.005) but not with AT alone (8.3±16.1%, P=0.1). AT/RT3 and AT/RT1 training yielded improvements in depression score (-4.0±7.7, P=0.04 and -3.0±5.1, P=0.02 respectively) but not with AT alone (-0.5±4.7, P=0.71). The improvement from baseline in physical HRQOL score (MOS, SF-36) averaged 8.2±11.2% for AT (P=0.04), 10.4±11.9% for AT/RT1 (P=0.006) and 12.0±12.9% for AT/RT3 (P=0.004). CONCLUSIONS: Both AT+RT groups with either 1 or 3 sets (AT 3 d∙wk-1and RT 2 d∙wk-1) each yield more pronounced psychosocial and HRQOL adaptations than AT alone (5 d∙wk-1). RT prescription beyond 1 set may further augment selected parameters in cardiac patients. CLINICAL REHABILITATION IMPACT: These results provide further rationale to develop combined AT+RT regimens for individuals with coronary artery disease.

Predictors of low bone mineral density of the stroke-affected hip among ambulatory individuals with chronic stroke.

UNLABELLED: Risk of hip fracture is greater poststroke than in an age-matched healthy population, in part because of declining hip BMD. We found that individuals may be at risk of loss of hip BMD from muscle atrophy, asymmetrical gait, and poor affected-side ankle dorsiflexor strength. These impairments may be targeted during rehabilitation. INTRODUCTION: This study aimed to determine predictors of low hip BMD on the stroke-affected side in people living in the community. METHODS: Forty-three participants (female; 27.9%), mean age 62.4 ± 13.5 and 17.9 ± 32.8 months, poststroke with motor impairments underwent dual energy X-ray absorptiometry scans. Gait characteristics, isometric strength, body composition, and fasting plasma lipids were measured. RESULTS: At entry, 34.9% (15/43) of the participants had low total hip BMD on the stroke-affected side. Of those with low BMD, 93.3% (14/15) had a step length symmetry ratio >1, indicating greater reliance on the non-paretic leg for weight bearing. Logistic regression analysis revealed that lower affected-side ankle dorsiflexor strength (ß = 0.700, p = 0.02), lower total body fat-free mass index (ß = 0.437, p = 0.02), and greater step length symmetry ratio during walking (ß = 1.135 × 10(3), p = 0.03) were predictors of low hip BMD. CONCLUSION: Low BMD of the stroke-affected side hip is prevalent in over a third of individuals with lower limb motor impairments. These individuals may be at particular risk of accelerated loss of BMD at the hip from asymmetrical gait pattern and poor affected-side ankle dorsiflexor strength. These impairments are intervention targets that may be addressed during rehabilitation which includes resistance training and addresses gait impairments.

Brain derived neurotrophic factor, cardiopulmonary fitness and cognition in patients with coronary artery disease.

OBJECTIVE: To assess serum brain derived neurotrophic factor (BDNF) concentrations as a correlate of cardiopulmonary fitness and as a predictor of cognitive performance in subjects with coronary artery disease (CAD). METHODS: Serum BDNF concentrations were assayed by ELISA and fitness was assessed using a standardized exercise stress test. The Mini Mental Status Examination (MMSE), California Verbal Learning Test 2nd Ed., Stroop, Trail Making Test B and the Digit Symbol-Coding task were administered. The val66met BDNF genotype and serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations were determined as potential confounders. RESULTS: In subjects with CAD (n=88; 85.2% male, mean age 62.8±10.5 yr), cardiopulmonary fitness was associated with higher serum BDNF concentrations (ß=.305, p=.013). Higher serum BDNF concentrations were associated with higher MMSE scores (F(1,87)=15.406, p<.0005) and better performance on the Digit Symbol-Coding task (F(1,87)=9.620, p=.003). IL-6, TNF-α and the val66met genotype did not influence these results. CONCLUSION: Serum BDNF concentrations were associated with cardiopulmonary fitness, psychomotor processing speed and overall cognition in subjects with CAD.

