The association between bacteriuria and adverse pregnancy outcomes: a systematic review and meta-analysis of observational studies.

BACKGROUND: Antibiotics for bacteriuria and urinary tract infection are commonly prescribed during pregnancy to avoid adverse pregnancy outcomes. The aim of this study was to evaluate the association between significant bacteriuria in pregnancy and any of the four pregnancy outcomes: preterm delivery; low birth weight; small for gestational age; and preterm labour. METHODS: Systematic review with meta-analysis of observational studies. We searched PubMed, EMBASE, the Cochrane CENTRAL library, and Web of Science for observational studies published before 1 March 2022. The risk of bias was assessed using the Newcastle-Ottawa scale. Study identification, data extraction and risk-of-bias assessment was performed by two independent authors. We combined the included studies in meta-analyses and expressed results as ORs with 95% CIs (Prospero CRD42016053485). RESULTS: We identified 58 studies involving 421 657 women. The quality of the studies was mainly poor or fair. The pooled, unadjusted OR for the association between any significant bacteriuria and: (i) preterm delivery was 1.62 (95% CI: 1.30-2.01; 27 studies; I2 = 61%); (ii) low birth weight was 1.50 (95% CI: 1.30-1.72; 47 studies; I2 = 74%); (iii) preterm labour was 2.29 (95% CI: 1.53-3.43; 3 studies; I2 = 0%); and (iv) small for gestational age was 1.33 (95% CI: 0.88-2.02; 7 studies; I2 = 54%). Four studies provided an adjusted OR, but were too diverse to combine in meta-analysis. CONCLUSIONS: This systematic review identified an association between significant bacteriuria in pregnancy and the three complications: preterm delivery; low birth weight; and preterm labour. However, the quality of the available evidence is insufficient to conclude whether this association is merely due to confounding factors. There is a lack of high-quality evidence to support active identification and treatment of bacteriuria in pregnancy.

Factors promoting and impeding efforts to deprescribe antidepressants among nursing home residents with dementia- a process evaluation guided by normalization process theory.

BACKGROUND: Despite recommendations against psychotropic medication in older nursing homes residents with behavioral and psychological symptoms of dementia (BPSD), antidepressants and other psychotropic drugs are still prescribed. We performed a cluster-randomized controlled trial to evaluate the effect of a complex intervention aiming to promote the deprescribing of antidepressants in institutionalized older persons with dementia. To understand the underlying mechanisms of trial outcomes, we conducted a process evaluation exploring the interventions implementation, areas of impact, and contextual factors. The aim of this study was to explore the implementation process and the key factors that promoted and inhibited intervention implementation in the care home setting (Clinicaltrials.gov: NCT04985305. Registered 30 July 2021). METHODS: Qualitative interviews were conducted between August 2022 and February 2023 with four general practitioners and eight nursing home staff from four associated nursing homes in the Capital Region of Denmark. We coded the interview data according to the four constructs of the Normalization Process Theory (coherence, cognitive participation, collective action, and reflexive monitoring). RESULTS: There was a common understanding of the intervention aim. We observed a raised awareness concerning the deprescription of antidepressants among healthcare professionals with good collaboration (coherence). An overall buy-in to a deprescribing mentality was seen (cognitive participation). There were barriers to the GPs and nursing home staff's use of the intervention elements and how they implemented it, but to some, a common language was created (collective action). Professionals overall valued the idea of deprescribing, but lack of time, high staff turnover, and low education level among nursing home staff hampered the integration (reflexive monitoring). CONCLUSION: Successful implementation seemed to be dependent on the quality of the relationship between the single GP and the single nursing home professional. A common deprescribing mentality promoted the uptake of the intervention. However, several barriers related to lack of resources hindered implementation. It is imperative to adapt complex interventions to the available resources and context.

Dose planning study of proton versus photon radiotherapy for head and neck squamous cell carcinoma of unknown primary in the primary and recurrent setting.

