Lifetime and point prevalence of psychotic symptoms in adults with bipolar disorders: a systematic review and meta-analysis.

Psychotic symptoms, that we defined as delusions or hallucinations, are common in bipolar disorders (BD). This systematic review and meta-analysis aims to synthesise the literature on both lifetime and point prevalence rates of psychotic symptoms across different BD subtypes, including both BD type I (BDI) and BD type II (BDII). We performed a systematic search of Medline, PsycINFO, Embase and Cochrane Library until 5 August 2021. Fifty-four studies (N = 23 461) of adults with BD met the predefined inclusion criteria for evaluating lifetime prevalence, and 24 studies (N = 6480) for evaluating point prevalence. Quality assessment and assessment of publication bias were performed. Prevalence rates were calculated using random effects meta-analysis, here expressed as percentages with a 95% confidence interval (CI). In studies of at least moderate quality, the pooled lifetime prevalence of psychotic symptoms in BDI was 63% (95% CI 57.5-68) and 22% (95% CI 14-33) in BDII. For BDI inpatients, the pooled lifetime prevalence was 71% (95% CI 61-79). There were no studies of community samples or inpatient BDII. The pooled point prevalence of psychotic symptoms in BDI was 54% (95 CI 41-67). The point prevalence was 57% (95% CI 47-66) in manic episodes and 13% (95% CI 7-23.5) in depressive episodes. There were not enough studies in BDII, BDI depression, mixed episodes and outpatient BDI. The pooled prevalence of psychotic symptoms in BDI may be higher than previously reported. More studies are needed for depressive and mixed episodes and community samples.Prospero registration number: CRD 42017052706.

Polypharmacy, functional outcome and treatment effect of intravenous alteplase for acute ischaemic stroke.

BACKGROUND AND PURPOSE: Polypharmacy is an important challenge in clinical practice. Our aim was to determine the effect of polypharmacy on functional outcome and treatment effect of alteplase in acute ischaemic stroke. METHODS: This was a post hoc analysis of the randomized, placebo-controlled WAKE-UP trial of magnetic resonance imaging guided intravenous alteplase in unknown onset stroke. Polypharmacy was defined as an intake of five or more medications at baseline. Comorbidities were assessed by the Charlson Comorbidity Index (CCI). The primary efficacy variable was favourable outcome defined by a score of 0-1 on the modified Rankin Scale at 90 days. Logistic regression analysis was used to test for an association of polypharmacy with functional outcome, and for interaction of polypharmacy and the effect of thrombolysis. RESULTS: Polypharmacy was present in 133/503 (26%) patients. Patients with polypharmacy were older (mean age 70 vs. 64 years; p < 0.0001) and had a higher score on the National Institutes of Health Stroke Scale at baseline (median 7 vs. 5; p = 0.0007). A comorbidity load defined by a CCI score ≥ 2 was more frequent in patients with polypharmacy (48% vs. 8%; p < 0.001). Polypharmacy was associated with lower odds of favourable outcome (adjusted odds ratio 0.50, 95% confidence interval 0.30-0.85; p = 0.0099), whilst the CCI score was not. Treatment with alteplase was associated with higher odds of favourable outcome in both groups, with no heterogeneity of treatment effect (test for interaction of treatment and polypharmacy, p = 0.29). CONCLUSION: In stroke patients, polypharmacy is associated with worse functional outcome after intravenous thrombolysis independent of comorbidities. However, polypharmacy does not interact with the beneficial effect of alteplase.

Acute endovascular reperfusion treatment in patients with ischaemic stroke and large-vessel occlusion (Denmark 2011-2017).

BACKGROUND AND PURPOSE: Acute endovascular reperfusion treatment (aERT) of stroke patients with large-vessel occlusions is efficacious and safe according to several clinical trials. Data on outcome and safety of aERT in daily clinical routine are warranted and, in this study, we present national data from Denmark during 2011-2017. METHODS: National data for Denmark from 2011 to 2017 on all aERT procedures in patients with acute ischaemic stroke and computed tomography angiography/magnetic resonance angiography-verified large-vessel occlusion were derived from the Danish Stroke Registry, a national clinical quality registry to which reporting is mandatory for all hospitals treating stroke patients. Outcome (modified Rankin Scale score) after 3 months, including time of death, was assessed prospectively based on clinical examination or the Danish Civil Registration System. RESULTS: During the 7 years of observation, a total of 1720 patients were treated with aERT. The annual number of procedures increased from 128 in 2011 to 409 in 2017. The median age was 70 years, 58% were males and median National Institutes of Health Stroke Scale score at baseline was 16. Median time from symptom onset to groin puncture was 238 min with a decreasing trend during the years. Successful recanalization was reported in 1306 (76%) patients. At 3-month follow-up, an modified Rankin Scale score of 0-2 was reported in 46% of patients, whereas 14% of patients had died. CONCLUSION: Routine data on aERT in acute ischaemic stroke in Denmark from 2011 to 2017 suggest that the procedure is safe and efficacious.

The influence of blood pressure management on neurological outcome in endovascular therapy for acute ischaemic stroke.

BACKGROUND: Observational studies have suggested that low blood pressure and blood pressure variability may partially explain adverse neurological outcome after endovascular therapy with general anaesthesia (GA) for acute ischaemic stroke. The aim of this study was to further examine whether blood pressure related parameters during endovascular therapy are associated with neurological outcome. METHODS: The GOLIATH trial randomised 128 patients to either GA or conscious sedation for endovascular therapy in acute ischaemic stroke. The primary outcome was 90 day modified Rankin Score. The haemodynamic protocol aimed at keeping the systolic blood pressure >140 mm Hg and mean blood pressure >70 mm Hg during the procedure. Blood pressure related parameters of interest included 20% reduction in mean blood pressure; mean blood pressure <70 mm Hg, <80 mm Hg, and <90 mm Hg, respectively; time with systolic blood pressure <140 mm Hg; procedural minimum and maximum mean and systolic blood pressure; mean blood pressure at the time of groin puncture; postreperfusion mean blood pressure; blood pressure variability; and use of vasopressors. Sensitivity analyses were performed in the subgroup of reperfused patients. RESULTS: Procedural average mean and systolic blood pressures were higher in the conscious sedation group (P<0.001). The number of patients with mean blood pressure <70-90 mm Hg and systolic blood pressure <140 mm Hg, blood pressure variability, and use of vasopressors were all higher in the GA group (P<0.001). There was no statistically significant association between any of the examined blood pressure related parameters and the modified Rankin Score in the overall patient population, and in the subgroup of patients with full reperfusion. CONCLUSION: We found no statistically significant association between blood pressure related parameters during endovascular therapy and neurological outcome. CLINICAL TRIAL REGISTRATION: NCT 02317237.

High prevalence and increasing incidence of multiple sclerosis in the Norwegian county of Buskerud.

OBJECTIVES: The objective was to investigate the incidence of multiple sclerosis (MS) as well as estimate the prevalence as of 1 January 2014 in the southeastern Norwegian county of Buskerud. MATERIALS AND METHODS: All patients with MS living in Buskerud county in Norway between 01 January 2003 and 01 January 2014 were identified. Point prevalence of MS was identified on 01 January 2014. RESULTS: We found a prevalence of 213.8 (95% CI 196.4-231.1) per 100 000. The sex ratio was 2.2:1 with a female prevalence of 293.4 (95% CI 264.7-322.2) per 100 000 and a male prevalence of 134.7 (95% CI 115.3-154.2) per 100 000. About 82% of our MS population had a confirmed relapsing-remitting MS at disease onset, while 16.8% had primary progressive MS. The mean annual incidence between 2003 and 2013 was 11.8 (95% CI 10.6-13.1) per 100 000. CONCLUSION: This study shows a high incidence of MS in Buskerud county in southeastern Norway, and the incidence may still be on the rise. We found a relatively high prevalence of MS in our population, although this does correspond with the recently published national data. Further studies investigating both changes in incidence and possible factors causing the increasing incidence are warranted.

Ischemic stroke subtype is associated with outcome in thrombolyzed patients.

OBJECTIVES: The impact of ischemic stroke subtype on clinical outcome in patients treated with intravenous tissue-type plasminogen activator (IV-tPA) is sparsely examined. We studied the association between stroke subtype and clinical outcome in magnetic resonance imaging (MRI)-evaluated patients treated with IV-tPA. MATERIAL AND METHODS: We conducted a single-center retrospective analysis of MRI-selected stroke patients treated with IV-tPA between 2004 and 2010. The Trial of ORG 10172 in Acute Stroke Treatment criteria were used to establish the stroke subtype by 3 months. The outcomes of interest were a 3-month modified Rankin Scale score of 0-1 (favorable outcome), and early neurological improvement defined as complete remission of neurological deficit or improvement of ≥4 on the National Institute of Health Stroke Scale at 24 h. The outcomes among stroke subtypes were compared with multivariable logistic regression. RESULTS: Among 557 patients, 202 (36%) had large vessel disease (LVD), 153 (27%) cardioembolic stroke (CE), 109 (20%) small vessel disease, and 93 (17%) were of other or undetermined etiology. Early neurological improvement was present in 313 (56.4%) patients, and 361 (64.8%) patients achieved a favorable outcome. Early neurological improvement and favorable outcome were more likely in CE patients compared with LVD patients (odds ratio (OR), 2.1 (95% confidence interval, 1.4-3.3), and 2.0 (95% confidence interval, 1.2-3.3), respectively). CONCLUSIONS: Cardioembolic stroke patients were more likely to achieve early neurological improvement and favorable outcome compared with LVD stroke following MRI-based IV-tPA treatment. This finding may reflect a difference in the effect of IV-tPA among stroke subtypes.

Anaesthesia practices for endovascular therapy of acute ischaemic stroke: a Nordic survey.

BACKGROUND: The optimal method of anaesthesia for endovascular therapy (EVT) in acute ischaemic stroke (AIS) has not been identified. Nordic departments of anaesthesiology may handle EVT cases for AIS differently. The aim of this survey was to describe the current practice patterns of Nordic anaesthesia departments in anaesthetic management of EVT in AIS. METHODS: A survey consisting of 13 questions was sent to one qualified individual at all Nordic departments of anaesthesiology who manage anaesthesia for EVT interventions. The individual completed the questionnaire on behalf of their department. RESULTS: Response rate was 100%. The majority of departments (84%) managed all EVT cases at their respective centres. Most departments have institutional guidelines on anaesthetic management (84%) including blood pressure management (63%) and were able to provide a 24-h immediate response to an EVT request (63%). Conscious sedation was favoured by 68% of the departments using a variety of sedation protocols. Propofol and remifentanil was preferred for GA (58%). Emergent conversion to GA due to uncontrolled patient movements or loss of airway was experienced by 82% and 35% of the departments, respectively. Majority of the departments (89%) responded that non-specialist anaesthetists occasionally handle EVT cases. CONCLUSIONS: This survey indicates that the majority of Nordic anaesthesia departments who manage anaesthesia for EVT are able to provide immediate 24-h response to an EVT request. Most of these departments have institutional guidelines for EVT anaesthesia and haemodynamic management. Conscious sedation appears to be the preferred method of anaesthetic care.

Modelling difficulties in abstract thinking in psychosis: the importance of socio-developmental background.

INTRODUCTION: Abstract thinking is important in modern understanding of neurocognitive abilities, and a symptom of thought disorder in psychosis. In patients with psychosis, we assessed if socio-developmental background influences abstract thinking, and the association with executive functioning and clinical psychosis symptoms. METHODS: Participants (n = 174) had a diagnosis of psychotic or bipolar disorder, were 17-65 years, intelligence quotient (IQ) > 70, fluent in a Scandinavian language, and their full primary education in Norway. Immigrants (N = 58) were matched (1:2) with participants without a history of migration (N = 116). All participants completed a neurocognitive and clinical assessment. Socio-developmental background was operationalised as human developmental index (HDI) of country of birth, at year of birth. Structural equation modelling was used to assess the model with best fit. RESULTS: The model with best fit, χ2 = 96.591, df = 33, p < .001, confirmed a significant indirect effect of HDI scores on abstract thinking through executive functioning, but not through clinical psychosis symptoms. CONCLUSIONS: This study found that socio-developmental background influences abstract thinking in psychosis by indirect effect through executive functioning. We should take into account socio-developmental background in the interpretation of neurocognitive performance in patients with psychosis, and prioritise cognitive remediation in treatment of immigrant patients.

