Study question Can treatment of the symptoms of uncomplicated urinary tract infection (UTI) with ibuprofen reduce the rate of antibiotic prescriptions without a significant increase in symptoms, recurrences, or complications? Methods Women aged 18-65 with typical symptoms of UTI and without risk factors or complications were recruited in 42 German general practices and randomly assigned to treatment with a single dose of fosfomycin 3 g (n=246; 243 analysed) or ibuprofen 3×400 mg (n=248; 241 analysed) for three days (and the respective placebo dummies in both groups). In both groups additional antibiotic treatment was subsequently prescribed as necessary for persistent, worsening, or recurrent symptoms. The primary endpoints were the number of all courses of antibiotic treatment on days 0-28 (for UTI or other conditions) and burden of symptoms on days 0-7. The symptom score included dysuria, frequency/urgency, and low abdominal pain. Study answer and limitations The 248 women in the ibuprofen group received significantly fewer course of antibiotics, had a significantly higher total burden of symptoms, and more had pyelonephritis. Four serious adverse events occurred that lead to hospital referrals; one of these was potentially related to the trial drug. Results have to be interpreted carefully as they might apply to women with mild to moderate symptoms rather than to all those with an uncomplicated UTI. What this paper adds Two thirds of women with uncomplicated UTI treated symptomatically with ibuprofen recovered without any antibiotics. Initial symptomatic treatment is a possible approach to be discussed with women willing to avoid immediate antibiotics and to accept a somewhat higher burden of symptoms. Funding, competing interests, data sharing German Federal Ministry of Education and Research (BMBF) No 01KG1105. Patient level data are available from the corresponding author. Patient consent was not obtained but the data are anonymised and risk of identification is low. Trial registration No ClinicalTrialGov Identifier NCT01488955.

Background: Uncomplicated lower urinary tract infections (UTI) are usually treated with antibiotics. However, there is little evidence for alternative therapeutic options. This pilot study was set out 1) to make a rough estimate of the equivalence of ibuprofen and ciprofloxacin for uncomplicated urinary tract infection with regard to symptom resolution, and 2) to demonstrate the feasibility of a double-blind, randomized controlled drug trial in German general practices. Methods: We performed a double-blind, randomized controlled pilot trial in 29 German general practices. Eighty otherwise healthy women aged 18 to 85 years, presenting with at least one of the main UTI symptoms dysuria and frequency and without any complicating factors, were randomly assigned to receive either ibuprofen 3 × 400 mg oral or ciprofloxacin 2 × 250 mg (+1 placebo) oral, both for three days. Intensity of main symptoms - dysuria, frequency, low abdominal pain - was recorded at inclusion and after 4, 7 and 28 days, scoring each symptom from 0 (none) to 4 (very strong). The primary endpoint was symptom resolution on Day 4. Secondary outcomes were the burden of symptoms on Days 4 and 7 (based on the sum score of all symptoms), symptom resolution on Day 7 and frequency of relapses. Equivalence margins for symptom burden on Day 4 were pre-specified as +/- 0.5 sum score points. Data analysis was done by intention to treat and per protocol. Randomization was carried out on patient level by computer programme in blocks of six. Results: Seventy-nine patients were analyzed (ibuprofen n = 40, ciprofloxacin n = 39). On Day 4, 21/36 (58.3%) of patients in the ibuprofen-group were symptom-free versus 17/33 (51.5%) in the ciprofloxacin-group. On Day 4, ibuprofen patients reported fewer symptoms in terms of total sum score (1; SD 1,42) than ciprofloxacin patients (1,3; SD 1,9), difference -0,33 (95% CI (-1,13 to +0,47)), PP (per protocol) analysis. During Days 0 and 9, 12/36 (33%) of patients in the ibuprofen-group received secondary antibiotic treatment due to ongoing or worsening symptoms, compared to 6/33 (18%) in the ciprofloxacin-group (non significant). A total of 58 non-serious adverse events were reported, 32 in the ibuprofen group versus 26 in the ciprofloxacin group (non significant). Conclusions: Our results support the assumption of non-inferiority of ibuprofen compared to ciprofloxacin for treatment of symptomatic uncomplicated UTI, but need confirmation by further trials. Trial registration: Trial registration number: ISRCTN00470468 See Commentary http://www.biomedcentral.com/1471-2296/11/42

