Treatment of vascular inner ear disease in vascular patients with pentoxifylline: a controlled, randomized trial

The efficacy of Pentoxifylline in vascular inner ear disease (VIED) was studied comparing PXF and placebo in a 4-week study; 40 patients with vascular disease and monolateral loss of hearing, vertigo, dizziness, tinnitus (analyzed with an analogue scale line), and cochlear flow reduction were included. The aims of the study were to study the effects of PXF (1600 mg daily) in VIED considering clinical outcome and cochlear flow. Of the 20 included patients, 19 completed the study. One dropout in the placebo group was due to low compliance. Intention-to-treat analysis indicated an improvement in cochlear flow (p<0.05) and a decrease in score in both groups. The cochlear flow increase was 287.5% in the PXF group vs 168% in the placebo group (119.5% difference; p<0.02). There was a difference in score decrease (44.1% larger) in the PXF group (p<0.05).Between-group analysis favors PXF considering blood flow and symptoms. Results indicate good efficacy and tolerability of PXF in VIED.     

Prevention of serious vascular events by aspirin amongst patients with peripheral arterial disease: randomized, double-blind trial

OBJECTIVE: To assess the prophylactic efficacy of aspirin and a high-dose antioxidant vitamin combination in patients with peripheral arterial disease (PAD) in terms of reduction of the risk of a first vascular event (myocardial infarction, stroke, vascular death) and critical limb ischaemia. DESIGN: Randomized, placebo-controlled, double-blind clinical trial with 2 x 2 factorial design. SETTING: Thirty-seven European angiology/vascular medicine units. SUBJECTS: A total of 366 outpatients with stage I-II PAD documented by angiography or ultrasound, with ankle/brachial index <0.85 or toe index <0.6; 210 patients completed the follow-up. INTERVENTIONS: Four treatment groups: (i) oral aspirin (100 mg daily), (ii) oral antioxidant vitamins (600 mg vitamin E, 250 mg vitamin C and 20 mg beta-carotene daily), (iii) both or (iv) neither, given for 2 years. MAIN OUTCOME MEASURE: Major vascular events (cardiovascular death, myocardial infarction or stroke) and critical leg ischaemia. RESULTS: Seven of 185 patients allocated aspirin and 20 of 181 allocated placebo suffered a major vascular event (risk reduction 64%, P = 0.022); five and eight patients, respectively, suffered critical leg ischaemia (total 12 vs. 28, P = 0.014). There was no evidence that antioxidant vitamins were beneficial (16/185 vs. 11/181 vascular events). Neither treatment was associated with any significant increase in adverse events. Inclusion of this trial in a meta-analysis of other randomized trials of anti-platelet therapy in PAD makes the overall results highly significant (P < 0.001) and suggests that low-dose aspirin reduces the incidence of vascular events by 26%. CONCLUSIONS: For the first time direct evidence shows that low-dose aspirin should routinely be considered for PAD patients, including those with concomitant type 2 diabetes.     

Treatment of vascular retinal disease with pentoxifylline: a controlled, randomized trial

The aim of this study was to evaluate the effect of PXF (1800 mg daily) in patients with sudden loss of vision (SLV) in a 4-week trial, evaluating clinical outcome and retinal flow parameters. Inclusion criteria were SLV associated with thrombosis of the retinal artery; decrease in retinal blood flow (PSF: peak-systolic flow; EDF: end-diastolic flow velocity) and asymmetry between the two retinal arteries (>40%) documented by duplex scanning. All 10 included patients completed the study. The groups were comparable. No side effects were reported. A significant improvement in flow velocity (p<0.05) and a decrease in analogue score in both groups were observed. PSF increase was 550% in the PXF group vs 288% in the placebo group (262% difference). EDF increase was 400% in the PXF group vs 200% in the placebo group (200% difference). There was a significant difference in the analogue score decrease (33.3% difference larger in the PXF group; p<0.05). In conclusion, PXF treatment improved retinal flow after retinal artery occlusion better than placebo and should be considered as an important option in this condition.     

