Six-month exercise training program to treat post-thrombotic syndrome: a randomized controlled two-centre trial

Background

Exercise training may have the potential to improve post-thrombotic syndrome, a frequent, chronic complication of deep venous thrombosis. We conducted a randomized controlled two-centre pilot trial to assess the feasibility of a multicentre-based evaluation of a six-month exercise training program to treat post-thrombotic syndrome and to obtain preliminary data on the effectiveness of such a program.

Methods

Patients were randomized to receive exercise training (a six-month trainer-supervised program) or control treatment (an education session with monthly phone follow-ups). Levels of eligibility, consent, adherence and retention were used as indicators of study feasibility. Primary outcomes were change from baseline to six months in venous disease-specific quality of life (as measured using the Venous Insufficiency Epidemiological and Economic Study Quality of Life [VEINES-QOL] questionnaire) and severity of post-thrombotic syndrome (as measured by scores on the Villalta scale) in the exercise training group versus the control group, assessed by t tests. Secondary outcomes were change in generic quality of life (as measured using the Short-Form Health Survey-36 [SF-36] questionnaire), category of severity of post-thrombotic syndrome, leg strength, leg flexibility and time on treadmill.

Results

Of 95 patients with post-thrombotic syndrome, 69 were eligible, 43 consented and were randomized, and 39 completed the study. Exercise training was associated with improvement in VEINES-QOL scores (exercise training mean change 6.0, standard deviation [SD] 5.1 v. control mean change 1.4, SD 7.2; difference 4.6, 95% CI 0.54 to 8.7; p = 0.027) and improvement in scores on the Villalta scale (exercise training mean change −3.6, SD 3.7 v. control mean change −1.6, SD 4.3; difference −2.0, 95% CI −4.6 to 0.6; p = 0.14). Most secondary outcomes also showed greater improvement in the exercise training group.

Interpretation

Exercise training may improve post-thrombotic syndrome. It would be feasible to definitively evaluate exercise training as a treatment for post-thrombotic syndrome in a large multicentre trial.Chronic post-thrombotic syndrome develops in up to one-half of patients with deep venous thrombosis and is associated with varying combinations of leg pain, heaviness, swelling, edema, hyperpigmentation and varicose collateral veins. In severe instances, lipodermatosclerosis and venous ulcers occur.¹ Patients with post-thrombotic syndrome have substantially impaired quality of life.^2,3 Given that effective treatments are lacking, new approaches to managing post-thrombotic syndrome are needed.⁴Exercise training is an effective treatment for arterial claudication^5,6 and may also improve post-thrombotic syndrome.⁷ Potential mechanisms include improved endurance resulting from increased aerobic capacity, reduced muscular effort from improved strength, reduced swelling and discomfort via improved function of the calf muscle pump and improved muscu-loskeletal function via increased flexibility of ankle and knee joints.^8,9We performed a pilot trial to obtain data on the effectiveness of exercise training to treat post-thrombotic syndrome and to assess the feasibility of performing a multicentre study to address this question.     

Combining behavioral weight loss treatment and a commercial program: A randomized clinical trial

Objective:

To test the hypothesis that a novel weight loss approach that combined the fundamental components of professionally delivered behavioral weight loss (BWL) treatment with the existing Weight Watchers (WW) program would produce better weight losses than WW alone no differences were expected between the novel treatment and BWL alone.

Design and Methods:

Participants were 141 overweight and obese adults (90% women, 67% non‐White, mean age = 49.7 ± 9.2 years, mean body mass index = 36.2 ± 5.5 kg/m²) randomly assigned to 48 weeks of BWL, 48 weeks of WW, or 12 weeks of BWL followed by 36 weeks of WW [combined treatment (CT)]. Assessments were conducted at baseline and weeks 12, 24, and 48, with weight change as the primary outcome.

Results:

Linear mixed model analysis showed that 24‐week weight losses did not differ significantly between treatment groups; however, weight losses at 48 weeks were greater in the WW group (M = ?6.0 kg, standard error (SE) = 0.8) compared with the CT group (M = ?3.6 kg, SE = 0.8; P = 0.032), with BWL not significantly different from either (M = ?5.4 kg, SE = 0.8). Further, a greater proportion of WW participants lost 10% of baseline weight by 48 weeks compared with BWL or CT (36.7%, 13.0%, and 15.2%, respectively, P < 0.05).

