Recommendations for the Outpatient Drug Treatment of Patients With COVID-19.

BACKGROUND: One of the purposes of outpatient treatment for COVID-19 patients is to prevent severe disease courses and hospitalization. There is a need for evidence-based recommendations to be applied in primary care and specialized outpatient settings. METHODS: This guideline was developed on the basis of publications that were retrieved by a systematic search for randomized controlled trials in the Cochrane COVID-19 trial registry. The quality of evidence was assessed with GRADE, and structured consensus generation was carried out with MAGICapp. RESULTS: Unvaccinated COVID-19 outpatients with at least one risk factor for a severe disease course may be treated in the early phase of the disease with sotrovimab, remdesivir, or nirmatrelvir/ritonavir. Molnupiravir may also be used for such patients if no other clinically appropriate treatment options are available. Immunosuppressed persons with COVID-19 who are at high risk, and whose response to vaccination is expected to be reduced, ought to be treated with sotrovimab. It should be noted, however, that the clinical efficacy of sotrovimab against infections with the omicron subtype BA.2 is uncertain at the currently used dose, as the drug has displayed reduced activity against this subtype in vitro. COVID-19 patients at risk of a severe course may be offered budesonide inhalation, according to an off-label recommendation of the German College of General Practitioners and Family Physicians (other medical societies do not recommend either for or against this treatment). Thrombo - embolism prophylaxis with low-molecular-weight heparin may be given to elderly patients or those with a pre-existing illness. No recommendation is made concerning fluvoxamine or colchicine. Acetylsalicylic acid, azithromycin, ivermectin, systemic steroids, and vitamin D should not be used for the outpatient treatment of COVID-19. CONCLUSION: Drug treatment is now available for outpatients with COVID-19 in the early phase. Nearly all of the relevant trials have been conducted in unvaccinated subjects; this needs to be kept in mind in patient selection.

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.

Antibiotics for community-acquired pneumonia in adult outpatients.

BACKGROUND: Lower respiratory tract infection (LRTI) is the third leading cause of death worldwide and the first leading cause of death in low-income countries. Community-acquired pneumonia (CAP) is a common condition that causes a significant disease burden for the community, particularly in children younger than five years, the elderly and immunocompromised people. Antibiotics are the standard treatment for CAP. However, increasing antibiotic use is associated with the development of bacterial resistance and side effects for the patient. Several studies have been published regarding optimal antibiotic treatment for CAP but many of these data address treatments in hospitalised patients. This is an update of our 2009 Cochrane Review and addresses antibiotic therapies for CAP in outpatient settings. OBJECTIVES: To compare the efficacy and safety of different antibiotic treatments for CAP in participants older than 12 years treated in outpatient settings with respect to clinical, radiological and bacteriological outcomes. SEARCH METHODS: We searched CENTRAL (2014, Issue 1), MEDLINE (January 1966 to March week 3, 2014), EMBASE (January 1974 to March 2014), CINAHL (2009 to March 2014), Web of Science (2009 to March 2014) and LILACS (2009 to March 2014). SELECTION CRITERIA: We looked for randomised controlled trials (RCTs), fully published in peer-reviewed journals, of antibiotics versus placebo as well as antibiotics versus another antibiotic for the treatment of CAP in outpatient settings in participants older than 12 years of age. However, we did not find any studies of antibiotics versus placebo. Therefore, this review includes RCTs of one or more antibiotics, which report the diagnostic criteria and describe the clinical outcomes considered for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors (LMB, TJMV) independently assessed study reports in the first publication. In the 2009 update, LMB performed study selection, which was checked by TJMV and MMK. In this 2014 update, two review authors (SP, SM) independently performed and checked study selection. We contacted trial authors to resolve any ambiguities in the study reports. We compiled and analysed the data. We resolved differences between review authors by discussion and consensus. MAIN RESULTS: We included 11 RCTs in this review update (3352 participants older than 12 years with a diagnosis of CAP); 10 RCTs assessed nine antibiotic pairs (3321 participants) and one RCT assessed four antibiotics (31 participants) in people with CAP. The study quality was generally good, with some differences in the extent of the reporting. A variety of clinical, bacteriological and adverse events were reported. Overall, there was no significant difference in the efficacy of the various antibiotics. Studies evaluating clarithromycin and amoxicillin provided only descriptive data regarding the primary outcome. Though the majority of adverse events were similar between all antibiotics, nemonoxacin demonstrated higher gastrointestinal and nervous system adverse events when compared to levofloxacin, while cethromycin demonstrated significantly more nervous system side effects, especially dysgeusia, when compared to clarithromycin. Similarly, high-dose amoxicillin (1 g three times a day) was associated with higher incidence of gastritis and diarrhoea compared to clarithromycin, azithromycin and levofloxacin. AUTHORS' CONCLUSIONS: Available evidence from recent RCTs is insufficient to make new evidence-based recommendations for the choice of antibiotic to be used for the treatment of CAP in outpatient settings. Pooling of study data was limited by the very low number of studies assessing the same antibiotic pairs. Individual study results do not reveal significant differences in efficacy between various antibiotics and antibiotic groups. However, two studies did find significantly more adverse events with use of cethromycin as compared to clarithromycin and nemonoxacin when compared to levofloxacin. Multi-drug comparisons using similar administration schedules are needed to provide the evidence necessary for practice recommendations. Further studies focusing on diagnosis, management, cost-effectiveness and misuse of antibiotics in CAP and LRTI are warranted in high-, middle- and low-income countries.

