Ildikó Gágyor

Symptomatic treatment (ibuprofen) or antibiotics (ciprofloxacin) for uncomplicated urinary tract infection? - Results of a randomized controlled pilot trial

BackgroundUncomplicated 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.MethodsWe 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.ResultsSeventy-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).ConclusionsOur 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 registrationTrial registration number: ISRCTN00470468See Commentary http://www.biomedcentral.com/1471-2296/11/42

Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: randomised controlled trial

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.

Resistance profiles of urinary tract infections in general practice - an observational study

BackgroundGuideline 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.MethodsIn a prospective, multi-center observational study general practitioner included all female patients ≥ 18 years with clinically suspected urinary tract infection. Only patients receiving an antibiotic therapy within the last two weeks were excluded.Results40 practices recruited 191 female patients (mean age 52 years; range 18–96) with urinary tract infections. Main causative agent was Escherichia coli (79%) followed by Enterococcus faecalis (14%) and Klebsiella pneumoniae (7.3%).Susceptibiliy of E.coli as the main causative agent was highest against fosfomycin and nitrofurantoin, with low resistance rates of 4,5%; 2,2%. In 17,5%, E.coli was resistant to trimethoprim and in 8,5% to ciprofloxacin.ConclusionsResistance rates of uropathogens from unselected patients in general practice differ from routinely collected laboratory data. These results can have an impact on antibiotic prescribing and treatment recommendations.

Immediate versus conditional treatment of uncomplicated urinary tract infection - a randomized-controlled comparative effectiveness study in general practices

BackgroundUncomplicated urinary tract infections (UTI) are usually treated with antibiotics as recommended by primary care guidelines. Antibiotic treatment supports clinical cure in individual patients but also leads to emerging resistance rates in the population. We designed a comparative effectiveness study to investigate whether the use of antibiotics for uncomplicated UTI could be reduced by initial treatment with ibuprofen, reserving antibiotic treatment to patients who return due to ongoing or recurrent symptoms.Methods/designThis is a randomized-controlled, double-blind, double dummy multicentre trial assessing the comparative effectiveness of immediate vs. conditional antibiotic therapy in uncomplicated UTI. Women > 18 and < 65 years, presenting at general practices with at least one of the typical symptoms dysuria or frequency/urgency of micturition, will be screened and enrolled into the trial. During an 18- months recruitment period, a total of 494 patients will have to be recruited in 45 general practices in Lower Saxony. Participating patients receive either immediate antibiotic therapy with fosfomycin-trometamol 1x3g or initial symptomatic treatment with ibuprofen 3x400mg for 3 days. The ibuprofen group will be provided with antibiotic therapy only if needed, i.e. for persistent or worsening symptoms. For a combined primary endpoint, we choose the number of all antibiotic prescriptions regardless of the medical indication day 0–28 and the “disease burden”, defined as a weighted sum of the daily total symptom scores from day 0 to day 7. The study is considered positive if superiority of conditional antibiotic treatment with respect to the first primary endpoint and non-inferiority of conditional antibiotic treatment with respect to the second primary endpoint is proven.DiscussionThis study aims at investigating whether the use of antibiotics for uncomplicated UTI could be reduced by initial treatment with ibuprofen. The comparative effectiveness design was chosen to prove the effectiveness of two therapeutic strategies instead of the pure drug efficacy.Trial registrationClinicaltrials.Gov: NCT01488955

The PRECIS-2 tool has good interrater reliability and modest discriminant validity

OBJECTIVES 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. STUDY DESIGN AND SETTING 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. RESULTS 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. CONCLUSION 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.

Frequency and perceived severity of negative experiences during medical education in Germany--results of an online-survery of medical students.

