Adult frequent presentation to emergency departments and adverse childhood experiences: a scoping review.

BACKGROUND: Extensive literature reports the influence of childhood adversity on adult health, however few studies have explored these life antecedents in people who frequently present to the emergency department. This review synthesizes literature exploring childhood adversity influences on emergency department presentations, if and how it is identified, and interventions addressing the health care needs of this group. METHODS: Eight electronic databases were searched. Arksey and O'Malley's framework guided this review, and a quality appraisal was undertaken. Searches included all published studies until August 2020. RESULTS: Twenty-one articles were included in this review. They revealed that childhood adversity is common among adults who frequently attend the emergency department. It impacts physical and psychological health into adulthood and there is no standardized approach described to documenting childhood adversity, nor any consistent intervention reported by emergency departments to address its sequelae in adulthood. CONCLUSIONS: Several studies call for screening, intervention, and education to identify and address impacts of childhood adversity for patients who frequently present to the emergency department. However, reliable high-level studies exploring these topics specific to the emergency department are uncommon. Consequently, definitive interventions to address the healthcare needs of this group is lacking and warrants further research.

Pharmacologic treatment of attention deficit hyperactivity disorder in adults: A systematic review and network meta-analysis.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) affects approximately 3% of adults globally. Many pharmacologic treatments options exist, yet the comparative benefits and harms of individual treatments are largely unknown. We performed a systematic review and network meta-analysis to assess the relative effects of individual pharmacologic treatments for adults with ADHD. METHODS: We searched English-language published and grey literature sources for randomized clinical trials (RCTs) involving pharmacologic treatment of ADHD in adults (December 2018). The primary outcome was clinical response; secondary outcomes were quality of life, executive function, driving behaviour, withdrawals due to adverse events, treatment discontinuation, serious adverse events, hospitalization, cardiovascular adverse events, and emergency department visits. Data were pooled via pair-wise meta-analyses and Bayesian network meta-analyses. Risk of bias was assessed by use of Cochrane's Risk of Bias tool, and the certainty of the evidence was assessed by use of the GRADE framework. RESULTS: Eighty-one unique trials that reported at least one outcome of interest were included, most of which were at high or unclear risk of at least one important source of bias. Notably, only 5 RCTs were deemed at overall low risk of bias. Included pharmacotherapies were methylphenidate, atomoxetine, dexamfetamine, lisdexamfetamine, guanfacine, bupropion, mixed amphetamine salts, and modafinil. As a class, ADHD pharmacotherapy improved patient- and clinician-reported clinical response compared with placebo (range: 4 to 15 RCTs per outcome); however, these findings were not conserved when the analyses were restricted to studies at low risk of bias, and the certainty of the finding is very low. There were few differences among individual medications, although atomoxetine was associated with improved patient-reported clinical response and quality of life compared with placebo. There was no significant difference in the risk of serious adverse events or treatment discontinuation between ADHD pharmacotherapies and placebo; however, the proportion of participants who withdrew due to adverse events was significantly higher among participants who received any ADHD pharmacotherapy. Few RCTs reported on the occurrence of adverse events over a long treatment duration. CONCLUSIONS: Overall, despite a class effect of improving clinical response relative to placebo, there were few differences among the individual ADHD pharmacotherapies, and most studies were at risk of at least one important source of bias. Furthermore, the certainty of the evidence was very low to low for all outcomes, and there was limited reporting of long-term adverse events. As such, the choice between ADHD pharmacotherapies may depend on individual patient considerations, and future studies should assess the long-term effects of individual pharmacotherapies on patient-important outcomes, including quality of life, in robust blinded RCTs. REGISTRATION: PROSPERO no. CRD 42015026049.

Impact of physician's sex/gender on processes of care, and clinical outcomes in cardiac operative care: a systematic review.