German medical students' exposure and attitudes toward pharmaceutical promotion: a cross-sectional survey.

OBJECTIVE: Early contact of medical students with pharmaceutical promotion has been shown in many international studies. We assessed the frequency and places of contact of German medical students to pharmaceutical promotion and examined their attitudes toward pharmaceutical promotional activities. METHODS: This cross-sectional survey was based on a self-developed questionnaire. It was distributed to all clinical students at the University of Goettingen Medical School in 2010. A 4-point rating scale was used to assess the attitudes toward different statements regarding pharmaceutical promotion. RESULTS: The overall response rate was 55% (702/1287). The proportion of students with direct contact to pharmaceutical sales representatives increased from 21% in the first clinical year up to 77% in the final year. 60% were contacted during their elective clerkship. 80% had accepted promotional gifts. 86% stated their prescribing behavior to be unsusceptible to the influence of accepting promotional gifts. However, 35% of the unsusceptible students assumed doctors to be susceptible. Almost all (90%) reported that dealing with pharmaceutical promotion was never addressed during lectures and 65% did not feel well prepared for interactions with the pharmaceutical industry. 19% agreed to prohibit contacts between medical students and the pharmaceutical industry. CONCLUSIONS: German medical students get in contact with pharmaceutical promotion early and frequently. There is limited awareness for associated conflicts of interests. Medical schools need to regulate contacts and incorporate the topic in their curriculum to prepare students for interactions with the pharmaceutical industry.

Low back pain patient subgroups in primary care: pain characteristics, psychosocial determinants, and health care utilization.

OBJECTIVES: In industrialized countries, low back pain (LBP) is one of the leading causes for prolonged sick leave, early retirement, and high health care costs. Providing the same treatments to all patients is neither effective nor feasible, and may impede patients' recovery. Recent studies have outlined the need for subgroup-specific treatment allocation. METHODS: This is a cross-sectional study that used baseline data from consecutively recruited patients participating in a guideline implementation trial regarding LBP in primary care. Classification variables were employment status, age, pain intensity, functional capacity (HFAQ), depression (CES-D), belief that activity causes pain (FABQ subscale), 2 scales of the SF-36 (general health, vitality), and days in pain per year. We performed k-means cluster analyses and split-half cross-validation. Subsequently, we investigated whether the resulting groups incurred different direct and indirect costs during a 6-month period before the index consultation. RESULTS: A 4-cluster solution showed good statistical quality criteria, even after split-half cross-validation. "Elderly patients adapted to pain" (cluster 1) and "younger patients with acute pain" (cluster 4) accounted for 55% of all patients. Cluster validation showed the lowest direct and indirect costs in these groups. About 72% of total costs per patient referred to clusters 2 and 3 ("patients with chronic severe pain with comorbid depression" and "younger patients with subacute pain and emotional distress"). DISCUSSION: Our study adds substantially to the knowledge of LBP-related case-mix in primary care. Information on differential health care needs may be inferred from our study, enabling decision makers to allocate resources more appropriately and to reduce costs.

