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Advances in cytotoxic chemotherapy, surgical oncology, genomic medicine, targeted small molecule treatment, cancer immunotherapy and biology-driven precision radiation oncology have resulted in significant improvements in outcomes of cancer treatment, with an increasing number of patients achieving long-term disease control or even being potentially cured. Concurrent advances in palliative care and geriatric oncology have also helped to ensure that patients are managed holistically by considering their physical, social, psychological and emotional needs in a personalised manner.

To better assess and reduce suicidal risk in first-episode psychosis (FEP), we aimed to investigate the evolution of suicidal thoughts and behaviors (STBs) and associated factors in FEP.This systematic review (PROSPERO-CRD42020168050) meets PRISMA guidelines. PubMed, Medline, PsycINFO, Embase, EBM Reviews and references lists of relevant articles were searched (February 2020) to identify longitudinal studies, published in English or in French, that assessed the prevalence of STBs at entry to services and over follow-up, and examined factors associated with STBs among all persons with affective and non-affective FEP from a defined catchment area. Screening, data extraction and quality assessment using the adapted Newcastle Ottawa Scale were done independently by two reviewers. Results on prevalence and associated factors are presented by type of STB.Of 3,177 references, 17 studies of 11 non-overlapping samples (n = 14,907) with varying lengths of follow-up (1-41.7 years) were included. The prevalence of STBs decreased over follow-up. Up to 21.6% made at least one suicide attempt, 27% had suicidal ideation, and 1-4.3% died by suicide during follow-up. Of 53 factors assessed across studies, only male sex, depressive symptoms, and STBs occurring early during follow-up were associated with subsequent STBs. Early intervention for psychosis decreased STBs in the first three years. Other factors were assessed in a single study, yielded conflicting results, or were not associated with STBs.The high prevalence of STBs following onset of psychosis highlights the need for early detection and intervention and ongoing assessment of suicidal risk throughout follow-up, with attention to identified risk factors. The heterogeneity of the studies precluded a meta-analysis and several factors were each assessed by a single study. Additional well-designed longitudinal studies of STBs and associated factors are warranted.

Patient: Female, 55-year-old Final Diagnosis: Diffuse pulmonary meningotheliomatosis (DPM) Symptoms: Chest discomfort • dry cough Medication: — Clinical Procedure: — Specialty: Pulmonology Objective: Rare disease Background: Diffuse pulmonary meningotheliomatosis (DPM) is an exceedingly rare diffuse pulmonary disease with a female predominance. It is characterized by the presence of widespread bilateral minute pulmonary meningothelial-like nodules (MPMNs) on chest imaging. Patients are generally asymptomatic or may present with nonspecific symptoms such as dyspnea. The nodules are typically detected incidentally on imaging for other indications. Here, we present a rare case of DPM in a 55-year-old woman. Case Report: A 55-year-old woman presented to the clinic with non-exertional chest pressure and dry cough of 4-month duration. She had a history of hypertension, hypercholesterolemia, hypothyroidism, gastroesophageal reflux disease, and impaired fasting blood glucose and was a lifelong nonsmoker. Physical examination was unre-markable. High-resolution chest computed tomography (CT) showed innumerable diffuse small ground-glass nodules. An extensive laboratory workup was negative for autoimmune and infectious etiologies. The patient underwent uncomplicated right video-assisted thoracoscopic surgery, and lung biopsy showed multiple well-circumscribed interstitial meningothelial-like nodules in perivenular distribution with occasional whorling of cells. The diagnosis of diffuse pulmonary meningotheliomatosis (DPM) was confirmed. The patient continued to complain of non-exertional chest pressure without pulmonary complaints, and a repeat chest CT showed stable findings 1 year after the diagnosis. Conclusions: DPM should be considered in the differential diagnosis for patients presenting with diffuse bilateral pulmonary nodules. Patients are typically asymptomatic and it is most commonly detected incidentally. Further research is needed to better understand this disease and its clinical significance.

Shared decision making (SDM) is the process by which health care providers and patients collaborate to make health care decisions. This collaboration leads to informed decision making and improved outcomes. However, research on SDM specific to the field of youth mental health is scarce. ACCESS Open Minds (ACCESS OM) is a youth mental health research and evaluation project that implemented and evaluated SDM practices within its various activities and operations. The ACCESS OM network spans a diversity of youth mental health settings across Canada, and includes various stakeholders such as youth, family members and carers, clinicians, researchers, and policy makers. The project values all types of knowledge (specifically, experiential, cultural, clinical, and scientific knowledge) as necessary to lead to better health research, care delivery, and outcomes for patients and their communities. Similarly, it acknowledges the lived experience of patients and, family and carers as expertise. Through the integration of SDM practices, ACCESS OM has formulated valuable insights that can be applied to other health problems and settings. This paper, written by youth and family council members, operational staff, and researchers from the project, will share challenges and solutions that arose in the integration of SDM practices within ACCESS OM’s knowledge translation strategy, governance structures, clinical contexts, and capacity-building initiatives. Video abstract Shared Decision Making in a Youth Mental Health Service Design and Research Project: Insights From the Pan-Canadian ACCESS Open Minds Network (MP4 234838 kb) Electronic supplementary material The online version of this article (10.1007/s40271-020-00444-5) contains supplementary material, which is available to authorized users., Plain Language Summary This paper describes how ACCESS Open Minds (ACCESS OM) uses shared decision making (SDM) strategies. ACCESS OM is a pan-Canadian youth mental health project, which is improving youth mental health services across Canada. Often, health care systems are not set up to prioritize patients’ expertise when it comes to decisions about care and services. SDM means that patients, service providers, and other relevant individuals collaborate to make decisions about health care. SDM strategies are important in how ACCESS OM is working to improve youth mental health services. This paper provides examples of how the ACCESS OM project has implemented SDM processes, and discusses challenges encountered in this regard, with the aim of helping other projects and organizations implement SDM strategies. Electronic supplementary material The online version of this article (10.1007/s40271-020-00444-5) contains supplementary material, which is available to authorized users.

