Omeprazole and ranitidine in treatment of reflux oesophagitis: double blind comparative trial

One hundred and sixty two patients with endoscopically proved reflux oesophagitis stratified for severity, 66 with grade 1 disease (erythema and friability) and 96 with grade 2 or 3 disease (including erosions or ulcerations), were allocated at random to double blind treatment with omeprazole 40 mg in the morning or ranitidine 150 mg twice daily for up to 12 weeks. A patient could be evaluated sooner if symptomatic relief and endoscopically normal mucosa (grade 0) were noted after four to eight weeks'' treatment. Patients treated with omeprazole responded significantly more rapidly than those treated with ranitidine (p<0.0001), cumulative healing rates at four, eight, and 12 weeks being 90%, 100%, and 100% respectively for those with grade 1 disease and 70%, 85%, and 91% respectively for those with grade 2 or 3 disease in the omeprazole group. Corresponding rates in the ranitidine group were 55%, 79%, and 88% (grade 1) and 26%, 44%, and 54% (grade 2 or 3). Relief of the major symptoms of heartburn, regurgitation, and dysphagia and improvements in the histological appearance of the mucosa occurred earlier and were again more pronounced during treatment with omeprazole than with ranitidine.This observed superiority of omeprazole 40 mg in the morning over ranitidine 150 mg twice daily in the short term treatment of reflux oesophagitis was obtained without major clinical or biochemical side effects, but further research is needed into longer term use of omeprazole and the effects of the acid inhibition it induces.     

Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial

ObjectivesTo assess the effects of rivastigmine on the core domains of Alzheimer’s disease.DesignProspective, randomised, multicentre, double blind, placebo controlled, parallel group trial. Patients received either placebo, 1-4 mg/day (lower dose) rivastigmine, or 6-12 mg/day (higher dose) rivastigmine. Doses were increased in one of two fixed dose ranges (1-4 mg/day or 6-12 mg/day) over the first 12 weeks with a subsequent assessment period of 14 weeks.Setting45 centres in Europe and North America.Participants725 patients with mild to moderately severe probable Alzheimer’s disease diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, and the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association.ResultsAt the end of the study cognitive function had deteriorated among those in the placebo group. Scores on the Alzheimer’s disease assessment scale improved in patients in the higher dose group when compared with patients taking placebo (P<0.05). Significantly more patients in the higher dose group had improved by 4 points or more than had improved in the placebo group (24% (57/242) v 16% (39/238)). Global function as rated by the clinician interview scale had significantly improved among those in the higher dose group compared with those taking placebo (P<0.001), and significantly more patients in the higher dose group showed improvement than did in the placebo group (37% (80/219) v 20% (46/230)). Mean scores on the progressive deterioration scale improved from baseline in patients in the higher dose group but fell in the placebo group. Adverse events were predominantly gastrointestinal, of mild to moderate severity, transient, and occurred mainly during escalation of the dose. 23% (55/242) of those in the higher dose group, 7% (18/242) of those in the lower dose group, and 7% (16/239) of those in the placebo group discontinued treatment because of adverse events.ConclusionsRivastigmine is well tolerated and effective. It improves cognition, participation in activities of daily living, and global evaluation ratings in patients with mild to moderately severe Alzheimer’s disease. This is the first treatment to show compelling evidence of efficacy in a predominantly European population.

Key messages

• In a 6 month trial rivastigmine was effective in treating the core cognitive and functional symptoms of patients with mild to moderate Alzheimer’s disease
• Rivastigmine at doses of 6-12 mg/day produces clinically relevant and statistically significant improvements in cognitive and global assessments, and in activities of daily living
• The effects of rivastigmine are dose dependent
• Rivastigmine was well tolerated in this population of elderly patients

     

Single blind, randomised controlled trial of pelvic floor exercises, electrical stimulation, vaginal cones, and no treatment in management of genuine stress incontinence in women

