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Has the impact of Helicobacter pylori therapy on ulcer recurrence in the United States been overstated? A meta-analysis of rigorously designed trials.

OBJECTIVE: The aim of this study was to assess the effect of H. pylori eradication on ulcer recurrence in North American duodenal ulcer patients by examining only treatment studies that met rigorous methodologic criteria. METHODS: Data sources were computerized bibliographic searches from 1983, review of reference lists, communication with companies that manufacture medications used for H. pylori therapy in the U.S., and H. pylori investigators, review of open presentations to the Food and Drug Administration, and review of abstracts from annual scientific meetings. Criteria for study inclusion were double blind, randomized North American trials of H. pylori therapy for duodenal ulcer, scheduled endoscopic follow-up exams for > or = 6 months, and H. pylori cure documented > or = 4 wk after completion of therapy by at least two endoscopic biopsy tests. Seven relevant trials were identified. Data were abstracted independently and disagreement was resolved by consensus. We obtained missing data and identified erroneous assessments through contact with an author or sponsor of all studies. RESULTS: The common odds ratio for ulcer recurrence was 0.20 (95% CI, 0.13-0.31) and 2.8 patients would need to be successfully treated to prevent one ulcer recurrence at 6 months. The pooled ulcer recurrence rate at 6 months in patients with H. pylori eradication was 20%. CONCLUSION: Results of North American studies of highest methodological quality confirm that H. pylori eradication markedly decreases ulcer recurrence. Nevertheless, 20% of patients in these studies had ulcer recurrence within 6 months, despite successful cure of infection and no reported use of NSAIDs. Non-H. pylori, non-NSAID ulcers may be more common in the U.S. than previously believed.

Double-Blind Method↗

Repeated measurements over time: statistical analysis of the angiographic outcomes in the Probucol Quantitative Regression Swedish Trial (PQRST).

An increasing use of non-invasive techniques and arteriographies of the coronary, carotid or femoral arteries has taken place during recent years. This has prompted researchers to perform long-term randomized trials aiming at reducing atherosclerosis progression or achieving regression by cholesterol lowering in high risk populations. These trials are designed to use outcomes such as various indices of atherosclerosis which are assessed repeatedly over time. There are major decisions to be made contingent on the data structures in these trials, such as sphericity, interaction, development over time, missing data, non-normality etc. So, the statistical analysis of such data needs to be planned and specified a priori in a unified manner. This is demonstrated for the Probucol Quantitative Regression Swedish Trial (PQRST) which is designed to answer the question whether the drug probucol, given in combination with diet and cholestyramine, can delay development of atherosclerosis in hypercholesterolemic patients up to 70 years old. Change in atheroma volume is assessed by a newly developed quantitative angiographic technique based on digitized angiograms.

Analysis of Variance↗

The use of a computer in the organization of a large-scale co-operative controlled clinical trial of the treatment of pulmonary tuberculosis.

The organization of controlled clinical trials requires well-defined clerical procedures which, with large-scale studies, are so monotonous that it is difficult to attract and keep staff of a sufficiently high calibre. In a large-scale trial of pulmonary tuberculosis, a computer is being used to undertake much of the routine clerical work, including (1) the preparation of an appointments diary, which also specifies the exact requirements for the trial, and (2) the storage of all the data on magnetic tape so that periodic checks can be made for missing data and interim and final analyses can be produced rapidly. These arrangements reduce the time spent by clerical and statistical staff to a minimum. Although a strict evaluation of the effect of introducing the computer has not yet been made, this approach does appear to be sufficiently promising to warrant further investigations of a similar type.

Antitubercular Agents↗

Postmarketing surveillance with computer-based patient records.

Postmarketing Surveillance (PMS) concerns the investigation of side-effects of drugs after they are introduced into the market. Traditionally, data collection for PMS-studies has been paper-based. The increasing number of general practitioners (GP) that use Computer-Based Patient Records (CBPR) and the central role these general practitioners in the Netherlands play in the delivery of care makes the use of CBPRs as a resource of data for PMS studies possible. Analysis of the current available CBPRs, however, proved them insufficient for PMS studies, because too much data is available only in free text, and other necessary data for PMS is lacking. To make the CBPR suitable for PMS, we had to build a software-module that could be plugged into the computer system of the GP. The module checks the data immediately after they it has been entered into the system, and missing data is requested. Initial filed studies have shown that, with this module, the collection of PMS data is feasible.

