[Better Reporting of Interventions: Template for Intervention Description and Replication (TIDieR) Checklist and Guide]. / Die TIDieR Checkliste und Anleitung - ein Instrument für eine verbesserte Interventionsbeschreibung und Replikation.

Without a complete published description of interventions, clinicians and patients cannot reliably implement interventions that are shown to be useful, and other researchers cannot replicate or build on research findings. The quality of description of interventions in publications, however, is remarkably poor. To improve the completeness of reporting, and ultimately the replicability, of interventions, an international group of experts and stakeholders developed the Template for Intervention Description and Replication (TIDieR) checklist and guide. The process involved a literature review for relevant checklists and research, a Delphi survey of an international panel of experts to guide item selection, and a face-to-face panel meeting. The resultant 12-item TIDieR checklist (brief name, why, what (materials), what (procedure), who intervened, how, where, when and how much, tailoring, modifications, how well (planned), how well (actually carried out)) is an extension of the CONSORT 2010 statement (item 5) and the SPIRIT 2013 statement (item 11). While the emphasis of the checklist is on trials, the guidance is intended to apply across all evaluative study designs. This paper presents the TIDieR checklist and guide, with a detailed explanation of each item, and examples of good reporting. The TIDieR checklist and guide should improve the reporting of interventions and make it easier for authors to structure the accounts of their interventions, reviewers and editors to assess the descriptions, and readers to use the information.

Optimal prostate-specific antigen screening interval for prostate cancer.

BACKGROUND: To identify the optimal interval for repeat prostate-specific antigen (PSA) testing to screen for prostate cancer in healthy adults. PATIENTS AND METHODS: A retrospective cohort study was conducted on 7332 healthy males without prostate cancer at baseline from 2005 to 2008. Participants underwent annual health checkups including PSA testing at the Center for Preventive Medicine in Japan. Participants with high PSA (≥ 4.0 ng/ml) underwent further examination for prostate cancer. A subgroup analysis was conducted age group (<50 years, ≥ 50 years). RESULTS: Mean age was 50 years. Mean PSA at baseline was 1.2 ng/ml. In over 50-year group, for those with initial PSA of <1.0, 1.0-1.9, 2.0-2.9, and 3.0-3.9 ng/ml at baseline, the 3-year cumulative incidence of prostate cancer was 0%, 0.1%, 0.3%, and 5.7%, respectively. No prostate cancer was identified in those <50 years, regardless of PSA level. CONCLUSIONS: If PSA screening is recommended, males >50 years with PSA of 3.0-3.9 ng/ml at baseline should undergo rescreening at 2 years. For men with PSA <3.0 ng/ml, PSA rescreening at intervals of ≥ 3 years is appropriate. PSA screening may not be indicated in males of <50 years of age.

Blood pressure re-screening for healthy adults: what is the best measure and interval?

Blood pressure (BP) screening is important to identify those at risk of cardiovascular disease, but there has been little data on the appropriate interval of screening. We aimed to evaluate the optimal interval and the best measure for BP re-screening by estimating the long-term, true change variance ('signal') and short-term, within-person variance ('noise'). Study design was a cohort study from 2005 to 2008. Target population was Japanese healthy adults not taking antihypertensive medication at baseline, in a teaching hospital. We measured annually the systolic BP (SBP) and the diastolic BP (DBP), and calculated the pulse pressure (PP) and the mean arterial pressure (MAP). A total of 15,055 individuals (51% male) with a mean age of 49 years had annual check-ups. Short-term coefficient of variation was lowest for MAP at 5.2%, followed by SBP (5.7%) and DBP (5.8%), and highest for PP (12%). After 3 years, the 'signal' of true BP changes of only SBP and MAP equaled the 'noise' of BP measurement; however, it was larger for those with higher initial BPs. SBP or MAP appears to be a better screening measure. The optimal interval should be 3 years or more, with SBP<130 mm Hg and 2 years for those with SBP ≥ 130 mm Hg.

Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study.

