General practitioner-centred paediatric primary care reduces risk of hospitalisation for mental disorders in children and adolescents with ADHD: findings from a retrospective cohort study

Background: General practitioners (GPs) play an essential role in the sustainable management of attention-deficit/hyperactivity disorder (ADHD). To our knowledge, the healthcare programme described here is the first integrated care programme for paediatric ambulatory care embedded in GP-centred-healthcare in Germany. Objectives: To compare the health-service-utilisation of patients with ADHD enrolled in a GP-centred-paediatric-primary-care-programme with usual care in terms of disease-related hospitalisation, pharmacotherapy and psychotherapy. Methods: In 2018, we conducted a retrospective cohort study of 3- to 18-year-old patients with ADHD in Baden-Wuerttemberg, southern Germany. The intervention group (IG) comprised patients enrolled in a GP-centred-paediatric-primary-healthcare-programme and consulted a participating GP for ADHD at least once. GP-centred-paediatric-primary-care provides high continuity of care, facilitated access to specialist care, extended routine examinations and enhanced transition to adult healthcare. Patients in the control group (CG) received usual care, meaning they consulted a non-participating GP for ADHD at least once. Main outcomes were disease-related hospitalisation, pharmacotherapy and psychotherapy. Multivariable logistic regression was performed to compare groups. Results: A total of 2317 patients were included in IG and 4177 patients in CG. Mean age was 8.9 ± 4.4. The risk of mental-disorder-related hospitalisations was lower in IG than CG (odds ratio (OR): 0.666, 95% confidence interval (CI): 0.509-0.871). The prescription rate for stimulants was lower in IG (OR: 0.817; 95% CI: 0.732-0.912). There was no statistically significant difference in the participation rate of patients in cognitive behavioural therapy between groups (OR: 0.752; 95% CI: 0.523-1.080). Conclusion: Children and adolescents with ADHD enrolled in GP-centred-paediatric-primary-care are at lower risk of mental-disorder-related hospitalisation and less likely to receive stimulants. Keywords: ADHD; claims data; health-care-utilisation; multivariate analysis; primary care

Collaborative Ambulatory Orthopaedic Care in Patients with Hip and Knee Osteoarthritis: A Retrospective Comparative Cohort Study on Health Utilisation and Economic Outcomes

Objective: To evaluate a novel healthcare programme for the treatment of patients with hip and knee osteoarthritis in southern Germany in terms of clinical and health economic outcomes. The study is based on claims data from 2014 to 2017. Methods: We conducted a retrospective comparative cohort study of 9768 patients with hip and knee osteoarthritis, of whom 9231 were enrolled in a collaborative ambulatory orthopaedic care programme (intervention group), and 537 patients received usual orthopaedic care (control group). Key features of the programme are coordinated care, morbidity-adapted reimbursement and extended consultation times. Multivariable analysis was performed to determine effects on health utilisation outcomes. The economic analysis considered annual costs per patient from a healthcare payer perspective, stratified by healthcare service sector. Besides multivariable regression analyses, bootstrapping was used to estimate confidence intervals for predicted mean costs by group. Results: Musculoskeletal-disease-related hospitalisation was much less likely among intervention group patients than control group patients [odds ratio (OR): 0.079; 95% CI: 0.062–0.099]. The number of physiotherapy prescriptions per patient was significantly lower in the intervention group (RR: 0.814; 95% CI: 0.721–0.919), while the likelihood of participation in exercise programmes over one year was significantly higher (OR: 3.126; 95% CI: 1.604–6.094). Enrolment in the programme was associated with significantly higher ambulatory costs (€1048 vs. €925), but costs for inpatient care, including hospital stays, were significantly lower (€1003 vs. €1497 and €928 vs. €1300 respectively). Overall annual cost-savings were €195 per patient. Conclusions: Collaborative ambulatory orthopaedic care was associated with reduced hospitalisation in patients with hip and knee osteoarthritis. Health costs for programme participants were lower overall, despite higher costs for ambulatory care