Medical Records Systems, Computerized↗

Cytogenetic effects of inhaled ozone in man.

Peripheral blood samples were collected from 30 normal male volunteers before and at intervals after inhaling 0.4 ppm ozone for 4 h. Data from 4 of the subjects were excluded from the analysis because of missing data points. The blood samples were cultured for 48 h, slides made and stained with a uniform Giemsa stain, and 100 metaphase spreads per subject per treatment scored for chromosome aberrations. Cells with suspected aberrations were photographed, destained, restained with a banding procedure and rephotographed to identify the specific chromosomes and regions involved. Pre-exposure, immediate post-exposure, 3 days post-exposure, 2 weeks post-exposure and 4 weeks post-exposure means for the percentage of cells with 46 chromosomes were 93.0, 93.6, 91.7, 94.5 and 94.2, respectively; in the same order, the mean number of cells with chromatid and/or chromosome breaks per order, the mean number of cells with chromatid and/or chromosome breaks per 100 cells was 0.96, 0.85, 1.00, 0.88 and 0.81 respectively, and for chromatid and/or chromosome gaps per 100 cells: 1.35, 0.96, 1.35, 0.81 and 0.77, respectively. The means for each of these parameters as well as the mean frequencies of complex aberrations are not statistically significantly different between blood sampling times. The distribution of aberrations by chromosome and light and dark bands is not significantly influenced by ozone exposure. These data indicate no apparent detectable human cytogenetic effect due to exposure to ozone under the conditions of this experiment.

Adult↗

How well do birth certificates describe the pregnancies they report? The Washington State experience with low-risk pregnancies.

OBJECTIVES: Birth certificates are a major source of population-based data on maternal and perinatal health, but their value depends on the accuracy of the data. This study assesses the validity of information recorded on the birth certificates for women in Washington State who were considered to be low risk at entry into care. METHODS: Birth certificates were matched to data abstracted from prenatal and intrapartum clinic and hospital records of a sample of 1937 Washington State obstetrical patients who were considered to be low risk at the beginning of their pregnancies. Accuracy of a variety of pregnancy characteristics (e.g., complications, procedures) on the birth certificate was analyzed using percentage agreement and sensitivity with record abstracts as the "gold standard." Next, we weighted the data from each source to produce estimates of pregnancy characteristics in the population. We compared these estimates from the two data sources to see whether they provide similar pictures of this subpopulation. RESULTS: Missing data for specific items on the birth certificates ranged from 0% to 24%. The birth certificate accurately captured gravidity and parity, but was less likely to report prenatal and intrapartum complications. The population estimates of the two data sources were significantly different. CONCLUSIONS: Because birth certificates significantly underestimated the complications of pregnancies, number of interventions, number of procedures, and prenatal visits, use of these data for health policy development or resource allocation should be tempered with caution.

Adult↗

Research ethics: ethical issues of data reporting and the quest for authenticity.

The search for truth and its unbiased reporting are ultimate goals of conducting scientific research. Ideally, the reporting of research data ought to be an objective task. In practice, however, it is fraught with numerous statistical and ethical pitfalls, seldom addressed in formal emergency medicine training. The lure of academic celebrity and related influences may persuade researchers to report results in ways that make data appear more interesting, or worthy of publication. Several examples of potentially misleading data reporting are illustrated, including using inappropriate statistical tests, neglecting negative results, omitting missing data points, failing to report actual numbers of eligible subjects, using inappropriate graph labels or terminology, data dredging, and others. Although potentially inaccurate or inflated methods of data reporting may not constitute overt scientific misconduct, the intentional misrepresentation of data is a form of fraud or deception. Publicly funded academic inquiry is a privilege and honor enjoyed by a trusted few. Regardless of outcome, every effort should be made to report data in the most scientifically accurate method. To this end, the Society for Academic Emergency Medicine Code of Conduct and American College of Emergency Physicians Code of Ethics provide important guidance toward the accurate, compassionate, competent, impartial, and honest conduct of scientific research. Accuracy and authenticity in data reporting are first and foremost a matter of individual integrity, and are crucial to the preservation of academic credibility, the protection of future patients, and the public's trust in the medical research enterprise.