Pharmacoeconomic evaluation of clozapine in treatment-resistant schizophrenia: a cost-utility analysis.

The high costs and efficacy of clozapine warrant a systematic pharmacoeconomic evaluation to assess its relative cost-utility compared with that of older antipsychotic therapies. An economic analysis of clozapine consisted of a meta-analysis and a cost-utility analysis. Clozapine was compared with haloperidol and chlorpromazine. An incidence-based deterministic decision analysis was used to model the management of chronic schizophrenia over one year. Probabilities of clinical outcomes were obtained from a random effects, single arm meta-analysis. Utility weights were evaluated in a cohort of patients by using a standard gamble methodology. A government payer perspective was adopted for this analysis. Clozapine was the dominant therapy in this analysis because it was associated with the lowest overall expected cost and highest expected number of quality-adjusted life years (QALYs). Compared with chlorpromazine, clozapine might save $38,879/year while producing 0.04 more QALYs. This analysis was limited in that studies were of short duration, the sample size for health utility analysis was small and the analysis was based on a model. Clozapine appears to be a very cost effective therapy in patients with treatment-resistant schizophrenia compared with haloperidol and chlorpromazine.

The health status of obese individuals in Canada.

OBJECTIVE: To determine whether there is a clinically relevant difference in the health state utilities of obese and non-obese individuals as measured by the Health Utility Index Mark III. METHODS: Secondary analysis of the population-based, cross-sectional, interviewer-administered National Population Health Survey (NPHS), 1996-1997. A probability sample of house-dwelling Canadians, excluding populations on First Nations Reserves, Canadian Armed Forces Bases, the Yukon and Northwest Territories, and long-term residents of hospitals or residential care facilities. The sub-sample used in this analysis consisted of 38 151 respondents (52.4% male) between the ages of 20 and 64 y, excluding pregnant women. Health Utilities Index-Mark III (HUI3) scores were used to define normal weight (body mass index (BMI) 19-24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)), obese (BMI 30-34.9 kg/m(2)), and morbidly obese (BMI> or =35 kg/m(2)) individuals. HUI3 scores were age- and gender-standardized. RESULTS: The overall prevalence of obesity (BMI> or =30 kg/m(2)) in this Canadian population was 13.3%. The average difference in HUI3 scores between normal weight and morbidly obese respondents was 0.04 (P<0.001). Statistically significant (P<0.05) differences across BMI categories were found in each of the eight component attributes of the HUI3. The attributes with the most substantial difference between normal and obese patients were cognition, mobility and pain. All demonstrated a > or =2-fold increase in the proportion of individuals in poorer classifications of health when normal weight respondents were compared with the morbidly obese. The magnitude of the decrement in utility ratings associated with obesity was comparable with other chronic non-cardiovascular conditions such as migraine or colitis. CONCLUSION: The results indicate that changes in self-rated health status appear to be due to significant changes across several relevant domain attributes. Obesity has a significant impact on both quality of life and health.

The economic impact of methicillin-resistant Staphylococcus aureus in Canadian hospitals.

OBJECTIVES: To determine the costs associated with the management of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA), and to estimate the economic burden associated with MRSA in Canadian hospitals. DESIGN: Patient-specific costs were used to determine the attributable cost of MRSA associated with excess hospitalization and concurrent treatment. Excess hospitalization for infected patients was identified using the Appropriateness Evaluation Protocol, a criterion-based chart review process to determine the need for each day of hospitalization. Concurrent treatment costs were identified through chart review for days in isolation, antimicrobial therapy, and MRSA screening tests. The economic burden to Canadian hospitals was estimated based on 3,167,521 hospital discharges for 1996 and 1997 and an incidence of 4.12 MRSA cases per 1,000 admissions. SETTING: A tertiary-care, university-affiliated teaching hospital in Toronto, Ontario, Canada. PATIENTS: Inpatients with at least one culture yielding MRSA between April 1996 and March 1998. RESULTS: A total of 20 patients with MRSA infections and 79 colonized patients (with 94 admissions) were identified. This represented a rate of 2.9 MRSA cases per 1,000 admissions. The mean number of additional hospital days attributable to MRSA infection was 14, with 11 admissions having at least 1 attributable day. The total attributable cost to treat MRSA infections was $287,200, or $14,360 per patient The cost for isolation and management of colonized patients was $128,095, or $1,363 per admission. Costs for MRSA screening in the hospital were $109,813. Assuming an infection rate of 10% to 20%, we determined the costs associated with MRSA in Canadian hospitals to be $42 million to $59 million annually. CONCLUSIONS: These results indicate that there is a substantial economic burden associated with MRSA in Canadian hospitals. These costs will continue to rise if the incidence of MRSA increases further.