Standardisation of magnetic nanoparticles in liquid suspension

Suspensions of magnetic nanoparticles offer diverse opportunities for technology innovation, spanning a large number of industry sectors from imaging and actuation based applications in biomedicine and biotechnology, through large-scale environmental remediation uses such as water purification, to engineering-based applications such as position-controlled lubricants and soaps. Continuous advances in their manufacture have produced an ever-growing range of products, each with their own unique properties. At the same time, the characterisation of magnetic nanoparticles is often complex, and expert knowledge is needed to correctly interpret the measurement data. In many cases, the stringent requirements of the end-user technologies dictate that magnetic nanoparticle products should be clearly defined, well characterised, consistent and safe; or to put it another way—standardised. The aims of this document are to outline the concepts and terminology necessary for discussion of magnetic nanoparticles, to examine the current state-of-the-art in characterisation methods necessary for the most prominent applications of magnetic nanoparticle suspensions, to suggest a possible structure for the future development of standardisation within the field, and to identify areas and topics which deserve to be the focus of future work items. We discuss potential roadmaps for the future standardisation of this developing industry, and the likely challenges to be encountered along the way

Subjektive Informiertheit von Patient*innen zum Thema Patientensicherheit: Ergebnisse einer Bevölkerungsbefragung in Deutschland

INTRODUCTION The growing number of people with multimorbidity and polypharmacy in Germany has led to increasing complexity in health care and risks to patient safety. A high priority should therefore be placed on identifying and preventing avoidable adverse events. The patient perspective plays an important role in improving patient safety. In this study, we conducted a representative, population-based survey of knowledge, perceptions and experiences of patient safety, especially of subjectively experienced errors in health care. Our aim was in particular to assess patient safety from the patients' point of view, and to analyze differences in assessments of risk and preventability between persons that felt well or poorly informed about patient safety topics. METHODS In 2019, computer-assisted telephone interviews were conducted nationwide as part of the "TK-Monitor Patient Safety" project. Recruitment was carried out by using multistage selection and forming a stratified random sample. Adults (18 years and older) with sufficient knowledge of German were included. The survey was conducted using a structured guideline containing 21 questions concerning perceptions and experiences of patient safety, and 12 questions on sociodemographic factors. The results were analyzed both descriptively and using inferential statistical methods. RESULTS Of a total of 1,000 respondents (51% female), approx. half (52%) were gainfully employed, and 57% rated their state of health as "very good" or "good". The patients regarded data protection, medication errors, hospital infections and diagnostic (un)certainty as of major relevance to patient safety. Overall, 55% of the respondents rated their knowledge of patient safety as "very good" or "good". The results showed that subjective knowledge was negatively associated with important outcome parameters such as having experience of medication errors or suspecting errors had been made in a medical examination or treatment. Patients that considered themselves well-informed also reckoned they could contribute towards increasing safety in health care. DISCUSSION The respondents considered diagnostic uncertainty to be one of the greatest risks to their person. This shows that they recognized a need for further information and felt this need was inadequately satisfied in the German research landscape. With regard to the correlation between subjective knowledge and outcome parameters, it is also necessary to analyze whether the respondents' subjective knowledge reflects their actual knowledge, as this would be necessary for preventive measures to be effective. This question will be the subject of further studies. CONCLUSION The patient perspective is an important addition to the study of the safety of medical care in Germany. Factors influencing subjective knowledge should be investigated. Furthermore, regular surveys would be desirable in order to gain greater insight into the topic.Hintergrund Die Zunahme von Multimorbidität und Multimedikation in Deutschland führt zu einer steigenden Komplexität der Gesundheitsversorgung und damit zu vermehrten Sicherheitsrisiken. Vermeidbare unerwünschte Ereignisse zu identifizieren und zu verhindern muss eine hohe Priorität haben. Bei der Verbesserung der Patientensicherheit spielt die Perspektive von Patientinnen und Patienten eine wichtige Rolle. In dieser Studie wurde eine Befragung zu Wissen, Wahrnehmung und Erfahrungen der Bevölkerung zum Thema Patientensicherheit, dabei vor allem zu subjektiv erlebten Fehlern im Versorgungsgeschehen, durchgeführt. Ziel war es insbesondere, den Stand der Patientensicherheit aus Sicht der Patientinnen und Patienten zu erheben und Unterschiede zwischen den Gruppen der subjektiv gut und den subjektiv schlecht zum Thema Patientensicherheit Informierten hinsichtlich der Einschätzung von Risiken und deren Vermeidbarkeit zu analysieren. Methode Im Rahmen des „TK-Monitor Patientensicherheit“ wurden bundesweit computer-assistierte Telefoninterviews durchgeführt. Die Rekrutierung erfolgte durch ein mehrstufiges Auswahlverfahren unter Bildung einer geschichteten Stichprobe. Eingeschlossen wurden Erwachsene (≥ 18 Jahre) die über ausreichend Deutschkenntnisse verfügten. Die Befragung erfolgte mittels eines strukturierten Leitfadens mit 21 Fragen zur Wahrnehmung und Erfahrung mit Patientensicherheit sowie 12 Fragen zu soziodemographischen Daten. Die Ergebnisse wurden deskriptiv und mittels inferenzstatistischen Verfahren ausgewertet. Ergebnisse Von insgesamt 1000 teilnehmenden Personen (51% weiblich) war etwa die Hälfte (52%) erwerbstätig und 57% schätzten ihren Gesundheitszustand als „sehr gut“ oder „gut“ ein. Insbesondere Datenschutz, Arzneimittelfehler, Infektionen im Krankenhaus und Diagnose(un)sicherheit wurden als besonders sicherheitsrelevante Problemfelder betrachtet. 55% der Befragten schätzen ihren subjektiven Informationsstand zum Thema Patientensicherheit als „sehr gut“ oder „gut“ ein. Der subjektive Informationsstand war negativ assoziiert mit wesentlichen Outcome-Parametern wie erlittenen Medikationsfehlern oder vermuteten Fehlern bei einer medizinischen Untersuchung oder Behandlung. Auch gaben subjektiv gut Informierte eher an, selbst zu einer sicheren Gesundheitsversorgung beitragen zu können. Diskussion Das Thema der Diagnose(un)sicherheit stellt aus Sicht der Bevölkerung eine der größten persönlichen Gefährdungen dar. Hier zeigt sich ein Bedarf der Befragten an Bearbeitung und Information, der in der Forschungslandschaft in Deutschland bislang zu wenig abgedeckt ist. Bei den Zusammenhängen zwischen subjektivem Informationsstand und Outcome-Parametern bleibt zu analysieren, ob der subjektive Informationsstand den tatsächlichen Informationsstand abbildet, der wiederum für wirksame eigene Präventionsmaßnahmen nötig wäre. Dieser Frage sollte in weiteren Studien nachgegangen werden. Schlussfolgerung Die Perspektive von Patientinnen und Patienten ist eine wichtige Ergänzung in der Betrachtung der Sicherheit der medizinischen Versorgung in Deutschland. Einflussfaktoren auf die subjektive Informiertheit sollten untersucht und die subjektive Informiertheit der Bevölkerung erhöht werden. Weitere, regelmäßige Erhebungen sind wünschenswert, um die Thematik zu vertiefen