BACKGROUND: Patients with head and neck squamous cell carcinoma of unknown primary (HNCUP) are often treated with extensive radiotherapy (RT). Frequently, the bilateral nodal clinical target volume (nCTV) and the volumes of suspected mucosal primary sites (mCTV) of the pharynx and larynx is irradiated. This treatment is effective but toxic. New data suggest that omission of the contralateral nCTV and mCTV, results in few recurrences. The present study explores photon versus proton therapy, in the primary and recurrent setting. MATERIAL AND METHODS: An analysis of twelve patients previously treated for HNCUP was performed. A fictitious recurrence was defined in patients treated for unilateral disease. Independently a volumetric arc photon plan and an intensity-modulated proton plan was made for all cases and scenarios. RESULTS: Compared to the standard bilateral treatment this study shows that limiting the target to unilateral nCTV leads to a significant decrease in dysphagia of 18% and 17% and xerostomia of 4.0% and 5% for photon and protons, respectively. Comparing photon RT directly to proton RT shows a small and often insignificant gain, using protons for both bilateral and unilateral targets. Focusing on re-irradiation, benefits from using protons in both the primary setting and at re-irradiation were limited. However, using protons for re-irradiation only leads to a decrease in the tissue volume receiving a specific dose outside the target overlapping region, e.g., V90Gymean was 31, 25, and 22 cm3 for photons-photons, photons-protons, and protons-protons, respectively. For V100Gy of the ipsilateral carotid artery, no differences were observed. CONCLUSION: Omitting contralateral nCTV irradiation and mCTV irradiation will significantly reduce toxicity. The accumulated high dose volumes can be minimised using protons for re-irradiation. However, the use of protons for primary treatment provides limited benefit in most patients.

Consistency in contouring of organs at risk by artificial intelligence vs oncologists in head and neck cancer patients.

BACKGROUND: In the Danish Head and Neck Cancer Group (DAHANCA) 35 trial, patients are selected for proton treatment based on simulated reductions of Normal Tissue Complication Probability (NTCP) for proton compared to photon treatment at the referring departments. After inclusion in the trial, immobilization, scanning, contouring and planning are repeated at the national proton centre. The new contours could result in reduced expected NTCP gain of the proton plan, resulting in a loss of validity in the selection process. The present study evaluates if contour consistency can be improved by having access to AI (Artificial Intelligence) based contours. MATERIALS AND METHODS: The 63 patients in the DAHANCA 35 pilot trial had a CT from the local DAHANCA centre and one from the proton centre. A nationally validated convolutional neural network, based on nnU-Net, was used to contour OARs on both scans for each patient. Using deformable image registration, local AI and oncologist contours were transferred to the proton centre scans for comparison. Consistency was calculated with the Dice Similarity Coefficient (DSC) and Mean Surface Distance (MSD), comparing contours from AI to AI and oncologist to oncologist, respectively. Two NTCP models were applied to calculate NTCP for xerostomia and dysphagia. RESULTS: The AI contours showed significantly better consistency than the contours by oncologists. The median and interquartile range of DSC was 0.85 [0.78 - 0.90] and 0.68 [0.51 - 0.80] for AI and oncologist contours, respectively. The median and interquartile range of MSD was 0.9 mm [0.7 - 1.1] mm and 1.9 mm [1.5 - 2.6] mm for AI and oncologist contours, respectively. There was no significant difference in ΔNTCP. CONCLUSIONS: The study showed that OAR contours made by the AI algorithm were more consistent than those made by oncologists. No significant impact on the ΔNTCP calculations could be discerned.

Disentangling concepts of inappropriate polypharmacy in old age: a scoping review.