Conclusion:

This study shows that the WW program can produce clinically meaningful weight losses and provides no evidence that adding brief BWL to the WW program improves outcome.

     

A randomized double blind crossover placebo-controlled clinical trial to assess the effects of a mouthwash containing chlorine dioxide on oral malodor

Background

Each year in the UK 2000 children attend emergency departments and 500 are admitted to hospital following a bath water scald. The long term effects can include disability, disfigurement or psychological harm and repeated skin grafts may be required as the child grows. The costs of treating a severe scald are estimated at 250,000 GBP. Children living in the most deprived wards are at greatest risk of thermal injuries; hospital admission rates are three times that for children living in the least deprived wards. Domestic hot water, which is usually stored at around 60 degrees Celsius, can result in a second-degree burn after 3 seconds and a third-degree burn after 5 seconds. Educational strategies to encourage testing of tap water temperature and reduction of hot water thermostat settings have largely proved unsuccessful. Legislation in the USA mandating pre-setting hot water heater thermostats at 49 degrees Celsius was effective in reducing scald injuries, suggesting passive measures may have a greater impact. Thermostatic mixer valves (TMVs), recently developed for the domestic market, fitted across the hot and cold water supply pipes of the bath, allow delivery of water set at a fixed temperature from the hot bath tap. These valves therefore offer the potential to reduce scald injuries.

Design/Methods

A pragmatic, randomised controlled trial to assess the effectiveness of TMVs in reducing bath hot tap water temperatures in the homes of families with young children in rented social housing. Two parallel arms include an intervention group and a control group where the intervention will be deferred. The intervention will consist of fitting a TMV (set at 44 degrees Celsius) by a qualified plumber and provision of educational materials. The control arm will not receive a TMV or the educational materials for the study duration but will be offered the intervention after collection of follow-up data 12 months post randomisation. The primary outcome measure will be the bath hot tap water temperature. Fifteen families per arm are required to detect a reduction in the mean bath hot tap water temperature from 60.4 degrees Celsius (SD 9.1) in the control group to 46 degrees Celsius in the intervention group, with 90% power and a 5% significance level (2 sided). Secondary outcome measures including acceptability will require a sample size of 120 participants.

Discussion

Whilst TMVs have the potential to reduce scald injuries, to date there have been no randomised controlled trials assessing their effectiveness, acceptability and cost effectiveness.

Trial Registration

ISRCTN21179067     

A randomized pilot trial of a full subsidy vs. a partial subsidy for obesity treatment

Intensive obesity treatment is mandated by federal health care reform but is costly. A partial subsidy for obesity treatment could lower the cost of treatment, without reducing its efficacy. This study sought to test whether a partial subsidy for obesity treatment would be feasible, as compared to a fully subsidized intervention. The study was a pilot randomized trial. Participants (n = 50) were primary care patients with obesity and at least one comorbid condition (diabetes, hypertension, dyslipidemia, or obstructive sleep apnea). Each participant received eight weight loss counseling visits as well as portion-controlled foods for weight loss. Participants were randomized to full subsidy or partial subsidy (2 vs. 1 meal per day provided). The primary outcome was weight change after 4 months. Secondary outcomes included changes in blood pressure, waist circumference, and health-related quality of life. Participants in the full and partial subsidy groups lost 5.9 and 5.3 kg, equivalent to 5.3% and 5.1% of initial weight, respectively (P = 0.71). Changes in secondary outcomes were similar in the two groups. A partial subsidy was feasible and induced a clinically similar amount of weight loss, compared to a full subsidy. Large-scale testing of economic incentives for weight control is merited given the federal mandate to offer weight loss counseling to obese patients.     

Effects of the multiple risk factor intervention trial smoking cessation program on pulmonary function. A randomized controlled trial.