Cost-effectiveness studies of early intervention services (EIS) for psychosis have not included extension beyond the first 2 years. We sought to evaluate the cost-effectiveness of a 3-year extension of EIS compared to regular care (RC) from the public health care payer’s perspective. Following 2 years of EIS in a university setting in Montreal, Canada, patients were randomized to a 3-year extension of EIS (n = 110) or RC (n = 110). Months of total symptom remission served as the main outcome measure. Resource use and cost data for publicly covered health care services were derived mostly from administrative systems. The incremental cost-effectiveness ratio (ICER) and cost-effectiveness acceptability curve were produced. Relative cost-effectiveness was estimated for those with duration of untreated psychosis (DUP) of 12 weeks or less vs longer. Extended early intervention had higher costs for psychiatrist and nonphysician interventions, but total costs were not significantly different. The ICER was $1627 per month in total remission. For the intervention to have an 80% chance of being cost-effective, the decision-maker needs to be willing to pay $5942 per month of total symptom remission. DUP ≤ 12 weeks was associated with a reduction in costs of $12 276 even if no value is placed on additional months in total remission. Extending EIS for psychosis for people, such as those included in this study, may be cost-effective if the decision-maker is willing to pay a high price for additional months of total symptom remission, though one commensurate with currently funded interventions. Cost-effectiveness was much greater for people with DUP ≤12 weeks.

Background: Several clinical studies have implicated nicotine in reducing cough reflex sensitivity in both healthy smoking and non-smoking subjects. Bradanicline, a highly selective α7 nicotinic acetylcholine receptor (nAChR) agonist, may therefore be effective for refractory chronic cough (RCC), possibly through sensory gating in the central nervous systems. Rationale: To evaluate the efficacy of bradanicline in RCC patients. Methods: This randomized, double-blinded, placebo-controlled, crossover study recruited 46 RCC patients (39 females, mean age 63 years, median cough duration 18 years) from November 2018 to February 2019. Patients were allocated to bradanicline-placebo or placebo-bradanicline, 1:1 ratio, after screening for a minimum ≥10 coughs/hr. Following an initial loading dose (50mg bradanicline or matched placebo), study treatment was escalated weekly from 25mg to 75mg, and then 150mg or a matched placebo regimen for a total of 3 weeks of treatment. After a 14-day washout, patients were crossed over. Cough frequency was monitored for 24 hours (VitaloJAK). The primary endpoint was the relationship between bradanicline dose and awake cough frequency (ACF). Results: All but one patient completed the study and 409/414 cough recordings were available for analysis. Mean ACF at baseline was 36.4 (SD 29.3) coughs/hour. Neither bradanicline nor placebo reduced ACF, with no meaningful difference between the two treatments. Patient reported outcomes also showed no treatment effects. The frequency of adverse effects was similar for bradanicline (n = 16) and placebo (n = 17). Conclusions: Despite good tolerability, escalating doses of bradanicline did not reduce awake cough frequency in RCC patients compared with placebo.

Objective Early life adversity is suspected to play an important role for onset and course of psychosis, but its relationship with longer-term clinical outcome is not entirely clear. In this longitudinal study, we investigated the impact of childhood trauma (CT) on positive and negative symptom remission in first episode psychosis (FEP) patients over two years. Methods A total of 210 FEP patients were assessed with the Childhood Trauma Questionnaire. Patients reporting moderate to severe trauma (CT; N = 114; 54.3%) were compared to those without trauma (N-CT; N = 96; 45.7%). Positive (PSR) and negative symptom remission (NSR) were determined monthly over 24 months following established criteria using the Scale for Assessment of Positive Symptoms and the Scale for Assessment of Negative Symptoms. Global Functioning was evaluated at baseline and 24 months of follow-up. Results Compared to N-CT patients, CT patients had achieved significantly lower rates of PSR at 12 months and significantly lower rates of NSR at 24 months. A dose-response relationship was observed between the number of trauma categories fulfilled and the number of patients not achieving PSR and NSR at these time points. Higher trauma scores were significantly associated with poor functioning and higher positive and negative symptom severity at 24 months, but not at baseline and 12 months of follow-up. Conclusion Differential effects of CT on clinical outcome may not be apparent at psychosis onset, but only become evident through poor symptomatic remission and general functioning over time. Targeted diagnostic and therapeutic efforts after illness onset might limit these detrimental consequences.

International audience; Schizophrenia is an illness characterized by positive symptoms, negative symptoms, and cognitive impairments. Cognitive impairments occur before the onset of psychosis and could reflect glutamatergic dysregulation. Thus, identifying associations between genetic variations in genes coding for glutamatergic receptors and cognitive impairment in schizophrenia may help in understanding the basis of these deficits and in identifying potential drug targets. In a discovery cohort of 144 first-episode of psychosis patients (FEP), we genotyped 58 candidate Single Nucleotide Polymorphisms (SNPs) located in NMDA and metabotropic glutamatergic receptors. These SNPs were selected according to the results from the Psychiatric Genomic Consortium and were tested for association with intellectual quotient (IQ) as assessed with the Wechsler Intelligence Scales. For replication, we used the ICAAR cohort including 121 ultra-high-risk patients (UHR) with the same cognitive assessment. A polymorphism located in GRM7, rs1396409, was significantly associated with performance IQ in the discovery cohort of FEP. This association was replicated in the UHR cohort. This polymorphism is also associated with total IQ and verbal IQ in the merged dataset, with a predominant effect on the arithmetic subtest. The rs1396409 polymorphism is significantly associated with cognitive impairment during the onset of psychosis. This genetic association highlights the possible impact of glutamatergic genes in cognitive deficits in the early phases of psychosis and enforces the interest for new therapeutic interventions targeting the glutamatergic pathway.

Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is a rare multisystem vascular disorder that causes chronic gastrointestinal bleeding, epistaxis, and severe anemia. Bevacizumab, an anti-vascular endothelial growth factor antibody, may be effective to treat bleeding in HHT. This international, multicenter, retrospective study evaluated the use of systemic bevacizumab to treat HHTassociated bleeding and anemia at 12 HHT treatment centers. Hemoglobin, Epistaxis Severity Score (ESS), red cell units transfused, and intravenous iron infusions before and after treatment were evaluated using paired means testing and mixed-effects linear models. Bevacizumab was given to 238 HHT patients for a median of 12 (range, 1-96) months. Compared with pretreatment, bevacizumab increased mean hemoglobin by 3.2 g/dL (95% confidence interval: 2.9-3.5 g/dL); i.e., from a mean hemoglobin of 8.6 (8.5-8.8) g/dL to 11.8 (11.5-12.1) g/dL; P

AIM We investigated whether individuals varied in their satisfaction with being randomized to an extension of early intervention (EI) for psychosis or regular care after 2 years of EI, and whether satisfaction was associated with service engagement 3 years later. METHODS Following randomization, patients (N = 220) indicated if they were happy with, unhappy or indifferent to their group assignment. Follow-up with service providers was recorded monthly. RESULTS Patients randomized to extended EI were more likely to express satisfaction with their group assignment than those in the regular care group (88.2% vs 31.5%, χ2 = 49.96, P

Objectives: Views on who bears how much responsibility for supporting individuals with mental health problems may vary across stakeholders (patients, families, clinicians) and cultures. Perceptions about responsibility may influence the extent to which stakeholders get involved in treatment. Our objective was to report on the development, psychometric properties and usability of a first-ever tool of this construct. Methods: We created a visual weighting disk called ‘ShareDisk’, measuring perceived extent of responsibility for supporting persons with mental health problems. It was administered (twice, 2 weeks apart) to patients, family members and clinicians in Chennai, India ( N = 30, 30 and 15, respectively) and Montreal, Canada ( N = 30, 32 and 15, respectively). Feedback regarding its usability was also collected. Results: The English, French and Tamil versions of the ShareDisk demonstrated high test–retest reliability ( rs = .69–.98) and were deemed easy to understand and use. Conclusion: The ShareDisk is a promising measure of a hitherto unmeasured construct that is easily deployable in settings varying in language and literacy levels. Its clinical utility lies in clarifying stakeholder roles. It can help researchers investigate how stakeholders’ roles are perceived and how these perceptions may be shaped by and shape the organization and experience of healthcare across settings.

Background:\ud India has a large youth population whose mental health needs must be addressed. This includes promotion of positive mental health, with early detection and effective intervention for mental health disorders. Understanding the perspectives of community stakeholders working with youth is pivotal to this effort. Current study aimed to bring together a group of community stakeholders (eg, parents, teachers, policy makers) to understand their perspectives on youth mental health problems, challenges in provision of care, and to provide recommendations to address these concerns at national level.\ud \ud Materials and methods:\ud The study was conducted across two sites in India: Chennai and New Delhi. Three group meetings were conducted involving 52 participants, including governmental, non‐governmental and community representatives working with youth. The proceedings were manually recorded, transcribed, and analyzed using thematic analysis method.\ud \ud Results:\ud Many youth mental health problems were similar across the two sites. The commonest drivers of mental health problems were reported to be academic pressure, substance use and problematic internet/social media use. Stigma and lack of awareness were identified as the most important challenges acting as barriers to seeking mental health help by youth. Prioritizing youth mental health as a national programmes along with strong political will were the major recommendations suggested by the stakeholders.\ud \ud Conclusion:\ud Initial findings suggest that prioritizing youth mental health programmes in India would be advantageous. Inclusive and collaborative approach, involving community stakeholders working with youth in providing services that promote mental health and early access to care will help in developing healthy young citizens.

A novel approach for phenotype prediction is developed for mass spectrometric data. First, the data-independent acquisition (DIA) mass spectrometric data is converted into a novel file format called “DIA tensor” (DIAT) which contains all the peptide precursors and fragments information and can be used for convenient DIA visualization. The DIAT format is fed directly into a deep neural network to predict phenotypes without the need to identify peptides or proteins. We applied this strategy to a collection of 102 hepatocellular carcinoma samples and achieved an accuracy of 96.8% in classifying malignant from benign samples. We further applied refined model to 492 samples of thyroid nodules to predict thyroid cancer; and achieved a predictive accuracy of 91.7% in an independent cohort of 216 test samples. In conclusion, DIA tensor enables facile 2D visualization of DIA proteomics data as well as being a new approach for phenotype prediction directly from DIA-MS data.

BackgroundSystems transformation for health promotion, involving engagement from multiple disciplines and levels of influence, requires an investment in partnership development. Integrated youth service is a collaborative model that brings organisations together to provide holistic care for youth. Frayme is an international knowledge translation network designed to support the uptake and scaling of integrated youth service. Social network analysis (SNA) is the study of relationships among social units and is useful to better understand how partners collaborate within a network to achieve major objectives. The purpose of this paper is to apply SNA to the Frayme network in order to (1) examine the level and strength of partnerships, (2) identify the strategies being employed to promote the main objectives and (3) apply the findings to current research in youth mental health and system transformation.MethodsThe PARTNER tool includes a validated survey and analysis software designed to examine partner interconnections. This tool was used to perform the SNA and 51 of the 75 partners completed the survey (14 researchers, 2 advisory groups and 35 organisations). A network map was created and descriptive frequencies were calculated.ResultsThe overall network scores for the Frayme network were 20.6% for density, 81.5% for centralisation and 71.7% for overall trust. The Frayme secretariat received a 3.84 out of a possible 4 for value. In addition, the youth and family advisories each received a value score of 4 and all Leadership Team organisations received a score of 2.97 or above.ConclusionsThe Frayme secretariat links many partners who would otherwise be disconnected and acts as a significant conduit for novel information. Frayme may have the opportunity to enhance value perceptions among broader network members by profiling individual organisations and the potential leveraging opportunities that might exist through their work. These findings increase understanding with respect to the mechanisms of network development and will be helpful to inform partnership development in the future. In addition, they contribute to the literature with respect to knowledge translation practice as well as the scaling of collaborative interventions within youth mental health.

© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: The Lancet Commission on Global Surgery established the Three Delays framework, categorising delays in accessing timely surgical care into delays in seeking care (First Delay), reaching care (Second Delay), and receiving care (Third Delay). Globally, knowledge gaps regarding delays for fracture care, and the lack of large prospective studies informed the rationale for our international observational study. We investigated delays in hospital admission as a surrogate for accessing timely fracture care and explored factors associated with delayed hospital admission. Methods: In this prospective observational substudy of the ongoing International Orthopaedic Multicenter Study in Fracture Care (INORMUS), we enrolled patients with fracture across 49 hospitals in 18 low-income and middle-income countries, categorised into the regions of China, Africa, India, south and east Asia, and Latin America. Eligible patients were aged 18 years or older and had been admitted to a hospital within 3 months of sustaining an orthopaedic trauma. We collected demographic injury data and time to hospital admission. Our primary outcome was the number of patients with open and closed fractures who were delayed in their admission to a treating hospital. Delays for patients with open fractures were defined as being more than 2 h from the time of injury (in accordance with the Lancet Commission on Global Surgery) and for those with closed fractures as being a delay of more than 24 h. Secondary outcomes were reasons for delay for all patients with either open or closed fractures who were delayed for more than 24 h. We did logistic regression analyses to identify risk factors of delays of more than 2 h in patients with open fractures and delays of more than 24 h in patients with closed fractures. Logistic regressions were adjusted for region, age, employment, urban living, health insurance, interfacility referral, method of transportation, number of fractures, mechanism of injury, and fracture location. We further calculated adjusted relative risk (RR) from adjusted odds ratios, adjusted for the same variables. This study was registered with ClinicalTrials.gov, NCT02150980, and is ongoing. Findings: Between April 3, 2014, and May 10, 2019, we enrolled 31 255 patients with fractures, with a median age of 45 years (IQR 31–62), of whom 19 937 (63·8%) were men, and 14 524 (46·5%) had lower limb fractures, making them the most common fractures. Of 5256 patients with open fractures, 3778 (71·9%) were not admitted to hospital within 2 h. Of 25 999 patients with closed fractures, 7141 (27·5%) were delayed by more than 24 h. Of all regions, Latin America had the greatest proportions of patients with delays (173 [88·7%] of 195 patients with open fractures; 426 [44·7%] of 952 with closed fractures). Among patients delayed by more than 24 h, the most common reason for delays were interfacility referrals (3755 [47·7%] of 7875) and Third Delays (cumulatively interfacility referral and delay in emergency department: 3974 [50·5%]), while Second Delays (delays in reaching care) were the least common (423 [5·4%]). Compared with other methods of transportation (eg, walking, rickshaw), ambulances led to delay in transporting patients with open fractures to a treating hospital (adjusted RR 0·66, 99% CI 0·46–0·93). Compared with patients with closed lower limb fractures, patients with closed spine (adjusted RR 2·47, 99% CI 2·17–2·81) and pelvic (1·35, 1·10–1·66) fractures were most likely to have delays of more than 24 h before admission to hospital. Interpretation: In low-income and middle-income countries, timely hospital admission remains largely inaccessible, especially among patients with open fractures. Reducing hospital-based delays in receiving care, and, in particular, improving interfacility referral systems are the most substantial tools for reducing delays in admissions to hospital. Funding: National Health and Medical Research Council of Australia, Canadian Institutes of Health Research, McMaster Surgical Associates, and Hamilton Health Sciences.

To determine the efficacy of IL-5 inhibitory therapy in severe, refractory asthma in a real-world clinical setting from a tertiary referral center.A retrospective chart review of patients with severe asthma treated with IL-5 biologic therapy for ≥ 6 months at Mayo Clinic in Rochester, Minnesota between January 1, 2013 and August 31, 2019.Over the study period, we identified 63 patients with a mean age of 54 who received an IL-5 inhibitor for ≥ 6 months. A total of 55 patients received mepolizumab, 2 received benralizumab, and 9 patients received both. Patients were followed up for a mean of 25 months. The mean number of months of oral prednisone use prior to biologic initiation was 64. There was a significant reduction in the median dose of prednisone in the 24 months after drug initiation (15 mg vs. 0 mg; p = 0.0001). Similarly; there was a significant decline in the median number of asthma exacerbations in the 24 months before and after drug initiation (7 vs. 2; p = 0.0001). The mean number of emergency room (ER) visits and hospitalizations decreased from 5.1 and 2.0 to 1.6 and 0.4 in the 24 months before and after therapy initiation (p 0.0001 and p = 0.007, respectively) CONCLUSIONS: IL-5 inhibitory therapy is associated with significant and long-term sustained reductions in asthma exacerbation frequency, ER visits, hospitalizations, as well as oral steroid usage in a patient population with refractory steroid-dependent asthma referred to a tertiary referral center.

Background: Cognitive difficulties are a core deficit for people with schizophrenia and are generally assessed with neuropsychological tests. Self-report assessments are also useful in understanding difficulties from the service user’s perspective. This study aims to introduce and test the shorter version of the Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS) to improve its acceptability and comprehensibility. Methods: In consultation with service users and clinicians, we identified items from the original 21-item SSTICS that were found difficult and these were excluded. The reduced scale was explored with Confirmatory Factor Analysis (CFA) in two independent samples in the UK and Canada. Convergent validity with symptoms and IQ was assessed and compared between the original and the reduced scale. Results: Six-hundred and seven people with schizophrenia and first-episode psychosis took part in this study. Seven items were removed to produce the SSTICS-Brief. This had good reliability and the CFA confirmed a unidimensional structure. Convergent validity with symptoms and IQ were optimal between the long and short versions. Conclusions: The SSTICS-B has better acceptability than its longer form and could be administered in less time. The resulting measure is likely to be a valuable short self-assessment of cognitive complaints for people with schizophrenia.

