Exercise therapy,cardiorespiratory fitness and their effect on brain volumes: A randomised controlled trial in patients with schizophrenia and healthy controls

The objective of this study was to examine exercise effects on global brain volume, hippocampal volume, and cortical thickness in schizophrenia patients and healthy controls. Irrespective of diagnosis and intervention, associations between brain changes and cardiorespiratory fitness improvement were examined. Sixty-three schizophrenia patients and fifty-five healthy controls participated in this randomised controlled trial. Global brain volumes, hippocampal volume, and cortical thickness were estimated from 3-Tesla MRI scans. Cardiorespiratory fitness was assessed with a cardiopulmonary ergometer test. Subjects were assigned exercise therapy or occupational therapy (patients) and exercise therapy or life-as-usual (healthy controls) for six months 2 h weekly. Exercise therapy effects were analysed for subjects who were compliant at least 50% of sessions offered. Significantly smaller baseline cerebral (grey) matter, and larger third ventricle volumes, and thinner cortex in most areas of the brain were found in patients versus controls. Exercise therapy did not affect global brain and hippocampal volume or cortical thickness in patients and controls. Cardiorespiratory fitness improvement was related to increased cerebral matter volume and lateral and third ventricle volume decrease in patients and to thickening in the left hemisphere in large areas of the frontal, temporal and cingulate cortex irrespective of diagnosis. One to 2 h of exercise therapy did not elicit significant brain volume changes in patients or controls. However, cardiorespiratory fitness improvement attenuated brain volume changes in schizophrenia patients and increased thickness in large areas of the left cortex in both schizophrenia patients and healthy controls.     

氟哌噻吨与氟奋乃静治疗精神分裂症的随机对照试验

目的：探索氟哌噻吨治疗精神分裂症的疗效及不良反应。方法：用氟哌噻吨和氟奋乃静随机双盲对照治疗精神分裂症共５２例，每组２６例，治疗期为６ｗｋ。采用ＢＰＲＳ，ＳＡＮＳ，ＣＧＩ和ＴＥＳＳ量表评分。结果：ＢＰＲＳ总分显著下降，Ｐ值均＜０．０１，在焦虑抑郁因子分及产生显效时间方面，氟哌噻吨组优于氟奋乃静组。ＳＡＮＳ总分及因子分方面氟哌噻吨组Ｐ值均＜０．０５，氟奋乃静组无统计学意义。结论：氟哌噻吨疗效优于氟奋乃静，氟奋乃静的锥体外系不良反应较氟哌噻吨为重。     

Enalapril dosage in progressive chronic nephropathy: a randomised, controlled trial

Objective In chronic renal failure, clearance of enalapril is reduced. Hence, a renoprotective effect may be achieved with lower doses than conventionally used. Since marked inter-patient variation in concentrations of enalaprilat has been shown in patients with renal failure despite equivalent dosage of enalapril, a direct comparison of the effect of high versus low plasma concentrations of enalaprilat on the progression of renal failure was undertaken.Methods Forty patients with a median glomerular filtration rate (GFR) of 17 (6–35) ml/min/1.73 m² were studied in an open-label, randomised trial comparing patients with a high (>50 ng/ml) with patients with a low (<10 ng/ml) target trough plasma concentration of enalaprilat. The dose of enalapril was titrated accordingly. The patients were followed for 12 months or until they needed renal replacement therapy. GFR was measured at 3-month intervals by the plasma clearance of ⁵¹ Cr-EDTA, and the individual rates of progression of renal failure were calculated as the slope of GFR versus time plot.Results In the high-concentration group, the median enalaprilat trough concentration was 92.9 ng/ml (21.8–371.0 ng/ml) and in the low-concentration group it was 9.1 ng/ml (2.5–74.8 ng/ml) at 3 months follow-up (P<0.001). The median daily doses of enalapril were 10 mg (2.5–30 mg) and 1.88 mg (1.25–5 mg) in the high and low groups, respectively (P<0.001). In the high-concentration group, the mean±SE decline in renal function was 6.1±1.5 ml/min/1.73 m² per year and in the low-concentration group it was 4.3±14.4 ml/min/1.73 m² per year (P=0.48). Five patients in the high-concentration group reached end-stage renal failure whereas none in the low-concentration group did (P=0.04). There were no statistically significant differences in blood pressure level, concomitant antihypertensive therapy or urinary albumin excretion. However, the high-enalaprilat concentration group had an overall higher plasma potassium concentration of 0.42 mmol/l than the low group (P<0.001).Conclusion In patients with moderate to severe renal insufficiency, a low concentration of enalaprilat afforded the same degree of renoprotection, blood pressure control and minimisation of proteinuria as a high concentration, during 12 months of follow-up. The high-dosage treatment was associated with a more pronounced tendency to hyperkalaemia. Thus, there seems to be no indication for increasing the daily dose of enalapril beyond what achieves adequate blood pressure control in this group of patients.     

