Time trends in opioid use for patients undergoing hip fracture surgery in 1997-2018: A Danish population-based cohort study.

BACKGROUND: Although opioids are a mainstay for perioperative pain management in hip fracture patients, no studies have described changes in opioid use over the last two decades. The aim of this study was to describe time trends in opioid use in a population-based cohort of patients undergoing a first-time hip fracture surgery during 1997-2018. METHODS: Opioid-naïve hip fracture patients >55 years old were identified in Danish medical databases (n = 115,962). By 2-year calendar periods, we calculated prevalence rates (PR) of opioid use in the four quarters after surgery (Q1-Q4). Corresponding prevalence rate ratios (PRR) with 1997-1998 as a reference were estimated with 95% confidence intervals. Further, we calculated the median morphine milligram equivalents (MME) for each quarter. RESULTS: For Q1, the PR of opioid use increased from 29% in 1997-1998 to 78% in 2017-2018 corresponding to a PRR of 2.7 (2.6-2.8). For Q4, the PR was 15% in 1997-1998, peaked in 2003-2004 and then decreased, but stayed high at 13% in 2017-2018. The median MME did not increase when comparing 2017-2018 with 1997-1998, irrespective of the quarter. Tramadol was most frequently used in 1997-1998 shifting to oxycodone in 2017-2018. CONCLUSION: The PRs of opioid use in Q1 after surgery increased substantially from 1997 to 2018, but this did not translate into increased opioid use up to 1 year after hip fracture surgery or higher dosage. Our findings underline the importance of sustained focus on opioid tapering, dosage and use of opioids with the lowest potential for addiction and other adverse events. SIGNIFICANCE STATEMENT: Overall, opioid use in Q1 after hip fracture surgery increased 2.7 times from 1997 to 2018, but the doses and opioid use up to 1 year after surgery remained stable. Compared to elderly, younger patients were more likely to use opioid in Q1, while the tendency was opposite in Q2-Q4. The most used opioid type changed from tramadol to oxycodone. Our findings underline the importance of personalized opioid tapering and doses, and use of opioids with the lowest potential for addiction and other adverse events.

Prevalence of suicidal ideation in German psychotherapy outpatients: A large multicenter assessment.

BACKGROUND: Suicidal ideation is a major concern in clinical practice. Yet, little is known about prevalence rates of suicidal ideation in patients undergoing outpatient psychotherapeutic treatment. Therefore, the aim of the current study is to assess the prevalence of suicidal ideation in a large sample of psychotherapy outpatients in Germany. The data analyzed in this study is taken from the KODAP-project on the coordination of data collection and analysis at German university-based research and training outpatient clinics for psychotherapy. METHODS: A total of N = 10,357 adult outpatients (64.4 % female; age: M(SD) = 35.94 (13.54), range: 18-92 years of age) starting cognitive-behavioral therapy at one of 27 outpatient clinics in Germany were included in the current study. Prevalence of suicidal ideation was assessed with the Suicide Item (Item 9) of the Beck-Depression Inventory II. RESULTS: Suicidal ideation was reported by 36.7 % (n = 3795) of the participants. Borderline Personality Disorder, Posttraumatic Stress Disorder, and recurrent Major Depression were the diagnoses most strongly associated with the presence and severity of suicidal ideation. LIMITATION: Suicide ideation was assessed only with the respective item of the Beck Depression Inventory II. CONCLUSION: Suicidal ideation is very common among adult patients who start psychotherapy in Germany. A well-founded knowledge of risk assessment in suicidal patients and suicide-specific treatment options is therefore highly relevant.

Comorbidity and risk of infection among patients with hip fracture: a Danish population-based cohort study.

