Physical activity as an exogenous risk factor for amyotrophic lateral sclerosis: a review of the evidence.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder. The only established epidemiological risk factors for ALS are male sex and increasing age. The role of physical activity has been debated as an environmental risk factor. Over the last decade multiple studies have attempted to delineate the architecture of ALS. These have not yet established definite risk factors, often due to low-powered studies, lack of focus on at-risk genotypes and sub-optimal methodology. We have conducted a review of all the studies published between 2009 and December 2021. The free text search terms were [(motor neuron disease) OR (MND) OR (Amyotrophic Lateral Sclerosis) OR (ALS)] AND [(Exercise) or (Physical Activity) or (PA) or (sport)]. We identified common themes, for example soccer, head injury and the physiological mechanisms that differ in ALS patients. We have analysed the relevant, available studies (n = 93), highlighting the underlying reasons for any reported discrepancies. Overall, we have found that the more highly powered studies using validated exposure methodologies, linked strenuous, anaerobic physical activity as a risk factor for ALS. Future large-scale studies focusing on specific at-risk genotypes and physical activity should be conducted to confirm this finding. This will strengthen the evidence already surrounding strenuous physical activity as an environmental risk factor for ALS and allow advice to be given to at-risk family members. Increasing our understanding of the genetic-environmental interactions in the pathophysiology of ALS will allow for the possibility of developing preventative therapeutic approaches.

Gene Expression Studies in Down Syndrome: What Do They Tell Us about Disease Phenotypes?

Down syndrome is a well-studied aneuploidy condition in humans, which is associated with various disease phenotypes including cardiovascular, neurological, haematological and immunological disease processes. This review paper aims to discuss the research conducted on gene expression studies during fetal development. A descriptive review was conducted, encompassing all papers published on the PubMed database between September 1960 and September 2022. We found that in amniotic fluid, certain genes such as COL6A1 and DSCR1 were found to be affected, resulting in phenotypical craniofacial changes. Additionally, other genes such as GSTT1, CLIC6, ITGB2, C21orf67, C21orf86 and RUNX1 were also identified to be affected in the amniotic fluid. In the placenta, dysregulation of genes like MEST, SNF1LK and LOX was observed, which in turn affected nervous system development. In the brain, dysregulation of genes DYRK1A, DNMT3L, DNMT3B, TBX1, olig2 and AQP4 has been shown to contribute to intellectual disability. In the cardiac tissues, dysregulated expression of genes GART, ETS2 and ERG was found to cause abnormalities. Furthermore, dysregulation of XIST, RUNX1, SON, ERG and STAT1 was observed, contributing to myeloproliferative disorders. Understanding the differential expression of genes provides insights into the genetic consequences of DS. A better understanding of these processes could potentially pave the way for the development of genetic and pharmacological therapies.

Racial Differences in the Diagnosis of Lyme Disease in Children.

Black children with Lyme disease compared with children of other races were less likely to have an erythema migrans lesion diagnosed (adjusted odds ratio, 0.34; 95% confidence interval, .14-.79) but more likely to have a swollen joint (adjusted odds ratio, 3.68; 95% confidence interval, 2.13-6.36) after adjustment for age and local Lyme incidence.

Intranasal fentanyl and discharge from the emergency department among children with sickle cell disease and vaso-occlusive pain: A multicenter pediatric emergency medicine perspective.

Children with sickle cell disease (SCD) commonly experience vaso-occlusive pain episodes (VOE) due to sickling of erythrocytes, which often requires care in the emergency department. Our objective was to assess the use and impact of intranasal fentanyl for the treatment of children with SCD-VOE on discharge from the emergency department in a multicenter study. We conducted a cross-sectional study at 20 academic pediatric emergency departments in the United States and Canada. We used logistic regression to test bivariable and multivariable associations between the outcome of discharge from the emergency department and candidate variables theoretically associated with discharge. The study included 400 patients; 215 (54%) were female. The median age was 14.6 (interquartile range 9.8, 17.6) years. Nineteen percent (n = 75) received intranasal fentanyl in the emergency department. Children who received intranasal fentanyl had nearly nine-fold greater adjusted odds of discharge from the emergency department compared to those who did not (adjusted odds ratio 8.99, 95% CI 2.81-30.56, p < .001). The rapid onset of action and ease of delivery without intravenous access offered by intranasal fentanyl make it a feasible initial parenteral analgesic in the treatment of children with SCD presenting with VOE in the acute-care setting. Further study is needed to determine potential causality of the association between intranasal fentanyl and discharge from the emergency department observed in this multicenter study.