Implementation of a community liaison pharmacy service: a randomised controlled trial

Objective The aim of this study was to provide a pharmacy service to improve continuity of patient care across the primary‐secondary care interface. Setting The study involved patients discharged from two acute‐care tertiary teaching hospitals in Melbourne, Australia, returning to independent living. Methods Consecutive patients admitted to both hospitals who met the study criteria and provided consent were recruited. Recruited patients were randomised to receive either standard care (discharge counselling, provision of compliance aids and communication with primary healthcare providers when necessary) or the intervention (standard care and a home visit from a community liaison pharmacist (CLP) within 5 days of discharge). Participant medication was reviewed during the visit according to set protocols and compliance and medication understanding was measured. All participants were telephoned 8–12weeks after discharge to assess the impact of the intervention on adherence and medication knowledge. Key findings The CLP visited 142 patients with a mean time of 4.2 days following hospital discharge (range = 1–14 days). Consultations lasted 15–105 min (mean, 49 min; SD, ± 21 min). The CLPs retrospectively coded 766 activities and interventions that occurred during home visits, subsequently categorised into three groups: counselling and education, therapeutic interventions and other interventions. No statistical difference was detected in the number of medications patients reported taking at follow‐up: the mean value was 7.72 (SD, ± 3.27) for intervention patients and 7.55 (SD, ± 3.27) for standard‐care patients (P = 0.662). At follow‐up self‐perceived medication understanding was found to have improved in intervention patients (P < 0.001) and significant improvements from baseline in medication adherence were found in both standard‐care (P < 0.022) and intervention (P < 0.005) groups; however, adherence had improved more in intervention patients. Conclusion The community liaison pharmacy service provided critical and useful interventions and support to patients, minimising the risk of medication misadventure when patients were discharged from hospital to home.     

Topiramate add-on treatment in schizophrenia: a randomised, double-blind, placebo-controlled clinical trial

Glutamate antagonists such as topiramate have been proposed based on the glutamate hypothesis of schizophrenia because its properties encourage its exploration and possible development as a medication for the treatment of schizophrenia. A randomised, double-blind, placebo-controlled clinical trial was performed on 18- to 45-year-old patients with schizophrenia. Baseline information including vital signs, height, weight, smoking status, demographic characteristics, (past) psychiatric history, medication history and medication-related adverse effects were collected. Patients were randomly assigned to a topiramate or placebo group. Efficacy of medication was measured by administering Positive and Negative Syndrome Scale (PANSS), and tolerability of treatment was recorded on day 0 (baseline), day 28 and day 56. PANSS values (95% confidence interval) at baseline, day 28 and day 56 in the topiramate group were 96.87 (85.37-108.37), 85.68 (74.67-96.70) and 76.87 (66.06-87.69), respectively; compared with 101.87 (90.37-113.37), 100.31 (89.29-111.32) and 100.56 (89.74-111.37) in the placebo group. General linear model for repeated measures analysis showed that topiramate has lowered PANSS values significantly compared with the placebo group. Similar significant decline patterns were found in all three subscales (negative, positive and psychopathology sign). Clinical response (more than 20% reduction in PANSS) was significantly higher in topiramate-treated subjects than controls (50% vs 12.5%). Topiramate can be an effective medication in controlling schizophrenic symptoms, considering its effect on negative symptoms and controlling antipsychotic-associated weight gain.     

Pharmacist intervention program to enhance hypertension control: a randomised controlled trial

Objective Studies have demonstrated that hypertension remains inadequately managed throughout the world, with lack of adherence to BP-lowering medication being a major factor. The aim of the present study was to evaluate if a pharmaceutical care program could improve antihypertensive medication adherence and blood pressure control. Setting This study was conducted in a secondary care hypertension/dyslipidemia outpatient clinic in the university teaching hospital of Cova da Beira Hospital Centre, Covilhã, located in the Eastern Central Region of Portugal. Method This report evaluates the pharmacist’s interventions during a prospective randomised controlled trial, from July 2009 to June 2010. Patients with diagnosis of essential hypertension attending the clinic for routine follow-up were randomly allocated either to a control group (no pharmaceutical care) or to an intervention group (quarterly follow-up by a hospital pharmacist during a 9-month period). The pharmacist interventions, aimed to increase medication adherence and blood pressure control, involved educational interventions and counselling tips directed to the patient. Main outcome measure Systolic blood pressure, diastolic blood pressure and blood pressure control (according to JNC 7 guidelines) assessed at the baseline visit and at the end of pharmaceutical care were the main outcome measures. Blood pressure measurements were performed by blinded nurses. Medication adherence was also evaluated, using a validated questionnaire at baseline and at the end of investigation. Results A total of 197 hypertensive patients were randomly assigned to the study (99 in the control group and 98 in the intervention group). Although there were no significant differences (P > 0.05) in both groups concerning mean age, gender, body mass index, and antihypertensive pharmacotherapy, blood pressure control was higher in the intervention group (P = 0.005) at the end of the study. Significant lower systolic blood pressure (?6.8 mmHg, P = 0.006) and diastolic blood pressure (?2.9 mmHg, P = 0.020) levels were observed in the intervention group. Medication adherence was also significantly higher in the intervention group at the end of the study (74.5% vs. 57.6%, P = 0.012).Conclusion Pharmacist intervention can significantly improve medication adherence and blood pressure control in patients treated with antihypertensive agents.