AIMS/HYPOTHESIS: Fenofibrate caused an acute, sustained plasma creatinine increase in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies. We assessed fenofibrate's renal effects overall and in a FIELD washout sub-study. METHODS: Type 2 diabetic patients (n = 9,795) aged 50 to 75 years were randomly assigned to fenofibrate (n = 4,895) or placebo (n = 4,900) for 5 years, after 6 weeks fenofibrate run-in. Albuminuria (urinary albumin/creatinine ratio measured at baseline, year 2 and close-out) and estimated GFR, measured four to six monthly according to the Modification of Diet in Renal Disease Study, were pre-specified endpoints. Plasma creatinine was re-measured 8 weeks after treatment cessation at close-out (washout sub-study, n = 661). Analysis was by intention-to-treat. RESULTS: During fenofibrate run-in, plasma creatinine increased by 10.0 µmol/l (p < 0.001), but quickly reversed on placebo assignment. It remained higher on fenofibrate than on placebo, but the chronic rise was slower (1.62 vs 1.89 µmol/l annually, p = 0.01), with less estimated GFR loss (1.19 vs 2.03 ml min(-1) 1.73 m(-2) annually, p < 0.001). After washout, estimated GFR had fallen less from baseline on fenofibrate (1.9 ml min(-1) 1.73 m(-2), p = 0.065) than on placebo (6.9 ml min(-1) 1.73 m(-2), p < 0.001), sparing 5.0 ml min(-1) 1.73 m(-2) (95% CI 2.3-7.7, p < 0.001). Greater preservation of estimated GFR with fenofibrate was observed with baseline hypertriacylglycerolaemia (n = 169 vs 491 without) alone, or combined with low HDL-cholesterol (n = 140 vs 520 without) and reductions of ≥ 0.48 mmol/l in triacylglycerol over the active run-in period (pre-randomisation) (n = 356 vs 303 without). Fenofibrate reduced urine albumin concentrations and hence albumin/creatinine ratio by 24% vs 11% (p < 0.001; mean difference 14% [95% CI 9-18]; p < 0.001), with 14% less progression and 18% more albuminuria regression (p < 0.001) than in participants on placebo. End-stage renal event frequency was similar (n = 21 vs 26, p = 0.48). CONCLUSIONS/INTERPRETATION: Fenofibrate reduced albuminuria and slowed estimated GFR loss over 5 years, despite initially and reversibly increasing plasma creatinine. Fenofibrate may delay albuminuria and GFR impairment in type 2 diabetes patients. Confirmatory studies are merited. TRIAL REGISTRATION: ISRCTN64783481.

Antibiotics for sore throat.

