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Background: Immune-related adverse events (irAEs) are frequently encountered by patients during immune checkpoint inhibitor (ICI) treatment and are associated with better treatment outcomes. The sequencing of radiotherapy (RT) and ICIs is widely used in current clinical practice, but its effect on survival has remained unclear. Methods: In a real-world multicenter study including 521 patients who received ICI treatment for metastatic or locally advanced cancer, RT schedules and timing, irAEs, time to progression, overall survival, and treatment responses were retrospectively reviewed. Results: Patients who received previous RT and developed irAE (RT +/AE +) had the best overall response rate (ORR 44.0%). The ORR was 40.1% in the RT −/AE + group, 26.7% in the RT −/AE − group and 18.3% in the RT + /AE − group (p < 0.001). There was a significantly longer time to progression (TTP) in the RT + /AE + group compared to the RT −/AE − and RT + /AE − groups (log rank p = 0.001 and p < 0.001, respectively), but the trend toward longer TTP in the RT + /AE + group did not reach statistical significance in pairwise comparison to that in the RT −/AE + group. Preceding RT timing and intent had no statistically significant effect on TTP. In a multivariate model, ECOG = 0 and occurrence of irAEs remained independent positive prognostic factors for TTP (HR 0.737; 95% CI 0.582–0.935; p = 0.012, and HR 0.620; 95% CI 0.499–0.769; p < 0.001, respectively). Conclusions: Better ORR and a trend toward longer TTP were demonstrated for patients with RT preceding ICI treatment and development of irAEs, which suggests that RT may boost the therapeutic effect of immunotherapy in patients with metastatic cancers.

Antipsychotics (APs), especially second-generation antipsychotics, are being increasingly used around the world. At the same time their off-label use has also increased worldwide, as well as in Finland. The aim of our study was to find out the off-label prescribing of APs in Finland among physicians in different healthcare units. The study was conducted as a questionnaire survey. Particular attention was paid to practices between psychiatrists and other physicians (mostly general practitioners and occupational health doctors). Similar studies have not been conducted on this topic in Finland before. Altogether 216 physicians answered the questionnaire. The most common indications for off-label prescription were insomnia and anxiety, and this was evident for both psychiatrists as well as other physicians. Quetiapine was the one most commonly prescribed off-label AP. Over one-third of psychiatrists (39%) and about one-third of other physicians (30%) did not give instructions on the length of the treatment. The metabolic values were reported to be followed by 44% of the psychiatrists and by 18% of other physicians. Nearly two-thirds of all respondents thought that off-label use had more benefits than harms. Compared to other physicians, psychiatrists prescribed APs for off-label use more frequently and for more varied psychiatric conditions. Off-label use of APs seems to be a clinical reality in Finland. There is need for further studies on efficacy and adverse effects of APs in off-label use, and also a need for clinical guidelines on monitoring the patients using APs off-label.

Purpose: Populations living in the Nordic countries are at high risk for vitamin D (VitD) deficiency or insufficiency. To reduce the risk, nationwide interventions based on food fortification and supplementation are being implemented. However, there is limited evidence about the impact of such public health campaigns on target populations. Methods: We studied an unselected sample of 3650 participants (56.2% females) from the longitudinal Northern Finland Birth Cohort 1966 with repeated measures of serum 25-hydroxyvitamin D [25(OH)D] at ages 31 (1997) and 46 (2012–2013). Timepoints corresponded to the period before and during the food fortification. We examined the effect of VitD intake from the diet and supplementation, body mass index and previous 25(OH)D concentration on 25(OH)D concentration at 46 years using a multivariable linear regression analysis. A 25(OH)D z score adjusted for sex, season, latitude and technical effect was used in the analysis. Results: We observed an increase of 10.6 nmol/L in 25(OH)D, when the baseline 25(OH)D was 54.3 nmol/L. The prevalence of serum 25(OH)D below < 50 nmol/L was halved. The changes were found for both sexes and were more pronounced in winter compared to summer months. Regular VitD supplementation had a significant positive effect on 25(OH)D at the age of 46, as well as had the dietary intake of fortified dairy products and fish, and the previous 25(OH)D concentration. However, the intake of fat-spreads albeit VitD-fortified, did not predict 25(OH)D. Conclusions: Our results demonstrated the positive impact of the fortification programme on VitD status in middle-aged population.