No progressive brain changes during a 1-year follow-up of patients with first-episode psychosis.

BACKGROUND: First-episode psychosis (FEP) patients show structural brain abnormalities. Whether the changes are progressive or not remain under debate, and the results from longitudinal magnetic resonance imaging (MRI) studies are mixed. We investigated if FEP patients showed a different pattern of regional brain structural change over a 1-year period compared with healthy controls, and if putative changes correlated with clinical characteristics and outcome. METHOD: MRIs of 79 FEP patients [SCID-I-verified diagnoses: schizophrenia, psychotic bipolar disorder, or other psychoses, mean age 27.6 (s.d. = 7.7) years, 66% male] and 82 healthy controls [age 29.3 (s.d. = 7.2) years, 66% male] were acquired from the same 1.5 T scanner at baseline and 1-year follow-up as part of the Thematically Organized Psychosis (TOP) study, Oslo, Norway. Scans were automatically processed with the longitudinal stream in FreeSurfer that creates an unbiased within-subject template image. General linear models were used to analyse longitudinal change in a wide range of subcortical volumes and detailed thickness and surface area estimates across the entire cortex, and associations with clinical characteristics. RESULTS: FEP patients and controls did not differ significantly in annual percentage change in cortical thickness or area in any cortical region, or in any of the subcortical structures after adjustment for multiple comparisons. Within the FEP group, duration of untreated psychosis, age at illness onset, antipsychotic medication use and remission at follow-up were not related to longitudinal brain change. CONCLUSIONS: We found no significant longitudinal brain changes over a 1-year period in FEP patients. Our results do not support early progressive brain changes in psychotic disorders.

Pain trajectories and neuropathic pain symptoms following lung cancer surgery: A prospective cohort study.

BACKGROUND: Persistent postsurgical pain (PPSP) after lung cancer surgery is common and current definitions are based on evaluations at a single time point after surgery. Pain intensity and symptoms may however fluctuate and change over time, and be impacted by multiple and shifting factors. Studies of postoperative recovery patterns and transition from acute to chronic pain are needed for further investigation of preventive measures and treatments to modify unfavourable recovery paths. METHODS: In this explorative study, 85 patients undergoing surgery due to either presumptive or confirmed lung cancer reported pain intensities bi-monthly for 12 months. Pain trajectories during recovery were investigated, using group-based trajectory modelling. Associations with possible risk factors for PPSP, including clinical variables and anxiety and depression score (HADS), were also explored. RESULTS: A trajectory model containing three 12-month pain recovery groups was computed. One group without PPSP fully recovered (50%) within two to three months. Another group with mild-intensity PPSP followed a protracted recovery trajectory (37%), while incomplete recovery was observed in the last group (13%). Acute postoperative pain and younger age were associated with a less favourable recovery trajectory. More neuropathic pain symptoms were observed in patients with incomplete recovery. CONCLUSIONS: Three clinically relevant recovery trajectories were identified, based on comprehensive pain tracking. Higher acute postoperative pain intensity was associated with an unfavourable pain recovery trajectory. SIGNIFICANCE STATEMENT: Understanding the transition from acute to chronic postoperative pain and identifying preoperative risk factors is essential for the development of targeted treatments and the implementation of preventive measures. This study (1) identified distinct recovery trajectories based on frequent pain assessment follow-ups for 12 months after surgery and (2) evaluated risk factors for unfavourable postoperative pain recovery paths. Findings suggest that early higher postoperative pain intensity is associated with an unfavourable long-term recovery path.

Predictors of medication adherence in patients with schizophrenia and bipolar disorder.

