Alternative methods for analysis of radiographic damage in a randomized, double blind, parallel group clinical trial comparing hydroxychloroquine and sulfasalazine

Radiographic data of a 48-week double-blind, randomized, parallel trial comparing hydroxychloroquine (HCQ) and sulfasalazine (SASP) and its open label extension to 3 years of follow-up are analyzed in various ways. The focus of the paper is the methodological issues involved in analyses of radiographic data in a trial. Both the traditional method of increase in erosions and total score calculated on a group level, as well as individual progression on a patient level are presented. Regardless of which method is used, there is a statistically significant reduction in radiographic progression in the SASP group compared to the HCQ group.     

Long-term indoramin therapy in congestive heart failure: a double-blind, randomized, parallel placebo-controlled trial

Twenty-one patients with moderately severe congestive heart failure participated in a double-blind, randomized, parallel placebo-controlled trial designed to evaluate the effects of long-term (2 months) indoramin therapy on rest and exercise hemodynamics, exercise capacity and clinical status of patients with this clinical syndrome. The long-term administration of indoramin in patients (mean dose 50 mg every 12 hours) caused a mild reduction from baseline values in supine rest mean systemic blood pressure and, after dosing, elicited a significant reduction in systemic and pulmonary vascular resistances, pulmonary capillary wedge pressure and heart rate as well as a mild increase in stroke volume. Long-term indoramin therapy caused a small decrease, as compared with baseline exercise responses, in systemic and pulmonary vascular resistance and pulmonary capillary wedge pressure at submaximal levels of exercise. It did not alter hemodynamic variables at maximal exercise, exercise capacity or overall clinical status, compared with findings at baseline or with placebo.     

Effects of a home visiting program for older people with poor health status: a randomized, clinical trial in The Netherlands

OBJECTIVES: To evaluate the effectiveness of a home visiting program on health-related measures in a population of older people with poor health status.
DESIGN: Randomized, clinical trial.
SETTING: Community-dwelling citizens in the Netherlands.
PARTICIPANTS: Three hundred thirty people aged 70 to 84 randomly assigned to an intervention group (n=160) or a control group (n=170).
INTERVENTION: Eight home visits, lasting 1 hour or more, with telephone follow-up, over an 18-month period, conducted by experienced home nurses under supervision of a public health nurse; key elements of the (systematic) visits were assessment of health problems and risks, advice, and referral to professional and community services.
MEASUREMENTS: Self-rated health, functional status, quality of life, and changes in self-reported problems.
RESULTS: No differences were found between the intervention and control group in these and other outcome measures at the end of the intervention period (18 months).
CONCLUSION: The home visiting program did not appear to have any effect on the health status of older people with poor health and are probably not beneficial for such persons.     

Noninvasive ventilation in severe hypoxemic respiratory failure: a randomized clinical trial

The efficacy of noninvasive ventilation (NIV) to avoid intubation and improve survival was assessed in 105 patients with severe acute hypoxemic respiratory failure (arterial O2 tension or saturation persistently 60 mm Hg or less or 90% or less, respectively; breathing conventional Venturi oxygen at a maximal concentration [50%]), excluding hypercapnia, admitted into intensive care units of three hospitals. Patients were randomly allocated within 24 hours of fulfilling inclusion criteria to receive NIV (n=51) or high-concentration oxygen therapy (n=54). The primary end-point variable was the decrease in the intubation rate. Both groups had similar characteristics. Compared with oxygen therapy, NIV decreased the need for intubation (13, 25% vs. 28, 52%, p=0.010), the incidence of septic shock (6, 12% vs. 17, 31%, p=0.028), and the intensive care unit mortality (9, 18% vs. 21, 39%, p=0.028) and increased the cumulative 90-day survival (p=0.025). The improvement of arterial hypoxemia and tachypnea was higher in the noninvasive ventilation group with time (p=0.029 each). Multivariate analyses showed NIV to be independently associated with decreased risks of intubation (odds ratio, 0.20; p=0.003) and 90-day mortality (odds ratio, 0.39; p=0.017). The use of noninvasive ventilation prevented intubation, reduced the incidence of septic shock, and improved survival in these patients compared with high-concentration oxygen therapy.     