INTRODUCTION: Polypharmacy is a common concern, especially in the older population. In some countries more that 50% of all individuals over 60 receive five or more drugs, most often due to multimorbidity and increased longevity. However, polypharmacy is associated with multiple adverse events, and more medication may not always be the answer. The terms "appropriate" and "inappropriate" are often used to distinguish between "much" and "too much" medications in relation to polypharmacy in research and practice, but no explicit definition exists to describe what these terms encompass. The aim of this review is to unfold the different understandings of and perspectives on (in)appropriate polypharmacy and suggest a framework for further research and practice. METHOD: A scoping review was conducted using the framework of Arksey and O'Malley and Levac et al. Pubmed, Embase, PsycINFO, CINAHL, Cochrane database, Scopus and Web of Science were searched for references in English, Danish, Norwegian and Swedish using the search string "Polypharmacy" AND "Appropriate" OR "Inappropriate". Data was extracted on author information, aims and objectives, methodology, study population and setting, country of origin, main findings and implications, and all text including the words "appropriate," "inappropriate," and "polypharmacy." Qualitative meaning condensation analysis was used and data charted using descriptive and thematic analysis. RESULTS: Of 3982 references, a total of 92 references were included in the review. Most references were from 2016-2021, from fields related to medicine or pharmacy, and occurred within primary and secondary healthcare settings. Based on the qualitative analysis, a framework were assembled consisting of Context, three domains (Standardization, Practices and Values & Concerns) and Patient Perspective. CONCLUSION: Inappropriate polypharmacy is a concept loaded by its heterogeneity and the usefulness of a single definition is doubtful. Instead, the framework suggested in this article representing different dimensions of inappropriate polypharmacy may serve as an initial strategy for focusing research and practice on polypharmacy in old age.

Tailoring a complex intervention to reduce antidepressants in institutionalized older persons with dementia.

INTRODUCTION: First-line treatment for behavioral and psychiatric symptoms of dementia is non-pharmacological. Still, psychotropic medication is widely used, despite its limited effect and harmful side-effects. More than half of all nursing home residents with dementia receive antidepressants, even though deprescribing is safe and feasible. Interventions to promote deprescribing of antidepressants in nursing homes are few and complex. To optimize the deprescribing process through an intervention, transparency for the development of the intervention is needed. We aim to describe the steps in the development and tailoring of an intervention targeting GPs, nursing home staff, and relatives to enhance collaboration on reducing the use of antidepressants in institutionalized older persons with dementia in Denmark. METHOD: A step-wise process guided by the core elements in the Medical Research Council constituted the tailoring process. Five steps were included; 1) a literature search, 2) interviews with stakeholders, 3) drafting the intervention prototype, 4) professionals' assessment of the intervention, and 5) refinement of the intervention. The steps were conducted from June 2020 to June 2022. RESULTS: Based on the literature search, interviews with stakeholders, and professionals' assessment of the intervention, four main themes were identified; 1) focusing on antidepressants, 2) importance of professional qualifications, 3) collaboration and communication, and 4) patient and relative involvement. They guided intervention development and refinement of the final intervention, which included 1) a case-based training course and 2) a dialog tool including a symptom assessment scale to be used in a structured consultation at the nursing home. CONCLUSION: This study presents a detailed account of the tailoring process for a complex intervention to optimize deprescribing of antidepressants for older persons with dementia at nursing homes. By presenting a thorough development process, we expect to achieve increased adherence to the intervention which is currently being tested in an ongoing cluster randomized controlled trial. The transparency of the process will also increase the future development of other similar complex interventions.

Density calibrated cone beam CT as a tool for adaptive radiotherapy.

BACKGROUND: Visual inspections of anatomical changes observed on daily cone-beam CT (CBCT) images are often used as triggers for radiotherapy plan adaptation to avoid unacceptable dose levels to the target or OARs. Direct CBCT dose calculations would improve the ability to adapt only those plans where dosimetric changes are observed. This study investigates the accuracy of dose calculations on CBCTs. MATERIALS AND METHODS: Calibration curves were obtained for CBCT imagers at nine identical accelerators. CBCT scans of a phantom with different density inserts were recorded for two scan modes (Head-Neck and Pelvis) and mean calibration curves were calculated. Subsequently, CBCT scans of the phantom with six different density inserts were recorded, the dose distributions on the CBCTs were calculated and compared to dose on the planning CT (pCT). The uncertainty was quantified by the dosimetric difference between the pCT and the CBCT. The two mean calibration curves were used to calculate the daily delivered CBCT dose for ten Head-Neck-, eleven Lung-, and ten pelvic patients. Additional patient calculations were performed using low-HU empirically corrected calibration curves. Patient doses were compared on target coverage and mean dose, and D1cc for OARs. RESULTS: The dose differences between pCT and CBCT for phantom data were small for all DVH parameters, with mean deviations below ±0.6% for both CBCT modes. For patient data, it was found that low-HU corrected calibration curves performed the best. The mean deviations for the mean dose and coverage of the target were 0.2%±0.7% and 0.1%±0.6%, across all patient groups. CONCLUSION: Dose calculation on CBCT images results in target coverage and mean dose with an accuracy of the order of 1%, which makes this acceptable for clinical use. The CBCT mode specific calibration curves can be used at all identical imaging devices and for all patient groups.

