Single dose oral treatment in urinary schistosomiasis: a double blind trial.

A double blind trial of three oral preparations given in single doses for the treatment of Schistosoma haematobium infection was carried out in schoolchildren; selection was biased towards those who excreted large quantities of eggs. Praziquantel 40 mg/kg was the most effective drug giving a greater than 97% reduction in egg output six months after treatment; combined treatment with niridazole 25 mg/kg and metrifonate 10 mg/kg gave a reduction of greater than 92% and metrifonate 10 mg/kg alone a reduction of greater than 86%. Fewer children continued to have moderate to heavy infections (excretion greater than 124 ova/10 ml urine) six months after treatment with praziquantel (5%) and the combined regimen (7%) than with metrifonate (16%). Though our findings show that praziquantel appears to be the most effective and convenient drug available for individuals with S haematobium infection, the combined regimen is a cheaper alternative for treatment where cost is important and parasitological cure not an essential objective.     

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.     

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.     

Effectiveness of Ginkgo biloba in treating tinnitus: double blind, placebo controlled trial

ObjectiveTo determine whether Ginkgo biloba is effective in treating tinnitus.DesignDouble blind, placebo controlled trial using postal questionnaires.Participants1121 healthy people aged between 18 and 70 years with tinnitus that was comparatively stable; 978 participants were matched (489 pairs).Intervention12 weeks'' treatment with either 50 mg Ginkgo biloba extract LI 1370 three times daily or placebo.ResultsThere were no significant differences in primary or secondary outcome measures between the groups. 34 of 360 participants receiving active treatment reported that their tinnitus was less troublesome after 12 weeks of treatment compared with 35 of 360 participants who took placebo.Conclusions50 mg Ginkgo biloba extract LI 1370 given 3 times daily for 12 weeks is no more effective than placebo in treating tinnitus.     

Acyclovir given as prophylaxis against oral ulcers in acute myeloid leukaemia: randomised,double blind,placebo controlled trial.

OBJECTIVES--To evaluate (a) the prophylactic effect of the antiherpetic drug acyclovir on oral ulcers in patients with acute myeloid leukaemia receiving remission induction chemotherapy and thus (b), indirectly, the role of herpes simplex virus in the aetiology of these ulcers. DESIGN--Randomised, double blind, placebo controlled trial. SUBJECTS--74 herpes simplex virus seropositive patients aged 18-84. Thirty seven patients received acyclovir (800 mg by mouth daily) and 37 placebo. The patients were examined daily for 28 days. MAIN OUTCOME MEASURES--Occurrence of herpes labialis, intraoral ulcers, and acute necrotising ulcerative gingivitis. RESULTS--The two populations were comparable in age, sex, type of antineoplastic treatment, and history of herpes labialis. Acute oral infections occurred in 25 of the acyclovir treated patients and 36 of the placebo treated patients (relative risk 0.69 (95% confidence interval 0.55 to 0.87)). This difference was due to a reduction in the incidence of herpes labialis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)), intraoral ulcers excluding the soft palate (one case versus 13 cases; relative risk 0.08 (0.01 to 0.56)), and acute necrotising ulcerative gingivitis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)). However, ulcers on the soft palate were diagnosed with similar frequency in the two groups. Isolation of herpes simplex virus type 1 in saliva was reduced from 15 cases in the placebo group to one case in the acyclovir group (relative risk 0.07 (0.01 to 0.48)). CONCLUSION--Intraoral ulcers excluding the soft palate are most often due to infection with herpes simplex virus, whereas ulcers on the soft palate have a non-herpetic aetiology. The findings suggest that acute necrotising ulcerative gingivitis may also be due to herpes simplex virus. Prophylaxis with acyclovir should be considered for patients with acute myeloid leukaemia during remission induction therapy.     

Adverse reactions to influenza vaccine in elderly people: randomised double blind placebo controlled trial.

