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The dynamic growth of the skeleton during childhood and adolescence renders it vulnerable to adverse effects of cancer treatment. The lifetime risk and patterns of skeletal morbidity have not been described in a population-based cohort of childhood cancer survivors. A cohort of 26,334 one-year cancer survivors diagnosed before 20 years of age was identified from the national cancer registries of Denmark, Finland, Iceland and Sweden as well as a cohort of 127,531 age- and sex-matched comparison subjects randomly selected from the national population registries in each country. The two cohorts were linked with data from the national hospital registries and the observed numbers of first-time hospital admissions for adverse skeletal outcomes among childhood cancer survivors were compared with the expected numbers derived from the comparison cohort. In total, 1,987 childhood cancer survivors had at least one hospital admission with a skeletal adverse event as discharge diagnosis, yielding a rate ratio (RR) of 1.35 (95% CI, 1.29-1.42). Among the survivors, we observed an increased risk for osteonecrosis with a RR of 25.9 (15.0-44.5), osteoporosis, RR 4.53 (3.28-6.27), fractures, RR 1.27 (1.20-1.34), osteochondropathies, RR 1.57 (1.28-1.92) and osteoarthrosis, RR 1.48 (1.28-1.72). The hospitalization risk for any skeletal adverse event was higher among survivors up to the age of 60 years, but the lifetime pattern was different for each type of skeletal adverse event. Understanding the different lifetime patterns and identification of high-risk groups is crucial for developing strategies to optimize skeletal health in childhood cancer survivors. This article is protected by copyright. All rights reserved.

Contains fulltext : 229846.pdf (Publisher’s version ) (Closed access) BACKGROUND: Early reports on patients with cancer and COVID-19 have suggested a high mortality rate compared with the general population. Patients with thoracic malignancies are thought to be particularly susceptible to COVID-19 given their older age, smoking habits, and pre-existing cardiopulmonary comorbidities, in addition to cancer treatments. We aimed to study the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with thoracic malignancies. METHODS: The Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry is a multicentre observational study composed of a cross-sectional component and a longitudinal cohort component. Eligibility criteria were the presence of any thoracic cancer (non-small-cell lung cancer [NSCLC], small-cell lung cancer, mesothelioma, thymic epithelial tumours, and other pulmonary neuroendocrine neoplasms) and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms. Patients of any age, sex, histology, or stage were considered eligible, including those in active treatment and clinical follow-up. Clinical data were extracted from medical records of consecutive patients from Jan 1, 2020, and will be collected until the end of pandemic declared by WHO. Data on demographics, oncological history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes were collected. Associations between demographic or clinical characteristics and outcomes were measured with odds ratios (ORs) with 95% CIs using univariable and multivariable logistic regression, with sex, age, smoking status, hypertension, and chronic obstructive pulmonary disease included in multivariable analysis. This is a preliminary analysis of the first 200 patients. The registry continues to accept new sites and patient data. FINDINGS: Between March 26 and April 12, 2020, 200 patients with COVID-19 and thoracic cancers from eight countries were identified and included in the TERAVOLT registry; median age was 68.0 years (61.8-75.0) and the majority had an Eastern Cooperative Oncology Group performance status of 0-1 (142 [72%] of 196 patients), were current or former smokers (159 [81%] of 196), had non-small-cell lung cancer (151 [76%] of 200), and were on therapy at the time of COVID-19 diagnosis (147 [74%] of 199), with 112 (57%) of 197 on first-line treatment. 152 (76%) patients were hospitalised and 66 (33%) died. 13 (10%) of 134 patients who met criteria for ICU admission were admitted to ICU; the remaining 121 were hospitalised, but were not admitted to ICU. Univariable analyses revealed that being older than 65 years (OR 1.88, 95% 1.00-3.62), being a current or former smoker (4.24, 1.70-12.95), receiving treatment with chemotherapy alone (2.54, 1.09-6.11), and the presence of any comorbidities (2.65, 1.09-7.46) were associated with increased risk of death. However, in multivariable analysis, only smoking history (OR 3.18, 95% CI 1.11-9.06) was associated with increased risk of death. INTERPRETATION: With an ongoing global pandemic of COVID-19, our data suggest high mortality and low admission to intensive care in patients with thoracic cancer. Whether mortality could be reduced with treatment in intensive care remains to be determined. With improved cancer therapeutic options, access to intensive care should be discussed in a multidisciplinary setting based on cancer specific mortality and patients' preference. FUNDING: None.

Background Surgery is the main curative treatment for colorectal cancer. Yet the immunologic and humoral response to surgery may facilitate progression of micro-metastases. It has been suggested that epidural analgesia preserves immune competency and prevents metastasis formation. Hence, the authors tested the hypothesis that epidural analgesia would result in less cancer recurrence after colorectal cancer surgery. Methods The Danish Colorectal Cancer Group Database and the Danish Anesthesia Database were used to identify patients operated for colorectal cancer between 2004 and 2018 with no residual tumor tissue left after surgery. The exposure group was defined by preoperative insertion of an epidural catheter for analgesia. The primary outcome was colorectal cancer recurrence, and the secondary outcome was mortality. Recurrences were identified using a validated algorithm based on data from Danish health registries. Follow-up was until death or September 7, 2018. The authors used propensity score matching to adjust for potential preoperative confounders. Results In the study population of 11,618 individuals, 3,496 (30.1%) had an epidural catheter inserted before surgery. The epidural analgesia group had higher proportions of total IV anesthesia, laparotomies, and rectal tumors, and epidural analgesia was most frequently used between 2009 and 2012. The propensity score–matched study cohort consisted of 2,980 individuals in each group with balanced baseline covariates. Median follow-up was 58 months (interquartile range, 29 to 86). Recurrence occurred in 567 (19.0%) individuals in the epidural analgesia group and 610 (20.5%) in the group without epidural analgesia. The authors found no association between epidural analgesia and recurrence (hazard ratio, 0.91; 95% CI, 0.82 to 1.02) or mortality (hazard ratio, 1.01; 95% CI, 0.92 to 1.10). Conclusions In colorectal cancer surgery, epidural analgesia was not statistically significantly associated with less cancer recurrence. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background & aims Cirrhosis affects hemostasis, but its effects across the spectrum of thromboses remain poorly understood. We examined risks and outcomes of venous and arterial thrombosis. Approach & results We used nationwide Danish healthcare registries to identify outpatients with cirrhosis and a sex- and age-matched comparison cohort without cirrhosis from the general population. Patients with cirrhosis and comparators were followed until they had a venous thromboembolism, acute myocardial infarction, ischemic stroke, or died. We computed absolute risks and hazard ratios of thrombosis, and compared outcomes after thrombosis. We included 5,854 patients with cirrhosis (median MELD score 9, IQR 7-13), and their risk of any of the thrombotic events was 0.8% after 1 year and 6.3% after 10 years. They were more likely than the 23,870 matched comparators to have venous thromboembolism (adjusted hazard ratio [HR] 2.0, 95% CI 1.5-2.6) or ischemic stroke (adjusted HR 1.7, 95% CI 1.3-2.3), but not myocardial infarction (adjusted HR 0.7, 95% CI 0.5-0.9). Among patients with cirrhosis, decompensation increased the risk of acute myocardial infarction but not the other thromboses. Following thrombosis, patients with cirrhosis had higher 90-day mortality than comparators (after venous thromboembolism: 17% vs. 7%; after acute myocardial infarction: 27% vs. 5%; after ischemic stroke: 10% vs. 7%) and were less likely to receive antithrombotic treatment. Conclusions Patients with cirrhosis had an increased risk of venous thromboembolism and ischemic stroke, but not acute myocardial infarction. Among patients with cirrhosis, decompensation increased the risk of myocardial infarction, exclusively. Mortality after thrombosis was higher in patients with cirrhosis than in other patients. These findings are relevant for decisions about antithrombotic prophylaxis in patients with cirrhosis.