Beneficial self-management support and user involvement in Healthy Life Centres-A qualitative interview study in persons afflicted by overweight or obesity.

BACKGROUND: Relapse is high in lifestyle interventions involving behavioural change and weight loss maintenance. The purpose of lifestyle self-management interventions offered at Healthy Life Centres (HLCs) is to empower the participants, leading to self-management and improved health. Exploring beneficial self-management support and user involvement in HLCs is critical for quality, improving effectiveness and guiding approaches to lifestyle change support in overweight and obesity. OBJECTIVE: The aim of this study was to explore how persons afflicted by overweight or obesity attending lifestyle interventions in Norwegian HLCs experience beneficial self-management support and user involvement. METHOD: Semi-structured in-depth interviews were conducted with 13 service users (5 men and 8 women). Data were analysed using qualitative content analysis. RESULTS: One main theme was identified: regaining self-esteem and dignity through active involvement and long-term self-worth support in partnership with others. This main theme comprised four themes: (a) self-efficacy through active involvement and better perceived health, (b) valued through health-care professionals (HPs) acknowledgement, equality and individualized support, (c) increased motivation and self-belief through fellowship and peer support; and (d) maintenance of lifestyle change through accessibility and long-term support. CONCLUSION: Service users' active involvement, acknowledgement and long-term self-worth support from HPs and peers seem to support self-management and user involvement and may be some of the successful ingredients to lifestyle change. However, prolonged follow-up support is needed. A collectivistic and long-term perspective can integrate the importance of significant others and shared responsibility.

Understanding beneficial self-management support and the meaning of user involvement in lifestyle interventions: a qualitative study from the perspective of healthcare professionals.

BACKGROUND: In light of the high prevalence of overweight and obesity among adults and the subsequent stigmatization and health consequences, there is a need to develop effective interventions to support lifestyle change. The literature supports the key role of healthcare professionals (HPs) in facilitating self-management through lifestyle interventions for those with chronic conditions. However, there is a lack of knowledge about how HPs practice self-management support (SMS) and user involvement for persons afflicted by overweight or obesity in lifestyle interventions in primary care Healthy Life Centres (HLC). The aim of this study was to explore how HPs provide SMS and what user involvement implies for HPs in HLCs. METHODS: An interpretative exploratory design, using qualitative thematic analysis of data from two focus group interviews with ten HPs from eight different HLCs, was conducted. RESULTS: The analysis resulted in one overall theme; A partnership based on ethical awareness, non-judgemental attitude, dialogue and shared responsibility, comprising four interrelated themes: 1) Supporting self-efficacy, self-worth and dignity through an attitude of respect, acknowledgement and generosity, 2) Promoting self-belief and self-perceived health, 3) Collaborating and sharing responsibility, and 4) Being flexible, adjusting and sharing time. CONCLUSION: HPs in HLCs see service users as equal partners in a collaboration based on shared responsibility, acknowledgement and generosity. In order to help, their practice involves a heightened level of ethical awareness, including a non-judgemental attitude and dialogue. HPs in HLCs have something to teach us about ethical acting and helping persons who are struggling with overweight or obesity to change their lifestyle and regain dignity. They seem to see the service users' existential needs and have learned the art of meeting the other in her/his most vulnerable situation i.e., seeking help for a "wrong lifestyle". It may be time to highlight the need for SMS and user involvement to focus on shared responsibility in partnership rather than personal responsibility. More research is required to explore the conditions for such practice.

Prescription of antibiotics for urinary tract infection in general practice in Denmark.

