Lessons Learned in Conducting School Health Research in Massachusetts: A Massachusetts School Nurse Research Network (MASNRN) Project

The Institute of Medicine (2007) and the Robert Wood Johnson Foundation (RWJF) (2010) recognized that the school environment plays a role in shaping children’s health and health behaviors, and school health services are positioned to model these approaches. The majority of school health services are school nurse (SN) managed (RWJF, 2012; Schainker, 2005), but a research gap exists linking school health services with improved student outcomes (Hootman, 2002; Lear, 2007). In Massachusetts, the student health research question ideally has roots in the expertise of the SN. The researcher conducting a school-based student health study interacts with SNs and administrators in school districts that vary by the type and number of health staff , as well as district location and size. These variables confound the research design in terms of structure and process. IRB issues and permission for research conduction in the school district are particularly vexing. Consent of parents and assent of children are required, and SNs participating in the research must complete human subjects training. Massachusetts School Nurse Research Network (MASNRN) was founded in 2004 by a group of SN experts to conduct school based research. The 100 members of MASNRN have conducted studies across the state and within school districts on asthma, availability of epinephrine for anaphylaxis, bullying, immunizations, training modules and mental health. Particular lessons learned from the unique experience of conducting research in schools are presented

Respite care and short breaks for young adults aged 18–40 with complex health-care needs: mixed-methods systematic review and conceptual framework development

BackgroundThe number of young adults with complex health-care needs due to life-limiting conditions/complex physical disability has risen significantly over the last 15 years, as more children now survive into adulthood. The transition from children to adult services may disrupt provision of essential respite/short break care for this vulnerable population, but the impact on young adults, families and providers is unclear.AimTo review the evidence on respite care provision for young adults (aged 18–40 years) with complex health-care needs, provide an evidence gap analysis and develop a conceptual framework for respite care.DesignA two-stage mixed-methods systematic review, including a knowledge map of respite care and an evidence review of policy, effectiveness, cost-effectiveness and experience.Data sourcesElectronic databases and grey/unpublished literature were searched from 2002 to September 2019. The databases searched included Cumulative Index to Nursing and Allied Health Literature, MEDLINE, EMBASE, PsycINFO, Applied Social Sciences Index and Abstracts, Health Management Information Consortium, PROSPERO, Turning Research into Practice, COnNECT+, British Nursing Index, Web of Science, Social Care Online, the National Institute for Health Research Journals Library, Cochrane Effective Practice and Organisation of Care specialist register, databases on The Cochrane Library and international clinical trials registers. Additional sources were searched using the CLUSTER (Citations, Lead authors, Unpublished materials, Scholar search, Theories, Early examples, Related projects) approach and an international ‘call for evidence’.Methods and analysisMultiple independent reviewers used the SPICE (Setting, Perspective, Intervention/phenomenon of interest, Comparison, Evaluation) framework to select and extract evidence for each stage, verified by a third reviewer. Study/source characteristics and outcomes were extracted. Study quality was assessed using relevant tools. Qualitative evidence was synthesised using a framework approach and UK policy was synthesised using documentary content analysis. GRADE-CERQual (Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative Research) was used to assess confidence in the evidence. Logic models developed for each type of respite care constituted the conceptual framework.ResultsWe identified 69 sources (78 records) from 126,267 records. The knowledge map comprised the following types of respite care: residential, home based, day care, community, leisure/social provision, funded holidays and emergency. Seven policy intentions included early transition planning and prioritising respite care according to need. No evidence was found on effectiveness and cost-effectiveness. Qualitative evidence focused largely on residential respite care. Facilitators of accessible/acceptable services included trusted and valued relationships, independence and empowerment of young adults, peer social interaction, developmental/age-appropriate services and high standards of care. Barriers included transition to adult services, paperwork, referral/provision delay and travelling distance. Young adults from black, Asian and minority ethnic populations were under-represented. Poor transition, such as loss of or inappropriate services, was contrary to statutory expectations. Potential harms included stress and anxiety related to safe care, frustration and distress arising from unmet needs, parental exhaustion, and a lack of opportunities to socialise and develop independence.LimitationsNo quantitative or mixed-methods evidence was found on effectiveness or cost-effectiveness of respite care. There was limited evidence on planned and emergency respite care except residential.ConclusionsPolicy intentions are more comprehensively met for young people aged Future workResearch to quantify the effectiveness and cost-effectiveness of respite care to support service development and commissioning. Development of a core set of outcomes measures to support future collation of evidence.Study registrationThis study is registered as PROSPERO CRD42018088780.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 9, No. 6. See the NIHR Journals Library website for further project information

What have our patients learnt after being hospitalised for an acute myocardial infarction?

Background: Education for hospitalised patients is an important aspect of care for people who have an acute cardiovascular event. Objective: To investigate the cardiovascular risk factor behaviours of patients together with their acute coronary syndrome (ACS) knowledge, attitudes and beliefs following admission to hospital for an acute myocardial infarction. Methods: Patients diagnosed with an acute myocardial infarction participated in an observational study. Patients completed a questionnaire consisting of cardiovascular risk factor behaviour questions and the ACS Response Index prior to discharge and at follow-up 10 weeks later. Results: Of the 135 participants enrolled, 114 (84%) completed follow-up, 70% were males; mean age was 63 (±11.6) years. The median length of hospital stay was 3 days (IQR 1) and the time to follow-up after discharge was 10 weeks. Self-reported risk factor behaviours improved significantly for diet (p < 0.001) and smoking cessation (p = 0.023) following discharge. At discharge 39% of patients had inadequate knowledge of ACS symptoms. The ACS Response Index improved significantly after discharge for attitudes (p = 0.004) and beliefs (p = 0.008). Despite 85% of patients indicating they would attend cardiac rehabilitation only 30% had commenced a programme at follow-up. Conclusion: Patients reported implementing a number of healthy lifestyle changes following discharge including smoking cessation and healthy eating. Attitudes and beliefs regarding ACS showed a significant improvement following discharge. More than one third of patients had inadequate knowledge at discharge, suggesting current education practices may not be meeting the needs of patients with a myocardial infarction

Advances in the treatment of prolactinomas

Prolactinomas account for approximately 40% of all pituitary adenomas and are an important cause of hypogonadism and infertility. The ultimate goal of therapy for prolactinomas is restoration or achievement of eugonadism through the normalization of hyperprolactinemia and control of tumor mass. Medical therapy with dopamine agonists is highly effective in the majority of cases and represents the mainstay of therapy. Recent data indicating successful withdrawal of these agents in a subset of patients challenge the previously held concept that medical therapy is a lifelong requirement. Complicated situations, such as those encountered in resistance to dopamine agonists, pregnancy, and giant or malignant prolactinomas, may require multimodal therapy involving surgery, radiotherapy, or both. Progress in elucidating the mechanisms underlying the pathogenesis of prolactinomas may enable future development of novel molecular therapies for treatment-resistant cases. This review provides a critical analysis of the efficacy and safety of the various modes of therapy available for the treatment of patients with prolactinomas with an emphasis on challenging situations, a discussion of the data regarding withdrawal of medical therapy, and a foreshadowing of novel approaches to therapy that may become available in the future

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Abstract: Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating

Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups

IntroductionWhile complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.MethodsWe therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome.ResultsWe show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p&lt;0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID.ConclusionIn conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted