A double blind randomized controlled trial to evaluate the efficacy of green tea in gingivitis

Gingivitis is the most common form of oral disease especially among patients undergoing fixed orthodontic treatment. Green tea, which is extensively used in Asian countries, can help to improve the overall gingival health, which can be assessed by using the gingival indices. Evaluation of the effectiveness of green tea on the gingival health of patients undergoing Orthodontic treatment is of interest. 40 otherwise healthy patients undergoing fixed orthodontic treatment were randomly divided in two groups namely (1) study group and (2) control group. Gingival indices were scored for all the patients. Study group was given mouth rinse with green tea extract and control group was given placebo with no green tea extract. Gingival indices were measured for all the patients after 21 days. Mann Whitney U test and Wilcoxon test was used for statistical analysis. The gingival indices scoring in which the values before and after the use of mouthwash were compared. The p value was found to be statistically significant (p<0.05) in study group. But in control group statistical significant could not be reached.     

Outcomes in registered, ongoing randomized controlled trials of patient education

Background

With the increasing prevalence of chronic noncommunicable diseases, patient education is becoming important to strengthen disease prevention and control. We aimed to systematically determine the extent to which registered, ongoing randomized controlled trials (RCTs) evaluated an educational intervention focus on patient-important outcomes (i.e., outcomes measuring patient health status and quality of life).

Methods

On May 6, 2009, we searched for all ongoing RCTs registered in the World Health Organization International Clinical Trials Registry platform. We used a standardized data extraction form to collect data and determined whether the outcomes assessed were 1) patient-important outcomes such as clinical events, functional status, pain, or quality of life or 2) surrogate outcomes, such as biological outcome, treatment adherence, or patient knowledge.

Principal Findings

We selected 268 of the 642 potentially eligible studies and assessed a random sample of 150. Patient-important outcomes represented 54% (178 of 333) of all primary outcomes and 46% (286 of 623) of all secondary outcomes. Overall, 69% of trials (104 of 150) used at least one patient-important outcome as a primary outcome and 66% (99 of 150) as a secondary outcome. Finally, for 31% of trials (46 of 150), primary outcomes were only surrogate outcomes. The results varied by medical area. In neuropsychiatric disorders, patient important outcomes represented 84% (51 of 61) of primary outcomes, as compared with 54% (32 of 59) in malignant neoplasm and 18% (4 of 22) in diabetes mellitus trials.In addition, only 35% assessed the long-term impact of interventions (i.e., >6 months).

Conclusions

There is a need to improve the relevance of outcomes and to assess the long term impact of educational interventions in RCTs.     

Diagnostic randomized controlled trials: the final frontier

ABSTRACT: Clinicians, patients, governments, third-party payers, and the public take for granted that diagnostic tests are accurate, safe and effective. However, we may be seriously misled if we are relying on robust study design to ensure accurate, safe, and effective diagnostic tests. Properly conducted, randomized controlled trials are the gold standard for assessing the effectiveness and safety of interventions, yet are rarely conducted in the assessment of diagnostic tests. Instead, diagnostic cohort studies are commonly performed to assess the characteristics of a diagnostic test including sensitivity and specificity. While diagnostic cohort studies can inform us about the relative accuracy of an experimental diagnostic intervention compared to a reference standard, they do not inform us about whether the differences in accuracy are clinically important, or the degree of clinical importance (in other words, the impact on patient outcomes). In this commentary we provide the advantages of the diagnostic randomized controlled trial and suggest a greater awareness and uptake in their conduct. Doing so will better ensure that patients are offered diagnostic procedures that will make a clinical difference.     

Efficacy of a small single dose of oral dexamethasone for outpatient croup: a double blind placebo controlled clinical trial.

OBJECTIVE--To assess the efficacy of a single dose of oral dexamethasone 0.15 mg/kg in children with mild croup not admitted to hospital. DESIGN--Double blind, randomised, placebo controlled clinical trial. SETTING--The emergency department of a tertiary paediatric hospital. SUBJECTS--100 children aged 4-122 months presenting with mild croup. INTERVENTION--A single oral dose of dexamethasone 0.15 mg/kg or placebo. MAIN OUTCOME MEASURE--Return to medical care with ongoing croup. RESULTS--Baseline characteristics of the two treatment groups were similar. Eight children (all from the placebo group) returned to medical care with ongoing croup, one being admitted. There was no reported difference in duration of croup symptoms, duration of viral symptoms, or rate of return to medical care for other reasons. CONCLUSION--Oral dexamethasone in a dose of 0.15 mg/kg is effective in reducing return to medical care with ongoing croup in children with mild croup.     