OBJECTIVE: To investigate potential risk factors for medication non-adherence in patients with schizophrenia and bipolar disorder. METHOD: A total of 255 patients underwent clinical assessments, neurocognitive testing and blood sampling. The patients were divided into groups of 'No', 'Partial' or 'Full' adherence. Relationships to different risk factors were analyzed. RESULTS: In schizophrenia, use of illicit substances, alcohol and poor insight were related to worse adherence. Schizophrenia patients with No adherence did better on tests of executive functioning, verbal learning and memory and had higher IQ than patients with better adherence. There were higher levels of autonomic side effects in the non-adherence group, but body mass index was lower in the Partial adherence group than in the Full adherence group. In the bipolar disorder patients, there was an association between the use of illicit substances and alcohol and poor adherence. We found no relationship between adherence behavior and neurocognition in the bipolar disorder group. CONCLUSION: Substance use is an important risk factor for non-adherence in patients with schizophrenia and bipolar disorder. Poor insight is also a risk factor in schizophrenia. The results suggest that cognitive dysfunction is not a risk factor for non-adherence in these diagnostic groups.

Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis.

OBJECTIVE: An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and previous meta-analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view. METHOD: Individual patient and control data were obtained from original authors for 11 measures from four common neuropsychological tests: California or Rey Verbal Learning Task (VLT), Trail Making Test (TMT), Digit Span and/or Wisconsin Card Sorting Task. RESULTS: Impairments were found for all 11 test-measures in the bipolar group after controlling for age, IQ and gender (Ps ≤ 0.001, E.S. = 0.26-0.63). Residual mood symptoms confound this result but cannot account for the effect sizes found. Impairments also seem unrelated to drug treatment. Some test-measures were weakly correlated with illness severity measures suggesting that some impairments may track illness progression. CONCLUSION: This reanalysis supports VLT, Digit Span and TMT as robust measures of cognitive impairments in bipolar disorder patients. The heterogeneity of some test results explains previous differences in meta-analyses. Better controlling for confounds suggests deficits may be smaller than previously reported but should be tracked longitudinally across illness progression and treatment.

Specialized Outpatient Clinic vs Stroke Unit for TIA and Minor Stroke: A Cohort Study.

Objective: To evaluate the effects of an outpatient clinic set-up for minor stroke/TIA using subsequent admission of patients at 'high risk' of re-stroke.Methods: A cohort study of all patients with suspected minor stroke/TIA seen in an outpatient clinic at Aarhus University Hospital, Denmark, between September 2013 and August 2014. Stroke patients were compared to historic (same hospital) and contemporary (another comparable hospital) matched, hospitalized controls on the non-prioritized outcomes: Length-of-stay, re-admissions, care quality (10 process-performance measures) and mortality. TIA patients were compared to contemporary matched, hospitalized controls.Following complete diagnostic work-up, patients with stroke/TIA were classified into 'low'/high risk' of re-stroke ≤7 days. RESULTS: We analyzed 1,076 consecutive patients of whom 253 (23.5%) were subsequently admitted to the stroke ward. Stroke/TIA was diagnosed in 215/171 patients, respectively. Fifty-six percent (121/215) of the stroke patients were subsequently admitted to the stroke ward. Comparison with the historic stroke cohort (n=191) showed a shorter acute hospital stay for the strokes (median 1 vs 3 days); adjusted length-of-stay ratio 0.49 (95% CI 0.33-0.71). Furthermore, 30-day readmission rate was 3.2% vs 11.6%; adjusted hazard ratio 0.23 (0.09-0.59); and care quality was higher with a risk ratio of 1.30 (1.15-1.47). The comparison of stroke and TIAs to contemporary controls showed similar results. Only one patient in the 'low risk' category and not admitted experienced stroke within 7 days (0.6%). CONCLUSIONS: An outpatient clinic set-up for patients with minor stroke/TIA yields shorter acute hospital stay, lower re-admissions rates, and better quality than hospitalization in stroke units. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that a neurovascular specialist driven outpatient clinic for minor stroke/TIA patients with the ability of subsequent admission is safe and yields shorter acute hospital stay, lower re-admissions rates, and better quality than hospitalization in stroke units.

Isolation of a complementary DNA clone encoding a precursor to human eosinophil major basic protein.