BACKGROUND: Sore throat is a very common reason for people to present for medical care. Although it remits spontaneously, primary care doctors commonly prescribe antibiotics for it. OBJECTIVES: To assess the benefits of antibiotics for sore throat. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library, Issue 1, 2006), MEDLINE (January 1966 to March 2006) and EMBASE (January 1990 to December 2005). SELECTION CRITERIA: Trials of antibiotic against control with either measures of the typical symptoms (throat soreness, headache or fever), or suppurative or non-suppurative complications of sore throat. DATA COLLECTION AND ANALYSIS: Potential studies were screened independently by two authors for inclusion, with differences in opinion resolved by discussion. Data were then independently extracted from studies selected by inclusion by two authors. Researchers from three studies were contacted for additional information. MAIN RESULTS: There were 27 studies with 2835 cases of sore throat. 1. Non-suppurative complications: There was a trend for antibiotics to protect against acute glomerulonephritis, but there were insufficient cases to be sure. Several studies found antibiotics reduced acute rheumatic fever by more than two thirds (relative risk (RR) 0.22; 95% CI 0.02 to 2.08). 2. Suppurative complications: Antibiotics reduced the incidence of acute otitis media (RR 0.30; 95% CI 0.15 to 0.58); of acute sinusitis (RR 0.48; 95% CI 0.08 to 2.76); and of quinsy (peritonsillar abscess) compared to those taking placebo (RR 0.15; 95% CI 0.05 to 0.47). 3. SYMPTOMS: Throat soreness and fever were reduced by antibiotics by about one half. The greatest difference was seen at about 3 to 4 days (when the symptoms of about 50% of untreated patients had settled). By one week about 90% of treated and untreated patients were symptom-free. The overall number need to treat to prevent one sore throat at day 3 was just under six (95% CI 4.9 to 7.0); at week 1 it was 21 (95% CI 13.2 to 47.9). 4. Subgroup analyses of symptom reduction: Analysis by: age; blind versus unblinded; or use of antipyretics, found no significant differences. Analysis of results of throat swabs showed that antibiotics were more effective against symptoms at day 3, RR 0.58 (95% CI 0.48 to 0.71) if the swabs were positive for Streptococcus, compared to RR 0.78 (95% CI 0.63 to 0.97) if negative. Similarly at week 1, RRs 0.29 (95% CI 0.12 to 0.70) for positive, and 0.73 (95% CI 0.50 to 1.07) for negative swabs. AUTHORS' CONCLUSIONS: Antibiotics confer relative benefits in the treatment of sore throat. However, the absolute benefits are modest. Protecting sore throat sufferers against suppurative and non-suppurative complications in modern Western society can only be achieved by treating many with antibiotics, most of whom will derive no benefit. In emerging economies (where rates of acute rheumatic fever are high, for example), the number needed to treat may be much lower for antibiotics to be considered effective. Antibiotics shorten the duration of symptoms by about sixteen hours overall.

Identifying studies for systematic reviews of diagnostic tests was difficult due to the poor sensitivity and precision of methodologic filters and the lack of information in the abstract.

BACKGROUND AND OBJECTIVES: Methods to identify studies for systematic reviews of diagnostic accuracy are less well developed than for reviews of intervention studies. This study assessed (1) the sensitivity and precision of five published search strategies and (2) the reliability and accuracy of reviewers screening the results of the search strategy. METHODS: We compared the results of the search filters with the studies included in two systematic reviews, and assessed the interobserver reliability of two reviewers screening the list of articles generated by a search strategy. RESULTS: In the first review, the search strategy published by van der Weijden had the greatest sensitivity, and in the second, four search strategies had 100% sensitivity. There was "substantial" agreement between two reviewers, but in the first review each reviewer working on their own would have missed one paper eligible for inclusion in the review. Ascertainment intersection techniques indicate that it is unlikely that further papers have been missed in the screening process. CONCLUSION: Published search strategies may miss papers for reviews of diagnostic test accuracy. Papers are not easily identified as studies of diagnostic test accuracy, and the lack of information in the abstract makes it difficult to assess the eligibility for inclusion in a systematic review.

Antibiotics for sore throat.

