Hospital-based, prospective, multicentre surveillance to determine the incidence of intussusception in children aged below 15 years in Germany

<p>Abstract</p> <p>Background</p> <p>A new vaccine against Rotavirus (RV) gastroenteritis was introduced in Germany in 2006. In 1997 the first RV vaccine was withdrawn due to an increased incidence in intussusception (IS). Thus, an accurate estimation of the incidence of IS is important for post-licensure surveillance.</p> <p>Methods</p> <p>IS-Data were obtained from the 'Erhebungseinheit für seltene pädiatrische Erkrankungen Deutschland' (ESPED, German surveillance unit for rare pediatric diseases) collaborations' central register where all cases of intussusception in Germany for the years 2006 and 2007 are collected (n = 1200). In order to obtain an unbiased estimate of the incidence, it is necessary to determine the population under risk out of which these cases originated, and the proportion of real cases not reported to the registry (underreporting). In order to assess underreporting, a random sample of 31 hospitals was re-assessed by an outside reviewer. The estimation of incidence was done using a single Maximum-Likelihood (ML) estimator based on data from both the registry and the sample.</p> <p>Results</p> <p>The uncorrected observed incidence was calculated to be 26.6/100,000 child-years for children below 1 year old, 23.8 for those below 2 years old, and 5.2 for those below 15 years old. The review revealed a mean reporting quota of about 41% and the ML approach yielded an incidence of 51.5/100,000 child-years (95%CI [41.7;61.1]) for children below 2 years of age.</p> <p>Conclusions</p> <p>While substantial under-reporting led to very conservative estimates of the IS incidence, the approach described here allows an accurate estimation of IS incidence including corresponding confidence bands. Therefore, ML estimation is a straightforward instrument to derive stable, unbiased estimates in epidemiological studies with incomplete data.</p

The effect of time-to-surgery on outcome in elderly patients with proximal femoral fractures

<p>Abstract</p> <p>Background</p> <p>Whether reducing time-to-surgery for elderly patients suffering from hip fracture results in better outcomes remains subject to controversial debates.</p> <p>Methods</p> <p>As part of a prospective observational study conducted between January 2002 and September 2003 on hip-fracture patients from 268 acute-care hospitals all over Germany, we investigated the relationship of time-to-surgery with frequency of post-operative complications and one-year mortality in elderly patients (age ≥65) with isolated proximal femoral fracture (femoral neck fracture or pertrochanteric femoral fracture). Patients with short (≤12 h), medium (> 12 h to ≤36 h) and long (> 36 h) times-to-surgery, counting from the time of the fracture event, were compared for patient characteristics, operative procedures, post-operative complications and one-year mortality.</p> <p>Results</p> <p>Hospital data were available for 2916 hip-fracture patients (mean age (SD) in years: 82.1 (7.4), median age: 82; 79.7% women). Comparison of groups with short (n = 802), medium (n = 1191) and long (n = 923) time-to-surgery revealed statistically significant differences in a few patient characteristics (age, American Society of Anesthesiologists ratings classification and type of admission) and in operative procedures (total hip endoprosthesis, hemi-endoprosthetic implants, other osteosynthetic procedures). However, comparison of these same groups for frequency of postoperative complications revealed only some non-significant associations with certain complications such as post-operative bleeding requiring treatment (early surgery patients) and urinary tract infections (delayed surgery patients). Both unadjusted rates of one-year all-cause mortality (between 18.1% and 20.5%), and the multivariate-adjusted hazard ratios (HR for time-to-surgery: 1.04; p = 0.55) showed no association between mortality and time-to-surgery.</p> <p>Conclusion</p> <p>Although this study found a trend toward more frequent post-operative complications in the longest time-to-surgery group, there was no effect of time-to-surgery on mortality. Shorter time-to-surgery may be associated with somewhat lower rates of post-operative complications such as decubitus ulcers, urinary tract infections, thromboses, pneumonia and cardiovascular events, and with somewhat higher rates of others such as post-operative bleeding or implant complications.</p

General practitioner advice on physical activity: Analyses in a cohort of older primary health care patients (getABI)