A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer's disease

OBJECTIVES: To assess whether doxycycline and rifampin have a therapeutic role in patients with Alzheimer's disease (AD). DESIGN: Randomized, triple-blind, controlled trial. SETTING: Three tertiary care and two community geriatric clinics in Canada. PARTICIPANTS: One hundred one patients with probable AD and mild to moderate dementia. INTERVENTION: Oral daily doses of doxycycline 200 mg and rifampin 300 mg for 3 months. MEASUREMENTS: The primary outcome was a change in Standardized Alzheimer's Disease Assessment Scale cognitive subscale (SADAScog) at 6 months. Secondary outcomes were changes in the SADAScog at 12 months and tests of dysfunctional behavior, depression, and functional status. RESULTS: There was significantly less decline in the SADAScog score at 6 months in the antibiotic group than in the placebo group, (-2.75 points, 95% confidence interval (CI)=-5.28 to -0.22, P=.034). At 12 months, the difference between groups in the SADAScog was -4.31 points (95% CI=-9.17-0.56, P=.079). The antibiotic group showed significantly less dysfunctional behavior at 3 months. There was no significant difference in adverse events between groups (P=.34). There were no differences in Chlamydia pneumoniae detection using polymerase chain reaction or antibodies (immunoglobulin (Ig)G or IgA) between groups. CONCLUSION: Therapy with doxycycline and rifampin may have a therapeutic role in patients with mild to moderate AD. The mechanism is unlikely to be due to their effect on C. pneumoniae. More research is needed to investigate these agents.     

Metformin in patients with non-alcoholic fatty liver disease: A randomized,controlled trial

Objective. The antidiabetic agent metformin is regularly discussed as a promising treatment for non-alcoholic fatty liver disease (NAFLD), which is characterized by insulin resistance. However, the evidence for its beneficial effects is limited, and conflicting reports have been published. The purpose of this study was to conduct a randomized, double-blind, placebo-controlled trial to test whether metformin improves liver histology in patients with non-alcoholic fatty liver disease. Material and methods. Forty-eight patients with biopsy-proven NAFLD were randomized to treatment with metformin (n=24) or placebo (n=24) for 6 months. A second liver biopsy was obtained in all subjects who completed the trial (n=44). Data analyses are restricted to this group (per-protocol analyses). The primary outcome was changes in histologically assessed liver steatosis. Secondary outcomes were changes in NAFLD activity (NAS)-score, liver steatosis assessed by computed tomography (CT), liver transaminases, body-weight, metabolic variables and inflammatory markers. Results. No significant differences between treatment with metformin or placebo were observed for changes in liver steatosis, assessed either histologically or by CT, NAS-score, liver transaminases or on markers of insulin resistance or inflammation. In contrast, beneficial effects of metformin were observed on changes in body-weight (p<0.001), serum levels of cholesterol (p=0.004), LDL-cholesterol (p<0.001), glucose (p=0.032) and on HbA1c (p=0.020). Conclusions. Treatment with metformin for 6 months was no better than placebo in terms of improvement in liver histology in patients with NAFLD. Nevertheless, the use of metformin could still be beneficial in this group as it is associated with a reduction in serum levels of lipids and glucose. (ClinicalTrials.gov number, NCT00303537)     

A multiprofessional education programme for patients with inflammatory bowel disease: A randomized controlled trial

Objective. Health-related quality of life is impaired in patients with inflammatory bowel disease and improved disease-related information can improve this situation. The aims of this study were to create an education programme that could be readily applicable at the clinic and would be suitable for newly diagnosed patients with inflammatory bowel disease, and to investigate whether the programme could improve their health-related quality of life. Material and methods. Ninety-three patients with inflammatory bowel disease in remission were included and randomized to an intervention group or a control group. The intervention group attended a multiprofessional education programme while the control group received regular information. Four questionnaires were used for measuring health-related quality of life. Both groups completed the questionnaires at baseline and after 6 months. The intervention group also completed the questionnaires after 1 month. Results. No significant differences were found when comparing the two groups at 6 months. However, the multiprofessional education programme was highly appreciated by the patients. Conclusions. In the present study no improvement could be seen in health-related quality of life in patients with inflammatory bowel disease after participating in an education programme in comparison with the control group. This might be due to the fact that the questionnaires were not sensitive enough or that some patients were not in clinical remission. The patients’ enthusiasm for the multiprofessional education programme has led to its being part of the regular care at the clinic.     

Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial

A beneficial effect of recombinant activated factor VII (rFVIIa) in Child-Pugh class B and C patients with cirrhosis who have variceal bleeding has been suggested. This randomized controlled trial assessed the efficacy and safety of rFVIIa in patients with advanced cirrhosis and active variceal bleeding. At 31 hospitals in an emergency setting, 256 patients (Child-Pugh > 8; Child-Pugh B = 26%, C = 74%) were randomized equally to: placebo; 600 microg/kg rFVIIa (200 + 4x 100 microg/kg); or 300 microg/kg rFVIIa (200 + 100 microg/kg). Dosing was intravenous at 0, 2, 8, 14, and 20 hours after endoscopy, in addition to standard vasoactive, prophylactic antibiotic, and endoscopic treatment. The primary composite endpoint consisted of failure to control 24-hour bleeding, or failure to prevent rebleeding or death at day 5. Secondary endpoints included adverse events and 42-day mortality. Baseline characteristics were comparable between groups. Administration of rFVIIa had no significant effect on the composite endpoint compared with placebo (P = 0.37). There was no significant difference in 5-day mortality between groups; however, 42-day mortality was significantly lower with 600 microg/kg rFVIIa compared with placebo (odds ratio 0.31, 95% confidence interval = 0.13-0.74), and bleeding-related deaths were reduced from 12% (placebo) to 2% (600 microg/kg). A marked heterogeneity in the failure rate in all treatment groups was observed across participating centers. Adverse events, including overall thromboembolic events, were comparable between groups. CONCLUSION: Treatment with rFVIIa had no significant effect on the primary composite endpoint compared with placebo. Therefore, decision on the use of this hemostatic agent in acute variceal bleeding should be carefully considered, because results of this study do not support the routine use of rFVIIa in this setting. Adverse events were comparable across groups.     

Alcoholism as a risk factor in methadone maintenance: A randomized controlled trial

A randomized controlled trial of 625 addicts on methadone maintenance identified 105 (17 percent) as active alcoholics, 47 (8 percent) as inactive alcoholics, and 473 (75 percent) as nonalcoholics. Subjects were followed for up to 29 months (mean 53.7 weeks) to assess the influence of alcoholism on the rehabilitative process. During the study, alcohol consumption significantly decreased (p < 0.001) in active alcoholics. Indexes of productive activity on entry or during follow-up revealed no significant differences between active alcoholics and other patients with the exception of alcohol-related hospitalizations (p < 0.001). Behavioral indexes consistently improved with treatment in all patients, being greatest among active alcoholics (p < 0.01). During the study, 28 (7 percent) of 399 nonalcoholics were recategorized as active alcoholics, and remission from alcoholism was noted in 28 (27 percent) of patients who were initially classified as alcoholic. These findings suggest that alcoholism does not significantly affect rehabilitation from narcotic use and therefore should not be cause for detoxification from methadone maintenance.     

A multiprofessional education programme for patients with inflammatory bowel disease: a randomized controlled trial

OBJECTIVE: Health-related quality of life is impaired in patients with inflammatory bowel disease and improved disease-related information can improve this situation. The aims of this study were to create an education programme that could be readily applicable at the clinic and would be suitable for newly diagnosed patients with inflammatory bowel disease, and to investigate whether the programme could improve their health-related quality of life. MATERIAL AND METHODS: Ninety-three patients with inflammatory bowel disease in remission were included and randomized to an intervention group or a control group. The intervention group attended a multiprofessional education programme while the control group received regular information. Four questionnaires were used for measuring health-related quality of life. Both groups completed the questionnaires at baseline and after 6 months. The intervention group also completed the questionnaires after 1 month. RESULTS: No significant differences were found when comparing the two groups at 6 months. However, the multi-professional education programme was highly appreciated by the patients. CONCLUSIONS: In the present study no improvement could be seen in health-related quality of life in patients with inflammatory bowel disease after participating in an education programme in comparison with the control group. This might be due to the fact that the questionnaires were not sensitive enough or that some patients were not in clinical remission. The patients' enthusiasm for the multiprofessional education programme has led to its being part of the regular care at the clinic.     