Odanacatib for the treatment of postmenopausal osteoporosis : Results of the LOFT multicentre, randomised, double-blind, placebo-controlled trial and LOFT Extension study

Background Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. Methods The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between −2·5 and −4·0 if no previous radiographic vertebral fracture, or between −1·5 and −4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than −4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Findings Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43–40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45–60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40–0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39–0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68–0·87; all p<0·0001. Combined results from LOFT plus LOFT Extension for cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 4·9% (341/6909) versus 9·6% (675/7011), HR 0·48, 95% CI 0·42–0·55; hip fractures 1·1% (86/8043) versus 2·0% (162/8028), 0·52, 0·40–0·67; non-vertebral fractures 6·4% (512/8043) versus 8·4% (675/8028), 0·74, 0·66–0·83; all p<0·0001. In LOFT, the composite cardiovascular endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 273 (3·4%) of 8043 patients in the odanacatib group versus 245 (3·1%) of 8028 in the placebo group (HR 1·12, 95% CI 0·95–1·34; p=0·18). New-onset atrial fibrillation or flutter occurred in 112 (1·4%) of 8043 patients in the odanacatib group versus 96 (1·2%) of 8028 in the placebo group (HR 1·18, 0·90–1·55; p=0·24). Odanacatib was associated with an increased risk of stroke (1·7% [136/8043] vs 1·3% [104/8028], HR 1·32, 1·02–1·70; p=0·034), but not myocardial infarction (0·7% [60/8043] vs 0·9% [74/8028], HR 0·82, 0·58–1·15; p=0·26). The HR for all-cause mortality was 1·13 (5·0% [401/8043] vs 4·4% [356/8028], 0·98–1·30; p=0·10). When data from LOFT Extension were included, the composite of cardiovascular death, myocardial infarction, or stroke occurred in significantly more patients in the odanacatib group than in the placebo group (401 [5·0%] of 8043 vs 343 [4·3%] of 8028, HR 1·17, 1·02–1·36; p=0·029, as did stroke (2·3% [187/8043] vs 1·7% [137/8028], HR 1·37, 1·10–1·71; p=0·0051). Interpretation Odanacatib reduced the risk of fracture, but was associated with an increased risk of cardiovascular events, specifically stroke, in postmenopausal women with osteoporosis. Based on the overall balance between benefit and risk, the study's sponsor decided that they would no longer pursue development of odanacatib for treatment of osteoporosis