Emergency Medicine↗

Methodological issues facing studies of atherosclerotic change.

BACKGROUND: The association between coronary heart disease and lesions of the coronary arteries has led to investigations of different interventions on atherosclerotic change. Currently, B-mode ultrasound of the peripheral arterial vessels, rather than arteriography of the coronary arteries, provides the most accurate evaluation of atherosclerotic disease extent in the patient. METHODS AND RESULTS: When measuring the effect of risk factor modification on atherosclerotic change, it is important to select appropriate methods and end points for quantifying disease and evaluating subsequent change. Measurements must be valid, precise, and reliable and require appropriate a priori definitions of end points and their change. Consistent methodology within studies is crucial. Multiple measurements and data reduction methods can increase the efficiency of comparisons and merit careful consideration. Missing data arising from nonvisualization of sites complicate analyses. Identifying both covariates of atherosclerotic change and possible confounding interventions require monitoring biochemical, physiological, and/or clinical variables and making inferences from these. CONCLUSIONS: To strengthen the rationale for use of B-mode ultrasonography in assessing the natural history of atherosclerosis, four methodological issues must be addressed: evaluation of primary end points using composite and/or individual measurements of atherosclerotic assessment from the carotid arteries, evaluation of new methodology that may allow assessment of the anatomy of specific lesions and/or their potential for rupture, development of methods making complementary use of both angiographic measurements of lumen diameter and ultrasound assessment of the arterial wall, and concrete demonstration of a direct link between increasing intimal-medial thickness and subsequent clinical events. The use of a continuous variable (intimal-medial thickness) in ultrasound studies offers cost/benefit advantages; this methodology continues to evolve.

Arteriosclerosis↗

Creation and validation of medical data.

The problems of creating and validating medical data are discussed. These difficulties relate to the structuring of data and its definiton. The necessity for clarity of thought, coherence and logic in data collection is stressed. Difficulty in medical and lay staff training shows that this is a continuing problem. Data validation must be the major province of senior as well as junior doctors. It is an absoulte essential continuing process and without valid data most analyses are not worthwhile because of high error rates and/or too much missing data.

Humans↗

Reconstruction algorithm for incomplete projections in the framework of linear operators in normed linear spaces.

Based on the linearity of the Radon transform and the convolution-backprojection reconstruction algorithm, a new linear-vector space notation is introduced that is of general use in computed tomography (CT). Using this notation, a consistency condition for the completion of incomplete projection data is described. This consistency condition leads to singular or ill-conditioned systems of linear equations for the unknown projection data. Using regularization methods, an algorithm for the consistent projection completion is presented that can exploit symmetries of the missing data region. The performance of the new algorithm is documented with simulated and actualy measured CT-projection data. The algorithm quantitatively improves CT reconstructions with realistic amounts of data and noise and can be used for the completion of arbitrary regions of missing projections.

Fourier Analysis↗

Estimation by data augmentation in regression models with continuous and discrete covariates measured with error.

Estimation methods are considered for regression models which have both misclassified discrete covariates and continuous covariates measured with error. Adjusted parameter estimates are obtained using the method of data augmentation, where the true values of the covariates measured with error are regarded as missing data. Validation data on the covariates are assumed to be available. The distinction between internal and external validation data is emphasized, and its effects on the analysis are examined. The method is illustrated with simulated data.