<p>Abstract</p> <p>Background</p> <p>Although the benefits of physical activity for health and functioning are recognized to extend throughout life, the physical activity level of most older people is insufficient with respect to current guidelines. The primary health care setting may offer an opportunity to influence and to support older people to become physically active on a regular basis. Currently, there is a lack of data concerning general practitioner (GP) advice on physical activity in Germany. Therefore, the aim of this study was to evaluate the rate and characteristics of older patients receiving advice on physical activity from their GP.</p> <p>Methods</p> <p>This is a cross-sectional study using data collected at 7 years of follow-up of a prospective cohort study (German epidemiological trial on ankle brachial index, getABI). 6,880 unselected patients aged 65 years and above in the primary health care setting in Germany were followed up since October 2001. During the 7-year follow-up telephone interview, 1,937 patients were asked whether their GP had advised them to get regular physical activity within the preceding 12 months. The interview also included questions on socio-demographic and lifestyle variables, medical conditions, and physical activity. Logistic regression analysis (unadjusted and adjusted for all covariables) was used to examine factors associated with receiving advice. Analyses comprised only complete cases with regard to the analysed variables. Results are expressed as odds ratios (ORs) with 95% confidence intervals (95% CI).</p> <p>Results</p> <p>Of the 1,627 analysed patients (median age 77; range 72-93 years; 52.5% women), 534 (32.8%) stated that they had been advised to get regular physical activity. In the adjusted model, those more likely to receive GP advice on physical activity were men (OR [95% CI] 1.34 [1.06-1.70]), patients suffering from pain (1.43 [1.13-1.81]), coronary heart disease and/or myocardial infarction (1.56 [1.21-2.01]), diabetes mellitus (1.79 [1.39-2.30]) or arthritis (1.37 [1.08-1.73]), and patients taking a high (> 5) number of medications (1.41 [1.11-1.80]).</p> <p>Conclusions</p> <p>The study revealed a relatively low rate of older primary health care patients receiving GP advice on physical activity. GPs appeared to focus their advice on patients with chronic medical conditions. However, there are likely to be many more patients who would benefit from advice.</p

Are Anticholinergic Symptoms a Risk Factor for Falls in Older General Practice Patients With Polypharmacy?: Study Protocol for the Development and Validation of a Prognostic Model

Background: Cumulative anticholinergic exposure, also known as anticholinergic burden, is associated with a variety of adverse outcomes. However, studies show that anticholinergic effects tend to be underestimated by prescribers, and anticholinergics are the most frequently prescribed potentially inappropriate medication in older patients. The grading systems and drugs included in existing scales to quantify anticholinergic burden differ considerably and do not adequately account for patients' susceptibility to medications. Furthermore, their ability to link anticholinergic burden with adverse outcomes such as falls is unclear. This study aims to develop a prognostic model that predicts falls in older general practice patients, to assess the performance of several anticholinergic burden scales, and to quantify the added predictive value of anticholinergic symptoms in this context. Methods: Data from two cluster-randomized controlled trials investigating medication optimization in older general practice patients in Germany will be used. One trial (RIME, n = 1,197) will be used for the model development and the other trial (PRIMUM, n = 502) will be used to externally validate the model. A priori, candidate predictors will be selected based on a literature search, predictor availability, and clinical reasoning. Candidate predictors will include socio-demographics (e.g. age, sex), morbidity (e.g. single conditions), medication (e.g. polypharmacy, anticholinergic burden as defined by scales), and well-being (e.g. quality of life, physical function). A prognostic model including sociodemographic and lifestyle-related factors, as well as variables on morbidity, medication, health status, and well-being, will be developed, whereby the prognostic value of extending the model to include additional patient-reported symptoms will be also assessed. Logistic regression will be used for the binary outcome, which will be defined as "no falls" vs. "≥1 fall" within six months of baseline, as reported in patient interviews. Discussion: As the ability of different anticholinergic burden scales to predict falls in older patients is unclear, this study may provide insights into their relative importance as well as into the overall contribution of anticholinergic symptoms and other patient characteristics. The results may support general practitioners in their clinical decision-making and in prescribing fewer medications with anticholinergic properties

Predicting negative health outcomes in older general practice patients with chronic illness: Rationale and development of the PROPERmed harmonized individual participant data database.