ObjectivesThe association between obesity and atrial fibrillation (AF) is well-established. We aimed to evaluate the impact of index body mass index (BMI) on AF recurrence at 12 months following catheter ablation using propensity-weighted analysis. In addition, periprocedural complications and fluoroscopy details were examined to assess overall safety in relationship to increasing BMI ranges.MethodsBaseline, periprocedural and follow-up data were collected on consecutive patients scheduled for AF ablation. There were no specific exclusion criteria. Patients were categorised according to baseline BMI in order to assess the outcomes for each category.ResultsAmong 3333 patients, 728 (21.8%) were classified as normal (BMI 2), 1537 (46.1%) as overweight (BMI 25.5–29.0 kg/m2) and 1068 (32.0%) as obese (BMI ≥30.0 kg/m2). Procedural duration and radiation dose were higher for overweight and obese patients compared with those with a normal BMI (p=0.002 and p2led to a 1.2-fold increased likelihood of experiencing recurrent AF at 12-months follow-up as compared with overweight patients (HR 1.223; 95% CI 1.047 to 1.429; p=0.011), while no significant correlation was found between overweight and normal BMI groups (HR 0.954; 95% CI 0.798 to 1.140; p=0.605) and obese versus normal BMI (HR 1.16; 95% CI 0.965 to 1.412; p=0.112).ConclusionsPatients with a baseline BMI ≥30 kg/m2have a higher recurrence rate of AF following catheter ablation and therefore lifestyle modification to target obesity preprocedure should be considered in these patients.

Inzicht krijgen in: (a) het aantal patiënten dat tijdens de eerste golf van de covid-19-pandemie buiten het ziekenhuis – onder de zorg van de huisarts – overleed aan de gevolgen van een PCR-bewezen of vermeende SARS-CoV-2-infectie; en (b) het aantal kwetsbare patiënten met een PCR-bewezen of vermeende SARS-CoV-2-infectie dat in die periode buiten het ziekenhuis intensieve en zo nodig palliatieve zorg kreeg door de huisarts.

METHOD: Registration system initiated by General Practice Research Consortium Netherlands (GPRC-NL).AIM: To obtain national estimates on clinically suspected Covid-19 mortality in general practice and on intensive and palliative covid-19 care provided by general practitioners (GPs) outside hospital, including palliative medication, availability of personal protective equipment, and reasons for not referring to hospital of vulnerable patients during the first three months of the Covid-19 pandemic in The Netherlands.DESIGN: Nationwide registration study, in which 2.331 GP practices in The Netherlands participated from March-June 2020.METHOD: Registration system initiated by General Practice Research Consortium Netherlands (GPRC-NL) through existing digital referral platform ZorgDomein, in which GPs could report PCR-proven and clinically suspected Covid-19 deceased patients to estimate the impact of the Covid-19 pandemic in primary care.RESULTS: GPs reported 1,566 Covid-19 deceased patients, of which 61% (949/1,566) were clinically suspected but not PCR-tested, with large regional differences, and most deaths being reported in the provinces of Brabant and Limburg. Patients had a median duration from onset of symptoms to death of 8 days and a median age of 87 years. GPs reported 1,030 patients for which they delivered intensive or palliative care, of which 56% had a Clinical Frailty Score higher or equal to six. Most mentioned reason for GPs and patients in the decision not going to hospital were the explicit wish of the patient (59%) and somatic vulnerability (52%).CONCLUSION: GPs provided palliative care to a large number of clinically suspected Covid-19 vulnerable patients with large regional differences across The Netherlands. Reported GPs' and patients' considerations to refrain from hospital care can be used to guide future primary care for vulnerable Covid-19 patients.

METHOD: Registration system initiated by General Practice Research Consortium Netherlands (GPRC-NL). AIM: To obtain national estimates on clinically suspected Covid-19 mortality in general practice and on intensive and palliative covid-19 care provided by general practitioners (GPs) outside hospital, including palliative medication, availability of personal protective equipment, and reasons for not referring to hospital of vulnerable patients during the first three months of the Covid-19 pandemic in The Netherlands. DESIGN: Nationwide registration study, in which 2.331 GP practices in The Netherlands participated from March-June 2020. METHOD: Registration system initiated by General Practice Research Consortium Netherlands (GPRC-NL) through existing digital referral platform ZorgDomein, in which GPs could report PCR-proven and clinically suspected Covid-19 deceased patients to estimate the impact of the Covid-19 pandemic in primary care. RESULTS: GPs reported 1,566 Covid-19 deceased patients, of which 61% (949/1,566) were clinically suspected but not PCR-tested, with large regional differences, and most deaths being reported in the provinces of Brabant and Limburg. Patients had a median duration from onset of symptoms to death of 8 days and a median age of 87 years. GPs reported 1,030 patients for which they delivered intensive or palliative care, of which 56% had a Clinical Frailty Score higher or equal to six. Most mentioned reason for GPs and patients in the decision not going to hospital were the explicit wish of the patient (59%) and somatic vulnerability (52%). CONCLUSION: GPs provided palliative care to a large number of clinically suspected Covid-19 vulnerable patients with large regional differences across The Netherlands. Reported GPs' and patients' considerations to refrain from hospital care can be used to guide future primary care for vulnerable Covid-19 patients.

Purpose of Review Cancer diagnosis in young pregnant women challenges oncological decision-making. The International Network on Cancer, Infertility and Pregnancy (INCIP) aims to build on clinical recommendations based on worldwide collaborative research. Recent Findings A pregnancy may complicate diagnostic and therapeutic oncological options, as the unborn child must be protected from potentially hazardous exposures. Pregnant patients should as much as possible be treated as non-pregnant patients, in order to preserve maternal prognosis. Some approaches need adaptations when compared with standard treatment for fetal reasons. Depending on the gestational age, surgery, radiotherapy, and chemotherapy are possible during pregnancy. A multidisciplinary approach is the best guarantee for experience-driven decisions. A setting with a high-risk obstetrical unit is strongly advised to safeguard fetal growth and health. Research wise, the INCIP invests in clinical follow-up of children, as cardiac function, neurodevelopment, cancer occurrence, and fertility theoretically may be affected. Furthermore, parental psychological coping strategies, (epi)genetic alterations, and pathophysiological placental changes secondary to cancer (treatment) are topics of ongoing research. Summary Further international research is needed to provide patients diagnosed with cancer during pregnancy with the best individualized management plan to optimize obstetrical and oncological care.