Algorithms↗

Home care by outreach nursing for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction, worsening exercise performance and deterioration in health. It is associated with significant morbidity, mortality and costs to health care systems. Care strategies, such as outreach nursing in the community, may reduce this burden. OBJECTIVES: To evaluate the effectiveness of outreach respiratory health care worker programmes for patients with COPD in terms of improving lung function, exercise tolerance and health related quality of life (HRQL) of patient and carer, and reducing mortality and hospital service utilisation. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group database. Bibliographies of identified RCTs were searched for additional relevant RCTs. Authors of identified RCTS were contacted for other published and unpublished studies. SELECTION CRITERIA: Only randomised control trials of patients with COPD were included. The intervention was an outreach nurse visiting patients in their homes, providing support, education, monitoring patient status and providing liaison with physicians. Interventions that used nurse practitioners who provided therapeutic intervention were also included. Studies in which the therapeutic intervention under test was physical training were not included. DATA COLLECTION AND ANALYSIS: Data extraction and study quality assessment were performed independently by two reviewers. Where further or missing data was required, authors of studies were contacted. MAIN RESULTS: Four studies were found. Three assessed mortality following twelve months of care (n=96, 152 and 301), and one after seven months(n=75). Meta-analysis demonstrated that mortality was not significantly reduced by the intervention, Peto Odds Ratio 0.72; 95 % confidence interval 0.43, 1.21. Post hoc subgroup analysis suggested that mortality was reduced by the outreach nursing programme in patients with less severe disease. Significant improvements in health related quality of life were reported in one study in moderate COPD, but not in a study in patients with severe disease. No changes in lung function or exercise performance were found in the studies where data were available. Hospital admissions were reported in only one study in patients with severe disease and no benefit was observed. REVIEWER'S CONCLUSIONS: Patients with moderate COPD may have mortality and health related quality of life gains from a nursing outreach programme, but there are no data about reductions in hospital utilisation. Patients with severe COPD do not appear to have benefit from such programmes and one large study found no reduction in hospital admissions in such patients.

Community-Institutional Relations↗

Long-acting beta2-agonists for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation which is only partially reversible. Long acting beta2-agonists, effective in the management of asthma,are also recommended for COPD management so it is important to establish whether these drugs are effective in reducing COPD symptoms in view of the potential side effect and cost burden. OBJECTIVES: To determine the effectiveness of long acting beta2-adrenoceptor agonists in improving lung function and quality of life and reducing dyspnoea in patients with COPD. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group register. Bibliographies of identified RCTs were searched for additional relevant RCTs. Authors of identified RCTs were contacted for other published and unpublished studies. In addition, unpublished studies were also obtained from the pharmaceutical companies that manufacture long acting beta2- adrenoceptor agonists. SELECTION CRITERIA: All randomised controlled trials over four weeks in duration comparing treatment with long-acting beta2-adrenoceptor agonists (salmeterol and formoterol) with placebo in patients with stable non-reversible COPD. Outcome measures included forced expiratory volume in one second (FEV1), peak expiratory flow rate (PEFR), symptom scores, six minute walk distance, quality of life scores, Borg scores for dyspnoea and rescue bronchodilator use. DATA COLLECTION AND ANALYSIS: Data extraction and study quality assessment was performed independently by two reviewers. Where further or missing data were required, authors of studies were contacted. MAIN RESULTS: Thirty three abstracts were identified as potentially relevant. Of these, four randomised controlled trials (RCTs) were included in this review. Two were parallel group studies of 16 week duration and two were cross-over studies with four week treatment arms. All four RCTs assessed the efficacy of salmeterol in COPD. In a 16 week study of salmeterol 50 mcg and 100 mcg twice daily treatment, a significant increase in FEV1 was seen in both treatment groups. The weighted mean difference (WMD) for the increase in FEV1 for the 50 mcg group was 0.10 litre (95% CI: 0.05;0. 15) and in the 100 mcg group the WMD was 0.12 litre (95% CI: 0.06; 0. 17 ). In the two cross-over studies of four weeks treatment, salmeterol 50 mcg twice daily treatment did not show significant increases in FEV1 (WMD = 0.04 litre, 95% CI: -0.06; 0.15). Similarly, morning and night time PEFR was not significantly improved with salmeterol treatment. In a 16 week study, disease-specific quality of life, measured using the St. George's Respiratory Questionnaire (SGRQ), showed a significant improvement after 50 mcg twice daily, but not after 100 mcg twice daily. This improvement exceeded the threshold for a clinically significant change with this questionnaire. General health status, as measured by the Medical Outcomes Short Form 36, did not improve in any of the eight components with either salmeterol dose. No significant difference was demonstrated in the mean change from baseline in the six minute walk distance (WMD = 1.9 metres, 95% CI: -15.4;19.3). Breathlessness was reduced in one study in patients receiving salmeterol 50 mcg twice daily group. Significantly more patients in this group had Borg scores for breathlessness less than three (a score of three indicating moderate dyspnoea) compared to the placebo treated group (Peto Odds Ratio = 0.60, 95% CI: 0.40; 0.88). Neither dose of salmeterol influenced the incidence of COPD exacerbations, (50 mcg: Peto Odds Ratio = 0.74, 95% CI: 0.47, 1.15) and (100 mcg: Peto Odds Ratio = 0.98, 95% CI: 0.64, 1.52). REVIEWER'S CONCLUSIONS: Treatment of patients with COPD with long acting beta2-agonists produces only small increases in FEV1. In one study, a dose of salmeterol 50 mcg twice daily produced a reduction in breathlessness and a clinically significant improvement in quality of life. (ABSTRACT TRUNCATED)