A 14-kD protein was purified from human PMNs and its NH2-terminal sequence was determined. Comparison of a portion of the NH2-terminal sequence of this protein to the recently reported NH2-terminal sequence of eosinophil major basic protein (MBP) showed them to be identical. To aid further characterization of the structural and functional properties of this molecule, we isolated from an HL-60 cDNA library a single class of cDNA clones whose sequence matched exactly the NH2-terminal amino acid sequence of the 14-kD polypeptide. Northern analysis of HL-60 cells suggests that MBP is constitutively expressed in HL-60 cells and is highly transcribed from a single copy gene. The sequence of the full-length cDNA clones predicts that MBP is synthesized as a 23-kD precursor form (pro-MBP) which is subsequently cleaved to release the mature 14-kD MBP. The putative pro-MBP has a predicted pI of 6.0, but both the charged and the hydrophobic residues are asymmetrically distributed, creating a bipolar molecule. The NH2-terminal half has a predicted pI of 3.7 and is hydrophilic, while the COOH-terminal half (corresponding to mature MBP) has a predicted pI of 11.1 and is hydrophobic.

Opposite relationships between cannabis use and neurocognitive functioning in bipolar disorder and schizophrenia.

BACKGROUND: Cannabis use is associated with altered neurocognitive functioning in severe mental disorders, but data are still inconclusive and there are no studies of bipolar disorder. The aim of this study was to investigate the association between cannabis use and neurocognition in bipolar disorder compared with schizophrenia in a naturalistic setting. METHOD: A total of 133 patients with bipolar disorder and 140 patients with schizophrenia underwent neuropsychological assessments and clinical characterization including measures of substance use. Relationships between cannabis users and neurocognitive function were explored in the two diagnostic groups. Possible interactions between diagnosis and cannabis use were investigated, and findings were controlled for possible confounders. RESULTS: In bipolar disorder subjects, cannabis use was associated with better neurocognitive function, but the opposite was the case for the schizophrenia subjects. There was a statistically significant interaction effect of diagnosis and cannabis use on focused attention (p=0.019), executive functioning (verbal fluency--set shifting) (p=0.009), logical memory-learning (p=0.007) and on logical memory-recall (p=0.004). These differences in neurocognitive function could not be explained by putative confounders. CONCLUSIONS: The findings suggest that cannabis use may be related to improved neurocognition in bipolar disorder and compromised neurocognition in schizophrenia. The results need to be replicated in independent samples, and may suggest different underlying disease mechanisms in the two disorders.

Patients Requiring Conversion to General Anesthesia during Endovascular Therapy Have Worse Outcomes: A Post Hoc Analysis of Data from the SAGA Collaboration.

BACKGROUND AND PURPOSE: Endovascular therapy for acute ischemic stroke is often performed with the patient under conscious sedation. Emergent conversion from conscious sedation to general anesthesia is sometimes necessary. The aim of this study was to assess the functional outcome in converted patients compared with patients who remained in conscious sedation and to identify predictors associated with the risk of conversion. MATERIALS AND METHODS: Data from 368 patients, included in 3 trials randomizing between conscious sedation and general anesthesia before endovascular therapy (SIESTA, ANSTROKE, and GOLIATH) constituted the study cohort. Twenty-one (11%) of 185 patients randomized to conscious sedation were emergently converted to general anesthesia. RESULTS: Absence of hyperlipidemia seemed to be the strongest predictor of conversion to general anesthesia, albeit a weak predictor (area under curve = 0.62). Sex, hypertension, diabetes, smoking status, atrial fibrillation, blood pressure, size of the infarct, and level and side of the occlusion were not significantly associated with conversion to general anesthesia. Neither age (mean age, 71.3 ± 13.8 years for conscious sedation versus 71.6 ± 12.3 years for converters, P = .58) nor severity of stroke (mean NIHSS score, 17 ± 4 versus 18 ± 4, respectively, P = .27) were significantly different between converters and those who tolerated conscious sedation. The converters had significantly worse outcome with a common odds ratio of 2.67 (P = .015) for a shift toward a higher mRS score compared with the patients remaining in the conscious sedation group. CONCLUSIONS: Patients undergoing conversion had significantly worse outcome compared with patients remaining in conscious sedation. No factor was identified that predicted conversion from conscious sedation to general anesthesia.

Effects of high-intensity exercise training on physical fitness, quality of life and treatment outcomes after oesophagectomy for cancer of the gastro-oesophageal junction: PRESET pilot study.