Aim Over the past two decades, the youth mental health field has expanded and advanced considerably. Yet, mental disorders continue to disproportionately affect adolescents and young adults. Their prevalence and associated morbidity and mortality in young people have not substantially reduced, with high levels of unmet need and poor access to evidence‐based treatments even in high‐income countries. Despite the potential return on investment, youth mental disorders receive insufficient funding. Motivated by these continual disparities, we propose a strategic agenda for youth mental health research. Method Youth mental health experts and funders convened to develop youth mental health research priorities, via thematic roundtable discussions, that address critical evidence‐based gaps. Results Twenty‐one global youth mental health research priorities were developed, including population health, neuroscience, clinical staging, novel interventions, technology, socio‐cultural factors, service delivery, translation and implementation. Conclusions These priorities will focus attention on, and provide a basis for, a systematic and collaborative strategy to globally improve youth mental health outcomes.

Worldwide, growing concern with young people’s mental health is spurring service reform efforts. Such reform requires a full understanding of the experiences of young people and their carers when seeking mental health help. To generate such an understanding, we conducted a meta-synthesis of qualitative literature on the perspectives of youths and their carers on navigating mental health systems. Five electronic databases were searched (Medline, PsycINFO, EMBASE, CINAHL, HealthSTAR). Studies were included if they explored the experiences of pathways to mental health services of persons aged 11–30 years and/or their carers; were published in English or French; and used qualitative methodology. Quality appraisal was conducted using the CASP tool. The synthesis of 31 included studies yielded three themes—initiating contact with mental health services; characteristics of services’ response; and youths’ and carers’ appraisal of services. Themes about initiating contact included mental health literacy, structural barriers, and social support. Service response-related themes included complex pathways, waitlists, eligibility, and fragmented care. In terms of service appraisal, positive encounters featured providers who were accessible and perceived as caring. Negative appraisals resulted from feeling misunderstood and excluded and being ill-informed about treatment. Across diagnoses and settings, youths and carers had difficult experiences accessing mental healthcare. While individual, social, and healthcare factors shaping pathways to care varied, systemic complexities were a common inhibitor. This synthesis informs recommendations for improving mental health services and youths’ pathways to them. It underlines the need for grounding reform in youths’ and carers’ perspectives and needs.

Background While chemotherapeutic agents result in an improvement in both disease-free and overall survival in cancer patients, treatment can result in short and long-term complications. One well-known complication is neuropathy which can result from a number of chemotherapeutic agents. However, chemotherapy-induced phrenic neuropathy is an exceedingly rare phenomenon with few cases reported in the literature. Case A 34-year-old male with metastatic testicular cancer presented with progressive dyspnea on exertion after initiation of chemotherapy with bleomycin, cisplatin, and etoposide. Multiple diagnostic studies were performed including pulmonary function testing, chest computed tomography, fluoroscopic sniff evaluation, in addition to phrenic nerve electromyography. Based on results of these tests, the diagnosis of chemotherapy-induced phrenic neuropathy was made. Conclusion Chemotherapy-induced phrenic neuropathy, although rare, should be considered as a cause of dyspnea in cancer patients following initiation of chemotherapy.

The influence of culture is inextricably entwined with the experience and interpretation of psychotic symptoms. This chapter will orient clinicians to the wide array of issues at the intersection of culture, clinical practice, and psychosis, including how culture shapes the onset, meaning, course, and outcome of psychotic illness and influences systems of care; the challenges and practical strategies/tips for working with cultural diversity in patients with psychosis; and the importance of fostering cultural competence in clinicians. Strengths and weaknesses of culturally adapted and/or translated assessments and treatments for psychotic symptoms will be discussed. Different approaches to help clinicians develop a cultural formulation will be reviewed, with particular emphasis on DSM 5’s Outline for Cultural Formulation (OCF)—a framework designed to assist clinicians to understand cultural issues during diagnostic assessment.

Introduction Discontinuation of the initial oral antipsychotic prescribed for a first episode of psychosis (FEP) can derail outcome. Our objective was to examine the rate of and time to all-cause discontinuation of the first antipsychotic prescribed and the factors influencing such discontinuation. Methods In a sample of 390 FEP patients, we estimated the rate of and time to discontinuation of the initial antipsychotic over a one-year period. The effects of a number of putative predictors of discontinuation were estimated using regression analyses. Results Rate of discontinuation of the first antipsychotic was 72%, with no difference between the 3 investigated antipsychotics (olanzapine (73%), risperidone (68%) and aripiprazole (75%)), (χ2 (2) = 1.89, p = 0.388). Mean time to discontinuation was 7.2 (4.6) months and was not different among the three antipsychotics (Log-rank χ2 (2) = 0.257, p = 0.879). Binary logistic regression showed that higher positive and negative symptoms remission and baseline functioning were associated with lower rates of discontinuation (Nagelkerke R2 = 0.36, χ2 (10) = 66.9, p Conclusion Discontinuation of the initial antipsychotic is a major concern in the course of treating FEP. Symptom relief, better functioning and lower side effects appear to be the major factors associated with continuing an antipsychotic medication.

