Between-treatment Group Differences Research Articles

Does Radiographic Alignment Correlate With Patient-Reported Functional Outcomes and Posttreatment Complications in Older Patients Treated for Wrist Fractures?

Surgical treatment of distal radius fractures provides better fracture alignment than closed reduction; however, surgical treatment does not lead to better patient-reported function at 12 months. The aims of this study were to report the radiographic outcomes from the Combined Randomized and Observational Study of Surgery for Fractures In the distal Radius in the Elderly trial, investigate the association between radiographic outcomes and patient-reported function, and explore whether this association was affected by posttreatment complications and direction of malalignment. This study used the outcomes of the Combined Randomized and Observational Study of Surgery for Fractures In the distal Radius in the Elderly trial, which is a combined randomized and observational trial that compared volar-locking plate fixation with closed reduction and cast immobilization, to treat distal radius fractures in patients aged ≥60 years. Four radiographic outcomes (dorsal angulation, radial inclination, ulnar variance, and articular step) were reported at the following three time frames: (1) baseline, (2) after treatment, and (3) ≥6 weeks by treatment group. Secondary analysis was correlation of 12-month patient-reported function scores with 6-week radiographic measures for each of four radiographic parameters, and a subgroup analysis was conducted to investigate if this was affected by posttreatment complications. Tertiary analysis investigated if direction of malalignment affected the secondary analysis. We recruited 300 participants (166 randomized and 134 observational); 113 had volar-locking plate fixation, and 187 had closed reduction. There were no between-group differences for each of the four pretreatment radiographic parameters, but there were between-treatment group differences for all four radiographic parameters apart from articular step. We found no association between patient-reported function at 12 months and each of the four radiographic parameters at 6 weeks. This lack of association was unaffected by posttreatment complications and the direction of malalignment. For patients with wrist fractures aged ≥60 years, final radiographic alignment did not correlate with patient-reported function at 12 months. These findings were not affected by treatment type, and there was no association between radiographic alignment and posttreatment complications. Therapeutic IV.

6030Effects of adjunctive treatment with low-dose alteplase during primary percutaneous coronary intervention according to ischaemic time

Abstract Background Microvascular obstruction affects half of patients with acute ST-segment elevation myocardial infarction and confers an adverse prognosis. Purpose We aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intra-coronary alteplase infused early after coronary reperfusion associates with ischaemic time. Methods We conducted a prospective, multicentre, parallel group, 1:1:1 randomised, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischaemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified sub-group of interest. Between March 17, 2016, and December 21, 2017, 440 patients presenting at 11 hospitals in the UK were enrolled with follow up to 3 months. Patients with acute myocardial infarction due to occlusion of a major coronary artery presenting ≤6 hours from symptom onset were randomly assigned to treatment with placebo, alteplase 10mg or alteplase 20mg. The primary outcome was the amount of microvascular obstruction disclosed by cardiac magnetic resonance imaging at 2–7 days. Secondary outcomes included infarct size, myocardial haemorrhage, left ventricular ejection fraction, and troponin T area-under-the curve. Results 440 patients were randomized (figure), the primary endpoint was achieved in 396 (90%), seventeen (3.9%) withdrew and all other patients were followed up to 3 months. In the primary analysis, the amount of microvascular obstruction did not differ between the groups. Their ischaemic times were: ≤2 hours, n=98; ≥2–<4 hours, n=215; and ≥4–6 hours, n=83. In patients with an ischaemic time ≥4 hours, treatment with alteplase (10 mg, n=26; 20 mg, n=30) was associated with a dose dependent increase in the amount (mean) of microvascular obstruction (% left ventricular mass) compared to placebo (n=27) 1.14 vs. 3.11 vs. 5.20; mean difference on square root scale 0.81 (95% CI 0.21, 1.42), p=0.009. The interaction test between ischaemic time and treatment (active vs. placebo) was not statistically significant p=0.06, however when the interaction was assessed for a trend across treatment groups this did reach statistical significance, p=0.018. Furthermore, a higher proportion of patients presenting ≥4–6 hours treated with 20 mg of alteplase had myocardial haemorrhage (59.3%) compared to the placebo group (28.0%), odds ratio 3.81 (95% CI 1.19, 12.25), p=0.025. The amount of haemorrhage was also greater; estimated mean difference 3.49 (95% CI 1.22, 5.75), p=0.0026. No between-treatment group differences for myocardial haemorrhage were observed in patients presenting with shorter ischaemic times. Study flow diagram Conclusions In patients presenting with an ischaemic time ≥4 hours, adjunctive treatment with low-dose intra-coronary alteplase during primary PCI was associated with increases in microvascular obstruction and myocardial haemorrhage. The mechanism may involve haemorrhagic transformation within the infarct core. Acknowledgement/Funding NIHR EME programme (reference: 12/170/45); British Heart Foundation (BHF reference FS/16/74/32573)

