Benzophenone as a cheap and effective photosensitizer for the photocatalytic synthesis of dimethyl cubane-1,4-dicarboxylate.

The key intramolecular [2 + 2] photochemical cycloaddition step in the synthesis of dimethyl cubane-1,4-dicarboxylate is performed with substoichiometric amounts of the photosensitizer benzophenone. The reaction proceeds via a Dexter energy transfer process between the triplet excited state benzophenone and a well-known cubane precursor diene. The use of the cheap and widely available benzophenone as the photosensitizer enables lower energy light to be used than the traditional photochemical process.

The emotional effects on professional interpreters of interpreting palliative care conversations for adult patients: A rapid review.

BACKGROUND: Professional interpreters working in palliative contexts improve patient care. Whilst literature identifies psychological distress in other healthcare professionals, research into emotional effects on professional interpreters in this highly emotive setting is limited. Isolating emotional responses may enable targeted interventions to enhance interpreter use and improve wellbeing. Timely evidence is needed to urgently familiarise the profession with issues faced by these valuable colleagues, to affect practice. AIM: Describe the emotional effects on professional interpreters of interpreting adult palliative care conversations. Collate recommendations to mitigate negative emotional effects. DESIGN: We performed a rapid review of studies identifying emotional effects on professional interpreters of interpreting adult palliative conversations. Rapid review chosen to present timely evidence to relevant stakeholders in a resource-efficient way. Thematic analysis managed using NVivo. Quality appraisal evaluated predominantly using CASP checklists. Reported using PRISMA guidelines. PROSPERO registration CRD42022301753. DATA SOURCES: Articles available in English on PubMed [1966-2021], MEDLINE [1946-2021], EMBASE [1974-2021], CINAHL [1981-2021] and PsycINFO [1806-2021] in December 2021. RESULTS: Eleven articles from the USA (5), Australia (3), Canada (2) and UK (1). Eight interview-based, two online surveys and one quality improvement project. Themes included (1) Identifying diversity of emotional effects: emotions including stress, discomfort, loneliness. (2) Identifying factors affecting interpreters' emotional responses: impact of morals, culture and role expectations; working with patients and families; interpreter experience and age. (3) Recommendations to mitigate negative emotional effects: pre-briefing, debriefing and interpreter/provider training. CONCLUSION: Professional interpreters experience myriad emotional responses to palliative conversations. Role clarity, collaborative working and formal training may alleviate negative effects.

The minimum clinically important difference on the sleep disorders inventory for people with dementia.

OBJECTIVES: Sleep disturbances in dementia causes distress to people with dementia and their family carers and are associated with care home admission. The Sleep Disorders Inventory (SDI) is a validated questionnaire of sleep disturbances in dementia often used to measure treatment effectiveness, but the minimum clinically important difference (MCID) is unknown. METHODS: We triangulated three investigative methods to determine the MCID of the SDI. Using data on SDI from a randomised controlled trial (RCT) with 62 participants in an intervention for sleep disorders in dementia, we (1) calculated distribution-based values where MCID = 0.33 of a SD (SD) (2) an anchor based approach using quality of life (measured using DEMQOL-Proxy) as an anchor. We also employed a Delphi consensus process asking 12 clinicians, sleep researchers and family carers to rate which changes on vignettes were equivalent to a MCID. RESULTS: We found that 0.33 SD in the SDI = 4.86. Reduction in SDI total score was not significantly correlated with improvement in DEMQOL-Proxy (Pearson's correlation = -0.01; P = 0.96) score. The Delphi consensus required two rounds to reach a consensus and concluded that changes equivalent to three points on the SDI equated to the MCID. CONCLUSIONS: Taking into account both the distribution-based values and the Delphi process we used a whole number at the midpoint and judged the minimum clinically important difference MCID to be equal to four points. We note the clinicians and carers opinions from the Delphi process determined the MCID to be lower at three points.

Kontinuierliche medizinische Fortbildung in der Dermatologie für Ärzte und Studierende während der Coronavirus­Pandemie ­ eine große Herausforderung.

