[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.

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.

Meta-analysis adjusting for compliance: the example of screening for breast cancer.

Randomized controlled trials are usually analysed by the group to which the patient was randomized, i.e. by "intention-to-treat", regardless of the degree of compliance. However, the "explanatory" effect, i.e. the effect that would occur if we had 100% compliance, is often of interest. This "explanatory" effect is diluted by poor compliance, and hence meta-analyses should ideally avoid both the heterogeneity of effect due to variation in compliance rates among studies, and the undeserved weight given to trials with poor compliance. Newcombe's deattenuation method, which adjusts estimates for the degree of compliance, is extended and applied to a meta-analysis of the five reported randomized controlled trials of mammographic screening. Compliance with screening varied across studies: from 61 to 93% assigned to screening had one or more mammograms. The adjusted estimate of the reduction in breast cancer mortality at 9 years follow-up is 0.37 (95% confidence interval: 0.21, 0.49).

Meta-analysis of diagnostic tests with imperfect reference standards.

We present a method to estimate the summary receiver operating characteristic (SROC) curve for combining information on a diagnostic test from several different studies. Unlike previous methods that assume the reference standard to be error free, our approach allows for the possibility of errors in the reference standard, through use of a latent class model. The model provides estimates of the sensitivity and specificity of the diagnostic test and the case prevalence in each study; these parameters can then be used in a meta-analysis, for example, using the regression method proposed by Moses et al., of a measure of test discrimination on a measure of the diagnostic threshold, to fit the SROC. The method is illustrated with an example on Pap smears that shows how adjusting for imperfection in the reference standard typically reduces the scatter of data in the SROC plot, and tends to indicate better performance of the test than otherwise.

A cardiovascular extension of the Health Measurement Questionnaire.

OBJECTIVE: To investigate the psychometric properties of a cardiovascular extension of an existing utility-based quality of life questionnaire (Health Measurement Questionnaire). The new instrument has been named the Utility Based Quality of life--Heart questionnaire, or UBQ-H. DESIGN: Explored the test-retest reliability, construct validity, and responsiveness of the UBQ-H. PATIENTS: A sample of 322 patients attending cardiac outpatient clinics were recruited from two large metropolitan teaching hospitals. A second sample of 1112 patients taking part in the LIPID trial was also used to investigate the validity and responsiveness of the UBQ-H. RESULTS: Ninety per cent of all UBQ-H questionnaires were returned, and item completion rates were high (median of less than 1% missing or N/A answers). Cronbach's alpha measure of internal consistency for the scales ranged between 0.79-0.91, and each item was also most strongly correlated with its hypothesised domain than alternative domains. The intra-class test-retest reliability of the UBQ-H scales ranged from 0.65 to 0.81 for patients with stable health. Results supported the construct validity of the UBQ-H. The UBQ-H was significantly correlated with other information on quality of life (for example, General Health Questionnaire) as anticipated. The instrument was able to distinguish between contrasted groups of patients (for example, with versus without symptoms of dyspnoea, prior myocardial infarction versus none, etc), and was responsive to changes in health associated with adverse events requiring hospitalisation. CONCLUSIONS: The modifications made to the Health Measurement Questionnaire has resulted in an assessment designed for cardiovascular patients that has proved to be both reliable and valid.

Meta-analysis and quality of evidence in the economic evaluation of drug trials.

Meta-analysis is an important part of assessing cost-effectiveness in that it may help determine which treatments are indeed effective and estimate the level of effectiveness of each. Meta-analysis uses the data from all the relevant trials and is a powerful tool for detecting effects too small to be picked up by individual trials. The assessment of quality of studies in a meta-analysis is critical, with priority needing to be given to high quality randomised studies. A written protocol, literature retrieval system, evaluation and selection criteria, choice of endpoints and ways to evaluate bias must all be pre-defined. Nevertheless, problems can arise when meta-analysis is used for cost-effectiveness analysis, due to variation in study medication protocols, duration of follow-up, and difficulties in interpreting patient subgroups and compliance. Despite being subject to the design flaws of both the trials analysed and the methods used in the analysis itself, meta-analysis provides a more objective and thorough means of evaluating effectiveness and hence the cost-effectiveness of treatments. Based on the meta-analysis evidence, we recommend that the current QALY league tables be split into an implementation table for clearly effective therapies, and a research priority table where the evidence of treatment effectiveness is less clear and more research is needed.

A pitfall in utility assessment--patients' undisclosed investment decisions.

Among those decisions that may be made by a patient in response to an illness, the authors single out a certain class: contingent investment decisions. They are characterized by the patient's committing him- or herself, on the basis of prognostic counseling, to a certain action or non-action that he or she may regret in retrospect. Examples show that, when assessing utilities, the decision analyst runs a risk of handling such investment decisions incorrectly, unless they are made explicit and incorporated into the medical decision process. The anomaly is explained as a violation of the structural rules for decision trees and is also interpreted in terms of "the price of prognostic ignorance," a quantity closely related to the expected utility value of perfect information.