BACKGROUND: Treatment for cancer of the gastro-oesophageal junction (GOJ) can result in considerable and persistent impairment of physical fitness and health-related quality of life (HRQoL). This controlled follow-up study investigated the feasibility and safety of postoperative exercise training. METHODS: Patients with stage I-III GOJ cancer were allocated to 12 weeks of postoperative concurrent aerobic and resistance training (exercise group) or usual care (control group). Changes in cardiorespiratory fitness, muscle strength and HRQoL were evaluated. Adherence to adjuvant chemotherapy, hospitalizations and 1-year overall survival were recorded to assess safety. RESULTS: Some 49 patients were studied. The exercise group attended a mean of 69 per cent of all prescribed sessions. After exercise, muscle strength and cardiorespiratory fitness were increased and returned to pretreatment levels. At 1-year follow-up, the exercise group had improved HRQoL (+13·5 points, 95 per cent c.i. 2·2 to 24·9), with no change in the control group (+3·7 points, -5·9 to 13·4), but there was no difference between the groups at this time point (+9·8 points, -5·1 to 24·8). Exercise was safe, with no differences in patients receiving adjuvant chemotherapy (14 of 16 versus 16 of 19; relative risk (RR) 1·04, 95 per cent c.i. 0·74 to 1·44), relative dose intensity of adjuvant chemotherapy (mean 57 versus 63 per cent; P = 0·479), hospitalization (7 of 19 versus 6 of 23; RR 1·41, 0·57 to 3·49) or 1-year overall survival (80 versus 79 per cent; P = 0·839) for exercise and usual care respectively. CONCLUSION: Exercise in the postoperative period is safe and may have the potential to improve physical fitness in patients with GOJ cancer. No differences in prognostic endpoints or HRQoL were observed. Registration number: NCT02722785 ( https://www.clinicaltrials.gov).

ANTECEDENTES: El tratamiento del cáncer de la unión gastroesofágica (gastroesophageal junction, GEJ) puede determinar un deterioro considerable y persistente de la condición física y de la calidad relacionada con la salud (health-related quality of life, HRQoL). El objetivo de este estudio controlado de seguimiento fue investigar la factibilidad y seguridad del entrenamiento físico postoperatorio. MÉTODOS: Pacientes con cáncer de GEJ en estadio I-III fueron asignados a 12 semanas de entrenamiento postoperatorio simultáneo aeróbico y de resistencia o a cuidados médicos habituales. Se evaluaron los cambios en el estado cardiorrespiratoria, fuerza muscular y HRQoL. Se recogieron datos de la adherencia a la quimioterapia adyuvante, hospitalizaciones y supervivencia global a 1 año para evaluar la seguridad. RESULTADOS: Se estudiaron un total de 49 pacientes. El grupo con ejercicio asistió al 69% de todas las sesiones planificadas. Después del ejercicio, la fuerza muscular y el estado cardiorrespiratorio aumentaron y volvieron a los niveles previos al tratamiento. Si bien al año de seguimiento, el grupo con ejercicio presentó una mejoría de la HRQoL (+13,5 puntos (i.c. del 95% 2,2 a 24,9)), sin cambios en el grupo con atención médica habitual (+3,7 puntos (i.c. del 95% −5,9 a 13,4)), no hubo diferencias entre los grupos en ese momento (+9,8 puntos (i.c. del 95% −5,1 a 24,8)). El ejercicio fue seguro, sin diferencias entre el ejercicio o la atención médica habitual en pacientes que recibían quimioterapia adyuvante 87,5% versus 84,2% (RR 1,04 (i.c. del 95% 0,74 a 1,44)), intensidad relativa de la dosis de quimioterapia adyuvante 56,8% versus 63,3% (P = 0,479), hospitalizaciones 36,8% versus 26,1% (RR 1,41 (i.c. del 95% 0,57 a 3,49)) o supervivencia global a 1 año 80,0% versus 79,3% (P = 0,839). CONCLUSIÓN: El ejercicio en el periodo postoperatorio es seguro y puede tener potencial para mejorar la condición física en pacientes con cáncer de GEJ. No se observaron diferencias en los resultados pronósticos o en la HRQoL.

Detection of antibodies to herpes simplex virus with a continuous cell line expressing cloned glycoprotein D.