OBJECTIVE--To assess the frequency and type of side effects after influenza vaccination in elderly people. DESIGN--Randomised double blind placebo controlled study. SETTING--15 general practices in the southern Netherlands. SUBJECTS--1806 patients aged 60 or older, of whom 904 received influenza vaccine and 902 placebo. MAIN OUTCOME MEASURES--Adverse reactions reported on postal questionnaire completed four weeks after vaccination. RESULTS--210 (23%) patients given vaccine reported one or more adverse reactions compared with 127 (14%) given placebo. The frequency of local adverse reactions were 17.5% in the vaccine group and 7.3% in the placebo group (p < 0.001). There was no difference in systemic adverse reactions (11% v 9.4%; p = 0.34). In general, men reported fewer side effects than women. CONCLUSION--Only local side effects were more common in vaccinated patients and all side effects were mild.     

Randomised,double blind,placebo controlled clinical trial of efficacy of vitamin A treatment in non-measles childhood pneumonia.

OBJECTIVE: To evaluate the impact on clinical recovery and severity of the addition of large doses of vitamin A to the standard treatment for childhood pneumonia. DESIGN: A randomised, double blind, placebo controlled trial. SETTING: Study children were recruited at a public hospital in Recife, north east Brazil, an area of marginal vitamin A deficiency. SUBJECTS: 472 children aged 6 to 59 months with clinical diagnosis of pneumonia. INTERVENTIONS: 200,000 IU (infants) or 400,000 IU (1-4 year olds) of vitamin A in oil or similar capsules of placebo divided into two daily oral doses, in addition to the standard treatment. MAIN OUTCOME MEASURES: Duration of the episode and incidence of adverse outcomes. RESULTS: The groups were similar with respect to overall duration of pneumonia and incidence of adverse outcomes. Children who received vitamin A, however, were less likely to have fever by day 3 (P = 0.008) and were 29% less likely to fail to respond to the first line antibiotic (P = 0.054). CONCLUSION: There was little evidence for an effect of vitamin A treatment on the immediate outcome of the pneumonia episode.     

Zinc supplementation during pregnancy: a double blind randomised controlled trial.

OBJECTIVE--To see whether zinc supplementation during pregnancy improves maternal and fetal outcome. DESIGN--Prospective study started at booking and continued till discharge of mother and baby from the maternity hospital. Mothers were randomly assigned to receive zinc supplementation or placebo in a double blind trial. SETTING--Mothers booking at one hospital. PATIENTS--Women booking before 20 weeks of gestation who agreed to take part in the study. 494 Mothers were followed up till the end of pregnancy. There was no difference between the groups given zinc and placebo in their social or medical backgrounds. INTERVENTIONS--Mothers in the active treatment group received one capsule of 20 mg elemental zinc daily and those in the placebo treated group a capsule identical in appearance and taste with the active capsule but which contained inert substances. MAIN OUTCOME MEASURE--Various adverse outcomes were tested, including maternal bleeding, hypertension, complications of labour and delivery, gestational age, Apgar scores, and neonatal abnormalities. The main outcome measure was birth weight. RESULTS--There were no differences whatsoever between mothers given a zinc supplement and those given a placebo. CONCLUSION--Zinc supplementation in pregnancy in the United Kingdom does not seem to offer any benefits to the mother or her fetus.     

Salmeterol in nocturnal asthma: a double blind,placebo controlled trial of a long acting inhaled beta 2 agonist.