Fundoplication versus medical management of gastroesophageal reflux disease: systematic review and meta-analysis.

BACKGROUND: Medical, endoscopic, and open/laparoscopic surgical methods are used to treat gastroesophageal reflux disease (GERD). This study aimed to perform a systematic review of randomized controlled trials comparing medical and surgical treatments of GERD in adult patients. METHODS: For the study, MEDLINE and EMBASE (1980-2012) were searched. Two reviewers independently assessed methodologic aspects and extracted data from eligible studies, focusing on patient-relevant outcomes. The primary outcomes were health-related and GERD-specific quality-of-life aspects. Standardized mean differences (SMDs) between treatment groups were calculated and combined using random-effect meta-analysis. RESULTS: The study identified 11 publications reporting on 7 trials comparing surgical (open or laparoscopic) and medical treatment of GERD. Meta-analysis of both quality-of-life aspects showed a pooled-effect estimate in favor of fundoplication (SMD 0.18; 95 % confidence interval [CI] 0.01-0.35; SMD 0.33; 95 % CI 0.13-0.54). Heartburn and regurgitation were less frequent after surgical intervention. However, a considerable proportion of patients still needed antireflux medication after fundoplication. Nevertheless, the surgical patients were significantly more satisfied with their symptom control and showed higher satisfaction with the treatment received. CONCLUSIONS: This systematic review showed that surgical management of GERD is more effective than medical management with respect to patient-relevant outcomes in the short and medium term. However, long-term studies still are needed to determine whether antireflux surgery is an equivalent alternative to lifelong medical treatment.

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

BACKGROUND: Uncomplicated 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/DESIGN: This 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. DISCUSSION: This 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.

Implementation of a guideline for low back pain management in primary care: a cost-effectiveness analysis.

STUDY DESIGN: Cost-effectiveness analysis alongside a cluster randomized controlled trial. OBJECTIVE: To study the cost-effectiveness of 2 low back pain guideline implementation (GI) strategies. SUMMARY OF BACKGROUND DATA: Several evidence-based guidelines on management of low back pain have been published. However, there is still no consensus on the effective implementation strategy. Especially studies on the economic impact of different implementation strategies are lacking. METHODS: This analysis was performed alongside a cluster randomized controlled trial on the effectiveness of 2 GI strategies (physician education alone [GI] or physician education in combination with motivational counseling [MC] by practice nurses)--both compared with the postal dissemination of the guideline (control group, C). Sociodemographic data, pain characteristics, and cost data were collected by interview at baseline and after 6 and 12 months. low back pain-related health care costs were valued for 2004 from the societal perspective. RESULTS: For the cost analysis, 1322 patients from 126 general practices were included. Both interventions showed lower direct and indirect costs as well as better patient outcomes during follow-up compared with controls. In addition, both intervention arms showed superiority of cost-effectiveness to C. The effects attenuated when adjusting for differences of health care utilization prior to patient recruitment and for clustering of data. CONCLUSION: Trends in cost-effectiveness are visible but need to be confirmed in future studies. Researchers performing cost-evaluation studies should test for baseline imbalances of health care utilization data instead of judging on the randomization success by reviewing non-cost parameters like clinical data alone.

Serum levels of interleukin-6 and interleukin-10 in relation to depression scores in patients with cardiovascular risk factors.

It is currently unknown whether elevated cytokine levels in depression are confined to any specific subgroup of depressive patients. In this study, medical out-patients presenting with cardiovascular risk factors (N = 356) were assessed for both cognitive-affective and physical symptoms of depression using the Hospital Anxiety and Depression Scale (HADS) and the Maastricht questionnaire (MQ), respectively. In study participants assigned to the highest (≥21) and lowest (≤5) quartile for the MQ score, serum levels of cytokines were measured. We found highly significant associations between cognitive-affective symptoms of depression and elevated serum levels of interleukin-6 (IL-6; ρ = .231; p = .002) and interleukin-10 (IL-10; ρ = .370; p < .001), respectively. In multiple regression models elevated IL-10 serum concentration was independently related to cognitive-affective symptoms of depression (ρ = .165; p = .002). When all cytokines were included in one model, elevated IL-10 serum concentrations remained a significant predictor for depressive mood (ρ = .157; p = .009). In patients with cardiovascular risk factors and extreme scores for vital exhaustion, elevated serum IL-6 and even more IL-10 concentrations are linked to the presence of depressive mood. Future studies will have to test whether the so far unreported association of IL-10 with depressive mood represents a causal pathway involved in the pathogenesis or in the prognostic effect of depressive mood in cardiac patients.