ObjectiveTo compare the effect of pelvic floor exercises, electrical stimulation, vaginal cones, and no treatment for genuine stress incontinence.DesignStratified, single blind, randomised controlled trial.SettingMulticentre.Participants107 women with clinically and urodynamically proved genuine stress incontinence. Mean (range) age was 49.5 (24-70) years, and mean (range) duration of symptoms 10.8 (1-45) years.InterventionsPelvic floor exercise (n=25) comprised 8-12 contractions 3 times a day and exercise in groups with skilled physical therapists once a week. The electrical stimulation group (n=25) used vaginal intermittent stimulation with the MS 106 Twin at 50 Hz 30 minutes a day. The vaginal cones group (n=27) used cones for 20 minutes a day. The untreated control group (n=30) was offered the use of a continence guard. Muscle strength was measured by vaginal squeeze pressure once a month.ResultsImprovement in muscle strength was significantly greater (P=0.03) after pelvic floor exercises (11.0 cm H₂O (95% confidence interval 7.7 to 14.3) before v 19.2 cm H₂O (15.3 to 23.1) after) than either electrical stimulation (14.8 cm H₂O (10.9 to 18.7) v 18.6 cm H₂O (13.3 to 23.9)) or vaginal cones (11.8 cm H₂O (8.5 to 15.1) v 15.4 cm H₂O (11.1 to 19.7)). Reduction in leakage on pad test was greater in the exercise group (−30.2 g; −43.3 to 16.9) than in the electrical stimulation group (−7.4 g; −20.9 to 6.1) and the vaginal cones group (−14.7 g; −27.6 to −1.8). On completion of the trial one participant in the control group, 14 in the pelvic floor exercise group, three in the electrical stimulation group, and two in the vaginal cones group no longer considered themselves as having a problem.ConclusionTraining of the pelvic floor muscles is superior to electrical stimulation and vaginal cones in the treatment of genuine stress incontinence.

Key messages

• Training to increase the strength of pelvic floor muscles was superior to electrical stimulation and vaginal cones in treatment of genuine stress incontinence
• Adverse effects were reported with use of electrical stimulation and vaginal cones but not with exercises
• Patients’ tolerance for electrical stimulation and vaginal cones was low
• Pelvic floor exercise should be first choice of treatment for genuine stress incontinence

     

Quality of life among patients with severe aortic stenosis

BackgroundThe disease burden of patients with severe aortic stenosis is not often explored, while the incidence is increasing and many patients who have an indication for aortic valve replacement are not referred for surgery. We studied the quality of life of 191 patients with severe aortic stenosis, hypothesising that symptomatic patients have a far worse quality of life than the general population, which could enforce the indication for surgery.MethodsThe SF-36v2 Health Survey was completed by 191 consecutive patients with symptomatic or asymptomatic severe aortic stenosis.ResultsAsymptomatic patients (n = 59) had health scores comparable with the general Dutch population but symptomatic patients (n = 132) scored significantly lower across different age categories. Physical functioning, general health and vitality were impaired, as well as social functioning and emotional well-being. There was no relation between degree of stenosis and physical or mental health scores.ConclusionsBoth physical and emotional problems have a major impact on normal daily life and social functioning of symptomatic patients with severe aortic stenosis, regardless of age. If the aortic stenosis is above the ‘severe’ threshold, the degree of stenosis does not predict disease burden. These results encourage to reconsider a conservative approach in symptomatic patients with severe aortic stenosis. Using the SF-36v2 Health Survey together with this study, an individual patient’s quality of life profile can be assessed and compared with the patient group or with the general population. This can assist in decision making for the individual patient.     

Double blind, cluster randomised trial of low dose supplementation with vitamin A or beta carotene on mortality related to pregnancy in Nepal. The NNIPS-2 Study Group

ObjectiveTo assess the impact on mortality related to pregnancy of supplementing women of reproductive age each week with a recommended dietary allowance of vitamin A, either preformed or as β carotene.DesignDouble blind, cluster randomised, placebo controlled field trial.SettingRural southeast central plains of Nepal (Sarlahi district).Subjects44 646 married women, of whom 20 119 became pregnant 22 189 times.Intervention270 wards randomised to 3 groups of 90 each for women to receive weekly a single oral supplement of placebo, vitamin A (7000 μg retinol equivalents) or β carotene (42 mg, or 7000 μg retinol equivalents) for over 3½ years.ResultsMortality related to pregnancy in the placebo, vitamin A, and β carotene groups was 704, 426, and 361 deaths per 100 000 pregnancies, yielding relative risks (95% confidence intervals) of 0.60 (0.37 to 0.97) and 0.51 (0.30 to 0.86). This represented reductions of 40% (P<0.04) and 49% (P<0.01) among those who received vitamin A and β carotene. Combined, vitamin A or β carotene lowered mortality by 44% (0.56 (0.37 to 0.84), P<0.005) and reduced the maternal mortality ratio from 645 to 385 deaths per 100 000 live births, or by 40% (P<0.02). Differences in cause of death could not be reliably distinguished between supplemented and placebo groups.ConclusionSupplementation of women with either vitamin A or β carotene at recommended dietary amounts during childbearing years can lower mortality related to pregnancy in rural, undernourished populations of south Asia.