OBJECTIVES: This systematic review aimed to assess the role of physician's sex and gender in relation to processes of care and/or clinical outcomes within the context of cardiac operative care. DESIGN: A systematic review. DATA SOURCES: Searches were conducted in PsycINFO, Embase and Medline from inception to 6 September 2018. The reference lists of relevant systematic reviews and included studies were also searched. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Quantitative studies of any design were included if they were published in English or French, involved patients of any age undergoing a cardiac surgical procedure and specifically assessed differences in processes of care or clinical patient outcomes by physician's sex or gender. Studies were screened in duplicate by two pairs of independent reviewers. OUTCOME MEASURES: Processes of care, patient morbidity and patient mortality. RESULTS: The search yielded 2095 publications after duplicate removal, of which two were ultimately included. These studies involved various types of surgery, including cardiac. One study found that patients treated by female surgeons compared with male surgeons had a lower 30-day mortality. The other study, however, found no differences in patient outcomes by surgeon's sex. There were no studies that investigated anaesthesiologist's sex/gender. There were also no studies investing physician's sex or gender exclusively in the cardiac operating room. CONCLUSIONS: The limited data surrounding the impact of physician's sex/gender on the outcomes of cardiac surgery inhibits drawing a robust conclusion at this time. Results highlight the need for primary research to determine how these factors may influence cardiac operative practice, in order to optimise provider's performance and improve outcomes in this high-risk patient group.

Ongoing improvements in postoperative survival of glioblastoma in the temozolomide era: a population-based data linkage study.

BACKGROUND: Translating outcomes achieved by clinical trials into routine care is crucial to improving outcomes of glioblastoma (GBM). This study examines the extent to which an advance in treatment for GBM has translated into meaningful, population-level survival benefits in New South Wales (NSW), Australia. METHODS: This retrospective cohort study used linked population-based cancer registry, admitted patient, and mortality datasets. The cohort (n = 2604) included NSW residents aged ≥18 years with a histologically confirmed GBM and a surgical resection between July 2001 and December 2012. The study outcome was all-cause survival, examined using multivariable proportional hazard models. The main study factor was period of surgery, categorized into 4 periods corresponding to different eras in temozolomide (TMZ) use. Survival was examined over time by age (≤70 and >70 years) and for a subcohort selected to approximate the seminal European Organisation for Research and Treatment of Cancer (Stupp) protocol trial cohort. TMZ use was estimated using aggregate prescription claims data. RESULTS: Median survival in 2001-2003, 2004-2006, 2007-2009, and 2010-2012 was 7.4, 9.0, 9.8, and 10.6 months, and risk-adjusted 2-year survival was 8.2%, 13.8%, 15.5%, and 18.3%, respectively. Survival improved for those aged ≤70 years and those aged >70 years. In the proxy trial subcohort, median and 2-year survival were 14.3 months and 27.3%, respectively. The volume of TMZ prescribed annually increased rapidly from 2005. CONCLUSIONS: Introduction of TMZ into standard care in 2005 coincided with improvements in survival and a rapid increase in TMZ prescribing. Optimization of care has continued to improve survival of people with GBM in subsequent years.

Sex Differences in Long-Term Survival After Major Cardiac Surgery: A Population-Based Cohort Study.

Background Little attention has been paid to the importance of sex in the long-term prognosis of patients undergoing cardiac surgery. Methods and Results We conducted a retrospective cohort study of Ontario residents, aged ≥40 years, who underwent coronary artery bypass grafting (CABG) and/or aortic, mitral, or tricuspid valve surgery between October 1, 2008, and December 31, 2016. The primary outcome was all-cause mortality. The mortality rate in each surgical group was calculated using the Kaplan-Meier method. The risk of death was assessed using multivariable Cox proportional hazard models. Sex-specific mortality risk factors were identified using multiplicative interaction terms. A total of 72 824 patients were included in the study (25% women). The median follow-up period was 5 (interquartile range, 3-7) years. The long-term age-standardized mortality rate was lowest in patients who underwent isolated CABG and highest among those who underwent combined CABG/multiple valve surgery. Women had significantly higher age-standardized mortality rate than men after CABG and combined CABG/mitral valve surgery. Men had lower rates of long-term mortality than women after isolated mitral valve repair, whereas women had lower rates of long-term mortality than men after isolated mitral valve replacement. We observed a statistically significant association between female sex and long-term mortality after adjustment for key risk factors. Conclusions Female sex was associated with long-term mortality after cardiac surgery. Perioperative optimization and long-term follow-up should be tailored to younger women with a history of myocardial infarction and percutaneous coronary intervention and older men with a history of chronic obstructive pulmonary disease and depression.