The gene for glycoprotein D of herpes simplex virus type 1 (HSV-1) was expressed in stable mammalian cell lines. Glycoprotein D produced in these cells has a number of antigenic determinants in common with the native glycoprotein. Cell lines expressing glycoprotein D were used in an enzyme-linked immunosorbent assay to detect human antibodies to glycoprotein D. This strategy should prove useful in determining the extent to which the immune response to HSV-1 is directed toward glycoprotein D.

Safety and feasibility of preoperative exercise training during neoadjuvant treatment before surgery for adenocarcinoma of the gastro-oesophageal junction.

Background: Neoadjuvant chemotherapy or chemoradiotherapy is used widely before tumour resection in cancer of the gastro-oesophageal junction (GOJ). Strategies to improve treatment tolerability are warranted. This study examined the safety and feasibility of preoperative exercise training during neoadjuvant treatment in these patients. Methods: Patients were allocated to a standard-care control group or an exercise group, who were prescribed standard care plus twice-weekly high-intensity aerobic exercise and resistance training sessions. The primary endpoint was the incidence of serious adverse events (SAEs) that prevented surgery, including death, disease progression or physical deterioration. Preoperative hospital admission, postoperative complications, changes in patient-reported quality of life and pathological treatment response were also recorded. In the exercise group, adherence to exercise and changes in aerobic fitness, muscle strength and body composition were measured. Results: The incidence of SAEs was not increased in the exercise group. The risk of failure to reach surgery was 5 versus 21 per cent in the control group (risk ratio (RR) 0·23, 95 per cent c.i. 0·04 to 1·29), the risk of preoperative hospital admission was 15 versus 38 per cent respectively (RR 0·39, 0·12 to 1·23) and the risk of postoperative complications was 58 versus 57 per cent (RR 1·06, 0·61 to 1·73). The exercise group attended a mean of 17·5 sessions, and improved fitness, muscle strength and Functional Assessment of Cancer Therapy - Esophageal (FACT-E) total score compared with the baseline level. Conclusion: Preoperative exercise training during neoadjuvant treatment in patients with GOJ cancer is safe and feasible, with improvements in fitness, strength and quality of life. Preoperative exercise training may be associated with a lower risk of critical SAEs that preclude surgery or result in hospitalization.

Development and validation of a subject-specific moving-axis tibiofemoral joint model using MRI and EOS imaging during a quasi-static lunge.

The aims of this study were to introduce and validate a novel computationally-efficient subject-specific tibiofemoral joint model. Subjects performed a quasi-static lunge while micro-dose radiation bi-planar X-rays (EOS Imaging, Paris, France) were captured at roughly 0°, 20°, 45°, 60°, and 90° of tibiofemoral flexion. Joint translations and rotations were extracted from this experimental data through 2D-to-3D bone reconstructions, using an iterative closest point optimization technique, and employed during model calibration and validation. Subject-specific moving-axis and hinge models for comparisons were constructed in the AnyBody Modeling System (AMS) from Magnetic Resonance Imaging (MRI)-extracted anatomical surfaces and compared against the experimental data. The tibiofemoral axis of the hinge model was defined between the epicondyles while the moving-axis model was defined based on two tibiofemoral flexion angles (0° and 90°) and the articulation modeled such that the tibiofemoral joint axis moved linearly between these two positions as a function of the tibiofemoral flexion. Outside this range, the joint axis was assumed to remain stationary. Overall, the secondary joint kinematics (ML: medial-lateral, AP: anterior-posterior, SI: superior-inferior, IE: internal-external, AA: adduction-abduction) were better approximated by the moving-axis model with mean differences and standard errors of (ML: -1.98 ±â€¯0.37 mm, AP: 6.50 ±â€¯0.82 mm, SI: 0.05 ±â€¯0.20 mm, IE: 0.59 ±â€¯0.36°, AA: 1.90 ±â€¯0.79°) and higher coefficients of determination (R2) for each clinical measure. While the hinge model achieved mean differences and standard errors of (ML: -0.84 ±â€¯0.45 mm, AP: 10.11 ±â€¯0.88 mm, SI: 0.66 ±â€¯0.62 mm, IE: -3.17 ±â€¯0.86°, AA: 11.60 ±â€¯1.51°).