Key messages

• Maternal vitamin A deficiency, evident as night blindness or low serum retinol concentration during pregnancy, is widely prevalent in rural south Asia
• In Nepal, women of reproductive age who were given 7000 μg retinol equivalents of vitamin A on a weekly basis showed a reduction in mortality related to pregnancy of 40%
• Weekly dosing with 42 mg β carotene (also providing 7000 μg retinol equivalents) lowered their mortality by 49%
• Preventing maternal vitamin A deficiency in rural South Asia can lower the risk of mortality of women during and after pregnancy

     

Drugs, bugs, and esophageal pH profiles

Until relatively recently, gastroesophageal reflux disease (GERD) was thought to be a relatively trivial problem, and pharmaceutical companies initially had remarkably little interest in clinical trials for GERD. Over the last ten years, GERD therapy has become the subject of intense interest, since reflux disease is now recognized as a major market for antisecretory and prokinetic drugs. Even low-technology antacids are now known to effectively neutralize esophageal acid prevent acid reflux for up to 90 minutes. Esophageal pH profiling is known to be an excellent surrogate for clinical efficacy of GERD drugs, particularly in erosive esophagitis. Years ago, famotidine normalized esophageal mucosal exposure to pH < 4.0 only when administered in doses of 40 mg twice a day. Subsequent studies confirmed that multiple daily dosing of histamine-2 receptor antagonists (H2RAs) was mandatory for GERD treatment, with clear dose-response relationships for each agent. Proton pump inhibitors (PPIs) have each been carefully assessed in terms esophageal and gastric pH profiles. Omeprazole has a particularly flat dose response curve, making it difficult to differentiate pH or clinical effects of 20 vs. 40 mg doses. Improved rapidity of onset and/or enhanced potency is demonstrable in pH data obtained with lansoprazole, rabeprazole and pantoprazole. Such differences will translate to improved clinical efficacy, based on the meta-analyses of Richard Hunt and his group in Canada that correlate pH effects and symptom relief/healing. PPI's have dependably surpassed H2RAs and prokinetic drugs in management of the more severe grades of esophagitis. Helicobacter pylori has a peculiar relationship to GERD. There has been some concern that PPIs given to patients with H. pylori might accelerate development of severe atrophic gastritis. It is also now known that eradication of H. pylori may increase symptomatic GERD (possibly as a result of increased gastric acid secretion once the bacteria have been eliminated). New data confirm nocturnal breakthrough of acid secretion and esophageal acid exposure in three-fourths of patients on omeprazole 20 mg twice daily. This nocturnal acidity can be controlled more effectively with a nighttime dose of an H2RA than with a third dose of omeprazole. Control of acid secretion and improved gastric and esophageal pH profiles are goals of modern GERD therapy, and the product that most cost effectively normalizes esophageal acid exposure will have a substantial advantage in the ever-growing GERD marketplace.     

Curing Helicobacter pylori infection in patients with duodenal ulcer does not provoke gastroesophageal reflux disease

Background. It has been suggested that the incidence of gastroesophageal reflux disease (GERD) increases after successful eradication of Helicobacter pylori infection. We present data on development of GERD from a controlled study of H. pylori eradication in 165 duodenal ulcer patients.
Methods. Patients (mean age, 55 years; 102 men; current smokers; n = 74) were randomly assigned 2 : 1 to receive omeprazole, 40 mg twice daily, in combination with either amoxicillin, 750 mg twice daily, or placebo. Endoscopy and dyspeptic symptoms, including heartburn, were assessed at inclusion and at 6, 12, and 24 months after treatment. In addition, symptoms were assessed at 18 months. Patients with erosive esophagitis or reflux symptoms requiring treatment at inclusion were not included in the study.
Results. Fifty-one of 145 (35%) evaluable patients developed heartburn, and 13 of 145 (9%) developed esophagitis during follow-up. The life-table analysis of the cumulated risk of developing heartburn showed that patients whose H. pylori infection was eradicated had a significantly lower risk for developing heartburn than those with persistent H. pylori infection. The groups did not show any difference in cumulative risk of developing esophagitis.
Conclusion. Our data show that successful eradication of H. pylori infection does not increase the incidence of GERD in duodenal ulcer patients.     

奥美拉唑联合法莫替丁治疗反流性食管炎的临床效果分析

目的：观察并分析奥关拉唑联合法莫替丁治疗反流性食管炎的临床效果。方法：选取2008年5月至2012年5月在本院确诊并治疗的反流性食管炎患者45例,随机平均分为三组。联合用药组（15例）：每日早餐前口服20mg奥关拉唑,睡前口服20mg法莫替丁;奥关拉唑组（15例）：每日口服两次奥美拉唑,每次20mg;法莫替丁组（15例）：每日口服两次法莫替丁,每次20mg。每组的治疗时间均为8周。在内镜指导下观察并比较三组患者的胸痛、反酸和烧心等主要病征的改善情况,综合评价三种治疗方法的临床疗效。结果：联合用药组较其他两组获得的疗效更明显,患者的症状得到较好的改善,差异有统计学意义（P〈0．05）。结论：奥美拉唑联合法莫替丁能够有效地抑制胃酸的分泌,对于反流性食管炎的,临床治疗具有良好的效果。     

Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks

ObjectivesTo assess the efficacy and safety of hypericum extract (STEI 300, Steiner Arzneimittel, Berlin) compared with imipramine and placebo in patients in primary care with a current episode of moderate depression.DesignRandomised, double blind, multicentre, parallel group trial for 8 weeks.SettingTrained panel of 18 general practitioners from four German states: Bavaria, Berlin, Rhineland Palatinate, and Saxony.Participants263 patients (66 men, 197 women) with moderate depression according to ICD-10 (international classification of diseases, 10th revision) codes F32.1 and F33.1.Interventions1050 mg hypericum extract (350 mg three times daily), 100 mg imipramine (50 mg, 25 mg, and 25 mg daily), or placebo three times daily.ResultsHypericum extract was more effective at reducing Hamilton depression scores than placebo and as effective as imipramine (mean −15.4 (SD 8.1), −12.1 (7.4), and –14.2 (7.3) respectively). Comparable results were found for Hamilton anxiety and clinical global impressions scales and were most pronounced for the Zung self rating depression scale. Quality of life was more improved in the standardised mental component scale of the SF-36 with both active treatments than with placebo but in the physical component scale was improved only by hypericum extract compared with placebo. The rate of adverse events with hypericum extract was in the range of the placebo group but lower than that of the imipramine group (0.5, 0.6, and 1.2 events per patient respectively).ConclusionsAt an average dose of 350 mg three times daily hypericum extract was more effective than placebo and at least as effective as 100 mg imipramine daily in the treatment of moderate depression. Treatment with hypericum extract is safe and improves quality of life.

Key messages

• Hypericum extract (STEI 300) was effective after 4, 6, and 8 weeks of treatment in patients with moderate depression
• Simultaneous analysis confirmed hypericum extract to be at least as efficacious as imipramine 100 mg daily after eight weeks of treatment
• Besides better antidepressive efficacy both hypericum extract and imipramine improved quality of life
• Patients tolerate hypericum extracts much better than they do tricyclics and therefore by improving patients'' compliance hypericum extracts are promising drugs for long term treatment

     

Challenges of Correlating pH Change with Relief of Clinical Symptoms in Gastro Esophageal Reflux Disease: A Phase III,Randomized Study of Zegerid versus Losec

BackgroundZegerid (on demand immediate-release omeprazole and sodium bicarbonate combination therapy) has demonstrated earlier absorption and more rapid pH change compared with Losec (standard enteric coated omeprazole), suggesting more rapid clinical relief of heartburn. This Phase III, multicenter, double-blind, double-dummy, randomized study assessed the clinical superiority of Zegerid versus Losec for rapid relief of heartburn associated with gastro-esophageal reflux disease (GERD).MethodsPatients with a history of frequent (2 3 days/week) uncomplicated GERD, were randomized to receive Zegerid (20mg) or Losec (20mg) with corresponding placebo. Study medication was self-administered on the first episode of heartburn, and could be taken for up to 3 days within a 14 day study period. Heartburn severity was self assessed up to 180 minutes post dose (9 point Likert scale). Primary endpoint was median time to sustained response (≥3 point reduction in heartburn severity for ≥45 minutes).ResultsOf patients randomized to Zegerid (N=122) or Losec (N=117), 228/239 had recorded ≥1 evaluable heartburn episodes and were included in the modified intent-to-treat population. No significant between-group differences were observed for median time to sustained response (60.0 vs. 52.2 minutes, Zegerid [N=117] and Losec [N=111], respectively), sustained partial response (both, 37.5 minutes) and sustained total relief (both, 105 minutes). Significantly more patients treated with Zegerid reached sustained total relief within 0–30 minutes post dose in all analysis sets (p<0.05). Both treatments were well tolerated and did not raise any safety concerns.ConclusionsSuperiority of Zegerid over Losec for rapid heartburn relief was not demonstrated; both treatments were equally effective however the rapid onset of action of Losec was unexpected. Factors, including aspects of study design may have contributed to this. This study supports previously reported difficulty in correlating intra-gastric pH change with clinical effect in GERD therapy, highlighting the significance of several technical considerations for studies of this type.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01493089","term_id":"NCT01493089"}}NCT01493089     

The 5-HT1A receptor agonist buspirone improves esophageal motor function and symptoms in systemic sclerosis: a 4-week,open-label trial

BackgroundAcute administration of the oral 5-HT₁A receptor agonist buspirone, which is commonly used as an anxiolytic drug, may improve compromised lower esophageal sphincter function. In an open-label trial we assessed the effects of buspirone on esophageal motor function and symptoms in patients with esophageal involvement associated with systemic sclerosis (SSc).MethodsThirty consecutive patients with SSc and symptomatic esophageal involvement, despite treatment with proton pump inhibitors, underwent high resolution manometry and chest computed tomography for assessment of motor function and esophageal dilatation, respectively. Regurgitation, heartburn, dysphagia, and chest pain severity was subjectively scored by visual analog scales. Manometric parameters (primary endpoint) and symptom severity (secondary endpoint) were re-examined after 4-week daily administration of 20 mg buspirone. Other medications remained unchanged.ResultsEight patients did not complete the trial because of buspirone-associated dizziness (n = 2), or nausea (n = 2), or reluctancy to undergo final manometry. In the remaining 22 patients lower esophageal sphincter (LES) resting pressure increased from 7.7 ± 3.9 to 12.2 ± 4.6 mmHg (p = 0.00002) after buspirone administration; other manometric parameters did not change. Statistical analysis revealed negative correlation between individual increases in resting LES pressure and supra-aortic esophageal diameter (r = -0.589, p = 0.017), suggesting a more beneficial effect in patients with less severely affected esophageal function. Heartburn and regurgitation scores decreased at 4 weeks compared to baseline (p = 0.001, and p = 0.022, respectively).ConclusionOur findings warrant more conclusive evaluation with a double-blind controlled study; however, buspirone could potentially be given under observation for objective improvement in all patients with SSc who report reflux symptoms despite undergoing standard treatment.

Trial registration

ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02363478","term_id":"NCT02363478"}}NCT02363478 Registered: 21-02-2014.     

兰索拉唑与奥美拉唑治疗活动期胃溃疡的效果及对血清抗氧化因子的影响

目的:观察和比较兰索拉唑与奥美拉唑治疗活动期胃溃疡的临床效果及其对患者血清抗氧化因子水平的影响。方法:选取2016年1月至2017年1月我院收治的活动期胃溃疡患者88例,将其随机分成研究组和对照组,每组各44例。对照组给予奥美拉唑于睡前口服治疗,一次20mg,每日1次。研究组给予兰索拉唑于睡前口服治疗,一次30mg,每日1次。两组患者均以7d为一个疗程,连续治疗8个疗程。比较两组患者的临床总有效率和治疗前后血清超氧化物歧化酶(Superoxide dismutase,SOD)、丙二醛(Methylene dioxyamphetamine,MDA)、内皮素-1(Endothelin-1,ET-1)和一氧化氮(Nitric oxide,NO)水平的变化。结果:(1)研究组治疗总有效率为97.73%,对照组治疗总有效率为79.55%,研究组治疗总有效率显著高于对照组(P0.05);(2)治疗前,两组患者血清SOD、MDA、ET-1和NO水平比较差异无统计学意义(P0.05),研究组患者治疗后血清MDA、ET-1水平均明显低于对照组,血清SOD、NO水平均显著高于对照组(P0.05)。结论:兰索拉唑治疗活动期胃溃疡的临床效果明显优于奥美拉唑,可能与其显著提高患者血清SOD、NO水平及降低血清MDA、ET-1水平有关。     