OBJECTIVE--To determine whether inhaled salmeterol, a new long acting inhaled beta adrenergic agonist, reduces nocturnal bronchoconstriction and improves sleep quality in patients with nocturnal asthma. DESIGN--Randomised, double blind, placebo controlled crossover study. SETTING--Hospital outpatient clinics in Edinburgh. SUBJECTS--Twenty clinically stable patients (13 women, seven men) with nocturnal asthma, median age 39 (range 18-60) years. INTERVENTIONS--Salmeterol 50 micrograms and 100 micrograms and placebo taken each morning and evening by metered dose inhaler. Rescue salbutamol inhalers were provided throughout the run in and study periods. MAIN OUTCOME MEASURES--Improvement in nocturnal asthma as measured by peak expiratory flow rates and change in sleep quality as measured by electroencephalography. RESULTS--Salmeterol improved the lowest overnight peak flow rate at both 50 micrograms (difference in median values (95% confidence interval for difference in medians) 69 (18 to 88) l/min) and 100 micrograms (72 (23 to 61) l/min) doses twice daily. While taking salmeterol 50 micrograms twice daily patients had an objective improvement in sleep quality, spending less time awake or in light sleep (-9 (-4 to -44) min) and more time in stage 4 sleep (26 (6-34) min). CONCLUSIONS--Salmeterol is an effective long acting inhaled bronchodilator for patients with nocturnal asthma and at a dose of 50 micrograms twice daily improves objective sleep quality.     

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.     

Loperamide in acute diarrhoea in childhood: results of a double blind,placebo controlled multicentre clinical trial. Diarrhoeal Diseases Study Group (UK).

A total of 315 young children with acute diarrhoea were included in a double blind, hospital based multicentre trial of loperamide at two dose levels (0.8 mg and 0.4 mg/kg/24 h), given with standard oral rehydration therapy versus placebo plus oral rehydration therapy. The overall recovery rate was slowest in the placebo group and fastest in the group given loperamide 0.8 mg. Comparisons between weights on admission and weights by day 3 showed that a larger proportion of children in the loperamide groups gained weight than in the placebo group. No serious side effects of loperamide were observed, but the drug was withdrawn in one infant because of mild abdominal distention. The results indicate that loperamide, in the doses employed, is safe and may in selected cases be a useful adjunct to oral rehydration in the management of acute diarrhoea in well nourished children.     

Oxytocin infusion during second stage of labour in primiparous women using epidural analgesia: a randomised double blind placebo controlled trial.

OBJECTIVE--To determine whether the high rate of forceps delivery associated with the use of epidural analgesia could be reduced through giving an intravenous infusion of oxytocin during the second stage of labour. DESIGN--A randomised, double blind, placebo controlled trial. SETTING--Delivery suites in three hospitals. SUBJECTS--226 Primiparous women with adequate epidural analgesia in whom full dilatation of the cervix had been achieved without prior stimulation with oxytocin. INTERVENTION--An infusion of oxytocin or placebo starting at the diagnosis of full cervical dilatation at an initial dose rate of 2 mU/min increasing to a maximum of 16 mU/min. MAIN OUTCOME MEASURES--The outcome of labour was assessed in terms of the duration of the second stage, mode of delivery, fetal condition at birth, postpartum blood loss, and the incidence of perineal trauma. RESULTS--Treatment with oxytocin was associated with a shorter second stage (p = 0.01), a reduction in the number of non-rotational forceps deliveries (p = 0.03), and less perineal trauma (p = 0.03) but was not associated with any reduction in the number of rotational forceps deliveries performed for malposition of the occiput. No adverse effects on fetal condition at birth or in the early puerperium were seen in association with the use of oxytocin. CONCLUSIONS--The use of an oxytocin infusion may reduce the high rate of operative delivery associated with epidural analgesia provided that the fetal occiput is in an anterior position at the onset of the second stage of labour but within the dose range studied does not seem to correct malposition of the fetal occiput.     