Kontinuierliche medizinische Fortbildung (Continuing Medical Education, CME) ist die wesentliche Grundlage der studentischen Lehre sowie der Aus- und Weiterbildung von Ärzten. Eine moderne und adäquate Patientenversorgung ist ohne sie nicht denkbar. Vor kurzem zwang die durch das schwere akute respiratorische Syndrom-Coronavirus 2 (SARS-CoV-2) verursachte Pandemie die gesamte medizinische Gemeinschaft, ihre Gewohnheiten bezüglich der medizinischen Fortbildung und Lehre sowie des Lernens in der Medizin zu ändern. Infolgedessen rückten über soziale Medien (Social Media) verbreitete digitale Aus-, Fortbildungs- und Lehrformate, medizinische Online-Enzyklopädien, webbasierte medizinische Lernportale und medizinische Podcasts in den Vordergrund. In diesem Beitrag geben wir einen Überblick zu aktuelle Konzepten in der medizinischen Online-Fortbildung, unter besonderer Berücksichtigung der Dermatologie.

Continuing medical and student education in dermatology during the coronavirus pandemic - a major challenge.

Continuing medical education (CME) is the essential basis for student teaching and for training and further development of physicians. Without it, modern and adequate patient care is unthinkable. Recently, the coronavirus pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARSCoV2), forced the entire medical community to change its usual habits of advanced medical training, teaching and learning. As a result, digital training and teaching via social media, online medical encyclopedias, web-based learning platforms and educational podcasts moved to the fore. Here, we give an overview on current concepts for online medical education, with special consideration of dermatology.

Advanced care planning 5 years on: An observational study of multi-centred service development for children with life-limiting conditions.

AIM: The purpose of this study was to compare how planning has developed over the 5 years across a range of children's health care services in a single U.K. city. BACKGROUND: Advanced planning for end of life care (EOLC) is an essential component of care for children with life-limiting and life-threatening (LLLT) conditions. We report the findings of a follow-up study (R2) completed 5 years after the initial review (R1). Documented advanced care planning (ACP) was measured against published children's palliative care standards. METHOD: We used a manual retrospective review of health care records, using focused data collection. Inclusion criteria were children who died before the age of 18 years, as a consequence of an LLLT condition, over an 18-month period and had lived locally to a regional children's hospital. RESULTS: The first review (R1) included 48 patients with 114 health care records: median age at death 0 years (range 0 to 18 years). The follow-up review (R2) included 47 patients, with 80 health care records: median age at death 2 years (range 0 to 17 years). The proportion of records containing evidence of a prognostic discussion had risen from 73% (R1) to 91% (R2), p < 0.005. The proportion of health care records with ACP was consistent between R1 and R2 (75% and 72%, respectively). An ACP tool was found to be in regular use in R2 compared with no examples in R1. The acute hospital trust plans were more detailed in R2 than R1. The proportion of cases where preferred location of death matched actual location was stable, around half. CONCLUSIONS: EOLC conversations increased over the 5 years studied. In the acute hospital trust, there is evidence of a better quality ACP although quantity is stable: enabled by the implementation of an ACP tool and education programme. Challenges remain in engaging children and young people in advanced planning.

Recurrent Abdominal Pain in Children: Summary Evidence From 3 Systematic Reviews of Treatment Effectiveness.

OBJECTIVES: Between 4% and 25% of school-aged children complain of recurrent abdominal pain (RAP) severe enough to interfere with their daily activities. METHODS: We carried out a systematic review of randomised controlled trials (RCTs) in eleven databases and 2 trials registries from inception to June 2016. An update search was run in November 2017. All screening was performed by 2 independent reviewers. Included studies were appraised using the Cochrane risk of bias tool and the evidence assessed using GRADE. We included any dietary, pharmacological or psychosocial intervention for RAP, defined by Apley or an abdominal pain-related functional gastrointestinal disorder, as defined by the Rome III criteria, in children and adolescents. RESULTS: We included 55 RCTs, involving 3572 children with RAP (21 dietary, 15 pharmacological, 19 psychosocial, and 1 multiarm). We found probiotic diets, cognitive-behavioural therapy (CBT) and hypnotherapy were reported to reduce pain in the short-term and there is some evidence of medium term effectiveness. There was insufficient evidence of effectiveness for all other dietary interventions and psychosocial therapies. There was no robust evidence of effectiveness for pharmacological interventions. CONCLUSIONS: Overall the evidence base for treatment decisions is poor. These data suggest that probiotics, CBT, and hypnotherapy could be considered as part of holistic management of children with RAP. The evidence regarding relative effectiveness of different strains of probiotics is currently insufficient to guide clinical practice. The lack of evidence of effectiveness for any drug suggests that there is little justification for their use outside of well-conducted clinical trials. There is an urgent need for high-quality RCTs to provide evidence to guide management of this common condition.