Cost-effectiveness analysis of six strategies for cardiovascular surgery prophylaxis in patients labeled penicillin allergic.

The cost-effectiveness of different approaches to antimicrobial prophylaxis for cardiovascular surgery patients labeled penicillin allergic was studied. A decision-analytic model was used to examine the cost-effectiveness of six strategies for antimicrobial prophylaxis in cardiovascular surgery patients at a tertiary care hospital. The strategies consisted of (1) giving vancomycin to all patients labeled penicillin allergic, (2) giving cefazolin to all patients labeled penicillin allergic, (3) giving vancomycin to all patients with a history suggesting an immunoglobulin E (IgE)-mediated reaction to penicillin and cefazolin to patients without such a history, (4) administering a penicillin skin test to patients with a history suggesting an IgE-mediated reaction to penicillin and giving vancomycin to patients with positive results and cefazolin to all others, (5) skin testing all patients labeled penicillin allergic and giving vancomycin to those with positive results and cefazolin to those with negative results, regardless of history, and (6) skin testing all patients and giving vancomycin to those with positive results or a history suggesting an IgE-mediated reaction to penicillin and cefazolin to all others. Giving cefazolin to all patients labeled penicillin allergic was the least expensive strategy but was associated with the highest rate of both anaphylactic and non-life-threatening serious reactions. Selective use of vancomycin in patients with a history suggesting an IgE-mediated reaction to penicillin was associated with an added cost and a slightly lower rate of anaphylaxis. Although skin-testing strategies may decrease both non-life-threatening and anaphylactic reactions, the incremental cost was high. When vancomycin was given to all patients labeled penicillin allergic, the incremental cost was very high. A decision-analytic model indicated that selective use of vancomycin is more cost-effective than indiscriminate use of vancomycin for surgical prophylaxis in cardiovascular surgery patients labeled penicillin allergic.

Holistic versus composite preferences for lifetime treatment sequences for type 2 diabetes.

This study of patient preferences for lifetime treatment sequences for type 2 diabetes had three objectives: to assess the feasibility of obtaining holistic preference assessments using the time-tradeoff (TTO) technique; to compare composite and holistic preference scores for the same lifetime treatment paths; and to assess the validity of composite and holistic preference measures in terms of their congruence with an individual's rank-order preferences. 101 persons with type 2 diabetes provided preference ratings for hyperglycemic treatments lasting 30 years, including eight discrete treatment states and four treatment paths. Scenarios described drug and glucose-testing regimens, efficacy of glucose control, and side effects. After ranking and rating scenarios on a thermometer scale, subjects provided TTO preferences for each treatment state or path scenario. Holistic assessment of treatment paths was feasible with the TTO technique, in terms of useable data (88% of interviews) and effect on coefficients of variation. Holistic and composite preference scores were not statistically different. Agreement was poor between rankings implied by holistic and composite scores and direct rankings. The authors conclude that lifetime treatment paths with minor differences in health effects can be assessed using either composite (QALY) or holistic (HYE) measures. The validity of these TTO-based preference measures remains unknown.

Quantifying the costs of serious adverse drug reactions to antiepileptic drugs.

