Weak Study Designs Research Articles

Genetic variants in association studies – review of strengths and weaknesses in study design and current knowledge of impact on cancer risk

Sequencing of the human genome has recently been completed and mapping of the complete genomic variation is ongoing. During the last decade there has been a huge expansion of studies of genetic variants, both with respect to association studies of disease risk and for studies of genetic factors of prognosis and treatments response, i.e., pharmacogenomics. The use of genetics to predict a patient's risk of disease or treatment response is one step toward an improved personalised prevention and screening modality for the prevention of cancer and treatment selection. The technology and statistical methods for completing whole genome tagging of variants and genome wide association studies has developed rapidly over the last decade. After identifying the genetic loci with the strongest, statistical associations with disease risk, future studies will need to further characterise the genotype-phenotype relationship to provide a biological basis for prevention and treatment decisions according to genetic profile. This review discusses some of the general issues and problems of study design; we also discuss challenges in conducting valid association studies in rare cancers such as paediatric brain tumours, where there is support for genetic susceptibility but difficulties in assembling large sample sizes. The clinical interpretation and implementation of genetic association studies with respect to disease risk and treatment is not yet well defined and remains an important area of future research.

Rotator Cuff Repair Rehabilitation: A Level I and II Systematic Review

BackgroundThere is no consensus for the optimal postoperative rehabilitation protocol after rotator cuff repairs.ObjectiveTo determine if there is sufficient level I or II evidence available in the literature for establishment of a uniform, optimal rotator cuff rehabilitation protocol.Data SourcesA systematic review of level I and II English-language, prospective, randomized controlled trials published between 1966 and 2008 was performed. MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, and secondary references were appraised for studies that met the inclusion criteria. Search terms included rotator cuff, supraspinatus, infraspinatus, subscapularis, teres minor, rehab, rehabilitation, physical therapy, and physiotherapy.Study SelectionInclusion criteria were English-language level I or level II studies, including randomized clinical trials involving the rehabilitation of rotator cuff repairs. Exclusion criteria were non-English language, level IV or V studies, or studies involving shoulder rehabilitation of diagnoses other than rotator cuff repairs. Three independent reviewers arrived at a consensus for including 4 studies in this review out of 12 studies identified by the literature search.Data ExtractionIncluded studies underwent worksheet quality appraisal independently by each of the 3 authors identifying strengths, weaknesses, and biases. The quality appraisal was then discussed among the authors and consensus reached regarding the strengths, weaknesses, and value of the included studies.ResultsTwo studies examined the use of continuous passive motion for rotator cuff rehabilitation, and 2 studies compared an unsupervised, standardized rehabilitation program to a supervised, individualized rehabilitation program. These studies did not support the use of continuous passive motion in rotator cuff rehabilitation, and no advantage was shown with a supervised, individualized rehabilitation protocol compared to an unsupervised, standardized home program. Each investigation had weaknesses in study design that decreased the validity of its findings.ConclusionThere is not enough high-level evidence to develop an evidence-based medicine approach to rotator cuff rehabilitation. There is a need for well-designed level I and level II trials to elucidate the optimal rotator cuff repair rehabilitation protocol.

Health effects of relocation following disaster: a systematic review of the literature

This paper reviews the literature on the effects of post-disaster relocation on physical and mental heath, and develops a conceptual framework to guide future research. Forty articles were selected for full-text review and incorporation into the conceptual framework. Twenty-four articles were reviewed for results and methodology. These overwhelmingly tracked mental health outcomes. Only four (16 per cent) focused on physical health. Eight of ten showed an association between relocation and psychological morbidity. Certain outcomes (such as mortality, injury and cardiovascular disease risk factors) revealed inconsistent results, but these were rarely studied. Despite the frequency of post-disaster relocation and evidence of its effect on psychological morbidity, there is a relative paucity of studies; the few examples in the literature reveal weak study designs, inconsistent results, and inattention to physical health impacts and the challenges facing vulnerable populations. Further research guided by theory is needed to inform emergency preparedness and recovery policy.

Total body irradiation before an allogeneic stem cell transplantation: is there a magic dose?