OBJECTIVE: The aim of this study was to describe and characterize the prescription of antibiotics for urinary tract infection (UTI) in general practice in Denmark and to evaluate compliance with current recommendations. DESIGN: National registry-based study Setting: Danish general practice Patients: 267.539 patients who redeemed a prescription for antibiotics with the clinical indication UTI at community pharmacies between July 1st 2012 and June 31st 2013. MAIN OUTCOME MEASURES: Antibiotics prescribed for 1) acute lower UTI, 2) acute upper UTI and 3) recurrent UTI presented as amount of prescriptions, number of treatments per 1000 inhabitants per day (TID) and defined daily doses per 1000 inhabitants per day (DID). RESULTS: A total of 507.532 prescriptions were issued to 267.539 patients during the one year study period, representing 2.35 DID. Acute lower UTI was the most common reason for prescription of antibiotics (89.5%) followed by recurrent UTI (8.4%). The majority of the prescriptions were issued to people above 60 year old (57.6%). Pivmecillinam was the most commonly prescribed antibiotic in acute lower (45.8%) and acute upper (63.3%) UTI. Trimethroprim was the most commonly prescribed antibiotic in recurrent UTI (45.9%). Prescription of quinolones increased with increasing patient-age (p = <.0001). CONCLUSION: Compliance with current Danish recommendations was moderately high. Pivmecillinam is the first line antibiotic for the management of acute lower and upper UTI, and trimethroprim is the first line option of recurrent UTI. A high proportion of the antibiotic prescriptions were issued in the elderly population including a relatively high prescription rate of quinolones. Key points Urinary tract infection (UTI) is a common cause for prescription of antibiotics in general practice Poor compliance in general practice with recommendations for first-line treatment of UTI may increase antibiotic resistance Danish general practitioners are generally compliant with national and regional guidelines for antibiotic treatment of UTI There is high use of antibiotics in the elderly population including a worrisome high use of broad-spectrum antibiotics, such as Quinolones.

Validity of microscopy for diagnosing urinary tract infection in general practice - a systematic review.

Objective: To investigate the validity of microscopy as a diagnostic tool for urinary tract infection in general practice. Methods: (Design/setting) A systematic review was conducted by searching Medline for clinical studies made in general practice, outpatient clinics or similar settings in which the accuracy/validity of microscopy was evaluated with urine culture as the reference standard. Results: Our search resulted in 108 titles. 28 potentially eligible studies were retrieved for full-text reading. We included eight studies involving 4582 patients in this review. The quality of the studies was moderate to high. Specificity ranged from 27% to 100%, sensitivity from 47% to 97%. The variation between studies did not allow for meta-analysis. Conclusion: We did not find substantial evidence to determine the clinical validity of microscopy performed in general practice on urine samples from patients with symptoms of UTI. Key points Urinary tract infection is common in general practice. Methods for precise diagnosis are needed in order to avoid inappropriate treatment. Currently no evidence-based consensus exists regarding the use of urinary microscopy in general practice. We did not find substantial evidence to determine the overall clinical validity of microscopy performed in general practice on urine samples from patients with symptoms of UTI. Light microscopy with oil immersion had high sensitivity and specificity but is time-consuming. Phase-contrast microscopy is quick and had high specificity but lower sensitivity.

Comparison of antibiotic prescribing and antimicrobial resistance in urinary tract infections at the municipal level among women in two Nordic regions.

Objectives: To describe and compare the prescribing of antibiotics used for urinary tract infections and its correlation with resistance in Escherichia coli in urinary samples across two adjacent regions-the Capital Region and the Skaane Region-and their municipalities in Denmark and Sweden. Methods: The Capital Region consists of 29 municipalities and 725 960 female inhabitants aged ≥18 years and the Skaane Region consists of 33 municipalities and 515 668 female inhabitants aged ≥18 years. Aggregated data from outpatient care on the prescribing of pivmecillinam, trimethoprim and nitrofurantoin from both regions were analysed. The Department of Clinical Microbiology in both regions provided data on E. coli resistance in urinary samples from women aged ≥18 years. Data were measured as the number of prescriptions/1000 women/year, number of DDDs/1000 women/year and DDDs/prescription. Correlation analyses between antibiotic prescribing and antibiotic resistance rates were performed. Results: Antibiotic prescribing and resistance rates were significantly higher in the Capital Region compared with the Skaane Region. Large variations in prescription and resistance rates were found at the municipal level, but there were no correlations between the antibiotic prescription and resistance rates when each region was analysed separately. Conclusions: Although closely related, there are large differences in antibiotic prescribing and antibiotic resistance. It is suggested that the regional guidelines are an important driver and explanatory factor for the variations; however, further research is needed in this new field and factors such as the influence of cultural aspects should be the target of further research.