Medium-term mortality after hip fractures and COVID-19: A prospective multi-centre UK study.

PURPOSE: The COVID-19 pandemic has caused 1.4 million deaths globally and is associated with a 3-4 times increase in 30-day mortality after a fragility hip fracture with concurrent COVID-19 infection. Typically, death from COVID-19 infection occurs between 15 and 22 days after the onset of symptoms, but this period can extend up to 8 weeks. This study aimed to assess the impact of concurrent COVID-19 infection on 120-day mortality after a fragility hip fracture. METHODS: A multi-centre prospective study across 10 hospitals treating 8% of the annual burden of hip fractures in England between 1st March and 30th April, 2020 was performed. Patients whose surgical treatment was payable through the National Health Service Best Practice Tariff mechanism for "fragility hip fractures" were included in the study. Patients' 120-day mortality was assessed relative to their peri-operative COVID-19 status. Statistical analysis was performed using SPSS version 27. RESULTS: A total of 746 patients were included in this study, of which 87 (11.7%) were COVID-19 positive. Mortality rates at 30- and 120-day were significantly higher for COVID-19 positive patients relative to COVID-19 negative patients (p < 0.001). However, mortality rates between 31 and 120-day were not significantly different (p = 0.107), 16.1% and 9.4% respectively for COVID-19 positive and negative patients, odds ratio 1.855 (95% CI 0.865-3.978). CONCLUSION: Hip fracture patients with concurrent COVID-19 infection, provided that they are alive at day-31 after injury, have no significant difference in 120-day mortality. Despite the growing awareness and concern of "long-COVID" and its widespread prevalence, this does not appear to increase medium-term mortality rates after a hip fracture.

Development of teaching, mentoring and supervision skills for basic training registrars: a frustrated apprenticeship?

BACKGROUND: Teaching, mentoring and supervision (TMS) are fundamental skills with a specific commitment within the Royal Australasian College of Physicians professional practice framework. The new basic training standards include 'use of appropriate educational techniques to facilitate the learning of peers, junior colleagues and other health professionals and to provide supervision for junior colleagues' but it is unclear how basic physician trainees and equivalent grade doctors (hereinafter 'registrars') will provide, learn or develop TMS skills. AIMS: To explore how registrars provide, learn and develop TMS skills. METHODS: Mixed methods approach. New Zealand registrars were invited to participate in anonymous survey regarding TMS experiences and learning. Focus groups explored skill acquisition and development more deeply. RESULTS: A total of 121 registrars from 16 District Health Boards responded. Registrars supervise two juniors daily (range 0-4+). Fewer than 1:4 have formal training in TMS skills. Free text and focus group themes include: informal development by observing role models plus personal experience of giving and receiving TMS, inequitable access to development opportunities and formal training, barriers include workload and unsupportive learning cultures. Some registrars lack confidence in delivering TMS. CONCLUSIONS: Registrars are expected to teach, mentor and supervise junior colleagues but experience a 'frustrated apprenticeship': formal training is minimal and informal training is dependent on variable role models, opportunities and systematic support. Registrars feel unprepared and lack confidence despite wanting to succeed in this domain. Suggestions for improvement include baseline formal training, purposeful role modelling by seniors and equitable promotion of TMS opportunities.

How do hospitals help patients prepare for and participate in outpatient clinics?