To review the outcomes of allogeneic transplantation with regimens of varying total body irradiation (TBI) doses (0-1575 cGy), with an emphasis on reduced-intensity conditioning (RIC) regimens. RIC regimens with a broad range of TBI doses (0, 200, 400, 550, and 800 cGy) have been studied. Durable donor stem cell engraftment occurred in most patients, with a low rate of toxicity and nonrelapse mortality. Patients excluded from myeloablative regimens were able to tolerate RIC regimens. Retrospective comparisons of patients treated with RIC and myeloablative regimens showed lower nonrelapse mortality but higher relapse risk with RIC; however, overall survivals were similar though a larger fraction of RIC patients had high-risk pretransplant features. Study design weaknesses limit the ability to generalize and apply these results. RIC and myeloablative TBI-based regimens result in durable engraftment of donor stem cells, tolerable toxicity, and acceptable rates of relapse risk and overall survival. Determination of the optimal dose of TBI for allogeneic transplantation is complex and depends on several variables and may vary based on a specific permutation of these variables. A broad range of TBI doses for RIC regimens are effective; however, all conclusions are limited by the lack of prospective, randomized trials comparing RIC and myeloablative regimens.

Evaluating the Evidence

Health outcomes research applies a wide range of methods to identify optimal approaches to determine optimal approaches to determine the effects of healthcare interventions and policies. Critical evaluation skills are necessary to navigate the evidence and identify studies that should influence clinical decision making and policy. A hierarchical “pyramid of evidence” that emphasizes randomized controlled clinical trials (RCTs) has been promulgated as the approach to judging study design and quality. Whereas this hierarchy may be suitable for the evaluation of efficacy, it may be inappropriate for many health outcomes research questions. This article examines the relevance of this construct to questions beyond those of therapeutic efficacy and discusses the essential role of study designs beyond RCTs. The strengths and weaknesses of study designs commonly encountered in the medical literature are reviewed. The article concludes with 2 case studies that apply the concepts reviewed and illustrate the need to match the study design with the research question. Of note, the concepts of internal validity, external validity, confounding, and bias are central to the discussion of the strengths and weaknesses of study designs in the medical literature. Readers not familiar with these concepts should refer to the Appendix in the online-only Data Supplement for clarification. ### The Pyramid of Evidence: A Useful Construct? Traditionally, the design of a study has been considered a principal barometer of the validity of its findings. In this construct, different study designs are considered in the context of a pyramid of evidence, in which studies most susceptible to threats to internal validity reside at the bottom and those least prone reside at the top (Figure). This hierarchy is widely used in discussions about the quality of medical studies and is integrated into the grading of evidence in practice guidelines.1 However, although the pyramid of evidence is undoubtedly well suited for questions of therapeutic efficacy, …

Factors contributing to nursing leadership: A systematic review

Leadership practices of health care managers can positively or negatively influence outcomes for organizations, providers and, ultimately, patients. Understanding the factors that contribute to nursing leadership is fundamental to ensuring a future supply of nursing leaders who can positively influence outcomes for health care providers and patients. The purpose of this study was to systematically review the multidisciplinary literature to examine the factors that contribute to nursing leadership and the effectiveness of educational interventions in developing leadership behaviours among nurses. The search strategy began with 10 electronic databases (e.g. CINAHL, Medline). Published quantitative studies were included that examined the factors that contribute to leadership or the development of leadership behaviours in nurse leaders. Quality assessments, data extraction and analysis were completed on all included studies. A total of 27,717 titles/abstracts were screened resulting in 26 included manuscripts reporting on 24 studies. Twenty leadership factors were examined and categorized into four groups - behaviours and practices of individual leaders, traits and characteristics of individual leaders, influences of context and practice settings, and leader participation in educational activities. Specific behaviours and practices of individual leaders, such as taking on or practising leadership styles, skills and roles, were reported as significantly influencing leadership in eight studies. Traits and characteristics of individual leaders were examined in six studies with previous leadership experience (three studies) and education levels (two of three studies) having positive effects on observed leadership. Context and practice settings had a moderate influence on leadership effectiveness (three of five studies). Nine studies that examined participation in leadership development programs all reported significant positive influences on observed leadership. These findings suggest that leadership can be developed through specific educational activities, and by modelling and practising leadership competencies. However, the relatively weak study designs provide limited evidence for specific factors that could increase the effectiveness of current nursing leadership or guide the identification of future nurse leaders. Robust theory and research on interventions to develop and promote viable nursing leadership for the future are needed to achieve the goal of developing healthy work environments for health care providers and optimizing care for patients.

