Risk factors for mortality in patients admitted to a psychiatric acute ward: A prospective cohort study.

INTRODUCTION: Associations between psychiatric disorders and mortality have been extensively studied, but limited evidence exists regarding influence of clinical characteristics on mortality risk, at the time of acute psychiatric hospitalization. METHODS: A prospective total-cohort study included all patients consecutively admitted to Haukeland University Hospital's psychiatric acute ward in Bergen, Norway between 2005 and 2014 (n = 6125). Clinical interviews were conducted at the first admission within the study period, and patients were subsequently followed for up to 15 years in the Norwegian Cause of Death Registry. Competing risks regression models were used to investigate associations between clinical characteristics at first admission and the risk of natural and unnatural death during follow-up. RESULTS: The mean age at first admission and at time of death was 42.5 and 62.8 years, respectively, and the proportion of women in the sample was 47.2%. A total of 1381 deaths were registered during follow-up, of which 65.5% had natural, 30.4% unnatural, and 4.1% unknown causes. Higher age, male sex, unemployment, cognitive deficits, and physical illness were associated with increased risk of natural death. Male sex, having no partner, physical illness, suicide attempts, and excessive use of alcohol and illicit substances were associated with increased risk of unnatural death. CONCLUSION: Psychiatric symptoms, except suicide attempts, were unrelated to increased mortality risk. In the endeavor to reduce the increased mortality risk in people with mental disorders, focus should be on addressing modifiable risk factors linked to physical health and excessive use of alcohol and illicit substances.

Differential Effectiveness of Atypical Antipsychotics on Hallucinations: A Pragmatic Randomized Controlled Trial.

BACKGROUND: Most studies investigating antipsychotic effectiveness report either total psychopathology or symptom cluster findings. Studies focusing on a separate symptom, such as hallucinations, a hallmark symptom in schizophrenia, are scarce.Therefore, the current study aims to compare the antihallucinatory effectiveness of 3 pharmacologically different antipsychotics: olanzapine, amisulpride, and aripiprazole. METHODS: The present study is part of the Bergen-Stavanger-Innsbruck-Trondheim study, a 12-month prospective, randomized, pragmatic antipsychotic drug trial in active-phase schizophrenia spectrum disorders. The primary outcome of the present study was change of hallucinations as measured by item P3 (hallucinatory behavior) from the Positive and Negative Syndrome Scale in the subgroup with hallucinations at baseline. Primary analyses were intention to treat. RESULTS: A total of 144 participants were included in the study, where 105 (72%) had a score of 3 or more on the Positive and Negative Syndrome Scale P3 item at baseline, indicating the presence of hallucinations (HALL subgroup).In the HALL subgroup, a significantly less reduction of hallucinations was revealed for participants using olanzapine in weeks 12, 26, 39, and 52 when compared with amisulpride and in weeks 26 and 52 when compared with aripiprazole. In subanalyses for participants never exposed to antipsychotic drugs (antipsychotic-naive) and those who had used antipsychotics before entering the study, antihallucinatory differences were revealed only in the latter group. CONCLUSIONS: A differential antihallucinatory effect of the 3 study drugs was present. The inferior effect of olanzapine seems to be driven by the subgroup of participants exposed to antipsychotic treatment before entering the study.

Short-term Revision Risk of Patellofemoral Arthroplasty Is High: An Analysis from Eight Large Arthroplasty Registries.

