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Objectives: This study determined associations between respiratory viruses and subsequent illness course in primary care adult patients presenting with acute cough and/or suspected lower respiratory tract infection. Methods: A prospective European primary care study recruited adults with symptoms of lower respiratory tract infection between November 2007 and April 2010. Real-time in-house polymerase chain reaction (PCR) was performed to test for six common respiratory viruses. In this secondary analysis, symptom severity (scored 1 = no problem, 2 = mild, 3 = moderate, 4 = severe) and symptom duration were compared between groups with different viral aetiologies using regression and Cox proportional hazard models, respectively. Additionally, associations between baseline viral load (cycle threshold (Ct) value) and illness course were assessed. Results: The PCR tested positive for a common respiratory virus in 1354 of the 2957 (45.8%) included patients. The overall mean symptom score at presentation was 2.09 (95% confidence interval (CI) 2.07-2.11) and the median duration until resolution of moderately bad or severe symptoms was 8.70 days (interquartile range 4.50-11.00). Patients with influenza virus, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), coronavirus (CoV) or rhinovirus had a significantly higher symptom score than patients with no virus isolated (0.07-0.25 points or 2.3-8.3% higher symptom score). Time to symptom resolution was longer in RSV infections (adjusted hazard ratio (AHR) 0.80, 95% CI 0.65-0.96) and hMPV infections (AHR 0.77, 95% CI 0.62-0.94) than in infections with no virus isolated. Overall, baseline viral load was associated with symptom severity (difference 0.11, 95% CI 0.06-0.16 per 10 cycles decrease in Ct value), but not with symptom duration. Conclusions: In healthy, working adults from the general community presenting at the general practitioner with acute cough and/or suspected lower respiratory tract infection other than influenza impose an illness burden comparable to influenza. Hence, the public health focus for viral respiratory tract infections should be broadened. (C) 2020 Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.

Contains fulltext : 249595.pdf (Publisher’s version ) (Open Access) PURPOSE OR OBJECTIVES: The FLAME trial (NCT01168479) showed that by adding a focal boost to conventional fractionated EBRT in the treatment of localized prostate cancer, the five-year biochemical disease-free survival increased, without significantly increasing toxicity. The aim of the present study was to investigate the association between radiation dose to the bladder and urethra and genitourinary (GU) toxicity grade ≥2 in the entire cohort. MATERIAL AND METHODS: The dose-effect relations of the urethra and bladder dose, separately, and GU toxicity grade ≥2 (CTCAE 3.0) up to five years after treatment were assessed. A mixed model analysis for repeated measurements was used, adjusting for age, diabetes mellitus, T-stage, baseline GU toxicity grade ≥1 and institute. Additionally, the association between the dose and separate GU toxicity subdomains were investigated. RESULTS: Dose-effect relations were observed for the dose (Gy) to the bladder D2 cm(3) and urethra D0.1 cm(3), with adjusted odds ratios of 1.14 (95% CI 1.12-1.16, p

Contains fulltext : 287303.pdf (Publisher’s version ) (Open Access) Clinical trials have shown that baricitinib, an oral selective Janus kinase 1/2 inhibitor, is effective for the treatment of moderate-to-severe atopic dermatitis. However, daily practice data are limited. Therefore, this multicentre prospective study evaluated the effectiveness and safety of 16-weeks' treatment with baricitinib in adult patients with moderate-to-severe atopic dermatitis in daily practice. A total of 51 patients from the BioDay registry treated with baricitinib were included and evaluated at baseline and after 4, 8 and 16 weeks of treatment. Effectiveness was assessed using clinician- and patient-reported outcome measurements. Adverse events and laboratory assessments were evaluated at every visit. At week 16, the probability (95% confidence interval) of achieving Eczema Area and Severity Index ≤ 7 and numerical rating scale pruritus ≤ 4 was 29.4% (13.1-53.5) and 20.5% (8.8-40.9), respectively. No significant difference in effectiveness was found between dupilumab non-responders and responders. Twenty-two (43.2%) patients discontinued baricitinib treatment due to ineffectiveness, adverse events or both (31.4%, 9.8% and 2.0%, respectively). Most frequently reported adverse events were nausea (n = 6, 11.8%), urinary tract infection (n = 5, 9.8%) and herpes simplex infection (n = 4, 7.8%). In conclusion, baricitinib can be an effective treatment option for moderate-to-severe atopic dermatitis, including patients with non-responsiveness on dupilumab. However, effectiveness of baricitinib is heterogeneous, which is reflected by the high discontinuation rate in this difficult-to-treat cohort.

Background The long‐term burden of cardiovascular disease after repair of coarctation of the aorta (CoA) has not been elucidated. We aimed to determine the incidence of and risk factors for cardiovascular events in adult patients with repaired CoA. Additionally, mortality rates were compared between adults with repaired CoA and the general population. Methods and Results Using the Dutch Congenital Corvitia (CONCOR) registry, patients aged ≥16 years with previous surgical or transcatheter CoA repair from 5 tertiary referral centers were included. Cardiovascular events were recorded, comprising coronary artery disease, stroke/transient ischemic attack, aortic complications, arrhythmias, heart failure hospitalizations, endocarditis, and cardiovascular death. In total, 920 patients (median age, 24 years [range 16–74 years]) were included. After a mean follow‐up of 9.3±5.1 years, 191 patients (21%) experienced at least 1 cardiovascular event. A total of 270 cardiovascular events occurred, of which aortic complications and arrhythmias were most frequent. Older age at initial CoA repair (hazard ratio [HR], 1.017; 95% CI, 1.000–1.033 [ P =0.048]) and elevated left ventricular mass index (HR, 1.009; 95% CI, 1.005–1.013 [ P P Conclusions This large, prospective cohort of adults with repaired CoA showed a high burden of cardiovascular events, particularly aortic complications and arrhythmias, during long‐term follow‐up. Older age at initial CoA repair and elevated left ventricular mass index were independent risk factors for the occurrence of cardiovascular events. Mortality was 3.3‐fold higher compared with the general population. These results advocate stringent follow‐up after CoA repair and emphasize the need for improved preventive strategies.

IntroductionAlmost 60% of antibiotics in frail elderly are prescribed for alleged urinary tract infections (UTIs). A substantial part of this comprises prescriptions in case of non-specific symptoms or asymptomatic bacteriuria, for which the latest guidelines promote restrictiveness with antibiotics. We aim to reduce inappropriate antibiotic use for UTIs through an antibiotic stewardship intervention (ASI) that encourages to prescribe according to these guidelines. To develop an effective ASI, we first need a better understanding of the complex decision-making process concerning suspected UTIs in frail elderly. Moreover, the implementation approach requires tailoring to the heterogeneous elderly care setting.Methods and analysisFirst, we conduct a qualitative study to explore factors contributing to antibiotic prescribing for UTIs in frail elderly, using semi-structured interviews with general practitioners, nursing staff, patients and informal caregivers. Next, we perform a pragmatic cluster randomised controlled trial in elderly care organisations. A multifaceted ASI is implemented in the intervention group; the control group receives care as usual. The ASI is centred around a decision tool that promotes restrictive antibiotic use, supported by a toolbox with educational materials. For the implementation, we use a modified participatory-action-research approach, guided by the results of the qualitative study. The primary outcome is the number of antibiotic prescriptions for suspected UTIs. We aim to recruit 34 clusters with in total 680 frail elderly residents ≥70 years. Data collection takes place during a 5-month baseline period and a 7-month follow-up period. Finally, we perform a process evaluation. The study has been delayed for 6 months due to COVID-19 and is expected to end in July 2021.Ethics and disseminationEthical approvals and/or waivers were obtained from the ethical committees in Poland, the Netherlands, Norway and Sweden. The results will be disseminated through publication in peer-reviewed journals and conference presentations.Trial registration numberNCT03970356.

Background Hypnotherapy for irritable bowel syndrome (IBS) has been used primarily in patients with refractory symptoms in specialised departments and delivered on an individual basis. We aimed to test the hypothesis that hypnotherapy would be more effective than educational supportive therapy, and that group hypnotherapy would be non-inferior to individual hypnotherapy for patients with IBS referred from primary and secondary care.Methods We did a multicentre randomised controlled trial (IMAGINE) in 11 hospitals in the Netherlands. Patients with IBS, aged 18-65 years, who were referred from primary or secondary care were randomly allocated (3:3:1) in blocks of six using a computer-based random number table procedure by staff not involved in the treatment to receive six sessions of individual or group hypnotherapy or group educational supportive therapy (control group). The primary outcome was adequate relief of IBS symptoms, with responders defined as patients who reported adequate relief when asked once weekly on three or four occasions in 4 consecutive weeks. We compared hypnotherapy (both groups) with control in the intention-to-treat population (excluding individuals subsequently found to be ineligible for enrolment), and assessed non-inferiority of group hypnotherapy versus individual hypnotherapy in the per-protocol population (with a non-inferiority margin of 15%) at 3 months and 12 months. This trial is registered with ISRCTN, number IS RCTN22888906, and is completed.Findings Between May 31, 2011, and April 6, 2016, 494 patients referred for psychological treatment for IBS were assessed for eligibility, of whom 354 were randomly allocated to the three groups: 150 to individual hypnotherapy, 150 to group hypnotherapy, and 54 to educational supportive therapy. After exclusion of individuals subsequently found to be ineligible for enrolment, 142 patients in the individual hypnotherapy group, 146 in the group hypnotherapy group, and 54 in the control group were included in the intention-to-treat population. Of these, 22 (15%) patients in the individual hypnotherapy group, 22 (15%) in the group hypnotherapy group, and 11 (20%) in the control group dropped out before or during therapy. In the intention-to-treat analysis, the adequate response rate was 40.8% (95% CI 31.7-50.5) in the individual hypnotherapy group, 33.2% (24.3-43.5) in the group hypnotherapy group, and 16.7% (7.6-32.6) in the control group at 3 months. At 12 months, 40.8% (31.3-51.1) of patients in the individual hypnotherapy group, 49.5% (38.8-60.0) of patients in the group hypnotherapy group, and 22.6% (11.5-39.5) of patients in the control group reported adequate relief. Hypnotherapy was more effective than control at 3 months (odds ratio 2.9, 95% CI 1.2-7.4,13=0.0240) and 12 months (2.8, 1.2-6.7, p=0.0185). In the per-protocol analysis, 49.9% (39.2-60.6) in the individual hypnotherapy group and 42.7% (32.3-53.8) in the group hypnotherapy group had adequate relief at 3 months, and 55.5% (43.4-67.1) of individual and 51.7% (40.2-63.0) of group hypnotherapy patients reported adequate relief at 12 months. Group hypnotherapy was therefore non-inferior to individual hypnotherapy. Eight unexpected serious adverse reactions (six in the individual hypnotherapy group and two in the group hypnotherapy group) were reported, most of which were cancer or inflammatory bowel disease, and were judged by the medical ethics committee as not being related to the therapy.Interpretation Hypnotherapy should be considered as a possible treatment for patients with IBS in primary and secondary care. Furthermore, group therapy could allow many more patients to be treated for the same cost. Copyright (C) 2018 Elsevier Ltd. All rights reserved.

Background Recognition of temporomandibular joint (TMJ) involvement in children with juvenile idiopathic arthritis (JIA) has gained increasing attention in the past decade. The clinical assessment of mandibular range of motion characteristics is part of the recommended variables to detect TMJ involvement in children with JIA. The aim of this study was to explore explanatory variables for mandibular range of motion outcomes in children with JIA, with and without clinically established TMJ involvement, and in healthy children. Methods This cross-sectional study included children with JIA and healthy children of age 6–18 years. Mandibular range of motion variables included active and passive maximum interincisal opening (AMIO and PMIO), protrusion, laterotrusion, dental midline shift in AMIO and in protrusion. Additionally, the TMJ screening protocol and palpation pain were assessed. Adjusted linear regression analyses of AMIO, PMIO, protrusion, and laterotrusion were performed to evaluate the explanatory factors. Two adjusted models were constructed: model 1 to compare children with JIA and healthy children, and model 2 to compare children with JIA with and without TMJ involvement. Results A total of 298 children with JIA and 169 healthy children were included. Length was an explanatory variable for the mandibular range of motion excursions. Each centimeter increase in length increased AMIO (0.14 mm), PMIO (0.14 mm), and protrusion (0.02 mm). Male gender increased AMIO by 1.35 mm. Having JIA negatively influenced AMIO (3.57 mm), PMIO (3.71 mm), and protrusion (1.03 mm) compared with healthy children, while the discrepancy between left and right laterotrusion raised 0.68 mm. Children with JIA and TMJ involvement had a 8.27 mm lower AMIO, 7.68 mm lower PMIO and 0.96 mm higher discrepancy in left and right laterotrusion compared to healthy children. Conclusion All mandibular range of motion items were restricted in children with JIA compared with healthy children. In children with JIA and TMJ involvement, AMIO, PMIO and the discrepancy between left and right laterotrusion were impaired more severely. The limitation in protrusion and laterotrusion was hardly clinically relevant. Overall, AMIO is the mandibular range of motion variable with the highest restriction (in millimeters) in children with JIA and clinically established TMJ involvement compared to healthy children.

Background Home telemonitoring in heart failure (HF) patients may reduce workload of HF nurses by reducing face-to-face contacts. The aim of this study is to assess whether telemonitoring as a substitution could have negative effects as expressed by less reduction in circulating natriuretic peptide levels between baseline and one-year of follow up compared to usual care. Methods A post-hoc analysis of the e-Vita HF trial, a three-arm parallel randomized trial conducted in stable HF patients. Patients were randomized into three arms: (i) usual HF outpatient care, (ii) usual care combined with the use of the website heartfailurematters.org, and (iii) telemonitoring (e-Vita HF platform) instead of face-to-face consultations. Mixed linear model analyses were applied to assess differences in the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels between the three arms over a year. Results A total of 223 participants could be included (mean age 67.1 ± 10.1 years, 27% women, New York Heart Association class I–IV; 39%, 38%, 14%, and 9%). The mean left ventricular ejection fraction was 35 ± 10%. The median of routine face-to-face contacts over a year was 1.0 lower (2.0 vs. 3.0) in the third arm compared with usual care. Median NT-proBNP levels did not significantly differ between the three arms. Conclusion In stable and optimally treated HF patients, telemonitoring causing a reduction of routine face-to-face contacts seems not to negatively affect hemodynamic status as measured by NT-proBNP levels over time.

Background In children with juvenile idiopathic arthritis (JIA), the temporomandibular joint (TMJ) can be involved, resulting in dysfunction of the masticatory system. Bite force is one of the variables that reflects the function of the masticatory system. The aim of this study was to compare maximum bite force in children with JIA, with and without TMJ involvement and with healthy children. Methods Children with JIA and healthy children between the ages 6 and 18 were included in this cross‐sectional study. The clinical examination consisted of measuring the anterior maximum voluntary bite force (AMVBF), assessment of the TMJ screening protocol items and TMJ, masseter and temporal muscle palpation pain. Unadjusted linear regression analyses were performed to evaluate the explanatory factors for AMVBF. Two adjusted models were constructed with corrections for age and gender differences: model 1 to compare children with JIA and healthy children and model 2 to compare children with JIA with and without TMJ involvement. Results In this cross‐sectional study, 298 children with JIA and 169 healthy children participated. AMVBF was 24 Newton (N) lower in children with JIA, when compared with healthy children (95%CI: −35.5–−12.4, p = .000). When children with JIA also had clinically established TMJ involvement, AMVBF was reduced 42 N (component JIA:−16.78, 95% CI −28.96–−4.59, p = .007 and component TMJ involvement:−25.36, 95% CI −40.08–−10.63, p = .001). Age and male gender increased AMVBF. Conclusion Children with JIA had a reduction in the AMVBF compared with healthy children. In children with JIA and clinically established TMJ involvement, AMVBF was more reduced., This study found a considerable bite force reduction and less functioning of the TMJ in children with JIA compared to healthy children, and even more reduction of these issues in children with JIA and TMJ involvement compared to JIA without TMJ involvement. For all children, the demographic variables age, length and male gender increased the maximum bite force.

Aims Exergaming is a new tool to increase physical activity. This study aimed to determine the effects of access to a home-based exergame (Nintendo Wii) in patients with heart failure (HF) on exercise capacity, self-reported physical activity and patient-reported outcome measures. Methods and results We enrolled 605 HF patients in New York Heart Association functional class I-IV, independent of ejection fraction, in an international multicentre randomized controlled trial. Patients were randomized to exergame (intervention) or motivational support (control). The primary endpoint was change in submaximal aerobic exercise capacity as measured by the distance walked in 6 min (6MWT) between baseline and 3 months. Secondary endpoints included long-term submaximal aerobic exercise capacity, muscle function, self-reported physical activity, exercise motivation, exercise self-efficacy at 3, 6 and 12months. At baseline, patients on average walked 403142m on the 6MWT. Patients in the exergame group walked further compared to controls at 3 months (454123 vs. 420 +/- 127m, P = 0.005), at 6 months (452 +/- 123 vs. 426 +/- 133m, P = 0.015) and 12months (456 +/- 122 vs. 420 +/- 135m, P = 0.004). However, correcting for baseline 6MWT values by means of a linear mixed-effects model revealed no main effect for the intervention on 6MWT. Small significant effects on muscle function were found. Statistically significant treatment effects were found for muscle function but after correction for baseline and confounders, only the treatment effect for the heel-rise left at 6 months was significant (PFunding Agencies|Swedish National Science Council [K2013-69X-22302-01-3, 2016-01390]; Swedish National Science Council/Swedish Research Council for Health, Working Life and Welfare, VR-FORTE [2014-4100]; Swedish Heart and Lung AssociationSwedish Heart-Lung Foundation [E085/12]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation [20130340, 20160439]; Vardal Foundation [2014-0018]; Medical Research Council of Southeast Sweden [FORSS 474681]

Item does not contain fulltext IMPORTANCE: Unruptured intracranial aneurysms not undergoing preventive endovascular or neurosurgical treatment are often monitored radiologically to detect aneurysm growth, which is associated with an increase in risk of rupture. However, the absolute risk of aneurysm rupture after detection of growth remains unclear. OBJECTIVE: To determine the absolute risk of rupture of an aneurysm after detection of growth during follow-up and to develop a prediction model for rupture. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data were obtained from 15 international cohorts. Patients 18 years and older who had follow-up imaging for at least 1 untreated unruptured intracranial aneurysm with growth detected at follow-up imaging and with 1 day or longer of follow-up after growth were included. Fusiform or arteriovenous malformation-related aneurysms were excluded. Of the 5166 eligible patients who had follow-up imaging for intracranial aneurysms, 4827 were excluded because no aneurysm growth was detected, and 27 were excluded because they had less than 1 day follow-up after detection of growth. EXPOSURES: All included aneurysms had growth, defined as 1 mm or greater increase in 1 direction at follow-up imaging. MAIN OUTCOMES AND MEASURES: The primary outcome was aneurysm rupture. The absolute risk of rupture was measured with the Kaplan-Meier estimate at 3 time points (6 months, 1 year, and 2 years) after initial growth. Cox proportional hazards regression was used to identify predictors of rupture after growth detection. RESULTS: A total of 312 patients were included (223 [71%] were women; mean [SD] age, 61 [12] years) with 329 aneurysms with growth. During 864 aneurysm-years of follow-up, 25 (7.6%) of these aneurysms ruptured. The absolute risk of rupture after growth was 2.9% (95% CI, 0.9-4.9) at 6 months, 4.3% (95% CI, 1.9-6.7) at 1 year, and 6.0% (95% CI, 2.9-9.1) at 2 years. In multivariable analyses, predictors of rupture were size (7 mm or larger hazard ratio, 3.1; 95% CI, 1.4-7.2), shape (irregular hazard ratio, 2.9; 95% CI, 1.3-6.5), and site (middle cerebral artery hazard ratio, 3.6; 95% CI, 0.8-16.3; anterior cerebral artery, posterior communicating artery, or posterior circulation hazard ratio, 2.8; 95% CI, 0.6-13.0). In the triple-S (size, site, shape) prediction model, the 1-year risk of rupture ranged from 2.1% to 10.6%. CONCLUSION AND RELEVANCE: Within 1 year after growth detection, rupture occurred in approximately 1 of 25 aneurysms. The triple-S risk prediction model can be used to estimate absolute risk of rupture for the initial period after detection of growth.

