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Descriptive data on late effects associated with castrate-resistant prostate cancer (CRPC) are sparse. We aimed to define the timing and incidence of cardiovascular disease (CVD), fractures, and diabetes in a patient population with CRPC.In the population-based STHLM0 cohort 1464 men with CRPC were identified and matched with three men free from prostate cancer (PC) in the Stockholm region of Sweden. Kaplan-Meier estimates of net survival were used to describe time to CVD, fracture, and diabetes. Cox regression was used to compare incidence rates (IRRs) for the respective late effects. Cumulative incidence analyses of late effects in the presence of the competing risk of death were performed to estimate absolute risks.The Kaplan Meier estimates demonstrated a higher net probability for CVD, fracture, and diabetes among men diagnosed with CRPC compared to the matched comparators. The IRRs were 1.94 (95% CI: 1.79-2.12) for CVD, 2.08 (95% CI: 1.70-2.53) for fracture, and 2.00 (95% CI: 1.31-3.05) for diabetes, respectively, comparing men diagnosed with CRPC to men free from PC. The cumulative incidence of CVD at 12 months of follow-up was higher in men diagnosed with CRPC compared to healthy controls regardless of age with a difference in cumulative incidence being 0.20 for men aged65 and 0.11 for men aged84.In this cohort, the incidence of CVD was significantly higher among men with CRPC compared to healthy controls. Despite having this end-stage disease this finding proves that clinicians must recognize this late effect in men diagnosed with CRPC to improve preventive actions. These men did not have a higher absolute risk of fractures and diabetes after accounting for deaths due to any cause compared to healthy controls.

Meta-analyses suggest an association between autism spectrum disorder (ASD) and obesity, but the factors underlying this association remain unclear. This study investigated the association between ASD and obesity stratified on intellectual disability (ID). In addition, in order to gain insight into possible shared etiological factors, the potential role of shared familial liability was examined.We studied a cohort of 3,141,696 individuals by linking several Swedish nationwide registers. We identified 35,461 individuals with ASD and 61,784 individuals with obesity. Logistic regression models were used to estimate the association between ASD and obesity separately by ID and sex and by adjusting for parental education, psychiatric comorbidity, and psychotropic medication. Potential shared familial etiologic factors were examined by comparing the risk of obesity in full siblings, maternal and paternal half-siblings, and full- and half-cousins of individuals with ASD to the risk of obesity in relatives of individuals without ASD.Individuals with ASD + ID (OR = 3.76 [95% CI, 3.38-4.19]) and ASD-ID (OR = 3.40 [95% CI, 3.23-3.58]) had an increased risk for obesity compared with individuals without ASD. The associations remained statistically significant when adjusting for parental education, psychiatric comorbidity, and medication. Sex-stratified analyses indicated a higher relative risk for males compared with females, with statistically significant interaction effects for ASD-ID, but not for ASD+ID in the fully adjusted model. First-degree relatives of individuals with ASD+ID and ASD-ID had an increased risk of obesity compared with first-degree relatives of individuals without ASD. The obesity risk was similar in second-degree relatives of individuals with ASD+ID but was lower for and ASD-ID. Full cousins of individuals with ASD+ID had a higher risk compared with half-cousins of individuals with ASD+ID). A similar difference in the obesity risk between full cousins and half-cousins was observed for ASD-ID.Individuals with ASD and their relatives are at increased risk for obesity. The risk might be somewhat higher for males than females. This warrants further studies examining potential common pleiotropic genetic factors and shared family-wide environmental factors for ASD and obesity. Such research might aid in identifying specific risks and underlying mechanisms in common between ASD and obesity.

This study aimed to investigate the prevalence of sexually transmitted infections (STIs) and colonizing bacteria in relation to urogenital symptoms.In this cross-sectional study, patients visiting the STI clinic at Umeå University Hospital were asked for symptoms and condom use. Samples from 759 patients (465 male and 294 female) were analyzed for 4 STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium) and 3 colonizing bacteria (Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum).Chlamydia trachomatis prevalence was 11% among women and 9.5% among men. Neisseria gonorrhoeae prevalence was 0.7% among women and 0.9% among men. Mycoplasma genitalium was found in 11% and 5.6% of women and men, respectively. Asymptomatic men and women had similar distribution patterns of microorganisms as those with urogenital symptoms, with the exceptions of Neisseria gonorrhoeae- and Mycoplasma genitalium-infected men who declared symptoms more frequently. Of 158 men with urogenital symptoms, 55% were test-negative. Of 129 women with urogenital symptoms, 12% were test-negative.This study reveals a complex picture, where a large number of multi-positive tests made it complicated to correlate urogenital symptoms with microorganisms. A high number of test-negative but symptomatic patients indicate a need of searching for additional pathogens.

Aims Heart failure (HF) is a leading cause of hospitalization and is associated with high morbidity and mortality. We examined the impact of recurrent HF hospitalizations (HFHs) on cardiovascular (CV) mortality among patients with HF in Sweden. Methods and results Adults with incident HF were identified from linked national health registers and electronic medical records from 01 January 2005 to 31 December 2013 for Uppsala and until 31 December 2014 for Västerbotten. CV mortality and all‐cause mortality were evaluated. A time‐dependent Cox regression model was used to estimate relative CV mortality rates for recurrent HFHs. Assessment was also done for ejection fraction‐based HF phenotypes and for comorbid atrial fibrillation, diabetes, or chronic renal impairment. Overall, 3878 patients with HF having an index hospitalization were included, providing 9691.9 patient‐years of follow‐up. Patients were relatively old (median age: 80 years) and were more frequently male (55.5%). Compared with patients without recurrent HFHs, the adjusted hazard ratio (HR [95% confidence interval; CI]) for CV mortality and all‐cause mortality were statistically significant for patients with one, two, three, and four or more recurrent HFHs. The risk of CV mortality and all‐cause mortality increased approximately six‐fold in patients with four or more recurrent HFHs vs. those without any HFHs (HR [95% CI]: 6.26 [5.24–7.48] and 5.59 [4.70–6.64], respectively). Similar patterns were observed across the HF phenotypes and patients with comorbidities. Conclusions There is a strong association between recurrent HFHs and CV and all‐cause mortality, with the risk increasing progressively with each recurrent HFH.

The goal of this investigation is to assess the association between prehospital use of aspirin (ASA) and patient-centered outcomes in a large global cohort of hospitalized COVID-19 patients.This study utilizes data from the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) Registry. Adult patients hospitalized from February 15th, 2020, to September 30th, 2021, were included. Multivariable regression analyses were utilized to assess the association between pre-hospital use of ASA and the primary outcome of overall hospital mortality.21,579 patients were included from 185 hospitals (predominantly US-based, 71.3%), with 4691 (21.7%) receiving pre-hospital ASA. Patients receiving ASA, compared to those without pre-admission ASA use, were generally older (median 70 vs. 59 years), more likely to be male (58.7 vs. 56.0%), caucasian (57.4 vs. 51.6%), and more commonly had higher rates of medical comorbidities. In multivariable analyses, patients receiving pre-hospital ASA had lower mortality (HR: 0.89, 95% CI 0.82-0.97, p=0.01) and reduced hazard for progression to severe disease or death (HR: 0.91, 95% CI 0.84-0.99, p=0.02) and more hospital free days (1.00 days, 95% CI 0.66-1.35, p=0.01) compared to those without pre-hospital ASA use. The overall direction and significance of the results remained the same in sensitivity analysis, after adjusting the multivariable model for time since pandemic.In this large international cohort, pre-hospital use of ASA was associated with a lower hazard for death in hospitalized patients with COVID-19. Randomized controlled trials may be warranted to assess the utility of pre-hospital use of ASA.

The aim of this study was to investigate whether Swedish swingers constitute a risk group for sexually transmitted infections (STIs). Two swinger clubs were invited to participate. At swinger meetings, members were offered an STI sampling kit and a questionnaire. Samples were analyzed for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis using a multiplex real-time polymerase chain reaction assay. In total, 235 swingers participated (118 women and 117 men). Urogenital C. trachomatis prevalence was 1.7%. Urogenital M. genitalium prevalence was 7.6% for women and 4.3% for men. No one tested positive for N. gonorrhoeae or T. vaginalis. For women, the mean number of unprotected temporary sex partners within the last 12 months was four men (range 0–35) and three women (range 0–50). Among men, the mean number of unprotected temporary sex partners within the last 12 months was five women (range 0–50) and 0 men (range 0–10). During vaginal sex, 46.6% women and 38.5% men always used protection with a temporary sex partner. Swedish swingers did not seem to have an increased prevalence of STIs. However, there was high-risk sexual behavior with unprotected sex and multiple sex partners, thereby making them a vulnerable group for acquiring STIs.