Pharmacological interventions for recurrent abdominal pain in childhood.

BACKGROUND: Between 4% and 25% of school-aged children at some stage complain of recurrent abdominal pain (RAP) of sufficient severity to interfere with their daily lives. When no clear organic cause is found, the children are managed with reassurance and simple measures; a large range of pharmacological interventions have been recommended for use in these children. OBJECTIVES: To determine the effectiveness of pharmacological interventions for RAP in children of school age. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, and eight other electronic databases up to June 2016. We also searched two trials registers and contacted researchers of published studies. SELECTION CRITERIA: Randomised controlled trials involving children aged five to 18 years old with RAP or an abdominal pain-related functional gastrointestinal disorder, as defined by the Rome III criteria (Rasquin 2006). The interventions were any pharmacological intervention compared to placebo, no treatment, waiting list, or standard care. The primary outcome measures were pain intensity, pain duration or pain frequency, and improvement in pain. The secondary outcome measures were school performance, social or psychological functioning, and quality of daily life. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts, and potentially relevant full-text reports for eligible studies. Two review authors extracted data and performed a 'Risk of bias' assessment. We used the GRADE approach to rate the overall quality of the evidence. We deemed a meta-analysis to be not appropriate as the studies were significantly heterogeneous. We have consequently provided a narrative summary of the results. MAIN RESULTS: This review included 16 studies with a total of 1024 participants aged between five and 18 years, all of whom were recruited from paediatric outpatient clinics. Studies were conducted in seven countries: seven in the USA, four in Iran, and one each in the UK, Switzerland, Turkey, Sri Lanka, and India. Follow-up ranged from two weeks to four months. The studies examined the following interventions to treat RAP: tricyclic antidepressants, antibiotics, 5-HT4 receptor agonists, antispasmodics, antihistamines, H2 receptor antagonists, serotonin antagonists, selective serotonin re-uptake inhibitors, a dopamine receptor antagonist, and a hormone. Although some single studies reported that treatments were effective, all of these studies were either small or had key methodological weaknesses with a substantial risk of bias. None of these 'positive' results have been reproduced in subsequent studies. We judged the evidence of effectiveness to be of low quality. No adverse effects were reported in these studies. AUTHORS' CONCLUSIONS: There is currently no convincing evidence to support the use of drugs to treat RAP in children. Well-conducted clinical trials are needed to evaluate any possible benefits and risks of pharmacological interventions. In practice, if a clinician chooses to use a drug as a 'therapeutic trial', they and the patient need to be aware that RAP is a fluctuating condition and any 'response' may reflect the natural history of the condition or a placebo effect, rather than drug efficacy.

Dietary interventions for recurrent abdominal pain in childhood.