Contains fulltext : 238196.pdf (Publisher’s version ) (Open Access) BACKGROUND AND PURPOSE: The phase III FLAME trial (NCT01168479) showed an increase in five-year biochemical disease-free survival, with no significant increase in toxicity when adding a focal boost to external beam radiotherapy (EBRT) for localized prostate cancer [Kerkmeijer et al. JCO 2021]. The aim of this study was to investigate the association between delivered radiation dose to the anorectum and gastrointestinal (GI) toxicity (grade >/=2). MATERIAL AND METHODS: All patients in the FLAME trial were analyzed, irrespective of treatment arm. The dose-effect relation of the anorectal dose parameters (D2cm(3) and D50%) and GI toxicity grade >/=2 in four years of follow-up was assessed using a mixed model analysis for repeated measurements, adjusted for age, cardiovascular disease, diabetes mellitus, T-stage, baseline toxicity grade >/=1, hormonal therapy and institute. RESULTS: A dose-effect relation for D2cm(3) and D50% was observed with adjusted odds ratios of 1.17 (95% CI 1.13-1.21, p < 0.0001) and 1.20 (95% CI 1.14-1.25, p < 0.0001) for GI toxicity, respectively. CONCLUSION: Although there was no difference in toxicity between study arms, a higher radiation dose to the anorectum was associated with a statistically significant increase in GI toxicity following EBRT for prostate cancer. This dose-effect relation was present for both large and small anorectal volumes. Therefore, further increase in dose to the anorectum should be weighed against the benefit of focal dose escalation for prostate cancer.

Background Cerebrospinal fluid (CSF) leakage is a common complication after neurosurgical intervention. It is associated with substantial morbidity and increased healthcare costs. The current systematic review and meta-analysis aim to quantify the incidence of cerebrospinal fluid leakage in the pediatric population and identify its risk factors. Methods The authors followed the PRISMA guidelines. The Embase, PubMed, and Cochrane database were searched for studies reporting CSF leakage after intradural cranial surgery in patients up to 18 years old. Meta-analysis of incidences was performed using a generalized linear mixed model. Results Twenty-six articles were included in this systematic review. Data were retrieved of 2929 patients who underwent a total of 3034 intradural cranial surgeries. Surprisingly, only four of the included articles reported their definition of CSF leakage. The overall CSF leakage rate was 4.4% (95% CI 2.6 to 7.3%). The odds of CSF leakage were significantly greater for craniectomy as opposed to craniotomy (OR 4.7, 95% CI 1.7 to 13.4) and infratentorial as opposed to supratentorial surgery (OR 5.9, 95% CI 1.7 to 20.6). The odds of CSF leakage were significantly lower for duraplasty use versus no duraplasty (OR 0.41 95% CI 0.2 to 0.9). Conclusion The overall CSF leakage rate after intradural cranial surgery in the pediatric population is 4.4%. Risk factors are craniectomy and infratentorial surgery. Duraplasty use is negatively associated with CSF leak. We suggest defining a CSF leak as “leakage of CSF through the skin,” as an unambiguous definition is fundamental for future research.

BackgroundPain management in acute otitis media (AOM) is often suboptimal, potentially leading to unnecessary discomfort, GP reconsultation, and antibiotic prescribing.AimTo assess the effectiveness of a GP-targeted educational intervention to improve pain management in children with AOM.Design and settingPragmatic, cluster randomised controlled trial (RCT). GPs in 37 practices (intervention n = 19; control n = 18) across the Netherlands recruited 224 children with GP-confirmed AOM and ear pain (intervention n = 94; control n = 130) between February 2015 and May 2018.MethodGPs in practices allocated to the intervention group were trained (online and face-to-face) to discuss pain management with parents using an information leaflet, and prompted to prescribe weight-appropriate dosed paracetamol. Ibuprofen was additionally prescribed if pain control was still insufficient. GPs in the control group provided usual care.ResultsMean ear pain scores over the first 3 days were similar between groups (4.66 versus 4.36; adjusted mean difference = −0.05; 95% confidence intervals [CI] = −0.93 to 0.83), whereas analgesic use, in particular ibuprofen, was higher in the intervention group. The total number of antibiotic prescriptions during the 28-day follow-up was similar (mean rate 0.43 versus 0.47; adjusted rate ratio [aRR] 0.97; 95% CI = 0.68 to 1.38). Parents of children in the intervention group were more likely to reconsult for AOM-related complaints (mean rate 0.70 versus 0.41; aRR 1.73; 95% CI = 1.14 to 2.62).ConclusionAn intervention aimed at improving pain management for AOM increases analgesic use, particularly ibuprofen, but does not provide symptomatic benefit. GPs are advised to carefully weigh the potential benefits of ibuprofen against its possible harms.

Background Treatment options for advanced head and neck adenoid cystic carcinoma (AdCC) are limited. Prostate-Specific Membrane Antigen (PSMA), a transmembrane protein that is known for its use in diagnostics and targeted therapy in prostate cancer, is also expressed by AdCC. This study aimed to analyse PSMA expression in a large cohort of primary, recurrent and metastasized AdCC of the head and neck. Methods One hundred ten consecutive patients with histologically confirmed AdCC in the period 1990–2017 were included. An analysis was made of clinical details, revised pathology and semiquantitative immunohistochemical expression of PSMA on tissue microarray and whole slides. Associations of PSMA expression with clinicopathological parameters were explored and survival was analysed by multivariate Cox-proportional Hazard analysis. Results PSMA expression was present in 94% of the 110 primary tumours, with a median of 31% positive cells (IQR 15–60%). Primary tumours (n = 18) that recurred (n = 15) and/or had metastases (n = 10) demonstrated 40, 60 and 23% expression respectively. Expression was not independently related to increased pathological stage, tumour grade, and the occurrence of locoregional recurrence or metastasis. After dichotomization, only primary tumour PSMA expression ≤10% appeared to be associated with reduced 10-years recurrence-free survival (HR 3.0, 95% CI 1.1–8.5, p = .04). Conclusions PSMA is highly expressed in primary, recurrent and metastatic AdCC of the salivary and seromucous glands. PSMA expression has no value in predicting clinical behaviour of AdCC although low expression may indicate a reduced recurrence-free survival. This study provides supporting results to consider using PSMA as target for imaging and therapy when other diagnostic and palliative treatment options fail.

Background Patients with unprovoked (i.e., without the presence of apparent transient risk factors such as recent surgery) venous thromboembolism (VTE) are at risk of recurrence if anticoagulants are stopped after 3–6 months, yet their risk remains heterogeneous. Thus, prolonging anticoagulant treatment should be considered in high-risk patients, whereas stopping is likely preferred in those with a low predicted risk. The Vienna Prediction Model (VPM) could aid clinicians in estimating this risk, yet its clinical effects and external validity are currently unknown. The aim of this study was to investigate the clinical impact of this model on reducing recurrence risk in patients with unprovoked VTE, compared to usual care. Methods and findings In a randomized controlled trial, the decision to prolong or stop anticoagulant treatment was guided by predicted recurrence risk using the VPM (n = 441), which was compared with usual care (n = 442). Patients with unprovoked VTE were recruited from local thrombosis services in the Netherlands (in Utrecht, Harderwijk, Ede, Amersfoort, Zwolle, Hilversum, Rotterdam, Deventer, and Enschede) between 22 July 2011 and 30 November 2015, with 24-month follow-up complete for all patients by early 2018. The primary outcome was recurrent VTE during 24 months of follow-up. Secondary outcomes included major bleeding and clinically relevant non-major (CRNM) bleeding. In the total study population of 883 patients, mean age was 55 years, and 507 (57.4%) were men. A total of 96 recurrent VTE events (10.9%) were observed, 46 in the intervention arm and 50 in the control arm (risk ratio 0.92, 95% CI 0.63–1.35, p = 0.67). Major bleeding occurred in 4 patients, 2 in each treatment arm, whereas CRNM bleeding occurred in 20 patients (12 in intervention arm versus 8 in control arm). The VPM showed good discriminative power (c-statistic 0.76, 95% CI 0.69–0.83) and moderate to good calibration, notably at the lower spectrum of predicted risk. For instance, in 284 patients with a predicted risk of >2% to 4%, the observed rate of recurrence was 2.5% (95% CI 0.7% to 4.3%). The main limitation of this study is that it did not enroll the preplanned number of 750 patients in each study arm due to declining recruitment rate. Conclusions Our results show that application of the VPM in all patients with unprovoked VTE is unlikely to reduce overall recurrence risk. Yet, in those with a low predicted risk of recurrence, the observed rate was also low, suggesting that it might be safe to stop anticoagulant treatment in these patients. Trial registration Netherlands Trial Register NTR2680, Geert-Jan Geersing and colleagues investigate the clinical impact of the Vienna Prediction model on reducing recurrence risk in patients with unprovoked venous thromboembolism, compared to usual care., Author summary Why was this study done? Patients with clots in the leg or lung without a clear explanation are treated with anticoagulants. After the initial treatment phase is complete (after 3–6 months), a relatively large group of patients will then experience new clots if treatment is then discontinued. Physicians struggle with identifying the group of patients in need of prolonged anticoagulant treatment, which can be protective for recurrent clots, yet also inherently introduces bleeding risk. What did the researchers do and find? The researchers performed a randomized trial comparing the use of a prediction tool with usual care. This prediction tool can help identify patients at increased risk of recurrent clots. Treatment can then be tailored accordingly. The study found that, overall, the risk of recurrent clots was not reduced by applying this tool. The prediction tool, however, was able to identify a group of patients with a low risk of recurrent clots. What do these findings mean? On a population level, the researchers were unable to find a difference in the risk of recurrent clots by using this prediction tool. The study, however, did suggest that it might be safe to stop anticoagulant treatment after the initial treatment phase in those with a low predicted risk of recurrent clots.