Objective Patients in Sweden’s rural community hospitals have not been clinically characterised. We compared characteristics of patients in general practitioner-led community hospitals in northern Sweden with those admitted to general hospitals. Design Retrospective register study. Setting Community and general hospitals in Västerbotten and Norrbotten counties, Sweden. Patients Patients enrolled at community hospitals and hospitalised in community and general hospitals between 1 January 2010 and 31 December 2014. Outcome measures Age, sex, number of admissions, main, secondary and total number of diagnoses. Results We recorded 16,133 admissions to community hospitals and 60,704 admissions to general hospitals. Mean age was 76.8 and 61.2 years for community and general hospital patients (p

Background Pancreatic cancer is a devastating disease with a dismal prognosis. Despite profound medical advances in systemic therapies for other types of aggressive tumours during recent years, a diagnosis of pancreatic cancer is still often synonymous with a fatal outcome. The term periampullary cancer includes pancreatic cancer and applies to the group of tumours found in proximity to the ampulla of Vater. Molecular events and immune response in the host during chemotherapy remain largely unexplored in this group of tumours. Therefore, the “Chemotherapy, Host Response and Molecular Dynamics in Periampullary Cancer (CHAMP)” study aims to monitor these processes to gain new insight into this perplexing disease. Methods The CHAMP study is a prospective, single-arm observational study. All patients diagnosed with pancreatic or other periampullary adenocarcinoma undergoing adjuvant or palliative chemotherapy treatment in the Department of Oncology, Skåne University Hospital, are invited to participate. Clinical and pathological data will be compiled at study entry. A single tissue microarray (TMA) block is constructed for each patient with a resected tumour and blood samples are drawn before, during and after chemotherapy in order to sample peripheral blood mononuclear cells (PBMC), cytokines and circulating tumour DNA (ctDNA). Next generation sequencing will be performed on tumour tissue and ctDNA to detect changes in the clonal landscape over space and time. Discussion Despite the recent emergence of some promising biomarkers for periampullary cancer, there has been a lack of success in clinical implementation. Cancer cells continuously adapt and become resistant to treatment during chemotherapy. To be able to keep pace with and hopefully overtake this rapid evolution we must, with the help of new diagnostic tools, be ready to adapt and alter treatment accordingly. It seems to us that the only way forward is to gain a better understanding of the dynamics of the disease during treatment. With insights gained from the CHAMP study we hope to find answers to key questions in this largely unexplored territory. Trial registration This study has been registered 30th October 2018 at clinicaltrials.gov as NCT03724994.

Cutibacterium is a genus often considered a contaminant when present in blood cultures, but it can also cause severe infections, especially related to implanted foreign materials. We investigated the incidence and features of patients with true Cutibacterium infection. Patients with positive Cutibacterium blood cultures between the years 2015–2020 in southern Sweden were identified through microbiology records and medical records were studied retrospectively. Cutibacterium isolates were species determined using MALDI-TOF MS. Patients were classified as having true infection or contamination according to a definition considering both clinical and microbiological features and these groups were compared. A total of 313 episodes of positive Cutibacterium blood cultures were identified in 312 patients. Of these, 49 (16%, corresponding to an incidence of 6 cases per million inhabitants per year) were classified as true infections. The most common species was Cutibacterium acnes (87%), and the majority were elderly men with comorbidities. Patients with true Cutibacterium infection often had an unknown focus of infection (n = 21) or a focus in the respiratory tract (n = 18). We identified one episode of ventriculo-peritoneal shunt infection, three episodes of aortic stent-graft infection, and one episode of infective endocarditis. Two patients, where Cutibacterium was isolated at the site of infection, had only one positive blood culture. The finding of positive Cutibacterium blood cultures should not always be considered contamination. Definitions of true Cutibacterium bacteremia with a demand that more than one blood culture must be positive may miss true infections.

Key Points Question What is the risk of acute respiratory distress syndrome (ARDS) and death in patients with COVID-19 with metabolic syndrome? Findings In this cohort study including 46 441 patients hospitalized for COVID-19, metabolic syndrome was associated with significantly increased odds of ARDS and death. With each metabolic syndrome criterion added from 1 to 4 criteria, the risk of ARDS significantly increased in an additive fashion. Meaning These findings suggest that metabolic syndrome and its associated comorbidities were critical risk factors associated with COVID-19–related ARDS and death., This cohort study examines the association of metabolic syndrome with risk of acute respiratory distress syndrome and death in hospitalized patients with COVID-19., Importance Obesity, diabetes, and hypertension are common comorbidities in patients with severe COVID-19, yet little is known about the risk of acute respiratory distress syndrome (ARDS) or death in patients with COVID-19 and metabolic syndrome. Objective To determine whether metabolic syndrome is associated with an increased risk of ARDS and death from COVID-19. Design, Setting, and Participants This multicenter cohort study used data from the Society of Critical Care Medicine Discovery Viral Respiratory Illness Universal Study collected from 181 hospitals across 26 countries from February 15, 2020, to February 18, 2021. Outcomes were compared between patients with metabolic syndrome (defined as ≥3 of the following criteria: obesity, prediabetes or diabetes, hypertension, and dyslipidemia) and a control population without metabolic syndrome. Participants included adult patients hospitalized for COVID-19 during the study period who had a completed discharge status. Data were analyzed from February 22 to October 5, 2021. Exposures Exposures were SARS-CoV-2 infection, metabolic syndrome, obesity, prediabetes or diabetes, hypertension, and/or dyslipidemia. Main Outcomes and Measures The primary outcome was in-hospital mortality. Secondary outcomes included ARDS, intensive care unit (ICU) admission, need for invasive mechanical ventilation, and length of stay (LOS). Results Among 46 441 patients hospitalized with COVID-19, 29 040 patients (mean [SD] age, 61.2 [17.8] years; 13 059 [45.0%] women and 15713 [54.1%] men; 6797 Black patients [23.4%], 5325 Hispanic patients [18.3%], and 16 507 White patients [57.8%]) met inclusion criteria. A total of 5069 patients (17.5%) with metabolic syndrome were compared with 23 971 control patients (82.5%) without metabolic syndrome. In adjusted analyses, metabolic syndrome was associated with increased risk of ICU admission (adjusted odds ratio [aOR], 1.32 [95% CI, 1.14-1.53]), invasive mechanical ventilation (aOR, 1.45 [95% CI, 1.28-1.65]), ARDS (aOR, 1.36 [95% CI, 1.12-1.66]), and mortality (aOR, 1.19 [95% CI, 1.08-1.31]) and prolonged hospital LOS (median [IQR], 8.0 [4.2-15.8] days vs 6.8 [3.4-13.0] days; P

Background Interleukin-6 receptor antagonists (IL-6RAs) and steroids are emerging immunomodulatory therapies for severe and critical coronavirus disease (COVID-19). In this preliminary report, we aim to describe the epidemiology, clinical characteristics, and outcomes of adult critically ill COVID-19 patients, requiring invasive mechanical ventilation (iMV), and receiving IL-6RA and steroids therapy over the last 11 months. Materials and methods International, multicenter, cohort study derived from Viral Infection and Respiratory Illness University Study registry and conducted through Discovery Network, Society of Critical Care Medicine. Data were collected between March 01, 2020, and January 10, 2021. Results Of 860 patients who met eligibility criteria, 589 received steroids, 170 IL-6RAs, and 101 combinations. Patients who received IL-6RAs were younger (median age of 57.5 years vs. 61.1 and 61.8 years in the steroids and combination groups, respectively). The median C-reactive protein level was > 75 mg/L, indicating a hyperinflammatory phenotype. The median daily steroid dose was 7.5 mg dexamethasone or equivalent (interquartile range: 6–14 mg); 80.8% and 19.2% received low-dose and high-dose steroids, respectively. Of the patients who received IL-6RAs, the majority received one dose of tocilizumab and sarilumab (dose range of 600–800 mg for tocilizumab and 200–400 mg for sarilumab). Regarding the timing of administration, we observed that steroid and IL-6RA administration on day 0 of ICU admission was only 55.6% and 39.5%, respectively. By day 28, when compared with steroid use alone, IL-6RA use was associated with an adjusted incidence rate ratio (aIRR) of 1.12 (95% confidence interval [CI] 0.88, 1.4) for ventilator-free days, while combination therapy was associated with an aIRR of 0.83 (95% CI 0.6, 1.14). IL-6RA use was associated with an adjusted odds ratio (aOR) of 0.68 (95% CI 0.44, 1.07) for the 28-day mortality rate, while combination therapy was associated with an aOR of 1.07 (95% CI 0.67, 1.70). Liver dysfunction was higher in IL-6RA group (p = 0.04), while the bacteremia rate did not differ among groups. Conclusions Discordance was observed between the registry utilization patterns (i.e., timing of steroids and IL-6RA administration) and new evidence from the recent randomized controlled trials and guideline recommendations. These data will help us to identify areas of improvement in prescribing patterns and enhance our understanding of IL-6RA safety with different steroid regimens. Further studies are needed to evaluate the drivers of hospital-level variation and their impact on clinical outcomes. Trial registration ClinicalTrials.gov: NCT04486521. Registered on July 2020