BACKGROUND: This is an update of the original Cochrane review, last published in 2009 (Huertas-Ceballos 2009). Recurrent abdominal pain (RAP), including children with irritable bowel syndrome, is a common problem affecting between 4% and 25% of school-aged children. For the majority of such children, no organic cause for their pain can be found on physical examination or investigation. Many dietary inventions have been suggested to improve the symptoms of RAP. These may involve either excluding ingredients from the diet or adding supplements such as fibre or probiotics. OBJECTIVES: To examine the effectiveness of dietary interventions in improving pain in children of school age with RAP. SEARCH METHODS: We searched CENTRAL, Ovid MEDLINE, Embase, eight other databases, and two trials registers, together with reference checking, citation searching and contact with study authors, in June 2016. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing dietary interventions with placebo or no treatment in children aged five to 18 years with RAP or an abdominal pain-related, functional gastrointestinal disorder, as defined by the Rome III criteria (Rasquin 2006). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We grouped dietary interventions together by category for analysis. We contacted study authors to ask for missing information and clarification, when needed. We assessed the quality of the evidence for each outcome using the GRADE approach. MAIN RESULTS: We included 19 RCTs, reported in 27 papers with a total of 1453 participants. Fifteen of these studies were not included in the previous review. All 19 RCTs had follow-up ranging from one to five months. Participants were aged between four and 18 years from eight different countries and were recruited largely from paediatric gastroenterology clinics. The mean age at recruitment ranged from 6.3 years to 13.1 years. Girls outnumbered boys in most trials. Fourteen trials recruited children with a diagnosis under the broad umbrella of RAP or functional gastrointestinal disorders; five trials specifically recruited only children with irritable bowel syndrome. The studies fell into four categories: trials of probiotic-based interventions (13 studies), trials of fibre-based interventions (four studies), trials of low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diets (one study), and trials of fructose-restricted diets (one study).We found that children treated with probiotics reported a greater reduction in pain frequency at zero to three months postintervention than those given placebo (standardised mean difference (SMD) -0.55, 95% confidence interval (CI) -0.98 to -0.12; 6 trials; 523 children). There was also a decrease in pain intensity in the intervention group at the same time point (SMD -0.50, 95% CI -0.85 to -0.15; 7 studies; 575 children). However, we judged the evidence for these outcomes to be of low quality using GRADE due to an unclear risk of bias from incomplete outcome data and significant heterogeneity.We found that children treated with probiotics were more likely to experience improvement in pain at zero to three months postintervention than those given placebo (odds ratio (OR) 1.63, 95% CI 1.07 to 2.47; 7 studies; 722 children). The estimated number needed to treat for an additional beneficial outcome (NNTB) was eight, meaning that eight children would need to receive probiotics for one to experience improvement in pain in this timescale. We judged the evidence for this outcome to be of moderate quality due to significant heterogeneity.Children with a symptom profile defined as irritable bowel syndrome treated with probiotics were more likely to experience improvement in pain at zero to three months postintervention than those given placebo (OR 3.01, 95% CI 1.77 to 5.13; 4 studies; 344 children). Children treated with probiotics were more likely to experience improvement in pain at three to six months postintervention compared to those receiving placebo (OR 1.94, 95% CI 1.10 to 3.43; 2 studies; 224 children). We judged the evidence for these two outcomes to be of moderate quality due to small numbers of participants included in the studies.We found that children treated with fibre-based interventions were not more likely to experience an improvement in pain at zero to three months postintervention than children given placebo (OR 1.83, 95% CI 0.92 to 3.65; 2 studies; 136 children). There was also no reduction in pain intensity compared to placebo at the same time point (SMD -1.24, 95% CI -3.41 to 0.94; 2 studies; 135 children). We judged the evidence for these outcomes to be of low quality due to an unclear risk of bias, imprecision, and significant heterogeneity.We found only one study of low FODMAP diets and only one trial of fructose-restricted diets, meaning no pooled analyses were possible.We were unable to perform any meta-analyses for the secondary outcomes of school performance, social or psychological functioning, or quality of daily life, as not enough studies included these outcomes or used comparable measures to assess them.With the exception of one study, all studies reported monitoring children for adverse events; no major adverse events were reported. AUTHORS' CONCLUSIONS: Overall, we found moderate- to low-quality evidence suggesting that probiotics may be effective in improving pain in children with RAP. Clinicians may therefore consider probiotic interventions as part of a holistic management strategy. However, further trials are needed to examine longer-term outcomes and to improve confidence in estimating the size of the effect, as well as to determine the optimal strain and dosage. Future research should also explore the effectiveness of probiotics in children with different symptom profiles, such as those with irritable bowel syndrome.We found only a small number of trials of fibre-based interventions, with overall low-quality evidence for the outcomes. There was therefore no convincing evidence that fibre-based interventions improve pain in children with RAP. Further high-quality RCTs of fibre supplements involving larger numbers of participants are required. Future trials of low FODMAP diets and other dietary interventions are also required to facilitate evidence-based recommendations.

Psychosocial interventions for recurrent abdominal pain in childhood.