Impact of comorbidity on infection risk among hip fracture patients is unclear. We found high incidence of infection. Comorbidity was an important risk factor for infection up to 1 year after surgery. Results indicates a need for additional investment in pre- and postoperative programs that assist patients with high comorbidity. PURPOSE: Comorbidity level and incidence of infection have increased among older patients with hip fracture. The impact of comorbidity on infection risk is unclear. We conducted a cohort study examining the absolute and relative risks of infection in relation to comorbidity level among hip fracture patients. METHODS: Utilizing Danish population-based medical registries, we identified 92,600 patients aged ≥ 65 years undergoing hip fracture surgery between 2004 and 2018. Comorbidity was categorized by Charlson comorbidity index scores (CCI): none (CCI = 0), moderate (CCI = 1-2), or severe (CCI ≥ 3). Primary outcome was any hospital-treated infection. Secondary outcomes were hospital-treated pneumonia, urinary tract infection, sepsis, reoperation due to surgical-site infection (SSI), and a composite of any hospital- or community-treated infection. We calculated cumulative incidence and hazard ratios (aHRs) adjusted for age, sex, and surgery year, including 95% confidence intervals (CIs). RESULTS: Prevalence of moderate and severe comorbidity was 40% and 19%, respectively. Incidence of any hospital-treated infection increased with comorbidity level within 0-30 days (none 13% vs. severe 20%) and 0-365 days (none 22% vs. 37% severe). Patients with moderate and severe comorbidity, compared to no comorbidity, had aHRs of 1.3 (CI: 1.3-1.4) and 1.6 (CI: 1.5-1.7) within 0-30 days, and 1.4 (CI: 1.4-1.5) and 1.9 (CI: 1.9-2.0) within 0-365, respectively. Highest incidence was observed for any hospital- or community-treated infection (severe 72%) within 0-365 days. Highest aHR was observed for sepsis within 0-365 days (severe vs. none: 2.7 (CI: 2.4-2.9)). CONCLUSION: Comorbidity is an important risk factor for infection up to 1 year after hip fracture surgery.

Collimation border with U-Net segmentation on chest radiographs compared to radiologists.

INTRODUCTION: Chest Radiography (CXR) is a common radiographic procedure. Radiation exposure to patients should be kept as low as reasonably achievable (ALARA), and monitored continuously as part of quality assurance (QA) programs. One of the most effective dose reduction tools is proper collimation practice. The purpose of this study is to determine whether a U-Net convolutional neural networks (U-CNN) can be trained to automatically segment the lungs and calculate an optimized collimation border on a limited CXR dataset. METHODS: 662 CXRs with manual lung segmentations were obtained from an open-source dataset. These were used to train and validate three different U-CNNs for automatic lung segmentation and optimal collimation. The U-CNN dimensions were 128 × 128, 256 × 256, and 512 × 512 pixels and validated with five-fold cross validation. The U-CNN with the highest area under the curve (AUC) was tested externally, using a dataset of 50 CXRs. Dice scores (DS) were used to compare U-CNN segmentations with manual segmentations by three radiographers and two junior radiologists. RESULTS: DS for the three U-CNN dimensions with segmentation of the lungs ranged from 0.93 to 0.96, respectively. DS of the collimation border for each U-CNN was 0.95 compared to the ground truth labels. DS for lung segmentation and collimation border between the junior radiologists was 0.97 and 0.97. One radiographer differed significantly from the U-CNN (p = 0.016). CONCLUSION: We demonstrated that a U-CNN could reliably segment the lungs and suggest a collimation border with great accuracy compared to junior radiologists. This algorithm has the potential to automate collimation auditing of CXRs. IMPLICATIONS FOR PRACTICE: Creating an automatic segmentation model of the lungs can produce a collimation border, which can be used in CXR QA programs.

Assessing how routes to diagnosis vary by the age of patients with cancer: a nationwide register-based cohort study in Denmark.

BACKGROUND: Older patients with cancer have poorer prognosis compared to younger patients. Moreover, prognosis is related to how cancer is identified, and where in the healthcare system patients present, i.e. routes to diagnosis (RtD). We investigated whether RtD varied by patients' age. METHODS: This population-based national cohort study used Danish registry data. Patients were categorized into age groups and eight mutually exclusive RtD. We employed multinomial logistic regressions adjusted for sex, region, diagnosis year, cohabitation, education, income, immigration status and comorbidities. Screened and non-screened patients were analysed separately. RESULTS: The study included 137,876 patients. Both younger and older patients with cancer were less likely to get diagnosed after a cancer patient pathways referral from primary care physician compared to middle-aged patients. Older patients were more likely to get diagnosed via unplanned admission, death certificate only, and outpatient admission compared to younger patients. The patterns were similar across comorbidity levels. CONCLUSIONS: RtD varied by age groups, and middle-aged patients were the most likely to get diagnosed after cancer patient pathways with referral from primary care. Emphasis should be put on raising clinicians' awareness of cancer being the underlying cause of symptoms in both younger patients and in older patients.

Time trends in use of non-steroidal anti-inflammatory drugs and opioids one year after total hip arthroplasty due to osteoarthritis during 1996-2018: a population-based cohort study of 103,209 patients.