The NRMN STAR program was created to address the persistent underrepresenta­tion in grant submissions and receipt of National Institutes of Health (NIH) awards by racial/ethnic minority groups. In our current study, we assessed program impact on trainees’ self-efficacy related to grant writing. The program was conducted with two cohorts: one in June 2014 and one in June 2015. We used a 19-item grant writing self-efficacy scale drawn from the 88-item Clinical Research Assessment Inventory of three domains (conceptualizing, designing, and funding a study) to predict whether self-efficacy influences researchers’ grant submissions. Trainees were assessed prior to and following program completion with subsequent assessments at 6 and 12 months beyond participation. The majority of trainees were Black (62%), female (62%), and had obtained a PhD (90%). More than half (52%) were assistant professors and 57% had none or

Background In Scandinavia, the distribution of ticks is expanding and tick-borne diseases constitute growing health risks. While the probability of getting a tick-borne disease after a tick bite is low, the health impacts can be large. This, as well as other characteristics of these diseases make tick-related risks difficult for laypeople to assess and perceived risk may differ substantially from actual risk. Understanding risk perceptions is important since it is the perceived risk, rather than actual risk, that determine behaviour and even more so for new and emerging risks. The aim of this study is to investigate knowledge and risk perceptions related to tick bites and the tick-borne diseases Lyme borreliosis (LB) and tick-borne encephalitis (TBE). By analysing risk perceptions and knowledge, the study helps inform the development of public health strategies in response to the increasing incidence of these diseases in Scandinavia. Methods Two thousand, six hundred sixty-eight respondents in Denmark, Norway and Sweden answered an online questionnaire with 48 questions, including 7 questions on risk perceptions and 9 knowledge questions. Chi-squared tests were used to analyse statistical differences between country sub-samples, gender and age groups. A multivariate regression model was used to analyse factors associated with risk perceptions. Results Risk perceptions were on average high in comparison with scientific estimates, with respondents grossly overrating the probability of contracting LB or TBE if bitten by a tick. Also, the average perceived seriousness of a single tick bite and of getting LB or TBE was high. Knowledge on the other hand was low, especially among men and the youngest age group (18–29 years). Higher levels of knowledge about tick-borne diseases were associated with lower perceived seriousness of tick bites and LB and higher perceived seriousness of TBE. Also, having been diagnosed with LB was negatively associated with the perceived seriousness of LB. Conclusions Our results indicate that informing about ticks and tick-borne diseases would be a relevant public health strategy as it could make risk perceptions better aligned with actual risk. Should the TBE virus spread further in Denmark and Norway, increasing knowledge about TBE vaccination would be especially important.

Study objective The transfusion of older packed RBCs may be harmful in critically ill patients. We seek to determine the association between packed RBC age and mortality among trauma patients requiring massive packed RBC transfusion. Methods We analyzed data from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial. Subjects in the parent trial included critically injured adult patients admitted to 1 of 12 North American Level I trauma centers who received at least 1 unit of packed RBCs and were predicted to require massive blood transfusion. The primary exposure was volume of packed RBC units transfused during the first 24 hours of hospitalization, stratified by packed RBC age category: 0 to 7 days, 8 to 14 days, 15 to 21 days, and greater than or equal to 22 days. The primary outcome was 24-hour mortality. We evaluated the association between transfused volume of each packed RBC age category and 24-hour survival, using random-effects logistic regression, adjusting for total packed RBC volume, patient age, sex, race, mechanism of injury, Injury Severity Score, Revised Trauma Score, clinical site, and trial treatment group. Results The 678 patients included in the analysis received a total of 8,830 packed RBC units. One hundred patients (14.8%) died within the first 24 hours. On multivariable analysis, the number of packed RBCs greater than or equal to 22 days old was independently associated with increased 24-hour mortality (adjusted odds ratio [OR] 1.05 per packed RBC unit; 95% confidence interval [CI] 1.01 to 1.08): OR 0.97 for 0 to 7 days old (95% CI 0.88 to 1.08), OR 1.04 for 8 to 14 days old (95% CI 0.99 to 1.09), and OR 1.02 for 15 to 21 days old (95% CI 0.98 to 1.06). Results of sensitivity analyses were similar only among patients who received greater than or equal to 10 packed RBC units. Conclusion Increasing quantities of older packed RBCs are associated with increased likelihood of 24-hour mortality in trauma patients receiving massive packed RBC transfusion (≥10 units), but not in those who receive fewer than 10 units.

Walking with different types of cueing/stimulus (i.e. auditory, visual) has shown to alter gait variability, thus emerging as an innovative therapeutical tool to restore abnormal gait variability in clinical populations. However, the majority of the research in this area has focused on auditory stimulus, while visual stimulus is an understudied alternative that needs more attention, particularly due to the natural dependence on vision during walking. Furthermore, the time differences between the occurrences of the walking steps and the sensory cues, also known as asynchronies, have also received minimal attention even though how well will synchronize with different stimuli is of great importance. This study investigated how synchronizing to visual stimulus that is presented with different temporal structures could affect gait variability and their respected asynchronies. Participants performed four 15-minute walking trials around an indoor track while wearing insole footswitches for the following conditions: a) self-paced walking, and b) walking with glasses that instructed the subjects to step in sync with a virtual moving bar. The stepping occurences of the moving bar were presented in three different ways b1) non-variable, b2) variable and b3) random. Stride times and asynchronies were determined, and the mean values along with the fractal scaling (an indicator of the complexity) in their time series, were calculated. The fractal scaling of the stride times was unaltered when participants walked with the variable stimulus as compared to the self-paced walking condition; while significantly decreased during the non-variable and random conditions indicating a loss of complexity for these two conditions. Regarding the asynchronies, no differences were observed in the means or the fractal scaling of the asynchronies. The correlation analysis between stride times and asynchronies revealed a strong relationship for the non-variable condition but a weak one for both variable and random conditions. Taken together, the present study results supports the idea of an existing internal timekeeper that exhibits complexity. We have shown that this complex pattern is similar regardless of the stimulus condition, suggesting that the system’s complexity is likely to be expressed at the task performance level – asyncrhonies – when walking to a stimulus. Thus, future research in sensoriomotor gait synchronization should focus and further explore the role of the asynchronies as it may be of clinical significance.

Despite substantial increases in the use of antipsychotics to treat various psychiatric conditions in children, there is a lack of literature regarding long-term effects of early treatment. Some studies have indicated that early administration results in differential alterations to neurotransmission systems, but few studies have investigated whether there are long-term behavioral modifications. Therefore, the aim of the current study was to investigate the neurobehavioral effects of low dose risperidone (a commonly prescribed antipsychotic) treatment using juvenile rats. Twenty-four male Sprague-Dawley rats were either subcutaneously implanted with a continuous release risperidone pellet (.04 mg/day) or a placebo pellet. To encompass the peri-adolescent to adolescent timeframe (postnatal day 40–70) thought to be important for brain development, male rats began risperidone treatment at post-natal day 35. Six weeks following commencement of risperidone treatment, all rats were tested on a battery of behavioral assessments including open field, object recognition, Morris Water Maze , and Y-Maze tasks. Risperidone treatment did not affect performance on the open field, object recognition, or Morris Water maze. A significant effect was found on the Y-maze. Although all rats exhibited normal spontaneous alternation, risperidone treated rats demonstrated significantly higher same arm returns, indicative of a working memory deficit. Continued research is needed to determine whether early exposure to risperidone may lead to differences in working memory at longer time-points. These results seem to indicate that early low dose risperidone treatment during the peri-adolescent and adolescent period does not severely impair behavior.