Treatment of long-distance intermittent claudication with pentoxifylline: a 12-month, randomized trial

The efficacy, safety, and cost of pentoxifylline (PXF) in long-range (>400 m interval) intermittent claudication was studied comparing PXF and placebo in a 12-month study. A standardized treadmill test was performed at inclusion and at 6 and 12 months. A training plan based on walking was associated with the control of risk factor levels. Of the 194 included patients, 135 completed the study: 75 in the PXF group and 60 in the placebo group. There were 59 dropouts (due to low compliance). The authors observed a 148% increase in total walking distance (TWD) at 6 months with PXF (vs 110% with placebo; p<0.05); at 12 months, the increase was 170% with PXF (vs 131% with placebo; p<0.02). There was a 38% difference at 6 months and 39% at 12 months in favor of PXF. Treatment was well tolerated. In conclusion, PXF improved walking distance significantly better than placebo.     

卡维地洛治疗慢性心力衰竭的随机对照研究

目的 评价卡维地洛对于慢性心力衰竭的治疗效果.方法 59例慢性心力衰竭病人随机分为卡维地洛组（n=30）和对照组（n=29）,对照组给予美托洛尔口服.比较两组病人在治疗前后的临床症状及心功能指标.结果 卡维地洛可有效改善病人的临床症状和心功能指标（P＜0.05）.与对照组相比,卡维地洛在减少左心室舒张末期内径（left ventricular end diastolic dimension,LVEDd）和提高心左心室射血分数（left ventricular ejection fraction,LVEF）方面较美托洛尔更有效（P＜0.05）.结论 卡维地洛可有效改善慢性心力衰竭病人心功能,并在减少LVEDd和提高LVEF方面优于美托洛尔.     

Long-term DHEA replacement in primary adrenal insufficiency: a randomized, controlled trial

CONTEXT: Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are the major circulating adrenal steroids and substrates for peripheral sex hormone biosynthesis. In Addison's disease, glucocorticoid and mineralocorticoid deficiencies require lifelong replacement, but the associated near-total failure of DHEA synthesis is not typically corrected. OBJECTIVE AND DESIGN: In a double-blind trial, we randomized 106 subjects (44 males, 62 females) with Addison's disease to receive either 50 mg daily of micronized DHEA or placebo orally for 12 months to evaluate its longer-term effects on bone mineral density, body composition, and cognitive function together with well-being and fatigue. RESULTS: Circulating DHEAS and androstenedione rose significantly in both sexes, with testosterone increasing to low normal levels only in females. DHEA reversed ongoing loss of bone mineral density at the femoral neck (P < 0.05) but not at other sites; DHEA enhanced total body (P = 0.02) and truncal (P = 0.017) lean mass significantly with no change in fat mass. At baseline, subscales of psychological well-being in questionnaires (Short Form-36, General Health Questionnaire-30), were significantly worse in Addison's patients vs. control populations (P < 0.001), and one subscale of SF-36 improved significantly (P = 0.004) after DHEA treatment. There was no significant benefit of DHEA treatment on fatigue or cognitive or sexual function. Supraphysiological DHEAS levels were achieved in some older females who experienced mild androgenic side effects. CONCLUSION: Although further long-term studies of DHEA therapy, with dosage adjustment, are desirable, our results support some beneficial effects of prolonged DHEA treatment in Addison's disease.     

Effects on health care use and associated cost of a home visiting program for older people with poor health status: a randomized clinical trial in the Netherlands

BACKGROUND: Home visiting programs have been developed to improve the functional abilities of older people and subsequently to reduce the use of institutional care services. The results of trials have been inconsistent and their cost-effectiveness uncertain. Home visits for a high-risk population rather than the general population seems a promising approach. We therefore studied the effects of a home visiting program for older people with poor health. This article describes the effects on health care use and associated cost. METHODS: We conducted a randomized clinical trial among 330 community-dwelling citizens, aged 70-84 years, in the Netherlands. Participants in the intervention group (n = 160) received eight home visits by a trained home nurse over an 18-month period; a multidimensional geriatric assessment of problems was included. The main outcomes are: admissions to hospital, nursing home, and home for older persons; contacts with medical specialists, general practitioners, and paramedics; and hours of home care help. The data on health care use were mostly obtained from computerized databases of various medical administration offices; the follow-up period was 24 months. RESULTS: Inpatient and outpatient health care use was similar for both groups, with the exception of a higher distribution of aids and in-home modifications in favor of the intervention group. No differences were found between the intervention and control group in health care cost. CONCLUSION: The home visiting program did not appear to have any effect on the health care use of older people with poor health and had a low chance of being cost-effective. We conclude that these visits are probably not beneficial for such persons within the health care setting in the Netherlands or comparable settings in other Western countries.     

Depression and health status in elderly patients with heart failure: a 6-month prospective study in primary care

To determine the prevalence and effects of depression on health status among elderly outpatients with heart failure, the authors conducted a 6-month prospective cohort study of 139 older outpatients with heart failure managed in primary care and 80 of their spouses. Primary care heart failure diagnosis was confirmed through chart review. The Primary Care Evaluation of Mental Disorders psychiatric diagnostic interview and Hamilton Depression Rating Scale were administered by phone. EQ-5D feeling thermometer, Medical Outcomes Study Short Form 36-Item Questionnaire, Kansas City Cardiomyopathy Questionnaire, and heart failure symptom severity questionnaires were administered by self-report. Depression diagnoses at baseline were: major depression and/or dysthymia (n=12, 9%), minor depression (n=14, 10%), and no depression (n=113, 81%). After adjusting for age, gender, and medical comorbidity, these depression groups differed by repeated measures analysis of covariance on most health status measures including the EQ-5D feeling thermometer; Medical Outcomes Study Short Form 36-Item Questionnaire general health and physical role function subscales; Kansas City Cardiomyopathy Questionnaire total score, symptom total, physical limitations, and quality of life subscales; as well as severity of chest pain and fatigue. Depression has significant and persistent effects on health status of elderly patients with heart failure, including heart failure symptoms, physical and role function, and quality of life. This may help explain why depression has been associated with increased health care utilization and costs in this population.     

Comparison of lung volume reduction surgery and physical training on health status and physiologic outcomes: a randomized controlled clinical trial

STUDY OBJECTIVES: In 1996, researchers in Sweden initiated a collaborative randomized study comparing lung volume reduction surgery (LVRS) and physical training with physical training alone. The primary end point was health status; secondary end points included survival and physiologic measurements. DESIGN: After an initial 6-week physical training program, researchers' patients were randomized to either LVRS (surgical group [SG]) with continued training for 3 months, or to continued training alone (training group [TG]) for 1 year. SETTING: All seven thoracic surgery centers in Sweden. PATIENTS: All patients in Sweden with severe emphysema fulfilling inclusion criteria for LVRS. INTERVENTIONS: Patients randomized to surgery underwent a median sternotomy, except for a few patients in whom thoracotomy or video-assisted thoracoscopy were performed. In the TG, supervised physical training continued for 1 year; in the SG, supervised physical training continued for 3 months postoperatively. MEASUREMENTS AND RESULTS: Fifty-three patients were included in each group. Six in-hospital deaths occurred after surgery (12%), and one more death occurred during follow-up. Two deaths occurred in the TG. The difference in death rates between the groups was not statistically significant. Health status, as measured by St. George Respiratory Questionnaire (SGRQ) [total scale score mean difference at 1 year, 14.7; 95% confidence interval (CI), 9.8 to 19.7] as well as by the Medical Outcomes Study Short-Form General Health Survey (physical function scale score mean difference at 1 year, 19.7; 95% CI, 12.1 to 27.3) was improved from baseline in the SG compared with the TG. FEV(1), residual volume, and shuttle walking test values also improved in the SG but not in the TG after 6 months and 12 months. CONCLUSIONS: In severe emphysema, LVRS can improve health status in survivors but is associated with mortality risk. The effects are stable for at least 1 year. Physical training alone failed to achieve a similar improvement.     