OBJECTIVE: To examine time trends in the use of NSAIDs and opioids for patients with osteoarthritis undergoing total hip arthroplasty (THA) during 1996-2018. METHOD: Using Danish population-based medical databases, we identified 103,209 THA patients. Prevalence rates of NSAID and opioid use among preoperative users and non-users were calculated in four quarters (Q1-Q4) after THA by calendar periods (1996-2000, 2001-2006, 2007-2012 and 2013-2018). Prevalence rate ratios (PRR) were adjusted for age and gender. RESULTS: Among preoperative NSAID users and non-users, NSAID use in Q1 increased from 32.6% in 1996-2000 to 48.0% in 2013-2018 (PRR = 1.49, 95% CI: 1.42-1.55) and from 12.9% to 32.0% (PRR = 2.49 (2.32-2.67)), respectively. Among preoperative opioid users and non-users, opioid use in Q1 increased from 42.7% in 1996-2000 to 76.9% in 2013-2018 (PRR = 1.81 (1.73-1.89)) and from 15.2% to 58.2% (PRR = 3.85 (3.65-4.05)), respectively. NSAID use in Q4 decreased from 24.5% in 1996-2000 to 21.4% in 2013-2018 (PRR = 0.88 (0.83-0.93)) and from 6.9% to 5.6% (PRR = 0.81 (0.73-0.91)) in preoperative NSAIDs users and non-users, respectively. Opioid use in Q4 increased from 26.6% in 1996-2000 to 28.6% (PRR = 1.08 (1.02-1.15)) in 2013-2018 and from 4.1% to 5.0% (PRR = 1.25 (1.11-1.40)) in preoperative opioid users and non-users, respectively. CONCLUSION: We observed up to a 4-fold increase in NSAID and opioid use in Q1 during 1996-2018, while usage in Q4 did not change substantially. However, 5-6% of the preoperative non-users of NSAIDs and opioids were users in Q4, which might relate to inaccurate indication for or timing of THA and the post-surgical phasing out of analgesics use.

Using multi-event hydrologic and hydraulic signatures from water level sensors to diagnose locations of uncertainty in integrated urban drainage models used in living digital twins.

Digital twins of urban drainage systems require simulation models that can adequately replicate the physical system. All models have their limitations, and it is important to investigate when and where simulation results are acceptable and to communicate the level of performance transparently to end users. This paper first defines a classification of four possible 'locations of uncertainty' in integrated urban drainage models. It then develops a structured framework for identifying and diagnosing various types of errors. This framework compares model outputs with in-sewer water level observations based on hydrologic and hydraulic signatures. The approach is applied on a real case study in Odense, Denmark, with examples from three different system sites: a typical manhole, a small flushing chamber, and an internal overflow structure. This allows diagnosing different model errors ranging from issues in the underlying asset database and missing hydrologic processes to limitations in the model software implementation. Structured use of signatures is promising for continuous, iterative improvements of integrated urban drainage models. It also provides a transparent way to communicate the level of model adequacy to end users.

Risk of infections and mortality in Danish patients with cancer diagnosed with bone metastases: a population-based cohort study.

OBJECTIVES: Risk of infections in patients with solid cancers and bone metastases (BM) and the subsequent impact on prognosis is unclear. We examined the risk of infections among patients with cancer diagnosed with BM and the subsequent impact of infections on mortality. DESIGN: Population-based cohort study. SETTING: Danish medical databases holding information on all hospital contacts in Denmark. PARTICIPANTS: Adult patients with solid cancers and BM between 1 January 1994 and 30 November 2013. OUTCOME MEASURES: In the risk analyses, the outcome was time to hospitalisation for common severe infections, pneumonia, sepsis and urinary tract infections. In the mortality analysis, we used Cox regression to compute HRs of death, modelling infection as time-varying exposure, stratifying for primary cancer type and adjusting for age, sex and comorbidities. RESULTS: Among 23 336 patients with cancer and BM, cumulative incidences of common severe infections were 4.6%, 14.0% and 20.0% during 1 month, 1 year and 10 years follow-up. The highest incidence was observed for pneumonia, followed by urinary tract infections and sepsis. Infection was a strong predictor of 1 month mortality (adjusted HR: 2.1 (95% CI 1.8 to 2.3)) and HRs increased after 1 and 10 years: 2.4 (95% CI 2.3 to 2.6) and 2.4 (95% CI 2.4 to 2.6). Sepsis and pneumonia were the strongest predictors of death. Results were consistent across cancer types. CONCLUSION: Patients with cancer and BM were at high risk of infections, which was associated with a more than twofold increased risk of death for up to 10 years of follow-up. The findings underscore the importance of preventing infections in patients with cancer and BM.