Use of diagnostic tests and the appropriateness of the treatment decision in patients with suspected urinary tract infection in primary care in Denmark - observational study.

BACKGROUND: Inappropriate prescription of antibiotics is the leading driver of antimicrobial resistance (AMR). The majority of antibiotics are prescribed in primary care. Understanding how general practitioners (GPs) use diagnostic tests and the effect on treatment decision under daily practice conditions is important to reduce inappropriate prescription of antibiotics. The aim of the study was to investigate the use of diagnostic tests in primary care patients with suspected urinary tract infection (UTI) and to assess the appropriateness of the treatment decision (TD) under daily practice conditions in Denmark. METHODS: Prospective observational study. Symptomatic adult patients consulting general practice with suspected UTI recruited over 12 months. The diagnostic workup was registered in a standardized form. The appropriateness of the TD was assessed based on the results of a culture performed at a reference microbiological laboratory. TD was considered appropriate if a patient had a positive culture and was prescribed antibiotics or had a negative culture and was not prescribed antibiotics. TD was considered inappropriate if a patient had a negative culture and was prescribed antibiotics (overtreatment) or had a positive culture and was not prescribed antibiotics (undertreatment). RESULTS: Four hundred and eighty-eight patients were included. Dipstick was used in 98% of the patients and urine culture was used in 89% of the patients; 317 had the culture performed in practice and 117 had the culture performed at the hospital. The appropriateness of the final TD was significantly (p = 0.04) lower in patients without culture (55%) than in patients with culture performed in practice (71%) or at hospital (69%). CONCLUSION: In a context with wide availability of diagnostic tests, GPs use diagnostic tests for the decision-making process in all patients with suspected UTI. Urine culture is used in the majority of the patients and is associated with a higher proportion of appropriate treatment decisions. Performance of urine culture is therefore important in reducing inappropriate antibiotic prescribing in patients with suspected UTI seeking care in general practice in Denmark. TRIAL REGISTRATION: ClinicalTrials.gov NCT02249273 .

Characterization of Microfibrillar-associated Protein 4 (MFAP4) as a Tropoelastin- and Fibrillin-binding Protein Involved in Elastic Fiber Formation.

MFAP4 (microfibrillar-associated protein 4) is an extracellular glycoprotein found in elastic fibers without a clearly defined role in elastic fiber assembly. In the present study, we characterized molecular interactions between MFAP4 and elastic fiber components. We established that MFAP4 primarily assembles into trimeric and hexameric structures of homodimers. Binding analysis revealed that MFAP4 specifically binds tropoelastin and fibrillin-1 and -2, as well as the elastin cross-linking amino acid desmosine, and that it co-localizes with fibrillin-1-positive fibers in vivo. Site-directed mutagenesis disclosed residues Phe(241) and Ser(203) in MFAP4 as being crucial for type I collagen, elastin, and tropoelastin binding. Furthermore, we found that MFAP4 actively promotes tropoelastin self-assembly. In conclusion, our data identify MFAP4 as a new ligand of microfibrils and tropoelastin involved in proper elastic fiber organization.

Functional image-guided dose escalation in gliomas using of state-of-the-art photon vs. proton therapy.