BACKGROUND: Sore throat is a very common reason for people to seek medical care. It is a disease that remits spontaneously, that is, 'cure' is not dependent on treatment. Nonetheless primary care doctors commonly prescribe antibiotics for sore throat and other upper respiratory tract infections. OBJECTIVES: To assess the benefits of antibiotics in the management of sore throat. SEARCH STRATEGY: Systematic search of the literature from 1945 to 2003, using electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, issue 2, 2003); MEDLINE (January 1966 to May 2003); EMBASE (January 1990 to March 2003), and the reference sections of the articles identified. We applied no language restrictions. We used abstracts of identified articles to identify trials. SELECTION CRITERIA: Trials of antibiotic against control with either measures of the typical symptoms (throat soreness, headache or fever), or suppurative complications (meaning: forming pus) and non-suppurative complications of sore throat. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened potential studies for inclusion and resolved differences in opinion by discussion. The reviewers then independently extracted the data from the selected studies. We contacted the authors of three studies to acquire additional information not available in published articles. Potential studies were screened independently by two reviewers for inclusion, with differences in opinion resolved by discussion. Data was then independently extracted from studies selected by inclusion by two reviewers. Authors of three studies were contacted to acquire additional information not available in published articles. MAIN RESULTS: We included twenty-six studies, covering 12,669 cases of sore throat in the review.1. Non-suppurative complications There was a trend for protection against acute glomerulonephritis by antibiotics, but insufficient cases were recorded to be sure of this effect. Several studies found that antibiotics reduced acute rheumatic fever, to less than one third (odds ratio (OR) = 0.30; 95% confidence interval (CI) = 0.20 to 0.45). 2. Suppurative complications Antibiotics reduced the incidence of acute otitis media to about one quarter of that in the placebo group (OR = 0.22; 95% CI 0.11 to 0.43) and reduced the incidence of acute sinusitis to about one half of that in the placebo group (OR = 0.46; 95% CI 0.10 to 2.05). The incidence of quinsy was also reduced in relation to placebo group (OR = 0.16; 95% CI 0.07 to 0.35). 3. Symptoms Symptoms of headache, throat soreness and fever were reduced by antibiotics to about one half. The greatest time for this to be evident was at about three and a half days (when the symptoms of about 50% of untreated patients had settled). About 90% of treated and untreated patients were free of symptoms by one week. The overall number needed to treat to prevent one sore throat at day three was about 5.0 (95% CI 4.5 to 5.8); and at one week was 14.2 (95% CI 11.5 to 20.6). 4. Subgroup analyses of symptom reduction Subgroup analysis by age; blind versus unblinded; or use of antipyretics yielded no significant differences. The results of swabs of the throat for Streptococcus influenced the effect of antibiotics. If the swab was positive, antibiotics were more effective (the OR reduced to 0.16, 95% CI 0.09 to 0.26) than if it was negative (OR 0.65; 95% CI 0.38 to 1.12). REVIEWERS' CONCLUSIONS: Antibiotics confer relative benefits in the treatment of sore throat. However, the absolute benefits are modest. Protecting sore throat sufferers against suppurative and non-suppurative complications in modern Western society can be achieved only by treating with antibiotics many who will derive no benefit. In emerging economies where rates of for example acute rheumatic fever are high, the number needed to treat may be much lower. Antibiotics shorten the duration of symptoms by a mean of one day about half way through the illness (the time of maximal effect), and by about sixteen hours overall.

Antibiotics for acute otitis media in children.

BACKGROUND: Acute otitis media is one of the most common diseases in early infancy and childhood. Antibiotic use for acute otitis media varies from 31% in the Netherlands to 98% in the USA and Australia. OBJECTIVES: The objective of this review was to assess the effects of antibiotics for children with acute otitis media. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE, Index Medicus (pre 1965), Current Contents and reference lists of articles from 1958 to January 2000. The search was updated in 2003. SELECTION CRITERIA: Randomised trials comparing antimicrobial drugs with placebo in children with acute otitis media. DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Ten trials were eligible based on design, only eight of the trials, with a total of 2,287 children, included patient-relevant outcomes. The methodological quality of the included trials was generally high. All trials were from developed countries. The trials showed no reduction in pain at 24 hours, but a 30% relative reduction (95% confidence interval 19% to 40%) in pain at two to seven days. Since approximately 80% of patients will have settled spontaneously in this time, this means an absolute reduction of 7% or that about 15 children must be treated with antibiotics to prevent one child having some pain after two days. There was no effect of antibiotics on hearing problems of acute otitis media, as measured by subsequent tympanometry. However, audiometry was done in only two studies and incompletely reported. Nor did antibiotics influence other complications or recurrence. There were few serious complications seen in these trials: only one case of mastoiditis occurred in a penicillin treated group. REVIEWER'S CONCLUSIONS: Antibiotics provide a small benefit for acute otitis media in children. As most cases will resolve spontaneously, this benefit must be weighed against the possible adverse reactions. Antibiotic treatment may play an important role in reducing the risk of mastoiditis in populations where it is more common.

Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative.