BACKGROUND: Patients attending general medicine outpatient clinics (GM OPC) at hospital face multiple healthcare demands in an environment that has evolved with the clinician at its centre. The ideas, knowledge and understanding that patients bring to their clinic appointments are not well studied in the New Zealand setting. AIMS: To assess how hospitals prepare patients for their outpatient appointments and encourage people to participate actively in their own care. METHODS: A prospective survey of 50 patients attending follow-up GM OPC was performed. Participants' understanding of the purpose of their appointment and knowledge of their prescription medications was explored using a nine-item questionnaire. Patient-directed hospital communication was then analysed to assess the information supplied to patients. RESULTS: Two-thirds (66%) of participants attending follow-up GM OPC recalled being informed of an appointment at the time of leaving hospital; only half (54%) felt they had been informed of the purpose of these appointments. Patient-directed communication was not completed in half (50%) of the analysed discharge letters. One-third (36%) of participants did not have specific questions for their clinic visits. CONCLUSIONS: Limited information and support is provided to patients attending follow-up GM OPC and is not tailored to individuals' health literacy. This practice assumes patients have comparable health literacy to clinicians, which may have downstream impacts on the usefulness of the clinic experience. The information that health users bring to clinic may be improved by increasing pre-clinic user engagement and deploying patient-centred tools within the healthcare environment.

Engraftment syndrome following hematopoietic stem cell transplant: A review of the literature.

Engraftment syndrome (ES) is a poorly understood condition which continues to present a significant cause of morbidity following haematopoietic stem cell transplantation (HSCT). Yet a standard approach to diagnosis and treatment of ES remains elusive and has the potential to impact patient outcomes. A literature search was performed using the databases ProQuest Health, PubMed, Medline and Embase. Included studies were published in English from 2001-2019 that reported on engraftment syndrome following HSCT. Articles were organized by study design, ES diagnostic criteria, symptom classification and treatment. The review consolidated an array of literature relating to all types of HSCT. Timing of ES onset, risk factors and outcomes were compared within the literature. Signs and symptoms of reported ES were collated to establish a concise set of diagnostic criteria that can provide rapid recognition. The use of a standard approach to ES diagnosis has the potential to improve patient outcomes and provide a uniform approach to future research.

Dermoid Cyst: Outcome Analysis in a Pediatric Referral Hospital.

PURPOSE: To describe the management of dermoid cysts in a pediatric referral hospital. METHODS: Retrospective review of 115 patients with pathological diagnosis of dermoid cyst in a pediatric referral hospital between 2003 and 2019. RESULTS: One hundred fifteen patients, 51 (44.3%) males, and 64 (55.7%) females were retrospectively reviewed. There were fifty-one (44.3%) right eyes and 64 (55.7%) left eyes. Mean age at surgery was 39.15 months (5.6 months-16.4 years). One hundred four (90.4%) lesions were superficial, and 11 (9.6%) were deep. Quadrant location was 63 (54.8%) superior-temporal, 45 (39.1%) superior-nasal, 4 (3.5%) inferior-temporal, and 2 (1.7%) in the nasal inferior quadrant. Most patients only had aesthetic concerns, but 3 (2.61%) showed lacrimal drainage obstruction symptoms, 2 (1.74%) had proptosis, and 1 case spontaneously drained to the cutaneous surface. Imaging was performed in 51 (44.3%) patients. Regarding to their radiodensity, 71.9% had low density content, 28.1% high density, and only 1 patient showed full liquid content; 10.9% showed heterogeneous content; 53.1% showed bone remodeling. Every patient but 1 underwent surgery for a barely accessible asymptomatic retrobulbar cyst. Nine cysts (7.8%) were breached during surgery. Three recurrences were found (2.6%), but only 1 was related to intraoperative breach. CONCLUSIONS: Dermoid cysts are the most common benign periorbital tumors in the pediatric population. Imaging is required for evaluation of lesions in atypical locations, deep or fixed to underlying tissue. Surgical removal is the gold standard of treatment. Multidisciplinary approach may be required in the most complex cases. After surgery, few complications and recurrences were found in our series.

Implementation of Situational Awareness in the Pediatric Oncology Setting. Does a 'huddle' Work and Is it Sustainable?