Background: As the burden of treatment-resistant schizophrenia (TRS) on patients and society is high it is important to identify predictors of response to medications in TRS. The aim was to analyse whether baseline patient and study characteristics predict treatment response in TRS in drug trials. Methods: A comprehensive search strategy completed in PubMed, Cochrane and Web of Science helped identify relevant studies. The studies had to meet the following criteria: English language clinical trial of pharmacological treatment of TRS, clear definition of TRS and response, percentage of response reported, at least one baseline characteristic presented, and total sample size of at least 15. Meta-regression techniques served to explore whether baseline characteristics predict response to medication in TRS. Results: 77 articles were included in the systematic review. The overall sample included 7546 patients, of which 41% achieved response. Higher positive symptom score at baseline predicted higher response percentage. None of the other baseline patient or study characteristics achieved statistical significance at predicting response. When analysed in groups divided by antipsychotic drugs, studies of clozapine and other atypical antipsychotics produced the highest response rate. Conclusions: This meta-analytic review identified surprisingly few baseline characteristics that predicted treatment response. However, higher positive symptoms and the use of atypical antipsychotics — particularly clozapine — was associated with the greatest likelihood of response. The difficulty involved in the prediction of medication response in TRS necessitates careful monitoring and personalised medication management. There is a need for more investigations of the predictors of treatment response in TRS.

A commercial deep learning (DL)-based automated segmentation tool (AST) for computed tomography (CT) is evaluated for accuracy and efficiency gain within prostate cancer patients. Thirty patients from six clinics were reviewed with manual- (MC), automated- (AC) and automated and edited (AEC) contouring methods. In the AEC group, created contours (prostate, seminal vesicles, bladder, rectum, femoral heads and penile bulb) were edited, whereas the MC group included empty datasets for MC. In one clinic, lymph node CTV delineations were evaluated for interobserver variability. Compared to MC, the mean time saved using the AST was 12 min for the whole data set (46%) and 12 min for the lymph node CTV (60%), respectively. The delineation consistency between MC and AEC groups according to the Dice similarity coefficient (DSC) improved from 0.78 to 0.94 for the whole data set and from 0.76 to 0.91 for the lymph nodes. The mean DSCs between MC and AC for all six clinics were 0.82 for prostate, 0.72 for seminal vesicles, 0.93 for bladder, 0.84 for rectum, 0.69 for femoral heads and 0.51 for penile bulb. This study proves that using a general DL-based AST for CT images saves time and improves consistency.

Introduction: Community services are gaining ground when it comes to attention to patients with psychiatric diseases. Regarding patients with treatment-resistant schizophrenia (TRS), the use of information and communication technology (ICT) could help to shift the focus from hospital-centered attention to community services. This study compares the differences in mental health services provided for patients with TRS in Budapest (Hungary), Tel-Aviv (Israel) and Catalonia (Spain) by means of a method for the quick appraisal of gaps among the three places, for a potential implementation of the same ICT tool in these regions. Methods: An adapted version of the Description and Standardised Evaluation of Services and Directories in Europe for Long Term Care (DESDE-LTC) instrument was made by researchers in Semmelweis University (Budapest, Hungary), Gertner Institute (Tel-Aviv, Israel) and Hospital de la Santa Creu I Sant Pau and Parc Sanitari Sant Joan de Déu (Catalonia, Spain). Results: Two types of outpatient care services were available in the three regions. Only one type of day-care facility was common in the whole study area. Two residential care services, one for acute and the other for non-acute patients were available in every region. Finally, two self-care and volunteer-care facilities were available in the three places. Conclusion: Although the availability of services was different in each region, most of the services provided were sufficiently similar to allow the implementation of the same ICT solution in the three places., The m-RESIST Group The m-RESIST Group is composed of: Francisco Alcalde Enrico d’Amico Caritat Almazán Anna Alonso-Solís Jesús Berdún István Bitter Walter Baccinelli Chiara Bonizzi María Bulgheroni Johanna Caro Mendivelso Asaf Caspi Tanguy Coenen Anat Cohen Xavier Constant Iluminada Corripio Marisol Escobar Kinga Farkas Kata Fazekas Yoram Feldman Emmanuel Gimenez Shenja van der Graaf Eva Grasa Levente Herman Margarita Hospedales Elena Huerta-Ramos Matti Isohanni Erika Jääskeläinen Charlotte Jewel Teija Juola Timo Jämsä Rachelle Kaye Panagiotis Kokkinakis Hannu J. Koponen Silvia Marcó Gregoris Mentzas Jouko Miettunen Jani Moilanen Susana Ochoa Ilias Papas Fotis Paraskevopoulos Elisabeth Reixach Alexandra Roldán Katya Rubinstein Elena Rubio-Abadal Garifalia Sebú Annika Seppälä Jussi Seppälä Valentina Simonetti Matthias Stevens Vittorio Tauro Anna Triantafillou Zsolt Szabolcs Unoka Judith Usall Vincenzo Vella David Vermeir Ilaria de Vita