National, clinical cohort study of late effects among survivors of acute lymphoblastic leukaemia: the ALL-STAR study protocol.

INTRODUCTION: More than 90% of patients diagnosed with childhood acute lymphoblastic leukaemia (ALL) today will survive. However, half of the survivors are expected to experience therapy-related chronic or late occurring adverse effects, reducing quality of life. Insight into underlying risk trajectories is warranted. The aim of this study is to establish a Nordic, national childhood ALL survivor cohort, to be investigated for the total somatic and psychosocial treatment-related burden as well as associated risk factors, allowing subsequent linkage to nation-wide public health registers. METHODS AND ANALYSIS: This population-based observational cohort study includes clinical follow-up of a retrospective childhood ALL survivor cohort (n=475), treated according to a common Nordic ALL protocol during 2008-2018 in Denmark. The study includes matched controls. Primary endpoints are the cumulative incidence and cumulative burden of 197 health conditions, assessed through self-report and proxy-report questionnaires, medical chart validation, and clinical examinations. Secondary endpoints include organ-specific outcome, including cardiovascular and pulmonary function, physical performance, neuropathy, metabolic disturbances, hepatic and pancreatic function, bone health, oral and dental health, kidney function, puberty and fertility, fatigue, and psychosocial outcome. Therapy exposure, acute toxicities, and host genome variants are explored as risk factors. ETHICS AND DISSEMINATION: The study is approved by the Regional Ethics Committee for the Capital Region in Denmark (H-18035090/H-20006359) and by the Danish Data Protection Agency (VD-2018-519). Results will be published in peer-reviewed journals and are expected to guide interventions that will ameliorate the burden of therapy without compromising the chance of cure.

Validation of the Danish versions of the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaires (BRAFs).

Objective: This study aimed to validate the Danish versions of the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ) and BRAF Numerical Rating Scale version 2 (NRSv2).Method: We tested face and content validity, internal consistency, criterion validity, construct validity, and reproducibility for the BRAF-MDQ, and face and criterion validity and reproducibility for the BRAF-NRS.Results: In all, 224/236 patients (95%) completed the questionnaires [70% female, mean ± sd age 59 ± 13.04 years, disease duration 11.2 ± 9.49 years, Health Assessment Questionnaire (HAQ) 0.724 ± 0.70, and 28-joint Disease Activity Score-C-reactive protein 2.55 ± 1.24]. The unidimensionality for the physical and cognitive fatigue subscales was confirmed, whereas the living with fatigue and emotional fatigue subscales were not unidimensional. Cronbach's α was 0.94 for the BRAF-MDQ total and 0.78-0.92 for the four subscales. The correlations between BRAF-MDQ and various measures were: 36-item Short Form Health Survey (SF-36) vitality subscale, 0.75; Hospital Anxiety and Depression Scale (HADS) anxiety subscale, 0.65; HADS depression subscale, 0.62; visual analogue scale (VAS) pain, 0.62; VAS global, 0.73; and HAQ, 0.62. The intraclass correlation coefficient for agreement was 0.995. A Bland-Altman plot showed a mean ± sd difference of -1.9 ± 3.62 for BRAF-MDQ. Correlation coefficients between the BRAF-NRSv2 subscales and other subscales were: BRAF-MDQ subscales, 0.57-0.93; SF-36 vitality subscale, 0.54-0.68; and VAS fatigue, 0.66-0.82.Conclusions: The Danish BRAFs are considered valid and reliable for use among Danish patients with rheumatoid arthritis, despite the subscales living with fatigue and emotional fatigue not being unidimensional, as they are in the original version.

A reduced CP level without medicinal zinc oxide does not alter the intestinal morphology in weaned pigs 24 days post-weaning.