Background Corticosteroids are widely used in the treatment of idiopathic facial paralysis (Bell's palsy), but the effectiveness of additional treatment with an antiviral agent is uncertain. This review was first published in 2001 and most recently updated in 2015. Since a significant benefit of corticosteroids for the early management of Bell's palsy has been demonstrated, the main focus of this update, as in the previous version, was to determine the effect of adding antivirals to corticosteroid treatment. We undertook this update to integrate additional evidence and to better assess the robustness of findings, taking risk of bias fully into account. Objectives To assess the effects of antiviral treatments alone or in combination with any other therapy for Bell's palsy. Search methods We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS in July 2019. We reviewed the bibliographies of the identified trials and contacted trial authors to identify additional published or unpublished data. We searched clinical trials registries for ongoing studies. Selection criteria We considered randomised controlled trials (RCTs) or quasi‐RCTs of antivirals with and without corticosteroids versus control therapies for the treatment of Bell's palsy. We excluded trials that followed‐up participants for less than three months. Data collection and analysis We independently assessed trials for relevance, eligibility, and risk of bias, using standard Cochrane procedures. We performed sensitivity analyses excluding trials at high or unclear risk of bias in at least five domains, and reported these data as the primary analyses. Main results Fourteen trials, including 2488 participants, met the inclusion criteria. Most were small, and most were at high or unclear risk of bias in multiple domains. We included four new studies at this update. Incomplete recovery A combination of antivirals and corticosteroids may have little or no effect on rates of incomplete recovery in people with Bell's palsy compared to corticosteroids alone (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.38 to 1.74; 3 trials, N = 766; random‐effects; low‐certainty evidence). We excluded 10 trials that were at high or unclear risk of bias in several domains from this analysis and limited all analyses to studies at lower risk of bias. Recovery rates were better in participants receiving corticosteroids alone than antivirals alone (RR 2.69, 95% CI 0.73 to 10.01; 2 trials, N = 667; random‐effects), but the result was imprecise and allowed for the possibility of no effect. The rate of incomplete recovery was lower with antivirals plus corticosteroids than with placebo or no treatment (RR 0.56, 95% CI 0.42 to 0.76; 2 trials, N = 658; random‐effects). Antivirals alone had no clear effect on incomplete recovery rates compared with placebo, but the result was imprecise (RR 1.10, 95% CI 0.87 to 1.40; 2 trials, N = 658; fixed‐effect). For people with severe Bell's palsy (House‐Brackmann score of 5 and 6, or equivalent on other scales), we found that the combination of antivirals and corticosteroids had no clear effect on incomplete recovery at month six compared to corticosteroids alone, although the result was again imprecise (RR 0.82, 95% CI 0.57 to 1.17; 2 trials, N = 98; random‐effects). Motor synkinesis or crocodile tears Antivirals plus corticosteroids reduced the proportion of participants who experienced these long‐term sequelae from Bell's palsy compared to placebo plus corticosteroids (RR 0.56, 95% CI 0.36 to 0.87; 2 trials, N = 469; fixed‐effect; moderate‐certainty evidence). Antivirals plus corticosteroids reduced long‐term sequelae compared to placebo but there was no clear difference in this outcome with antivirals alone compared to placebo. Adverse events Adverse event data were available in four studies providing data on 1592 participants. None of the four comparisons showed clear differences in adverse events between treatment and comparison arms (very low‐certainty evidence); for the comparison of antivirals plus corticosteroids and corticosteroids alone in studies at lower risk of bias, the RR was 1.17 (95% CI 0.81 to 1.69; 2 trials, N = 656; fixed‐effect; very low‐certainty evidence). Authors' conclusions The combination of antivirals and corticosteroids may have little or no effect on rates of incomplete recovery in comparison to corticosteroids alone in Bell's palsy of various degrees of severity, or in people with severe Bell's palsy, but the results were very imprecise. Corticosteroids alone were probably more effective than antivirals alone and antivirals plus corticosteroids were more effective than placebo or no treatment. There was no clear benefit from antivirals alone over placebo. The combination of antivirals and corticosteroids probably reduced the late sequelae of Bell's palsy compared with corticosteroids alone. Studies also showed fewer episodes of long‐term sequelae in corticosteroid‐treated participants than antiviral‐treated participants. We found no clear difference in adverse events from the use of antivirals compared with either placebo or corticosteroids, but the evidence is too uncertain for us to draw conclusions. An adequately powered RCT in people with Bell’s palsy that compares different antiviral agents may be indicated.

Guideline recommendations on therapy in urinary tract infections are based on antibiotic resistance rates. Due to a lack of surveillance data, little is known about resistance rates in uncomplicated urinary tract infection (UTI) in general practice in Germany. In a prospective observational study, urine cultures of all women presenting with urinary tract infections in general practice were analysed. Resistance rates against antibiotics recommended in German guidelines on UTI are presented.

PRagmatic Explanatory Continuum Indicator Summary (PRECIS)-2 is a tool that could improve design insight for trialists. Our aim was to validate the PRECIS-2 tool, unlike its predecessor, testing the discriminant validity and interrater reliability. Over 80 international trialists, methodologists, clinicians, and policymakers created PRECIS-2 helping to ensure face validity and content validity. The interrater reliability of PRECIS-2 was measured using 19 experienced trialists who used PRECIS-2 to score a diverse sample of 15 randomized controlled trial protocols. Discriminant validity was tested with two raters to independently determine if the trial protocols were more pragmatic or more explanatory, with scores from the 19 raters for the 15 trials as predictors of pragmatism. Interrater reliability was generally good, with seven of nine domains having an intraclass correlation coefficient over 0.65. Flexibility (adherence) and recruitment had wide confidence intervals, but raters found these difficult to rate and wanted more information. Each of the nine PRECIS-2 domains could be used to differentiate between trials taking more pragmatic or more explanatory approaches with better than chance discrimination for all domains. We have assessed the validity and reliability of PRECIS-2. An elaboration study and web site provide guidance to help future users of the tool which is continuing to be tested by trial teams, systematic reviewers, and funders.