BACKGROUND: This review supersedes the original Cochrane review first published in 2008 (Huertas-Ceballos 2008).Between 4% and 25% of school-aged children complain of recurrent abdominal pain (RAP) severe enough to interfere with their daily activities. No organic cause for this pain can be found on physical examination or investigation for the majority of such children. Although many children are managed by reassurance and simple measures, a large range of psychosocial interventions involving cognitive and behavioural components have been recommended. OBJECTIVES: To determine the effectiveness of psychosocial interventions for reducing pain in school-aged children with RAP. SEARCH METHODS: In June 2016 we searched CENTRAL, MEDLINE, Embase, eight other databases, and two trials registers. We also searched the references of identified studies and relevant reviews. SELECTION CRITERIA: Randomised controlled trials comparing psychosocial therapies with usual care, active control, or wait-list control for children and adolescents (aged 5 to 18 years) with RAP or an abdominal pain-related functional gastrointestinal disorder defined by the Rome III criteria were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Five review authors independently selected studies, assessed them for risk of bias, and extracted relevant data. We also assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: This review includes 18 randomised controlled trials (14 new to this version), reported in 26 papers, involving 928 children and adolescents with RAP between the ages of 6 and 18 years. The interventions were classified into four types of psychosocial therapy: cognitive behavioural therapy (CBT), hypnotherapy (including guided imagery), yoga, and written self-disclosure. The studies were carried out in the USA, Australia, Canada, the Netherlands, Germany, and Brazil. The majority of the studies were small and short term; only two studies included more than 100 participants, and only five studies had follow-up assessments beyond six months. Small sample sizes and the degree of assessed risk of performance and detection bias in many studies led to the overall quality of the evidence being rated as low to very low for all outcomes.For CBT compared to control, we found evidence of treatment success postintervention (odds ratio (OR) 5.67, 95% confidence interval (CI) 1.18 to 27.32; Z = 2.16; P = 0.03; 4 studies; 175 children; very low-quality evidence), but no evidence of treatment success at medium-term follow-up (OR 3.08, 95% CI 0.93 to 10.16; Z = 1.85; P = 0.06; 3 studies; 139 children; low-quality evidence) or long-term follow-up (OR 1.29, 95% CI 0.50 to 3.33; Z = 0.53; P = 0.60; 2 studies; 120 children; low-quality evidence). We found no evidence of effects of intervention on pain intensity scores measured postintervention (standardised mean difference (SMD) -0.33, 95% CI -0.74 to 0.08; 7 studies; 405 children; low-quality evidence), or at medium-term follow-up (SMD -0.32, 95% CI -0.85 to 0.20; 4 studies; 301 children; low-quality evidence).For hypnotherapy (including studies of guided imagery) compared to control, we found evidence of greater treatment success postintervention (OR 6.78, 95% CI 2.41 to 19.07; Z = 3.63; P = 0.0003; 4 studies; 146 children; low-quality evidence) as well as reductions in pain intensity (SMD -1.01, 95% CI -1.41 to -0.61; Z = 4.97; P < 0.00001; 4 studies; 146 children; low-quality evidence) and pain frequency (SMD -1.28, 95% CI -1.84 to -0.72; Z = 4.48; P < 0.00001; 4 studies; 146 children; low-quality evidence). The only study of long-term effect reported continued benefit of hypnotherapy compared to usual care after five years, with 68% reporting treatment success compared to 20% of controls (P = 0.005).For yoga therapy compared to control, we found no evidence of effectiveness on pain intensity reduction postintervention (SMD -0.31, 95% CI -0.67 to 0.05; Z = 1.69; P = 0.09; 3 studies; 122 children; low-quality evidence).The single study of written self-disclosure therapy reported no benefit for pain.There was no evidence of effect from the pooled analyses for any type of intervention on the secondary outcomes of school performance, social or psychological functioning, and quality of daily life.There were no adverse effects for any of the interventions reported. AUTHORS' CONCLUSIONS: The data from trials to date provide some evidence for beneficial effects of CBT and hypnotherapy in reducing pain in the short term in children and adolescents presenting with RAP. There was no evidence for the effectiveness of yoga therapy or written self-disclosure therapy. There were insufficient data to explore effects of treatment by RAP subtype.Higher-quality, longer-duration trials are needed to fully investigate the effectiveness of psychosocial interventions. Identifying the active components of the interventions and establishing whether benefits are sustained in the long term are areas of priority. Future research studies would benefit from employing active control groups to help minimise potential bias from wait-list control designs and to help account for therapist and intervention time.

Communicating with disabled children when inpatients: barriers and facilitators identified by parents and professionals in a qualitative study.

BACKGROUND: Communication is a fundamental part of health care, but can be more difficult with disabled children. Disabled children are more frequently admitted to hospital than other children. AIMS: To explore experiences of ward staff and families to identify barriers and facilitators to effective communication with disabled children whilst inpatients. DESIGN: This was an exploratory qualitative study. METHODS: We consulted 25 staff working on paediatric wards and 15 parents of disabled children recently admitted to those wards. We had difficulty in recruiting children and evaluating their experiences. Data were collected through interviews and focus groups. A thematic analysis of the data supported by the Framework Approach was used to explore experiences and views about communication. Emerging themes were subsequently synthesised to identify barriers and facilitators to good communication. RESULTS: Barriers to communication included time, professionals not prioritising communication in their role and poor information sharing between parents and professionals. Facilitators included professionals building rapport with a child, good relationships between professionals and parents, professionals having a family-centred approach, and the use of communication aids. CONCLUSIONS: Communication with disabled children on the ward was perceived as less than optimal. Parents are instrumental in the communication between their children and professionals. Although aware of the importance of communication with disabled children, staff perceived time pressures and lack of priority given to communicating directly with the child as major barriers.