Practices, patients and (im)perfect data--feasibility of a randomised controlled clinical drug trial in German general practices.

BACKGROUND: Randomised controlled clinical (drug) trials supply high quality evidence for therapeutic strategies in primary care. Until now, experience with drug trials in German general practice has been sparse. In 2007/2008, the authors conducted an investigator-initiated, non-commercial, double-blind, randomised controlled pilot trial (HWI-01) to assess the clinical equivalence of ibuprofen and ciprofloxacin in the treatment of uncomplicated urinary tract infection (UTI). Here, we report the feasibility of this trial in German general practices and the implementation of Good Clinical Practice (GCP) standards as defined by the International Conference on Harmonisation (ICH) in mainly inexperienced general practices. METHODS: This report is based on the experience of the HWI-01 study conducted in 29 German general practices. Feasibility was defined by 1) successful practice recruitment, 2) sufficient patient recruitment, 3) complete and accurate data collection and 4) appropriate protection of patient safety. RESULTS: The final practice recruitment rate was 18%. In these practices, 79 of 195 screened UTI patients were enrolled. Recruitment differed strongly between practices (range 0-12, mean 2.8 patients per practice) and was below the recruitment goal of approximately 100 patients. As anticipated, practice nurses became the key figures in the screening und recruitment of patients. Clinical trial demands, in particular for completing symptom questionnaires, documentation of source data and reporting of adverse events, did not agree well with GPs' documentation habits and required support from study nurses. In many cases, GPs and practice staff seemed to be overwhelmed by the amount of information and regulations. No sudden unexpected serious adverse reactions (SUSARs) were observed during the trial. CONCLUSIONS: To enable drug trials in general practice, it is necessary to adapt the setup of clinical research infrastructure to the needs of GPs and their practice staff. Risk adaption of clinical trial regulations is necessary to facilitate non-commercial comparative effectiveness trials in primary health care. TRIAL REGISTRATION NUMBER: ISRCTN00470468.

The association between a journal's source of revenue and the drug recommendations made in the articles it publishes.

BACKGROUND: There is evidence to suggest that pharmaceutical companies influence the publication and content of research papers. Most German physicians rely on journals for their continuing medical education. We studied the influence of pharmaceutical advertising on the drug recommendations made in articles published in 11 German journals that focus on continuing medical education. METHODS: We conducted a cross-sectional study of all of the issues of 11 journals published in 2007. Only journals frequently read by general practitioners were chosen. Issues were screened for pharmaceutical advertisements and recommendations made in the editorial content for a specified selection of drugs. Each journal was rated on a five-point scale according to the strength with which it either recommended or discouraged the use of these drugs. We looked for differences in these ratings between free journals (i.e., those financed entirely by pharmaceutical advertising), journals with mixed sources of revenue and journals financed solely by subscription fees. The journals were also screened for the simultaneous appearance of advertisements and recommendations for the same drug within a certain period, which was adjusted for both journal and class of drug. RESULTS: We identified 313 issues containing at least one advertisement for the selected drugs and 412 articles in which drug recommendations were made. Free journals were more likely to recommend the specified drugs than journals with sources of revenue that were mixed or based solely on subscriptions. The simultaneous appearance of advertisements and recommendations for the same drug in the same issue of a journal showed an inconsistent association. INTERPRETATION: Free journals almost exclusively recommended the use of the specified drugs, whereas journals financed entirely with subscription fees tended to recommend against the use of the same drugs. Doctors should be aware of this bias in their use of material published in medical journals that focus on continuing medical education.

Sensitivity to change of the Neck Pain and Disability Scale.