BACKGROUND: Patellofemoral arthroplasty (PFA) is one option for the treatment of isolated patellofemoral osteoarthritis, but there are limited data regarding the procedure and results. Because isolated patellofemoral arthritis is relatively uncommon, available case series generally are small, and even within national registries, sample sizes are limited. Combining data from multiple registries may aid in assessing worldwide PFA usage and survivorship. QUESTIONS/PURPOSES: We combined and compared data from multiple large arthroplasty registries worldwide to ask: (1) What proportion of patients undergoing primary knee arthroplasty have PFA? (2) What are the patient and prosthesis characteristics associated with PFA in common practice, as reflected in registries? (3) What is the survivorship free from revision of PFA and what are the reasons for and types of revisions? METHODS: Data were provided by eight registries that are members of the International Society of Arthroplasty Registries (ISAR) who agreed to share aggregate data: Australia, New Zealand, Canada, Sweden, Finland, Norway, the Netherlands, and the United States. De-identified data were obtained for PFA performed from either the beginning of year 2000, or the earliest recorded implantation date after that in each individual registry when PFA data collection commenced, up to December 31, 2016. This included patient demographics, implant use, all-cause revision rate (determined by cumulative percent revision [CPR]), and reasons for and type of revision. RESULTS: During the data collection period, 6784 PFAs were performed in the eight countries. PFAs comprised less than 1% of primary knee replacements in all registries. Patient demographics were comparable in all countries. Patients were generally more likely to be women than men, and the mean age ranged from 50 years to 60 years. All registries showed a high rate of revision for PFA. The 5-year CPR for any reason ranged from 8.0% (95% CI 4.5 to 11.5) in Norway to 18.1% (95% CI 15.5 to 20.7) in the Netherlands. The most common reason for revision across all countries was disease progression (42%, 434 of 1034). Most PFAs (83%, 810 of 980) were revised to a TKA. CONCLUSIONS: The revision risk of PFA in all registries surveyed was more than three times higher than the reported revision risk of TKA at the same times. The survivorship of PFA is similar to that of the no-longer-used procedure of metal-on-metal conventional hip replacement. Although there may be potential functional benefits from PFA, these findings of consistent and alarmingly high rates of revision should create concern, particularly as this procedure is often used in younger patients. LEVEL OF EVIDENCE: Level III, therapeutic study.

Hospital volume and the risk of revision in Oxford unicompartmental knee arthroplasty in the Nordic countries -an observational study of 14,496 cases.

BACKGROUND: High procedure volume and dedication to unicompartmental knee arthroplasty (UKA) has been suggested to improve revision rates. This study aimed to quantify the annual hospital volume effect on revision risk in Oxfordu nicompartmental knee arthroplasty in the Nordic countries. METHODS: 14,496 cases of cemented medial Oxford III UKA were identified in 126 hospitals in the four countries included in the Nordic Arthroplasty Register Association (NARA) database from 2000 to 2012. Hospitals were divided by quartiles into 4 annual procedure volume groups (≤11, 12-23, 24-43 and ≥44). The outcome was revision risk after 2 and 10 years calculated using Kaplan Meier method. Multivariate Cox regression analysis was used to assess the Hazard Ratio (HR) of any revision due to specific reasons with 95% confidence intervals (CI). RESULTS: The implant survival was 80% at 10 years in the volume group ≤11 procedures per year compared to 83% in other volume groups. The HR adjusted for age category, sex, year of surgery and nation was 0.87 (95% CI: 0.76-0.99, p = 0.036) for the group 12-23 procedures per year, 0.78 (95% CI: 0.68-0.91, p = 0.002) for the group 24-43 procedures per year and 0.82 (95% CI: 0.70-0.94, p = 0.006) for the group ≥44 procedures per year compared to the low volume group. Log-rank test was p = 0.003. The risk of revision for unexplained pain was 40-50% higher in the low compared with other volume groups. CONCLUSION: Low volume hospitals performing ≤11 Oxford III UKAs per year were associated with an increased risk of revision compared to higher volume hospitals, and unexplained pain as revision cause was more common in low volume hospitals.

Remission in schizophrenia spectrum disorders: A randomized trial of amisulpride, aripiprazole and olanzapine.