To determine whether the decline in pulmonary function in smokers is modified by stop-smoking intervention, a randomized controlled study (the Multiple Risk Factor Intervention Trial) was done comparing participants in a special intervention group that included an intensive smoking cessation program with those assigned to usual care. The subjects were 6,347 middle-aged male smokers who had serial measurements of pulmonary function--principally the forced expiratory volume in 1 second (FEV1)--during 6 to 7 years of follow-up. No overall differences were detected in the rate of loss of FEV1 in the two groups. The use of beta-blockers, which had detrimental effects on FEV1, was significantly more common in the intervention group. Among nonusers of beta-blockers, heavy smokers lost FEV1 at a rate about 11 ml per year slower in the intervention group than in the control group (2P = .09) and ended the trial with an FEV1 about 90 ml higher (2P = .05). These results support the inference from observational studies that smoking cessation has a beneficial effect on pulmonary function in heavy smokers.     

Aerobic endurance training versus relaxation training in patients with migraine (ARMIG): study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: Migraine is one of the most frequent headache diseases and impairs patients' quality of life. Up to now, many randomized studies reported efficacy of prophylactic therapy with medications such as beta-blockers or anti-epileptic drugs. Non-medical treatment, like aerobic endurance training, is considered to be an encouraging alternative in migraine prophylaxis. However, there is still a lack of prospective, high-quality randomized trials. We therefore designed a randomized controlled trial to evaluate the efficacy of aerobic endurance training versus relaxation training in patients with migraine (ARMIG). METHODS: This is a single-center, open-label, prospective, randomized trial. Sixty participants with migraine are randomly allocated to either endurance training or a relaxation group. After baseline headache diary documentation over at least 4 weeks, participants in the exercise group will start moderate aerobic endurance training under a sport therapist's supervision at least 3 times a week over a 12-week period. The second group will perform Jacobson's progressive muscle relaxation training guided by a trained relaxation therapist, also at least 3 times a week over a 12-week period. Both study arms will train in groups of up to 10 participants. More frequent individual training is possible. The follow-up period will be 12 weeks after the training period. The general state of health, possible state of anxiety or depression, impairments due to the headache disorder, pain-related disabilities, the headache-specific locus of control, and the motor fitness status are measured with standardized questionnaires. DISCUSSION: The study design is adequate to generate meaningful results. The trial will be helpful in gaining important data on exercise training for non-medical migraine prophylaxis. Trial registration The trial is registered at ClinicalTrials.gov: NCT01407861.     

A randomized triple blind trial to assess the effect of an anthelmintic programme for working equids in Morocco

Background  

Gastro-intestinal parasitism has been identified as a significant cause of disease in working equids in many countries. This randomized triple-blind trial was designed to assess the impact of an anthelmintic treatment programme (using oral ivermectin and fenbendazole) comparing treated and placebo control populations of working donkeys, mules and horses in field conditions in Morocco. In particular, we assessed animal body weight and condition score, together with a questionnaire-based owner evaluation of number of subjective animal health parameters. Faecal worm egg count was also measured.     

Mental practice-based rehabilitation training to improve arm function and daily activity performance in stroke patients: a randomized clinical trial

Background  

Over 50% of patients with upper limb paresis resulting from stroke face long-term impaired arm function and ensuing disability in daily life. Unfortunately, the number of effective treatments aimed at improving arm function due to stroke is still low. This study aims to evaluate a new therapy for improving arm function in sub-acute stroke patients based on mental practice theories and functional task-oriented training, and to study the predictors for a positive treatment result. It is hypothesized that a six-week, mental practice-based training program (additional to regular therapy) targeting the specific upper extremity skills important to the individual patient will significantly improve both arm function and daily activity performance, as well as being cost effective.     

A multi-center randomized trial to assess the efficacy of gatifloxacin versus ciprofloxacin for the treatment of shigellosis in Vietnamese children

Background

The bacterial genus Shigella is the leading cause of dysentery. There have been significant increases in the proportion of Shigella isolated that demonstrate resistance to nalidixic acid. While nalidixic acid is no longer considered as a therapeutic agent for shigellosis, the fluoroquinolone ciprofloxacin is the current recommendation of the World Health Organization. Resistance to nalidixic acid is a marker of reduced susceptibility to older generation fluoroquinolones, such as ciprofloxacin. We aimed to assess the efficacy of gatifloxacin versus ciprofloxacin in the treatment of uncomplicated shigellosis in children.