Montelukast, a leukotriene receptor antagonist, was marketed in 1998 as an oral supplementary treatment to patients with mild to moderate asthma. The aim of this study was to describe the early discontinuation pattern among montelukast users in Denmark in the period of 1 March 1998 to 31 December 2016, and to identify demographic characteristics possibly associated with early discontinuation. This nationwide drug utilization study was based on data collected from three nationwide Danish registers. All montelukast users who redeemed at least one prescription in the study period were identified. Early discontinuation was defined as failing to fill a second prescription for montelukast within at least a year after the initial montelukast prescription. Among 135,271 included montelukast users, 47,480 (35%) discontinued the use of montelukast after a single redeemed prescription. The trend in early discontinuation increased throughout the years. The most predominant demographic risk factors for early discontinuation were prescription for only nasal topical anti-allergic treatment up to a year prior to montelukast initiation [adjusted odds ratio (OR) 2.25; 95% confidence interval (CI) 2.13-2.38], as well as suspected off-label use (adjusted OR 2.02; 95% CI 1.97-2.08). Several risk factors were associated with a decreased risk of early discontinuation; most pronounced was a prescription of inhaled corticosteroids within a year up to montelukast initiation [adjusted OR 0.47 (95% CI 0.46-0.49)]. Early discontinuation was more pronounced after patent expiry in 2012 [adjusted OR 1.42 (95% CI 1.38-1.45)]. In conclusion, we found that early montelukast discontinuation increased during the last 19 years. Appropriateness of the treatment indication as estimated by concomitant prescription of adequate inhalation therapy was associated with a low risk of early discontinuation. A more pronounced early discontinuation was observed after patent expiry in 2012, which could reflect a more liberal approach to montelukast prescription.

Childhood cancer survivors face risks from a variety of late effects, including cardiac events, second cancers, and late mortality. The aim of the pan-European PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies (PanCareSurFup) Consortium was to collect data on incidence and risk factors for these late effects among childhood cancer survivors in Europe. This paper describes the methodology of the data collection for the overall PanCareSurFup cohort and the outcome-related cohorts. In PanCareSurFup 13 data providers from 12 countries delivered data to the data centre in Mainz. Data providers used a single variable list that covered all three outcomes. After validity and plausibility checks data was provided to the outcome-specific working groups. In total, we collected data on 115,596 patients diagnosed with cancer from 1940 to 2011, of whom 83,333 had survived 5 years or more. Due to the eligibility criteria and other requirements different numbers of survivors were eligible for the analysis of each of the outcomes. Thus, 1014 patients with at least one cardiac event were identified from a cohort of 39,152 5-year survivors; for second cancers 3995 survivors developed at least one second cancer from a cohort of 71,494 individuals, and from the late mortality cohort of 79,441 who had survived at least 5 years, 9247 died subsequently. Through the close cooperation of many European countries and the establishment of one central data collection and harmonising centre, the project succeeded in generating the largest cohort of children with cancer to date.

Background: Trauma histories may increase risk of perinatal psychiatric episodes and other comorbidity. We designed an epidemiological population-based cohort study to explore if adverse childhood experiences (ACE) in girls increases risk of later postpartum psychiatric episodes. Methods: Using Danish registers, we identified women born in Denmark between January 1980 and December 1998, (129,439 childbirths). Exposure variables were ACE between age 0-15 including: (1) family disruption, (2) parental somatic illness, (3) parental labor market exclusion, (4) parental criminality, (5) parental death, (6) placement in out-of-home care, and (7).parental psychopathology excluding substance use disorders and (8) parental substance use disorder. The primary outcome was first occurrence of in- or outpatient contact 0-6 months (0-182 days) postpartum at a psychiatric treatment facility with any psychiatric diagnoses, ICD-10, F00-F99 (N=651). We conducted survival analyses using Cox proportional hazard regressions of postpartum psychiatric episodes. Results: Approximately 52% of the sample experienced ACE that significantly increased risk of any postpartum psychiatric diagnosis. Highest risks were observed among women who experienced out of home placement, hazard ratio (HR) 2.57 (95% CI: 1.90-3.48). Women experiencing 2 adverse life events had higher risks of postpartum psychiatric diagnosis HR: 1.88 (95% CI: 1.51-2.36), compared to those with 1 ACE, HR: 1.24 (95% CI: 1.03-49) and no ACE, HR: 1.00 (reference group). Conclusions: ACE primarily due to parental psychopathology and disability contributes to increased risk of postpartum psychiatric episodes; and greater numbers of ACE increases risk for postpartum psychiatric illness with an observed dose-response effect. Future work should explore genetic and environmental factors that increase risk and/or confer resilience.

Supplemental Digital Content is available in the text., A small number of studies have investigated breast cancer (BC) risk among women with a history of false-positive recall (FPR) in BC screening, but none of them has used time-to-event analysis while at the same time quantifying the effect of false-negative diagnostic assessment (FNDA). FNDA occurs when screening detects BC, but this BC is missed on diagnostic assessment (DA). As a result of FNDA, screenings that detected cancer are incorrectly classified as FPR. Our study linked data recorded in the Flemish BC screening program (women aged 50–69 years) to data from the national cancer registry. We used Cox proportional hazards models on a retrospective cohort of 298 738 women to assess the association between FPR and subsequent BC, while adjusting for potential confounders. The mean follow-up was 6.9 years. Compared with women without recall, women with a history of FPR were at an increased risk of developing BC [hazard ratio=2.10 (95% confidence interval: 1.92–2.31)]. However, 22% of BC after FPR was due to FNDA. The hazard ratio dropped to 1.69 (95% confidence interval: 1.52–1.87) when FNDA was excluded. Women with FPR have a subsequently increased BC risk compared with women without recall. The risk is higher for women who have a FPR BI-RADS 4 or 5 compared with FPR BI-RADS 3. There is room for improvement of diagnostic assessment: 41% of the excess risk is explained by FNDA after baseline screening.

No clinical risk score is universally accepted for coronary artery disease. In 603 patients (mean age, 61.2 ± 12.3 yr) with stable coronary artery disease, we investigated the predictive power of clinical risk scores derived from the Framingham, the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID), and the Vienna and Ludwigshafen Coronary Artery Disease (VILCAD) studies. Secondary outcomes were the recurrence of an acute thrombotic event (coronary events, strokes, or transient ischemic attacks), or heart failure or death. The primary outcome was the combination of secondary outcomes. During follow-up (duration, 2.08 ± 0.97 yr), 42 patients had an acute thrombotic event; 22, heart failure or death; and 60, the primary outcome. The Framingham score predicted acute thrombotic events: hazard ratio (HR)=1.05; 95% confidence interval (CI), 1.01–1.08; P=0.03; net reclassification index (NRI, calculated to evaluate improvement in prediction gained by adding different risk scores to models constructed with variables excluded from the calculation of that score)=9.7% (95% CI, 9.6–9.8). The LIPID (HR=1.13; 95% CI, 1.04–1.22; P=0.005) and VILCAD scores (HR=1.99; 95% CI, 1.48–2.67; P We conclude that the accuracy of these risk scores varies in accordance with the outcome studied.