Garlic for hypertension: A systematic review and meta-analysis of randomized controlled trials

BackgroundIn the past decade, garlic has become one of the most popular complementary therapies for blood pressure (BP) control used by hypertensive patients. Numerous clinical studies have focused on the BP-lowering effect of garlic, but results have been inconsistent. Overall, there is a dearth of information available to guide the clinical community on the efficacy of garlic in hypertensive patients.AimTo systematically review the medical literature to investigate the current evidence of garlic for the treatment of hypertension.MethodsPubMed, the Cochrane Library and EMBASE were searched for appropriate articles from their respective inceptions until August 2014. Randomized, placebo-controlled trials comparing garlic vs. a placebo in patients with hypertension were considered. Papers were independently reviewed by two reviewers and were analyzed using Cochrane software Revman 5.2.ResultsA total of seven randomized, placebo-controlled trials were identified. Compared with the placebo, this meta-analysis revealed a significant lowering effect of garlic on both systolic BP (WMD: −6.71 mmHg; 95% CI: −12.44 to −0.99; P = 0.02) and diastolic BP (WMD: −4.79 mmHg; 95% CI: −6.60 to −2.99; P < 0.00001). No serious adverse events were reported in any of the trials.ConclusionThe present review suggests that garlic is an effective and safe approach for hypertension. However, more rigorously designed randomized controlled trials focusing on primary endpoints with long-term follow-up are still warranted before garlic can be recommended to treat hypertensive patients.     

Randomised double blind trial of single dose doxycycline for treating cholera in adults.

OBJECTIVE--To compare the efficacy of a single dose of doxycycline (200 or 300 mg) with the standard multiple doses of tetracycline in patients with cholera. DESIGN--Randomised double blind controlled trial. Patients were given a single 200 mg dose of doxycycline, a single 300 mg dose of doxycycline, or multiple doses of tetracycline (500 mg, six hourly intervals). SETTING--Hospital in Bangladesh treating diarrhoea. PATIENTS--261 Patients aged over 15 admitted to the hospital with severe dehydration due to acute watery diarrhoea associated with Vibrio cholerae. All vibrios isolated from the stools and rectal swabs of patients, including those patients with prolonged excretion of vibrios, were sensitive to tetracycline. The stools of all patients at admission were negative for shigella and salmonella. INTERVENTIONS--All patients received rapid intravenous acetate solution for the first four hours after admission to hospital. They were then entered in the study and randomised. Oral rehydration was started immediately after the intravenous treatment. If signs of severe dehydration reappeared during oral treatment patients were given rapid intravenous acetate solution until dehydration was fully corrected. MAIN OUTCOME MEASURES--Stool output in first 24 hours and till diarrhoea stopped, total intake of oral rehydration fluid, duration of diarrhoea, and excretion of vibrio after receiving antibiotic treatment. RESULTS--The median stool outputs during the first 24 hours (275 ml/kg body weight) and till diarrhoea stopped (296 ml/kg body weight) were significantly higher in patients receiving 200 mg doxycycline as a single dose than in patients receiving either standard tetracycline (242 ml/kg body weight and 254 ml/kg body weight) or 300 mg doxycycline (226 ml/kg body weight and 255 ml/kg body weight). Similarly, median consumption of oral rehydration solution (18.45 l) was significantly higher in patients receiving 200 mg doxycycline than in patients receiving either 300 mg doxycycline (16.10 l) or standard tetracycline (14.80 l). Almost equal numbers of patients in each group required unscheduled intravenous acetate solution to correct dehydration during antibiotic treatment. Patients treated with doxycycline (low or high dose), however, had more prolonged excretion of bacteria. CONCLUSIONS--A single 300 mg dose of doxycycline is as effective as the standard multiple dose tetracycline treatment for cholera in terms of stool output, duration of diarrhoea, vomiting, and requirement for oral rehydration solution.     

A double blind placebo controlled crossover study of prostacyclin in man.

Prostacyclin sodium (PGI₂) was administered in a double blind crossover trial to 6 normal males at infusion rates of 2, 4 and 8 ng/kg/minute. Substantial (p < 0.001) shifts of the log dose response curve of ADP induced platelet aggregation occured during the highest infusion rate of PGI₂. This was associated with a small but significant fall in diastolic blood pressure (?6.3± 1.6 mm Hg, p < 0.01) and a rise in heart rate (+25.5 ± 6.5 beats/minute, p < 0.001). Plasma renin activity rose in a dose related manner with PGI₂ but plasma aldosterone and plasma norepinephrine did not change. Marked facial flushing occured with PGI₂.     