BACKGROUND: Recurrences of glioma are usually local, suggesting the need for higher tumor dose. We investigated the boundaries for dose escalation of an 18F-fluoro-ethyl-tyrosine positron emission tomography defined target by intensity-modulated photon therapy (IMRT), volumetric modulated arc therapy (VMAT) and intensity-modulated proton therapy (IMPT). MATERIALS AND METHODS: Standard dose (60 Gy) and dose-escalated plans were calculated for seven patients using IMRT, VMAT and IMPT. The achieved boost dose, the dose to the organs at risk (OAR), the dose homogeneity (defined as overdose volume, ODV) and the ratio of the 30 Gy isodose curve and the boost volume (R30) were compared. The risk of radionecrosis was estimated using the ratio of the dose volume histograms of the brain (range 30-60 Gy). RESULTS: The mean boost dose was 77.1 Gy for IMRT, 79.2 Gy for VMAT and 85.1 GyE for IMPT. Compared with the standard plan, the ODV was unchanged and the R30 increased (17%) for IMRT. For VMAT, the ODV decreased (7%) and the R30 was unchanged whereas IMPT substantially decreased ODV (61%), R30 (22%), OAR doses as well as the risk of radionecrosis. CONCLUSIONS: Dose escalation can be achieved with IMRT, VMAT and IMPT while respecting normal tissue constraints, yet with IMPT being most favorable.

Prevalence of antimicrobial resistant Escherichia coli from patients with suspected urinary tract infection in primary care, Denmark.

BACKGROUND: Escherichia coli is the most common pathogen causing Urinary Tract Infections (UTI). Data from the current National Surveillance program in Denmark (DANMAP) may not accurately represent the prevalence of resistant E. coli in primary care, because only urine samples from complicated cases may be forwarded to the microbiological departments at hospitals for diagnostic examination. The aim of this study was to assess the prevalence of resistant E. coli to the most commonly used antimicrobial agents in primary care in a consecutive sample of patients from general practice. METHODS: Observational study carried out from December 2014 to December 2015. Thirty-nine general practices from The Capital Region of Denmark included adult patients with urinary tract symptoms and suspected UTI. All urine samples were sent to the central laboratory Statens Serum Institut (SSI). Significant bacteriuria was interpreted according to the European Urinalysis Standards. Susceptibility testing was performed and interpreted according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) standards. RESULTS: From the 39 general practices 505 patients were recruited. Completed data were obtained from 485 (96%) patients. According to the European Urinalysis Standards, 261 (54%) patients had positive bacteriuria. The most common uropathogen in patients with uncomplicated (uUTI) and complicated (cUTI) urinary tract infection was E. coli 105 (69%) and 76 (70%), respectively. Eighty-two (45%) of 181 E. coli isolates were resistant to at least one of the tested antibiotics and 50 out of 82 isolates were resistant to two or more antimicrobial agents. The highest resistance-rate was found against ampicillin 34% (95% CI 24;42) in uUTI and 36% (24;46) in cUTI. There were no differences in the distribution of resistance between uncomplicated and complicated cases. The prevalence of resistance was similar to the one reported in DANMAP 2014. CONCLUSION: In E. coli from uUTI there is high resistance rates to antimicrobial agents commonly used in primary care. There was no difference in the distribution of resistant E. coli in suspected uUTI vs cUTI. In Denmark, data from the National Surveillance program DANMAP can guide the decision for choice of antibiotic in patients with suspected UTI seeking care in primary care. TRIAL REGISTRATION: ClinicalTrials.gov NCT02249273 .

Development and validation of a condition-specific diary to measure severity, bothersomeness and impact on daily activities for patients with acute urinary tract infection in primary care.

BACKGROUND: Urinary tract infection (UTI) is a common condition in primary care. Patient-reported outcome measures (PROMs) are crucial in the evaluation of interventions to improve diagnosis, treatment and prognosis of UTI. The aim of this study was to identify an existing condition-specific PROM to measure symptom severity, bothersomeness and impact on daily activities for adult patients with suspected urinary tract infection in primary care; or, in the absence of such a PROM, to test items identified from existing PROMs for coverage and relevance in single and group interviews and to psychometrically validate the resulting PROM. METHODS: The literature was searched for existing PROMs covering the three domains. Items from the identified PROMs were tested in single and group interviews. The resulting symptom diary was psychometrically validated using the partial credit Rasch model for polytomous items in a cohort of 451 women participating in two studies regarding UTI. RESULTS: No existing PROM fulfilled the inclusion criteria. Content validation resulted in one domain concerning symptom severity (18 items), one concerning bothersomeness (18 items), and one concerning impact on daily activities (7 items). Psychometrical validation resulted in four dimensions in each of the first two domains and one dimension in the third domain. CONCLUSIONS: Domains were not unidimensional, which meant that we identified dimensions of patient-experienced UTI that differed substantially from those previously found. We recommend that future studies on UTI, in which PROMs are to be used, should ensure high content validity of their outcome measures and unidimensionality of the included dimensions.

