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ObjectiveTo evaluate whether antibiotic prescribing for suspected urinary tract infections in frail older adults can be reduced through a multifaceted antibiotic stewardship intervention.DesignPragmatic, parallel, cluster randomised controlled trial, with a five month baseline period and a seven month follow-up period.Setting38 clusters consisting of one or more general practices (n=43) and older adult care organisations (n=43) in Poland, the Netherlands, Norway, and Sweden, from September 2019 to June 2021.Participants1041 frail older adults aged 70 or older (Poland 325, the Netherlands 233, Norway 276, Sweden 207), contributing 411 person years to the follow-up period.InterventionHealthcare professionals received a multifaceted antibiotic stewardship intervention consisting of a decision tool for appropriate antibiotic use, supported by a toolbox with educational materials. A participatory-action-research approach was used for implementation, with sessions for education, evaluation, and local tailoring of the intervention. The control group provided care as usual.Main outcome measuresThe primary outcome was the number of antibiotic prescriptions for suspected urinary tract infections per person year. Secondary outcomes included the incidence of complications, all cause hospital referrals, all cause hospital admissions, all cause mortality within 21 days after suspected urinary tract infections, and all cause mortality.ResultsThe numbers of antibiotic prescriptions for suspected urinary tract infections in the follow-up period were 54 prescriptions in 202 person years (0.27 per person year) in the intervention group and 121 prescriptions in 209 person years (0.58 per person year) in the usual care group. Participants in the intervention group had a lower rate of receiving an antibiotic prescription for a suspected urinary tract infection compared with participants in the usual care group, with a rate ratio of 0.42 (95% confidence interval 0.26 to 0.68). No differences between intervention and control group were observed in the incidence of complications (<0.01 v0.05 per person year), hospital referrals (<0.01 v0.05), admissions to hospital (0.01 v0.05), and mortality (0 v0.01) within 21 days after suspected urinary tract infections, nor in all cause mortality (0.26 v0.26).ConclusionsImplementation of a multifaceted antibiotic stewardship intervention safely reduced antibiotic prescribing for suspected urinary tract infections in frail older adults.Trial registrationClinicalTrials.gov NCT03970356.

OBJECTIVE: To compare the clinical efficacy of ear drops containing acetic acid, corticosteroid and acetic acid, and steroid and antibiotic in acute otitis externa in primary care. DESIGN: Randomised controlled trial. SETTING: 79 general practices, Netherlands. PARTICIPANTS: 213 adults with acute otitis externa. MAIN OUTCOME MEASURES: Primary outcome: duration of symptoms (days) according to patient diaries. Secondary outcome: cure rate according to general practitioner completed questionnaires and recurrence of symptoms between days 21 and 42. RESULTS: Symptoms lasted for a median of 8.0 days (95% confidence interval 7.0 to 9.0) in the acetic acid group, 7.0 days (5.8 to 8.3) in the steroid and acetic acid group, and 6.0 days (5.1 to 6.9) in the steroid and antibiotic group. The overall cure rates at seven, 14, and 21 days were 38%, 68%, and 75%, respectively. Compared with the acetic acid group, significantly more patients were cured in the steroid and acetic acid group and steroid and antibiotic group at day 14 (odds ratio 2.4, 1.1 to 5.3, and 3.5, 1.6 to 7.7, respectively) and day 21 (5.3, 2.0 to 13.7, and 3.9, 1.7 to 9.1, respectively). Recurrence of symptoms between days 21 and 42 occurred in 29% (50/172) of patients and was seen significantly less in the steroid and acetic acid group (0.3, 0.1 to 0.7) and steroid and antibiotic group (0.4, 0.2 to 1.0) than in the acetic acid group. CONCLUSIONS: Ear drops containing corticosteroids are more effective than acetic acid ear drops in the treatment of acute otitis externa in primary care. Steroid and acetic acid or steroid and antibiotic ear drops are equally effective.

ObjectiveTo assess the accuracy of the Wells rule for excluding deep vein thrombosis and whether this accuracy applies to different subgroups of patients.DesignMeta-analysis of individual patient data. Data sourcesAuthors of 13 studies (n=10 002) provided their datasets, and these individual patient data were merged into one dataset.Eligibility criteriaStudies were eligible if they enrolled consecutive outpatients with suspected deep vein thrombosis, scored all variables of the Wells rule, and performed an appropriate reference standard.Main outcome measuresMultilevel logistic regression models, including an interaction term for each subgroup, were used to estimate differences in predicted probabilities of deep vein thrombosis by the Wells rule. In addition, D-dimer testing was added to assess differences in the ability to exclude deep vein thrombosis using an unlikely score on the Wells rule combined with a negative D-dimer test result.ResultsOverall, increasing scores on the Wells rule were associated with an increasing probability of having deep vein thrombosis. Estimated probabilities were almost twofold higher in patients with cancer, in patients with suspected recurrent events, and (to a lesser extent) in males. An unlikely score on the Wells rule (≤1) combined with a negative D-dimer test result was associated with an extremely low probability of deep vein thrombosis (1.2%, 95% confidence interval 0.7% to 1.8%). This combination occurred in 29% (95% confidence interval 20% to 40%) of patients. These findings were consistent in subgroups defined by type of D-dimer assay (quantitative or qualitative), sex, and care setting (primary or hospital care). For patients with cancer, the combination of an unlikely score on the Wells rule and a negative D-dimer test result occurred in only 9% of patients and was associated with a 2.2% probability of deep vein thrombosis being present. In patients with suspected recurrent events, only the modified Wells rule (adding one point for the previous event) is safe.ConclusionCombined with a negative D-dimer test result (both quantitative and qualitative), deep vein thrombosis can be excluded in patients with an unlikely score on the Wells rule. This finding is true for both sexes, as well as for patients presenting in primary and hospital care. In patients with cancer, the combination is neither safe nor efficient. For patients with suspected recurrent disease, one extra point should be added to the rule to enable a safe exclusion.

ObjectiveTo review the diagnostic accuracy of D-dimer testing in older patients (>50 years) with suspected venous thromboembolism, using conventional or age adjusted D-dimer cut-off values.DesignSystematic review and bivariate random effects meta-analysis. Data sourcesWe searched Medline and Embase for studies published before 21 June 2012 and we contacted the authors of primary studies. Study selectionPrimary studies that enrolled older patients with suspected venous thromboembolism in whom D-dimer testing, using both conventional (500 µg/L) and age adjusted (age×10 µg/L) cut-off values, and reference testing were performed. For patients with a non-high clinical probability, 2×2 tables were reconstructed and stratified by age category and applied D-dimer cut-off level.Results13 cohorts including 12 497 patients with a non-high clinical probability were included in the meta-analysis. The specificity of the conventional cut-off value decreased with increasing age, from 57.6% (95% confidence interval 51.4% to 63.6%) in patients aged 51-60 years to 39.4% (33.5% to 45.6%) in those aged 61-70, 24.5% (20.0% to 29.7% in those aged 71-80, and 14.7% (11.3% to 18.6%) in those aged >80. Age adjusted cut-off values revealed higher specificities over all age categories: 62.3% (56.2% to 68.0%), 49.5% (43.2% to 55.8%), 44.2% (38.0% to 50.5%), and 35.2% (29.4% to 41.5%), respectively. Sensitivities of the age adjusted cut-off remained above 97% in all age categories. ConclusionsThe application of age adjusted cut-off values for D-dimer tests substantially increases specificity without modifying sensitivity, thereby improving the clinical utility of D-dimer testing in patients aged 50 or more with a non-high clinical probability.