Cardiac resynchronization therapy: a meta-analysis of randomized controlled trials

Background

Studies of cardiac resynchronization therapy in addition to an implantable cardioverter defibrillator in patients with mild to moderate congestive heart failure had not been shown to reduce mortality until the recent RAFT trial (Resynchronization/Defibrillation for Ambulatory Heart Failure Trial). We performed a meta-analysis including the RAFT trial to determine the effect of cardiac resynchronization therapy with or without an implantable defibrillator on mortality.

Methods

We searched electronic databases and other sources for reports of randomized trials using a parallel or crossover design. We included studies involving patients with heart failure receiving optimal medical therapy that compared cardiac resynchronization therapy with optimal medical therapy alone, or cardiac resynchronization therapy plus an implantable defibrillator with a standard implantable defibrillator. The primary outcome was mortality. The optimum information size was considered to assess the minimum amount of information required in the literature to reach reliable conclusions about cardiac resynchronization therapy.

Results

Of 3071 reports identified, 12 studies (n = 7538) were included in our meta-analysis. Compared with optimal medical therapy alone, cardiac resynchronization therapy plus optimal medical therapy significantly reduced mortality (relative risk [RR] 0.73, 95% confidence interval [CI] 0.62–0.85). Compared with an implantable defibrillator alone, cardiac resynchronization therapy plus an implantable defibrillator significantly reduced mortality (RR 0.83, 95% CI 0.72–0.96). This last finding remained significant among patients with New York Heart Association (NYHA) class I or II disease (RR 0.80, 95% CI 0.67–0.96) but not among those with class III or IV disease (RR 0.84, 95% CI 0.69–1.07). Analysis of the optimum information size showed that the sequential monitoring boundary was crossed, which suggests no need for further clinical trials.

Interpretation

The cumulative evidence is now conclusive that the addition of cardiac resynchronization to optimal medical therapy or defibrillator therapy significantly reduces mortality among patients with heart failure.Congestive heart failure is currently reaching epidemic proportions in Canada, with 500 000 Canadians affected and 50 000 new patients identified each year.¹ It accounts for more than 100 000 hospital admissions per year and has a one-year mortality ranging from 15% to 50%, depending on the severity of heart failure.² By 2050, the number of patients with heart failure is projected to increase threefold.²Advances in medical therapies have resulted in substantial reductions in mortality associated with congestive heart failure.^3–7 The use of devices has recently become an important adjuvant therapy.⁸ Cardiac resynchronization therapy involves pacing from both the right and left ventricles simultaneously to improve myocardial efficiency (see radiographs in Appendix 1, at www.cmaj.ca/cgi/content/full/cmaj.101685/DC1). Cardiac resynchronization therapy has been shown to reduce morbidity and, when compared with medical therapy alone, to reduce mortality.^9–13 Until recently, it was not shown to reduce mortality among patients who also received an implantable cardioverter defibrillator. Among patients receiving optimal medical therapy, the Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT) showed the superiority of cardiac resynchronization therapy in addition to an implantable defibrillator over a standard implantable defibrillator in reducing mortality and the combined outcome of death from any cause or hospital admission related to heart failure.¹⁴We performed a meta-analysis to further assess the effect on mortality of cardiac resynchronization therapy with and without an implantable defibrillator among patients with mildly symptomatic and advanced heart failure.     

Respiratory fluoroquinolones for the treatment of community-acquired pneumonia: a meta-analysis of randomized controlled trials

Background

We investigated whether the use of respiratory fluoroquinolones was associated with better clinical outcomes compared with the use of macrolides and β-lactams among adults with pneumonia.

Methods

We searched PubMed, Current Contents, Scopus, EMBASE, ClinicalTrials.gov and Cochrane with no language restrictions. Two reviewers independently extracted data from published trials that compared fluoroquinolones (levofloxacin, moxifloxacin, gemifloxacin) with macrolides or β-lactams or both. A meta-analysis was performed with the clinical outcomes of mortality, treatment success and adverse outcomes.