A Review of Interventions and System Changes to Improve Time to Reperfusion for ST-Segment Elevation Myocardial Infarction

Identify and describe interventions to reduce time to reperfusion for patients with ST-segment elevation myocardial infarction (STEMI). Key word searches of five research databases: MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Web of Science, and Cochrane Clinical Trials Registry. We included controlled and uncontrolled studies of interventions to reduce time to reperfusion. One researcher reviewed abstracts and 2 reviewed full text articles. Articles were subsequently abstracted into structured data tables, which included study design, setting, intervention, and outcome variables. We inductively developed intervention categories from the articles. A second researcher reviewed data abstraction for accuracy. We identified 666 articles, 42 of which met inclusion criteria. We identified 11 intervention categories and classified them as either process specific (e.g., emergency department administration of thrombolytic therapy, activation of the catheterization laboratory by emergency department personnel) or system level (e.g., continuous quality improvement, critical pathways). A majority of studies (59%) were single-site pre/post design, and nearly half (47%) had sample sizes less than 100 patients. Thirty-two studies (76%) reported significantly lower door to reperfusion times associated with an intervention, 12 (29%) of which met or exceeded guideline recommended times. Relative decreases in times to reperfusion ranged from 15 to 82% for door to needle and 13-64% for door to balloon. We identified an array of process and system-based quality improvement interventions associated with significant improvements in door to reperfusion time. However, weak study designs and inadequate information about implementation limit the usefulness of this literature.

Role of Metformin for Weight Management in Patients Without Type 2 Diabetes

To evaluate the efficacy and safety of metformin for weight management in overweight and obese patients without type 2 diabetes. Literature was obtained through MEDLINE Ovid (1950-February week 3, 2008), EMBASE (all years), and a bibliographic review of relevant articles. Key words included metformin, obesity, overweight, and weight loss. All studies published in the English language that evaluated the effects of metformin on weight in obese or overweight individuals were critically analyzed. Relevant articles were selected for inclusion in this review. Metformin is first-line pharmacotherapy in the treatment of overweight or obese patients with type 2 diabetes, with beneficial effects on weight in this population. Multiple trials have evaluated the effect of metformin on weight and other metabolic parameters in adults and adolescents without diabetes. Five of 12 trials in adults evaluated weight loss as a primary endpoint. Significant weight reduction was found in 4 of these studies; however, the trials were small and of weak design. Weight reduction was significant in 5 of the 6 adolescent trials; similarly, these studies were limited by weak study design and small patient population. Metabolic parameters (blood pressure, waist circumference, cholesterol parameters, insulin/glucose levels) often showed varying results. Metformin was well tolerated; gastrointestinal effects were the most frequently reported adverse effects. The weight loss effects of metformin in overweight or obese adults and adolescents without diabetes appear promising; however, trials have been limited by small patient populations and weak design. Metformin may also have a positive effect on metabolic parameters such as waist circumference, fasting insulin and glucose levels, and triglycerides. Further research involving large-scale trials that evaluate weight loss as a primary outcome is necessary to firmly establish the role of metformin in this population.

Gabapentin in the Treatment of Mental Illness: The Echo Chamber of the Case Series