Background: Cranial radiotherapy may damage the cerebral vasculature. The aim of this study was to understand the prevalence and risk factors of cerebrovascular disease (CVD) and white matter hyperintensities (WMHs) in childhood brain tumors (CBT) survivors treated with radiotherapy. Methods: Seventy CBT survivors who received radiotherapy were enrolled in a cross-sectional study at a median 20 years after radiotherapy cessation. The prevalence of and risk factors for CVD were investigated using MRI, MRA, and laboratory testing. Tumors, their treatment, and stroke-related data were retrieved from patients’ files. Results: Forty-four individuals (63%) had CVD at a median age of 27 years (range, 16–43 years). The prevalence rates at 20 years for CVD, small-vessel disease, and large-vessel disease were 52%, 38%, and 16%, respectively. Ischemic infarcts were diagnosed in 6 survivors, and cerebral hemorrhage in 2. Lacunar infarcts were present in 7, periventricular or deep WMHs in 34 (49%), and mineralizing microangiopathy in 21 (30%) survivors. Multiple pathologies were detected in 44% of the participants, and most lesions were located in a high-dose radiation area. Higher blood pressure was associated with CVD and a presence of WMHs. Higher cholesterol levels increased the risk of ischemic infarcts and WMHs, and lower levels of high-density lipoprotein and higher waist circumference increased the risk of lacunar infarcts. Conclusions: Treating CBTs with radiotherapy increases the risk of early CVD and WMHs in young adult survivors. These results suggest an urgent need for investigating CVD prevention in CBT patients.

Background: We studied the cumulative incidence of physical illnesses, and the effect of early environmental factors (EEFs) on somatic comorbidity in schizophrenia, in nonschizophrenic psychosis and among nonpsychotic controls from birth up to the age of 50 years. Methods: The sample included 10,933 members of the Northern Finland Birth Cohort 1966, of whom, 227 had schizophrenia and 205 had nonschizophrenic psychosis. Diagnoses concerning physical illnesses were based on nationwide registers followed up to the end of 2016 and classified into 13 illness categories. Maternal education and age, family type at birth and paternal socioeconomic status were studied as EEFs of somatic illnesses. Results: When adjusted by gender and education, individuals and especially women with nonschizophrenic psychosis had higher risk of morbidity in almost all somatic illness categories compared to controls, and in some categories, compared to individuals with schizophrenia. The statistically significant adjusted hazard ratios varied from 1.27 to 2.42 in nonschizophrenic psychosis. Regarding EEFs, single-parent family as the family type at birth was a risk factor for a higher somatic score among men with schizophrenia and women with nonschizophrenic psychosis. Maternal age over 35 years was associated with lower somatic score among women with nonschizophrenic psychosis. Conclusions: Persons with nonschizophrenic psychoses have higher incidence of somatic diseases compared to people with schizophrenia and nonpsychotic controls, and this should be noted in clinical work. EEFs have mostly weak association with somatic comorbidity in our study.