Methodology/Principal Findings

We conducted a randomized, open-label, controlled trial with two parallel arms at two hospitals in southern Vietnam. The study was designed as a superiority trial and children with dysentery meeting the inclusion criteria were invited to participate. Participants received either gatifloxacin (10 mg/kg/day) in a single daily dose for 3 days or ciprofloxacin (30 mg/kg/day) in two divided doses for 3 days. The primary outcome measure was treatment failure; secondary outcome measures were time to the cessation of individual symptoms. Four hundred and ninety four patients were randomized to receive either gatifloxacin (n  =  249) or ciprofloxacin (n  =  245), of which 107 had a positive Shigella stool culture. We could not demonstrate superiority of gatifloxacin and observed similar clinical failure rate in both groups (gatifloxacin; 12.0% and ciprofloxacin; 11.0%, p  =  0.72). The median (inter-quartile range) time from illness onset to cessation of all symptoms was 95 (66–126) hours for gatifloxacin recipients and 93 (68–120) hours for the ciprofloxacin recipients (Hazard Ratio [95%CI]  =  0.98 [0.82–1.17], p  =  0.83).

Conclusions

We conclude that in Vietnam, where nalidixic acid resistant Shigellae are highly prevalent, ciprofloxacin and gatifloxacin are similarly effective for the treatment of acute shigellosis.

Trial Registration

Controlled trials number ISRCTN55945881     

Efficacy of intra-lesional injections of meglumine antimoniate once a week vs. twice a week in the treatment of cutaneous leishmaniasis caused by L. tropica in Iran: A randomized controlled clinical trial

Treatment of Cutaneous leishmaniasis (CL) is based on using antimoniate derivatives; patients’ compliance for systemic injections is low due to the pain and systemic complications. In this randomized open trial, the efficacy of intra-lesional (IL) injections of meglumine antimoniate (MA) once a week vs. twice a week in the treatment of Anthrpoponothic CL caused by L. tropica was studied. Eligible volunteer patients were selected according to inclusion/exclusion criteria. The included patients were randomly allocated to receive IL-MA injections once a week or twice a week. The primary outcome was set as complete healing of the lesion(s), and defined as complete re-epithelialization and absence of induration in the lesions. A total of 180 parasitologicaly proven CL patients caused by L. tropica were recruited, 90 patients were treated with weekly IL-MA and 90 patients received IL-MA twice a week. The complete cure was 87.9% vs. 89.2% in the group received weekly and twice a week IL-MA injections, respectively (P = 0.808). Patients’ compliance was acceptable and side effects were limited to a few local allergic reactions to MA. Median time to healing was significantly shorter in patients who received IL-MA twice a week (median ± SE) 37±3.8, (CI: 29.6–44.4) days compared to whom received IL-MA once a week 60±2.3, (CI: 55.6–64.5) days (P< 0.001), however the number of injections was higher in group who received IL-MA twice a week (12 vs. 9 injections). In conclusion, the rate of cure in the group of CL patients with IL-MA twice a week was not significantly different from the group who received IL-MA once a week shorten, but the duration of healing was shorter in the group who received IL-MA twice a week while the group received more injections so is recommended to use IL-MA once a week due to the fact the compliance is acceptable with limited side effects.Clinical Trial Registration: IRCT20081130001475N13; https://en.irct.ir/.     

A randomized, placebo-controlled, double-blind clinical trial of curcuminoids in oral lichen planus.