A scoping review of behavioural science approaches and frameworks for health protection and emergency response.

AIMS: Rapid intervention development, implementation, and evaluation are required for emergency public health contexts, such as the recent COVID-19 pandemic. A novel Agile Co-production and Evaluation (ACE) framework has been developed to assist this endeavour in future public health emergencies. This scoping review aimed to map available behavioural science resources that can be used to develop and evaluate public health guidance, messaging, and interventions in emergency contexts onto components of ACE: rapid development and implementation, co-production with patients or the public including seldom heard voices from diverse communities, and inclusion of evaluation. METHODS: A scoping review methodology was used. Searches were run on MEDLINE, EMBASE, PsycINFO, and Google, with search terms covering emergency response and behavioural science. Articles published since 2014 and which discussed a framework or guidance for using behavioural science in response to a public health emergency were included. A narrative synthesis was conducted. RESULTS: Seventeen records were included in the synthesis. The records covered a range of emergency contexts, the most frequent of which were COVID-19 (n = 7) and non-specific emergencies (n = 4). One record evaluated existing approaches, 6 proposed new approaches, and 10 described existing approaches. Commonly used approaches included the Behavioural Change Wheel; Capability, Opportunity, and Motivation Behaviour model; and social identity theory. Three records discuss co-production with the target audience and consideration of diverse populations. Four records incorporate rapid testing, evaluation, or validation methods. Six records state that their approaches are designed to be implemented rapidly. No records cover all components of ACE. CONCLUSION: We recommend that future research explores how to create guidance involving rapid implementation, co-production with patients or the public including seldom heard voices from diverse communities, and evaluation.

Upstream-downstream gradient in infection levels by fish parasites: a common river pattern?

Physical habitat structure can influence the distribution and abundance of organisms. In rivers, stream drift, a common process originating from the unidirectional water flow, favours the displacement and downstream dispersion of invertebrates. This process could also generate a gradient in infection levels, leading to decreasing numbers of parasites per host as one moves upstream from the river mouth. We tested this hypothesis using 4 trematode species infecting the fish Gobiomorphus breviceps in the Manuherikia River (New Zealand). We analysed the abundance of each trematode infrapopulation as a function of distance from the river junction and fish size by generalized linear models. Our results supported the existence of a longitudinal gradient in trematode abundance along the river with a decreasing downstream-to-upstream continuum. This applied to 3 out of the 4 trematode species studied, suggesting that this might be a common pattern in river populations. Thus, the unidirectional river flow and a major process like drift in lotic systems, that influences the dynamics and distribution of invertebrate hosts, can also affect trematodes. Host properties like habitat preference, and parasite traits, particularly those related to transmission mode can influence the strength of the observed gradient, as may other environmental and biotic factors.

Comprehensive epigenomic profiling reveals the extent of disease-specific chromatin states and informs target discovery in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis characterized by enthesitis of the spine and sacroiliac joints. Genome-wide association studies (GWASs) have revealed more than 100 genetic associations whose functional effects remain largely unresolved. Here, we present a comprehensive transcriptomic and epigenomic map of disease-relevant blood immune cell subsets from AS patients and healthy controls. We find that, while CD14+ monocytes and CD4+ and CD8+ T cells show disease-specific differences at the RNA level, epigenomic differences are only apparent upon multi-omics integration. The latter reveals enrichment at disease-associated loci in monocytes. We link putative functional SNPs to genes using high-resolution Capture-C at 10 loci, including PTGER4 and ETS1, and show how disease-specific functional genomic data can be integrated with GWASs to enhance therapeutic target discovery. This study combines epigenetic and transcriptional analysis with GWASs to identify disease-relevant cell types and gene regulation of likely pathogenic relevance and prioritize drug targets.

Incidence and Time Trends of Pregnancy-Related Stroke Between 2010 and 2018: The Nationwide CONCEPTION Study.