Influence of prolonged treatment with omalizumab on the development of solid epithelial cancer in patients with atopic asthma and chronic idiopathic urticaria: A systematic review and meta-analysis.

OBJECTIVE: We investigated whether prolonged treatment with omalizumab influences development or progression of solid epithelial cancer in patients with atopic asthma or chronic idiopathic urticaria. DESIGN: Systematic review and meta-analysis of intervention and observational studies. Randomized controlled trials were assessed for risk of bias using the Cochrane Risk of Bias tool, comparative observational studies were assessed using the Newcastle-Ottawa Scale, and non-comparative observational studies were assessed using the Joanna Briggs Institute Checklist for Prevalence Studies. DATA SOURCES: We searched MEDLINE, EMBASE, Cochrane Library and grey literature for eligible studies to November 2017. All searches were updated in January 2019. ELIGIBILITY CRITERIA FOR INCLUDED STUDIES: Randomized, quasi-randomized, controlled clinical trials and observational studies were included if they involved patients ≥ 12 years with moderate-to-severe persistent asthma or chronic idiopathic urticaria treated with omalizumab for ≥ 40 weeks. Eligible comparators included standard of care, placebo, cromoglycate or no treatment. RESULTS: One hundred and sixty seven unique studies were eligible for inclusion; however, only twelve (7.2%, n = 11 758) reported any outcome of interest, none of which involved patients with urticaria. 195 cancer events were reported. We found no statistically significant increase in the odds of study-emergent solid epithelial cancer in patients randomized to long-term treatment with omalizumab compared to standard of care (Peto OR: 0.65, 95% CI: 0.11, 3.74, I2  = 41%). Less than one per cent of participants of non-comparative observational studies (n = 2350) were diagnosed with a solid epithelial tumour (meta-proportion: 0.86% [95% CI: 0.24, 1.86%, I2  = 56%]). In the only comparative observational study reporting on cancer, the proportion of study-emergent solid epithelial tumour events was nearly identical in both study groups (omalizumab: 2.3%, standard of care: 2.2%). CONCLUSIONS: There is insufficient evidence to determine whether long-term treatment with omalizumab influences development or progression of solid epithelial cancer in these patient populations. PROSPERO registration # CRD 42018082211.

Risk of emergency hospitalisation and survival outcomes following adjuvant chemotherapy for early breast cancer in New South Wales, Australia.

OBJECTIVE: To examine risk of emergency hospital admission and survival following adjuvant chemotherapy for early breast cancer. METHODS: Linked data from New South Wales population-based and clinical cancer registries (2008-2012), hospital admissions, official death records and pharmaceutical benefit claims. Women aged ≥18 years receiving adjuvant chemotherapy for early-stage operable breast cancer in NSW public hospitals were included. Odds ratios (OR) for emergency hospitalisation within 6 months following chemotherapy initiation were estimated using logistic regression and survival using Kaplan-Meier and Cox proportional hazards methods. RESULTS: A total of 3,950 women were included and 30.6% were hospitalised. The most common principal diagnosis at admission was neutropenia (30.8%). Women receiving docetaxel/carboplatin/trastuzumab (TCH) and docetaxel/cyclophosphamide (TC) were the most frequently hospitalised. After adjustment for demographic and clinical factors, the increased risk of hospitalisation for TCH and TC remained compared with doxorubicin/cyclophosphamide 3-weekly (OR 1.71, 95% confidence interval [CI] 1.24-2.37 and OR 1.47, 95% CI 1.17-1.85 respectively). Five-year overall survival was similar for women who were (92.2%, 95% CI 90.7-93.8) and were not hospitalised (93.1%, 95% CI 92.1-94.1). CONCLUSION: Emergency hospitalisations following chemotherapy for early breast cancer were relatively common, especially following docetaxel-containing protocols. Further examination of reasons for admission is needed to inform actions to improve patient safety.

Accelerated induction regimens of TNF-alpha inhibitors in patients with inflammatory bowel disease: a scoping review protocol.

INTRODUCTION: Tumour necrosis factor (TNF)-alpha inhibitors are commonly used to treat inflammatory bowel disease (IBD). In patients with IBD who are unresponsive to their first induction dose, the implementation of an 'accelerated' induction dose schedule (doses more frequent than recommended in product monographs) is becoming increasingly common. It is unclear whether this practice results in favourable patient outcomes, such as avoidance of surgery and disease remission. As such, there is a need to identify and map the current evidence base on accelerated induction schedules of these medications in the treatment of IBD. METHODS AND ANALYSIS: A scoping review will be employed to systematically identify and characterise the nature of scientific literature on accelerated induction regimens of TNF-alpha inhibitors. MEDLINE, Embase, International Pharmaceutical Abstracts and grey literature will be searched to identify relevant studies. The titles/abstracts of all records and full text of potentially relevant articles will be independently screened for inclusion by two reviewers. Data will be abstracted from included studies by one reviewer and verified for accuracy by another. The findings will be synthesised descriptively. ETHICS AND DISSEMINATION: We intend to report the findings of this scoping review in a peer-reviewed journal and a scientific conference. TRIAL REGISTRATION: This research was registered prospectively with the Open Science Framework (https://osf.io/z7n2d/).

Testosterone therapy in hypogonadal men: a systematic review and network meta-analysis.

OBJECTIVE: To assess the relative effects of individual testosterone products among hypogonadal men. DESIGN: Systematic review and network meta-analysis. METHODS: We searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (25 May 2017) for randomised-controlled trials (RCTs) and non-randomised studies (NRS) that involved hypogonadal men given testosterone replacement therapy (TRT) for ≥3 months. Comparators were placebo, another TRT, or the same product at a different dose. Outcomes were quality of life, depression, libido, erectile function, activities of daily living and testosterone levels, as well as cardiovascular death, myocardial infarction, stroke, prostate cancer, heart disease, diabetes, serious adverse events, withdrawals due to adverse events and erythrocytosis. RCT data were pooled via meta-analysis and network meta-analysis. Risk of bias was assessed using Cochrane's risk of bias tool (RCTs) andScottish Intercollegiate Guidelines Network (SIGN)50 (NRS). RESULTS: Eighty-seven RCTs and 51 NRS were included. Most were at high or unclear risk of bias, with short treatment duration and follow-up. When compared as a class against placebo, TRT improved quality of life (standardised mean difference (SMD) -0.26, 95% CI -0.41 to -0.11), libido (SMD 0.33, 95% CI 0.16 to 0.50), depression (SMD -0.23, 95% CI -0.44 to -0.01) and erectile function (SMD 0.25, 95% CI 0.10 to 0.41). Most individual TRTs were significantly better than placebo at improving libido (6/10). Only one TRT was better than placebo at improving quality of life, and no individual TRTs improved depression or erectile function. There was no increased risk of adverse events, with the exception of withdrawals due to adverse events with the use of some TRTs. CONCLUSION: Despite a class effect of improving quality of life, depression, erectile function and libido, major improvements were not observed with the use of any individual product. We observed no statistically significant increase in the risk of adverse events; however, longer-term high-quality trials are needed to fully assess the risk of harm. PROSPERO REGISTRATION NUMBER: CRD42014009963.