The prevalence of multimorbidity and polypharmacy increases significantly with age and are associated with negative health consequences. However, most current interventions to optimize medication have failed to show significant effects on patient-relevant outcomes. This may be due to ineffectiveness of interventions themselves but may also reflect other factors: insufficient sample sizes, heterogeneity of population. To address this issue, the international PROPERmed collaboration was set up to obtain/synthesize individual participant data (IPD) from five cluster-randomized trials. The trials took place in Germany and The Netherlands and aimed to optimize medication in older general practice patients with chronic illness. PROPERmed is the first database of IPD to be drawn from multiple trials in this patient population and setting. It offers the opportunity to derive prognostic models with increased statistical power for prediction of patient-relevant outcomes resulting from the interplay of multimorbidity and polypharmacy. This may help patients from this heterogeneous group to be stratified according to risk and enable clinicians to identify patients that are likely to benefit most from resource/time-intensive interventions. The aim of this manuscript is to describe the rationale behind PROPERmed collaboration, characteristics of the included studies/participants, development of the harmonized IPD database and challenges faced during this process

Predicting negative health outcomes in older general practice patients with chronic illness: Rationale and development of the PROPERmed harmonized individual participant data database.

The prevalence of multimorbidity and polypharmacy increases significantly with age and are associated with negative health consequences. However, most current interventions to optimize medication have failed to show significant effects on patient-relevant outcomes. This may be due to ineffectiveness of interventions themselves but may also reflect other factors: insufficient sample sizes, heterogeneity of population. To address this issue, the international PROPERmed collaboration was set up to obtain/synthesize individual participant data (IPD) from five cluster-randomized trials. The trials took place in Germany and The Netherlands and aimed to optimize medication in older general practice patients with chronic illness. PROPERmed is the first database of IPD to be drawn from multiple trials in this patient population and setting. It offers the opportunity to derive prognostic models with increased statistical power for prediction of patient-relevant outcomes resulting from the interplay of multimorbidity and polypharmacy. This may help patients from this heterogeneous group to be stratified according to risk and enable clinicians to identify patients that are likely to benefit most from resource/time-intensive interventions. The aim of this manuscript is to describe the rationale behind PROPERmed collaboration, characteristics of the included studies/participants, development of the harmonized IPD database and challenges faced during this process

Feasibility of a multidimensional home-based exercise programme for the elderly with structured support given by the general practitioner's surgery: Study protocol of a single arm trial preparing an RCT [ISRCTN58562962]

<p>Abstract</p> <p>Background</p> <p>Physical activity programmes can help to prevent functional decline in the elderly. Until now, such programmes use to target either on healthy community-dwelling seniors or on elderly living in special residences or care institutions. Sedentary or frail people, however, are difficult to reach when they live in their own homes. The general practitioner's (GP) practice offers a unique opportunity to acquire these people for participation in activity programmes. We conceptualised a multidimensional home-based exercise programme that shall be delivered to the target group through cooperation between GPs and exercise therapists. In order to prepare a randomised controlled trial (RCT), a feasibility study is being conducted.</p> <p>Methods</p> <p>The study is designed as a single arm interventional trial. We plan to recruit 90 patients aged 70 years and above through their GPs. The intervention lasts 12 weeks and consists of physical activity counselling, a home-exercise programme, and exercise consultations provided by an exercise therapist in the GP's practice and via telephone. The exercise programme consists of two main components: 1. a combination of home-exercises to improve strength, flexibility and balance, 2. walking for exercise to improve aerobic capacity. Primary outcome measures are: appraisal by GP, undesirable events, drop-outs, adherence. Secondary outcome measures are: effects (a. motor tests: timed-up-and-go, chair rising, grip strength, tandem stand, tandem walk, sit-and-reach; b. telephone interview: PRISCUS-Physical Activity Questionnaire, Short Form-8 Health Survey, three month recall of frequency of falls, Falls Efficacy Scale), appraisal by participant, exercise performance, focus group discussion. Data analyses will focus on: 1. decision-making concerning the conduction of a RCT, 2. estimation of the effects of the programme, detection of shortcomings and identification of subgroups with contrary results, 3. feedback to participants and to GPs.</p> <p>Conclusion</p> <p>A new cooperation between GPs and exercise therapists to approach community-dwelling seniors and to deliver a home-exercise programme is object of research with regard to feasibility and acceptance. In case of success, an RCT should examine the effects of the programme. A future implementation within primary medical care may take advantage from the flexibility of the programme.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN58562962.</p

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5–14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4–8·6]; rate ratio 1·37 [95% CI 1·17–1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94–1·15]; p=0·45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered—eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy