Rachel Jordan

Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials

Abstract Objective To determine the average reduction in blood pressure, prevalence of adverse effects, and reduction in risk of stroke and ischaemic heart disease events produced by the five main categories of blood pressure lowering drugs according to dose, singly and in combination. Design Meta-analysis of 354 randomised double blind placebo controlled trials of thiazides, β blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, and calcium channel blockers in fixed dose. Subjects 40 000 treated patients and 16 000 patients given placebo. Main outcome measures Placebo adjusted reductions in systolic and diastolic blood pressure and prevalence of adverse effects, according to dose expressed as a multiple of the standard (recommended) doses of the drugs. Results All five categories of drug produced similar reductions in blood pressure. The average reduction was 9.1 mm Hg systolic and 5.5 mm Hg diastolic at standard dose and 7.1 mm Hg systolic and 4.4 mm Hg diastolic (20% lower) at half standard dose. The drugs reduced blood pressure from all pretreatment levels, more so from higher levels; for a 10 mm Hg higher blood pressure the reduction was 1.0 mm Hg systolic and 1.1 mm Hg diastolic greater. The blood pressure lowering effects of different categories of drugs were additive. Symptoms attributable to thiazides, β blockers, and calcium channel blockers were strongly dose related; symptoms caused by ACE inhibitors (mainly cough) were not dose related. Angiotensin II receptor antagonists caused no excess of symptoms. The prevalence of symptoms with two drugs in combination was less than additive. Adverse metabolic effects (such as changes in cholesterol or potassium) were negligible at half standard dose. Conclusions Combination low dose drug treatment increases efficacy and reduces adverse effects. From the average blood pressure in people who have strokes (150/90 mm Hg) three drugs at half standard dose are estimated to lower blood pressure by 20 mm Hg systolic and 11 mm Hg diastolic and thereby reduce the risk of stroke by 63% and ischaemic heart disease events by 46% at age 60-69.

The effectiveness of the levonorgestrel‐releasing intrauterine system in menorrhagia: a systematic review

Objective To determine whether the levonorgestrel‐releasing intrauterine device (LNG‐IUS), licensed at present for contraceptive use, may reduce menstrual blood loss with few side effects. If effective, surgery could be avoided with consequent resource savings.

Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy

Abstract Objective: To assess the evidence for the effectiveness of increasing numbers of drugs in antiretroviral combination therapy. Design: Systematic review, meta-analysis, and meta-regression of fully reported randomised controlled trials. All studies included compared quadruple versus triple therapy, triple versus double therapy, double versus monotherapy, or monotherapy versus placebo or no treatment. Participants: Patients with any stage of HIV infection who had not received antiretroviral therapy. Main outcome measures: Changes in disease progression or death (clinical outcomes); CD4 count and plasma viral load (surrogate markers). Search strategy: Six electronic databases, including Medline, Embase, and the Cochrane Library, searched up to February 2001. Results: 54 randomised controlled trials, most of good quality, with 66 comparison groups were included in the analysis. For both the clinical outcomes and surrogate markers, combinations with up to and including three (triple therapy) were progressively and significantly more effective. The odds ratio for disease progression or death for triple therapy compared with double therapy was 0.6 (95% confidence interval 0.5 to 0.8). Heterogeneity in effect sizes was present in many outcomes but was largely related to the drugs used and trial quality. Conclusions: Evidence from randomised controlled trials supports the use of triple therapy. Research is needed on the effectiveness of quadruple therapies and the relative effectiveness of specific combinations of drugs. What is already known on this topic Triple combination antiretroviral therapy is accepted by clinicians and patients as the usual treatment for HIV and has evolved through an incremental strategy in the numbers of drugs combined Guidance on treatment, however, has predominantly been based on early reports of research There are no published analyses that assess the effectiveness of the increasing numbers of drugs used in combination What this study adds The results of this systematic review support the use of triple therapy but there is inadequate evidence for quadruple or higher combinations Heterogeneity in the effect estimates seems to result from variable effectiveness of different drug combinations, trial duration, and problems with study quality

Prior TB, Smoking, and Airflow Obstruction: A Cross-Sectional Analysis of the Guangzhou Biobank Cohort Study