Effect of once-yearly zoledronic acid on the spine and hip as measured by quantitative computed tomography: results of the HORIZON Pivotal Fracture Trial.

Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength. INTRODUCTION: To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength. METHODS: In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated. RESULTS: Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p &lt; 0.01) and QCT (5.7%, p &lt; 0.0001). Between-treatment differences were significant for trabecular spine (p = 0.0017) [non-parametric test], trabecular trochanter (10.7%, p &lt; 0.0001), total hip (10.8%, p &lt; 0.0001), and compressive strength indices at femoral neck (8.6%, p = 0.0001), and trochanter (14.1%, p &lt; 0.0001). CONCLUSIONS: Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength

Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31â127 anaesthetic procedures in 30â874 children with a mean age of 6·35 years (SD 4·50) were included. The incidence of perioperative severe critical events was 5·2% (95% CI 5·0â5·5) with an incidence of respiratory critical events of 3·1% (2·9â3·3). Cardiovascular instability occurred in 1·9% (1·7â2·1), with an immediate poor outcome in 5·4% (3·7â7·5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10â000. This was independent of type of anaesthesia. Age (relative risk 0·88, 95% CI 0·86â0·90; p<0·0001), medical history, and physical condition (1·60, 1·40â1·82; p<0·0001) were the major risk factors for a serious critical event. Multivariate analysis revealed evidence for the beneficial effect of years of experience of the most senior anaesthesia team member (0·99, 0·981â0·997; p<0·0048 for respiratory critical events, and 0·98, 0·97â0·99; p=0·0039 for cardiovascular critical events), rather than the type of health institution or providers. Interpretation This study highlights a relatively high rate of severe critical events during the anaesthesia management of children for surgical or diagnostic procedures in Europe, and a large variability in the practice of paediatric anaesthesia. These findings are substantial enough to warrant attention from national, regional, and specialist societies to target education of anaesthesiologists and their teams and implement strategies for quality improvement in paediatric anaesthesia. Funding European Society of Anaesthesiology

Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31 127 anaesthetic procedures in 30 874 children with a mean age of 6.35 years (SD 4.50) were included. The incidence of perioperative severe critical events was 5.2% (95% CI 5.0-5.5) with an incidence of respiratory critical events of 3.1% (2.9-3.3). Cardiovascular instability occurred in 1.9% (1.7-2.1), with an immediate poor outcome in 5.4% (3.7-7.5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10 000. This was independent of type of anaesthesia. Age (relative risk 0.88, 95% CI 0.86-0.90; p<0.0001), medical history, and physical condition (1.60, 1.40-1.82; p<0.0001) were the major risk factors for a serious critical event. Multivariate analysis revealed evidence for the beneficial effect of years of experience of the most senior anaesthesia team member (0.99, 0.981-0.997; p<0.0048 for respiratory critical events, and 0.98, 0.97-0.99; p=0.0039 for cardiovascular critical events), rather than the type of health institution or providers. Interpretation This study highlights a relatively high rate of severe critical events during the anaesthesia management of children for surgical or diagnostic procedures in Europe, and a large variability in the practice of paediatric anaesthesia. These findings are substantial enough to warrant attention from national, regional, and specialist societies to target education of anaesthesiologists and their teams and implement strategies for quality improvement in paediatric anaesthesia