Adrenergic beta-Agonists↗

Short-acting beta 2 agonists for stable chronic obstructive pulmonary disease.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a chronic condition characterised by progressive airflow limitation that is at most partially reversible. Despite the lack of reversibility patients often report symptomatic improvement with short-acting beta 2 bronchodilator medications. They are used on either an "as required" or a "regular plus as required basis" and they may be used in conjunction with other bronchodilator medicines such as ipratropium and methylxanthines. These medicines are used in the management of both stable and acute exacerbations of COPD. This review examined the effect of short-acting beta 2 bronchodilators given by inhalation in stable COPD. OBJECTIVES: To determine the clinical effect and assess the adverse effects of inhaled short-acting beta 2 agonist bronchodilators compared with placebo in stable COPD. SEARCH STRATEGY: Only randomised controlled trials (RCTs) were considered. RCTs were identified using the Cochrane Airways Group database (CENTRAL). In addition, the reference lists of review articles and RCTs retrieved in full were searched for other potentially relevant citations. SELECTION CRITERIA: Only trials with adult patients with stable COPD, as defined by internationally accepted guidelines (ATS, ERS or BTS) were included in this review. All trials had a minimum duration of 7 days of regular treatment with short-acting beta 2 bronchodilators given by inhalation and compared with placebo. Data from trials where beta 2 agonists were used alone or in combination with other medicines (e.g. ipratropium bromide) were used only if there was a direct comparison between beta 2 bronchodilator alone and placebo. DATA COLLECTION AND ANALYSIS: Outcomes were analysed as continuous or dichotomous outcomes, using standard statistical techniques. For continuous outcomes, the weighted mean difference (WMD) and 95% confidence intervals were calculated and for dichotomous outcomes, the odds ratio was calculated with 95% confidence intervals by Peto's methods. Funnel plots were used to test for publication bias. MAIN RESULTS: Thirteen studies were included in this review. Most had small sample sizes and some of the sutides used very short-acting outdated compounds. All the studies used a cross-over design and were of high quality. Spirometry done at the end of study period was measured after administration of treatment (post-bronchodilator) which showed both FEV1 (0.150 L/min, 95%CI: 0. 02-0.28) and FVC (0.310 L, 95%CI: 0.00-0.62) to improve significanly but slightly when compared to placebo. A few studies measured FRC, airway resistance or conductance at the end of the study period. In all cases these measurements were done several hours after treatment, and no significant differences (p>0.05 in all cases) were found between the bronchodilator and placebo groups. Walking test Large increases in 6MW distance was observed in two studies, however one study did not show any positive improvements. There was a large increase in the 12MW distance as shown by one study. Due to the small number of studies reporting this outcome no significant differences were found in the walking distance between the bronchodilator and placebo groups. Peak Flow Rate Both morning (36. 04 L/min; 95%CI: 0.80-71.27) and evening (36.68 L/min; 95%CI: 2. 47-70.89) PEFR were significantly higher during active treatment than during placebo. Symptoms Breatlessness was measured on various scales therefore data that were presented in a suitable form were combined using standardized means for inclusion in the analysis. A significant improvement (-0.33; 95%CI: -0.58 to -0.07 with p=0.01) in the breathlessness score was observed during treatment with beta-2 agonist when compared to placebo. Cough was reported to improve significantly (data not usable) during treatment with beta2 agonist in one study but not in two others. A non-significant decrease in sputum production was reported by Wilson 1980, however four other studies reported no

Administration, Inhalation↗

Correspondence analysis as a tool in fungal taxonomy.