Nursing Management of the Patient Undergoing Focused Ultrasound: A New Treatment Option for Essential Tremor.

Essential tremor (ET) is among the most common neurological movement disorders that causes postural or action tremors, with an estimated prevalence nationwide of less than 3% of the population. The incidence of ET increases with age but often affects younger adults and has a familial trait association. Depending on disease progression, ET can cause significant limitations for individuals, in many cases, significantly limiting their ability to perform activities of daily living and occupational responsibilities. Until recently, treatment of ET heavily relied on medication management and invasive surgery, such as deep brain stimulation. With advances in the use of focused ultrasound (FUS) for treatment of various medical conditions, recent clinical trials have revealed positive outcomes with the use of FUS as a less invasive approach to treat patients with medication-refractory ET. In a large academic medical center in the mid-Atlantic region, the Department of Neurosurgery conducted a continued access study, recently approved by the Food and Drug Administration, to evaluate the effectiveness of transcranial FUS thalamotomy for the treatment of medication-refractory ET. One patient's experience will be introduced, including discussion of evidence-based treatment options for ET and information on the nursing management of the patient undergoing FUS thalamotomy.

A novel autotaxin inhibitor reduces lysophosphatidic acid levels in plasma and the site of inflammation.

Autotaxin is the enzyme responsible for the production of lysophosphatidic acid (LPA) from lysophosphatidyl choline (LPC), and it is up-regulated in many inflammatory conditions, including but not limited to cancer, arthritis, and multiple sclerosis. LPA signaling causes angiogenesis, mitosis, cell proliferation, and cytokine secretion. Inhibition of autotaxin may have anti-inflammatory properties in a variety of diseases; however, this hypothesis has not been tested pharmacologically because of the lack of potent inhibitors. Here, we report the development of a potent autotaxin inhibitor, PF-8380 [6-(3-(piperazin-1-yl)propanoyl)benzo[d]oxazol-2(3H)-one] with an IC(50) of 2.8 nM in isolated enzyme assay and 101 nM in human whole blood. PF-8380 has adequate oral bioavailability and exposures required for in vivo testing of autotaxin inhibition. Autotaxin's role in producing LPA in plasma and at the site of inflammation was tested in a rat air pouch model. The specific inhibitor PF-8380, dosed orally at 30 mg/kg, provided >95% reduction in both plasma and air pouch LPA within 3 h, indicating autotaxin is a major source of LPA during inflammation. At 30 mg/kg PF-8380 reduced inflammatory hyperalgesia with the same efficacy as 30 mg/kg naproxen. Inhibition of plasma autotaxin activity correlated with inhibition of autotaxin at the site of inflammation and in ex vivo whole blood. Furthermore, a close pharmacokinetic/pharmacodynamic relationship was observed, which suggests that LPA is rapidly formed and degraded in vivo. PF-8380 can serve as a tool compound for elucidating LPA's role in inflammation.

Parent perceptions of nutritional issues during their child's treatment for cancer.

To examine family mealtime interactions, parental concerns about nutrition, and body mass index (BMI) among children with cancer who did not have primary central nervous system involvement. Parents of 95 children receiving treatment for cancer and 95 comparisons completed the About Your Child's Eating-Revised (AYCE-R) measure. Anthropometric data for children with cancer were obtained from medical charts at diagnosis and again when the AYCE-R was administered. No differences in mealtime interactions were found between children with cancer and comparisons, but parents of children with cancer reported greater concern about their child's weight. Anthropometric measures for children with cancer were consistent with national norms. However, children with cancer were somewhat underweight at diagnosis and became heavier over time. Lower BMI was associated with mother and father report of greater resistance from the child at mealtime, father report of his own aversion to family meals, and more severe treatment. The impact of cancer on family mealtime interactions and BMI appeared minimal during treatment. However, further longitudinal research is needed given the risk for late effects, such as growth problems and obesity, among cancer survivors. Families also may benefit from ongoing education to optimize healthy lifestyles among survivors.