Tannin-rich sainfoin pellet supplementation reduces fat volatile indoles content and delays digestive parasitism in lambs grazing alfalfa

Lambs grazing alfalfa or white clover are prone to flavour taint which can be an impediment to consumer acceptance. Here we investigated whether condensed tannin (CT)-rich sainfoin pellet supplementation of lambs grazing alfalfa influences meat sensory quality. Using three groups of 18 male Romane weaned lambs, we compared three feeding regimes: alfalfa grazing (AF), alfalfa grazing + daily supplementation with CT-rich sainfoin pellets (15 g dry matter (DM)/kg live weight, AS) and stall feeding with concentrate and grass hay indoors (SI). We also investigated the potential interest of sainfoin pellet supplementation for controlling digestive parasitism. The sainfoin pellets contained 42 g of CT/kg of DM and they represented on average 36% of the diet in AS lambs. Skatole and indole were detected in most of the AF and AS lambs, whereas in very few SI lambs. Skatole and indole concentrations in perirenal and dorsal fat were lower in the AS lambs than the AF lambs (P < 0.025 to P < 0.001), but the intensity of ‘animal’ odour and ‘animal’ flavour of the chops did not differ between both forage-grazing groups. Longissimus thoracis et lumborum muscle lightness was lower in the AF and AS lambs than the SI lambs (P < 0.001) with the other muscle colour coordinates being unaffected by the treatment and between-treatment group differences in muscle colour coordinates remaining constant throughout the 9-day display period. Subcutaneous fat colour coordinates were not influenced by the treatment. The number of individual anthelmintic drenches necessary to keep nematode faecal egg count below a threshold of 550 eggs/g of faeces was lower in the AS than the AF lambs (0.94 per lamb v. 1.63 per lamb; P < 0.001). Faecal oocyst count was lower in the AS than the AF lambs for the first measurement made 56 days after the beginning of the experiment (P < 0.001) and was not significantly different between both forage-grazing groups thereafter. The use of CT-rich sainfoin pellets to supplement lambs that are concurrently grazing alfalfa reduced fat volatile skatole and indole concentrations and delayed the onset of both helminth and coccidian infections.

Characteristics of Elderly Patients Initiating Sitagliptin or Non-DPP-4-Inhibitor Oral Antihyperglycemic Agents: Analysis of a Cross-Sectional US Claims Database.

IntroductionPrevious analyses concluded that patients initiating treatment with sitagliptin are older and have more comorbidities than patients initiating treatment with other oral antihyperglycemic agents (OAHAs). However, these studies focused on the general population or subjects ≤ 65 years of age. We sought to compare differences in baseline characteristics of elderly patients (≥ 65 years of age) with T2DM initiating sitagliptin vs. non-DPP-4 inhibitor (non-DPP-4i) OAHA in the MarketScan® Medicare Supplemental Database.MethodsRelevant patients were identified in the MarketScan® Medicare Supplemental Database and categorized according to the complexity of their antihyperglycemic treatment: initiating monotherapy, escalating to dual combination therapy, or escalating to triple combination therapy. Within each category, the comparison between patients initiating use of sitagliptin or non-DPP-4i OAHA was made within three age groups: 65–74, 75–84, and ≥ 85 years. Gender and comorbidity recorded within the 12 months prior to the index date (date of initiation/escalation of treatment) were assessed as baseline characteristics in each group. Between-treatment group differences in each covariate were compared using standardized differences.ResultsPatients with T2DM who initiated treatment with sitagliptin tended to be older and were more likely to have a pre-treatment history of arrhythmia, congestive heart failure, peripheral vascular disease, renal failure, and stroke than those initiating non-DPP-4i OAHAs, with the most pronounced differences observed between patients initiating monotherapy in all three age groups. As treatment complexity advanced to dual combination therapy, the differences were attenuated and mostly observed in the 75–84 and ≥ 85 age groups. In patients aged 65–74 years initiating triple therapy, no differences were observed between groups.ConclusionPatients ≥ 65 years with T2DM initiating sitagliptin tend to be older and have more comorbidities than those prescribed other classes of OAHA. Appropriate adjustment is required to minimize the impact of potential confounding and channeling bias in any comparative analyses including users of sitagliptin.FundingMerck & Co., Inc., Kenilworth, NJ, USA.