Efficacy and safety of a herbal drug of Coccinia grandis (Linn.) Voigt in patients with type 2 diabetes mellitus: A double blind randomized placebo controlled clinical trial

BackgroundSeveral lines of preclinical studies have shown promising antidiabetic effects of the aqueous leaves extract of Coccinia grandis (Linn.) Voigt (Cucurbitaceae) in vivo and in vitro.Purpose: The present study was conducted to evaluate the efficacy and safety of a newly developed herbal formulation of C. grandis in newly diagnosed patients with type 2 diabetes mellitus (T2DM).Study design: A three months long, randomized, double blind, placebo controlled clinical trial in patients with newly diagnosed T2DM.Method: Based on fasting plasma glucose (FPG) concentration, a total number of 158 newly diagnosed patients with T2DM (45 ± 15 years age) were recruited for the present trial from the University Medical Clinic, Teaching Hospital, Karapitiya, Galle, Sri Lanka. They were randomly assigned to the test or placebo group to receive 500 mg of herbal drug (n = 79) or placebo drug (n = 79) once daily for three months. Patients and investigators were blinded for the treatment. Percentage of glycated hemoglobin (HbA_1C %), insulin and lipid profile parameters were estimated at the base line and at the end of the intervention. Serum concentration of fructosamine was assessed at every other visit of the trial. The homeostatic model assessment for insulin resistance (HOMA-IR), atherogenic index (AI), cardio-protective index (CPI) and coronary risk index (CRI) were calculated. Furthermore, fasting plasma glucose concentration, renal and liver toxicity parameters, hematological parameters, blood pressure (BP) were assessed throughout the study in two weekly intervals till the end of three months.Results: Out of 158, a total number of 145 patients completed the entire clinical trial period successfully. Mean (SD) changes of variables from the baseline to the end of the intervention in test and placebo groups were 0.65 (0.54) and 0.08 (0.66) for HbA_1C % (p < 0.001), 1.91 (3.07) and -1.28 (9.77) for insulin (p < 0.001), 0.02 (0.03) and -0.01 (0.04) for frucosamine (p < 0.001), 1.51 (0.49) and 0.05 (0.50) for FPG (p < 0.001), 1.73 (1.36) and -0.37 (3.38) for HOMA-IR (p < 0.001), 0.16 (0.18) and -0.04 (0.42) for TG (p < 0.001), 0.07 (0.08) and -0.02 (0.19) for VLDL-C (p < 0.001), respectively. However, the herbal drug of C. grandis was unable to change other outcome variables significantly when compared to the placebo (p > 0.05). All the renal, liver and toxicity parameters, hematological parameters and BP were within the normal physiological reference ranges at each visit.Conclusion: Treatment with herbal drug of C. grandis (500 mg per day) for three months for patients with newly diagnosed T2DM significantly improved their glycemic and selected lipid profile parameters with well tolerated safety.     

Randomised,double blind placebo controlled trial of pentoxifylline in the treatment of venous leg ulcers

ObjectiveTo determine whether pentoxifylline 400 mg (Trental 400) taken orally three times daily, in addition to ambulatory compression bandages and dressings, improves the healing rate of pure venous ulcers.DesignRandomised, double blind placebo controlled trial, parallel group study of factorial design, permitting the simultaneous evaluation of alternative pharmaceutical, bandaging, and dressings materials.SettingLeg ulcer clinics of a teaching and a district general hospital in southern Scotland.Participants200 patients with confirmed venous ulcers and in whom other major causal factors were excluded.InterventionsPentoxifylline 400 mg three times daily or placebo.ResultsComplete healing occurred in 65 of the 101 (64%) patients receiving pentoxifylline and 52 of the 99 (53%) patients receiving placebo.ConclusionsThe difference in the healing rates between patients taking pentoxifylline and those taking placebo did not reach statistical significance.

Key messages

• Leg ulcers cost the NHS around £400 million per annum
• 50%-75% of venous leg ulcers can be succesfully treated with dressings and compression bandages but take many months to heal
• A drug that reduced the healing time of venous ulcers would be useful, although no agent has been proved to be effective to date
• Trials with pentoxifylline, a vasoactive drug used in the treatment of peripheral vascular diseases, as an adjunct to the treatment of venous ulcers have been inconclusive
• At the 5% level, pentoxifylline had a non-significant effect on healing rates of pure venous ulcers

     

Single dose vitamin A treatment in acute shigellosis in Bangladesh children: randomised double blind controlled trial.