The polyphasic approach to taxonomic problems has led to the creation of complex datasets that lend themselves to numerical analysis. The numerical study, however, has to deal with mathematical problems linked with the presence of mixed-type data originating from the investigations. Correspondence analysis (CA) is an ordination technique widely used in ecology and social sciences but only rarely applied to taxonomic problems. In CA corresponding variables and taxa ordination are obtained simultaneously, thus allowing to explore the taxonomic interrelationships between taxa and variables in a single analysis. CA can be used on large and small datasets, and can be applied to mixed-type data after appropriate coding. It is not sensitive to variation of class number and size and is useful to screen large unstructured datasets, to suggest which variables should be retained to discriminate samples, to detect outliers or erroneous data and to perform identification of unknown samples. It also has the advantage of handling missing data particularly well. On the other hand, CA is sensitive to outliers, which can cause a distortion of the geometric map of the points in the graphical display. Nevertheless, the sensitivity of correspondence analysis to outliers can be effectively used to verify data. Finally, based on symmetry of row and column analyses correspondence analysis can be applied to find out which characters can be used to construct identification keys and to selectively group variables by their importance for the discrimination of samples.

Cluster Analysis↗

Analyzing individual status and change with hierarchical linear models: illustration with depression in college students.

A recently developed class of multilevel or hierarchical linear models (HLM) provides an intuitive and efficient way to estimate individual growth or change curves. The approach also models the between-subjects variation of the individual change curves with treatment factors and individual attributes. Unlike other repeated measures analysis methods common in the behavioral sciences, HLM allows the fit of data with unequal numbers of repeated observations for each subject, variable timing of observations, and missing data, features which are often characteristic of data from field studies. The application of HLM for the analysis of repeated psychological measures is discussed and illustrated here with depression data for college students. Strengths and limitations of the approach are discussed.

Adaptation, Psychological↗

Descriptive study of prognostic factors influencing survival of compensated silicotic patients.

The objective of this study was to assess survival and the prognostic influencing survival of compensated silicotic patients. All workers compensated for silicosis in the Province of Quebec from 1938 to 1985 (n = 1,165) were included. Clinical data were those collected during the exam that led to a compensation decision. Due to missing data, a subcohort of 961 patients was used for multivariate analysis of clinical prognostic factors with the Cox proportional hazards model. The following factors made an independent contribution to survival: age at compensation, smoking, dyspnea, expectoration, abnormal breath sounds, radiographic appearance, and vital capacity. On the basis of the model, patients with small opacities alone on their chest radiograph and who did not have dyspnea, expectoration, or abnormal breath sounds had a survival similar to the average Quebec man; other patients had a poorer survival. We conclude that it is possible to identify at the time of compensation, silicotic patients who are likely to have a life expectancy similar to that of the general population. Symptoms and physical signs as well as radiographic and lung function abnormalities appear to be useful prognostic indicators in compensated silicotic patients.

Dyspnea↗

National birthweight percentiles by gestational age for twins born in Australia.

OBJECTIVE: To develop national charts of birthweight percentiles by gestational age and infant sex for liveborn twins born in Australia. METHODOLOGY: National data on live twin births to non-Indigenous Australian-born mothers during 1991-94 were derived from perinatal data collected by midwives in each State and Territory. RESULTS: During 1991-4 there were 20,075 liveborn twin infants. Of these births, missing data included: birthweight 36 (0.2%) births, gestational age 95 (0.5%) births, and sex (missing or indeterminate) 13 (0.06%) births. These births were excluded from the study. An additional 0.6% births were excluded because the recorded birthweights were extreme outliers for the recorded gestational ages. Forty-seven per cent of live twin births were preterm (< 37 weeks). At all gestational ages, the median birthweight of male twins was higher than that of female twins. At model gestational age of 38 weeks, the difference in the median birthweight was 130 g. CONCLUSIONS: The charts produced as a result of the study provide birthweight percentiles by gestational age for twins based on national data in Australia. They provide current population norms for the use of Australian clinicians and researchers.

Adult↗