Objective: The objective of this systematic review was to review the available evidence on the disparity between willingness to accept (WTA) and willingness to pay (WTP) for healthcare goods and services. Methods: A tiered approach consisting of (1) a systematic review, (2) an aggregate data meta-analysis, and (3) an individual participant data meta-analysis was used. MEDLINE, EMBASE, Scopus, Scisearch, and Econlit were searched for articles reporting both WTA and WTP for healthcare goods and services. Individual participant data were requested from the authors of the included studies. Results: Thirteen papers, reporting WTA and WTP from 19 experiments/subgroups, were included in the review. The WTA/WTP ratios reported in these papers, varied from 0.60 to 4.01, with means of 1.73 (median 1.31) for 15 estimates of the mean and 1.58 (median 1.00) for nine estimates of the median. Individual data obtained from six papers, covering 71.2% of the subjects included in the review, yielded an unadjusted WTA/WTP ratio of 1.86 (95% confidence interval 1.52–2.28) and a WTA/WTP ratio adjusted for age, sex, and income of 1.70 (95% confidence interval 1.42–2.02). Income category and age had a statistically significant effect on the WTA/WTP ratio. The approach to handling zero WTA and WTP values has a considerable impact on the WTA/WTP ratio found. Conclusions and Implications: The results of this study imply that losses in healthcare goods and services are valued differently from gains (ratio > 1), but that the degree of disparity found depends on the method used to obtain the WTA/WTP ratio, including the approach to zero responses. Irrespective of the method used, the ratios found in our meta-analysis are smaller than the ratios found in previous meta-analyses.

Background The majority of the world’s perinatal deaths occur in low- and middle-income countries. A substantial proportion occurs intrapartum and is avoidable with better care. At a low-resource tertiary hospital, this study assessed the quality of intrapartum care and adherence to locally-tailored clinical guidelines. Methods A non-participatory, structured, direct observation study was held at Mnazi Mmoja Hospital, Zanzibar, Tanzania, between October and November 2016. Women in active labour were followed and structure, processes of labour care and outcomes of care systematically recorded. Descriptive analyses were performed on the labour observations and compared to local guidelines and supplemented by qualitative findings. A Poisson regression analysis assessed factors affecting foetal heart rate monitoring (FHRM) guidelines adherence. Results 161 labouring women were observed. The nurse/midwife-to-labouring-women ratio of 1:4, resulted in doctors providing a significant part of intrapartum monitoring. Care during labour and two-thirds of deliveries was provided in a one-room labour ward with shared beds. Screening for privacy and communication of examination findings were done in 50 and 34%, respectively. For the majority, there was delayed recognition of labour progress and insufficient support in second stage of labour. While FHRM was generally performed suboptimally with a median interval of 105 (interquartile range 57–160) minutes, occurrence of an intrapartum risk event (non-reassuring FHR, oxytocin use or poor progress) increased assessment frequency significantly (rate ratio 1.32 (CI 1.09–1.58)). Conclusions Neither international nor locally-adapted standards of intrapartum routine care were optimally achieved. This was most likely due to a grossly inadequate capacity of birth attendants; without whom innovative interventions at birth are unlikely to succeed. This calls for international and local stakeholders to address the root causes of unsafe intrafacility care in low-resource settings, including the number of skilled birth attendants required for safe and respectful births.

Background and aimsA higher dairy product intake has been associated to higher blood concentrations of 15:0 (pentadecanoic acid), 17:0 (margaric acid), and 14:0 (myristic acid). This study investigates whether a diet high in dairy products influences cholesteryl ester fatty acid concentrations of these specific fatty acids (FA).Methods and resultsIn a randomized multiple cross-over study, 13 men and 17 women aged 22 ± 4 years with a BMI of 21.6 ± 2.2 kg/m2 received 3 isocaloric intervention diets (dairy, meat or grain) in random order. For this post-hoc analysis, FA in plasma cholesteryl esters were measured using gas chromatography. We performed a linear mixed model per centered log-ratio transformed FA, adjusting for period, and the interaction between diet and period. Consumed total fat intake per controlled intervention diet was 31.0 ± 0.9 en%/day (dairy), 31.5 ± 0.6 en%/day (meat), and 28.4 ± 1.2 en%/day (grain), respectively. The dairy diet led to higher relative concentrations of 15:0 when compared to diets high in meat and grain, (β; 0.27, 95%CI: 0.18,0.37; p = 1.2 × 10−5, and β: 0.15; 95%CI: 0.06,0.24; p = 1.2 × 10−2, respectively). The dairy diet also led to higher 14:0 when compared to the meat diet (β: 0.34; 95%CI: 0.21,0.46; p = 6.0 × 10−5), but not when compared to the grain diet. 17:0 did not differ between diets.ConclusionThe plasma cholesteryl ester fraction after a diet high in dairy was characterized by higher 15:0 levels. Concentrations of 14:0 were only higher when comparing the FA profile after a diet high in dairy when compared to a diet high in meat.Clinical trial registrationClinicalTrials.gov, NCT01314040.

Background Postpartum hemorrhage (PPH) is the leading cause of direct maternal mortality globally and in Suriname. We aimed to study the prevalence, risk indicators, causes, and management of PPH to identify opportunities for PPH reduction. Methods A nationwide retrospective descriptive study of all hospital deliveries in Suriname in 2017 was performed. Logistic regression analysis was applied to identify risk indicators for PPH (≥ 500ml blood loss). Management of severe PPH (blood loss ≥1,000ml or ≥500ml with hypotension or at least three transfusions) was evaluated via a criteria-based audit using the national guideline. Results In 2017, the prevalence of PPH and severe PPH in Suriname was 9.2% (n = 808/8,747) and 2.5% (n = 220/8,747), respectively. PPH varied from 5.8% to 15.8% across the hospitals. Risk indicators associated with severe PPH included being of African descent (Maroon aOR 2.1[95%CI 1.3–3.3], Creole aOR 1.8[95%CI 1.1–3.0]), multiple pregnancy (aOR 3.4[95%CI 1.7–7.1]), delivery in Hospital D (aOR 2.4[95%CI 1.7–3.4]), cesarean section (aOR 3.9[95%CI 2.9–5.3]), stillbirth (aOR 6.4 [95%CI 3.4–12.2]), preterm birth (aOR 2.1[95%CI 1.3–3.2]), and macrosomia (aOR 2.8 [95%CI 1.5–5.0]). Uterine atony (56.7%, n = 102/180[missing 40]) and retained placenta (19.4%, n = 35/180[missing 40]), were the main causes of severe PPH. A criteria-based audit revealed that women with severe PPH received prophylactic oxytocin in 61.3% (n = 95/155[missing 65]), oxytocin treatment in 68.8% (n = 106/154[missing 66]), and tranexamic acid in 4.9% (n = 5/103[missing 117]). Conclusions PPH prevalence and risk indicators in Suriname were similar to international and regional reports. Inconsistent blood loss measurement, varied maternal and perinatal characteristics, and variable guideline adherence contributed to interhospital prevalence variation. PPH reduction in Suriname can be achieved through prevention by practicing active management of the third stage of labor in every birth and considering risk factors, early recognition by objective and consistent blood loss measurement, and prompt treatment by adequate administration of oxytocin and tranexamic acid according to national guidelines.

Background To investigate trends over age by comorbidity status for the risk of limitations in individual activities of daily living for community-living older persons. Methods A longitudinal population-based study was conducted in 9,319 community-living Dutch persons aged 60 years and older. Self-reported multiple chronic conditions (MCC) and nine instrumental activities of daily livings (IADLs) were assessed in 15 studies of the Dutch National Care for the Elderly Program (TOPICS-MDS). Risks of limitations in IADLs, odds ratios (per 5 years), and rate ratios (per 5 years) were calculated with mixed logistic and negative binomial regression models with age as the underlying timescale, stratified by number of MCC (no, 1–2, ≥ 3 MCC), and corrected for confounders. Results At inclusion, the number of IADL limitations was highest for the “≥3 MCC” group (2.00 interquartile range [1.00–4.00]) and equal for “no MCC” or “1–2 MCC” (1.00 interquartile range [0.00–2.00]). Trends of individual IADLs depicted a higher risk in IADL limitation with increasing age over 2 years of follow-up, except for handling finances for the “no MCC” group. The longitudinal age effect on IADL limitations varied subject to MCC, being strongest for the “no MCC” group for most IADLs; grooming and telephone use were almost unaltered by age and MCC. Conclusion We observed a decline in IADL functioning with increasing age over 2 years of follow-up in persons with and without MCC. The impact of MCC on IADL decline varied per IADL activity.

© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Objectives: Antibiotics are too often prescribed in childhood respiratory tract infection (RTI), despite limited effectiveness, potential side effects and bacterial resistance. We aimed to reduce antibiotic prescribing for children with RTI by online training for general practitioners (GPs) and information for parents. Methods: A pragmatic cluster randomized controlled trial in primary care. The intervention consisted of online training for GPs and an information booklet for parents. The primary outcome was the antibiotic prescription rate for children presenting with RTI symptoms, as registered by GPs. Secondary outcomes were number of reconsultations within the same disease episode, consultations for new episodes, hospital referrals and pharmacydispensed antibiotic courses for children. This trial was registered at the Dutch Trial Register (NTR), registration number: NTR4240. Results: After randomization, GPs from a total of 32 general practices registered 1009 consultations. An antibiotic was prescribed in 21% of consultations in the intervention group, compared with 33% in the usual care group, controlled for baseline prescribing (rate ratio 0.65, 95% CI 0.46-0.91). The probability of reconsulting during the same RTI episode did not differ significantly between the intervention and control groups, and nor did the numbers of consultations for new episodes and hospital referrals. In the intervention group antibiotic dispensing was 32 courses per 1000 children/year lower than the control group, adjusted for baseline prescribing (rate ratio 0.78, 95% CI 0.66-0.92). The numbers and proportion of second-choice antibiotics did not differ significantly. Conclusions: Concise, feasible, online GP training, with an information booklet for parents, showed a relevant reduction in antibiotic prescribing for children with RTI.