Antibiotics for sore throat.

BACKGROUND: Sore throat is a very common reason for people to attend for 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 1999, using electronic searches of MEDLINE (using the keywords, "pharyngitis", "sore throat" and "tonsillitis") after 1966, the Cochrane Library, the Cochrane collection of hand-searched trials, and the reference sections of the articles identified. Abstracts of identified articles were used to determine which studies were trials. SELECTION CRITERIA: Trials of antibiotic against control with either measures of the typical symptoms (throat soreness, headache or fever), or complications (suppurative and non-suppurative) of sore throat. DATA COLLECTION AND ANALYSIS: RevMan 4.0.3 MAIN RESULTS: 25 studies were included in the review. A total number of 11, 452 cases of sore throat have been studied. 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 benefit from antibiotics for acute rheumatic fever, which reduced this complication to less than one third (OR = 0.30; 95% CI = 0.20-0.45). 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 = 0.11-0.43) and reduced the incidence of acute sinusitis to about one half of that in the placebo group (OR = 0.46; 95% CI = 0.10-2.05). The incidence of quinsy was also reduced in relation to placebo group (OR = 0.16; 95% CI = 0.07-0.35). 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 symptom-free by one week. 4. Subgroup analyses of symptom reduction Subgroup analysis by age; blind vs 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, 0.26) than if it was negative (OR 0.65; 95% CI 0.38,1.1.2). REVIEWER'S 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 who will derive no benefit. Antibiotics shorten the duration of symptoms, but by a mean of only 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 Controlled Trials Register, MEDLINE, Index Medicus (pre 1965), Current Contents and reference lists of articles from 1958 to January 2000. 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 but only seven trials, with a total of 2,202 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 28% relative reduction (95% confidence interval 15% to 38%) 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 5% or that about 17 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. [This abstract has been prepared centrally.]

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 sore throat.

BACKGROUND: Sore throat is a very common reason for people to attend for medical care. Sore throat is a disease that remits spontaneously, that is, 'cure' is not dependant 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 1999, using electronic searches of MEDLINE (using the keywords, "pharyngitis", "sore throat" and "tonsillitis") after 1966, the Cochrane Library, the Cochrane collection of hand-searched trials, and the reference sections of the articles identified. Abstracts of identified articles were used to determine which studies were trials. SELECTION CRITERIA: Trials of antibiotic against control with either measures of the typical symptoms (throat soreness, headache or fever), or complications (suppurative and non-suppurative) of sore throat. DATA COLLECTION AND ANALYSIS: RevMan 4.0.3 MAIN RESULTS: A total number of 10,484 cases of sore throat have been studied. 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 benefit from antibiotics for acute rheumatic fever, which reduced this complication to less than one third (OR = 0.30; 95% CI = 0.20-0.45). 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 = 0.11-0.43) and reduced the incidence of acute sinusitis to about one half of that in the placebo group (OR = 0.46; 95% CI = 0.10-2.05). The incidence of quinsy was also reduced in relation to placebo group (OR = 0.18; 95% CI = 0.08-0.43). 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 symptom-free by one week. 4. Subgroup analyses of symptom reduction Subgroup analysis by age; blind vs unblinded; us of antipyretics; or results of swabs for Streptococcus yielded no significant differences. REVIEWER'S 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 who will derive no benefit. Antibiotics shorten the duration of symptoms, but by a mean of only about half of one day at day 3 (the time of maximal effect), and by about eight 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 Controlled Trials Register, MEDLINE, Index Medicus, Current Contents and reference lists of articles from 1958 to January 1999. 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: Nine trials were eligible but only six trials, with a total of 1,962 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 34% relative reduction (95% confidence interval 16% to 48%) in pain at two to seven days. Since approximately 85% of patients will have settled spontaneously in this time, this means an absolute reduction of about 5% or that about 20 children must be treated with antibiotics to prevent one child having some pain after two days. There was no effect of antibiotics on deafness, as measured by subsequent tympanometry, other complications, or recurrence. However, audiometry was done in only two studies and incompletely reported, and there were few serious complications seen in these trials: only one case of mastoiditis occurred (in a penicillin treated group). One semi-randomised trial in Sweden in 1954 reported a rate of 17% in the untreated group versus none in the penicillin treated groups. 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.

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.

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.

Probability revision.

This article examines the principles of probability revision and four different ways of obtaining post-test probabilities: the hypothetical cohort method, likelihood ratios and odds, the Nomogram, and precalculation. The authors then show where pre-test probabilities can be obtained, and then how to interpret multiple tests.