Schizophrenia is a serious mental disorder, and monitoring remission is a widely used measure of effectiveness of the treatment provided. It is very important to identify possible factors correlating with remission. In our substudy of BeSt InTro, a randomized controlled trial of three antipsychotic drugs, 126 patients with ICD-10 diagnoses F20-29 (F23 excluded) were randomized to one of the second-generation antipsychotic drugs amisulpride, aripiprazole or olanzapine. Remission rate was calculated at seven assessment points, with and without using the time criterion of six months included in the consensus remission criteria. Because of drop-out (n = 77), we had data for 49 patients at one-year follow-up. These data were used to calculate the one-year remission rate to 55 % (27/49), without taking into consideration the 6-month time criterion. When we applied the consensus remission criteria with the 6-month time criterion included, the one-year remission rate was calculated for 59 patients: 29 % (17/59). Antipsychotic drug naivety and low negative symptom load at baseline correlated highly with belonging to the remission group. Use of amisulpride was more probable to lead to remission than that of aripiprazole, but it was not more probable than the use of olanzapine (in per-protocol analyses). Negative symptoms showed the largest resistance to treatment. The lack of remission for the majority of the participants in this closely monitored antipsychotic drug trial is alarming and could act as a reminder that novel treatment principles are needed, especially targeted towards the negative symptoms in schizophrenia.

Association between cytokines and suicidality in patients with psychosis: A multicentre longitudinal analysis.

Suicide is a common cause of death in all phases of schizophrenia spectrum disorder, particularly in the youngest patients. Clinical measures have demonstrated limited value in suicide prediction, spurring the search for potential biomarkers. The causes of suicidal behaviour are complex, but the immune system seems to be involved as it reflects or even causes mental suffering. We aimed to identify cytokines with associations to suicidality in a sample of patients with symptoms of active psychosis. Patients with schizophrenia spectrum disorder (N = 144) participating in a semi-randomized antipsychotic drug trial (the BeSt InTro study) were assessed with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) at eight visits across 12 months. The Clinical Global Impression for Severity of Suicidality scale (CGI-SS) was used for assessing suicidality. Serum concentrations of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, and IL-10 were measured using immunoassays. A logistic regression model was used to investigate the association between cytokine levels and suicidality. To enhance clinical significance, the CGI-SS scores were dichotomized into two groups before analyses: low (=1) and high (≥2) risk for suicidality. Both uni- and multi-variate analyses revealed an inverse correlation between IL-2 and IL-10 serum levels and suicidality, where lower cytokine concentrations of IL-2 and IL-10 were associated with higher suicidality scores. The results were consistent when adjusted for depression and substance use. These results indicate that inflammatory processes are linked to the risk of suicidality in patients with schizophrenia spectrum disorders.

Unmasking patient diversity: Exploring cognitive and antidepressive effects of electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is an established treatment for depression, but more data on effectiveness and safety in clinical practice is needed. The aim of this register-based study was to investigate short-term effectiveness and cognitive safety after ECT, evaluated by clinicians and patients. Secondary, we investigated predictors for remission and cognitive decline. METHODS: The study included 392 patients from the Regional Register for Neurostimulation Treatment in Western Norway. Depressive symptoms and cognitive function were assessed with Montgomery-Åsberg Depression Rating Scale and Mini-Mental State Examination (clinician-rated) and Beck Depression Inventory and Everyday Memory Questionnaire (patient-rated). Assessments were done prior to ECT-series and a mean of 1.7 days after (range 6 days before and 12 days after) end of ECT-series. Paired samples t-tests were extended by detailed, clinically relevant subgroups. Predictors were examined using logistic regression. RESULTS: Clinician- and patient-rated remission rates were 49.5 and 41.0%, respectively. There was a large reduction in depressive symptoms and a small improvement in cognition after ECT, but we also identified subgroups with non-response of ECT in combination with cognitive decline (4.6% clinician-rated, 15.7% patient-rated). Positive predictors for patient- and clinician-rated remission were increasing age, shorter duration of depressive episode, and psychotic features. Antipsychotic medication at the commencement of treatment and previous ECT-treatment gave higher odds of clinician-rated remission, whereas higher pretreatment subjective depression level was associated with lower odds for patient-rated remission. Clinician-rated cognitive decline was predicted by higher pretreatment MMSE scores, whereas psychotic features, increasing age, and greater pretreatment subjective memory concerns were associated with lower odds for patient-rated cognitive decline. CONCLUSIONS: Our study supports ECT as an effective and safe treatment, although subgroups have a less favorable outcome. ECT should be considered at an early stage for older patients suffering from depression with psychotic features. Providing comprehensive and balanced information from clinicians and patients perspectives on effects and side effects, may assist in a joint consent process.