Patients receiving frequent hemodialysis have better health-related quality of life compared to patients receiving conventional hemodialysis

Most patients with end-stage kidney disease value their health-related quality of life (HRQoL) and want to know how it will be affected by their dialysis modality. We extended the findings of two prior clinical trial reports to estimate the effects of frequent compared to conventional hemodialysis on additional measures of HRQoL. The Daily Trial randomly assigned 245 patients to receive frequent (six times per week) or conventional (three times per week) in-center hemodialysis. The Nocturnal Trial randomly assigned 87 patients to receive frequent nocturnal (six times per week) or conventional (three times per week) home hemodialysis. All patients were on conventional hemodialysis prior to randomization, with an average feeling thermometer score of 70 to 75 (a visual analog scale from 0 to 100 where 100 is perfect health), an average general health scale score of 40 to 47 (a score from 0 to 100where 100 is perfect health), and an average dialysis session recovery time of 2 to 3 hours. Outcomes are reported as the between-treatment group differences in one-year change in HRQoL measures and analyzed using linear mixed effects models. After one year in the Daily Trial, patients assigned to frequent in-center hemodialysis reported a higher feeling thermometer score, better general health, and a shorter recovery time after a dialysis session compared to standard thrice-weekly dialysis. Afterone year in the Nocturnal Trial, patients assigned tofrequent home hemodialysis also reported a shorter recovery time after a dialysis session, but no statistical difference in their feeling thermometer or general health scores compared to standard home dialysis schedules. Thus, patients receiving day or nocturnal hemodialysis on average recovered approximately one hour earlier from a frequent compared to conventional hemodialysis session. Patients treated in an in-center dialysis facility reported better HRQoL with frequent compared to conventional hemodialysis.

Calcium channel blockers for primary Raynaud's phenomenon.

Calcium channel blockers are the most commonly prescribed drugs for people with primary Raynaud's phenomenon. Primary Raynaud's phenomenon is a common condition characterised by an exaggerated vasospastic response to cold or emotion: classically the digits (fingers and toes) turn white, then blue, then red. This is an update of the review first published in 2014. To assess the effects of different calcium channel blockers for primary Raynaud's phenomenon as determined by attack rates, severity scores, participant-preference scores and physiological measurements. For this update the Cochrane Vascular Trial Search Co-ordinator searched the Specialised Register (last searched January 2016) and the Cochrane Register of Studies (CENTRAL) (2015, Issue 12). In addition the TSC searched clinical trials databases. Randomised controlled trials evaluating the effects of oral calcium channel blockers for the treatment of primary Raynaud's phenomenon. Three review authors independently assessed the trials for inclusion and their quality, and extracted the data. Data extraction included adverse events. We contacted trial authors for missing data. We included seven randomised trials with 296 participants. Four trials examined nifedipine and the remainder nicardipine. Comparisons were with placebo in six trials and with both dazoxiben and placebo in one trial (only the nifedipine versus placebo data were used within this review). Treatment with oral calcium channel blockers was minimally effective in primary Raynaud's phenomenon at decreasing the frequency of attacks (standardised mean difference of 0.23; 95% confidence interval (CI) 0.08 to 0.38, P = 0.003). This translates to 1.72 (95% CI 0.60 to 2.84) fewer attacks per week on calcium channel blockers compared to placebo. One trial provided details on duration of attacks reporting no statistically significant difference between the nicardipine and placebo groups (no P value reported). Only two trials provided any detail of statistical comparisons of (unvalidated) severity scores between treatment groups: one of these trials (60 participants) reported a mean severity score of 1.55 on placebo and 1.36 on nicardipine, difference 0.2 (95% CI of difference 0 to 0.4, no P value reported) and the other trial (three participants only with primary Raynaud's phenomenon) reported a median severity score of 2 on both nicardipine and placebo treatment (P > 0.999) suggesting little effect on severity. Participant-preference scores were included in four trials, but in only two were results specific to participants with primary Raynaud's phenomenon, and scoring systems differed between trials: scores differed between treatments in only one trial, in which 33% of participants on placebo and 73% on nifedipine reported improvement in symptoms (P < 0.001). Physiological measurements were included as outcome measures in five trials (different methodologies were used in each): none of these trials found any statistically significant between-treatment group differences. Treatment with calcium channel blockers appeared to be associated with a number of adverse reactions, including headaches, flushing and oedema (swelling). Overall, the trials were classed as being at low or unclear risk of bias; and the quality of the evidence presented was moderate for number of attacks, very low for duration of attacks, high for severity scores and low for patient preference scores. The randomised controlled trials included in this review provide moderate quality evidence that oral calcium channel blockers are minimally effective in the treatment of primary Raynaud's phenomenon as measured by the frequency of attacks and high-quality evidence that they have little effect on severity. We are unable to comment on duration of attacks or on patient preference due to the very low and low quality of evidence as a result of small sample sizes in the included studies and the variable data quality of outcome measures.