PURPOSE: We assessed from an institutional perspective the direct costs of severe adverse cutaneous or hypersensitivity reactions due to antiepileptic drug (AED) therapy that led to hospitalization or prolonged hospital stay. METHODS: Patients admitted for or developing severe AED-induced cutaneous or hypersensitivity reactions while in hospital from January 1990 through June 1996 were identified by ICD-9 codes E936, E937, E693, E695.1, E995.1, and E995.2. Identified cases were analyzed retrospectively by chart review and were included in the analysis if a causal relationship was determined to be possible, probable, or definite. Clinical outcomes were abstracted and related direct costs of the adverse drug reactions (ADRs) calculated. RESULTS: A total of 384 cases were identified by ICD-9 codes, of which 13 cases (mean age +/- SD 52.9+/-21.0 years) were included for further analysis. Eight patients (62%) were admitted because of an ADR (median length of stay 9.5 days; range 4-43), five (38%) experienced an ADR during hospitalization (median duration of ADR episodes 8.5 days; range: 7-21 days). The median direct medical costs of the ADRs were Canadian (CDN) $3,128 (range 1,149-21,293) per patient. CONCLUSIONS: The management of serious cutaneous and hypersensitivity ADRs due to AEDs is associated with considerable direct medical costs. These figures should be considered along with drug acquisition costs and treatment of clinical successes and failures in the overall assessment of the economic impact of pharmacotherapy. Prospective collection of direct costs associated with ADRs in clinical trials would be of value.

Efficacy and safety of neuroleptics in behavioral disorders associated with dementia.

BACKGROUND: Neuroleptics are commonly used to treat behavioral disorders associated with dementia. However, their safety and efficacy have not been well established in these patients. METHOD: A meta-analysis of randomized, controlled (either placebo or active drug), double-blind trials published since 1966 (N = 16; 499 treated, 112 active controls, and 123 placebo) was conducted. Data were collected on proportion of patients with clinically significant improvement, significant side effects, and dropout rates. RESULTS: Pooled mean percentages of patients who improved (95% CI): all neuroleptics, 64% (54% to 74%); low potency, 63% (54% to 72%); moderate potency, 70% (56% to 85%); moderate-high potency, 62% (49% to 75%); and high potency, 69% (49% to 90%). Thus, no differences in efficacy existed between different potencies of neuroleptics. Therapeutic effect (neuroleptic minus placebo) was only 26% (14% to 38%). Treatment-emergent side effects were more common for neuroleptics vs. placebo (mean difference = 25%, 13% to 37%), but pooled mean dropout rates were not different (mean difference = 4%, -7% to 14%). Neither weighting by clinical trial quality (3 raters; weighted agreement, 83% to 92%) nor exclusion of poor quality trials changed the results. CONCLUSION: Neuroleptics have small but significant efficacy over placebo in this population, and the efficacy rate is equivalent to the side effect rate. Comparing different neuroleptics shows they have similar efficacy, side effects, and dropout rates. Further study to determine more specific drug-responsive behaviors is needed to maximize benefits of these drugs.

Overtreatment of hypertension in the community?

Some patients currently receiving therapy for uncomplicated, mild to moderate essential hypertension may have been started on medication because of transient increases in office blood pressure (BP) or because of "white coat hypertension." As a consequence, many patients who do not have persistent hypertension may be receiving therapy for this diagnosis. This possibility was examined by discontinuing medication in 98 patients without target organ damage who were receiving longterm antihypertensive therapy under the care of their family physician in the community. Development of hypertension was based upon an increase in the patient's ambulatory BP (mm Hg) to > or = 160/95 recorded during usual daily activities. Evidence of early target organ damage was sought by using echocardiography to measure changes in left ventricular mass during the period off therapy. In the 50 patients who remained off treatment for 1 year, mean ambulatory BP increased (P < .001 from baseline (128 +/- 2/76 +/- 1) to 139 +/- 1/82 +/- 1 at 1 year, but remained lower (P < .001) than corresponding office readings performed by the patient's family physician (baseline: 138 +/- 2/83 +/- 1; 1 year: 150 +/- 2/89 +/- 1). At 1 year, ambulatory BP was < 150/90 and < 140/90 in 41 and 21 patients, respectively. Withdrawal of therapy did not produce any changes in left ventricular mass index (g/m2) with the mean value at 1 year (104 +/-3) being similar to baseline (103 +/- 3). Of the remaining patients, 35 redeveloped hypertension and 13 restarted therapy for reasons unrelated to BP. Many patients with treated, uncomplicated, mild to moderate hypertension may tolerate withdrawal of antihypertensive drug therapy without developing persistent hypertension or any increase in left ventricular mass.