Background Aneurysmal subarachnoid hemorrhage (aSAH) patients have an inflammatory response in the cerebrospinal fluid (CSF). We determined CSF cell counts, erythrocyte/leukocyte ratio, and glucose- and protein concentrations in patients ≤20 days after aSAH without bacterial meningitis. Such knowledge may help to interpret CSF parameters in patients with an external drain if nosocomial bacterial meningitis or ventriculitis is suspected. Methods Patients with aSAH admitted between 2010 and 2017 with at least one CSF sample ≤ 20 days after ictus were included from a prospectively collected database. CSF samples were excluded if the patient used antibiotics or if the CSF culture was positive. We calculated estimated marginal means with 95% confidence intervals (CIs) with linear mixed models for CSF cell counts, glucose- and protein concentrations. Results We included 209 patients with 306 CSF samples. Highest estimated median leukocyte count was 305 (95%CI:225–412) x10^6/L, and the lowest estimated median erythrocyte/leukocyte ratio was 109 (95%CI:73–163). Estimated mean glucose concentrations remained within the normal range. The estimated median protein concentration decreased from 3.3 g/L (95%CI:2.5–4.2) on day 0 to 1.0 g/L (95%CI:0.8–1.2) on day 14. Conclusion The limits we found for the inflammatory reaction in aSAH patients may help physicians to interpret CSF parameters in aSAH patients with an external CSF drain. Future studies are needed to compare CSF parameters in aSAH patients with and without bacterial meningitis or ventriculitis.

Background: This study investigated the trajectories of decline in individual instrumental activities of daily living (IADL) with aging and the effect of hearing loss, vision loss, or dual sensory loss on these trajectories in community-living frail older persons. Method: This longitudinal population-based study was conducted in 9,319 community-living frail Dutch persons aged 60 years and older. Self-reported hearing loss, vision loss, or dual sensory loss and nine IADL were assessed in 15 studies of the Dutch National Care for the Elderly Program (The Older Persons and Informal Caregivers Survey Minimum Dataset). Probabilities of limitations in IADL, odds ratios (per 5 years) for binary, and rate ratios (per 5 years) for score outcomes were calculated using mixed logistic and negative binomial models with age as the underlying timescale, stratified by sensory loss, and corrected for confounders. Results: At baseline, the number of IADL limitations was higher in dual sensory loss (2.00 [interquartile range 1.00–4.00]) and vision loss (2.00 [interquartile range 1.00–4.00]) compared to no sensory loss (1.00 [interquartile range 0.00–2.00]) or hearing loss (1.00 [interquartile range 0.00–3.00]). Trajectories of individual IADL showed an increase in limitations in all IADL with age. Household tasks, traveling, shopping, preparing a meal, and walking showed the most rapid decline. Handling finances, traveling, and walking followed a different pattern of decline based on sensory loss status. Conclusions: The age effect on limitations in IADL appears to be similar across all types of sensory loss, with the exception of handling finances, traveling, and walking. At baseline, persons with self-reported sensory loss had higher levels of self-reported functional limitations. Trajectories depict a decline in IADL competence with age.

Background and Purpose— Intracranial aneurysm (IA) size and location are important determinants of aneurysm rupture risk. In familial IAs there is concordance of location; however, if such concordance exists for size is unknown. We analyzed the concordance of aneurysm size at time of rupture in familial IAs. Methods— In pairs of affected relatives with aneurysmal subarachnoid hemorrhage, the ratio between the largest and the smallest aneurysm size at time of rupture was calculated. We also compared the proportion of families in which both IAs ruptured at a size < or ≥7 mm with the proportion of families in which one IA ruptured at Results— About 130 patients from 64 families were included. Of the 68 affected pairs 18 (26%) had a ratio ≤1.2, 38 (57%) had a ratio >1.2, and 12 (17%) had a ratio ≥3. We found no difference between the proportion of families (n=31; 49%) who both had IA at time of rupture P =0.86). Overall, the repeatability in aneurysm size at rupture within familial IAs was 0.10 (95% CI, 0–0.35). Conclusions— There is no good concordance in aneurysm size at rupture within familial IAs. These data suggest that size of a ruptured IA in a family member should not significantly impact on the management of a familial unruptured IA in a relative.

Background: Atopic dermatitis (AD) needs intensive treatment and has a negative impact on quality of life. Shared medical appointments (SMAs) showed to be effective in clinical outcomes of chronic diseases, but little is known about the effects on children and families. Objective: To evaluate the effects of SMAs compared to individual appointments (IA) for children with AD and their parents on coping and clinical outcomes. Methods: In a pragmatic randomized controlled trial, new patients in UMC Utrecht with AD, younger than 18 years, and their parents were assigned to the SMA group or the IA group using a covariate adaptive randomization method, controlled for age. Before the intervention, 2 months (primary time-point) and 6 months thereafter, we assessed parental emotional coping (primary outcome), quality of life, anxiety about corticosteroids and patient disease activity. Patients, parents and healthcare professionals could not be blinded to group assignment. Results: Of 140 patients, enrolled in the trial, 69 patients were assigned to the SMA and 71 to the IA intervention of whom 114 completed the intervention (SMA: 49; IA: 65). After 2 months, there were no differences between SMAs and IAs in effects on emotional coping: b 0.66, 95% CI −0.7 to 2.03; P = 0.33 (mean difference: 0.30; 95% CI −1.56 to 2.16; N SMA: 11; IA: 24), quality of life, anxiety about corticosteroids and disease activity. From the initial appointment to long-term follow-up, both groups showed substantial improvements, but not significant in disease activity and significant reduction in anxiety about corticosteroids. This study is limited by a low response rate; therefore, linear mixed models and dropout analyses were performed. No serious adverse events were reported. Conclusion and Clinical Relevance: For children with AD and their parents, there were no additional benefits of GMAs in parental emotional coping, anxiety about corticosteroids, quality of life and disease activity. Trial registration: www.ISRCTN.org, ISRCTN08506572.

Background: Physical activity has been shown to reduce side-effects of breast cancer and its treatment. As physical activity levels of patients with breast cancer are largely unknown, we investigated these levels and compared them to women from the general population. Methods: In this prospective cohort study, physical activity levels of women with breast cancer participating in the UMBRELLA cohort were assessed at radiotherapy intake and thereafter every 6 months up to 3 years with the SQUASH questionnaire, which was also used in a random sample of the Dutch population. We compared physical activity levels (no activity, low, moderate or high levels of sports, leisure time or total activity) between patients and the Dutch female population using multinomial logistic regression. Standardized Prevalence Ratios (SPR) were calculated to compare adherence to Dutch physical activity guidelines. Results: Women with breast cancer (nbaseline = 1655, n6 months = 1414, n12 months = 1186, n18 months = 957, n24 months = 744, n30 months = 555, and n36 months = 377) were less likely to spend time in physical activity compared to the general population (n = 11,710) until 3 years post-diagnosis, especially after 6 months (ORhigh-vs.-no activity = 0.34, 95% CI: 0.28–0.41). From 12 months onwards, patients were more likely to perform sports compared to the general population, especially patients who underwent systemic therapy. Guideline adherence was significantly lower in patients at baseline and 6 months (SPRbaseline = 89, 95% CI: 82–97; SPR6 months = 88, 95% CI: 81–96), and comparable to the general population at 12–36 months, especially in older women. Conclusions: Physical activity levels in women with breast cancer during and after treatment were lower compared to the Dutch female population. Three years post-treatment, they were still less physically active, although they spend more time in sport activities. As about half of the patients did not perform any sports, physical activity needs to be stimulated during and after treatment.

AimTreatment options for head and neck adenoid cystic carcinoma (AdCC) are limited in advanced disease. Chemokine receptor type 4 (CXCR4) is present in various tumour types, including AdCC. Upregulation is associated with tumour recurrence and metastasis. New CXCR4-specific diagnostic and therapeutic target agents have recently been available. This study aimed to analyse CXCR4 expression in a cohort of primary head and neck AdCC.MethodsAfter histopathological revision, tumour tissues of 73 consecutive patients with AdCC over 1990–2016 were sampled on a tissue microarray. Slides were immunohistochemically stained for CXCR4 and semiquantitatively scored. Associations between protein expression and cliniopathological parameters were tested. HRs were calculated using a Cox proportional hazard model.ResultsSixty-six tumours could be analysed. CXCR4 expression was present in 81% of the tumours with a median of 29% (IQR 1–70) positive cells. Expression was univariately correlated to perineural growth (Spearman ρ .26, p=0.04) and bone invasion (Spearman ρ .32, p=0.01), but not with tumour grade.CXCR4 expression in the primary tumour was significantly higher in tumours that recurred as compared with those that did not recur (median 60%, IQR 33–72 vs 12%, IQR 1–70, Kruskal-Wallis p=0.01). After dichotomisation, >25% of CXCR4 expressions proved an independent prognosticator for a reduced recurrence-free survival (RFS) (HR 7.2, 95% CI 1.5 to 72.4, p=0.04).ConclusionCXCR4 is expressed in the majority of primary AdCCs and independently correlated to worse RFS, suggesting CXCR4 as a target for imaging and therapy purposes in patients with advanced AdCC.