Acupuncture for patients with mild hypertension: A randomized controlled trial

Acupuncture may be beneficial for patients with mild hypertension, but the evidence is not convincing. We aimed to examine the effect of acupuncture on blood pressure (BP) reduction in patients with mild hypertension. We conducted a multicenter, single‐blind, sham‐controlled, randomized trial in eleven hospitals in China. The trial included 428 patients with systolic blood pressure (SBP) from 140 to 159 mm Hg and/or with diastolic blood pressure (DBP) from 90 to 99 mm Hg. The patients were randomly assigned to receive 18 sessions of affected meridian acupuncture (n = 107) or non‐affected meridian acupuncture (n = 107) or sham acupuncture (n = 107) during 6 weeks, or to stay in a waiting‐list control (n = 107). All patients received 24‐hour ambulatory blood pressure monitoring at weeks 6, 9, and 12. We included 415 participants in the intention‐to‐treat analysis. The two acupuncture groups were pooled in the analysis, since they had no difference in all outcomes. SBP decreased at week 6 in acupuncture group vs sham acupuncture vs waiting‐list group (7.2 ± 11.0 mm Hg vs 4.1 ± 11.5 mm Hg vs 4.1 ± 13.2 mm Hg); acupuncture was not superior to sham acupuncture (mean difference 2.7 mm Hg, 95% CI 0.4 to 5.9, adjusted P = 0.103) or waiting‐list control (2.9 mm Hg, 95% CI −0.2 to 6.0, adjusted P = 0.078). However, acupuncture was superior to sham acupuncture (3.3 mm Hg, 95% CI 0.2 to 6.3, adjusted P = 0.035) and waiting‐list control (4.8 mm Hg, 95% CI 1.8 to 7.8, P < 0.001) at week 9. Acupuncture had a small effect size on the reduction of BP in patients with mild hypertension.     

Aldosterone: A risk factor for vascular disease

Blockade of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor antagonists has resulted in beneficial effects in essential hypertensive patients. However, occurrence of cardiovascular events has not been appropriately controlled beyond a certain percentage. One reason could be the effects of aldosterone, the final component of the system. The aldosterone escape phenomenon could explain undesirable outcomes observed in hypertensive patients even under treatment with ACE inhibitors or angiotensin antagonists. Aldosterone has direct effects on the vasculature and has been associated with vascular smooth muscle cell hypertrophy, endothelial dysfunction, cardiac fibrosis, proteinuria, and renal vascular injury. Animal models and clinical trials have proven the benefit of aldosterone receptor antagonism. With increased recognition of the prevalence of hyperaldosteronism in patients thought to have "essential" hypertension, the use of drugs that block aldosterone action may become more widespread and protect the vasculature from the deleterious effects of aldosterone.     

Treatment of vascular inner ear disease with pentoxifylline: a 4-week, controlled, randomized trial

The efficacy of pentoxifylline (PXF) in vascular inner ear disease (VIED) was studied comparing PXF and placebo in a 4-week study; 60 patients with unilateral loss of hearing, vertigo, dizziness, tinnitus (analyzed with an analogue scale line), and cochlear flow reduction were included. The aim of the study was to study the effect of PXF (1800 mg/day) in VIED considering clinical outcome and cochlear flow. All patients completed the study. Improvement in cochlear flow (p<0.05) and a decrease in score in both groups were observed. The cochlear flow increase was 287.5% in the PXF group vs 168% in the placebo group (119.5% difference; p<0.02). There was a difference in score decrease (44.1% larger) in the PXF group (p<0.05). PXF was more effective considering flow and symptoms.     

Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery: study protocol for a randomized controlled trial (UPGRADE trial)

Background

The number of bariatric interventions for morbid obesity is increasing worldwide. Rapid weight loss is a major risk factor for gallstone development. Approximately 11 % of patients who underwent Roux-en-Y gastric bypass develop symptomatic gallstone disease. Gallstone disease can lead to severe complications and often requires hospitalization and surgery. Ursodeoxycholic acid (UDCA) prevents the formation of gallstones after bariatric surgery. However, randomized controlled trials with symptomatic gallstone disease as primary endpoint have not been conducted. Currently, major guidelines make no definite statement about postoperative UDCA prophylaxis and most bariatric centers do not prescribe UDCA.

Methods

A randomized, placebo-controlled, double-blind multicenter trial will be performed for which 980 patients will be included. The study population consists of consecutive patients scheduled to undergo Roux-en-Y gastric bypass or sleeve gastrectomy in three bariatric centers in the Netherlands. Patients will undergo a preoperative ultrasound and randomization will be stratified for pre-existing gallstones and for type of surgery. The intervention group will receive UDCA 900 mg once daily for six months. The placebo group will receive similar-looking placebo tablets. The primary endpoint is symptomatic gallstone disease after 24 months, defined as admission or hospital visit for symptomatic gallstone disease. Secondary endpoints consist of the development of gallstones on ultrasound at 24 months, number of cholecystectomies, side-effects of UDCA and quality of life. Furthermore, cost-effectiveness, cost-utility and budget impact analyses will be performed.

Discussion

The UPGRADE trial will answer the question whether UDCA reduces the incidence of symptomatic gallstone disease after Roux-en-Y gastric bypass or sleeve gastrectomy. Furthermore it will determine if treatment with UDCA is cost-effective.

Trial registration

Netherlands Trial Register (trialregister.nl) 6135. Date registered: 21-Nov-2016.