Comparison of Composite Measures of Disease Activity in Psoriatic Arthritis Using Data From an Interventional Study With Golimumab

To compare the performance of the Psoriatic Arthritis Disease Activity Score (PASDAS), the Arithmetic Mean of the Desirability Function (AMDF), the Composite Psoriatic Disease Activity Index (CPDAI), and the Disease Activity Index for Psoriatic Arthritis (DAPSA) in the GO-REVEAL data set. The Disease Activity Score using 28 joints (DAS28) was used as a comparator. The GO-REVEAL study did not allow full computation of all the composite scores (a modified version of CPDAI was used). The performance of the scores at baseline and followup (weeks 14 and 24) was compared using effect sizes. All indices could distinguish response to treatment at 14 and 24 weeks. Effect sizes at 24 weeks for the 50 mg (100 mg) golimumab doses were 2.18 (2.36), 2.08 (2.36), 1.09 (1.41), 1.80 (1.78), and 1.13 (1.18) for PASDAS, AMDF, modified CPDAI, DAS28, and DAPSA, respectively. Comparison of 24-week values across the 3 treatment groups (placebo, golimumab 50 mg, and golimumab 100 mg) by an analysis of covariance using the baseline values as covariates gave the following F statistics: PASDAS 18.3, AMDF 19.6, modified CPDAI 9.4, DAS28 13.6, and DAPSA 7.9; all of these are highly significant. When the analysis was confined to the 2 golimumab treatment groups, there were no significant between-treatment group differences with any of the composite measures. PASDAS and AMDF were better able to distinguish treatment effect, having larger effect sizes at 24 weeks. PASDAS, AMDF, and modified CPDAI better reflected domains such as skin, enthesitis, and dactylitis.

Efficacy of solanezumab in patients with mild or moderate Alzheimer's disease: Pooled analyses findings from two phase III studies

Solanezumab, a humanized monoclonal antibody that binds the mid-domain of soluble amyloid beta (A b) peptide, was developed for treatment of Alzheimer's disease (AD). Two identically-designed Phase 3 trials were conducted. Pooled analyses findings from two double-blind, placebo-controlled Phase 3 trials are presented Participants with mild (baseline Mini-Mental State Examination [MMSE] score 20–26) to moderate (MMSE score 16–19) AD were randomized 1:1 to 400 mg solanezumab or placebo infusion every 4 weeks for 80 weeks. Primary outcomes of cognition and daily functioning were assessed using several Alzheimer's Disease Assessment Scale-Cognitive subscales (ADAS-Cog) and the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) inventory, respectively. Additional measures of efficacy and safety were also assessed. Mixed model repeated measures (MMRM) analyses were conducted for each of the efficacy measures. In the mild population, approximately 34 % less cognitive decline (ADAS-Cog 11, ADAS-Cog 14 and MMSE) was observed in the solanezumab versus placebo group (Table). In this population, there was no significant difference in overall functional decline between solanezumab versus placebo, but using a subset of instrumental ADLs (ADCS-iADL), the difference reached statistical significance (Table). In the moderate population, there were no between-treatment group differences in any cognitive or functional measure. In both mild and moderate populations, there were no significant treatment group-differences for Clinical Dementia Rating Scale-Sum of Boxes, Neuropsychiatric Inventory or quality of life measures. No individual serious adverse event was common, but significant treatment group differences were observed for Angina Pectoris, Congestive Heart Failure and Syncope (more common with solanezumab), and for Behavioral and Psychiatric Symptoms of Dementia and Mental Status Change (more common with placebo). Frequencies of treatment-emergent amyloid-related imaging abnormalities-edema/effusions (1.1% vs. 0.5%) and -hemosiderin deposition (9.1% vs. 7.3%) were greater with solanezumab, but not significantly different from placebo. There were no significant treatment-group differences in treatment-emergent changes in vital signs or laboratory measures. In a pooled analysis of solanezumab trial data, solanezumab reduced cognitive and functional decline in the mild but not the moderate AD population. Safety findings supported a favorable risk/benefit ratio.