BackgroundStudies have indicated that the association of urbanicity at birth and during upbringing with schizophrenia may be driven by familial factors such as genetic liability. We used a population-based nested case–control study to assess whether polygenic risk score (PRS) for schizophrenia was associated with urbanicity at birth and at age 15, and to assess whether PRS and parental history of mental disorder together explained the association between urbanicity and schizophrenia.MethodsData were drawn from Danish population registries. Cases born since 1981 and diagnosed with schizophrenia between 1994 and 2009 were matched to controls with the same sex and birthdate (1549 pairs). Genome-wide data were obtained from the Danish Neonatal Screening Biobank and PRSs were calculated based on results of a separate, large meta-analysis.ResultsThose with higher PRS were more likely reside in the capital compared with rural areas at age 15 [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.01–1.40], but not at birth (OR 1.09, 95% CI 0.95–1.26). Adjustment for PRS produced almost no change in relative risks of schizophrenia associated with urbanicity at birth, but slightly attenuated those for urban residence at age 15. Additional adjustment for parental history led to slight attenuation of relative risks for urbanicity at birth [incidence rate ratio (IRR) for birth in capital = 1.54, 95% CI 1.18–2.02; overallp= 0.016] and further attenuation of relative risks for urbanicity at age 15 (IRR for residence in capital = 1.32, 95% CI 0.97–1.78; overallp= 0.148).ConclusionsWhile results regarding urbanicity during upbringing were somewhat equivocal, genetic liability as measured here does not appear to explain the association between urbanicity at birth and schizophrenia.

AIMS: Therapy with an implantable cardioverter defibrillator (ICD) is established for the prevention of sudden cardiac death (SCD) in high risk patients. We aimed to determine the effectiveness of primary prevention ICD therapy by analysing registry data from 14 centres in 11 European countries compiled between 2002 and 2014, with emphasis on outcomes in women who have been underrepresented in all trials. METHODS AND RESULTS: Retrospective data of 14 local registries of primary prevention ICD implantations between 2002 and 2014 were compiled in a central database. Predefined primary outcome measures were overall mortality and first appropriate and first inappropriate shocks. A multivariable model enforcing a common hazard ratio for sex category across the centres, but allowing for centre-specific baseline hazards and centre specific effects of other covariates, was adjusted for age, the presence of ischaemic cardiomyopathy or a CRT-D, and left ventricular ejection fraction ≤25%. Of the 5033 patients, 957 (19%) were women. During a median follow-up of 33 months (IQR 16-55 months) 129 women (13%) and 807 men (20%) died (HR 0.65; 95% CI: [0.53, 0.79], P-value

Objective: Negative symptoms and cognitive deficits are main features of schizophrenia but with limited treatment options. Earlier studies have suggested that central nervous system (CNS) stimulants have a small effect on these domains, but with inconclusive results. As the first study to date, we aimed to investigate whether CNS stimulants improve naturalistic outcomes (psychiatric admissions and antipsychotic use) in patients with schizophrenia. Methods: By using extensive health registers all patients with schizophrenia and their use of CNS stimulants in Denmark were identified. Two models were used to investigate the effectiveness of CNS stimulants in patients with schizophrenia between 1995 and 2014; a mirror-image model with 605 individuals, using paired t tests and Wilcoxon signed rank tests, and a follow-up study with 789 individuals, using a conditional risk-set model. Results: CNS stimulants use was associated with a reduction in number of psychiatric admissions from 3.43 (95% CI = 2.86 to 4.01) to 2.62 (95% CI = 1.99 to 3.25) (P =.009), with a more pronounced reduction for women (mean difference: ' '1.37, 95% CI = ' '2.34 to ' '0.40, P =.006). Psychiatric bed-days were reduced by 40 (95% CI = 24.5 to 55.6, P

Background New-onset atrial fibrillation (NOAF) is commonly encountered in critically ill adults. Evidence evaluating the association between NOAF and patient-important outcomes in this population is conflicting. Furthermore, little is known regarding the association between NOAF and resource use or hospital costs. Methods Retrospective analysis (2011–2016) of a prospectively collected registry from two Canadian hospitals of consecutive ICU patients aged ≥ 18 years. We excluded patients with a known history of AF prior to hospital admission. Any occurrence of atrial fibrillation (AF) was prospectively recorded by bedside nurses. The primary outcome was hospital mortality, and we used multivariable logistic regression to adjust for confounders. We used a generalized linear model to evaluate contributors to total cost. Results We included 15,014 patients, and 1541 (10.3%) had NOAF during their ICU admission. While NOAF was not associated with increased odds of hospital death among the entire cohort (adjusted odds ratio [aOR] 1.02 [95% confidence interval [CI] 0.97–1.08]), an interaction was noted between NOAF and sepsis, and the presence of both was associated with higher odds of hospital mortality (aOR 1.28 [95% CI 1.09–1.36]) than either alone. Patients with NOAF had higher total costs (cost ratio [CR] 1.09 [95% CI 1.02–1.20]). Among patients with NOAF, treatment with a rhythm-control strategy was associated with higher costs (CR 1.24 [95% CI 1.07–1.40]). Conclusions While NOAF was not associated with death or requiring discharge to long-term care among critically ill patients, it was associated with increased length of stay in ICU and increased total costs.

Background: Acute disseminated encephalomyelitis (ADEM) can cause cognitive impairment in children. However, long-term consequences for school performance and psychiatric morbidity have never been characterized. Our aim was to investigate long-term school performance and psychiatric morbidity after pediatric ADEM (

Background Radiofrequency ablation (RFA), combined with endoscopic resection, can be used as a primary treatment for low grade dysplasia, high grade dysplasia, and early esophageal adenocarcinoma (EAC) in Barrett’s esophagus (BE). The aim of the Belgian RFA registry is to capture the real-life outcome of endoscopic therapy for BE with RFA and to assess efficacy and safety outside study protocols, in the absence of reimbursement. Patients and methods Between February 2008 and January 2017, data from 7 different expert centers were prospectively collected in the registry. Efficacy outcomes included complete remission of intestinal metaplasia (CR-IM), complete remission of dysplasia (CR-D), and durability of remission. Safety outcomes included immediate and late adverse events. Results 684 RFA procedures in 342 different patients were registered. Of these, 295 patients were included in the efficacy analysis, with CR-IM achieved in 88 % and CR-D in 93 %, in per-protocol analysis; corresponding rates in intention-to-treat analysis were 82 % and 87 %, respectively. Sustained remission was seen in 65 % with a median (interquartile range) follow-up of 25 (12 – 47) months. No risk factors for recurrent disease were identified. Immediate complications occurred in 4 % of all procedures and 6 % of all patients, whereas late complications occurred in 9 % of all procedures and in 20 % of all patients. Conclusions Data from the Belgian registry confirm that RFA in combination with endoscopic resection is an efficient treatment for BE with dysplasia or early EAC. In the absence of reimbursement, more rescue treatments are used, not compromising outcome. Since there is recurrent disease after CR-IM in 35 %, surveillance endoscopy remains necessary.

ObjectiveTo develop and validate a prognostic model and a simple model to predict death due to bleeding in trauma patients.DesignCross-sectional study with multivariable logistic regression using data from two large trauma cohorts.Setting274 hospitals from 40 countries in the Clinical Randomisation of Anti-fibrinolytic in Significant Haemorrhage (CRASH-2) trial and 24 hospitals in the Northern French Alps Trauma registry.Participants13 485 trauma patients in the CRASH-2 trial and 9945 patients in the Northern French Alps Trauma registry who were admitted to hospital within 3 hours of injury.Main outcome measureIn-hospital death due to bleeding within 28 days.ResultsThere were 815 (6%) deaths from bleeding in the CRASH-2 trial and 102 (1%) in the Northern French Alps Trauma registry. The full model included age, systolic blood pressure (SBP), Glasgow Coma Scale (GCS), heart rate, respiratory rate and type of injury (penetrating). The simple model included age, SBP and GCS. In a cross-validation procedure by country, discrimination and calibration were adequate (pooled C-statistic 0.85 (95% CI 0.81 to 0.88) for the full model and 0.84 (95% CI 0.80 to 0.88) for the simple model).ConclusionThis prognostic model can identify trauma patients at risk of death due to bleeding in a wide range of settings and can support prehospital triage and trauma audit, including audit of tranexamic acid use.

ObjectivesTo assess associations between occupation and motor neuron disease (MND).MethodsWe conducted a population-based case–control study with cases (n=321) recruited through the New Zealand Motor Neurone Disease Association and hospital discharge data. Controls (n=605) were recruited from the Electoral Roll. Information on personal and demographic details, lifestyle factors and a full occupational history was collected using questionnaires and interviews. Associations with ever/never employed and employment duration were estimated using logistic regression stratified by sex and adjusted for age, ethnicity, socioeconomic deprivation, education and smoking.ResultsElevated risks were observed for field crop and vegetable growers (OR 2.93, 95% CI 1.10 to 7.77); fruit growers (OR 2.03, 95% CI 1.09 to 3.78); gardeners and nursery growers (OR 1.96, 95% CI 1.01 to 3.82); crop and livestock producers (OR 3.61, 95% CI 1.44 to 9.02); fishery workers, hunters and trappers (OR 5.62, 95% CI 1.27 to 24.97); builders (OR 2.90, 95% CI 1.41 to 5.96); electricians (OR 3.61, 95% CI 1.34 to 9.74); caregivers (OR 2.65, 95% CI 1.04 to 6.79); forecourt attendants (OR 8.31, 95% CI 1.79 to 38.54); plant and machine operators and assemblers (OR 1.42, 95% CI 1.01 to 2.01); telecommunications technicians (OR 4.2, 95% CI 1.20 to 14.64); and draughting technicians (OR 3.02, 95% CI 1.07 to 8.53). Industries with increased risks were agriculture (particularly horticulture and fruit growing), construction, non-residential care services, motor vehicle retailing, and sport and recreation. Positive associations between employment duration and MND were shown for the occupations fruit growers, gardeners and nursery growers, and crop and livestock producers, and for the horticulture and fruit growing industry.ConclusionsThis study suggests associations between MND and occupations in agriculture and several other occupations.

BACKGROUND: Population-based data on distal cholangiocarcinoma (DCC) from the Western world are not available, albeit essential to identify areas for improvement. This study investigated the incidence, treatment and outcomes, including time trends and predictors for survival, in a nationwide cohort of DCC.METHODS: This is a retrospective cohort study of patients diagnosed with DCC (2009-2016) derived from the Netherlands Cancer Registry. Overall survival (OS) and its predictors were analyzed using Kaplan-Meier and Cox regression analysis. Time trends (2009-2012 versus 2013-2016) were assessed.RESULTS: Overall, 1338 patients with DCC were included, with 1-, 3- and 5-year OS of 46%, 18%, and 11%. Incidence of DCC was 0.55-0.90 per 100.000 per year. Median OS was 10.4 months across all stages; 21.9 months for resected (n = 620, 46.3%), 6.7 months for unresected nonmetastatic (n = 445, 33.3%), and 3.6 months for metastatic DCC (n = 273, 20.4%) (p CONCLUSIONS: In a nationwide cohort of DCC, resection rates and the use of chemotherapy increased whereas OS remained stable at 10.4 months.

Variation in survival of pediatric acute myeloid leukemia (pAML) over time and between Western European countries exists. The aim of the current study is to assess the progress made for the Dutch pAML population (0–17 years) during 1990–2015, based on trends in incidence, survival and mortality. Data from the population-based Netherlands Cancer Registry were merged with leukemia-related characteristics and treatment specifics from the Dutch Childhood Leukemia Study Group (Dutch Childhood Oncology Group (DCOG) from 2002 onwards). Mortality data (1980–2016) were obtained from the cause of death registry of Statistics Netherlands. Trend analyses were performed over time and by treatment protocol. Between 1990 and 2015, a total of 635 children aged 0–17 years were diagnosed with AML for an average of 25 patients (range 18–36) per year. There was a slight increase in the incidence at age 1–4 years (average annual percentage change (AAPC) of +2.2% per year (95% CI 0.8–3.5, p < 0.01)). Overall, the 5-year survival significantly improved over the past 26 years and nearly doubled from 40% in the early 1990s to 74% in 2010–2015. Multivariable analysis showed a 49% reduction in risk of death for pAML patients treated according to the latest DB-AML 01 protocol (p = 0.03). The continuing decrease of mortality (AAPC −2.8% per year (95% CI −4.1 to −1.5)) supports the conclusion of true progress against pAML in the Netherlands.

Resumo: Introdução e objetivos: Foi nosso objetivo reportar a evolução da angioplastia coronária no tratamento do enfarte agudo do miocárdio com supradesnivelamento do segmento ST (EAMCST), entre 2002‐2013. Métodos: Os dados prospetivos multicêntricos do Registo Nacional de Cardiologia de Intervenção (RNCI) e os dados oficiais da Direção Geral de Saúde (DGS) foram conjugados para estudar os procedimentos no EAMCST entre 2002 e 2013. Resultados: Em 2013 realizaram‐se 3524 angioplastias primárias (ICP‐P), representando um crescimento de 315% relativamente ao ano de 2002. Em 2002 a ICP‐P representava 16% do total de angioplastias coronárias, passando a representar 25% nos anos de 2012‐2013. Entre 2002‐2013 o número de procedimentos por milhão de habitantes aumentou de 106 para 338 e a angioplastia de recurso decresceu de 70,7 para 2%. Durante o período em análise, a utilização de stents eluidores de fármaco cresceu de 9,9 para 69,5%. Após 2008, observou‐se uma utilização crescente da trombectomia de aspiração, atingindo 46,7% em 2013. Os inibidores das glicoproteínas IIb/IIIa registaram um decréscimo no seu uso, sendo de 73,2% em 2002 e de 23,6% em 2013. O acesso radial cresceu de 8,3% em 2008 até 54,6% em 2013. Conclusões: Durante o período em análise, a taxa de angioplastia coronária por milhão de habitantes triplicou. A angioplastia de recurso foi ultrapassada pela angioplastia primária a partir de 2006. Observaram‐se novas tendências no tratamento do enfarte agudo do miocárdio com supradesnivelamento do segmento ST, salientando‐se a utilização de stents eluidores de fármacos e o acesso radial. Abstract: Introduction and Objectives: The aim of the present paper was to report trends in coronary angioplasty for the treatment of ST‐elevation myocardial infarction (STEMI) in Portugal. Methods: Prospective multicenter data from the Portuguese National Registry of Interventional Cardiology (RNCI) and official data from the Directorate‐General for Health (DGS) were studied to analyze percutaneous coronary intervention (PCI) procedures for STEMI from 2002 to 2013. Results: In 2013, 3524 primary percutaneous coronary intervention (p‐PCI) procedures were performed (25% of all procedures), an increase of 315% in comparison to 2002 (16% of all interventions). Between 2002 and 2013 the rate increased from 106 to 338 p‐PCIs per million population per year. Rescue angioplasty decreased from 70.7% in 2002 to 2% in 2013. During this period, the use of drug‐eluting stents grew from 9.9% to 69.5%. After 2008, the use of aspiration thrombectomy increased, reaching 46.7% in 2013. Glycoprotein IIb‐IIIa inhibitor use decreased from 73.2% in 2002 to 23.6% in the last year of the study. Use of a radial approach increased steadily from 8.3% in 2008 to 54.6% in 2013. Conclusion: During the reporting period there was a three‐fold increase in primary angioplasty rates per million population. Rescue angioplasty has been overtaken by p‐PCI as the predominant procedure since 2006. New trends in the treatment of STEMI were observed, notably the use of drug‐eluting stents and radial access as the predominant approach. Palavras‐chave: Registo, Cardiologia de intervenção, Enfarte do miocárdio, Coronariografia, Angioplastia primária, Stent, Keywords: Registry, Interventional cardiology, Myocardial infarction, Coronary angiography, Primary angioplasty, Stent

Development of multiple colorectal cancers (CRCs), synchronously or metachronously, is associated with hereditary predisposition for cancer and accurate risk estimates of multiple tumour development are relevant to recommend rational surveillance programs. A cross-sectional study design was used to estimate the risks of synchronous CRC (SCRC) and metachronous CRC (MCRC) based on data from the National Danish Hereditary Nonpolyposis Register. In total, 7100 individuals from families within the subgroups Lynch syndrome, familial CRC (FCC) and moderate risk were used with estimates relative to a non-hereditary population control cohort. SCRC was diagnosed in 7.4% of the Lynch syndrome cases, in 4.2% of FCC cases and 2.5% of the moderate risk cases, which translated to relative risks of 1.9-5.6. The risk of MCRC was distinctively linked to Lynch syndrome with a life-time risk up to 70% and an incidence rate ratio of 5.0. The risk of SCRC was significantly increased in all subgroups of FCC and hereditary CRC, whereas the risk of MCRC was specifically linked to Lynch syndrome. These observations suggest that individuals with FCC or hereditary CRC should be carefully screened for second primary CRC at the time of diagnosis, whereas intensified surveillance for second primary CRC is motivated in Lynch syndrome with lower-intensity programs in families with yet unidentified genetic causes.

OBJECTIVE To investigate whether women with type 2 diabetes (T2D) develop a more advanced stage of breast cancer and whether treatment with insulin (analogs) is associated with specific breast cancer characteristics. RESEARCH DESIGN AND METHODS For this nested case-control study, women with breast cancer diagnosed in 2002–2014 were selected from the linked Netherlands Cancer Registry–PHARMO Database Network (N = 33,377). T2D was defined as receiving two or more dispensings of noninsulin blood glucose–lowering drugs prior to breast cancer diagnosis. Women with T2D were matched to women without diabetes. Among women with T2D, insulin users and nonusers were compared. Multivariable ordinal logistic regression was used to investigate the association between T2D/insulin and breast cancer characteristics, including TNM classification (tumor size, lymph node status, metastasis), morphology, grade, estrogen receptor and progesterone receptor (PR), human epidermal growth factor receptor 2, and molecular subtype. RESULTS Women with T2D (n = 1,567) were more often diagnosed with a more advanced tumor stage (odds ratio 1.28 [95% CI 13–1.44]) and a higher grade (1.22 [1.08–1.39]) though less often with a PR-negative breast tumor (0.77 [0.67–0.89]) than women without diabetes (n = 6,267). No associations were found for the other breast cancer characteristics. Women with T2D using insulin (n = 388) were not diagnosed with different breast cancer characteristics compared with women with T2D not using insulin (n = 1,179). CONCLUSIONS Our study suggests that women with T2D are at increased risk to be diagnosed with a more aggressive type of breast cancer than women without diabetes. No evidence was found that the use of insulin (analogs) is associated with developing more advanced breast cancer tumors.

Background The beneficial effects of a cardiac resynchronization defibrillator (CRT-D) in patients with heart failure, low left ventricular ejection fraction (LVEF), and wide QRS have clearly been established. Nevertheless, mortality remains high in some patients. The aim of this study was to develop and validate a risk score to identify patients at high risk for early mortality who are implanted with a CRT-D. Methods and Results For predictive modelling, 1282 consecutive patients from 5 centers (74% male; median age 66 years; median LVEF 25%; New York Heart Association class III–IV 60%; median QRS-width 160 ms) were randomly divided into a derivation and validation cohort. The primary endpoint is mortality at 3 years. Model development was performed using multivariate logistic regression by checking log likelihood, Akaike information criterion, and Bayesian information criterion. Model performance was validated using C statistics and calibration plots. The risk score included 7 independent mortality predictors, including myocardial infarction, LVEF, QRS duration, chronic obstructive pulmonary disease, chronic kidney disease, hyponatremia, and anemia. Calibration-in-the-large was suboptimal, reflected by a lower observed mortality (44%) than predicted (50%). The validated C statistic was 0.71 indicating modest performance. Conclusion A risk score based on routine, readily available clinical variables can assist in identifying patients at high risk for early mortality within 3 years after CRT-D implantation.

Posttransplant lymphoproliferative disorder (PTLD) is a devastating complication of organ transplant. In a hospital-based registry, we identified biopsy-proven cases of PTLD among children during a 15-year period and reviewed trends in PTLD rates, the sites of involvement, and the associated survival rates. Cases that were included had at least 1 year of follow-up after the diagnosis of PTLD. We studied 82 patients with first-episode PTLD. Median age at diagnosis was 6.4 years (IQR 3.2-12.3 years). The most frequent PTLD sites were tonsillar/adenoidal (T/A [34%]) and gastrointestinal (32%), followed by miscellaneous (defined as less common sites including central nervous system, kidney, lung, and soft tissue [12%]), lymph node (11%), and multisite (11%). Kaplan-Meier survival curves showed that T/A PTLD was associated with decreased all-cause mortality compared with PTLD at other sites (log-rank 0.004), even after adjustment for histological subtype (P = .047). PTLD-related mortality was also decreased among T/A PTLD (log-rank 0.012) but showed a trend toward significance only after adjustment for histological subtype (P = .09). Among first episodes of PTLD, T/A PTLD was associated with a survival advantage compared with PTLD at other sites, even after adjustment for potential confounders. Based on our observations, we propose a clinical categorization of PTLD according to anatomical site of occurrence.