Cellular adhesion molecules in drug-naïve and previously medicated patients with schizophrenia-spectrum disorders.

BACKGROUND: Endothelial inflammation may be involved in the pathogenesis of schizophrenia, and cellular adhesion molecules (CAMs) on endothelial cells may facilitate leukocyte binding and transendothelial migration of cells and inflammatory factors. The aim of the present study was to assess levels of soluble cellular adhesion molecules, including intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, mucosal addressin cell adhesion molecule (MADCAM), junctional adhesion molecule (JAM-A) and neural cadherin (N-CAD) in patients with schizophrenia compared to healthy controls. METHODS: The study population consists of 138 patients with schizophrenia-spectrum disorder, of whom 54 were drug-naïve, compared to 317 general population controls. The potential confounders age, gender, smoking and body mass index (BMI) were adjusted for in linear regression models. RESULTS: The total patient group showed significantly higher levels of ICAM-1 (p < 0.001) and VCAM-1 (p < 0.001) compared to controls. Previously medicated patients showed higher ICAM-1 levels compared to drug-naïve patients (p = 0.042) and controls (p < 0.001), and elevated VCAM-1 levels compared to controls (p < 0.001). Drug-naive patients had elevated levels of VCAM-1 (p = 0.031) compared to controls. CONCLUSIONS: In our study, patients with schizophrenia - including the drug-naïve - have higher levels of soluble CAMs compared to healthy controls. These findings suggest activation of the endothelial system as in inflammation.

Patients with schizophrenia and bipolar disorder display a similar global gene expression signature in whole blood that reflects elevated proportion of immature neutrophil cells with association to lipid changes.

Schizophrenia (SCZ) and bipolar disorder (BD) share clinical characteristics, genetic susceptibility, and immune alterations. We aimed to identify differential transcriptional patterns in peripheral blood cells of patients with SCZ or BD versus healthy controls (HC). We analyzed microarray-based global gene expression data in whole blood from a cohort of SCZ (N = 329), BD (N = 203) and HC (N = 189). In total, 65 genes were significantly differentially expressed in SCZ and 125 in BD, as compared to HC, with similar ratio of up- and downregulated genes in both disorders. Among the top differentially expressed genes, we found an innate immunity signature that was shared between SCZ and BD, consisting of a cluster of upregulated genes (e.g., OLFM4, ELANE, BPI and MPO) that indicate an increased fraction of immature neutrophils. Several of these genes displayed sex differences in the expression pattern, and post-hoc analysis demonstrated a positive correlation with triglyceride and a negative correlation with HDL cholesterol. We found that many of the downregulated genes in SCZ and BD were associated with smoking. These findings of neutrophil granulocyte-associated transcriptome signatures in both SCZ and BD point at altered innate immunity pathways with association to lipid changes and potential for clinical translation.

Electroconvulsive therapy triggers a reversible decrease in brain N-acetylaspartate.

Introduction: Based on previous research on electroconvulsive therapy (ECT) we have proposed a model where disruption, potentiation, and rewiring of brain networks occur in sequence and serve as the underlying therapeutic mechanism of ECT. This model implies that a temporary disturbance of neuronal networks (disruption) is followed by a trophic effect (potentiation), which enables the rewiring of neuronal circuits to a more euthymic functioning brain. We hypothesized that disruption of neuronal networks could trigger biochemical alterations leading to a temporary decrease in N-acetylaspartate (tNAA, considered a marker of neuronal integrity), while choline (a membrane component), myo-Inositol (mI, astroglia marker), and glutamate/glutamine (Glx, excitatory neurotransmitter) were postulated to increase. Previous magnetic resonance spectroscopy studies, reporting diverse findings, have used two different referencing methods - creatine ratios and tissue corrected values referenced to water - for the quantification of brain metabolites. Changes in creatine during ECT have also been reported, which may confound estimates adopting this as an internal reference. Methods: Using MR spectroscopy, we investigated 31 moderately to severely depressed patients and 19 healthy controls before, during, and after ECT or at similar time points (for controls). We tested whether biochemical alterations in tNAA, choline, mI, and Glx lend support to the disrupt, potentiate, and rewire hypothesis. We used both creatine ratios and water-scaled values for the quantification of brain metabolites to validate the results across referencing methods. Results: Levels of tNAA in the anterior cingulate cortex decreased after an ECT treatment series (average 10.6 sessions) by 6% (p = 0.007, creatine ratio) and 3% (p = 0.02, water referenced) but returned to baseline 6 months after ECT. Compared to after treatment series tNAA levels at 6-month follow-up had increased in both creatine ratio (+6%, p < 0.001) and water referenced data (+7%, p < 0.001). Findings for other brain metabolites varied and could not be validated across referencing methods. Discussion: Our findings suggest that prior research must be interpreted with care, as several referencing and processing methods have been used in the past. Yet, the results for tNAA were robust across quantification methods and concur with relevant parts of the disrupt, potentiate, and rewire model.

Trajectories of response in schizophrenia-spectrum disorders: A one-year prospective cohort study of antipsychotic effectiveness.

BACKGROUND: Antipsychotic drugs remain the mainstay of schizophrenia treatment; however, their effectiveness has been questioned, and it is not possible to predict the response to a specific antipsychotic drug in an individual patient. Thus, it is important to compare the effectiveness of the various antipsychotics and search for possible response predictors. AIM: To investigate the effectiveness of antipsychotic drugs, we examined response trajectories and predictors for belonging to different trajectory groups. METHODS: The Bergen-Stavanger-Innsbruck-Trondheim (BeSt InTro) trial compared the effectiveness of three atypical antipsychotics-amisulpride, aripiprazole, and olanzapine-in a prospective, semirandomized, rater-blind, head-to-head design. Adult participants with a schizophrenia spectrum disorder diagnosis, according to international classification of diseases, Tenth Revision (ICD-10) F20-29, were included. Participants were followed for a period of 12 mo, with assessments at baseline; after one, three and six weeks; and after three, six, nine and 12 mo. A latent class mixed model was fitted to our data. The three-trajectory model based on the Positive and Negative Syndrome Scale (PANSS) total score reduction was found to have adequate fit, and the study drugs, as well as various demographic and clinical parameters, were tested as predictors for belonging to the different trajectory groups. RESULTS: Overall, 144 participants were included, and 41% completed the 12-mo study period. The largest trajectory group, consisting of 74% of participants, showed a PANSS total score reduction of 59% from baseline to 12 mo (Good response group). A trajectory group comprising 13% of participants had their PANSS total score reduced by 82.5% at 12 mo (Strong response group), while the last response trajectory group comprising 13% of the participants had a PANSS total score reduction of 13.6% (Slight response group). The largest part of the total reduction for the Good and Strong response groups occurred at six weeks of treatment, amounting to 45% and 48% reductions from baseline, respectively. The use of amisulpride predicted belonging to the Strong response group, while unemployment, depression, and negative psychotic symptoms at baseline increased the chance of belonging to the Slight response group, indicating a poor response to antipsychotic drug treatment. CONCLUSION: Most of the participants (87%) had a good outcome after one year. Amisulpride users, more often than aripiprazole and olanzapine users, belonged to the response trajectory group with a strong response.

Imminent and Short-Term Risk of Death by Suicide in 7,000 Acutely Admitted Psychiatric Inpatients.