Duloxetine treatment and glycemic controls in patients with diagnoses other than diabetic peripheral neuropathic pain: a meta-analysis

Objective:Mood disorders are often associated with poor glycemic control, and antidepressant treatments for mood and pain disorders can alter plasma glucose levels in patients with diabetes. A previous meta-analysis from three studies showed that duloxetine modestly increased fasting plasma glucose (FPG) and HbA1c levels in patients with diabetic peripheral neuropathic pain (DPNP). This meta-analysis examined whether there were any short- and long-term effects of duloxetine (20–120 mg/day) on glycemic control in patients with diagnoses other than DPNP.Research design and methods:Short-term data (9–27 weeks): seven studies of duloxetine in general anxiety disorder, fibromyalgia, and chronic lower back pain (CLBP). Long-term data: 41-week, uncontrolled extension of the short-term CLBP study and 52-week study in patients with recurrence of major depressive disorder.Main outcome measures:Baseline-to-endpoint changes in FPG and HbA1c levels.Results:In short-term studies, patients were randomly assigned to placebo (n = 1098) or duloxetine (n = 1563). Mean baseline-to-endpoint changes in FPG and HbA1c did not significantly differ in duloxetine-treated patients compared with placebo-treated patients. In the 41-week study (n = 181), duloxetine-treated patients experienced a small but significant within-group baseline-to-endpoint increase in HbA1c (mean change = 0.1%; p < 0.001). This result was in contrast to absence of effect on mean baseline-to-endpoint within-group changes in FPG (p = 0.326) in that study, and to absence of between-treatment changes in FPG (p = 0.744) and HbA1c (p = 0.180) in the 52-week placebo-controlled study.Conclusion:Duloxetine treatment did not significantly alter FPG and HbA1c levels compared with placebo treatment in the short-term studies. A small but statistically significant within-group increase in HbA1c was found in the 41-week study, but not in between-treatment group differences in the 52-week study. Neither of the long-term studies showed significant changes in the FPG levels. The small, non-reproducible HbA1c increase in one study of patients without DPNP may have resulted from patients with unrecognized diabetes in these trials.

Topiramate Treatment of Chronic Migraine: A Randomized, Placebo‐Controlled Trial of Quality of Life and Other Efficacy Measures