Aims: Negative experiences during the course of medical education have been reported in many countries, but little is known about the perceived severity of these experiences. We studied for the first time how often students at a medical university in Germany have had negative experiences, and how severe they perceive these to be. Method: We asked medical students in an online survey whether they felt adequately appreciated, had experienced peer rivalry, verbal abuse by their mentors, physical abuse or mistreatment, sexual harassment, racial or ethnic discrimination, or any other kind of mistreatment. Results: Of 391 students, 56% stated that they felt insufficiently appreciated, 51% had experienced rivalry, and 34% had suffered verbal abuse. Fifty-nine percent of the students felt highly aggrieved because of verbal abuse, while 46% were aggrieved by the ongoing rivalry and 32% by the lack of appreciation. Significantly fewer students felt upset because they were passed over or ignored (21%). Generally, female students felt more often aggrieved by these negative experiences than their male colleagues. Conclusion: Of the possible negative experiences, the less prominent ones such as lack of appreciation or verbal abuse are not only frequent, they are also perceived as very upsetting. Medical teachers should reflect this more in their day-to-day dealings with students and aim to improve on their contact with the students accordingly.

Breaking bad news – an interdisciplinary curricular teaching-concept

Background: The concerns of patients suffering from life-threatening disease and end-of-life care aspects have gained increasing attention in public perception. The increasing focus on palliative medicine questions can be considered to be paradigmatic for this development. Palliative medicine became a compulsory subject of the undergraduate curriculum in Germany to be implemented until 2013. The preexisting conditions and qualifications at the medical faculties vary, though. We describe the conceptual process, didactic background, and first experiences with the new interdisciplinary course “Delivering bad news” as a compulsory part of the palliative medicine curriculum. Methods: Since autumn 2009, this course has been taught at the University Medical Center Göttingen, consisting of two double lessons in the final year of medical education. Considering the curriculum-based learning goals in Göttingen, the focus of this course is to impart knowledge, attitudes and communication skills relating to “bad news”. Results: Although the seminar requires adequate staff and is time-consuming, students have accepted it and gave high marks in evaluations. In particular, the teachers’ performance and commitment was evaluated positively. Discussion and Conclusions: We describe the first experiences with a new course. Didactic structure, theoretical contents, role-plays and usage of media (film, novel) are well- suited to communicate topics such as “bad news”. Additional experiences and evaluations are necessary. According to the progressive nature of learning, it might be worthwhile to repeat communication- centered questions several times during medical studies.

Original ArticleThe PRECIS-2 tool has good interrater reliability and modest discriminant validity

OBJECTIVES 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. STUDY DESIGN AND SETTING 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. RESULTS 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. CONCLUSION 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.

Antiviral Agents Added to Corticosteroids for Early Treatment of Adults With Acute Idiopathic Facial Nerve Paralysis (Bell Palsy).

CLINICAL QUESTION Compared with oral corticosteroids alone, are oral antiviral drugs associated with improved outcomes when combined with oral corticosteroids in patients presenting within 72 hours of the onset of Bell palsy? BOTTOM LINE Compared with oral corticosteroids alone, the addition of acyclovir, valacyclovir, or famcyclovir to oral corticosteroids for treatment of Bell palsy was associated with a higher proportion of people who recovered at 3- to 12-month follow-up. The quality of evidence is limited by heterogeneity, imprecision of the result estimates, and risk of bias.

[End of life care in general practice: results of an observational survey with general practitioners].

BACKGROUND Little is known about the amount of end of life care provided by general practitioners (GPs) in Germany. Therefore the aim of the HAVEL study is to describe the involvement of GPs in end of life care in more detail. METHODS Data from all patients who died from natural causes within a period of 12 months (n = 452) were collected from 30 general practices with a self-developed questionnaire and compared to data from patients who died in hospice or palliative care units. RESULTS Contact rates with GPs increased at the end of life and approximately half of the patients (48 %) were seen within 48 h prior to death. A different spectrum of diseases and symptoms were observed compared to hospice and palliative care units with predominantly chronic diseases (e.g. cardiovascular and mental diseases). DISCUSSION AND CONCLUSIONS General practitioners are highly involved in palliative health care, even for patients who eventually die in hospitals. Differences in patient characteristics and circumstances compared to specialized palliative care should be reflected in curricula for training in palliative care and the definition of a palliative situation.