We studied the efficacy of curcuminoids in the treatment of oral lichen planus (OLP), a chronic, mucocutaneous, immunological disease. Curcuminoids are components of turmeric (Curcuma longa) that have anti-inflammatory activity. Turmeric has been used in Ayurveda (Indian traditional medicine) for centuries. A randomized, double-blind, placebo-controlled trial was conducted. In all, 100 consecutive, eligible patients with OLP presenting to the oral medicine clinic at the University of California, San Francisco, were to be selected. Two interim analyses were to be conducted during the trial. The trial was conducted between February 2003 and September 2004. The first interim analysis was conducted in October 2004 using data from the first 33 subjects. Study subjects were randomized to receive either placebo or curcuminoids at 2000 mg/day for 7 weeks. In addition, all subjects received prednisone at 60 mg/day for the first 1 week. The primary outcome was a change in symptoms from baseline. Secondary outcomes were changes in clinical signs and occurrence of side effects. The first interim analysis did not show a significant difference between the placebo and curcuminoids groups. Conditional power calculations suggested a less than 2% chance that the curcuminoids group would have a significantly better outcome as compared with the placebo group if the trial were continued to completion. Therefore, the study was ended early for futility. Reaching a conclusion regarding the efficacy of curcuminoids based on the results of this study is not possible as it was ended early for futility. Curcuminoids at this dose were well tolerated and the results suggest that for future studies a larger sample size, a higher dose and/or longer duration of curcuminoids administration should be considered; however, for the next step, an RCT of a shorter duration, using a higher dose of curcuminoids, and without an initial course of prednisone, should be considered.     

A randomized trial to assess the impact of an antithrombotic decision aid in patients with nonvalvular atrial fibrillation: the DAAFI trial protocol [ISRCTN14429643]

Background

Surprisingly little information on symptoms of paroxysmal atrial fibrillation is available in scientific literature. Using questionnaires, we have analyzed the symptoms associated with arrhythmia attacks.

Methods

One hundred randomly-selected patients with idiopathic paroxysmal atrial fibrillation filled in a structured questionnaire.

Results

Psychic stress was the most common factor triggering arrhythmia (54%), followed by physical exertion (42%), tiredness (41%) coffee (25%) and infections (22%). Thirty-four patients cited alcohol, 26 in the form of red wine, 16 as white wine and 26 as spirits. Among these 34, red wine and spirits produced significantly more episodes of arrhythmia than white wine (p = 0.01 and 0.005 respectively). Symptoms during arrhythmia were palpitations while exerting (88%), reduced physical ability (87%), palpitations at rest (86%), shortage of breath during exertion (70%) and anxiety (59%). Significant differences between sexes were noted regarding swollen legs (women 21%, men 6%, p = 0.027), nausea (women 36%, men 13%, p = 0.012) and anxiety (females 79%, males 51%, p = 0.014).

Conclusion

Psychic stress was the commonest triggering factor in hospitalized patients with paroxysmal atrial fibrillation. Red wine and spirits were more proarrhythmic than white wine. Symptoms in women in connection with attacks of arrhythmia vary somewhat from those in men.     

A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms,signs and biomarkers of acute hepatitis

PurposeMilk thistle or its purified extract, silymarin (Silybum marianum), is widely used in treating acute or chronic hepatitis. Although silymarin is hepatoprotective in animal experiments and some human hepatotoxic exposures, its efficacy in ameliorating the symptoms of acute clinical hepatitis remains inconclusive. In this study, our purpose was to determine whether silymarin improves symptoms, signs and laboratory test results in patients with acute clinical hepatitis, regardless of etiology.MethodsThis is a randomized, placebo-controlled trial in which participants, treating physicians and data management staff were blinded to treatment group. The study was conducted at two fever hospitals in Tanta and Banha, Egypt where patients with symptoms compatible with acute clinical hepatitis and serum alanine aminotransferase (ALT) levels >2.5 times the upper limit of normal were enrolled. The intervention consisted of three times daily ingestion of either a standard recommended dose of 140 mg of silymarin (Legalon^®, MADAUS GmbH, Cologne, Germany), or a vitamin placebo for four weeks with an additional four-week follow-up. The primary outcomes were symptoms and signs of acute hepatitis and results of liver function tests on days 2, 4 and 7 and weeks 2, 4, and 8. Side-effects and adverse events were ascertained by self-report.ResultsFrom July 2003 through October 2005, 105 eligible patients were enrolled after providing informed consent. No adverse events were noted and both silymarin and placebo were well tolerated. Patients randomized to the silymarin group had quicker resolution of symptoms related to biliary retention: dark urine (p=0.013), jaundice (p=0.02) and scleral icterus (p=0.043). There was a reduction in indirect bilirubin among those assigned to silymarin (p=0.012), but other variables including direct bilirubin, ALT and aspartate aminotransferase (AST) were not significantly reduced.ConclusionsPatients receiving silymarin had earlier improvement in subjective and clinical markers of biliary excretion. Despite a modest sample size and multiple etiologies for acute clinical hepatitis, our results suggest that standard recommended doses of silymarin are safe and may be potentially effective in improving symptoms of acute clinical hepatitis despite lack of a detectable effect on biomarkers of the underlying hepatocellular inflammatory process.     