Objective To assess the reliability and validity of six patient-reported outcomes (PRO) instruments for evaluating health-related quality of life in adults with mild-severe hemophilia B and caregivers of children with hemophilia B, including affected women/girls. Methods Adults with hemophilia B and caregivers completed separate online surveys containing several PRO instruments, which were administered to adult participants only (EQ-5D-5L, Brief Pain Inventory v2 Short Form, Hemophilia Activities List, and International Physical Activities Questionnaire), both adults and caregivers (Patient Health Questionnaire [PHQ-9]), or caregivers only (Generalized Anxiety Disorder 7-Item [GAD-7] scale). Construct validity and item-total correlation were assessed using Pearson product-moment correlation, internal consistency was assessed using Cronbach's alpha coefficient, and known-group validity was assessed by comparisons to self-reported characteristics based on the Kruskal-Wallis test. Results Patient-reported outcomes instruments generally showed satisfactory reliability for adults (n = 299) and caregivers (n = 150). In adults, PRO instruments generally showed high construct validity. Most PRO instruments showed expected significant differences among known groups for adults and caregivers. PHQ-9 and GAD-7 did not show significant differences among caregiver age groups. Conclusions Patient-reported outcomes instruments administered in B-HERO-S demonstrated reliability and validity in the broader population of adults with hemophilia B and caregivers when including all severities and genders.

Neeraj N Iyer,1 Nicholas J Vendetti,2 Daniel I Levy,3 Jack Mardekian,4 Marko A Mychaskiw,2 Joseph Thomas III1 1Regenstrief Center for Healthcare Engineering and Center for Health Outcomes Research and Policy, College of Pharmacy, Purdue University, West Lafayette, IN, USA; 2Outcomes and Evidence, Pfizer Inc., Collegeville, PA, USA; 3Rare Disease Group, Global Product Development, Pfizer Inc., Collegeville, PA, USA; 4Biostatistics, Global Product Development, Pfizer Inc., Collegeville, PA, USA Purpose: Incremental health care resource utilization and expenditures associated with autosomal dominant polycystic kidney disease (ADPKD) were estimated. Methods: Study data were from a large administrative claims database. Individuals aged 18 years or older enrolled in tracked health plans for 12 months from April 1, 2011 through March 31, 2012, and with an International Classification of Disease, Ninth Revision, Clinical Modification diagnosis code for “polycystic kidney, autosomal dominant” (753.13) or for “polycystic kidney, unspecified type” (753.12) were identified as having ADPKD, and linked one-to-one with individuals without ADPKD based on age and gender. Zero-inflated negative binomial models estimated incremental health care resource utilization and expenditures, adjusting for risk factors. Results: A total of 3,844 individuals with ADPKD who satisfied selection criteria were linked one-to-one with 3,844 individuals without ADPKD. Multivariate, regression models adjusting for risk factors revealed incremental mean (standard error) resource use associated with ADPKD of 0.68 (0.090) hospital days, equal to 68 additional hospital days per 100 ADPKD patients, and 6.9 (0.28) outpatient visits, equal to 690 additional visits per 100 ADPKD patients. Mean (standard error) incremental total expenditures associated with ADPKD were US$8,639 ($470). Mean incremental expenditures were largest for outpatient expenditures at US$4,918 ($198), followed by mean incremental hospital expenditures of US$2,603 ($263), and mean incremental medication expenditures of US$1,589 ($77). Based on sub-group analysis, mean incremental total expenditures were US$2,944 ($417) among ADPKD patients without end-stage renal disease and US$38,962 ($6,181) for those with end-stage renal disease. Conclusion: ADPKD was associated with considerable incremental health care resource utilization and expenditures. Significant illness burden was found even before patients reached end-stage renal disease. Keywords: ADPKD, economic impact, disease burden, health care resource use, health care costs

We carried out the first matched retrospective cohort study aimed at studying the safety and efficacy of extracorporeal photopheresis (ECP) for bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT). Medical records of 1325 consecutive adult patients who underwent HCT between 2005 and 2015 were reviewed. Seventy-four patients (median age, 51 years) with a diagnosis of BOS were included in the study. After propensity-score matching for BOS severity, 26 patients who underwent ≥3 months of ECP were matched to 26 non–ECP-treated patients, who were assigned an index date corresponding to the ECP start date for their matched pairs. The rate of decline in FEV1 percentage predicted (FEV1PP) decreased after ECP initiation (and after index date in the non-ECP group), with no significant difference between the 2 groups (P = .33). On a multivariable analysis that included baseline transplant and pulmonary function test variables, matched related donor HCT (HR, .1; 95% CI, .03 to .5; P = .002), ECP (HR, .1; 95% CI, .01 to .3; P = .001), and slower rate of decline in FEV1PP before the ECP/index date (HR, .7; 95% CI, .6 to .8; P = .001) were associated with a better overall survival. At last follow-up, non–ECP-treated patients were more likely to be on >5 mg daily dose of prednisone (54% versus 23%; P = .04) and had a greater decline in their Karnofsky performance score (mean difference, −9.5 versus −1.6; P = .06) compared with ECP-treated-patients. In conclusion, compared with other BOS-directed therapies, ECP was found to improve survival in HCT patients with BOS, without significantly impacting measured pulmonary functions. These findings need prospective validation in a larger patient cohort.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) provides a comprehensive review and guidance for clinicians managing patients with chronic obstructive pulmonary disease (COPD). However, adherence to GOLD guidelines has been suboptimal over the years. The current review summarizes the current body of literature addressing the multitude of reasons for the lack of adherence to GOLD guidelines in clinical practice.There continue to be several reasons for suboptimal adoption of GOLD guidelines in clinical practice. A primary and recurrent theme appears to be both delayed as well as missed diagnosis of COPD. There are several reasons for this including lack of awareness about current COPD guidelines, lack of availability as well as utilization of office spirometry and improper symptom assessment. Other issues include improper selection of proper pharmacotherapy options, misdiagnosis/mislabeling of COPD phenotypes, lack of smoking cessation counselling as well as enrollment in pulmonary rehabilitation. Potential solutions include adoption of clinical decision support systems, self-care models and careful phenotyping of COPD patients.There are currently several barriers for the adoption of GOLD guidelines into routine clinical practice. These barriers are all amenable to systematic solutions that will increase adherence to current GOLD guidelines.