ObjectivesTo quantify the diagnostic accuracy of selected inflammatory markers in addition to symptoms and signs for predicting pneumonia and to derive a diagnostic tool.DesignDiagnostic study performed between 2007 and 2010. Participants had their history taken, underwent physical examination and measurement of C reactive protein (CRP) and procalcitonin in venous blood on the day they first consulted, and underwent chest radiography within seven days.SettingPrimary care centres in 12 European countries.ParticipantsAdults presenting with acute cough.Main outcome measuresPneumonia as determined by radiologists, who were blind to all other information when they judged chest radiographs.ResultsOf 3106 eligible patients, 286 were excluded because of missing or inadequate chest radiographs, leaving 2820 patients (mean age 50, 40% men) of whom 140 (5%) had pneumonia. Re-assessment of a subset of 1675 chest radiographs showed agreement in 94% (κ 0.45, 95% confidence interval 0.36 to 0.54). Six published “symptoms and signs models” varied in their discrimination (area under receiver operating characteristics curve (ROC) ranged from 0.55 (95% confidence interval 0.50 to 0.61) to 0.71 (0.66 to 0.76)). The optimal combination of clinical prediction items derived from our patients included absence of runny nose and presence of breathlessness, crackles and diminished breath sounds on auscultation, tachycardia, and fever, with an ROC area of 0.70 (0.65 to 0.75). Addition of CRP at the optimal cut off of >30 mg/L increased the ROC area to 0.77 (0.73 to 0.81) and improved the diagnostic classification (net reclassification improvement 28%). In the 1556 patients classified according to symptoms, signs, and CRP >30 mg/L as “low risk” (<2.5%) for pneumonia, the prevalence of pneumonia was 2%. In the 132 patients classified as “high risk” (>20%), the prevalence of pneumonia was 31%. The positive likelihood ratio of low, intermediate, and high risk for pneumonia was 0.4, 1.2, and 8.6 respectively. Measurement of procalcitonin added no relevant additional diagnostic information. A simplified diagnostic score based on symptoms, signs, and CRP >30 mg/L resulted in proportions of pneumonia of 0.7%, 3.8%, and 18.2% in the low, intermediate, and high risk group respectively.ConclusionsA clinical rule based on symptoms and signs to predict pneumonia in patients presenting to primary care with acute cough performed best in patients with mild or severe clinical presentation. Addition of CRP concentration at the optimal cut off of >30 mg/L improved diagnostic information, but measurement of procalcitonin concentration did not add clinically relevant information in this group.

OBJECTIVE: To determine which clinical variables provide diagnostic information in recognising heart failure in primary care patients with stable chronic obstructive pulmonary disease (COPD) and whether easily available tests provide added diagnostic information. Design Cross sectional diagnostic study. Setting 51 primary care practices. Participants 1186 patients aged ≥ 65 years with COPD diagnosed by their general practitioner who did not have a diagnosis of heart failure confirmed by a cardiologist. MAIN OUTCOME MEASURES: Independent diagnostic variables for concomitant heart failure in primary care patients with stable COPD. RESULTS: 405 patients (34% of eligible patients) underwent a systematic diagnostic investigation, which resulted in 83 (20.5%) receiving a new diagnosis of concomitant heart failure. Independent clinical variables for concomitant heart failure were a history of ischaemic heart disease, high body mass index, laterally displaced apex beat, and raised heart rate (area under the receiver operating characteristic curve (ROC area) 0.70, 95% confidence interval 0.64 to 0.76). Addition of measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) to the reduced "clinical model" had the largest added diagnostic value, with a significant increase of the ROC area to 0.77 (0.71 to 0.83), followed by electrocardiography (0.75, 0.69 to 0.81). C reactive protein and chest radiography had limited added value. A simplified diagnostic model consisting of the four independent clinical variables plus NT-proBNP and electrocardiography was developed. CONCLUSIONS: A limited number of items easily available from history and physical examination, with addition of NT-proBNP and electrocardiography, can help general practitioners to identify concomitant heart failure in individual patients with stable COPD.