Supplemental Digital Content is available in the text., Objectives: Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry. Design: Retrospective study. Setting: Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry. Patients: Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021. Interventions: None. Measurements and Main Results: The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, and 28-day mortality. A total of 874 children with coronavirus disease 2019 were reported to Viral Infection and Respiratory Illness Universal Study registry from 51 participating centers, majority in the United States. Median age was 8 years (interquartile range, 1.25–14 yr) with a male:female ratio of 1:2. A majority were non-Hispanic (492/874; 62.9%). Median body mass index (n = 817) was 19.4 kg/m2 (16–25.8 kg/m2), with 110 (13.4%) overweight and 300 (36.6%) obese. A majority (67%) presented with fever, and 43.2% had comorbidities. A total of 238 of 838 (28.2%) met the Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children, and 404 of 874 (46.2%) were admitted to the ICU. In multivariate logistic regression, age, fever, multisystem inflammatory syndrome in children, and pre-existing seizure disorder were independently associated with a greater odds of ICU admission. Hospital mortality was 16 of 874 (1.8%). Median (interquartile range) duration of ICU (n = 379) and hospital (n = 857) stay were 3.9 days (2–7.7 d) and 4 days (1.9–7.5 d), respectively. For patients with 28-day data, survival was 679 of 787, 86.3% with 13.4% lost to follow-up, and 0.3% deceased. Conclusions: In this observational, multicenter registry of children with coronavirus disease 2019, ICU admission was common. Older age, fever, multisystem inflammatory syndrome in children, and seizure disorder were independently associated with ICU admission, and mortality was lower among children than mortality reported in adults.

Background Increasing the proportion of adults living in smoke-free homes is a US Healthy People 2020 objective. Complete home smoking bans are associated with higher odds of smoking cessation attempts and cessation duration. Sexual minority adults have disproportionality higher rates of smoking. This study investigates correlates of having a complete home smoking ban among sexual minority adults in California. Methods Secondary data analyses of the California Behavioral Risk Factor Surveillance System (CA BRFSS), 2014–2016. The CA BRFSS telephone survey of adults was conducted in English and Spanish and used random digit dial for landline and cell numbers. Weighted descriptives were stratified by sexual orientation and biological sex. Weighted bivariate and multivariable logistic regression analyses included only sexual minorities (i.e., lesbian, gay, bisexual) and were analyzed as a group and separately by biological sex to account for intragroup variances. The final weighted total of sexual minority adults (N = 359,236) included sexual minority adult females (N = 163,490) and sexual minority adult males (N = 195,746). Results Sexual minority adults in California had a lower prevalence of complete home smoking bans (Female 76.2%; Male 75.7%), higher prevalence of current cigarette smoking (Female 23.3%; Male 17.4%) and of e-cigarette use (Female 5.8%; Male 6.4%) than their straight counterparts. Sexual minorities that smoke everyday (Female Adjusted Odds Ratio (AOR) 0.26, 95% Confidence Interval (CI) 0.11–0.63; Male AOR 0.24, 95% CI 0.01–0.56) or some days (Female AOR 0.28, 95% CI 0.09–0.90) had lower adjusted odds of having a complete home smoking ban compared to those who never smoked. Conclusions Smoking everyday was the only consistent predictor of not having a complete home smoking ban among sexual minority adults. Focused efforts to increase prevalence of complete home smoking bans should address smoking status to improve health equity among sexual minority adults.

Knowledge of the health challenges and mortality in people with intellectual disability (ID) should guide health policies and practices in contemporary society.To examine premature mortality in individuals with ID.This population-based longitudinal cohort study obtained data from several national health care, education, and population registers in Sweden. Two registers were used to identify individuals with ID: the National Patient Register and the Halmstad University Register on Pupils With Intellectual Disability. Two cohorts were created: cohort 1 comprised young adults (born between 1980 and 1991) with mild ID, and cohort 2 comprised individuals (born between 1932 and 2013) with mild ID or moderate to profound ID; each cohort had matched reference cohorts. Data analyses were conducted between June 1, 2020, and March 31, 2021.Mild or moderate to profound ID.The primary outcome was overall (all-cause) mortality, and the secondary outcomes were cause-specific mortality and potentially avoidable mortality.Cohort 1 included 13 541 young adults with mild ID (mean [SD] age at death, 24.53 [3.66] years; 7826 men [57.8%]), and its matched reference cohort consisted of 135 410 individuals. Cohort 2 included 24 059 individuals with mild ID (mean [SD] age at death, 52.01 [16.88] years; 13 649 male individuals [56.7%]) and 26 602 individuals with moderate to profound ID (mean [SD] age at death, 42.16 [21.68] years; 15 338 male individuals [57.7%]); its matched reference cohorts consisted of 240 590 individuals with mild ID and 266 020 with moderate to profound ID. Young adults with mild ID had increased overall mortality risk compared with the matched reference cohort (odds ratio [OR], 2.86; 95% CI, 2.33-3.50), specifically excess mortality in neoplasms (OR, 3.58; 95% CI, 2.02-6.35), diseases of the nervous system (OR, 40.00; 95% CI, 18.43-86.80) and circulatory system (OR, 9.24; 95% CI, 4.76-17.95). Among deaths that were amenable to health care (OR, 7.75; 95% CI, 4.85-12.39), 55% were attributed to epilepsy. In cohort 2, increased risk of overall mortality was observed among both individuals with mild ID (OR, 6.21; 95% CI, 5.79-6.66) and moderate to profound ID (OR, 13.15; 95% CI, 12.52-13.81) compared with the matched reference cohorts. Those with moderate to profound ID had a higher risk in several cause-of-death categories compared with those with mild ID or the matched reference cohort. Adjustment for epilepsy and congenital malformations attenuated the associations. The relative risk of premature death was higher in women (OR, 6.23; 95% CI, 4.42-8.79) than in men (OR, 1.99; 95% CI, 1.53-2.60), but the absolute risk of mortality was similar (0.9% for women vs 0.9% for men).This study found excess premature mortality and high risk of deaths with causes that were potentially amenable to health care intervention among people with ID. This finding suggests that this patient population faces persistent health challenges and inequality in health care encounters.

Background The response to neoadjuvant cisplatin-based chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) is impaired in up to 50% of patients due to chemoresistance, with no predictive biomarkers in clinical use. The proto-oncogene RNA-binding motif protein 3 (RBM3) has emerged as a putative modulator of chemotherapy response in several solid tumours but has a hitherto unrecognized role in MIBC. Methods RBM3 protein expression level in tumour cells was assessed via immunohistochemistry in paired transurethral resection of the bladder (TURB) specimens, cystectomy specimens and lymph node metastases from a consecutive cohort of 145 patients, 65 of whom were treated with NAC. Kaplan-Meier and Cox regression analyses were applied to estimate the impact of RBM3 expression on time to recurrence (TTR), cancer-specific survival (CSS), and overall survival (OS) in strata according to NAC treatment. The effect of siRNA-mediated silencing of RBM3 on chemosensitivity was examined in RT4 and T24 human bladder carcinoma cells in vitro. Cellular functions of RBM3 were assessed using RNA-sequencing and gene ontology analysis, followed by investigation of cell cycle distribution using flow cytometry. Results RBM3 protein expression was significantly higher in TURB compared to cystectomy specimens but showed consistency between primary tumours and lymph node metastases. Patients with high-tumour specific RBM3 expression treated with NAC had a significantly reduced risk of recurrence and a prolonged CSS and OS compared to NAC-untreated patients. In high-grade T24 carcinoma cells, which expressed higher RBM3 mRNA levels compared to RT4 cells, RBM3 silencing conferred a decreased sensitivity to cisplatin and gemcitabine. Transcriptomic analysis revealed potential involvement of RBM3 in facilitating cell cycle progression, in particular G1/S-phase transition, and initiation of DNA replication. Furthermore, siRBM3-transfected T24 cells displayed an accumulation of cells residing in the G1-phase as well as altered levels of recognised regulators of G1-phase progression, including Cyclin D1/CDK4 and CDK2. Conclusions The presented data highlight the potential value of RBM3 as a predictive biomarker of chemotherapy response in MIBC, which could, if prospectively validated, improve treatment stratification of patients with this aggressive disease.

This study applied supervised machine learning with multi-modal data to predict remission of major depressive disorder (MDD) after psychotherapy. Genotyped adult patients (n = 894, 65.5% women, age 18–75 years) diagnosed with mild-to-moderate MDD and treated with guided Internet-based Cognitive Behaviour Therapy (ICBT) at the Internet Psychiatry Clinic in Stockholm were included (2008–2016). Predictor types were demographic, clinical, process (e.g., time to complete online questionnaires), and genetic (polygenic risk scores). Outcome was remission status post ICBT (cut-off ≤10 on MADRS-S). Data were split into train (60%) and validation (40%) given ICBT start date. Predictor selection employed human expertise followed by recursive feature elimination. Model derivation was internally validated through cross-validation. The final random forest model was externally validated against a (i) null, (ii) logit, (iii) XGBoost, and (iv) blended meta-ensemble model on the hold-out validation set. Feature selection retained 45 predictors representing all four predictor types. With unseen validation data, the final random forest model proved reasonably accurate at classifying post ICBT remission (Accuracy 0.656 [0.604, 0.705], P vs null model = 0.004; AUC 0.687 [0.631, 0.743]), slightly better vs logit (bootstrap D = 1.730, P = 0.084) but not vs XGBoost (D = 0.463, P = 0.643). Transparency analysis showed model usage of all predictor types at both the group and individual patient level. A new, multi-modal classifier for predicting MDD remission status after ICBT treatment in routine psychiatric care was derived and empirically validated. The multi-modal approach to predicting remission may inform tailored treatment, and deserves further investigation to attain clinical usefulness.