BACKGROUND: Optimal treatment strategy for the oldest patients with diffuse large B-cell lymphoma (DLBCL) remains controversial, as this group often is precluded from clinical trials, and population-based studies are limited.METHODS: All Danish DLBCL-patients ≥75 years diagnosed from 2003 to 2012 were identified, using the Danish National Lymphoma Registry (LYFO). Information regarding baseline characteristics, treatment, comorbidities and outcomes was retrieved from LYFO, the Danish National health registries and medical records. Patients were stratified by age (75-79; 80-84 and 85 + years), comorbidity score and treatment modality (standard treatment [R-CHOP/CHOP-like], less intensive regimens or palliative treatment).FINDINGS: A total of 1011 patients were included. Standard treatment was initiated in 64%, ranging from 83% among patients aged 75-79 years to 32% among patient aged 85 + years. With standard treatment, median overall survival (OS) estimates were 4·6, 2·6, and 1·9 years for the age groups 75-79, 80-84 and 85+ years. Among patient aged 75-79 and 80-84 years, OS was superior with standard treatment, although high comorbidity scores attenuated this association. Among patients aged 85+ years, survival was not influenced by treatment intensity. Patients ≥80 years had similar OS regardless of intended (R-)CHOP dosing, whereas patients of 75-79 years scheduled for full dose had higher OS. Standard treatment was not associated with increased hospitalisation.INTERPRETATION: Standard treatment is feasible with good outcomes in a large proportion of elderly DLBCL-patients. Planned dose reduction in patients aged ≥80 years had no negative impact on OS.

Doel Evaluatie van de behandelstrategieën en overleving van patiënten met irresectabel melanoom stadium IIIc of IV sinds de introductie van nieuwe geneesmiddelen in 2012 in Nederland. Opzet Prospectieve cohortstudie. Methode Wij analyseerden gegevens uit de Dutch Melanoma Treatment Registry (DMTR) van patiënten die in de periode 1 juli 2012-31 december 2015 waren gediagnosticeerd met irresectabel melanoom stadium IIIc of IV. We schatten de overlevingsduur met de Kaplan-Meier-methode. De relatie tussen jaar van diagnose en overleving werd geschat met Cox-regressieanalyse, gecorrigeerd voor leeftijd, ‘WHO performance status’, lactaatdehydrogenasewaarde, tumorstadium, hersenmetastasen en afstandsmetastasen. Resultaten Van de geregistreerde 2768 patiënten kreeg ongeveer driekwart systemische therapie; deze behandeling was elk jaar aan verandering onderhevig. De mediane overlevingsduur was 10,7 maanden (95%-BI: 9,6-13,2) in 2012 en 13,8 maanden (95%-BI: 11,8-15,6) in 2015; de mediane overlevingsduur voor systemisch behandelde patiënten was 17,1 maanden in 2015. De 2-jaarsoverleving nam in deze periode toe van 23 tot 40%. Patiënten gediagnosticeerd in 2015 hadden een betere overleving dan patiënten uit 2014 (hazardratio (HR): 0,82; 95%-BI: 0,73-0,93). Dit effect gold ook voor patiënten die werden behandeld met systemische therapie (HR: 0,79; 95%-BI: 0,69-0,91). Conclusie De snelle beschikbaarheid van nieuwe geneesmiddelen, die door de toenmalige minister van VWS en de beroepsgroep is geïnitieerd, heeft de behandeling van patiënten met irresectabel melanoom stadium IIIc of IV ingrijpend veranderd. De gegevens uit de DMTR duiden op een veilig gebruik van deze nieuwe geneesmiddelen in de dagelijkse praktijk en een verbetering van de overleving van patiënten met gevorderd melanoom in de afgelopen jaren.

In this study, we compared complete pathological downstaging (pCD, ≤(y)pT1N0) and overall survival (OS) in patients with cT2 versus cT3–4aN0M0 UC of the bladder undergoing radical cystectomy (RC) with or without neoadjuvant chemo‐ (NAC) or radiotherapy (NAR). A population‐based sample of 5,517 patients, who underwent upfront RC versus NAC + RC or NAR + RC for cT2‐4aN0M0 UC between 1995–2013, was identified from the Netherlands Cancer Registry. Data were retrieved from individual patient files and pathology reports. pCD‐rates were compared using Chi‐square tests and OS was estimated by Kaplan–Meier analyses. Multivariable analyses were conducted to determine odds (OR) and hazard ratios (HR) for pCD‐status and OS, respectively. We included 4,504 (82%) patients with cT2 and 1,013 (18%) with cT3–4a UC. Median follow‐up was 9.2 years. In cT2 UC, pCD‐rate was 25% after upfront RC versus 43% (p < 0.001) and 33% (p = 0.130) after NAC + RC and NAR + RC, respectively. In cT3–4a UC, pCD‐rate was 8% after upfront RC versus 37% (p < 0.001) and 16% (p = 0.281) after NAC + RC and NAR + RC, respectively. In cT2 UC, 5‐year OS was 57% and 51% for NAC + RC and upfront RC, respectively (p = 0.135), whereas in cT3–4a UC, 5‐year OS was 55% for NAC + RC versus 36% for upfront RC (p < 0.001). In multivariable analysis for OS, NAC was beneficial in cT3–4a UC (HR: 0.67, 95%CI 0.51–0.89) but not in cT2 UC (HR: 0.91, 95%CI 0.72–1.15). NAR did not influence OS. In conclusion, NAC + RC was associated with superior pCD compared to RC alone and NAR + RC. Superior OS for NAC + RC compared to RC alone was especially evident in cT3–4a disease.

Objective: To describe the use of prescription drugs and their association with patient characteristics in patients with multiple functional somatic syndromes (FSS) focusing on drugs generally recommended and not recommended in FSS treatment. Method: Using data from a national prescription registry, we describe the drug use during a two-year period for 239 trial participants. Using regression models, we analyse the associations of patient characteristics with the patterns of use of antidepressants, anticonvulsants, opioids and sedatives. Results: The use of prescription drugs was highly heterogeneous. Antidepressants were used at least temporarily by 34% (88/239), anticonvulsants by 7% (16/239), opioids by 26% (61/239) and sedatives by 20% (47/239) of the patients. Severe impairment due to multiple FSS was associated with use of opioids or sedatives (OR 6.49 (95% CI 2.68–15.68; p < 0.001)) but also with use of antidepressants or anticonvulsants (OR 3.42 (95% CI 1.35–8.65; p = 0.009)). Poor self-reported physical health, additional physical comorbidities and low socioeconomic status were associated with use of opioids or sedatives only. Conclusion: Antidepressants and anticonvulsants were modestly used. Opioids and sedatives were especially used by the severely affected patients. Balancing treatment expectations and enhancing patients' understanding of FSS may direct treatments towards more generally recommended drugs.