Estimating treatment effects from a randomized clinical trial in the presence of a secondary treatment

In randomized clinical trials involving survival time, a challenge that arises frequently, for example, in cancer studies (Manegold, Symanowski, Gatzemeier, Reck, von Pawel, Kortsik, Nackaerts, Lianes and Vogelzang, 2005. Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma. Annals of Oncology 16, 923--927), is that subjects may initiate secondary treatments during the follow-up. The marginal structural Cox model and the method of inverse probability of treatment weighting (IPTW) have been proposed, originally for observational studies, to make causal inference on time-dependent treatments. In this paper, we adopt the marginal structural Cox model and propose an inferential method that improves the efficiency of the usual IPTW method by tailoring it to the setting of randomized clinical trials. The improvement in efficiency does not depend on any additional assumptions other than those required by the IPTW method, which is achieved by exploiting the knowledge that the study treatment is independent of baseline covariates due to randomization. The finite-sample performance of the proposed method is demonstrated via simulations and by application to data from a cancer clinical trial.     

A cluster randomized controlled trial of the effectiveness and cost-effectiveness of Intermediate Care Clinics for Diabetes (ICCD): study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: World-wide healthcare systems are faced with an epidemic of type 2 diabetes. In the United Kingdom, clinical care is primarily provided by general practitioners (GPs) rather than hospital specialists. Intermediate care clinics for diabetes (ICCD) potentially provide a model for supporting GPs in their care of people with poorly controlled type 2 diabetes and in their management of cardiovascular risk factors. This study aims to (1) compare patients with type 2 diabetes registered with practices that have access to an ICCD service with those that have access only to usual hospital care; (2) assess the cost-effectiveness of the intervention; and (3) explore the views and experiences of patients, health professionals and other stakeholders. METHODS: This two-arm cluster randomized controlled trial (with integral economic evaluation and qualitative study) is set in general practices in three UK Primary Care Trusts. Practices are randomized to one of two groups with patients referred to either an ICCD (intervention) or to hospital care (control).Intervention group: GP practices in the intervention arm have the opportunity to refer patients to an ICCD - a multidisciplinary team led by a specialist nurse and a diabetologist. Patients are reviewed and managed in the ICCD for a short period with a goal of improving diabetes and cardiovascular risk factor control and are then referred back to practice.orControl group: Standard GP care, with referral to secondary care as required, but no access to ICCD.Participants are adults aged 18 years or older who have type 2 diabetes that is difficult for their GPs to control. The primary outcome is the proportion of participants reaching three risk factor targets: HbA1c (<=7.0%); blood pressure (<140/80); and cholesterol (<4 mmol/l), at the end of the 18-month intervention period. The main secondary outcomes are the proportion of participants reaching individual risk factor targets and the overall 10-year risks for coronary heart disease(CHD) and stroke assessed by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Other secondary outcomes include body mass index and waist circumference, use of medication, reported smoking, emotional adjustment, patient satisfaction and views on continuity, costs and health related quality of life. We aimed to randomize 50 practices and recruit 2,555 patients. DISCUSSION: Forty-nine practices have been randomized, 1,997 patients have been recruited to the trial, and 20 patients have been recruited to the qualitative study. Results will be available late 2012.Trial registration[ClinicalTrials.gov: Identifier NCT00945204].     