Introduction: Fibrinolytic factors, plasminogen activator inhibitor-1, tissue plasminogen activator, tissue plasminogen activator/plasminogen activator-complex and the haemostatic factor von Willebrand factor are known markers of cardiovascular disease. Their plasma levels are adversely affected in patients with dysglycaemia, and glucose normalization with insulin glargine might improve the levels of these factors. Methods: Prespecified Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial (ClinicalTrials.gov number, NCT00069784). Tissue plasminogen activator activity, tissue plasminogen activator antigen, plasminogen activator inhibitor-1 antigen, tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor were analysed at study start, after 2 years and at the end of the study (median follow-up of 6.2 years). Results: Of 129 patients (mean age of 64 ± 7 years, females: 19%), 68 (53%) and 61 (47%) were randomized to the insulin glargine and standard care group, respectively. Allocation to insulin glargine did not significantly affect the studied fibrinolytic markers or von Willebrand factor compared to standard care. Likewise, there were no significant differences in plasminogen activator inhibitor-1, tissue plasminogen activator antigen and von Willebrand factor. During the whole study period, the within-group analysis revealed a curvilinear pattern and significant changes for tissue plasminogen activator/plasminogen activator inhibitor-1 complex, tissue plasminogen activator antigen and von Willebrand factor in the insulin glargine but not in the standard care group. Conclusion: In people with dysglycaemia and other cardiovascular risk factors, basal insulin does not improve the levels of markers of fibrinolysis or von Willebrand factor compared to standard glucose-lowering treatments.

ObjectivesTo examine healthcare resource use (HRU) and costs among heart failure (HF) patients using population data from Sweden.DesignRetrospective, non-interventional cohort study.SettingTwo cohorts were identified from linked national health registers (cohort 1, 2005–2014) and electronic medical records (cohort 2, 2010–2012; primary/secondary care patients from Uppsala and Västerbotten).ParticipantsPatients (aged ≥18 years) with primary or secondary diagnoses of HF (≥2 International Classification of Diseases and Related Health Problems, 10th revision classification) during the identification period of January 2005 to March 2015 were included.Outcome measuresHRU across the HF phenotypes was assessed with logistic regression. Costs were estimated based on diagnosis-related group codes and general price lists.ResultsTotal annual costs of secondary care of prevalent HF increased from SEK 6.23 (€0.60) to 8.86 (€0.85) billion between 2005 and 2014. Of 4648 incident patients, HF phenotype was known for 1715: reduced ejection fraction (HFrEF): 64.5%, preserved ejection fraction (HFpEF): 35.5%. Within 1 year of HF diagnosis, the proportion of patients hospitalised was only marginally higher for HFrEF versus HFpEF (all-cause (95% CI): 64.7% (60.8 to 68.4) vs 63.7% (60.8 to 66.5), HR 0.91, p=0.14; cardiovascular disease related (95% CI): 61.1% (57.1 to 64.8) vs 60.9% (58.0 to 63.7), HR 0.93, p=0.28). Frequency of hospitalisations and outpatient visits per patient declined after the first year. All-cause secondary care costs in the first year were SEK 122 758 (€12 890)/patient/year, with HF-specific care accounting for 69% of the costs. Overall, 10% of the most expensive population (younger; predominantly male; more likely to have comorbidities) incurred ~40% of total secondary care costs.ConclusionsHF-associated costs and HRU are high, especially during the first year of diagnosis. This is driven by high hospitalisations rates. Understanding the profile of resource-intensive patients being at younger age, male sex and high Charlson comorbidity index scores at the time of the HF diagnosis is most likely a sign of more severe disease.

Background Air pollution derived from combustion is associated with considerable cardiorespiratory morbidity and mortality in addition to environmental effects. Replacing petrodiesel with biodiesel may have ecological benefits, but impacts on human health remain unquantified. The objective was to compare acute cardiovascular effects of blended and pure biodiesel exhaust exposure against known adverse effects of petrodiesel exhaust (PDE) exposure in human subjects. In two randomized controlled double-blind crossover studies, healthy volunteers were exposed to PDE or biodiesel exhaust for one hour. In study one, 16 subjects were exposed, on separate occasions, to PDE and 30% rapeseed methyl ester biodiesel blend (RME30) exhaust, aiming at PM10 300 μg/m3. In study two, 19 male subjects were separately exposed to PDE and exhaust from a 100% RME fuel (RME100) using similar engine load and exhaust dilution. Generated exhaust was analyzed for physicochemical composition and oxidative potential. Following exposure, vascular endothelial function was assessed using forearm venous occlusion plethysmography and ex vivo thrombus formation was assessed using a Badimon chamber model of acute arterial injury. Biomarkers of inflammation, platelet activation and fibrinolysis were measured in the blood. Results In study 1, PDE and RME30 exposures were at comparable PM levels (314 ± 27 μg/m3; (PM10 ± SD) and 309 ± 30 μg/m3 respectively), whereas in study 2, the PDE exposure concentrations remained similar (310 ± 34 μg/m3), but RME100 levels were lower in PM (165 ± 16 μg/m3) and PAHs, but higher in particle number concentration. Compared to PDE, PM from RME had less oxidative potential. Forearm infusion of the vasodilators acetylcholine, bradykinin, sodium nitroprusside and verapamil resulted in dose-dependent increases in blood flow after all exposures. Vasodilatation and ex vivo thrombus formation were similar following exposure to exhaust from petrodiesel and the two biodiesel formulations (RME30 and RME100). There were no significant differences in blood biomarkers or exhaled nitric oxide levels between exposures. Conclusions Despite differences in PM composition and particle reactivity, controlled exposure to biodiesel exhaust was associated with similar cardiovascular effects to PDE. We suggest that the potential adverse health effects of biodiesel fuel emissions should be taken into account when evaluating future fuel policies. Trial registration ClinicalTrials.gov, NCT01337882/NCT01883466. Date of first enrollment March 11, 2011, registered April 19, 2011, i.e. retrospectively registered.

An estimated 350 million cases of STIs occur globally each year. In Sweden, Chlamydia is the most common STI with approximately 30 000 cases annually, disproportionally affecting youth. National surveys report low condom use among youth. Smartphone coverage is high among this tech-savvy group. In collaboration with youth, we developed an interactive smartphone application comprising games, peer experiences and information snippets to promote condom use.ObjectivesTo evaluate in a randomised controlled trial, the effectiveness of this smartphone application to improve condom use among youth in Stockholm, Sweden.MethodsThis two-arm, individually randomised controlled trial was implemented through the Youth Health Clinics (YHC) in Stockholm, Sweden. Youth aged 18–23 years, who owned a smartphone and had ≥2 sexual partners during the past 6 months were eligible. The intervention delivered the interactive elements described above over 180 days. The control group received a ‘dummy’ application. Both groups received standard of care at the YHC. The primary outcome was proportion of consistent (100%) self-reported condom use at 6 months. Secondary outcomes included self-reported number of partners, occurrence of STIs/pregnancy and STI tests during the study period. An intention-to-treat approach was used.Results214 and 219 youth were randomised to the intervention and control groups, respectively. Consistent condom use was reported for 32/214 (15.0%) in the intervention group and for 35/219 (16.0%) in the control group (OR 0.9, 95% CI 0.5 to 1.6). No significant differences in secondary outcomes were seen.ConclusionWe were unable to detect an effect of the intervention. Future research should focus on targeting different subgroups within the overall risk group, with tailored mHealth interventions. The potential for such interventions in settings where sexual health services are unavailable should be evaluated.Trial registration numberISRCTN13212899.

The aim of this study was to investigate prostate radiotherapy techniques for the patients with hip prosthesis in 4 different field setups. Volumetric Modulated Arc Therapy (VMAT) technique was used in 4 different cases: (1) using full VMAT arcs (VMAT_F); (2) same arcs as in case 1 but with avoidance sectors (VMAT_ASEC); (3) as case 2 but with the addition of a lateral static field through the prosthesis (VMAT_ASEC+STAT); (4) as in case 1 but with an automated structure avoidance option to avoid irradiation through the prosthesis (VMAT_ASTR). Fifteen previously treated prostate patients were retrospectively selected to this study. Treatment plans were created for all patients using all 4 techniques. The potential prosthesis misalignment in the treatment setup was modeled by moving the prosthesis 0.5, 1.0, and 1.5 cm ventrally and dorsally and recalculating the plans in each case. For VMAT_ASEC, the dose parameters for organs at risk were the highest and the dose coverage of the target volume was the poorest when compared to the other techniques. For VMAT_ASEC+STAT, the movement of the prosthesis changed the target dose distribution the most. VMAT_F and VMAT_ASTR fulfilled the planning criteria the best, even when the prosthesis was misaligned. VMAT_F radiated through the prosthesis more than VMAT_ASTR and increased the dose near the prosthesis surface when compared to VMAT_ASTR. VMAT_ASTR and VMAT_F were the most robust techniques for the patients with the hip prosthesis considering plan quality and the effect of positioning errors. The increased prosthesis surface dose with VMAT_F and possible dose calculation uncertainties favors the use of VMAT_ASTR.