AIM: To improve the accuracy and completeness of reporting of studies of diagnostic accuracy in order to allow readers to assess the potential for bias in a study and to evaluate the general isability of its results. METHODS: The standards for reporting of diagnostic accuracy (STARD) steering committee searched the literature to identify publications on the appropriate conduct and reporting of diagnostic studies and extracted potential items into an extensive list. Researchers, editors, and members of professional organisations shortened this list during a 2 day consensus meeting with the goal of developing a checklist and a generic flow diagram for studies of diagnostic accuracy. RESULTS: The search for published guidelines about diagnostic research yielded 33 previously published checklists, from which we extracted a list of 75 potential items. At the consensus meeting, participants shortened the list to a 25-item checklist, by using evidence whenever available. A prototype of a flow diagram provides information about the method of recruitment of patients, the order of test execution and the numbers of patients undergoing the test under evaluation, the reference standard, or both. CONCLUSIONS: Evaluation of research depends on complete and accurate reporting. If medical journals adopt the checklist and the flow diagram, the quality of reporting of studies of diagnostic accuracy should improve to the advantage of clinicians, researchers, reviewers, journals, and the public.

[Reporting studies of diagnostic accuracy according to a standard method; the Standards for Reporting of Diagnostic Accuracy (STARD)]. / Verslaglegging van diagnostisch evaluatieonderzoek volgens een standaardmethode; de 'standards for reporting of diagnostic accuracy' (STARD).

The objective of the 'Standards for Reporting of Diagnostic Accuracy' (STARD) initiative is to improve the reporting of studies of diagnostic accuracy, so as to allow readers to assess the potential for bias in a study and to evaluate the generalibility of its results. The group searched the literature to identify publications on the appropriate conduct and reporting of diagnostic studies. This was used to draw up a list of potential items. During a consensus meeting, a group of researchers, medical journal editors, and members of professional organisations reduced this list to a usable checklist. Wherever possible, evidence from the literature was used to justify the decisions made. The search for published guidelines about diagnostic research yielded 33 previously published checklists, from which a list of 75 potential items was extracted. At the consensus meeting, participants shortened the list to a 25-item checklist. A generic flow diagram was drawn up to provide guidance on the method for including patients, the order in which tests were to be conducted and the number of patients to undergo the test being evaluated, the reference standard, or both. A scientific publication can only be assessed when the reporting is both correct and complete. Use of the checklist and flow diagram will improve the quality of reports produced, to the advantage of clinicians, researchers, reviewers, journal editors and other interested parties.

Valerian does not appear to reduce symptoms for patients with chronic insomnia in general practice using a series of randomised n-of-1 trials.

OBJECTIVE: To investigate the effectiveness of valerian for the management of chronic insomnia in general practice. DESIGN: Valerian versus placebo in a series of n-of-1 trials, in Queensland, Australia. RESULTS: Of 42 enrolled patients, 24 (57%) had sufficient data for inclusion into the n-of-1 analysis. Response to valerian was fair for 23 (96%) participants evaluating their "energy level in the previous day" but poor or modest for all 24 (100%) participants' response to "total sleep time" and for 23 (96%) participants' response to "number of night awakenings" and "morning refreshment". As a group, the proportion of treatment successes ranged from 0.35 (95% CI 0.23, 0.47) to 0.55 (95% CI 0.43, 0.67) for the six elicited outcome sleep variables. There was no significant difference in the number (P=0.06), distribution (P=1.00) or severity (P=0.46) of side effects between valerian and placebo treatments. CONCLUSIONS: Valerian was not shown to be appreciably better than placebo in promoting sleep or sleep-related factors for any individual patient or for all patients as a group.

Investigating causes of heterogeneity in systematic reviews.

What causes heterogeneity in systematic reviews of controlled trials? First, it may be an artefact of the summary measures used, of study design features such as duration of follow-up or the reliability of outcome measures. Second, it may be due to real variation in the treatment effect and hence provides the opportunity to identify factors that may modify the impact of treatment. These factors may include features of the population such as: severity of illness, age and gender; intervention factors such as dose, timing or duration of treatment; and comparator factors such as the control group treatment or the co-interventions in both groups. The ideal way to study causes of true variation is within rather than between studies. In most situations however, we will have to make do with a study level investigation and hence need to be careful about adjusting for potential confounding by artefactual factors such as study design features. Such investigation of artefactual and true causes of heterogeneity form essential steps in moving from a combined effect estimate to application to particular populations and individuals.