A cost-utility analysis of second-line antibiotics in the treatment of acute otitis media in children.

Newer antibiotics have higher acquisition costs than the first-line antibiotics but may offer superior outcomes, including enhanced eradication of resistant organisms, safety, and compliance in the treatment of acute otitis media. A rational choice among differing therapies should systematically address all these factors. We conducted a cost-utility analysis to compare the commonly used second-line antibiotics--cefaclor (CEF), amoxicillin-clavulanate (AMX-CLA), and erythromycin-sulfisoxazole (ERY-SULF). A meta-analysis of comparative clinical trials was performed to derive point estimates with a 95% confidence interval for rates of success and adverse events. Costs for drugs, laboratory tests, and physician visits were obtained from the government formulary and fee schedules. The cost for management of adverse events was estimated from the findings of a survey of pediatricians. Utilities (preferences or ratings of health states) were derived from responses of physicians to a standardized scenario of acute otitis media with combinations of adverse events. These utilities were used to obtain quality-adjusted life-day (QALD) scores over a 30-day horizon as a measure of effectiveness. Overall cost and QALD were calculated using decision analytic modeling. CEF performed significantly better than the two other drug treatments with the lowest expected cost ($108.00) and highest outcome (28.15 QALD); AMX-CLA was second in cost and third in outcome ($119.00, 27.98 QALD); and ERY-SULF was third in cost and second in outcome ($120.00, 28.03 QALD). These rankings were robust to variations in event rates over the 95% confidence interval. In this analysis, CEF was the most cost-effective antibiotic strategy for second-line therapy when differential success rates, adverse-event profiles, and impact on quality-of-life were considered.

A crossover comparison of extended release felodipine with prolonged action nifedipine in hypertension.

In a crossover design, control of blood pressure by extended release felodipine was compared with control by prolonged action nifedipine in 21 children with renal hypertension. Compliance with once daily felodipine was higher than with nifedipine, at 95.6 (SEM 2.7)% v 78.9 (6.0)% (p = 0.02). Mean diastolic blood pressure was lower during the day with felodipine than with nifedipine, at 77.6 (2.4) v 84.4 (2.8) mm Hg (p = 0.05). Similarly, blood pressure load (the percentage of the day during which the child had blood pressure exceeding the upper limits of normal for age) was lower for felodipine than for nifedipine: 43.5 (5.5)% v 61.3 (6.3)%. There was an opposite trend during the night, though this did not reach statistical significance. These data suggest that once a day felodipine is effective in children with hypertension. This may be because of improved compliance.

Prevalence of white coat effect in treated hypertensive patients in the community.

Patients receiving drug therapy for hypertension in the tertiary care setting frequently exhibit higher office readings compared to ambulatory blood pressure values (white coat effect). In this study, the prevalence of a white coat effect was determined in an unselected population of 147 hypertensive patients receiving treatment from their family physicians in the community. The proportion of patients with a white coat effect (defined as office - ambulatory blood pressure > or = 20/10 mm Hg) was significantly (P < .001) higher when based upon the family physician's routine blood pressure readings (91/147), compared to special readings taken by the family physician for the study (54/147) or readings taken by a research nurse (30/147). There was a higher correlation (P < .05) between the ambulatory systolic blood pressure and the nurse's readings (r = 0.62) or special physician's readings (r = 0.55) v the routine physician's readings (r = 0.34). Left ventricular mass index as measured by echocardiography correlated (P < .01) with the special physician (r = 0.27), nurse (r = 0.23), and ambulatory systolic blood pressure readings (r = 0.24), but not with the routine physician's readings (r = 0.06). A white coat effect is frequently present in treated hypertensive patients when blood pressure is recorded by family physicians in routine clinical practice.