Results

We included 23 trials in our meta-analysis. There was no difference in mortality among patients who received fluoroquinolones or the comparator antibiotics (OR 0.85, 95% CI 0.65–1.12). Pneumonia resolved in more patients who received fluoroquinolones compared with the comparator antibiotics for the included outcomes in the intention-to-treat population (OR 1.17, 95% CI 1.00–1.36), clinically evaluable population (OR 1.26, 95% CI 1.06–1.50) and the microbiologically assessed population (OR 1.67, 95% CI 1.28–2.20). Fluoroquinolones were more effective than a combination of β-lactam and macrolide (OR 1.39, 95% CI 1.02–1.90). They were also more effective for patients with severe pneumonia (OR 1.84, 95% CI 1.02–3.29), those who required admission to hospital (OR = 1.30, 95% CI 1.04–1.61) and those who required intravenous therapy (OR = 1.44, 15% CI 1.13–1.85). Fluoroquinolones were more effective than β-lactam and macrolide in open-label trials (OR = 1.35, 95% CI 1.08–1.69) but not in blinded randomized controlled trials (OR = 1.13, 95% CI 0.85–1.50).

Interpretation

Fluoroquinolones were associated with higher success of treatment for severe forms of pneumonia; however, a benefit in mortality was not evident. A randomized controlled trial that includes patients with severe pneumonia with or without bacteremia is needed.Community-acquired pneumonia is among the leading reasons for hospital admission¹ and resource consumption.^2,3 It is the most frequent cause of community-acquired infections among patients admitted to intensive care units.⁴ In addition, it is among the leading causes of death worldwide.Physicians must choose an optimal therapeutic regimen that eliminates the infection effectively, minimizes the risk of developing drug resistance and does not compromise the safety of the patient. The combination of β-lactam and macrolide covers the most common possible pathogens involved in the pathogenesis of pneumonia.⁵ More recently, fluoroquinolones with enhanced activity against Streptococcus pneumoniae were introduced in clinical practice. The favourable pharmacokinetic profile of fluoroquinolones allows for once daily administration, often eliminating the need for parenteral treatment. Furthermore, initial treatment with fluoroquinolones was among the predictors of lower treatment failure among patients with pneumonia.⁶In 2007, the Infectious Diseases Society of America and the American Thoracic Society released new guidelines for the management of care for adult patients with community-acquired pneumonia.⁷ In these guidelines, levofloxacin, gemifloxacin and moxifloxacin were reported to be equally effective as the combination of β-lactam and macrolide, and were proposed to be the preferred treatment option for patients who require admission to hospital, as well as for patients with comorbidity who receive treatment as outpatients. In addition to being safe, these fluoroquinolones are more effective against the most common types of bacteria responsible for the development of community-acquired pneumonia.⁷ For example, S. pneumoniae strains are not fully susceptible to ciprofloxacin. On the other hand, trovafloxacin, clinafloxacin, gatifloxacin and other quinolones are not used because of safety concerns or because they are not widely available. The trials that compared fluoroquinolones with other antibiotics regimens for the treatment of pneumonia were designed on the basis of noninferiority (i.e., an antibiotic is equally effective to a comparator), and several were conducted in order to receive approval from the relevant agencies.We sought to examine whether the use of fluoroquinolones was associated with more advantages or disadvantages than the use of macrolides or β-lactams in terms of mortality, resolution of pneumonia and adverse effects.     

Unbiased research and the human spirit: the challenges of randomized controlled trials.

Research by Klein and associates provides useful information on the relation between episiotomy and outcomes such as perineal trauma, but the methodologic implications of their work are especially fascinating. Physicians who participated in their randomized controlled trial (RCT) were supposed to adhere to a policy of either liberal or restrictive use of episiotomy according to the study arm to which each patient was assigned. However, some used the procedure for approximately 90% of patients regardless of allocation. Klein and associates'' post-hoc study (see pages 769 to 779 of this issue) sheds light on the relation between physician attitudes and the practice of episiotomy. The author contends that the noncompliance encountered by Klein and associates reflects the fact that randomized trials are anathema to the human spirit. He offers suggestions for making RCTs more meaningful and stresses that, although RCTs are indispensible to the advancement of medical knowledge, they necessitate assiduous attention to matters of design and implementation.     

Omeprazole versus placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial.