Research output of Australian general practice: a comparison with medicine, surgery and public health.

OBJECTIVES: To compare the productivity of Australian general practice in terms of research publications with the productivity of other medical disciplines. DESIGN: A survey of Australian general practice, medicine, surgery and public health publications carried out by manual searching of specific journals and an electronic search of the US National Library of Medicine's "PubMed" database. MAIN OUTCOME MEASURES: The number of original research publications by Australian general practitioners, physicians, surgeons and public health physicians during 1999; the relative publication rate of Australian general practice, medicine, surgery and public health over the period 1990-1999. RESULTS: Of original research articles published in 1999, GPs authored 65% (17/26) in Australian Family Physician and 3% (3/90) in the Medical Journal of Australia; physicians published 4% and 37%, respectively. The electronic search identified 54 research articles relating to Australian general practice published in 1999 in 21 different journals, only two of which were primary care journals. Over the period 1990-1999, there was a publication rate of one general practice [discipline] article per 1000 GPs in practice per year. Corresponding rates for medicine, surgery and public health were 105/1000, 61/1000 and 148/1000, respectively. CONCLUSIONS: There is considerable disparity between the level of research output of general practice and that of the disciplines of medicine, surgery and public health. If we are to have effective general practice research, we urgently need to develop research skills, a supportive infrastructure and a culture that nurtures research.

Feasibility of an evidence-based literature search service for general practitioners.

OBJECTIVE: To test the feasibility of an evidence-based clinical literature search service to help answer general practitioners' (GPs') clinical questions. DESIGN: Two search services supplied GPs who submitted questions with the best available empirical evidence to answer these questions. The GPs provided feedback on the value of the service, and concordance of answers from the two search services was assessed. SETTING: Two literature search services (Queensland and Victoria), operating for nine months from February 1999. MAIN OUTCOME MEASURES: Use of the service; time taken to locate answers; availability of evidence; value of the service to GPs; and consistency of answers from the two services. RESULTS: 58 GPs asked 160 questions (29 asked one, 11 asked five or more). The questions concerned treatment (65%), aetiology (17%), prognosis (13%), and diagnosis (5%). Answering a question took a mean of 3 hours 32 minutes of personnel time (95% CI, 2.67-3.97); nine questions took longer than 10 hours each to answer, the longest taking 23 hours 30 minutes. Evidence of suitable quality to provide a sound answer was available for 126 (79%) questions. Feedback data for 84 (53%) questions, provided by 42 GPs, showed that they appreciated the service, and asking the questions changed clinical care. There were many minor differences between the answers from the two centres, and substantial differences in the evidence found for 4/14 questions. However, conclusions reached were largely similar, with no or only minor differences for all questions. CONCLUSIONS: It is feasible to provide a literature search service, but further assessment is needed to establish its cost effectiveness.

Ways of using evidence-based medicine in general practice.

General practitioners wanting to practise evidence-based medicine (EBM) are constrained by time factors and the great diversity of clinical problems they deal with. They need experience in knowing what questions to ask, in locating and evaluating the evidence, and in applying it. Conventional searching for the best evidence can be achieved in daily general practice. Sometimes the search can be performed during the consultation, but more often it can be done later and the patient can return for the "result". Case-based journal clubs provide a supportive environment for GPs to work together to find the best evidence at regular meetings. An evidence-based literature search service is being piloted to enhance decision-making for individual patients. A central facility provides the search and interprets the evidence in relation to individual cases. A request form and a "results" format make the service akin to pathology testing or imaging. Using EBM in general practice appears feasible. Major difficulties still exist before it can be practised by all GPs, but it has the potential to change the way doctors update their knowledge.