To define yet more clearly the utility of topiramate in the treatment of chronic migraine, we evaluated prespecified secondary endpoints from a recent randomized, double-blind, placebo-controlled, multicenter clinical trial. We previously reported that topiramate 100 mg per day produced a statistically significant reduction in mean monthly migraine/migrainous and migraine headache days compared with placebo treatment and that it was safe and generally well tolerated. Variables analyzed included between-treatment group differences in percent responders, change in the mean monthly rate of total headache days and headache-free days, change in average and worst daily headache severity, change in the mean monthly use of acute headache medications, and absolute change and percent change in a headache index. Additional analyses included evaluation of changes in: the associated symptoms of photophobia, phonophobia, and nausea; Migraine-Specific Quality of Life Questionnaire scores; Migraine Disability Assessment Scale scores; and Physician's and Subjects Global Impression of Change. The intent-to-treat population consisted of 306 patients (topiramate, n = 153; placebo, n = 153). Categorical responder rates of reductions in mean monthly migraine/migrainous days for topiramate- vs placebo-treated subjects were as follows: for > or =25% reduction: 68.6% vs 51.6% (P = .005); > or =50%: 37.3% vs 28.8% (P = .093); and > or =75%: 15.0% vs 9.2% (P = .061). The decrease in mean monthly total headache days and headache-free days for topiramate vs placebo treatment was 5.8 vs 4.7 days (P = .067). Compared with placebo, topiramate treatment resulted in statistically significant mean improvements in the Role Restrictive (P = .028) and Emotional Function (P = .036) domains of the Migraine-Specific Quality of Life Questionnaire, in the worst daily severity of migraine (P = .016), severity of photophobia (P = .032), frequency of vomiting (P = .018), photophobia (P = .038), phonophobia (P = .010), unilateral pain (P = .015), pulsatile pain (P = .023), and pain worsened because of physical activity (P = .047). In addition, there were trends observed (favoring topiramate) in average daily severity of migraine (P = .077), acute headache medication use (P = .127), severity of nausea (P = .098), frequency of nausea (P = .166), the Role Preventive domain of the Migraine-Specific Quality of Life Questionnaire (P = .061), and severity of phonophobia (P = .062). In addition to significantly reducing mean monthly migraine/migrainous and migraine headache days, treatment of chronic migraine with topiramate was effective with regard to several traditionally important and clinically relevant secondary outcomes in migraine prevention trials. Treatment with topiramate was well tolerated and not associated with serious adverse events.

Congestive heart failure is associated with lipoprotein components in statin-treated patients with coronary heart disease: Insights from the Incremental Decrease in End points Through Aggressive Lipid Lowering Trial (IDEAL)

Background Very few, if any, studies have assessed the ability of apolipoproteins to predict new-onset of congestive heart failure (HF) in statin-treated patients with coronary heart disease (CHD). Aims To employ the Incremental Decrease in End points Through Aggressive Lipid Lowering Trial (IDEAL) study database to assess the association of on-treatment lipoprotein components with prediction of HF events and to compare their predictive value with that of established risk factors such as hypertension and diabetes. Methods We used Cox regression models to study the relationships between on-treatment levels of apolipoproteins A1 and B to subsequent HF. Chi square information value from the log likelihood was used to compare the predictive value of lipoprotein components with established risk factors of HF. Findings In the IDEAL study, on-treatment apolipoproteins proved to be associated with the occurrence of new-onset HF. Variables related to low-density lipoprotein cholesterol (LDL-C) carried less predictive information than those related to high-density lipoprotein cholesterol (HDL-C), and apoA-1 was the single variable most strongly associated with HF. LDL-C was less predictive than both non-HDL-C (total cholesterol minus HDL-C) and apoB. The ratio of apoB to apoA-1 was most strongly related to HF after adjustment for potential confounders, among which diabetes had a stronger correlation with HF than did hypertension. ApoB/apoA-1 carried approximately 2.2 times more of the statistical information value than that of diabetes. Calculation of the net reclassification improvement index revealed that about 3.7% of the patients had to be reclassified into more correct categories of risk once apoB/apoA-1 was added to the adjustment factors. The reduction in risk by intensive lipid-lowering treatment as compared to usual-dose simvastatin was well predicted by the difference in apoB/apoA-1 on-treatment levels. Interpretation The on-treatment ratio of apoB/apoA-1 was the strongest predictor of HF in CHD patients of both IDEAL treatment arms combined, mostly driven by the strong association with apoA-1, whereas LDL-C and non-HDL-C were less able to predict HF outcome. The predictive information value contained within apoB/apoA-1 was about 2.2 times more than that of diabetes. Between-treatment group differences in HF were to a significant extent explained by on-treatment differences in apoB/apoA-1, mostly through the changes in apoB. We argue therefore, on-treatment lipoprotein components contribute to the overall future risk of HF in statin-treated patients with CHD.