Previous research has used functional near-infrared spectroscopy (fNIRS) to show that motor areas of the cortex are activated more while walking backward compared to walking forward. It is also known that head movement creates motion artifacts in fNIRS data. The aim of this study was to investigate cortical activation during forward and backward walking, while also measuring head movement. We hypothesized that greater activation in motor areas while walking backward would be concurrent with increased head movement. Participants performed forward and backward walking on a treadmill. Participants wore motion capture markers on their head to quantify head movement and pressure sensors on their feet to calculate stride-time. fNIRS was placed over motor areas of the cortex to measure cortical activation. Measurements were compared for forward and backward walking conditions. No significant differences in body movement or head movement were observed between forward and backward walking conditions, suggesting that conditional differences in movement did not influence fNIRS results. Stride-time was significantly shorter during backward walking than during forward walking, but not more variable. There were no differences in activation for motor areas of the cortex when outliers were removed. However, there was a positive correlation between stride-time variability and activation in the primary motor cortex. This positive correlation between motor cortex activation and stride-time variability suggests that forward walking variability may be represented in the primary motor cortex.

Purpose To assess the clinical outcome and evolution of recurrent afebrile seizures in children initially diagnosed with benign convulsions associated with mild gastroenteritis (CwG). Methods We reviewed and analyzed the medical records of 37 patients who were diagnosed as CwG at onset, followed by recurrent afebrile seizures and followed up for at least 24 months. Results The follow-up period ranged from 2 to 7 years (median, 40.1 months).Three patterns of recurrent afebrile seizures were recorded: afebrile seizures associated with gastrointestinal infection (AS-GI, n = 25), afebrile seizures associated with non-gastrointestinal infection (AS-nGI, n = 9), and unprovoked seizures (US, n = 3). Twenty eight patients (75.7%) had a second episode within 6 months after the first seizures. Five cases (13.5%) suffered three episodes of afebrile seizures. Seizure characteristics of the three patterns were similar, manifesting as clustered seizures in the majority. Focal epileptic activities in interictal EEG were found in 3 cases (9.4%) at onset, 10 cases (28.6%) at the second episode, respectively. Six patients were prescribed anti-epileptic drugs with apparently good responses. During at least 2 years’ follow-up, all the cases showed normal psychomotor development. Only one patient was diagnosed with epilepsy. Conclusions All the recurrent afebrile seizures initially diagnosed as CwG, irrespective of the kinds and frequency of relapses, showed favorable prognoses. CwG maybe falls within the category of situation-related seizures, rather than epilepsy.

BACKGROUND AND AIMS: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with cardiovascular disease. Statins lower both low-density lipoprotein (LDL)-cholesterol and C-reactive protein (CRP), resulting in improved outcomes. However, whether lipid-lowering therapy also lowers suPAR levels is unknown.METHODS: We investigated whether treatment with Simvastatin 40 mg and Ezetimibe 10 mg lowered plasma suPAR levels in 1838 patients with mild-moderate, asymptomatic aortic stenosis, included in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, using a pattern mixture model. A 1-year Cox analysis, adjusted for established cardiovascular risk factors, allocation to study treatment, peak aortic valve velocity and baseline suPAR, was performed to evaluate relationships between change in suPAR with all-cause mortality and the composite endpoint of major cardiovascular events (MCE) composed of ischemic cardiovascular events (ICE) and aortic valve related events (AVE).RESULTS: After 4.3 years of follow-up, suPAR levels had increased by 9.2% (95% confidence interval [CI]: 7.0%-11.5%) in the placebo group, but only by 4.1% (1.9%-6.2%) in the group with lipid-lowering treatment (pCONCLUSIONS: Simvastatin and Ezetimibe treatment impeded the progression of the time-related increase in plasma suPAR levels. Year-1 suPAR was associated with all-cause mortality, MCE, and AVE irrespective of baseline levels (SEAS study: NCT00092677).

AIMS AND OBJECTIVES: To describe how nurses communicate with older patients and their relatives in a department of medicine for older people in western Sweden. BACKGROUND: Communication is an essential tool for nurses when working with older patients and their relatives, but often patients and relatives experience shortcomings in the communication exchanges. They may not receive information or are not treated in a professional way. Good communication can facilitate the development of a positive meeting and improve the patient's health outcome. DESIGN: An ethnographic design informed by the sociocultural perspective was applied. METHODS: Forty participatory observations were conducted and analysed during the period October 2015-September 2016. The observations covered 135 hours of nurse-patient-relative interaction. Field notes were taken, and 40 informal field conversations with nurses and 40 with patients and relatives were carried out. Semistructured follow-up interviews were conducted with five nurses. RESULTS: In the result, it was found that nurses communicate with four different voices: a medical voice described as being incomplete, task-oriented and with a disease perspective; a nursing voice described as being confirmatory, process-oriented and with a holistic perspective; a pedagogical voice described as being contextualised, comprehension-oriented and with a learning perspective; and a power voice described as being distancing and excluding. The voices can be seen as context-dependent communication approaches. When nurses switch between the voices, this indicates a shift in the orientation or situation. CONCLUSION: The results indicate that if nurses successfully combine the voices, while limiting the use of the power voice, the communication exchanges can become a more positive experience for all parties involved and a good nurse-patient-relative communication exchange can be achieved. RELEVANCE TO CLINICAL PRACTICE: Working for improved communication between nurses, patients and relatives is crucial for establishing a positive nurse-patient-relative relationship, which is a basis for improving patient care and healthcare outcomes.

AIMS AND OBJECTIVES: To explore and describe the content of the communication exchanges between nurses, patients and their relatives in a department of medicine for older people in western Sweden. BACKGROUND: Information, messages and knowledge are constantly being communicated between nurses, older patients and relatives in the healthcare sector. The quality of communication between them has a major influence on patient outcomes. A prerequisite for good care to be given and received is that there is mutual understanding between the parties involved. DESIGN: An ethnographic study was informed by a sociocultural perspective. METHOD: Data were collected through 40 participatory observations of meetings between nurses and older patients and/or relatives which covered 135 hr of nurse-patient-relative interaction, field notes, 40 field conversations with 24 nurses and 40 field conversations with patients (n = 40) and relatives (n = 26). Five semi-structured interviews were conducted with nurses. An ethnographic analysis was performed. RESULTS: The analysis identified three categories of content of the communication exchanges: medical content focusing on the patient's medical condition, personal content focusing on the patient's life story and explanatory content focusing on the patient's health and nursing needs. The content is influenced by the situation and context. CONCLUSIONS: Nurses would benefit from more awareness and understanding of the importance of the communication content and of the value of asking the didactic questions (how, when, what and why) to improve the patients' and relatives' understanding of the information exchanges and to increase patient safety. RELEVANCE TO CLINICAL PRACTICE: Nurses can use the communication content to create conditions enabling them to obtain a holistic view of the patient's life history and to develop an appropriate person-centred care plan.

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.)

Underage drinking remains a pressing issue on college campuses across the United States. Though the most common form of addressing underage alcohol use on campuses is through deterrence-based policies, evidence suggests deterrence-based methods are ineffective and may produce negative outcomes.Using dyadic data, the objective of this study is to use a friendship-informed perspective on deterrence theory to examine how an individual's and his/her friend's perceptions of sanction certainty relate to self-reported underage alcohol use.Using multilevel mixed models which fall under the actor-partner interdependence modeling class, results demonstrate that respondents who perceive high levels of sanction certainty drink and heavily use alcohol more frequently than those who perceive low levels of sanction certainty. Additionally, those who have friends who perceive high levels of sanction certainty tend to drink at young ages significantly more frequently and in more dangerous patterns than those who have friends who perceive a low sanction certainty. The dyad members' levels of sanction certainty do not interact in relation to alcohol use.The significant relationships of the friends' sanction certainty support the notion of friendship-based deterrence. However, the consistent positive direction of all sanction certainty measures is the opposite of what deterrence theory hypothesizes. As such, it appears that deterrence is not only ineffective at stopping underage alcohol use on college campuses, but may be harmful due to increased rates of both drinking and high-risk drinking.