Purpose While early access to appropriate care can minimise the sequelae of mental illnesses, little is known about how youths come to access mental healthcare. We therefore conducted a systematic review to synthesise literature on the pathways to care of youths across a range of mental health problems. Methods Studies were identified through searches of electronic databases (MEDLINE, PsycINFO, Embase, HealthSTAR and CINAHL), supplemented by backward and forward mapping and hand searching. We included studies on the pathways to mental healthcare of individuals aged 11–30 years. Two reviewers independently screened articles and extracted data. Results Forty-five studies from 26 countries met eligibility criteria. The majority of these studies were from settings that offered services for the early stages of psychosis, and others included inpatient and outpatient settings targeting wide-ranging mental health problems. Generally, youths’ pathways to mental healthcare were complex, involved diverse contacts, and, sometimes, undue treatment delays. Across contexts, family/carers, general practitioners and emergency rooms featured prominently in care pathways. There was little standardization in the measurement of pathways. Conclusions Except in psychosis, youths’ pathways to mental healthcare remain understudied. Pathways to care research may need to be reconceptualised to account for the often transient and overlapping nature of youth mental health presentations, and the possibility that what constitutes optimal care may vary. Despite these complexities, additional research, using standardized methodology, can yield a greater understanding of the help-seeking behaviours of youths and those acting on their behalf; service responses to help-seeking; and the determinants of pathways. This understanding is critical to inform ongoing initatives to transform youth mental healthcare. Electronic supplementary material The online version of this article (10.1007/s00127-018-1578-y) contains supplementary material, which is available to authorized users.

Background: The abnormally high incidence of disorders of glucose metabolism (DGM) in psychotic-spectrum disorders (PSD) has often been attributed to the side effects of antipsychotics and unhealthy lifestyles. The influence of social determinants of health has been largely ignored, despite ample evidence linking social adversity with both PSD and DGM. The aim of this study is to examine the influence of well-established social determinants of health on preclinical levels of glycated hemoglobin (HbA1c) in a sample of first-episode psychosis (FEP) patients. Methods: In a sample of newly admitted FEP patients, univariate analyses were used to select the main predictors of HbA1c levels from the following social determinants of health: childhood trauma, immigrant background, visible minority status, and indices of social and material deprivation. The predictors identified in the univariate analyses were tested in multivariate linear regression models including age, sex, BMI, depression, and physical anergia (proxy of sedentary behaviour) as covariates. Results: Univariate analyses identified visible minority status and childhood physical abuse as predictors of HbA1c. After controlling for covariates, minority status significantly predicted higher levels of glycated hemoglobin (β = 0.23; P = 0.01), and physical abuse had a marginally significant effect (β = 0.23; P = 0.06). Other predictors were not significantly associated. Conclusion: FEP patients from a visible minority or who were victims of childhood physical abuse have higher levels of HbA1c at admission compared with other patients. This might suggest an increase in risk for the development of future DGM. If confirmed, preventive strategies could be tailored for these groups.

Background: Weight-based dosing strategy for norepinephrine in septic shock patients with extremes of body mass index has been lesser studied. Methods: This historical study of adult septic shock patients was conducted from January 1, 2010, to December 31, 2015, at all intensive care units (ICUs) in Mayo Clinic, Rochester. Patients with documented body mass index were classified into underweight (body mass index 2), normal weight (18.5-24.9 kg/m2), and morbidly obese (≥40 kg/m2) patients. Patients with repeat ICU admissions, ICU stay 2 were excluded. The primary outcome was in-hospital mortality, and secondary outcomes included cumulative norepinephrine exposure acute kidney injury, cardiac arrhythmias, and 1-year mortality. Two-tailed P < .05 was considered statistically significant. Results: From 2010 to 2015, 2016 patients met inclusion—145, 1406, and 466 patients, respectively, in underweight, normal weight, and morbidly obese cohorts. Underweight patients used the highest peak dose and absolute exposure was greatest for morbidly obese patients. In-hospital mortality decreased with increasing log10 body mass index: 41.4% (underweight), 28.4% (normal weight), and 24.7% (morbidly obese), respectively ( P < .001); however, this relationship was not noted at 1 year. Unadjusted log10 norepinephrine cumulative exposure (mg) was associated with higher in-hospital mortality, acute kidney injury, cardiac arrhythmias, and 1-year mortality. After adjustment for demographics, body mass index, comorbidity, and illness severity, log10 norepinephrine exposure was an independent predictor of in-hospital mortality (odds ratio 2.4 [95% confidence interval, 2.0-2.8]; P < .001) and 1-year mortality (odds ratio 1.7 [95% confidence interval, 1.5-2.0]; P < .001). In a propensity-matched analysis of 1140 patients, log10 norepinephrine was an independent predictor of in-hospital mortality (odds ratio 2.2 [95% confidence interval, 1.8-2.6]; P < .001). Conclusions: Morbidly obese patients had lower in-hospital mortality but had higher 1-year mortality compared to normal weight and underweight patients. Cumulative norepinephrine exposure was highest in morbidly obese patients. Total norepinephrine exposure was an independent mortality predictor in septic shock.

We study the connections between one-sided Hopf algebras and one-sided quantum quasigroups, tracking the four possible invertibility conditions for the left and right composite morphisms that combi...

AIM This paper aims to describe the entry protocol of the Prevention and Early Intervention for Psychosis Program (PEPP)-Montreal, an early intervention program for psychosis. The protocol is designed to fulfil a key objective of the early intervention movement-reducing delays to accessing high-quality care. The paper also aims to describe how this rapid entry protocol can be deployed in other services interested in reducing delays in initiating treatment. METHODS PEPP provides rapid, easy access to quality care by placing a single, well-trained professional, the intake clinician, at the point of entry. Anyone can refer a youth directly and without formalities to the intake clinician who responds promptly and sensitively to all help-seeking, whether by a youth, a family member, a school counsellor or anyone acting on behalf of a youth in need. To promote accessibility, PEPP guarantees an initial assessment within 72 hours; maintains relationships with referral sources; and conducts awareness-enhancing outreach activities. RESULTS Since 2003, PEPP has received 1750 referrals, which have all been responded to within 72 hours. Families have been involved in the intake process in 60% of the cases and hospitalization may have been averted in over half of the referrals originating from emergency-room services. Another indicator of success is the very low turnover in the intake clinician's position. Overall, the PEPP model has succeeded in providing rapid, engaging, easy and youth-friendly access to high-quality care. CONCLUSION The success of this protocol at PEPP has inspired the entry protocols at other first-episode psychosis services. Its ability to provide rapid, engaging access to high-quality services may allow this protocol to become a model for other early intervention services for psychosis and other mental illnesses.