BACKGROUND Prior pulmonary TB has been shown to be associated with a higher risk of airflow obstruction, which is the hallmark of COPD, but whether smoking modifies this relationship is unclear. We investigated the relationships between prior TB, smoking, and airflow obstruction in a Chinese population sample. METHODS Participants in the Guangzhou Biobank Cohort Study underwent spirometry, chest radiography, and a structured interview on lifestyle and exposures. Prior TB was defined as the presence of radiologic evidence suggestive of inactive TB. Airflow obstruction was based on spirometric criteria. RESULTS The prevalence of prior TB in this sample (N = 8,066, mean age: 61.9 years) was 24.2%. After controlling for sex, age, and smoking exposure, prior TB remained independently associated with an increased risk of airflow obstruction (odds ratio = 1.37; 95% CI, 1.13-1.67). Further adjustment for exposure to passive smoking, biomass fuel, and dust did not alter the relationship. Smoking did not modify the relationship between prior TB and airflow obstruction. CONCLUSIONS Prior TB is an independent risk factor for airflow obstruction, which may partly explain the higher prevalence of COPD in China. Clinicians should be aware of this long-term risk in individuals with prior TB, irrespective of smoking status, particularly in patients from countries with a high TB burden.

Laser resurfacing of the skin for the improvement of facial acne scarring: a systematic review of the evidence

This review presents and evaluates the evidence of the effectiveness of laser resurfacing for facial acne scars. Primary studies of all types of design in any language were identified from MEDLINE, EMBASE, the Cochrane database, Science Citation Index and various internet sites. Studies were accepted if they included patients treated by any laser for atrophic or ice‐pick acne scars. The quality of the studies was assessed and data extracted by two independent researchers. There were no controlled trials but 14 case series were found which reported the effects of either the carbon dioxide or erbium:YAG laser. All of the studies were of poor quality. The types and severity of scarring were poorly described and there was no standard scale used to measure scar improvement. There was no reliable or validated measure of patient satisfaction; most improvement was based on visual clinical judgement, in many cases without blinded assessment. The inaccurate use of ordinal scales meant that any improvement was impossible to quantify with any validity, although the evidence suggested that laser treatment had some efficacy (a range in individual patients of 25–90% for both the carbon dioxide laser and the erbium:YAG laser). Changes in pigmentation as a side‐effect were common (in up to 44% of patients), although lasting only a few weeks. Laser resurfacing technology is increasingly used in clinical practice to treat acne scars. Despite the poor quality evidence, it is plausible that there is some improvement of acne scarring; there is insufficient information, however, for patients to make informed decisions on whether to opt for treatment and there is not enough evidence to compare the two types of laser. There is a particular lack of information about the psychological effects of acne scar improvement. Good quality randomized controlled trials are needed with standardized scarring scales and validated patient outcome measures in order to assess the effectiveness of laser resurfacing in this group of patients.

An assessment of the quality of randomised controlled trials conducted in China

BackgroundDespite the rapid increase in research in China, little is known about the quality of clinical trials conducted there.MethodsA systematic review and critical appraisal of randomised controlled trials (RCTs) conducted in China and published in 2004 was undertaken to describe their characteristics, assess the quality of their reporting, and where possible, the quality of their conduct. Randomised controlled trials in all disease areas and types of interventions, which took place in China and included Chinese citizens were identified using PubMed and hand searching the Journal Series of the Chinese Medical Association. Quality was assessed against a subset of criteria adapted from the CONSORT statement.ResultsThree hundred and seven RCTs were included. One hundred and ninety-nine (64.8%) failed to report methods of randomization and 254 (82.4%) did not mention blinding of either participants or investigators. Reporting of baseline characteristics, primary outcome and length of follow-up was inadequate in a substantial proportion of studies. Fewer than 11% of RCTs mentioned ethical approval and only 18.0% adequately discussed informed consent. However, dropout rates were very favourable with nearly 44% of trials reporting a zero dropout rate.ConclusionReporting of RCTs in China requires substantial improvement to meet the targets of the CONSORT statement. The conduct of Chinese RCTs cannot be directly inferred from the standard of reporting; however without good reporting the methods of the trials cannot be clearly ascertained.