Objective: To prospectively investigate the predictive value of diagnosis, suicidal behavior, and subjectively experienced depressed mood for imminent risk of suicide death.Methods: This prospective study included a representative and diagnostically mixed sample of 7,000 acutely hospitalized psychiatric patients between May 2005 and July 2014 in a Norwegian catchment area of 400,000 inhabitants. Suicide deaths were registered at 1 and 2 weeks and at 1, 6, and 12 months following admission. Survival and hazard functions were estimated, and Cox regression was used to estimate the predictive values of suicidal ideation, suicide attempts, a diagnosis of depressive disorder, and severely depressed mood. Assessments were conducted at admission and included ICD-10 diagnosis, clinical interview in the form of the Health of the Nation Outcome Scales, and qualitative assessments of suicidal ideation and suicide attempts during the past week.Results: During 1-year follow-up, 101 patients (1.4%) died by suicide, of whom almost 70% were men. Only severely depressed mood, including inappropriate self-blame and guilt, predicted suicide within the first week after admission (hazard ratio [HR] = 7.3; 95% confidence interval [CI], 1.4-37.1; P = .01). Suicidal ideation predicted death by suicide at 2 weeks (HR = 3.8; 95% CI, 1.2-12.8; P = .02) and all follow-up time points after, whereas a recent suicide attempt predicted suicide from the 1-month follow-up (HR = 7.3; 95% CI, 2.2-23.7; P < .001) onward.Conclusions: We recommend thoroughly examining severity of depressed mood during assessment of imminent suicide risk.

The association between cytokines and psychomotor speed in a spectrum of psychotic disorders: A longitudinal study.

BACKGROUND: In schizophrenia, impaired psychomotor speed is a common symptom predicting worse functional outcome. Inflammation causes changes in white matter integrity, which may lead to reduced psychomotor speed. Therefore, we wanted to investigate if peripheral inflammation assessed with cytokines affected performance on psychomotor speed in patients with a spectrum of psychotic disorders. METHODS: The current study is a prospective cohort study, including participants from a pragmatic, randomised controlled trial comparing three atypical antipsychotics in patients with a spectrum of psychotic disorders. For the purposes of this sub-study, we analysed drug treatment groups collectively. Psychomotor speed was assessed at baseline, and at weeks 6, 12, 26 and 52 of follow-up, using the neuropsychological tests trail making test (TMT) A and B, and symbol coding. Serum concentration of the following cytokines were measured: interleukin (IL)-ß, IL-2, IL-4, IL-6, IL-10, IL12 p70, IL-17a, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. Blood samples were collected at baseline and after 1, 3, 6, 12, 26, 39 and 52 weeks. We analysed the effect of cytokines levels on psychomotor speed over time in linear mixed effects models. RESULTS: In our linear mixed effects models controlling for possible confounders, IFN-γ had a significant negative effect on TMT-A and symbol coding performance. None of the other tests for psychomotor speed were significantly associated with cytokines. Overall psychomotor speed performance increased significantly across the study period while cytokine levels remained stable. CONCLUSION: Our study indicates a negative association between IFN-γ and psychomotor speed, which might be of importance when understanding the mechanisms behind psychomotor deviations in psychotic disorders.

Sex differences in antipsychotic efficacy and side effects in schizophrenia spectrum disorder: results from the BeSt InTro study.

Current guidelines for patients with schizophrenia spectrum disease do not take sex differences into account, which may result in inappropriate sex-specific treatment. In the BeSt InTro study, a total of 144 patients (93 men and 51 women) with a schizophrenia spectrum diagnosis and ongoing psychosis were included and randomized to amisulpride, aripiprazole, or olanzapine in flexible dose. This trial is registered with ClinicalTrials.gov (NCT01446328). Primary outcomes were sex differences in dose, dose-corrected serum levels, efficacy, and tolerability. Dosing was higher for men than for women in the aripiprazole group (p = 0.025) and, at trend level, in the olanzapine group (p = 0.056). Dose-corrected serum levels were 71.9% higher in women than in men for amisulpride (p = 0.019) and 55.8% higher in women than in men for aripiprazole (p = 0.049). In the amisulpride group, men had a faster decrease in psychotic symptoms than women (p = 0.003). Moreover, amisulpride was more effective than the other medications in men but not in women. Prolactin levels were higher in women than in men, especially for amisulpride (p < 0.001). Also, women had higher BMI increase on amisulpride compared to the two other antipsychotics (p < 0.001). We conclude that clinicians should be aware of the risks of overdosing in women, especially for amisulpride and aripiprazole. Amisulpride is highly effective in men, but in women, amisulpride showed more severe side effects and may thus not be the drug of first choice. Our study shows that sex differences should be taken into account in future studies on antipsychotics. Future research is warranted to evaluate these preliminary results.