Introduction The National Health and Nutrition Examination Surveys show that many people with type 2 diabetes (T2D) in the USA fail to achieve recommended treatment targets. In the SUSTAIN 7 randomized controlled trial, once-weekly semaglutide (0.5 and 1.0 mg) was superior to comparative doses of dulaglutide (0.75 and 1.5 mg) in reducing glycated hemoglobin (HbA1c) and body weight in people with T2D. The present study estimated the cost per patient achieving HbA1c treatment targets and weight loss responses with once-weekly semaglutide and dulaglutide in the USA. Methods Numbers needed to treat and annual cost per patient achieving HbA1c targets (including a triple composite endpoint of HbA1c

Introduction Pain and functional impairment associated with joint disease are major problems for people with hemophilia, and impact on health-related quality of life (HRQoL) may vary across groups defined by demographic and treatment-related characteristics. Objective To evaluate differences in overall HRQoL, pain, function, and joint status between P-FiQ study subgroups. Methods Adult males with hemophilia and a history of joint pain/bleeding completed a pain history and the patient-reported outcome instruments EQ-5D-5L, Brief Pain Inventory v2 Short Form (BPI), International Physical Activity Questionnaire (IPAQ), and Hemophilia Activities List (HAL); optionally, joint status was assessed (Hemophilia Joint Health Score v2.1 [HJHS]). Scores were analyzed between subgroups across sets of participant characteristics. Results A total of 381 adult males with hemophilia were enrolled, with median age of 34 years. Worse scores on EQ-5D-5L index, BPI pain severity/interference, HAL overall score, and HJHS were generally associated with being college educated, unemployment, self-reporting both acute and chronic pain, and self-reporting anxiety/depression. Conclusions Measures of joint status and HRQoL were consistently lower in participants who had higher educational levels, were unemployed, self-reported having both acute and chronic pain, and self-reported having anxiety/depression. A greater understanding of the association of these factors with disease outcomes may improve individualized patient management.

To present a multiyear clinical experience with intravenous bevacizumab for the management of severe gastrointestinal bleeding and/or epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT).All patients treated with intravenous bevacizumab for severe hereditary hemorrhagic telangiectasia-related bleeding from June 1, 2013, through January 31, 2017, were included in this report. Severity of epistaxis (determined using the Epistaxis Severity Score questionnaire); hemoglobin, iron, and ferritin levels; and quality of life data were collected serially in all patients.Intravenous bevacizumab was administered to 34 patients using a standardized treatment protocol. Anemia was primarily related to severe epistaxis (n=15, 44%), severe gastrointestinal bleeding (n=4, 12%), or both (n=15, 44%), with a median baseline hemoglobin level of 9.1 g/dL (range, 8.3-10.5 gm/dL; to convert to mmol/L, multiply by 0.62). Red blood cell (RBC) transfusions had been administered to 28 patients (82%). Of these, 16 patients (47%) were RBC transfusion dependent and had received a median of 75 RBC transfusions (range, 4-500 RBC units) before bevacizumab initiation. The median length of follow-up was 17.6 months from the beginning of bevacizumab treatment (range, 3-42.5 months). There was a significant reduction in epistaxis severity scores (P.001) and RBC transfusion requirements (P=.007) after completion of the initial bevacizumab treatment cycle. New-onset or worsened hypertension was noted in 4 patients, with 1 patient experiencing hypertensive urgency with a temporary decline in renal function.Intravenous bevacizumab is an effective treatment option for patients with severe anemia related to epistaxis and/or gastrointestinal bleeding. Further studies are needed to establish a dose-response relationship as well as clinical, genetic, and biomarker predictors of response.

Background Most patients with restriction have a pulmonary function test (PFT) pattern in which total lung capacity (TLC), FVC, and FEV 1 are reduced to a similar degree. This pattern is called "simple restriction" (SR). In contrast, we commonly observe a pattern in which FVC percent predicted ( pp ) is disproportionately reduced relative to TLC pp . This pattern is termed "complex restriction" (CR), and we attempted to characterize its clinical, radiologic, and physiologic features. Methods This study reviewed PFT results of patients tested between November 2009 and June 2013 who had restriction (TLC less than the lower limit of normal). SR was defined as TLC pp -FVC pp ≤ 10%, and CR was stratified into four classes based on TLC pp -FVC pp discrepancy: Class 1 CR, TLC pp -FVC pp > 10% and ≤ 15%; Class 2 CR, TLC pp -FVC pp > 15% and ≤20%; Class 3 CR, TLC pp -FVC pp > 20% and ≤ 25%; and Class 4 CR, TLC pp -FVC pp > 25%. The medical records of 150 randomly selected patients with SR and 50 patients from each CR class were reviewed. Results Of 39,277 PFTs completed, we identified 4,532 patients (11.5%) with restriction: 2,407 (6.1%) with SR, 1,614 (4.1%) with CR, and 511 (1.3%) with a mixed pattern. Patients with CR were younger, were more often women, and had a higher prevalence of neuromuscular disease, BMI > 40 kg/m 2 or 2 , diaphragmatic dysfunction, bronchiectasis, CT mosaic attenuation, and pulmonary hypertension ( P P Conclusions CR is a common PFT pattern with distinct clinical features. The associated clinical entities share impaired lung emptying (eg, neuromuscular disease, occult obstruction, chest wall limitation). Clinicians should be aware of this novel PFT pattern and how it shapes the differential diagnosis.