OBJECTIVE: To assess whether implementing patient-controlled admission (PCA) can reduce coercion and improve other clinical outcomes for psychiatric in-patients.METHODS: During 2013-2016, 422 patients in the PCA group were propensity score matched 1:5 with a control group (n = 2110) that received treatment as usual (TAU). Patients were followed up for at least one year using the intention to treat principle utilising nationwide registers. In a paired design, the outcomes of PCA patients during the year after signing a contract were compared with the year before.RESULTS: No reduction in coercion (risk difference = 0.001; 95% CI: -0.038; 0.040) or self-harming behaviour (risk difference = 0.005; 95% CI: -0.008; 0.018) was observed in the PCA group compared with the TAU group. The PCA group had more in-patient bed days (mean difference = 28.4; 95% CI: 21.3; 35.5) and more medication use (P < 0.0001) than the TAU group. Before and after analyses showed reduction in coercion (P = 0.0001) and in-patient bed days (P = 0.0003).CONCLUSION: Implementing PCA did not reduce coercion, service use or self-harm behaviour when compared with TAU. Beneficial effects of PCA were observed only in the before and after PCA comparisons. Further research should investigate whether PCA affects other outcomes to better establish its clinical value.

Background: The availability of methotrexate and the introduction of multiple biological agents have revolutionized the treatment of juvenile idiopathic arthritis (JIA). Several international and national drug registries have been implemented to accurately monitor the long-term safety/efficacy of these agents. This report aims to present the combined data coming from Pharmachild/PRINTO registry and the national registries from Germany (BiKeR) and Sweden.Methods: Descriptive statistics was used for demographic, clinical data, drug exposure, adverse events (AEs) and events of special interest (ESIs). For the Swedish register, AE data were not available.Results: Data from a total of 15,284 patients were reported: 8274 (54%) from the Pharmachild registry and 3990 (26%) and 3020 (20%) from the German and the Swedish registries, respectively. Pharmachild children showed a younger age (median of 5.4 versus 7.6 years) at JIA onset and shorter disease duration at last available visit (5.3 versus 6.1–6.8) when compared with the other registries. The most frequent JIA category was the rheumatoid factor–negative polyarthritis (range of 24.6–29.9%). Methotrexate (61–84%) and etanercept (24%–61.8%) were the most frequently used synthetic and biologic disease-modifying anti-rheumatic drugs (DMARDs), respectively. There was a wide variability in glucocorticoid use (16.7–42.1%). Serious AEs were present in 572 (6.9%) patients in Pharmachild versus 297 (7.4%) in BiKeR. Infection and infestations were the most frequent AEs (29.4–30.1%) followed by gastrointestinal disorders (11.5–19.6%). The most frequent ESIs were infections (75.3–89%).Conclusions: This article is the first attempt to present a very large sample of data on JIA patients from different national and international registries and represents the first proposal for data merging as the most powerful tool for future analysis of safety and effectiveness of immunosuppressive therapies in JIA.Registry registration: The Pharmachild registry is registered at ClinicalTrials.gov (NCT01399281) and at the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) (http://www.encepp.eu/encepp/viewResource.htm?id=19362). The BiKeR registry is registered at ENCePP (http://www.encepp.eu/encepp/viewResource.htm?id=20591).

Information on the safety of paternal use of medications prior to the time of conception is limited, and there is little available evidence regarding possible adverse effects of paternal use of systemic corticosteroids (SCS). In this cohort study, based on nationwide data, we examined the association between paternal use of SCS prior to conception and adverse birth outcome. The study includes data from all singletons born in Denmark from 1 January 1997 through 2013 (N = 1,013,994). Children fathered by men who redeemed a prescription of SCS within 3 months before conception (N = 2380) constituted the exposed groups. The outcome was congenital abnormalities (CAs), pre-term birth and small-for-gestational age (SGA). We adjusted for co-variates in multi-level logistic regression analyses. The adjusted odds ratios for pre-term birth and SGA were 0.81 (95% CI: 0.55–1.21) and 1.06 (95% CI: 0.68–1.64), respectively. The adjusted odds ratios for CAs were 1.08 (95% CI: 0.87–1.40) in children fathered by men who redeemed one prescription within 3 months before conception and 1.33 (95% CI: 0.99–1.79) in children fathered by men who redeemed two or more prescriptions. This study is the largest to date examining the effect of paternal use of SCS prior to conception on birth outcome. We found no significantly increased risk of pre-term birth or SGA. In children of fathers who redeemed at least two prescriptions of SCS within 3 months before conception, we found an increased risk of CAs, though not statistically significant. The types of CAs did not show a distinct pattern.

Doel Evaluatie van de behandelstrategieën en overleving van patiënten met irresectabel melanoom stadium IIIc of IV sinds de introductie van nieuwe geneesmiddelen in 2012 in Nederland. Opzet Prospectieve cohortstudie. Methode Wij analyseerden gegevens uit de Dutch Melanoma Treatment Registry (DMTR) van patiënten die in de periode 1 juli 2012-31 december 2015 waren gediagnosticeerd met irresectabel melanoom stadium IIIc of IV. We schatten de overlevingsduur met de Kaplan-Meier-methode. De relatie tussen jaar van diagnose en overleving werd geschat met Cox-regressieanalyse, gecorrigeerd voor leeftijd, ‘WHO performance status’, lactaatdehydrogenasewaarde, tumorstadium, hersenmetastasen en afstandsmetastasen. Resultaten Van de geregistreerde 2768 patiënten kreeg ongeveer driekwart systemische therapie; deze behandeling was elk jaar aan verandering onderhevig. De mediane overlevingsduur was 10,7 maanden (95%-BI: 9,6-13,2) in 2012 en 13,8 maanden (95%-BI: 11,8-15,6) in 2015; de mediane overlevingsduur voor systemisch behandelde patiënten was 17,1 maanden in 2015. De 2- jaarsoverleving nam in deze periode toe van 23 tot 40%. Patiënten gediagnosticeerd in 2015 hadden een betere overleving dan patiënten uit 2014 (hazardratio (HR): 0,82; 95%-BI: 0,73-0,93). Dit effect gold ook voor patiënten die werden behandeld met systemische therapie (HR: 0,79; 95%-BI: 0,69-0,91). Conclusie De snelle beschikbaarheid van nieuwe geneesmiddelen, die door de toenmalige minister van VWS en de beroepsgroep is geïnitieerd, heeft de behandeling van patiënten met irresectabel melanoom stadium IIIc of IV ingrijpend veranderd. De gegevens uit de DMTR duiden op een veilig gebruik van deze nieuwe geneesmiddelen in de dagelijkse praktijk en een verbetering van de overleving van patiënten met gevorderd melanoom in de afgelopen jaren.