Long-term efficacy and tolerability of flutamide combined with oral contraception in moderate to severe hirsutism: a 12-month, double-blind, parallel clinical trial

OBJECTIVE: Our objective was to test the efficacy and tolerability of three doses of flutamide (125, 250, and 375 mg) combined with a triphasic oral contraceptive (ethynylestradiol/levonorgestrel) during 12 months to treat moderate to severe hirsutism in patients with polycystic ovary syndrome or idiopathic hirsutism. DESIGN: We conducted a randomized, double-blind, placebo-controlled, parallel clinical trial. PATIENTS: A total of 131 premenopausal women, suffering from moderate to severe hirsutism, were randomized to placebo or 125, 250, or 375 mg flutamide daily associated with a triphasic oral contraceptive pill. Hirsutism (Ferriman-Gallwey), acne and seborrhea (Cremoncini), and hormone serum levels were monitored at baseline and at 3 (except hormone serum levels), 6, and 12 months. Side effects and biochemical, hematological, and hepatic parameters were assessed. METHODS: We used three-way ANOVA (subject, dose, and visit) with Scheffé adjustment for multiple comparisons or nonparametrical Friedman test and least-squares mean (paired data) and Kruskall-Wallis test for unpaired data analyses. We used chi(2) or Fisher's test for categorical data. RESULTS: A total of 119 patients were included in the intention-to-treat analysis. All flutamide doses induced a significant decrease in hirsutism, acne, and seborrhea scores after 12 months compared with placebo without differences among dose levels. Similar related side effects were observed with placebo and 125 mg flutamide (12.5%), and slightly higher with 250 mg (17.3%) and 375 mg (21.2%). No statistically significant differences were observed either among doses or compared with placebo. CONCLUSIONS: Flutamide at 125 mg daily during 12 months was the minimum effective dose to diminish hirsutism in patients with polycystic ovary syndrome or with idiopathic hirsutism.     

卡维地洛治疗慢性心力衰竭的临床研究

目的　评价卡维地洛治疗慢性心力衰竭 (心衰 )的疗效和安全性。方法　在此多中心、随机安慰剂对照的临床研究中 ,以慢性轻、中度心衰患者为研究对象 ,在心衰标准用药的基础上 ,卡维地洛由小剂量开始 ,逐渐递增至目标剂量。在 7个月的疗程中 ,检查超声心动图 3次 ,以评价左室功能和容积。结果　 7家医疗中心共入选卡维地洛组 65例以及安慰剂组 31例。在试验结束 ,两组的左室射血分数 (LVEF)均有增加 ,卡维地洛组由 (2 7 9± 6 2 ) %增至 (35 2± 9 0 ) % ,安慰剂组由 (2 8 7±5 9) %增至 (32 2± 7 4) % ;但卡维地洛组LVEF的增加值显著高于安慰剂组 ,分别为 (7 5± 7 8) %和(3 0± 5 3) % ,P =0 0 0 4 1。经 7个月的治疗 ,卡维地洛组显著缩小左室舒张末期容积 (EDV)和收缩末期容积 (ESV) ,分别为 (- 1 8 3± 35 8)ml、P =0 0 0 0 3和 (- 2 6 8± 34 5)ml、P =0 0 0 0 1。而安慰剂组在试验终点 ,左室EDV和ESV均有增加 ,分别增加 (7 5± 33 0 )ml和 (2 9± 30 0 )ml。卡维地洛组有 40例 (61 5 % )耐受目标剂量 (50～ 1 0 0mg/d) ,其多见的不良反应为头晕 ,但不良反应发生率与安慰剂比较差异无显著性 ,两组均未发现肝、肾功能损害或血象、电解质和糖代谢变化。本研究中 3例死亡 ,均在安慰剂组。安慰     