Bipolar disorder is a common and debilitating psychiatric illness. Several antiepileptic drugs (AEDs) have been approved for the treatment of bipolar disorder. Gabapentin gained a large market share of AED use in the late 1990s in spite of a lack of randomized clinical trial (RCT) evidence and no labeled indication from the U.S. Food and Drug Administration for its use in psychiatric illness. This article describes the results of a literature review, the purpose of which was to examine the characteristics of studies conducted in humans concerning the efficacy of gabapentin in bipolar disorder. Publications relevant to this topic were identified based on a PUBMED search as well as an examination of references from a published systematic review and citations from relevant review articles. The search located 29 studies published between 1997 and 2007, with the greatest number of articles published in 1998 and 1999. Of these 29 publications, 15 involved uncontrolled case series, while 6 were single case reports. The sample size in the studies was generally small, and often we could not identify the funding source. Despite the generally weak study design in the identified publications, the authors of the articles often commented on the promising nature of gabapentin therapy for bipolar disorder. However, 4 small, randomized trials in heterogeneous populations demonstrated little if any evidence of such efficacy. Nine letters to the editor demonstrated a similar pattern. The large number of case series concerning gabapentin is striking. The number of reports and their distribution in many different journals created a type of "echo chamber" effect, through which the sheer number of publications and citations may give legitimacy to the practice of using gabapentin for bipolar disorder. Although the case series were generally of poor quality, their publication in peer-reviewed journals may have been partially responsible for the widespread use of an ineffective medication.

The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies

Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalisability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September, 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles.18 items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies.A detailed explanation and elaboration document is published separately and is freely available on the websites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE statement will contribute to improving the quality of reporting of observational studies

Factors Associated with Findings of Published Trials of Drug–Drug Comparisons: Why Some Statins Appear More Efficacious than Others

BackgroundPublished pharmaceutical industry–sponsored trials are more likely than non-industry-sponsored trials to report results and conclusions that favor drug over placebo. Little is known about potential biases in drug–drug comparisons. This study examined associations between research funding source, study design characteristics aimed at reducing bias, and other factors that potentially influence results and conclusions in randomized controlled trials (RCTs) of statin–drug comparisons.Methods and FindingsThis is a cross-sectional study of 192 published RCTs comparing a statin drug to another statin drug or non-statin drug. Data on concealment of allocation, selection bias, blinding, sample size, disclosed funding source, financial ties of authors, results for primary outcomes, and author conclusions were extracted by two coders (weighted kappa 0.80 to 0.97). Univariate and multivariate logistic regression identified associations between independent variables and favorable results and conclusions. Of the RCTs, 50% (95/192) were funded by industry, and 37% (70/192) did not disclose any funding source. Looking at the totality of available evidence, we found that almost all studies (98%, 189/192) used only surrogate outcome measures. Moreover, study design weaknesses common to published statin–drug comparisons included inadequate blinding, lack of concealment of allocation, poor follow-up, and lack of intention-to-treat analyses. In multivariate analysis of the full sample, trials with adequate blinding were less likely to report results favoring the test drug, and sample size was associated with favorable conclusions when controlling for other factors. In multivariate analysis of industry-funded RCTs, funding from the test drug company was associated with results (odds ratio = 20.16 [95% confidence interval 4.37–92.98], p < 0.001) and conclusions (odds ratio = 34.55 [95% confidence interval 7.09–168.4], p < 0.001) that favor the test drug when controlling for other factors. Studies with adequate blinding were less likely to report statistically significant results favoring the test drug.ConclusionsRCTs of head-to-head comparisons of statins with other drugs are more likely to report results and conclusions favoring the sponsor's product compared to the comparator drug. This bias in drug–drug comparison trials should be considered when making decisions regarding drug choice.