BACKGROUND AND OBJECTIVES: Despite the potentially devastating effects of pregnancy-related stroke, few studies have examined its incidence by type of stroke. We aimed to study the nationwide incidence rates and recent temporal trends for all types of pregnancy-related stroke and to compare these incidences with stroke incidence in nonpregnant women. METHODS: We conducted a study of 6,297,698 women aged 15-49 years who gave birth in France between 2010 and 2018 with no history of stroke before pregnancy by collecting data from the French National Health Insurance Information System database. Poisson regression was used to estimate the incidence by types of strokes for the different pregnancy periods and the incidence rate ratio of stroke in pregnant vs nonpregnant French women. RESULTS: Among the 6,297,698 women, 1,261 (24.0 per 100,000 person-years) experienced a first ever stroke during, antepartum peripartum, or the first 6 weeks of postpartum. Of the pregnancy-related strokes, 42.9% were ischemic (IS), 41.9% were hemorrhagic (with similar proportion of intracerebral and subarachnoid hemorrhage), and 17.4% were cerebral venous thrombosis (CVT). Compared with nonpregnant women, incidence rates of stroke were similar during pregnancy for IS (adjusted incidence risk ratio [IRR] 0.9 [0.8-1.1]), slightly higher for all hemorrhagic strokes (IRR 1.4 [1.2-1.8]), and considerably increased for CVT (IRR 8.1 [6.5-10.1]). Pregnancy-related stroke incidence rose between 2010 and 2018 for IS and HS but was stable for CVT. DISCUSSION: The risk of pregnancy-related CVT was more than 8-fold higher than that observed in nonpregnant women. The incidence of pregnancy-related IS and HS is increasing over time, and efforts should be made for prevention considering treatable cardiovascular risk factors and hypertensive disorders in pregnant women.

Management of severe pulmonary Langerhans cell histiocytosis in children.

Patients with pulmonary Langerhans cell histiocytosis (LCH) typically have a benign course but may have extensive cystic lung disease with rare life-threatening complications including multiple and recurrent pneumothoraces and respiratory failure. We report seven severely affected pediatric patients treated with chemotherapy, aggressive chest tube management, and pleurodesis of whom five survived. Patients with extraordinary amounts of pulmonary cystic disease and multiple pneumothoraces due to LCH can have remarkable, curative outcomes with early recognition, optimal LCH-directed therapy, and supportive care.

Computerized decision support for EPO dosing in hemodialysis patients.

BACKGROUND: Anemia management in hemodialysis patients poses significant challenges. The present study explored the hypothesis that computerized dosing of intravenous erythropoietin (EPO) would increase the percentage of hemoglobin (Hb) values within the target range and reduce staff time spent on anemia management. STUDY DESIGN: Retrospective cohort. SETTING & PARTICIPANTS: In-center hemodialysis patients who received EPO at Dialysis Clinic Inc dialysis units for at least 3 months between October 1, 2005, and April 30, 2006. QUALITY IMPROVEMENT PLAN: Computerized decision support (CDS) for EPO dosing is compared with manual physician-directed dosing. OUTCOMES: Achieved monthly Hb values, quantity of EPO administered, and time spent by dialysis unit personnel. MEASUREMENTS: Monthly Hb and quantity of EPO administered to 1,118 patients from 18 dialysis units treated using CDS and 7,823 patients from 125 dialysis units treated using manual dosing. RESULTS: There was no difference in the likelihood of a monthly Hb level of 11-12 or 10-12 g/dL using CDS compared with manual dosing. The likelihood of an Hb level > 12 g/dL decreased and the likelihood of an Hb level < 10 g/dL increased using CDS. EPO use was 4% lower using CDS, although the difference was not statistically significant. CDS was associated with a nearly 50% decrease (P < 0.001) in the time spent by dialysis unit staff on anemia management. LIMITATIONS: Retrospective and nonrandomized. CONCLUSION: The number of monthly Hb values in an 11- (and 10-) to 12-g/dL target range and EPO use did not differ with EPO dosing using CDS compared with manual dosing. Staff resources devoted to anemia management decreased significantly using CDS.

Probiotics for Children With Recurrent Abdominal Pain.

Clinical Question: Do dietary interventions, such as probiotics, improve pain in children with recurrent abdominal pain? Clinical Application: Compared with placebo, children who were treated with probiotic preparations were more likely to experience improvement in pain in the short term (odds ratio, 1.63; 95% CI, 1.07-2.47), suggesting that clinicians could consider probiotics as part of a holistic management strategy in recurrent abdominal pain.