OBJECTIVE: To evaluate the efficacy of a single large oral dose of vitamin A in treating acute shigellosis in children in Bangladesh. DESIGN: Randomised double blind controlled clinical trial. SETTING: Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh. SUBJECTS: 83 children aged 1-7 years with bacteriologically proved shigellosis but no clinical signs of vitamin A deficiency; 42 were randomised to treatment with vitamin A and 41 formed a control group. INTERVENTION: Children were given a single oral dose of 200,000 IU of vitamin A plus 25 IU vitamin E or a control preparation of 25 IU vitamin E. MAIN OUTCOME MEASURES: Clinical cure on study day 5 and bacteriological cure. RESULTS: Baseline characteristics of the subjects in the two treatment groups were similar. Significantly more children in the vitamin A group than in the control group achieved clinical cure (19/42 (45%) v 8/14 (20%); chi 2 = 5.14, 1 df, P = 0.02; risk ratio = 0.68 (95% confidence interval; 0.50 to 0.93)). When cure was determined bacteriologically, the groups had similar rates (16/42 (38%) v 16/41 (39%); chi 2 = 0.02, 1 df, P = 0.89; risk ratio = 0.98 (0.70 to 1.39)). CONCLUSIONS: Vitamin A reduces the severity of acute shigellosis in children living in areas where vitamin A deficiency is a major public health problem.     

Randomised double blind controlled clinical trial of intranasal budesonide in treatment of hay fever.

The effectiveness of budesonide, a new non-halogenated glucocorticoid administered by nasal inhaler, was evaluated in a double blind comparison with placebo in patients presenting with hay fever. Patients were supplied with antihistamine tablets and eye drops for use when they considered that their symptoms were inadequately controlled by their inhaler. Patients recorded the severity of their symptoms in a daily diary card and visited their general practitioner for assessment weekly for four weeks. All nasal symptoms of hay fever were appreciably reduced in the group taking budesonide and, although their eye symptoms were more severe than in the group taking placebo, they did not use appreciably more eye drops than the latter. The placebo group used appreciably more antihistamine tablets than those in the budesonide group. No patients were withdrawn from the budesonide group because of treatment failure or unacceptable side effects. The results suggest that budesonide is an acceptable and effective treatment for the nasal symptoms of hay fever.     

Randomised,double blind,placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea

Objective To determine the efficacy of oral morphine in relieving the sensation of breathlessness in patients in whom the underlying aetiology is maximally treated.Design Randomised, double blind, placebo controlled crossover study.Setting Four outpatient clinics at a hospital in South Australia.Participants 48 participants who had not previously been treated with opioids (mean age 76, SD 5) with predominantly chronic obstructive pulmonary disease (42, 88%) were randomised to four days of 20 mg oral morphine with sustained release followed by four days of identically formulated placebo, or vice versa. Laxatives were provided as needed.Main outcome measures Dyspnoea in the morning and evening as shown on a 100 mm visual analogue scale, quality of sleep, wellbeing, performance on physical exertion, and side effects as measured at the end of the four day treatment period.Results 38 participants completed the study; three withdrew because of definite and two because of possible side effects of morphine (nausea, vomiting, and sedation). Participants reported significantly different dyspnoea scores when treated with morphine: an improvement of 6.6 mm (95% confidence interval 1.6 mm to 11.6 mm) in the morning and of 9.5 mm (3.0 mm to 16.1 mm) in the evening (P = 0.011 and P = 0.006, respectively). During the period in which they were taking morphine participants also reported better sleep (P = 0.039). More participants reported distressing constipation while taking morphine (9 v 1, P = 0.021) in spite of using laxatives. All other side effects were not significantly worse with morphine, although the study was not powered to address side effects.Conclusions Sustained release, oral morphine at low dosage provides significant symptomatic improvement in refractory dyspnoea in the community setting.     

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.