To explore the relationships between anaemia or iron deficiency (ID) and symptoms, quality of life (QoL), morbidity, and mortality.A post-hoc, non-prespecified, explorative substudy of the prospective randomized PREFER trial. One centre study of outpatients with severe HF and palliative need managed with advanced home care. Associations between anaemia, ID, and the Edmonton Symptom Assessment Scale (ESAS), Euro QoL (EQ-5D), Kansas City Cardiomyopathy Questions (KCCQ) were examined only at baseline but at 6months for morbidity and mortality.Seventy-two patients (51 males, 21 females), aged 79.2±9.1years. Thirty-nine patients (54%) had anaemia and 34 had ID (47%). Anaemia was correlated to depression (r=0.37; p=0.001), anxiety (r=0.25; p=0.04), and reduced well-being (r=0.26; p=0.03) in the ESAS; mobility (r=0.33; p=0.005), pain/discomfort (r=0.27; p=0.02), and visual analogue scale of health state (r=-0.28; p=0.02) in the EQ-5D; and physical limitation (r=-0.27; p=0.02), symptom stability; (r=-0.43; p0.001); (r=-0.25; p=0.033), social limitation;(r=-0.26; p=0.03), overall summary score; (r=-0.24, p=0.046) and clinical summary score; (r=-0.27; p=0.02) in the KCCQ. ID did not correlate to any assessment item. Anaemia was univariably associated with any hospitalization (OR: 3.0; CI: 1.05-8.50, p=0.04), but not to mortality. ID was not significantly associated with any hospitalization or mortality.Anaemia, but not ID, was associated although weakly with symptoms and QoL in patients with advanced HF and palliative home care.

Objective:Chronic heart failure is a disease with high morbidity and symptom burden for patients, and it also places great demands on family members. Patients with heart failure should have access to palliative care for the purpose of improving quality of life for both patients and their families. In the PREFER randomized controlled intervention, patients with New York Heart Association classes III–IV heart failure received person-centered care with a multidisciplinary approach involving collaboration between specialists in palliative and heart failure care. The aim of the present study was to describe family members' experiences of the intervention, which integrated palliative advanced home and heart failure care.Method:This study had a qualitative descriptive design based on family member interviews. Altogether, 14 family members participated in semistructured interviews for evaluation after intervention completion. The data were analyzed by means of content analysis.Results:Family members expressed gratitude and happiness after witnessing the patient feeling better due to symptom relief and empowerment. They also felt relieved and less worried, as they were reassured that the patient was being cared for properly and that their own responsibility for care was shared with healthcare professionals. However, some family members also felt as though they were living in the shadow of severe illness, without receiving any support for themselves.Significance of results:Several benefits were found for family members from the PREFER intervention, and our results indicate the significance of integrated palliative advanced home and heart failure care. However, in order to improve this intervention, psychosocial professionals should be included on the intervention team and should contribute by paying closer attention and providing targeted support for family members.

A significant reduction in the incidence of cardiovascular disease, including abdominal aortic aneurysm (AAA), has been observed in the past decades. In this study, a small but geographically well defined and carefully characterized population, previously screened for AAA and risk factors, was re-examined 11 years later. The aim was to study the reduction of AAA prevalence and associated factors.All men and women aged 65 to 75 years living in the Norsjö municipality in northern Sweden in January 2010 were invited to an ultrasound examination of the abdominal aorta, registration of body parameters and cardiovascular risk factors, and blood sampling. An AAA was defined as an infrarenal aortic diameter ≥30 mm. Results were compared with a corresponding investigation conducted in 1999 in the same region.A total of 602 subjects were invited, of whom 540 (90%) accepted. In 2010, the AAA prevalence was 5.7% (95% confidence interval [CI], 2.8%-8.5%) among men compared with 16.9% (95% CI, 12.3%-21.6%) in 1999 (P .001). The corresponding figure for women was 1.1% (95% CI, 0.0%-2.4%) vs 3.5% (95% CI, 1.2%-5.8%; P = .080). A low prevalence of smoking was observed in 2010 as well as in 1999, with only 13% and 10% current smokers, respectively (P = .16). Treatment for hypertension was significantly more common in 2010 (58% vs 44%; P .001). Statins increased in the population (34% in 2010 vs 3% in 1999; P .001), and the lipid profile in women had improved significantly between 1999 and 2010.A highly significant reduction in AAA prevalence was observed during 11 years in Norsjö. Treatment for hypertension and with statins was more frequent, whereas smoking habits remained low. This indicates that smoking is not the only driver behind AAA occurrence and that lifestyle changes and treatment of cardiovascular risk factors may play an equally important role in the observed recent decline in AAA prevalence.

Objective: The discovery of anti-citrullinated protein antibodies (ACPAs) and the introduction of new therapeutic options have had profound impacts on early rheumatoid arthritis (RA) care. Since ACPA status, most widely assessed as reactivity to cyclic citrullinated peptides (CCPs), influences treatment decisions in early RA, we aimed to determine whether anti-CCP remains a predictor of disease activity and radiographic joint damage in more recent ‘real-world’ early RA. Method: Two observational early RA cohorts from Sweden enrolled patients in 1996–1999 (TIRA-1, n = 239) and 2006–2009 (TIRA-2, n = 444). Clinical and radiographic data and ongoing treatment were prospectively collected up to 3 years. Two other cohorts served as confirmation cohorts (TRAM-1, with enrolment 1996–2000, n = 249; and TRAM-2, 2006–2011, n = 528). Baseline anti-CCP status was related to disease activity, pharmacotherapy, and radiographic joint damage according to Larsen score. Results: In the TIRA-1 cohort, anti-CCP-positive patients had significantly higher 28-joint Disease Activity Score, swollen joint count, C-reactive protein level, and erythrocyte sedimentation rate during follow-up compared with anti-CCP-negative patients. In TIRA-2, no such differences were found, but baseline anti-CCP positivity was associated with higher 3 year Larsen score (5.4 vs 3.5, p = 0.039). In TRAM-2, anti-CCP also predicted radiographic damage (8.9 vs 6.7, p = 0.027), with no significant differences in disease activity. Conclusion: In the early RA cohorts recruiting patients in 2006–2011, baseline anti-CCP positivity was not associated with disease activity over time, but was associated with increased radiographic damage at follow-up. Hence, close radiographic monitoring is warranted in early anti-CCP-positive RA regardless of disease activity.

Background: There is lack of knowledge on how occupational therapists (OTs) assess daily time management (DTM) for persons with dementia (PwDs) and on which aspects affect prescription of time assistive technology (AT). Aim: To explore OTs' experiences of assessing the need for and prescribing time AT for PwDs. Material and methods: Focus group interviews with OTs that prescribe time AT for PwDs analyzed via qualitative content analysis. Results: A main category and four categories were identified. The categories illustrated a complex and time-consuming prescription process, which was facilitated if the PwD was supported by a significant other (SO). Support from a SO was especially important during implementation and follow-up. OTs had to take individual responsibility for staying informed about time AT. Organizational limitations and time constraints were barriers for OTs striving to work according to national prescription guidelines. Conclusions and significance: High demands are made on SO's participation during the prescription process. PwDs with no support from SOs are at risk not receiving or fully benefitting from time AT. To avoid inequalities, specific forms of support need to be developed and targeted at PwDs without SOs to ensure that they have sufficient opportunities to access and use time AT.

Background A diverse research workforce is essential for catalyzing biomedical advancements, but this workforce goal is hindered by persistent sex and racial/ethnic disparities among investigators receiving research grants from the National Institutes of Health (NIH). In response, the NIH-funded National Research Mentoring Network implemented a Grant Writing Coaching Program (GCP) to provide diverse cohorts of early-career investigators across the United States with intensive coaching throughout the proposal development process. We evaluated the GCP’s national reach and short-term impact on participants’ proposal submissions and funding outcomes. Methods The GCP was delivered as six similar but distinct models. All models began with an in-person group session, followed by a series of coaching sessions over 4 to 12 months. Participants were surveyed at 6-, 12- and 18-months after program completion to assess proposal outcomes (submissions, awards). Self-reported data were verified and supplemented by searches of public repositories of awarded grants when available. Submission and award rates were derived from counts of participants who submitted or were awarded at least one grant proposal in a category (NIH, other federal, non-federal). Results From June 2015 through March 2019, 545 investigators (67% female, 61% under-represented racial/ethnic minority, URM) from 187 different institutions participated in the GCP. Among them, 324 (59% of participants) submitted at least one grant application and 134 (41% of submitters) received funding. A total of 164 grants were awarded, the majority being from the NIH (93, 56%). Of the 74 R01 (or similar) NIH research proposals submitted by GCP participants, 16 have been funded thus far (56% to URM, 75% to women). This 22% award rate exceeded the 2016–2018 NIH success rates for new R01s. Conclusion Inter- and intra-institutional grant writing coaching groups are a feasible and effective approach to supporting the grant acquisition efforts of early-career biomedical investigators, including women and those from URM groups.