The use of medicinal zinc oxide (ZnO) to prevent diarrhoea post-weaning will be banned in the EU from 2022. Therefore, new alternatives are needed to avoid an increase in diarrhoea and higher antibiotic use. A low dietary CP level has shown to lower the frequency of diarrhoea in pigs, due to lower microbial protein fermentation in the colon as well as improved conditions in the small intestine after weaning. The objective of this study was to examine the effect of decreased CP levels post-weaning as an alternative to medicinal ZnO on gut morphology and histopathology. Five hundred and sixty pigs were randomly assigned into one of six groups receiving a two-phase diet from 5.5 to 15 kg: positive control group (PC) with medicinal ZnO and standard levels of protein (19.1-18.4% CP), negative control group (NC) without medicinal ZnO and standard levels of protein (19.1-18.4% CP). The remaining four low protein groups were a low-standard (LS) CP level (16.6-18.4% CP), a low-low (LL) CP level (16.6-16.2% CP), a very low-high (VLH) CP level (14-19.3% CP) and a very low-medium (VLM) CP level (14-17.4% CP). Individual BW was recorded at day 0, 10 and 24 post-weaning, and all antibiotic treatments were recorded. Tissue samples from the small intestine (mid-jejunum) for morphological and histopathologic analysis, organ weights, blood and urine samples were collected at day 10 and 24 post-weaning from a total of 90 sacrificed weaners. The results demonstrated no differences in intestinal morphology between groups, but the histopathology showed a damaged brush border score in VLM and VLH pigs . In addition, a lower blood urea nitrogen in VLM pigs at 24 days was found. The LL and VLM pigs had a significantly decreased average daily gain in the overall trial period compared to PC and NC pigs. Conclusively, intestinal brush border was damaged by the very low protein diet at 24 days post-weaning, but intestinal morphology was unaffected by dietary strategy.

DIAGNOSIS OF ENDOCRINE DISEASE: Sex steroid action in adolescence: too much, too little; too early, too late.

ABSTRACT: This review aims to cover the subject of sex steroid action in adolescence. It will include situations with too little sex steroid action, as seen in for example, Turners syndrome and androgen insensitivity issues, too much sex steroid action as seen in adolescent PCOS, CAH and gynecomastia, too late sex steroid action as seen in constitutional delay of growth and puberty and too early sex steroid action as seen in precocious puberty. This review will cover the etiology, the signs and symptoms which the clinician should be attentive to, important differential diagnoses to know and be able to distinguish, long-term health and social consequences of these hormonal disorders and the course of action with regards to medical treatment in the pediatric endocrinological department and for the general practitioner. This review also covers situations with exogenous sex steroid application for therapeutic purposes in the adolescent and young adult. This includes gender-affirming therapy in the transgender child and hormone treatment of tall statured children. It gives some background information of the cause of treatment, the patient's motivation for medicating (or self-medicating), long-term consequences of exogenous sex steroid treatment and clinical outcome of this treatment.

Next-generation sequencing of newborn screening genes: the accuracy of short-read mapping.

Newborn screening programs are an integral part of public health systems aiming to save lives and improve the quality of life for infants with treatable disorders. Technological advancements have driven the expansion of newborn screening programs in the last two decades and the development of fast, accurate next-generation sequencing technology has opened the door to a range of possibilities in the field. However, technological challenges with short-read next-generation sequencing technologies remain significant in highly homologous genomic regions such as pseudogenes or paralogous genes and need to be considered when implemented in screening programs. Here, we simulate 50 genomes from populations around the world to test the extent to which high homology regions affect short-read mapping of genes related to newborn screening disorders and the impact of differential read lengths and ethnic backgrounds. We examine a 158 gene screening panel directly relevant to newborn screening and identify gene regions where read mapping is affected by homologous genomic regions at different read lengths. We also determine that the patient's ethnic background does not have a widespread impact on mapping accuracy or coverage. Additionally, we identify newborn screening genes where alternative forms of sequencing or variant calling pipelines should be considered and demonstrate that alterations to standard variant calling can retrieve some formerly uncalled variants.

A comparison of nutrient uptake efficiency and growth rate between different macrophyte growth forms.