OBJECTIVE--To investigate the possible therapeutic role of omeprazole, a powerful proton pump inhibitor, in unselected patients presenting with upper gastrointestinal bleeding. DESIGN--Double blind placebo controlled parallel group study. Active treatment was omeprazole 80 mg intravenously immediately, then three doses of 40 mg intravenously at eight hourly intervals, then 40 mg orally at 12 hourly intervals. Treatment was started within 12 hours of admission and given for four days or until surgery, discharge, or death. SETTING--The medical wards of University and City Hospitals, Nottingham. SUBJECTS--1147 consecutive patients aged 18 years or more admitted over 40 months with acute upper gastrointestinal bleeding. MAIN OUTCOME MEASURES--Mortality from all causes; rate of rebleeding, transfusion requirements, and operation rate; effect of treatment on endoscopic appearances at initial endoscopy. RESULTS--Of 1147 patients included in the intention to treat analysis, 569 received placebo and 578 omeprazole. No significant differences were found between the placebo and omeprazole groups for rates of transfusion (302 (53%) placebo v 298 (52%) omeprazole), rebleeding (100 (18%) v 85 (15%)), operation (63 (11%) v 62 (11%)), and death (30 (5.3%) v 40 (6.9%)). However, there was an unexpected but significant reduction in endoscopic signs of upper gastrointestinal bleeding in patients treated with omeprazole compared with those treated with placebo (236 (45%) placebo v 176 (33%) omeprazole; p less than 0.0001). CONCLUSIONS--Omeprazole failed to reduce mortality, rebleeding, or transfusion requirements, although the reduction in endoscopic signs of bleeding suggests that inhibition of acid may be capable of influencing intragastric bleeding. Our data do not justify the routine use of acid inhibiting drugs in the management of haematemesis and melaena.     

Dexamethasone and bacterial meningitis. A meta-analysis of randomized controlled trials.

A meta-analysis of 5 randomized, controlled trials using dexamethasone as adjunctive therapy in the treatment of bacterial meningitis in children was done to assess the efficacy in reducing sequelae. A 6th study including both children and adults was analyzed separately. Results of the 5 pediatric studies indicated no significant difference in case-fatality rate between the placebo and dexamethasone groups. Significantly more neurologic sequelae were found in the placebo group during the period from discharge from hospital to 6 weeks after discharge (relative risk [RR] = 1.99, 95% confidence interval [CI] 1.13 to 3.53) and during the period beginning 6 months after discharge (RR = 3.90, 95% CI 1.72 to 8.85). The incidence of neurologic sequelae from 6 weeks to 6 months after discharge, though less with dexamethasone administration, did not reach statistical significance. The frequency of bilateral hearing loss was significantly greater in the placebo group (RR = 4.12, 95% CI 1.74 to 9.79), but unilateral loss was not statistically different in the two groups. Dexamethasone administration in addition to antimicrobial therapy appears to be effective in reducing neurologic sequelae and bilateral hearing loss associated with bacterial meningitis in children.     

Targeted maximum likelihood estimation for dynamic treatment regimes in sequentially randomized controlled trials

Sequential Randomized Controlled Trials (SRCTs) are rapidly becoming essential tools in the search for optimized treatment regimes in ongoing treatment settings. Analyzing data for multiple time-point treatments with a view toward optimal treatment regimes is of interest in many types of afflictions: HIV infection, Attention Deficit Hyperactivity Disorder in children, leukemia, prostate cancer, renal failure, and many others. Methods for analyzing data from SRCTs exist but they are either inefficient or suffer from the drawbacks of estimating equation methodology. We describe an estimation procedure, targeted maximum likelihood estimation (TMLE), which has been fully developed and implemented in point treatment settings, including time to event outcomes, binary outcomes and continuous outcomes. Here we develop and implement TMLE in the SRCT setting. As in the former settings, the TMLE procedure is targeted toward a pre-specified parameter of the distribution of the observed data, and thereby achieves important bias reduction in estimation of that parameter. As with the so-called Augmented Inverse Probability of Censoring Weight (A-IPCW) estimator, TMLE is double-robust and locally efficient. We report simulation results corresponding to two data-generating distributions from a longitudinal data structure.     

Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials

Background:

Results of randomized controlled trials evaluating zinc for the treatment of the common cold are conflicting. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zinc for such use.

Methods:

We searched electronic databases and other sources for studies published through to Sept. 30, 2011. We included all randomized controlled trials comparing orally administered zinc with placebo or no treatment. Assessment for study inclusion, data extraction and risk-of-bias analyses were performed in duplicate. We conducted meta-analyses using a random-effects model.