Analysis of Chinese herbal creams prescribed for dermatological conditions

ObjectiveTo determine whether Chinese herbal creams used for the treatment of dermatological conditions contain steroids.Design11 herbal creams obtained from patients attending general and paediatric dermatology outpatient clinics were analysed with high resolution gas chromatography and mass spectrometry. SettingDepartments of dermatology and clinical biochemistry.ResultsEight creams contained dexamethasone at a mean concentration of 456 μg/g (range 64 to 1500 μg/g). All were applied to areas of sensitive skin such as face and flexures.ConclusionGreater regulation needs to be imposed on Chinese herbalists to prevent illegal and inappropriate prescribing of potent steroids.

Key messages

• Patients with eczema often report improvement with Chinese herbal creams
• There may be no indication on the label about the contents of the cream
• Eight of the 11 creams analysed contained dexamethasone at concentrations inappropriate for use on the face or in children
• Inadvertent use of topical steroids can cause severe exacerbation of eczema herpeticum
• Closer regulation of herbal medicines is required

     

Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials

Objective: To determine the size of reduction in homocysteine concentrations produced by dietary supplementation with folic acid and with vitamins B-12 or B-6. Design: Meta-analysis of randomised controlled trials that assessed the effects of folic acid based supplements on blood homocysteine concentrations. Multivariate regression analysis was used to determine the effects on homocysteine concentrations of different doses of folic acid and of the addition of vitamin B-12 or B-6. Subjects: Individual data on 1114 people included in 12 trials. Findings: The proportional and absolute reductions in blood homocysteine produced by folic acid supplements were greater at higher pretreatment blood homocysteine concentrations (P<0.001) and at lower pretreatment blood folate concentrations (P<0.001). After standardisation to pretreatment blood concentrations of homocysteine of 12 μmol/l and of folate of 12 nmol/l (approximate average concentrations for Western populations), dietary folic acid reduced blood homocysteine concentrations by 25% (95% confidence interval 23% to 28%; P<0.001), with similar effects in the range of 0.5-5 mg folic acid daily. Vitamin B-12 (mean 0.5 mg daily) produced an additional 7% (3% to 10%) reduction in blood homocysteine. Vitamin B-6 (mean 16.5 mg daily) did not have a significant additional effect. Conclusions: Typically in Western populations, daily supplementation with both 0.5-5 mg folic acid and about 0.5 mg vitamin B-12 would be expected to reduce blood homocysteine concentrations by about a quarter to a third (for example, from about 12 μmol/l to 8-9 μmol/l). Large scale randomised trials of such regimens in high risk populations are now needed to determine whether lowering blood homocysteine concentrations reduces the risk of vascular disease.

Key messages

• Higher blood homocysteine concentrations seem to be associated with higher risks of occlusive vascular disease and with lower blood concentrations of folate and vitamins B-12 and B-6
• Proportional and absolute reductions in blood homocysteine concentrations with folic acid supplements are greater at higher pretreatment blood homocysteine concentrations and at lower pretreatment blood folate concentrations
• In typical Western populations, supplementation with both 0.5-5 mg daily folic acid and about 0.5 mg daily vitamin B-12 should reduce blood homocysteine concentrations by about a quarter to a third
• Large scale randomised trials of such regimens in people at high risk are now needed to determine whether lowering blood homocysteine concentrations reduces the risk of vascular disease

     

Peroxisome proliferator-activated receptor γ agonist effect on rheumatoid arthritis: a randomized controlled trial

Introduction

Rheumatoid arthritis (RA), a chronic inflammatory disease, is associated with insulin resistance. Experimental evidence indicates that the relationship between insulin resistance and inflammation is bidirectional: Inflammation promotes insulin resistance, and insulin resistance promotes inflammation. Therefore, we examined the hypothesis that pioglitazone, a thiazolidinedione peroxisome proliferator-activated receptor γ agonist, would decrease inflammation and disease activity and improve insulin resistance in patients with RA.

Methods

In a single-center, randomized, double-blind, placebo-controlled crossover study patients with RA (N = 34) receiving stable therapy were randomized to also receive either pioglitazone 45 mg daily (n = 17) or matching placebo (n = 17) for eight weeks. This was followed by a four-week washout period and alternative treatment for eight weeks. Outcomes included change in Disease Activity Score in 28 joints (DAS28) score, individual components of the DAS28 score and homeostatic model assessment for insulin resistance (HOMA). Intention-to-treat analysis and linear mixed-effects models were used.