Aquatic macrophytes grow abundantly in many lowland streams and play a key role in ecosystem functioning, such as nutrient retention. In this study, we performed a microcosm experiment to quantify and compare the contribution of two freshwater macrophyte growth forms to nutrient cycling. We measured and compared inorganic nitrogen (NH4-N and NO3-N) and phosphorus (PO4-P) uptake kinetic parameters (Vmax and Cmin) in 12 submerged and seven amphibious plant species. We tested whether relative growth rate (RGR) was related to high Vmax and low Cmin, and quantified changes in nutrient uptake kinetic in a subset of six out of 19 plants species during the growth season. Uptake rates of NH4-N were higher in submerged compared to amphibious plants, whereas uptake rates of NO3-N were significantly higher in amphibious species; PO4-P uptake kinetics were not significantly different between the two growth forms. There were also significant seasonal differences in Vmax NH4-N rate among both submerged and amphibious species and in Vmax NO3-N among amphibious species. Highest uptake rates were observed in summer for both submerged and amphibious species. Overall, we found that nutrient uptake kinetics differed between the two growth forms within and between seasons. Consequently, the presence of both growth forms should extend the period of nutrient uptake across the year and enhance nutrient uptake within seasons. We conclude that higher functional diversity enhances annual nutrient uptake in streams and that stream restoration efforts should consider increasing the niche space available for both submerged and amphibious species.

Injection of freshly collected autologous adipose tissue into non-healing wounds after closed incision pilonidal surgery.

BACKGROUND: Chronic non-healing wounds are a major problem after closed incision pilonidal surgery. Freshly collected autologous adipose tissue injected into perianal fistulas in patients with Crohn's disease seems to promote healing. We investigated this technique in patients with non-healing wounds after cleft-lift surgery for pilonidal sinus disease (PSD). METHOD: In a prospective interventional pilot study conducted at our institution autologous adipose tissue from the abdominal wall was harvested, and injected into chronic non-healing PS wounds after surgical revision, healing rate being the primary outcome. The wounds were left open. Patients were followed every 2 to 3 weeks until complete healing (skin coverage, no undermining). RESULTS: 7 male patients were included (mean age 24 ± 0,6 SD years) and complete healing was achieved in 6 patients (86%). Median time to healing was 90 days (range 36-403 days ) and mean follow-up time was 388± 45 days. All patients reported major symptom relief shortly after the procedure. The mean operation time was 80 ± 23 minutes and the mean amount of freshly collected adipose tissue injected was 27.4± 12 ml. There were no complications. CONCLUSIONS: Freshly collected autologous adipose tissue injected into chronic non-healing pilonidal wounds seems safe and efficient.

Cladribine modifies functional properties of microglia.

Cladribine (CdA), an oral prodrug approved for the treatment of relapsing multiple sclerosis, selectively depletes lymphocytes. CdA passes the blood-brain barrier, suggesting a potential effect on central nervous system (CNS) resident cells. We examined if CdA modifies the phenotype and function of naive and activated primary mouse microglia, when applied in the concentrations 0·1-1 µM that putatively overlap human cerebrospinal fluid (CSF) concentrations. Primary microglia cultures without stimulation or in the presence of proinflammatory lipopolysaccharide (LPS) or anti-inflammatory interleukin (IL)-4 were treated with different concentrations of CdA for 24 h. Viability was assessed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Phagocytotic ability and morphology were examined by flow cytometry and random migration using IncuCyte Zoom and TrackMate. Change in gene expression was examined by quantitative polymerase chain reaction (qPCR) and protein secretion by Meso Scale Discovery. We found that LPS and IL-4 up-regulated deoxycytidine kinase (DCK) expression. Only activated microglia were affected by CdA, and this was unrelated to viability. CdA 0·1-1 µM significantly reduced granularity, phagocytotic ability and random migration of activated microglia. CdA 10 µM increased the IL-4-induced gene expression of arginase 1 (Arg1) and LPS-induced expression of IL-1ß, tumor necrosis factor (TNF), inducible nitric oxide synthase (iNOS) and Arg1, but protein secretion remained unaffected. CdA 10 µM potentiated the increased expression of anti-inflammatory TNF receptor 2 (TNF-R2) but not TNF-R1 induced by LPS. This suggests that microglia acquire a less activated phenotype when treated with 0·1-1 µM CdA that putatively overlaps human CSF concentrations. This may be related to the up-regulated gene expression of DCK upon activation, and suggests a potential alternative mechanism of CdA with direct effect on CNS resident cells.

Safety, efficiency and health-related quality of telephone triage conducted by general practitioners, nurses, or physicians in out-of-hours primary care: a quasi-experimental study using the Assessment of Quality in Telephone Triage (AQTT) to assess audio-recorded telephone calls.