双盲对照吸入倍氯米松一年对气道高反应性与哮喘的防治作用

目的探讨长期吸入糖皮质激素对哮喘患者的治疗作用和对无症状的气道高反应性（ＢＨＲ）者发生哮喘的预防作用。方法以随机、双盲对照法比较５９例ＢＨＲ学生，年龄１２～１８岁，吸入倍氯米松干粉剂（ＢＤＰ，６００μｇ／ｄ）或安慰剂１年对气道反应性及哮喘症状的作用。结果试验１年后哮喘ＢＤＰ组气道高反应性（使ＦＥＶ１较基础值下降２０％的累积吸入组胺量的对数ｌｇＰＤ２０－ＦＥＶ１）显著下降（分别为０．３８５±０．４２４、１．１８７±０．６０３μｍｏｌ组胺，Ｐ＜０．０２），只有３０％哮喘者仍有喘息，而对照组则有８６％仍有喘息（Ｐ＝０．０７６）；无症状ＢＨＲ学生的ｌｇＰＤ２０－ＦＥＶ１在ＢＤＰ组及对照组间差异无显著性，但ＢＤＰ组不出现喘息症状，而对照组则有３例出现喘息（１５％）；ＢＨＲ者吸入ＢＤＰ组的累积症状计分显著低于对照组（分别为１．５０±２．５４分、５．５８±６．２２分，Ｐ＜０．０１）。结论ＢＤＰ能降低哮喘患者的ＢＨＲ及减轻其症状，且可能有预防无症状ＢＨＲ者发生哮喘的作用     

A pilot randomized clinical trial of a teamwork intervention for heart failure care dyads

BackgroundDyadic heart failure (HF) management can improve outcomes for patients and caregivers and can be enhanced through eHealth interventions.ObjectiveTo evaluate the feasibility, acceptability, and preliminary efficacy of an eHealth dyadic teamwork intervention, compared to an attention control condition.MethodsWe recruited 29 HF patient-caregiver dyads from inpatient units and randomized dyads to an intervention or a control group. We calculated enrollment and retention rates, described acceptability using interview and questionnaire data, and computed intervention effect sizes.Results37% of eligible dyads agreed to participate and 93% of randomized participants completed follow-up questionnaires. Participants found both study conditions to be acceptable. Between-group effect sizes suggested that the intervention led to improvements in relationship quality, self-efficacy, and quality of life for patients and caregivers.ConclusionsDyadic recruitment from acute care settings is challenging. Findings provide initial evidence that our intervention can contribute to better health outcomes for HF dyads.     

Nocturnal nutritional supplementation improves total body protein status of patients with liver cirrhosis: a randomized 12-month trial