Effects of a Life Skills Intervention for Increasing Physical Activity in Adolescent Girls

Although adolescence is a time when physical activity levels decline, few interventions have targeted high school-aged girls in the school setting. To evaluate the effects of a life skills-oriented physical activity intervention for increasing overall physical activity in high school-aged girls. Randomized controlled trial. Baltimore magnet high school. A total of 221 ninth-grade girls, 83.0% of whom were African American. Intervention Participants were randomized to an 8-month physical intervention conducted in physical education class or to a standard physical education class (control). Self-reported estimated daily energy expenditure (physical activity), self-reported sedentary activities (television viewing and computer or Internet use), cardiorespiratory fitness, and selected cardiovascular disease risk factors. Intervention classes spent 46.9% of physical education class time in moderate to vigorous activity compared with 30.5% of time for control classes (P<.001). There were no significant between-treatment group differences for mean daily energy expenditure (P = .93), moderate-intensity energy expenditure (P = .77), or hard to very hard energy expenditure (P = .69). The proportion of participants who spent 3 or more hours viewing television during school days declined from 22.3% to 17.0% in the intervention group, but remained at 26.7% for the control group (P = .03). Both groups improved their cardiorespiratory fitness (P<.001). A life skills-oriented physical education curriculum may need to be combined with other approaches to increase the magnitude of effects on physical activity behavior in predominantly African American high school-aged girls.

Efficacy and Safety of Lovastatin Therapy in Adolescent Girls With Heterozygous Familial Hypercholesterolemia

The present study was designed to evaluate the lipid-altering efficacy, safety, and tolerability of lovastatin treatment in adolescent girls with heterozygous familial hypercholesterolemia. A total of 54 postmenarchal girls, aged 10 to 17 years, were enrolled in a 24-week, double-blind, randomized, placebo-controlled study. After a 4-week diet/placebo run-in period, patients were randomized to 1 of 2 groups: (1) treatment with diet plus lovastatin 20 mg/day for 4 weeks, followed by diet plus lovastatin 40 mg/day for 20 weeks, or (2) diet plus placebo for 24 weeks. Baseline values of lipids, lipoproteins, and apolipoproteins (apo) were comparable between treatment groups. Lovastatin treatment was efficacious at reducing low-density lipoprotein cholesterol by 23% to 27%, total cholesterol by 17% to 22%, and apo B by 20% to 23% at weeks 4 and 24, respectively. Between-treatment group differences were not statistically significant for triglycerides, very-low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or apo A-I. Lovastatin was generally safe and well tolerated. There were no clinically significant alterations in vital signs (blood pressure and pulse rate), anthropomorphic measurements (height, weight, and BMI), hormone levels (luteinizing hormone, follicle-stimulating hormone, dehydroepiandrosterone sulfate, estradiol, and cortisol), menstrual cycle length, or tests of liver and muscle function. Lovastatin offers an efficacious and well-tolerated treatment option for improving lipid profiles in adolescent girls with familial hypercholesterolemia.

Correlates of Anticholinergic Activity in Patients With Dementia and Psychosis Treated With Risperidone or Olanzapine

Older individuals with dementia are highly sensitive to the effects of muscarinic receptor blockade. This was a 6-week multisite, randomized clinical trial. Eighty-six patients with probable Alzheimer's disease, vascular dementia, or mixed-etiology dementia (DSM-IV criteria) were randomly assigned to treatment with olanzapine or risperidone. Anticholinergic activity was measured with a radioreceptor assay, and plasma levels of antipsychotic medications were determined. Primary outcomes were assessed with the Udvalg for Kliniske Undersogelser (UKU) scale and somnolence adverse events; secondary outcome measures included scores on the Neuropsychiatric Inventory (NPI) and other scales. There were no between-treatment differences in the UKU scale or in somnolence adverse events. Statistically significant improvements (p < .001) from baseline were found for the NPI measures, with no between-treatment group differences. Olanzapine was associated with significant increases from baseline in anticholinergic activity, while risperidone was not; the between-treatment group differences were not statistically significant. Increase in anticholinergic activity was associated with an increase in anticholinergic side effects and slower performance on the Trail Making Test Part A. Higher endpoint anticholinergic activity was associated with higher endpoint scores on several items from the NPI, including delusions, anxiety, and aberrant motor behavior. Efficacious doses of olanzapine increased anticholinergic activity in older patients with dementia, while similarly efficacious doses of risperidone did not. Patients whose anticholinergic activity increased were more likely to experience anticholinergic side effects and to have worsening in certain cognitive domains. These data suggest that certain patients may be vulnerable to the anticholinergic activity associated with antipsychotic treatment.