Results

Patients had a mean (±SD) age of 51 (±14.2) years, 82.4% were female and baseline DAS28 high-sensitivity C-reactive protein (DAS28-CRP) was 4.58 (±1.1) units. Addition of pioglitazone was associated with a 9.3% reduction (95% confidence interval (CI) = 0.17% to 17.6%) in DAS28-CRP (P = 0.046), but no significant change in DAS28 erythrocyte sedimentation rate (DAS28-ESR) (P = 0.92). There was a 10.7mm (95% CI = 0.4 to 20.9 mm) improvement in patient-reported global health (P = 0.042), a 48.6% decrease (95% CI = 27.6% to 63.5%) in CRP (P < 0.001) and a 26.4% decrease (95% CI = 3.7% to 43.8%) in insulin resistance as measured by HOMA (P = 0.025), but no significant reduction in swollen or tender joint count or in ESR (all P > 0.05). Lower-extremity edema was more common during pioglitazone treatment (16%) than placebo (0%).

Conclusion

Addition of pioglitazone to RA therapy improves insulin resistance and modestly reduces RA disease activity measured by DAS28-CRP and two of its components, including patient-reported global health and CRP, but not DAS28-ESR or ESR.

Trial registration

{"type":"clinical-trial","attrs":{"text":"NCT00763139","term_id":"NCT00763139"}}NCT00763139     

Using thresholds based on risk of cardiovascular disease to target treatment for hypertension: modelling events averted and number treated

ObjectiveTo estimate the impact of using thresholds based on absolute risk of cardiovascular disease to target drug treatment to lower blood pressure in the community.DesignModelling of three thresholds of treatment for hypertension based on the absolute risk of cardiovascular disease. 5 year risk of disease was estimated for each participant using an equation to predict risk. Net predicted impact of the thresholds on the number of people treated and the number of disease events averted over 5 years was calculated assuming a relative treatment benefit of one quarter.SettingAuckland, New Zealand.Participants2158 men and women aged 35-79 years randomly sampled from the general electoral rolls.Results46 374 (12%) Auckland residents aged 35-79 receive drug treatment to lower their blood pressure, averting an estimated 1689 disease events over 5 years. Restricting treatment to individuals with blood pressure ⩾170/100 mm Hg and those with blood pressure between 150/90-169/99 mm Hg who have a predicted 5 year risk of disease ⩾10% would increase the net number for whom treatment would be recommended by 19 401. This 42% relative increase is predicted to avert 1139/1689 (68%) additional disease events overall over 5 years compared with current treatment. If the threshold for 5 year risk of disease is set at 15% the number recommended for treatment increases by <10% but about 620/1689 (37%) additional events can be averted. A 20% threshold decreases the net number of patients recommended for treatment by about 10% but averts 204/1689 (12%) more disease events than current treatment.ConclusionsImplementing treatment guidelines that use treatment thresholds based on absolute risk could significantly improve the efficiency of drug treatment to lower blood pressure in primary care.     

Endpiece: How to buy gadgets

Objective To assess the effect of additional training of practice nurses and general practitioners in patient centred care on the lifestyle and psychological and physiological status of patients with newly diagnosed type 2 diabetes.Design Pragmatic parallel group design, with randomisation between practice teams to routine care (comparison group) or routine care plus additional training (intervention group); analysis at one year, allowing for practice effects and stratifiers; self reporting by patients on communication with practitioners, satisfaction with treatment, style of care, and lifestyle.Setting 41 practices (21 in intervention group, 20 in comparison group) in a health region in southern England.Subjects 250/360 patients (aged 30-70 years) diagnosed with type 2 diabetes and completing follow up at one year (142 in intervention group, 108 in comparison group).Intervention 1.5 days’ group training for the doctors and nurses—introducing evidence for and skills of patient centred care and a patient held booklet encouraging questions.Main outcome measures Quality of life, wellbeing, haemoglobin A_1c and lipid concentrations, blood pressure, body mass index (kg/m²).Results Compared with patients in the C group, those in the intervention group reported better communication with the doctors (odds ratio 2.8; 95% confidence interval 1.8 to 4.3) and greater treatment satisfaction (1.6; 1.1 to 2.5) and wellbeing (difference in means (d) 2.8; 0.4 to 5.2). However, their body mass index was significantly higher (d=2.0; 0.3 to 3.8), as were triglyceride concentrations (d=0.4 mmol/l; 0.07 to 0.73 mmol/l), whereas knowledge scores were lower (d=−2.74; −0.23 to −5.25). Differences in lifestyle and glycaemic control were not significant.Conclusions The findings suggest greater attention to the consultation process than to preventive care among trained practitioners; those committed to achieving the benefits of patient centred consulting should not lose the focus on disease management.