Results:

We included 17 trials involving a total of 2121 participants. Compared with patients given placebo, those receiving zinc had a shorter duration of cold symptoms (mean difference −1.65 days, 95% confidence interval [CI] −2.50 to −0.81); however, heterogeneity was high (I² = 95%). Zinc shortened the duration of cold symptoms in adults (mean difference −2.63, 95% CI −3.69 to −1.58), but no significant effect was seen among children (mean difference −0.26, 95% CI −0.78 to 0.25). Heterogeneity remained high in all subgroup analyses, including by age, dose of ionized zinc and zinc formulation. The occurrence of any adverse event (risk ratio [RR] 1.24, 95% CI 1.05 to 1.46), bad taste (RR 1.65, 95% CI 1.27 to 2.16) and nausea (RR 1.64, 95% CI 1.19 to 2.27) were more common in the zinc group than in the placebo group.

Interpretation:

The results of our meta-analysis showed that oral zinc formulations may shorten the duration of symptoms of the common cold. However, large high-quality trials are needed before definitive recommendations for clinical practice can be made. Adverse effects were common and should be the point of future study, because a good safety and tolerance profile is essential when treating this generally mild illness.The common cold is a frequent respiratory infection experienced 2 to 4 times a year by adults and up to 8 to 10 times a year by children.^1–3 Colds can be caused by several viruses, of which rhinoviruses are the most common.⁴ Despite their benign nature, colds can lead to substantial morbidity, absenteeism and lost productivity.^5–7Zinc, which can inhibit rhinovirus replication and has activity against other respiratory viruses such as respiratory syncytial virus,⁸ is a potential treatment for the common cold. The exact mechanism of zinc’s activity on viruses remains uncertain. Zinc may also reduce the severity of cold symptoms by acting as an astringent on the trigeminal nerve.^9,10A recent meta-analysis of randomized controlled trials concluded that zinc was effective at reducing the duration and severity of common cold symptoms.¹¹ However, there was considerable heterogeneity reported for the primary outcome (I² = 93%), and subgroup analyses to explore between-study variations were not performed. The efficacy of zinc therefore remains uncertain, because it is unknown whether the variability among studies was due to methodologic diversity (i.e., risk of bias and therefore uncertainty in zinc’s efficacy) or differences in study populations or interventions (i.e., zinc dose and formulation).We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zinc for the treatment of the common cold. We sought to improve upon previous systematic reviews^11–17 by exploring the heterogeneity with subgroups identified a priori, identifying new trials by instituting a broader search and obtaining additional data from authors.     

Male inclusion in randomized controlled trials of lifestyle weight loss interventions

The prevalence of obesity is similar for men (32.2%) and women (35.5%). It has been assumed that lifestyle weight loss interventions have been developed and tested in predominately female samples, but this has not been systematically investigated. The aim of this review was to investigate total and ethnic male inclusion in randomized controlled trials of lifestyle interventions. PUBMED, MEDLINE, and PSYCHINFO were searched for randomized controlled trials of lifestyle weight loss interventions (N = 244 studies with a total of 95,207 participants) published in the last 10 years (1999-2009). A trial must be in English, included weight loss as an outcome, and tested a dietary, exercise, and/or other behavioral intervention for weight loss. Results revealed samples were on average 27% male vs. 73% female (P < 0.001). Trials recruiting a diseased sample included a larger proportion of males than those not targeting a disease (35% vs. 21%; P < 0.001). About 32% of trials used exclusively female samples, whereas only 5% used exclusively male samples (P < 0.001). No studies in the past 10 years specifically targeted minority males. Ethnic males identified composed 1.8% of total participants in US studies. Only 24% of studies that underrepresented males provided a reason. Males, especially ethnic males, are underrepresented in lifestyle weight loss trials.     

Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee – A randomized double blind placebo controlled trial

Osteoarthritis is a common, chronic, progressive, skeletal, degenerative disorder, which commonly affects the knee joint. Boswellia serrata tree is commonly found in India. The therapeutic value of its gum (guggulu) has been known. It posses good anti-inflammatory, anti-arthritic and analgesic activity. A randomized double blind placebo controlled crossover study was conducted to assess the efficacy, safety and tolerability of Boswellia serrata Extract (BSE) in 30 patients of osteoarthritis of knee, 15 each receiving active drug or placebo for eight weeks. After the first intervention, washout was given and then the groups were crossed over to receive the opposite intervention for eight weeks. All patients receiving drug treatment reported decrease in knee pain, increased knee flexion and increased walking distance. The frequency of swelling in the knee joint was decreased. Radiologically there was no change. The observed differences between drug treated and placebo being statistically significant, are clinically relevant. BSE was well tolerated by the subjects except for minor gastrointestinal ADRs. BSE is recommended in the patients of osteoarthritis of the knee with possible therapeutic use in other arthritis.