Original ResearchCOPDPrior TB, Smoking, and Airflow Obstruction: A Cross-Sectional Analysis of the Guangzhou Biobank Cohort Study

BACKGROUND Prior pulmonary TB has been shown to be associated with a higher risk of airflow obstruction, which is the hallmark of COPD, but whether smoking modifies this relationship is unclear. We investigated the relationships between prior TB, smoking, and airflow obstruction in a Chinese population sample. METHODS Participants in the Guangzhou Biobank Cohort Study underwent spirometry, chest radiography, and a structured interview on lifestyle and exposures. Prior TB was defined as the presence of radiologic evidence suggestive of inactive TB. Airflow obstruction was based on spirometric criteria. RESULTS The prevalence of prior TB in this sample (N = 8,066, mean age: 61.9 years) was 24.2%. After controlling for sex, age, and smoking exposure, prior TB remained independently associated with an increased risk of airflow obstruction (odds ratio = 1.37; 95% CI, 1.13-1.67). Further adjustment for exposure to passive smoking, biomass fuel, and dust did not alter the relationship. Smoking did not modify the relationship between prior TB and airflow obstruction. CONCLUSIONS Prior TB is an independent risk factor for airflow obstruction, which may partly explain the higher prevalence of COPD in China. Clinicians should be aware of this long-term risk in individuals with prior TB, irrespective of smoking status, particularly in patients from countries with a high TB burden.

Case finding for chronic obstructive pulmonary disease: a model for optimising a targeted approach

Objectives Case finding is proposed as an important component of the forthcoming English National Clinical Strategy for chronic obstructive pulmonary disease (COPD) because of accepted widespread underdiagnosis worldwide. However the best method of identification is not known. The extent of undiagnosed clinically significant COPD in England is described and the effectiveness of an active compared with an opportunistic approach to case finding is evaluated. Methods A cross-sectional analysis was carried out using using Health Survey for England (HSE) 1995–1996 data supplemented with published literature. A model comparing an active approach (mailed questionnaires plus opportunistic identification) with an opportunistic-only approach of case finding among ever smokers aged 40–79 years was evaluated. There were 20 496 participants aged ≥30 years with valid lung function measurements. The main outcome measure was undiagnosed clinically significant COPD (any respiratory symptom with both forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and FEV1 <80% predicted). Results 971 (4.7%) had clinically significant COPD, of whom 840 (86.5%) did not report a previous diagnosis. Undiagnosed cases were more likely to be female, and smoked less. 25.3% had severe disease (FEV1 <50% predicted), 38.5% Medical Research Council (MRC) grade 3 dyspnoea and 44.1% were current smokers. The active case-finding strategy can potentially identify 70% more new cases than opportunistic identification alone (3.8 vs 2.2 per 100 targeted). Treating these new cases could reduce hospitalisations by at least 3300 per year in England and deaths by 2885 over 3 years. Conclusions There is important undiagnosed clinically significant COPD in the population, and the addition of a systematic case-finding approach may be more effective in identifying these cases. The cost-effectiveness of this approach needs to be tested empirically in a prospective study.

Should healthcare workers have the swine flu vaccine

Evidence from decades of seasonal vaccination suggests likely benefits and low risk of adverse events

Effect of social factors on winter hospital admission for respiratory disease: a case–control study of older people in the UK

BACKGROUND Every winter, hospitals in the UK and other developed countries experience a surge in respiratory admissions. Ecological studies suggest that social circumstances may be an important determinant. AIM To establish the most important factors associated with winter hospital admissions among older people presenting with acute respiratory disease, especially the relative effect of social factors. DESIGN OF STUDY case-control study. SETTING Seventy-nine general practices in central England. METHOD Of a cohort of patients consulting medical services with lower respiratory tract infection or exacerbation of chronic respiratory disease, 157 hospitalised cases were compared to 639 controls. Social, medical, and other factors were examined by interview and GP records. RESULTS Measures of material deprivation were not significant risk factors for admission at either individual or area level, although social isolation (odds ratio [OR] 4.5; 95% confidence interval [CI] = 1.3 to 15.8) resulted in an increased risk of admission. The most important independent risk factor was the presence of chronic obstructive pulmonary disease (COPD; OR 4.0; 95% CI = 1.4 to 11.4), other chronic disease (OR 2.9; 95% CI = 1.2 to 7.0), or both (OR 6.7; 95% CI = 2.4 to 18.4). Being housebound was also an independent risk factor (OR 2.2; 95% CI = 1.0 to 4.8). CONCLUSION Socioeconomic factors had little relative effect compared with medical and functional factors. The most important was the presence of long-term medical conditions (especially COPD), being housebound, and having received two or more courses of oral steroid treatment in the previous year. This combination of factors could be used by primary medical services to identify older patients most vulnerable to winter admissions. Clinicians should ensure that patients with COPD are better supported to manage their condition.