Timely recognition of acute coronary syndrome remains a challenge as many biomarkers, including troponin, remain negative in the first hours following the onset of chest pain. We assessed the diagnostic accuracy of heart-type fatty acid binding protein (H-FABP), a cardiac biomarker with potential value immediately post symptom onset.Prospective monocentre diagnostic accuracy study of H-FABP bedside point of care (CardioDetect®) and ELISA tests in acute coronary syndrome suspected patients presenting within 24 hours of symptom onset to the emergency department, in addition to clinical findings, electrocardiography and the currently recommended biomarker high sensitivity troponin-T (hs-cTnT). The final diagnosis of acute coronary syndrome was adjudicated by two independent cardiologists, blinded to H-FABP results. Acute coronary syndrome was diagnosed in 149 (32.9%) of 453 unselected patients with suspected acute coronary syndrome (56% men, mean age 62.6 years). Negative predictive values were similar for H-FABP point of care and ELISA tests (79% vs. 78% respectively), but inferior to initial hs-cTnT (negative predictive value 86%). The addition of H-FABP point of care results to hs-cTnT increased the negative predictive value to 89%. In a multivariable logistic regression model, H-FABP point of care and ELISA tests yielded relevant diagnostic information in addition to clinical findings and ECG (likelihood ratio test p0.001) and increased area under the receiver operating characteristics curve (AUC; 0.82 vs. 0.84 and 0.84). This added value attenuated, however, after inclusion of hs-cTnT in the diagnostic model (AUC 0.88).In patients suspected of acute coronary syndrome presenting to the emergency department, H-FABP testing improves diagnostic accuracy in addition to clinical findings and electrocardiography. H-FABP, however, has no additional diagnostic value when hs-cTnT measurements are also available.

Background Access to echocardiography in primary care is limited, but is necessary to accurately diagnose heart failure (HF). Aim To determine the proportion of patients with a GP’s diagnosis of HF who really have HF. Design and setting A cross-sectional study of patients in 30 general practices with a GP’s diagnosis of heart failure, based on the International Classification of Primary Care (ICPC) code K77, between June and November 2011. Method Electronic medical records of the patients’ GPs were scrutinised for information on the diagnosis. An expert panel consisting of two cardiologists and an experienced GP used all available diagnostic information, and established the presence or absence of HF according to the criteria of the European Society of Cardiology (ESC) HF guidelines. Results In total, 683 individuals had a GP’s diagnosis of HF. The mean age was 77.9 (SD 11.4) years, and 42.2% were male. Of these 683, 79.6% received cooperative care from a cardiologist. In 73.5% of cases, echocardiography was available for panel re-evaluation. Based on consensus opinion of the panel, 434 patients (63.5%, 95% confidence interval [CI] = 59.9 to 67.1) had definite HF, of which 222 (32.5%, 95% CI = 30.9 to 34.1) had HF with a reduced ejection fraction (HFrEF), 207 (30.3%, 95% CI = 29.0 to 31.6) had HF with a preserved ejection fraction (HFpEF), and five (0.7%, 95% CI = 1.2 to 2.6) had isolated right-sided HF. In 17.3% of cases (95% CI = 14.4 to 20.0), the panel considered HF absent, and in 19.2% (95% CI = 16.3 to 22.2) the diagnosis remained uncertain. Conclusion More than one-third of primary care patients labelled with HF may not have HF, and such overdiagnosis may result in inadequate patient management.

Background Health care providers aim to stimulate self-management in type 2 diabetes (T2DM) patients. However, they have a limited number of patient contacts to do this. With the growing number of T2DM patients, innovative and cost-effective interventions to promote self-management are needed. We aim to evaluate the effectiveness of diabetes self-management education via a smartphone app in T2DM patients on insulin therapy. Methods Non-blinded two-arm multi-centre randomised controlled superiority trial with parallel-groups and equal randomisation (‘TRIGGER study’). Eligible patients are 40–70 years, on insulin therapy since at least 3 months, with HbA1c > 53 mmol/mol (> 7%). In total 228 patients will be recruited. The intervention group (n = 114) will receive diabetes self-management education via a smartphone app to trigger diabetes self-management: unidirectional text messages, free of charge, evidence and psychological theory based, with regard to dietary habits, physical activity, hypoglycaemia and glucose variability. Patients choose their preferred frequency (two to six times per week), topics (two or three additionally to hypoglycaemia, which is an obligatory topic), and duration (6 or 9 months). The control group (n = 114) will receive care-as-usual. The primary study endpoint is the HbA1c level after a follow-up of 6 months. The percentage of patients who achieve an HbA1c level ≤ 53 mmol/mol (≤7%) without hypoglycaemia (plasma glucose

Purpose. Many unhealthy behavioral habits often originate in adolescence. In the literature, the school-based whole school approach is stated be the most promising way to promote healthy behavior. Herein, interventions are evidence based and integrated into the curriculum, while embedded in complementary healthy school policies and environment. This study evaluates the effects of such an intervention on Dutch high schools. Methods. Two Dutch high schools and two controls were followed to evaluate the intervention’s effects on health behaviors, body mass index, and psychosocial problems after 1 year ( N = 969) and 2 years ( N = 605). Outcomes were measured via self-report surveys and analyzed with mixed methods regression analyses. To complement information on intervention effects, structured interviews were held with a representative sample of teachers per intervention school to map their respective whole school approach implementation success. Results. After 2 years, one intervention school showed significant improvements: Body mass index and excessive screen time use were reduced. In the other intervention school, priority targets did not improve. These findings reflected their respective success in intervention implementation, for example, differences in intervention integration and tailoring. Conclusions. This study shows that it is feasible for schools to implement a comprehensive Health Promoting School intervention themselves and that, when successful, effects in terms of improving behaviors and health outcomes are promising. The process evaluation helped understand these findings in context.

To predict the risk of future unfavourable health outcomes in older people it is common to assess the level of both basic and instrumental activities of daily living. To accomplish this, the commonly used Katz-6 and the Lawton IADL questionnaires can be combined to form the 'Modified Katz ADL' scale, also known as the Katz-15 scale. So far, the validity and reliability of the Katz-15 scale is unknown. The objective of the current study is to investigate how well the Katz-15 is able to predict future unfavorable health outcomes and how this is related to the existing Katz-6 scale.We performed a follow-up study using data from a group of 60 year and older participants from a large Dutch clinical trial.We included 2321 participants in the analysis. The average age of the study population was 74 years and 44% was male.We studied the relation between the Katz-15 scale and a number of unfavourable health outcomes, such as hospitalization, admission to a nursing home, admission to a home for the aged and death within one year of follow-up.We found the Katz-15 to be both internally consistent and strongly associated with quality of life measures. We observed moderate to strong associations between the Katz-15 and the unfavourable health outcomes All associations studied were stronger for the Katz-15 scale as compared to the Katz-6 scale.The results of our study indicate that the Katz-15 scale is able to reliably and validly predict future unfavorable health outcomes. This makes the scale a valuable measure in determining both basic and instrumental activities of daily living.

Objectives Computed tomography (CT) is the most widely used method to assess resectability of pancreatic and peri-ampullary cancer. One of the contra-indications for curative resection is the presence of extra-regional lymph node metastases. This meta-analysis investigates the accuracy of CT in assessing extra-regional lymph node metastases in pancreatic and peri-ampullary cancer. Methods We systematically reviewed the literature according to the PRISMA guidelines. Studies reporting on CT assessment of extra-regional lymph nodes in patients undergoing pancreatoduodenectomy were included. Data on baseline characteristics, CT-investigations and histopathological outcomes were extracted. Diagnostic accuracy, positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity were calculated for individual studies and pooled data. Results After screening, 4 cohort studies reporting on CT-findings and histopathological outcome in 157 patients with pancreatic or peri-ampullary cancer were included. Overall, diagnostic accuracy, specificity and NPV varied from 63 to 81, 80–100% and 67–90% respectively. However, PPV and sensitivity ranged from 0 to 100% and 0–38%. Pooled sensitivity, specificity, PPV and NPV were 25%, 86%, 28% and 84% respectively. Conclusions CT has a low diagnostic accuracy in assessing extra-regional lymph node metastases in pancreatic and peri-ampullary cancer. Therefore, suspicion of extra-regional lymph node metastases on CT alone should not be considered a contra-indication for exploration.

Objective Pacing technology and care have improved notably over the past decade, justifying an update on the long-term prognosis and pre-implantation determinants of prognosis of bradycardia pacemaker (PM) recipients. Design Prospective cohort study. Setting 23 Dutch pacemaker centres Patients Pre-implantation characteristics of 1517 patients receiving a first bradycardia PM between 2003–2007 were studied in relation to survival. Interventions None; patients were followed up during routine clinical practice. Main outcome measures Cause and time to death. Results At the end of a mean follow-up of 5.8 (SD 1.1) years, 512 patients (33%) died, mostly of non-cardiac cause (67%). There were two PM related deaths. Survival rates were 93%, 81%, 69%, and 61% after 1, 3, 5 and 7 years, respectively. PM recipients without concomitant cardiovascular disease at implantation showed survival rates comparable to age and sex matched controls. Predictors at time of implantation associated with cardiac mortality were: age, coronary artery disease (CAD), diabetes, heart failure, valve disease, and the indication for PM implantation. Predictors for all cause mortality were: male gender, age, body mass index, CAD, cardiac surgery, diabetes, heart failure, and maintained atrioventricular synchrony. Conclusions A pre-implantation history of heart failure, CAD, and diabetes are the most important predictors for worse prognosis in PM recipients. Without baseline heart disease, survival rates equal that of the general population, suggesting that the prognosis of contemporary PM recipients is mainly determined by comorbid diseases and a bradycardia pacing indication as such does not influence survival. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT00135174.

Aims Remote follow-up (FU) enables to cope with the expanding number of pacemaker (PM) FU. Although remote FU offers comparable monitoring options to in-office FU, reprogramming of device settings is not available, thereby imposing a potentially important restriction to the applicability of remote FU. The aim of this study was to assess in a large cohort of bradycardia PM recipients, the incidence of PM reprogramming during long-term FU and its predictors, to judge the possibilities for remote FU. Methods and results Between 2003 and 2010 all in-office FU of 1517 bradycardia PM recipients included in the FOLLOWPACE study were recorded. Only 24.5% of all 13 258 recorded FU visits >3 months after implantation were visits-with-reprogramming (VWRs), occurring in 1158 patients (79%). Fifty percent of patients were free of reprogramming at 9 months, and 29% at 24 months. Using multivariable binary logistic regression analysis, the following patient characteristics were predictive for frequent PM reprogramming, defined as >3 VWRs during 3 year FU: age, a history of atrial arrhythmias, PM complication 80%) do not need frequent reprogramming, suggesting a potential benefit of using remote FU to reduce the number of unnecessary in-office visits.