The Neck Pain and Disability Scale (NPAD) is a 20-item instrument to measure neck pain and related disability. The aim of this study was to assess sensitivity to change of the NPAD. A total of 411 participants from 15 general practices in the middle of Germany completed a multidimensional questionnaire including the German version of the NPAD and self-reported demographic and clinical information. Sensitivity to change was analysed by linear regression analysis of the NPAD at follow-up and educational level, age class, depression, anxiety, and deficits in social support, respectively, and by Pearson's correlation analyses between mean change in NPAD at follow-up and mean change in prognostic markers. Those having more than basic education (regression coefficient -7.2, p < 0.001) and/or being in a younger age class (-2.9, p = 0.020) consistently reported significantly lower average NPAD scores at follow-up compared to those with basic education and/or a older age class. In contrast, those who were classified to be depressed (regression coefficient 2.1, p < 0.001), anxious (1.9, p < 0.001), or having deficits in social support (5.5, p = 0.004) reported significantly higher NPAD scores. Change in depression, anxiety, and social support scale between baseline and follow-up was significantly correlated with change in the NPAD score. Hence, these data are in the direction anticipated across all baseline factors investigated. In conclusion, the NPAD seems to be a sensitive measure for use in clinical practice and future studies of neck pain and related disability.

Appropriateness of treatment recommendations for PPI in hospital discharge letters.

PURPOSE: The reasons for the dramatic increase in proton pump inhibitors (PPI) prescriptions remain unclear and cannot be explained solely by increased morbidity, new indications or a decrease in alternative medication. Inappropriate use and discharge recommendations in hospitals are considered to be possible explanations. As the quality of PPI recommendations in hospital discharge letters in Germany has not been investigated to date, we have studied the appropriateness of these referrals. METHODS: Hospital discharge letters with recommendations for PPI medication from 35 primary care practices in the county of Mecklenburg-Western Pomerania (MV; North-east Germany) were collected and analysed, and the appropriateness of the PPI indication was rated. RESULTS: No information justifying the recommendation for continuous PPI medication could be identified in 54.5% of the discharge letters; in 12.7%, the indication was uncertain, and in 32.7%, we found an evidence-based indication for PPI medication. The most common indication for adequate PPI use was nonsteroidal anti-inflammatory drug-prophylaxis in high-risk patients. CONCLUSIONS: Inadequate recommendations for PPIs in discharge letters are frequent. This may lead to a continuation of this therapy in primary care, thereby unnecessarily increasing polypharmacy and the risk of adverse events as well as burdening the public health budget. Hospitals should therefore critically review recommendations for PPI medication and the dosage thereof in their discharge letters and clearly document the reason for PPI use and the need for continuous prescription in primary care.

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

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 x 400 mg oral or ciprofloxacin 2 x 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 NUMBER: ISRCTN00470468. See Commentary http://www.biomedcentral.com/1471-2296/11/42.

Elevated serum levels of interleukin-10 and tumor necrosis factor α [corrected] are both associated with vital exhaustion in patients with cardiovascular risk factors.

BACKGROUND: Vital exhaustion, a psychological state characterized by unusual fatigue, irritability, and feelings of demoralization, has been identified as a risk factor for cardiovascular diseases and linked to elevated levels of pro-inflammatory cytokines. OBJECTIVE: The purpose of this study was to investigate the relationship between vital exhaustion and cytokine levels in patients with cardiovascular risk factors. METHOD: The entire cohort consisted of 356 primary-care patients with cardiovascular risk factors who participated in a study of early recognition of heart failure. All participants completed the Maastricht questionnaire (MQ) for assessing vital exhaustion. Cytokine serum levels were measured in all those subjects (N=178) who were assigned to the highest and lowest quartiles of the MQ, respectively. RESULTS: We found that elevated serum concentrations of IL-6, TNFα, and IL-10, but not IL-1ß or natriuretic peptides were associated with high MQ scores indicative of vital exhaustion. Using logistic regression analyses controlling for clinical variables and Type D personality, both TNFα (multivariate odds ratio [OR] =1.86; 95%-confidence interval [CI] =1.30-2.68; p=0.001) and IL-10(OR=1.62; 95%-CI=1.15-2.28; p=0.006), but not other cytokines significantly predicted vital exhaustion independently of other clinical and laboratory parameters examined [corrected]. CONCLUSION: The subjective state of vital exhaustion is linked to a substantial alteration in the pattern of secreted cytokines. Data suggest that a disturbance in the levels of both pro-inflammatory and anti-inflammatory mediators, rather than isolated stimulation by pro-inflammatory cytokines, is associated with the mental and physical changes of vital exhaustion.