Patients with liver cirrhosis exhibit early onset of gluconeogenesis after short-term fasting. This accelerated metabolic reaction to starvation may underlie their increased protein requirements and muscle depletion. A randomized controlled trial was conducted to test the hypothesis that provision of a late-evening nutritional supplement over a 12-month period would improve body protein stores in patients with cirrhosis. A total of 103 patients (68 male, 35 female; median age 51, range 28-74; Child-Pugh grading: 52A, 31B, 20C) were randomized to receive either daytime (between 0900 and 1900 hours) or nighttime (between 2100 and 0700 hours) supplementary nutrition (710 kcal/day). Primary etiology of liver disease was chronic viral hepatitis (67), alcohol (15), cholestatic (6), and other (15). Total body protein (TBP) was measured by neutron activation analysis at baseline, 3, 6, and 12 months. Total daily energy and protein intakes were assessed at baseline and at 3 months by comprehensive dietary recall. As a percentage of values predicted when well, TBP at baseline was similar for the daytime (85 +/- 2[standard error of the mean]%) and nighttime (84 +/- 2%) groups. For the nighttime group, significant increases in TBP were measured at 3 (0.38 +/- 0.10 kg, P = 0.0004), 6 (0.48 +/- 0.13 kg, P = 0.0007), and 12 months (0.53 +/- 0.17 kg, P = 0.003) compared to baseline. For the daytime group, no significant changes in TBP were seen. Daily energy and protein intakes at 3 months were higher than at baseline in both groups (P < 0.0001), and these changes did not differ between the groups. CONCLUSION: Provision of a nighttime feed to patients with cirrhosis results in body protein accretion equivalent to about 2 kg of lean tissue sustained over 12 months. This improved nutritional status may have important implications for the clinical course of these patients.     

Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction:A randomized clinical trial

Objective To determine the effect of the phosphodiesterase-5 inhibitor sildenafil compared with placebo on exercise capacity and clinical status in HFPEF.Design Multicenter,double-blind,placebo-controlled,parallel-group,randomized clinical trial of 216 stable outpatients with HF,ejection fraction ≥50%,elevated N-terminal brain-type natriuretic peptide or elevated invasively measured filling pressures,and reduced exercise capacity.Participants were randomized from October 2008 through February 2012 at 26 centers in North America.Follow-up was through August 30,2012.Interventions Sildenafil(n = 113) or placebo(n = 103) administered orally at 20 mg,3 times daily for 12 weeks,followed by 60 mg,3 times daily for 12 weeks.Main Outcome Measures Primary end point was change in peak oxygen consumption after 24 weeks of therapy.Secondary end points included change in 6-minute walk distance and a hierarchical composite clinical status score(range,1-n,a higher value indicates better status;expected value with no treatment effect,95) based on time to death,time to cardiovascular or cardiorenal hospitalization,and change in quality of life for participants without cardiovascular or cardiorenal hospitalization at 24 weeks.Results Median age was 69 years,and 48% of patients were women.At baseline,median peak oxygen consumption(11.7 mL /kg /min) and 6-minute walk distance(308 m) were reduced.The median E /e’(16),left atrial volume index(44 mL /m 2),and pulmonary artery systolic pressure(41 mm Hg) were consistent with chronically elevated left ventricular filling pressures.At 24 weeks,median(IQR) changes in peak oxygen consumption(mL /kg /min) in patients who received placebo(-0.20 [IQR,-0.70 to 1.00]) or sildenafil(-0.20 [IQR,-1.70 to 1.11]) were not significantly different(P = 0.90) in analyses in which patients with missing week-24 data were excluded,and in sensitivity analysis based on intention to treat with multiple imputation for missing values(mean between-group difference,0.01 mL /kg /min,[95% CI,-0.60 to 0.61]).The mean clinical status rank score was not significantly different at 24 weeks between placebo(95.8) and sildenafil(94.2)(P = 0.85).Changes in 6-minute walk distance at 24 weeks in patients who received placebo(15.0 m [IQR,-26.0 to 45.0]) or sildenafil(5.0 m [IQR,-37.0 to 55.0];P = 0.92) were also not significantly different.Adverse events occurred in 78 placebo patients(76%) and 90 sildenafil patients(80%).Serious adverse events occurred in 16 placebo patients(16%) and 25 sildenafil patients(22%).Conclusion and Relevance Among patients with HFPEF,phosphodiesterase-5 inhibition with administration of sildenafil for 24 weeks,compared with placebo,did not result in significant improvement in exercise capacity or clinical status.