Key messages

• A training programme in patient centred care for practitioners led to patients with newly diagnosed diabetes reporting better communication with doctors, greater wellbeing, and greater treatment satisfaction at one year, without loss of glycaemic control
• Knowledge scores were lower and weight and other cardiovascular risk factors higher among patients attending trained practice teams
• Trained practitioners may have found it difficult to integrate attention to wellbeing with management of disease risk
• Professionals using patient centred consulting should not lose the focus on disease

     

Prospective investigation of transfusion transmitted infection in recipients of over 20 000 units of blood. TTI Study Group

ObjectivesTo follow up recipients of 20 000 units of blood to identify any transmissions of infections through blood transfusion.DesignFollow up study of recipients of transfusion.Setting 22 hospitals in north London.ParticipantAdult patients who had recently been transfused.Results9220 patients were recruited, and 5579 recipients of 21 923 units of blood were followed up. No transfusion transmitted infections were identified. The incidence of transfusion transmitted infections was 0 in 21 043 units (95% confidence interval for risk 0 to 1 in 5706 recipients) for hepatitis B; 0 in 21 800 units (0 to 1 in 5911 recipients) for hepatitis C; 0 in 21 923 units (0 to 1 in 5944 recipients) for HIV; and 0 in 21 902 units (0 to 1 in 5939 recipients) for human T cell leukaemia/lymphoma virus. Three patients acquired hepatitis B during or after hospital admission but not through transfusion; 176 (3%) had pre-existing hepatitis B infection. Sixteen (0.29%) patients had hepatitis C, and five (0.09%) had human T cell leukaemia/lymphoma virus.ConclusionsThe current risk of transfusion transmitted infections in the United Kingdom is very small, though hospital acquired infections may arise from sources other than transfusion. A considerable proportion of patients have pre-existing infections.     

pH, healing rate, and symptom relief in patients with GERD

Gastroesophageal reflux symptoms are common and occur in all of us from time to time. In others, reflux may be associated with ulcerative esophagitis. The symptoms may be aggravated by large meals, coffee, smoking and position. Physiological and pathological reflux can be separated by the frequency and duration of the exposure of the lower esophagus to acid. Pathological reflux results in symptoms and also esophagitis and ulceration in some patients. Although gastroesophageal reflux disease (GERD) is considered to result from a disorder of motility in the esophagus, gastric acid and peptic activity are deemed pivotal to the initiation and continuation of the esophageal damage and the development of symptoms. Acid exposure in the esophagus is normally less than 4 percent of the 24 hours with a pH below 4. An increase over 4 percent of the time with a pH less than 4 is considered pathological. Hence, antisecretory drugs have become the principle approach to the treatment of reflux symptoms and esophagitis since they reduce the acidity, of gastric juice and the activity of pepsin. Importantly, they also reduce the volume of gastric juice available for reflux into the esophagus. There is a clear relationship between the degree and duration of acid suppression and the relief of heartburn and healing of esophagitis. Pharmacodynamic studies with different dose regimens of the H2-receptor antagonists and the proton pump inhibitors show a difference in the degree and duration of the antisecretory effect, and this correlates closely with the results of clinical trials with respect to the healing of esophagitis and the relief of symptoms. Proton pump inhibitors achieve healing rates by week four, which are not achieved by H2-receptor antagonists even after 12 weeks of treatment. The advantage of proton pump inhibitors over H2-receptor antagonists is due to the greater degree, longer duration of effect and more complete inhibition of acid secretion that maintains intragastric pH above 4 for a maximal duration. Although there is no significant difference between proton pump inhibitors with respect to healing of esophagitis, symptom relief occurs earlier with lansoprazole than omeprazole, and this is probably due to the greater oral bioavailability and faster onset of action of lansoprazole when compared to omeprazole.