Operating room ventilation-Validation of reported data on 108 067 primary total hip arthroplasties in the Norwegian Arthroplasty Register.

RATIONALE, AIMS, AND OBJECTIVES: The true effect of laminar airflow (LAF) systems on postoperative infection is disputed, partly due to uncertainty regarding the validity of ventilation data in register studies. The aim of this study was to validate the information on operating room (OR) ventilation reported by the orthopaedic surgeons to the Norwegian Arthroplasty Register (NAR) after primary total hip arthroplasty (THA). METHOD: Forty of the 62 public orthopaedic units performing primary THA in Norway during the period 1987-2015 were included. The hospitals' current and previous ventilation systems were evaluated in cooperation with the hospitals head engineer. We identified the type of ventilation system reported to the NAR and compared the information with the factual ventilation in the specific ORs at the time of primary THA. RESULTS: A total of 108 067 primary THAs were eligible for assessment. None of the hospitals performed THA in true "greenhouse" (GH) ventilation. Fifty-seven percent of the primary THAs were performed in ORs with LAF and 43% in ORs with conventional, turbulent ventilation (CV). Comparing the reported data with the validated data, LAF was reported with a sensitivity of 86%, specificity of 89%, and positive predictive value (PPV) of 92%, with an accuracy of 88%. CV was reported with a sensitivity of 89%, specificity of 87%, and PPV of 84%, with an accuracy of 88%. The total, mean misreporting rate was 12%. CONCLUSIONS: Surgeons were not fully aware of what kind of ventilation system they operated in. This study indicates that conclusions based on ventilation data reported on THA in the NAR should not be interpreted without considering the inaccuracy of the data.

Personalized estimation of one-year mortality risk after elective hip or knee arthroplasty for osteoarthritis.

AIMS: To develop and validate patient-centred algorithms that estimate individual risk of death over the first year after elective joint arthroplasty surgery for osteoarthritis. METHODS: A total of 763,213 hip and knee joint arthroplasty episodes recorded in the National Joint Registry for England and Wales (NJR) and 105,407 episodes from the Norwegian Arthroplasty Register were used to model individual mortality risk over the first year after surgery using flexible parametric survival regression. RESULTS: The one-year mortality rates in the NJR were 10.8 and 8.9 per 1,000 patient-years after hip and knee arthroplasty, respectively. The Norwegian mortality rates were 9.1 and 6.0 per 1,000 patient-years, respectively. The strongest predictors of death in the final models were age, sex, body mass index, and American Society of Anesthesiologists grade. Exposure variables related to the intervention, with the exception of knee arthroplasty type, did not add discrimination over patient factors alone. Discrimination was good in both cohorts, with c-indices above 0.76 for the hip and above 0.70 for the knee. Time-dependent Brier scores indicated appropriate estimation of the mortality rate (≤ 0.01, all models). CONCLUSION: Simple demographic and clinical information may be used to calculate an individualized estimation for one-year mortality risk after hip or knee arthroplasty (https://jointcalc.shef.ac.uk). These models may be used to provide patients with an estimate of the risk of mortality after joint arthroplasty. Cite this article: Bone Joint Res 2020;9(11):808-820.

Amisulpride, aripiprazole, and olanzapine in patients with schizophrenia-spectrum disorders (BeSt InTro): a pragmatic, rater-blind, semi-randomised trial.