Psychosocial interventions in people with multiple sclerosis

Upon diagnosis individuals with Multiple Sclerosis (MS) must cope with both day to day and disease-related stressors in addition to unpredictable, fluctuating and confusing symptoms. Furthermore, disease progression may interfere with employment, family life, relationships and social activities. Psychosocial interventions aim to help individuals manage these psychological, social and emotional challenges. However, there are no specific guidelines available regarding the most effective intervention content, format or delivery. Therefore, a review of the research that has utilised these interventions, specifically those which, by definition, aimed to improve quality of life (QoL) and/or well-being in people with MS, was considered essential in order to identify which aspects of these interventions may help alleviate the psychosocial challenges associated with MS. To identify all randomised controlled trials (RCTs), quasi-experimental, cohort, case control and case series studies that have investigated psychosocial interventions in people with MS which aimed to improve QoL and/or well-being, to establish the methodological quality of such studies, and to determine the effectiveness of the interventions. Searches were carried out using computerised databases with predefined search terms; this was supplemented by manual searches of reference lists of all retrieved articles. Relevant journals were also hand searched. Studies written in English and published before January 2006, investigating the effectiveness of psychosocial interventions on QoL and/or well-being in people with MS, were eligible for inclusion. Methodological quality was independently assessed by two reviewers using the Downs and Black quality scoring checklist. The qualitative and quantitative characteristics of studies were extracted using a data extraction sheet. Thirty-three studies fulfilled the inclusion criteria; however, interventions varied widely in content, delivery and duration. Furthermore, failure to report full methodological details, as well as weaknesses in study design, reduced the strength of inferences that could be drawn from these studies. These notwithstanding, there were three studies of sufficient quality to provide some evidence regarding the value of education/information, goal setting, homework assignments, exercise, discussion forums and multidisciplinary team support. Thus, this review has identified the potential benefit of the aforementioned activities in the psychosocial management of this population. However, further well designed clinical trials are warranted to determine, definitively, the effectiveness, or otherwise, of these components.

Evaluating disease management programme effectiveness: an introduction to the regression discontinuity design

Although disease management (DM) has been in existence for over a decade, there is still much uncertainty as to its effectiveness in improving health status and reducing medical cost. The main reason is that most programme evaluations typically follow weak observational study designs that are subject to bias, most notably selection bias and regression to the mean. The regression discontinuity (RD) design may be the best alternative to randomized studies for evaluating DM programme effectiveness. The most crucial element of the RD design is its use of a 'cut-off' score on a pre-test measure to determine assignment to intervention or control. A valuable feature of this technique is that the pre-test measure does not have to be the same as the outcome measure, thus maximizing the programme's ability to use research-based practice guidelines, survey instruments and other tools to identify those individuals in greatest need of the programme intervention. Similarly, the cut-off score can be based on clinical understanding of the disease process, empirically derived, or resource-based. In the RD design, programme effectiveness is determined by a change in the pre-post relationship at the cut-off point. While the RD design is uniquely suitable for DM programme evaluation, its success will depend, in large part, on fundamental changes being made in the way DM programmes identify and assign individuals to the programme intervention.

Has Relapse Prevention Received a Fair Shake? A Review and Implications for Future Transfer Research

As learning and performance improvement continues to dominate the training research landscape, so does the need to justify the results of relevant interventions. One area in training research that has continued to elude practitioners and researchers is enhancing the use of trained skills back on the job (i.e., training transfer). Relapse prevention (RP) is a posttraining transfer intervention that has been studied for decades but associated findings lack consistency in transfer research. In this article, the authors review studies using RP as a transfer intervention, examine the weaknesses of study design and methods, and suggest improvements for future research to seek a fair test of its ultimate effectiveness.