Clinical accuracy of point-of-care urine culture in general practice.

OBJECTIVE: To assess the clinical accuracy (sensitivity (SEN), specificity (SPE), positive predictive value and negative predictive value) of two point-of-care (POC) urine culture tests for the identification of urinary tract infection (UTI) in general practice. DESIGN: Prospective diagnostic accuracy study comparing two index tests (Flexicult™ SSI-Urinary Kit or ID Flexicult™) with a reference standard (urine culture performed in the microbiological department). SETTING: General practice in the Copenhagen area patients. Adult female patients consulting their general practitioner with suspected uncomplicated, symptomatic UTI. MAIN OUTCOME MEASURES: (1) Overall accuracy of POC urine culture in general practice. (2) Individual accuracy of each of the two POC tests in this study. (3) Accuracy of POC urine culture in general practice with enterococci excluded, since enterococci are known to multiply in boric acid used for transportation for the reference standard. (4) Accuracy based on expert reading of photographs of POC urine cultures performed in general practice. Standard culture performed in the microbiological department was used as reference standard for all four measures. RESULTS: Twenty general practices recruited 341 patients with suspected uncomplicated UTI. The overall agreement between index test and reference was 0.76 (CI: 0.71-0.80), SEN 0.88 (CI: 0.83-0.92) and SPE 0.55 (CI: 0.46-0.64). The two POC tests produced similar results individually. Overall agreement with enterococci excluded was 0.82 (0.77-0.86) and agreement between expert readings of photographs and reference results was 0.81 (CI: 0.76-0.85). CONCLUSIONS: POC culture used in general practice has high SEN but low SPE. Low SPE could be due to both misinterpretation in general practice and an imperfect reference standard. Registration number: ClinicalTrials.gov NCT02323087.

Long-term results of a modified Spitzy shelf operation for residual hip dysplasia and subluxation. A fifty year follow-up study of fifty six children and young adults.

PURPOSE: The purposes of this study were to establish long-term outcome of the Spitzy shelf-operation and evaluate whether the procedure would delay osteoarthritis. METHODS: During 1954-1976, 56 patients (70 hips) underwent Spitzy shelf operation at a mean age of 11.9 years (5 to 22). Indications included residual hip dysplasia or subluxation with Centre-Edge angle < 20°. We used survival analysis with conversion to total hip replacements as end-point. For patients without total hip replacement, information was provided from case records and radiographs. Avascular necrosis was assessed in pre-Spitzy radiographs, when available. Kaplan-Meier product-limit method was used to estimate survival function of the Spitzy shelf operation. Survival was assessed by Cox regression. Univariable Cox regression was performed separately for each variable. Potential predictors (p-value < 0.10) were entered into a multivariable regression model; p-value < 0.05 was considered significant. RESULTS: Mean survival of the shelf procedure was 39.9 years (21 to 53). Survival fell from 83 % 30 years post-operatively, to 22 % at 50 years. Fifty-three hips (76 %) had undergone total hip replacement at mean age of 49.4 years (33 to 64). Seventeen hips had not received total hip replacement, mean survival 47.9 years (39 to 53). CONCLUSION: The study showed that Spitzy shelf-operation had satisfactory long-term outcome with hip-survival in almost 90 % at patient age 40 years. The results indicate that Spitzy shelf-operation postpone total hip replacement. We consider Spitzy shelf-operation a good alternative in patients above 8 years. In younger children the procedure is not recommended due to increased frequency of graft resorption.