BACKGROUND: Amisulpride, aripiprazole, and olanzapine are first-line atypical antipsychotics that have not previously been compared head-to-head in a pragmatic trial. We aimed to compare the efficacy and safety of these agents in a controlled trial. METHODS: This pragmatic, rater-blind, randomised controlled trial was done in three academic centres of psychiatry in Norway, and one in Austria. Eligible patients were aged 18 years or older, met ICD-10 criteria for schizophrenia-spectrum disorders (F20-29), and had symptoms of active psychosis. Eligible patients were randomly assigned to receive oral amisulpride, aripiprazole, or olanzapine. Treatment allocation was open to patients and staff, and starting dose, treatment changes, and adjustments were left to the discretion of the treating physician. Computer-generated randomisation lists for each study centre were prepared by independent statisticians. Patients were followed up for 52 weeks after random assignment, during which assessments were done 8 times by researchers masked to treatment. The primary outcome was reduction of the Positive And Negative Syndrome Scale (PANSS) total score at 52 weeks, and primary analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01446328. FINDINGS: Between Oct 20, 2011, and Dec 30, 2016, we assessed 359 patients for eligibility. 215 patients were excluded (107 did not meet inclusion criteria, 82 declined to participate, 26 other reasons). 144 patients (mean baseline PANSS total estimated score 78·4 [SD 1·4]) were randomly assigned 1:1:1 to receive amisulpride (44 patients), aripiprazole (48 patients) or olanzapine (52 patients). After 52 weeks, the patients allocated to amisulpride had a PANSS total score reduction of 32·7 points (SD 3·1) compared with 21·9 points reduction with aripiprazole (SD 3·9, p=0·027) and 23·3 points with olanzapine (2·9, p=0·025). We observed weight gain and increases of serum lipids and prolactin in all groups. 26 serious adverse events (SAEs) among 20 patients were registered (four [9%] of 44 patients allocated to amisulpride, ten [21%] of 48 patients allocated to aripiprazole, and six [12%] of 52 patients allocated to olanzapine), with no statistically significant differences between the study drugs. 17 (65%) of the 26 SAEs occurred during the use of the study drug, with readmission or protracted hospital admission accounting for 13 SAEs. One death by suicide, one unspecified death, and one life-threatening accident occurred during follow-up, after cessation of treatment. INTERPRETATION: Amisulpride was more efficacious than aripiprazole or olanzapine for reducing the PANSS total scores in adults with schizophrenia-spectrum disorders. Side-effect differences among the groups were generally small. This study supports the notion that clinically relevant efficacy differences exist between antipsychotic drugs. Future research should aim to compare first-line antipsychotics directly in pragmatic clinical trials that reflect everyday clinical practice. FUNDING: The Research Council of Norway, the Western Norway Regional Health Trust, and participating hospitals and universities.

Homogeneity in prediction of survival probabilities for subcategories of hipprosthesis data: the Nordic Arthroplasty Register Association, 2000-2013.

Introduction: The four countries in the Nordic Arthroplasty Register Association (NARA) share geographic proximity, culture, and ethnicity. Pooling data from different sources in order to obtain higher precision and accuracy of survival-probability estimates is appealing. Nevertheless, survival probabilities of hip replacements vary between the countries. As such, risk prediction for individual patients within countries may be problematic if data are merged. In this study, our primary question was to address when data merging for estimating prosthesis survival in subcategories of patients is advantageous for survival prediction of individual patients, and at what sample sizes this may be advised. Methods: Patients undergoing total hip replacements for osteoarthritis between January 1, 2000 and December 31, 2013 in the four Nordic countries were studied. A total of 184,507 patients were stratified into 360 patient subcategories based on country, age-group, sex, fixation, head size, and articulation. For each patient category, we determined the sample size needed from a single country to obtain a more accurate and precise estimate of prosthesis-survival probability at 5 and 10 years compared to an estimate using data from all countries. The comparison was done using mean-square error. Results: We found large variations in the sample size needed, ranging from 40 to 2,060 hips, before an estimate from a single Nordic country was more accurate and precise than estimates based on the NARA data. Conclusion: Using pooled survival-probability estimates for individual risk prediction may be imprecise if there is heterogeneity in the pooled data sources. By applying mean-square error, we demonstrate that for small sample sizes, applying the larger NARA database may provide a more accurate and precise estimate; however, this effect is not consistent and varies with the characteristics of the subcategory.