BACKGROUND: To explore and compare safety, efficiency, and health-related quality of telephone triage in out-of-hours primary care (OOH-PC) services performed by general practitioners (GPs), nurses using a computerised decision support system (CDSS), or physicians with different medical specialities. METHODS: Natural quasi-experimental cross-sectional study conducted in November and December 2016. We randomly selected 1294 audio-recorded telephone triage calls from two Danish OOH-PC services triaged by GPs (n = 423), nurses using CDSS (n = 430), or physicians with different medical specialities (n = 441). An assessment panel of 24 physicians used a validated assessment tool (Assessment of Quality in Telephone Triage - AQTT) to assess all telephone triage calls and measured health-related quality, safety, and efficiency of triage. RESULTS: The relative risk (RR) of poor quality was significantly lower for nurses compared to GPs in four out of ten items regarding identifying and uncovering of problems. For most items, the quality tended to be lowest for physicians with different medical specialities. Compared to calls triaged by GPs (reference), the risk of clinically relevant undertriage was significantly lower for nurses, while physicians with different medical specialties had a similar risk (GP: 7.3%, nurse: 3.7%, physician: 6.1%). The risk of clinically relevant overtriage was significantly higher for nurses (9.1%) and physicians with different medical specialities (8.2%) compared to GPs (4.3%). GPs had significantly shorter calls (mean: 2 min 57 s, SD: 105 s) than nurses (mean: 4 min 44 s, SD: 168 s). CONCLUSIONS: Our explorative study indicated that nurses using CDSS performed better than GPs in telephone triage on a large number of health-related items, had a lower level of clinically relevant undertriage, but were perceived less efficient. Calls triaged by physicians with different medical specialities were perceived less safe and less efficient compared to GPs. Differences in the organisation of telephone triage may influence the distribution of workload in primary and secondary OOH services. Future research could compare the long-term outcomes following a telephone call to OOH-PC related to safety and efficiency.

Catchment properties and the photosynthetic trait composition of freshwater plant communities.

Unlike in land plants, photosynthesis in many aquatic plants relies on bicarbonate in addition to carbon dioxide (CO2) to compensate for the low diffusivity and potential depletion of CO2 in water. Concentrations of bicarbonate and CO2 vary greatly with catchment geology. In this study, we investigate whether there is a link between these concentrations and the frequency of freshwater plants possessing the bicarbonate use trait. We show, globally, that the frequency of plant species with this trait increases with bicarbonate concentration. Regionally, however, the frequency of bicarbonate use is reduced at sites where the CO2 concentration is substantially above the air equilibrium, consistent with this trait being an adaptation to carbon limitation. Future anthropogenic changes of bicarbonate and CO2 concentrations may alter the species compositions of freshwater plant communities.

Use of anti-osteoporosis medication dispensing by patients with hip fracture: could we do better?

Although Scandinavian countries have the highest incidence of hip fracture in the world, trends in anti-osteoporosis medication use have not been studied. We found less than one-third of Danish hip fracture patients had dispensing of anti-osteoporosis medication over a 10-year period using routinely collected data from population-based registries. INTRODUCTION: To examine trend in dispensing of anti-osteoporosis medication before and after hip fracture surgery in Denmark over a 10-year period using routinely collected data from population-based registries. METHODS: From the Danish Multidisciplinary Hip Fracture Registry, we included 65,011 patients aged 65 years or older with an incident hip fracture in 2005-2015. We calculated, for each calendar year of hip fracture diagnosis, the prevalence of use of anti-osteoporosis medication (at least one dispensing of bisphosphonates, strontium ranelate, denosumab, selective estrogen receptor modulators, or teriparatide) in the year before and in the year following hip fracture diagnosis. Among those without a dispensing in the year before hip fracture, we computed 1-year cumulative incidence of use following hip fracture. We treated death as a competing risk and stratified the analysis on sex, age, and comorbidity. RESULTS: The prevalence of use before hip fracture varied between 7 and 12%, increasing slightly from 2005 to 2015. The cumulative incidence of use following hip fracture decreased from 16% in 2005 to 13% in 2010, whereupon it increased to 20%. A similar pattern was seen with each stratum of sex, age groups, and comorbidity. The overall prevalence of use after hip fracture was below 22% in all calendar years. CONCLUSIONS: Less than one-third of hip fracture patients had dispensing of anti-osteoporosis medication up to 1 year after hip fracture. We observed only a slight increase in dispensing after hip fracture over the study period, irrespective of patient sex, age, and comorbidity at the time of hip fracture.