Surgical Management of Drooling

Source: Greensmith AL, Johnstone BR, Reid SM, et al. Prospective analysis of the outcome of surgical management of drooling in the pediatric population: a 10-year experience. Plast Reconstr Surg. 2005;116:1233–1242.Sialorrhea (excessive drooling) is a frequent problem in neurologically impaired children. Surgical intervention may be appropriate when conservative measures are ineffective. For this study, data were reviewed on 72 consecutive patients attending a multidisciplinary Salivary Control Clinic at The Royal Children’s Hospital in Melbourne, Australia who underwent bilateral submandibular duct transposition combined with sublingual gland excision from 1993–2001. The mean age at surgery of patients was 10.4 years (range 4–19 years). Results were analyzed prospectively at 2 and 5 years postoperatively.Sixty-seven patients were available for follow-up at 2 years. A drooling score was assigned to each patient by caregivers and clinicians using a 4-point frequency and 5-point severity scale.1 If more than 1 observer completed an assessment, the scores were averaged. Frequency was defined as: 1) never, 2) occasional, 3) frequent, and 4) constant. Severity was classed as: 1) dry, 2) mild – wet lips, 3) moderate – wet lips and chin, 4) severe – clothing damp, and 5) profuse – clothing, hands, and objects wet. Reductions in frequency from 4.0 to 2.9 (P<.001) and severity from 4.8 to 3 (P<.001) were recorded for the study group as a whole. In addition, there was a fall in number of clothing or bib changes from 4 to 0. Results were similar at 5 years postoperatively. A total of 13 surgical complications were reported, and 5 patients had unsatisfactory outcomes and subsequently required parotid duct ligation. The procedure was found to be effective in most patients, with 58% showing significant improvement in drooling frequency and 77% having decreased severity of drooling.Dr. Burstein has disclosed no financial relationships relevant to this commentary.Up to 37% of patients with cerebral palsy have been reported to have excessive drooling.2 Sequelae include social ostracism, skin maceration, fluid depletion, and aspiration pneumonia. Normally between 500 and 2000 ml of saliva are produced per day. In affected individuals, the basal salivary production rate is normal; however, there is inefficient involuntary swallowing of the saliva. According to these authors, 60% of saliva production is by the submandibular gland, 10% from the sublingual glands, and 20% from the parotid glands. Non-surgical treatments include correction of posture, nasopharyngeal obstruction, and malocclusion; biofeedback; and oral appliances. Pharmacologic remedies include various anticholinergic agents such as atropine, as well as Botox injection of the salivary glands.Parotid duct relocation followed by submandibular gland excision as a treatment for excessive drooling was reported in 1967.3 In that initial case series, although 90% of patients had effective control, over 30% had complications ranging from parotid duct stenosis and increased dental caries to septic parotitis. In the current study, the decision to focus surgical therapy on the main salivary secretors while avoiding the parotid gland was based on sound anatomic and physiologic principles. The avoidance of external incisions and parotid ligation appears to have markedly decreased dental and gingival problems as well as overall morbidity.This study illustrates why a case series can be of value even though it is methodologically a relatively weak study design. Herein, case selection was not random, interobserver reliability was not assessed, and the clinical meaningfulness of the observed effect size may be debated. Nonetheless, this study is a valuable, albeit not methodologically robust, critical analysis of a new therapy of a terribly difficult clinical problem. It will undoubtedly serve as the basis of an improved method to control continuous drooling.

Evaluation of a women's safe shelter experience to teach internal medicine residents about intimate partner violence. A randomized controlled trial.

Although intimate partner violence (IPV) remains a major public health problem, physicians often fail to screen female patients. Reported IPV training approaches suffer from weak study designs and limited outcome assessments. We hypothesized that an educational experience for residents at a women's safe shelter would have significantly greater impact on IPV competencies, screening, and care for victims than a workshop seminar alone. In a pre-post randomized controlled trial, we compared residents exposed to the workshop seminar alone (controls) to residents exposed to these methods plus an experience at a women's safe shelter (cases). Competencies were assessed by written questionnaire and included knowledge, skills, attitudes, resource awareness, and screening behaviors. Of the 36 residents in the trial, 22 (61%) completed both pre- and postquestionnaires. Compared to controls, cases showed significantly greater pre-post improvement in the knowledge composite subscale. There were no significant differences between cases and controls in the subscales of skills, attitudes, or resource awareness. Cases increased their self-reported screening frequency but this did not differ significantly from the controls. Enhancing traditional IPV curriculum with a women's safe shelter educational experience may result in small improvements in residents' knowledge about IPV.

A randomised controlled trial of clinics in secondary schools for adolescents with asthma