     

Cost-effectiveness of increased telephone contact for patients with osteoarthritis: A randomized,controlled trial

Objective. To evaluate the cost-effectiveness of telephone intervention for patients with osteoarthritis. Methods. Randomized, controlled trial. Results. The intervention did not significantly increase health care costs. The annual costs for a 1-unit improvement in physical functioning and in pain, as measured by the Arthritis Impact Measurement Scales, were $70.86 and $31.00, respectively. Conclusion. Telephone contact is a potentially cost-effective intervention in osteoarthritis.     

Effects of aerobic training and resistance training in reducing cardiovascular disease risk for patients with prediabetes: A multi-center randomized controlled trial

AimsAerobic training (AT) and resistance training (RT) can reduce blood glucose and type 2 diabetes risk, and increase muscle mass for prediabetes patients. However, the impact of long-term AT and RT on cardiovascular disease (CVD) risk remains unclear. The purpose of this study was to investigate the impact of AT and RT on CVD risk reduction in prediabetes patients.Materials and methods248 prediabetes patients were enrolled in this multi-center randomized controlled trial (RCT). Patients were randomly divided into 3 groups: RT (n = 82), aerobic training (AT (n = 83)), and control group (n = 83). Participants in RT and AT groups had moderate RT or AT 3 times a week (150 min/week) under supervision in 3 research centers for 24 months. Primary outcome was CVD risk measured by Framingham Risk Score (FRS) and The Chinese 10-year ischemic cardiovascular disease (ICVD) risk assessment tool. Secondary outcomes included in HOMA2-IR, HbA1c, blood pressure and serum lipid profile.ResultsBoth RT and AT groups experienced a significant reduction in HOMA2-IR, HbA1c, LDL-C, TC, SBP, and DBP at the end of 12 and 24 months. Compared to the control group, Both RT and AT groups had significant reduction of the Chinese 10-year ICVD risk (P < 0.05), but FRS CVD risk declined significantly only in the AT group (all P < 0.05). Although FRS CVD risk decreased more in the RT group than in the control group, the difference was not statistically significant. After adjusting for age, gender, statin use, BMI, and WHR, in COX’s proportional hazard model, RT (HR = 0.419, P = 0.037) and AT (HR = 0.310, P = 0.026) were protective factors for CVD risk in prediabetes patients. 24-month RT and AT decreased respectively 58.1% and 69.0% of CVD risk (10-year ICVD risk assessment) in prediabetes patients.ConclusionsThis study demonstrated that 24-month moderate AT reduces the Chinese 10-year ICVD risk and FRS CVD risk in prediabetes patients. RT groups had significant reduction of CVD risk (10-year ICVD risk assessment) in prediabetes patients.Trial registrationClinical trial registration number: NCT 02561377.Date of registration24/09/2015.     

Efficacy of a multidisciplinary fibromyalgia treatment adapted for women with low educational levels: A randomized controlled trial

Objective

Multidisciplinary treatments of fibromyalgia (FM) have demonstrated efficacy. Nevertheless, they have been criticized for not maintaining their benefits and for not being studied for specific populations. Our objectives were to determine the efficacy of a multidisciplinary treatment for FM adapted for patients with low educational levels and to determine the maintenance of its therapeutic benefits during a long‐term followup period.

Methods

Inclusion criteria consisted of female sex, a diagnosis of FM (using American College of Rheumatology criteria), age between 18 and 60 years, and between 3 and 8 years of schooling. Patients were randomly assigned to 1 of the 2 treatment conditions: conventional pharmacologic treatment or multidisciplinary treatment. Outcome measures were functionality, sleep disturbances, pain intensity, catastrophizing, and psychological distress. Analysis was by intent‐to‐treat and missing data were replaced following the baseline observation carried forward method.

Results

One hundred fifty‐five participants were recruited. No statistically significant differences regarding pretreatment measures were found between the 2 experimental groups. Overall statistics comparison showed a significant difference between the 2 groups in all of the variables studied (P < 0.0001). Mixed linear model analysis demonstrated the superiority of the multidisciplinary treatment in all of the studied variables at posttreatment. The differences were maintained at 12‐month followup in sleep disturbances (P < 0.0001), catastrophizing (P < 0.0001), and psychological distress (P < 0.01).

Conclusion

Multidisciplinary treatment adapted for individuals with low educational levels is effective in reducing key symptoms of FM. Some improvements were maintained 1 year after completing the multidisciplinary treatment.