Assessing the therapeutic use of Lafoensia pacari St. Hil. extract (mangava-brava) in the eradication of Helicobacter pylori: double-blind randomized clinical trial

BACKGROUND: The eradication of Helicobacter pylori is easily achieved by combining antisecretory agents and antibiotics; however, the cost of these associations is very high for the population of Third World countries, where the prevalence of the infection is even higher and leads to markedly reduced treatment effectiveness. We tested a plant (Lafoensia pacari) that is used in the central region of Brazil. According to previous studies, this plant has high concentrations of ellagic acid, which presents gastric antisecretory and antibacterial actions. MATERIAL AND METHODS: One hundred dyspeptic, urease-positive patients were randomized to receive 500 mg of methanolic extract of L. pacari (n = 55) or placebo (n = 45), for 14 days, in a double-blind clinical trial. The main variables assessed were the eradication of H. pylori 8 weeks after the intervention and complete symptom relief at the end of the treatment. RESULTS: The examinations (urease and histology) showed persistence of H. pylori in 100% of participants. Complete symptom relief was experienced by 42.5% of patients (95% CI: 29.4-55.8) in the intervention group and by 21% (95% CI: 8.8-33.1) in the control group, p = .020. The side-effects were minimal and similar in both groups. CONCLUSIONS: The extract of L. pacari as a single agent was not effective to eradicate H. pylori. However, it was well tolerated and many participants reported relief of symptoms. Future studies may test the agent using larger doses and longer periods, in monotherapy or in combination with antibiotics.     

Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial

Background

Vitamin K has been widely promoted as a supplement for decreasing bone loss in postmenopausal women, but the long-term benefits and potential harms are unknown. This study was conducted to determine whether daily high-dose vitamin K1 supplementation safely reduces bone loss, bone turnover, and fractures.

Methods and Findings

This single-center study was designed as a 2-y randomized, placebo-controlled, double-blind trial, extended for earlier participants for up to an additional 2 y because of interest in long-term safety and fractures. A total of 440 postmenopausal women with osteopenia were randomized to either 5 mg of vitamin K1 or placebo daily. Primary outcomes were changes in BMD at the lumbar spine and total hip at 2 y. Secondary outcomes included changes in BMD at other sites and other time points, bone turnover markers, height, fractures, adverse effects, and health-related quality of life. This study has a power of 90% to detect 3% differences in BMD between the two groups. The women in this study were vitamin D replete, with a mean serum 25-hydroxyvitamin D level of 77 nmol/l at baseline. Over 2 y, BMD decreased by −1.28% and −1.22% (p = 0.84) (difference of −0.06%; 95% confidence interval [CI] −0.67% to 0.54%) at the lumbar spine and −0.69% and −0.88% (p = 0.51) (difference of 0.19%; 95% CI −0.37% to 0.75%) at the total hip in the vitamin K and placebo groups, respectively. There were no significant differences in changes in BMD at any site between the two groups over the 2- to 4-y period. Daily vitamin K1 supplementation increased serum vitamin K1 levels by 10-fold, and decreased the percentage of undercarboxylated osteocalcin and total osteocalcin levels (bone formation marker). However, C-telopeptide levels (bone resorption marker) were not significantly different between the two groups. Fewer women in the vitamin K group had clinical fractures (nine versus 20, p = 0.04) and fewer had cancers (three versus 12, p = 0.02). Vitamin K supplements were well-tolerated over the 4-y period. There were no significant differences in adverse effects or health-related quality of life between the two groups. The study was not powered to examine fractures or cancers, and their numbers were small.

Conclusions

Daily 5 mg of vitamin K1 supplementation for 2 to 4 y does not protect against age-related decline in BMD, but may protect against fractures and cancers in postmenopausal women with osteopenia. More studies are needed to further examine the effect of vitamin K on fractures and cancers. Trial registration: ClinicalTrials.gov (#{"type":"clinical-trial","attrs":{"text":"NCT00150969","term_id":"NCT00150969"}}NCT00150969) and Current Controlled Trials (#ISRCTN61708241)