Aim To test the hypothesis that delivery of a programme of asthma care in nurse‐led clinics in school would improve access to care and health outcomes compared with care in general practice.Methods Pupils at four secondary schools in Bristol, North Somerset and South Gloucestershire, UK, were included in the randomized controlled trial. Another two schools were included to control for any cross‐contamination between school clinic attenders and general practice attenders in the trial schools. Pupils in trial schools were randomly assigned to receive an invitation for an asthma review at school or in general practice. Schools were stratified for deprivation and covered rural, urban and suburban populations. Pupils with asthma were identified using a screening questionnaire and then cross‐referenced with practice prescribing records. Four school nurses with additional specialist asthma training ran the school clinics weekly. Consultations concentrated on the needs and interests of adolescents and followed national guidelines for treatment changes. Reviews were arranged at 1 and 6 months, with an additional 3‐month review if needed. The pupil's GP was kept informed. General practice care was according to the practice's usual treatment protocols.Primary outcomes were the proportion of pupils who had had an asthma review in 6 months, health‐related quality of life and level of symptoms. Secondary outcomes were pupil knowledge and attitude to asthma, inhaler technique, the proportion taking inhaled steroids daily, school absence due to asthma, PEFR and pupil preference for the setting of care.Sample size was calculated to have an 80% chance of showing an increase from 40% to 60% having a review in 6 months and half a standard deviation improvement on the quality of life measure. Analysis was on an intention to treat basis.Results School clinic pupils were more likely to attend (91% vs. 51%). However, symptom control or quality of life were no better. School clinic pupils knew more about asthma, had a more positive attitude and better inhaler technique. Absence and PEFR showed no difference. 63% who attended school clinics preferred this model but, taking both groups together, just over half would prefer to attend their GP for follow‐up. Cost of care (including practice, school clinic, hospital and medication) was £32.10 at school, £19.80 at the trial practices and £18.00 at control practices.Conclusions Previous evaluations of nurse‐led asthma clinics in practice have also failed to show improvements in outcomes, though process measures do improve. This may be due to the need for nurses to refer patients to doctors for changes in medication, rather than doing this themselves. Some weaknesses in study design that may have affected outcome, but the essential conclusion is that nurse‐led asthma clinics in school are not cost effective. The study does suggest that such clinics can reach a high proportion of adolescents, but for asthma at least this does not result in any measurable improvement in outcome.

A profile of success and failure in telehealth--evidence and opinion from the Success and Failures in Telehealth conferences.

Papers presented at the three Successes and Failures in Telehealth conferences have made a helpful contribution to what is known about the practicalities of implementing and using telehealth. Ten of the 89 papers covered general concepts, 40 described primary studies and 26 discussed telehealth programmes or networks. Common themes that emerged on determinants of success and failure included the reliability of equipment, the reliability of vendors, political and budgetary issues,the perceived need for telehealth, the involvement of stakeholders, health professionals' opinions, the stability of management structures, the turnover of personnel and cooperation between organizations. Limitations in some papers included an absence of data, weak study designs, short-term perspectives and lack of information on health outcomes. Despite these limitations, the papers have made a valuable contribution to our knowledge of what has worked and what has failed in the field of telehealth.

Interferon for preventing and treating hepatocellular carcinoma associated with the hepatitis B and C viruses.

The possibility that interferon-alpha might be effective for the prevention or treatment of hepatocellular carcinoma is suggested by its efficacy against the associated hepatitis B and C viruses, by its efficacy in the treatment of some other human tumours, and by evidence that interferon-alpha may inhibit the growth of human hepatocellular carcinoma cell lines and their production of hepatitis B surface antigen. Few studies support the use of interferon-alpha for preventing hepatitis B virus-associated hepatocellular carcinoma. In contrast, benefit from the use of interferon-alpha to prevent hepatitis C virus-associated hepatocellular carcinoma is suggested in a large number of studies, but most of these studies have weaknesses of study design that preclude definitive conclusions. Nevertheless, most of these studies suggest that the incidence of hepatocellular carcinoma is lower in hepatitis C virus-infected patients receiving interferon-alpha, particularly in patients with a sustained response to interferon-alpha, compared to nonresponders. As a treatment for hepatocellular carcinoma, interferon-alpha was only evaluated in a small number of patients with advanced disease; 'partial responses' and prolongation of survival times in a few of these studies suggest that additional studies should be done in patients with less advanced disease.

How to Write a Research Article for the Journal of Genetic Counseling.

The purpose of this paper is to provide guidance to contributors to the Journal of Genetic Counseling about preparing manuscripts that report findings of original research. While variations in reporting formats and standards are acknowledged, the paper aims to assist contributors in recognizing the essential components of research studies and of manuscripts describing such studies. A description of the purpose of each section and guidelines for writing each section are provided. Criteria for assessing the strengths and weaknesses of study design, sampling, measures, procedures, and data analyses are also discussed.