Background Disruption of frontal-subcortical circuits by cerebral small-vessel disease is thought to predispose to depression characterized by motivational symptoms. We examined the influence of lacunar infarcts and white matter lesions (WML) on severity and course of depressive symptoms during 3 years follow-up. Methods Within the SMART-Medea study, analyses were performed in 650 patients with symptomatic atherosclerotic disease (62±9 years). Volumetric WML measures (deep and periventricular) were obtained with 1.5T magnetic resonance imaging at baseline; infarcts were rated visually. Depressive symptoms were assessed with Patient Health Questionnaire-9 at baseline and during five follow-up times and categorized into motivational and mood scores. Results Using generalized estimating equation models, a relation between lacunar infarcts in deep white matter and an increased severity (mean difference=1.47, 95% confidence interval .33–2.60) and more fluctuating course ( p value interaction infarcts ⁎ time=.04) of depressive symptoms during follow-up was found, adjusted for age, sex, education, vascular risk, and cognition. This relation was primarily driven by motivational symptoms. Lacunar infarcts were not associated with severity or course of depressive symptoms. Deep WML were associated with a more fluctuating but not more severe course of depressive symptoms. Excluding patients with major depressive disorder did not change the results. Conclusions In patients with symptomatic atherosclerotic disease and relatively mild depressive symptoms, depressive symptoms, characteristic of motivational problems, remained higher during 3 years follow-up in patients with lacunar infarcts in deep white matter and that symptom severity fluctuated over time.

Background Patients with cardiovascular disease have an increased risk for depression, and depression predicts poor prognosis in these patients, but the long-term course of depression is not known. We studied the natural course of elevated levels of depressive symptoms in patients with cardiovascular disease over eight years follow-up. Methods Within the Second Manifestations of ARTerial disease – Memory, depression and aging (SMART-Medea) study, depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9) in 690 patients (62±10 years) at baseline and bi-annually during 8 years follow-up. Natural course was described for symptom severity and course type (never, single episode, intermittent, and chronic) based on the cut-off point of ≥6 on the PHQ-9. Using multinomial regression analysis (reference: never depressed) we estimated age- and sex-adjusted odds ratios (OR) for the associations of demographic factors and vascular disease categories with course type. Results Of the 690 patients, 60% was never depressed, 10% had a single episode, 19% had an intermittent and 11% a chronic course of depression. Increased risk for chronic course was observed for women (OR=3.42; 95% CI=1.98–5.90), those with younger age (OR=3.20; 95% CI=1.73–5.94), and for patients with cerebrovascular disease when compared to patients with coronary artery disease (OR=2.50; 95% CI=1.31–4.78). Limitations No information was available on clinical diagnosed major depressive disorder and/or clinical events during follow-up. Conclusions In patients with cardiovascular disease, an intermittent or chronic course of elevated levels of depressive symptoms is very common. Patients with cardiovascular disease may require more careful clinical monitoring and management of depressive symptoms.

Aims Pulmonary vein antrum isolation (PVAI) is the cornerstone of atrial fibrillation (AF) ablation. There is an ongoing discussion on whether and when to add substrate modification to PVAI. This study evaluates (1) long-term efficacy of PVAI as a primary ablation strategy in all patients independently from AF type and (2) predictors of arrhythmia recurrence. Methods and results A total of 509 consecutive patients (mean age 57 years, 38.9% non-paroxysmal AF) with AF underwent PVAI. In redo procedures, ablation was restricted to re-pulmonary vein (PV) isolation in case of PV reconnection. If the PVs were found to be isolated, substrate modification was performed. In total, 774 procedures were performed. Mean follow-up duration after the first and last ablation was, respectively, 66 ± 23 and 55 ± 25 months. A single PVAI was sufficient in restoring and maintaining long-term sinus rhythm in 41.3% ( n = 210) of patients. Multiple procedures (mean 1.5) with re-PV isolation increased long-term success to 58.3% ( n = 297). Additional substrate modification ( n = 70) increased success to 62.5% ( n = 318). After the last ablation, 87.5% of patients experienced success or significant clinical improvement on or off antiarrhythmic drugs. The incidence of left-sided atrial flutter or atrial tachycardia was 5% after PVAI and increased to 32% after additional substrate modification. Independent predictors for arrhythmia recurrence after the last ablation were non-paroxysmal AF, female sex, body mass index, hypertension, and AF duration. Conclusion Five-year freedom of atrial tachyarrhythmia could be achieved by PVAI as primary ablation strategy in 58.3% of patients. Additional substrate modification only moderately increased overall success.

OBJECTIVES: To determine the effectiveness of a proactive primary care program on the daily functioning of older people in primary care. DESIGN: Single-blind, three-arm, cluster-randomized controlled trial with 1-year follow-up. SETTING: Primary care setting, 39 general practices in the Netherlands. PARTICIPANTS: Community-dwelling people aged 60 and older (N = 3,092). INTERVENTIONS: A frailty screening intervention using routine electronic medical record data to identify older people at risk of adverse events followed by usual care from a general practitioner; after the screening intervention, a nurse-led care program consisting of a comprehensive geriatric assessment, evidence-based care planning, care coordination, and follow-up; usual care. MEASUREMENTS: Primary outcome was daily functioning measured using the Katz-15 (6 activities of daily living (ADLs), 8 instrumental activities of daily living (IADLs), one mobility item (range 0–15)); higher scores indicat greater dependence. Secondary outcomes included quality of life, primary care consultations, hospital admissions, emergency department visits, nursing home admissions, and mortality. RESULTS: The participants in both intervention arms had less decline in daily functioning than those in the usual care arm at 12 months (mean Katz-15 score: screening arm, 1.87, 95% confidence interval (CI) = 1.77–1.97; screening and nurse-led care arm, 1.88, 95% CI = 1.80–1.96; control group, 2.03, 95% CI = 1.9 –2.13; P = .03). No differences in quality of life were observed. CONCLUSION: Participants in both intervention groups had less decline than those in the control group at 1-year follow-up. Despite the statistically significant effect, the clinical relevance is uncertain at this point because of the small differences. Greater customizing of the intervention combined with prolonged follow-up may lead to more robust results.

The prognosis of aneurysmal subarachnoid hemorrhage (aSAH) has improved during the past decades. However, a recent hospital-based study showed that 90-day case fatality is still 30%.1 Determinants of functional outcome after aSAH may include the severity of the initial hemorrhage, rebleeding of the aneurysm, and cerebral ischemia that can be distinguished into (1) acute ischemia at the time of bleeding when intracranial pressure rises and cerebral perfusion pressure drops, (2) procedure-related ischemia from endovascular or neurosurgical treatment of the aneurysm, and (3) delayed cerebral ischemia (DCI), which can occur between days 4 and 14 after the hemorrhage.2,3 Magnetic resonance diffusion weighted imaging (MRI-DWI) is increasingly used for the evaluation of ischemia after aSAH. The aims of the present review were to (1) analyze the proportion of patients with MRI-DWI lesions within 72 hours after aSAH, both before and after aneurysm treatment; (2) study determinants of MRI-DWI lesions within 72 hours after aSAH; (3) analyze the proportion of patients with MRI-DWI lesions between 72 hours and 21 days after aSAH; (4) investigate the predictive value of MRI-DWI lesions within 72 hours for the development of DCI; and 5) investigate whether MRI-DWI can be used for the diagnosis of DCI in patients with clinical deterioration. ### Search Strategy We searched the PUBMED, EMBASE, and Web of Science databases with the following combination of variables: MRI OR magnetic resonance AND subarachnoid hemorrhage OR SAH OR DCI OR delayed cerebral ischemia OR DIND. The last search was performed in June 28, 2016. Only studies published after January 1, 2000, were included to assure a similar degree of image quality, given the technical developments in MRI hardware and sequences. Both prospective and retrospective studies were included. Eligible articles were identified according to the PICO criteria. Type of patient population (P): (1) >95% of patients …

BACKGROUND: The first antenatal clinic (ANC) visit helps to distinguish pregnant women who require standard care, from those with specific problems and so require special attention. There are protocols to guide care providers to provide optimal care to women during ANC. Our objectives were to determine the level of provider adherence to first antenatal visit guidelines in the Safe Motherhood Protocol (SMP), and assess patient factors that determine complete provider adherence. METHODS: This cross-sectional study is part of a cohort study that recruited women who delivered in eleven health facilities and who had utilized antenatal care services during their pregnancy in the Greater Accra region of Ghana. A record review of the first antenatal visit of participants was carried out to assess the level of adherence to the SMP, using a thirteen-point checklist. Information on their socio-demographic characteristics and previous pregnancy history was collected using a questionnaire. Percentages of adherence levels and baseline characteristics were estimated and cluster-adjusted odds ratios (OR) calculated to identify determinants. RESULTS: A total of 948 women who had delivered in eleven public facilities were recruited with a mean age (SD) of 28.2 (5.4) years. Overall, complete adherence to guidelines pertained to only 48.1% of pregnant women. Providers were significantly more likely to completely adhere to guidelines when caring for multiparous women [OR = 5.43 (1.69-17.44), p

PURPOSE: We sought to determine the prevalence of airway obstruction and bronchodilator responsiveness in adults consulting for acute cough in primary care. METHODS: Family physicians recruited 3,105 adult patients with acute cough (28 days or shorter) attending primary care practices in 12 European countries. After exclusion of patients with preexisting physician-diagnosed asthma or chronic obstructive pulmonary disease (COPD), we undertook complete case analysis of spirometry results (n = 1,947) 28 to 35 days after inclusion. Bronchodilator responsiveness was diagnosed if there were recurrent complaints of wheezing, cough, or dyspnea and an increase of the forced expiratory volume in 1 second (FEV(1)) of 12% or more after bronchodilation. Airway obstruction was diagnosed according to 2 thresholds for the (postbronchodilator) ratio of FEV(1) to forced vital capacity (FEV(1):FVC): less than 0.7 and less than the lower limit of normal. RESULTS: There were 240 participants who showed bronchodilator responsiveness (12%), 193 (10%) had a FEV(1)/FVC ratio of less than 0.7, and 126 (6%) had a ratio of less than the lower limit of normal. Spearman's correlation between the 2 definitions of obstruction was 0.71 (P