Leptin, an adipocyte-derived hormone, is involved in the regulation of body weight and is associated with obesity-related complications, notably cardiovascular disease (CVD). A putative link between obesity and CVD could be induction of plasminogen activator inhibitor-1 (PAI-1) synthesis by leptin. In this study, we hypothesized that the beneficial effect of the angiotensin-converting enzyme inhibitor (ACEi) enalapril on PAI-1 levels is mediated by effects on leptin levels. The association between leptin and components of the fibrinolytic system was evaluated in a non-prespecified post hoc analysis of a placebo-controlled randomized, double-blind trial where the effect of the ACEi enalapril on fibrinolysis was tested. A total of 46 men and 37 women were randomized to treatment with enalapril or placebo after (median 12 months) an uncomplicated myocardial infarction. At baseline, the participants were stable and had no signs of congestive heart failure. Leptin and fibrinolytic variables (mass concentrations of PAI-1, tissue plasminogen activator (tPA) and tPA–PAI complex) were measured at baseline, and after 10 days, 6 months and 12 months. Enalapril treatment did not change leptin levels, which increased significantly during 1 year of follow-up (p = .007). Changes in leptin levels were strongly associated with changes of tPA mass (p = .001), tPA–PAI complex (p = .003) and of PAI-1 (p = .006) in men, but not in women. Leptin levels are not influenced by treatment with an ACEi. In contrast, leptin associates strongly with changes in fibrinolytic variables notably with a sex difference, which could be of importance for obesity-related CVD.

Therapist guided Internet-Delivered Cognitive Behavior Therapy (ICBT) is effective, but as in traditional CBT, not all patients improve, and clinicians generally fail to identify them early enough. We predict treatment failure in 12-week regular care ICBT for Depression, Panic disorder and Social anxiety disorder, using only patients' weekly symptom ratings to identify when the accuracy of predictions exceed 2 benchmarks: (a) chance, and (b) empirically derived clinician preferences for actionable predictions.Screening, pretreatment and weekly symptom ratings from 4310 regular care ICBT-patients from the Internet Psychiatry Clinic in Stockholm, Sweden was analyzed in a series of regression models each adding 1 more week of data. Final score was predicted in a holdout test sample, which was then categorized into Success or Failure (failure defined as the absence of both remitter and responder status). Classification analyses with Balanced Accuracy and 95% Confidence intervals was then compared to predefined benchmarks.Benchmark 1 (better than chance) was reached 1 week into all treatments. Social anxiety disorder reached Benchmark 2 (65%) at week 5, whereas Depression and Panic Disorder reached it at week 6.For depression, social anxiety and panic disorder, prediction with only patient-rated symptom scores can detect treatment failure 6 weeks into ICBT, with enough accuracy for a clinician to take action. Early identification of failing treatment attempts may be a viable way to increase the overall success rate of existing psychological treatments by providing extra clinical resources to at-risk patients, within a so-called Adaptive Treatment Strategy. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Background A range of factors can reduce the effectiveness of treatment prescribed for the long-term management of chronic health conditions, such as growth disorders. In particular, prescription medications may not achieve the positive outcomes expected because approximately half of patients adhere poorly to the prescribed treatment regimen. Methods Adherence to treatment has previously been assessed using relatively unreliable subjective methods, such as patient self-reporting during clinical follow-up, or counting prescriptions filled or vials returned by patients. Here, we report on a new approach, the use of electronically recorded objective evidence of date, time, and dose taken which was obtained through a comprehensive eHealth ecosystem, based around the easypod™ electromechanical auto-injection device and web-based connect software. The benefits of this eHealth approach are also illustrated here by two case studies, selected from the Finnish cohort of the easypod™ Connect Observational Study (ECOS), a 5-year, open-label, observational study that enrolled children from 24 countries who were being treated with growth hormone (GH) via the auto-injection device. Results Analyses of data from 9314 records from the easypod™ connect database showed that, at each time point studied, a significantly greater proportion of female patients had high adherence (≥ 85%) than male patients (2849/3867 [74%] vs 3879/5447 [71%]; P P Conclusions The data and case studies presented herein illustrate the importance of adherence to GH therapy and how good growth outcomes can be achieved by following treatment as described. They also show how the device, software, and database ecosystem can complement normal clinical follow-up by providing HCPs with reliable information about patient adherence between visits and also providing researchers with real-world evidence of adherence and growth outcomes across a large population of patients with growth disorders treated with GH via the easypod™ device.

ObjectiveTo investigate whether aging differentially affects neural activity serving visuospatial processing in a large functional neuroimaging study of HIV-infected participants and to determine whether such aging effects are attributable to differences in the duration of HIV infection.MethodsA total of 170 participants, including 93 uninfected controls and 77 HIV-infected participants, underwent neuropsychological assessment followed by neuroimaging with magnetoencephalography (MEG). Time-frequency analysis of the MEG data followed by advanced image reconstruction of neural oscillatory activity and whole-brain statistical analyses were used to examine interactions between age, HIV infection, and cognitive status. Post hoc testing for a mediation effect of HIV infection duration on the relationship between age and neural activity was performed using a quasi-Bayesian approximation for significance testing.ResultsCognitively impaired HIV-infected participants were distinguished from unimpaired HIV-infected and control participants by their unique association between age and gamma oscillations in the parieto-occipital cortex. This relationship between age and gamma was fully mediated by the duration of HIV infection in cognitively impaired participants. Impaired HIV-infected participants were also distinguished by their atypical relationship between alpha oscillations and age in the superior parietal cortex.ConclusionsImpaired HIV-infected participants exhibited markedly different relationships between age and neural responses in the parieto-occipital cortices relative to their peers. This suggests a differential effect of chronological aging on the neural bases of visuospatial processing in a cognitively impaired subset of HIV-infected adults. Some of these relationships were fully accounted for by differences in HIV infection duration, whereas others were more readily associated with aging.

BackgroundStudies on the individual gender-specific risk and familial co-aggregation of suicidal behaviour in autism spectrum disorder (ASD) are lacking.MethodsWe conducted a matched case-cohort study applying conditional logistic regression models on 54 168 individuals recorded in 1987–2013 with ASD in Swedish national registers: ASD without ID n = 43 570 (out of which n = 19035, 43.69% with ADHD); ASD + ID n = 10 598 (out of which n = 2894 individuals, 27.31% with ADHD), and 270 840 controls, as well as 347 155 relatives of individuals with ASD and 1 735 775 control relatives.ResultsThe risk for suicidal behaviours [reported as odds ratio OR (95% confidence interval CI)] was most increased in the ASD without ID group with comorbid ADHD [suicide attempt 7.25 (6.79–7.73); most severe attempts i.e. requiring inpatient stay 12.37 (11.33–13.52); suicide 13.09 (8.54–20.08)]. The risk was also increased in ASD + ID group [all suicide attempts 2.60 (2.31–2.92); inpatient only 3.45 (2.96–4.02); suicide 2.31 (1.16–4.57)]. Females with ASD without ID had generally higher risk for suicidal behaviours than males, while both genders had highest risk in the case of comorbid ADHD [females, suicide attempts 10.27 (9.27–11.37); inpatient only 13.42 (11.87–15.18); suicide 14.26 (6.03–33.72); males, suicide attempts 5.55 (5.10–6.05); inpatient only 11.33 (9.98–12.86); suicide 12.72 (7.77–20.82)]. Adjustment for psychiatric comorbidity attenuated the risk estimates. In comparison to controls, relatives of individuals with ASD also had an increased risk of suicidal behaviour.ConclusionsClinicians treating patients with ASD should be vigilant for suicidal behaviour and consider treatment of psychiatric comorbidity.

The aim of the study was to investigate whether the use of dating apps is a risk factor for acquiring Chlamydia trachomatis (CT) infections.Patients attending the drop-in facility at the STI clinic at Umeå University Hospital between April 2016 and November 2017 were asked to fill in a survey about their sexual preferences and behaviors, including dating app use.Of 943 participants, 80 (8.5%) received a CT diagnosis (34 women and 46 men). Dating app users did not seem to have an increased risk of CT infection. Having 3 or more sex partners within the last year was a risk factor for CT only among those not using a dating app. Alcohol use before sex and unprotected sex with a new partner were risk factors for CT infection in the univariate but not in the multivariate analysis.Dating app users did not seem to have an increased risk of acquiring CT and for dating app users the seemingly well-established risk factor of having many partners was not valid.