Walter Bouwmeester and colleagues investigated the reporting and methods of prediction studies in 2008, in six high-impact general medical journals, and found that the majority of prediction studies do not follow current methodological recommendations., Background We investigated the reporting and methods of prediction studies, focusing on aims, designs, participant selection, outcomes, predictors, statistical power, statistical methods, and predictive performance measures. Methods and Findings We used a full hand search to identify all prediction studies published in 2008 in six high impact general medical journals. We developed a comprehensive item list to systematically score conduct and reporting of the studies, based on recent recommendations for prediction research. Two reviewers independently scored the studies. We retrieved 71 papers for full text review: 51 were predictor finding studies, 14 were prediction model development studies, three addressed an external validation of a previously developed model, and three reported on a model's impact on participant outcome. Study design was unclear in 15% of studies, and a prospective cohort was used in most studies (60%). Descriptions of the participants and definitions of predictor and outcome were generally good. Despite many recommendations against doing so, continuous predictors were often dichotomized (32% of studies). The number of events per predictor as a measure of statistical power could not be determined in 67% of the studies; of the remainder, 53% had fewer than the commonly recommended value of ten events per predictor. Methods for a priori selection of candidate predictors were described in most studies (68%). A substantial number of studies relied on a p-value cut-off of p, Editors' Summary Background There are often times in our lives when we would like to be able to predict the future. Is the stock market going to go up, for example, or will it rain tomorrow? Being able predict future health is also important, both to patients and to physicians, and there is an increasing body of published clinical “prediction research.” Diagnostic prediction research investigates the ability of variables or test results to predict the presence or absence of a specific diagnosis. So, for example, one recent study compared the ability of two imaging techniques to diagnose pulmonary embolism (a blood clot in the lungs). Prognostic prediction research investigates the ability of various markers to predict future outcomes such as the risk of a heart attack. Both types of prediction research can investigate the predictive properties of patient characteristics, single variables, tests, or markers, or combinations of variables, tests, or markers (multivariable studies). Both types of prediction research can include also studies that build multivariable prediction models to guide patient management (model development), or that test the performance of models (validation), or that quantify the effect of using a prediction model on patient and physician behaviors and outcomes (impact assessment). Why Was This Study Done? With the increase in prediction research, there is an increased interest in the methodology of this type of research because poorly done or poorly reported prediction research is likely to have limited reliability and applicability and will, therefore, be of little use in patient management. In this systematic review, the researchers investigate the reporting and methods of prediction studies by examining the aims, design, participant selection, definition and measurement of outcomes and candidate predictors, statistical power and analyses, and performance measures included in multivariable prediction research articles published in 2008 in several general medical journals. In a systematic review, researchers identify all the studies undertaken on a given topic using a predefined set of criteria and systematically analyze the reported methods and results of these studies. What Did the Researchers Do and Find? The researchers identified all the multivariable prediction studies meeting their predefined criteria that were published in 2008 in six high impact general medical journals by browsing through all the issues of the journals (a hand search). They then scored the methods and reporting of each study using a comprehensive item list based on recent recommendations for the conduct of prediction research (for example, the reporting recommendations for tumor marker prognostic studies—the REMARK guidelines). Of 71 retrieved studies, 51 were predictor finding studies, 14 were prediction model development studies, three externally validated an existing model, and three reported on a model's impact on participant outcome. Study design, participant selection, definitions of outcomes and predictors, and predictor selection were generally well reported, but other methodological and reporting aspects of the studies were suboptimal. For example, despite many recommendations, continuous predictors were often dichotomized. That is, rather than using the measured value of a variable in a prediction model (for example, blood pressure in a cardiovascular disease prediction model), measurements were frequently assigned to two broad categories. Similarly, many of the studies failed to adequately estimate the sample size needed to minimize bias in predictor effects, and few of the model development papers quantified and validated the proposed model's predictive performance. What Do These Findings Mean? These findings indicate that, in 2008, most of the prediction research published in high impact general medical journals failed to follow current guidelines for the conduct and reporting of clinical prediction studies. Because the studies examined here were published in high impact medical journals, they are likely to be representative of the higher quality studies published in 2008. However, reporting standards may have improved since 2008, and the conduct of prediction research may actually be better than this analysis suggests because the length restrictions that are often applied to journal articles may account for some of reporting omissions. Nevertheless, despite some encouraging findings, the researchers conclude that the poor reporting and poor methods they found in many published prediction studies is a cause for concern and is likely to limit the reliability and applicability of this type of clinical research. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001221. The EQUATOR Network is an international initiative that seeks to improve the reliability and value of medical research literature by promoting transparent and accurate reporting of research studies; its website includes information on a wide range of reporting guidelines including the REMARK recommendations (in English and Spanish) A video of a presentation by Doug Altman, one of the researchers of this study, on improving the reporting standards of the medical evidence base, is available The Cochrane Prognosis Methods Group provides additional information on the methodology of prognostic research

Item does not contain fulltext Background: In the Netherlands we select candidates for the postgraduate GP training by assessing personal qualities in interviews. Because of differences in the ratio of number of candidates and number of vacancies between the eight departments of GP training we questioned whether the risk of being rejected diverged amongst them. Objective: The research question of this study was to which degree department of choice, candidates' characteristics and qualities assessed during interviews explain admission into GP training. Methods: A nationwide observational study was conducted of all candidates who applied for postgraduate GP training in 2009/ 2010. Application ratio per department, candidates' characteristics (gender, age, region of medical school and times of application) and qualities (motivation, orientation on the job, personal attributes and learning needs) were collected. Outcome measures were admission to interview and admission to GP training. Results: The study population addressed 542 candidates. Sixty three candidates were rejected on application letter (11.6%). So 479 candidates were admitted to the interview, of which 340 were admitted to the GP training (71%). Gender and region of medical school outside North West Europe were associated with admission to the interview. Department of choice had a strong association with admission in both stages (RR: 0.30 to 0.74; 0.20 to 0.79 respectively), while candidates' qualities explained admission (RR: 1.09- 1.25) as well. Conclusion:The influence of department of choice yields doubts about fairness of the procedure. So advantages and disadvantages of a national procedure are discussed as well as those of a competency based procedure.

Aims The number of patients >80 years receiving pacemakers (PMs) is increasing. Little is known about survival and complications in this specific subgroup. We aim to determine predictors of long-term survival. Methods and results Pacemaker-related complications and death occurring in patients receiving a first PM for conventional bradycardia indications were systematically documented (the FollowPace registry). This report describes 481 patients ≥80 years during a mean follow-up of 5.8 (SD 1.2) years. Within 2 months 54 PM complications occurred in 47 patients (9.8%). During follow-up, 35 adverse PM events were reported in 33 patients (6.9%). Complication rates in patients ≥80 years were comparable with those for patients

Background. Detection rates of depression in primary care are

Background. Women with diabetes have an increased risk of urinary tract infections (UTIs), especially recurrences. Aim. To investigate diabetes characteristics associated with the risk of recurrent lower UTIs and the antibiotic prescription pattern. Methods. In an exploratory retrospective study involving 7063 women aged >30 years, we studied the incidence of recurrent UTI (relapses and reinfection) in women with (n = 340) and without diabetes (n = 6618). Multivariable logistic regression and multilevel multinomial logistic analyses were used to determine the adjusted associations between diabetes characteristics and recurrent UTI [odds ratio (OR); 95% confidence interval (CI)] and the influence of diabetes on the pattern of antibiotic prescriptions for UTI, respectively. Results. Relapses and reinfections were reported in 7.1% and 15.9% of women with diabetes versus 2.0% and 4.1% of women without diabetes. There was an independent higher risk of recurrent UTI in women with diabetes compared with women without diabetes (OR 2.0; 95% CI 1.4–2.9). Women taking oral blood glucose-lowering medication (OR 2.1; 95% CI 1.2–3.5) or insulin (OR 3.0; 95% CI 1.7–5.1) or who had had diabetes for >5 years (OR 2.9; 95% CI 1.9–4.4) or who had retinopathy (OR 4.1; 95% CI 1.9–9.1) were at risk of recurrent UTI. The pattern of antibiotic prescriptions for UTI was not influenced by diabetes. Conclusions. Women with diabetes >5 years or with glucose-lowering medication or with retinopathy have an increased risk of recurrent UTI. Diabetes itself does not seem to influence the antibiotic prescription pattern. Research focusing on effective antibiotic treatment of UTI in women at risk of recurrence is needed and may help limit the development of antibiotic resistance.

Major depressive disorder often remains unrecognized in primary care.Development of a clinical prediction rule using easily obtainable predictors for major depressive disorder in primary care patients.A total of 1046 subjects, aged 18-65 years, were included from seven large general practices in the center of The Netherlands. All subjects were recruited in the general practice waiting room, irrespective of their presenting complaint. Major depressive disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Text Revision edition criteria was assessed with the Composite International Diagnostic Interview. Candidate predictors were gender, age, educational level, being single, number of presented complaints, presence of non-somatic complaints, whether a diagnosis was assigned, consultation rate in past 12 months, presentation of depressive complaints or prescription of antidepressants in past 12 months, number of life events in past 6 months and any history of depression.The first multivariable logistic regression model including only predictors that require no confronting depression-related questions had a reasonable degree of discrimination (area under the receiver operating characteristic curve or concordance-statistic (c-statistic) = 0.71; 95% Confidence Interval (CI): 0.67-0.76). Addition of three simple though more depression-related predictors, number of life events and history of depression, significantly increased the c-statistic to 0.80 (95% CI: 0.76-0.83). After transforming this second model to an easily to use risk score, the lowest risk category (sum score5) showed a 1% risk of depression, which increased to 49% in the highest category (sum scoreor = 30).A clinical prediction rule allows GPs to identify patients-irrespective of their complaints-in whom diagnostic workup for major depressive disorder is indicated.