BACKGROUND: Huddles are short, regular debriefings that are designed to engage clinical staff in discussions about existing or emerging safety issues. They allow a brief conversation to take place creating a 'situational awareness' about the complexities of the healthcare environment for that day. METHODS: The huddle was implemented in a pediatric oncology service as an intervention aimed at improving patient safety and staff communication to enhance situational awareness. To ensure an efficient format for each huddle a huddle observational tool (HOT) was developed. An initial electronic anonymous survey focusing on safety and situational awareness was distributed to all of the multi-disciplinary (MDT) team. A second survey was disseminated 18 months post huddle introduction to scrutinize its effectiveness. Sustainability was assessed using staff attendance and huddle numbers. RESULTS: Four key areas demonstrated high situational awareness; safety awareness, incident management, communication and teamwork. Positive/negative pooled responses from both survey time points demonstrated a high percentage of positive responses, particularly relating to teamwork enhancement. The overwhelming finding was sustainability of the intervention of the huddle. The pediatric oncology services have now conducted over 700 huddles events over a three-year period. CONCLUSION: The initiation of the huddle has led to increased situational awareness and promotion of safety. It has been shown to be sustainable in the pediatric oncology setting, with durability and attendance of the huddle being the most significant outcome.

ICare-ACS (Improving Care Processes for Patients With Suspected Acute Coronary Syndrome): A Study of Cross-System Implementation of a National Clinical Pathway.

BACKGROUND: Efforts to safely reduce length of stay for emergency department patients with symptoms suggestive of acute coronary syndrome (ACS) have had mixed success. Few system-wide efforts affecting multiple hospital emergency departments have ever been evaluated. We evaluated the effectiveness of a nationwide implementation of clinical pathways for potential ACS in disparate hospitals. METHODS: This was a multicenter pragmatic stepped-wedge before-and-after trial in 7 New Zealand acute care hospitals with 31 332 patients investigated for suspected ACS with serial troponin measurements. The implementation was a clinical pathway for the assessment of patients with suspected ACS that included a clinical pathway document in paper or electronic format, structured risk stratification, specified time points for electrocardiographic and serial troponin testing within 3 hours of arrival, and directions for combining risk stratification and electrocardiographic and troponin testing in an accelerated diagnostic protocol. Implementation was monitored for >4 months and compared with usual care over the preceding 6 months. The main outcome measure was the odds of discharge within 6 hours of presentation RESULTS: There were 11 529 participants in the preimplementation phase (range, 284-3465) and 19 803 in the postimplementation phase (range, 395-5039). Overall, the mean 6-hour discharge rate increased from 8.3% (range, 2.7%-37.7%) to 18.4% (6.8%-43.8%). The odds of being discharged within 6 hours increased after clinical pathway implementation. The odds ratio was 2.4 (95% confidence interval, 2.3-2.6). In patients without ACS, the median length of hospital stays decreased by 2.9 hours (95% confidence interval, 2.4-3.4). For patients discharged within 6 hours, there was no change in 30-day major adverse cardiac event rates (0.52% versus 0.44%; P=0.96). In these patients, no adverse event occurred when clinical pathways were correctly followed. CONCLUSIONS: Implementation of clinical pathways for suspected ACS reduced the length of stay and increased the proportions of patients safely discharged within 6 hours. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au/ (Australian and New Zealand Clinical Trials Registry). Unique identifier: ACTRN12617000381381.

Normal saline bolus use in pediatric emergency departments is associated with poorer pain control in children with sickle cell anemia and vaso-occlusive pain.

Vaso-occlusive pain events (VOE) are the leading cause of emergency department (ED) visits in sickle cell anemia (SCA). This study assessed the variability in use of intravenous fluids (IVFs), and the association of normal saline bolus (NSB), on pain and other clinical outcomes in children with SCA, presenting to pediatric emergency departments (PED) with VOE. Four-hundred charts of children age 3-21 years with SCA/VOE receiving parenteral opioids at 20 high-volume PEDs were evaluated in a retrospective study. Data on type and amount of IVFs used were collected. Patients were divided into two groups: those who received NSB and those who did not. The association of NSB use on change in pain scores and admission rates was evaluated. Among 400 children studied, 261 (65%) received a NSB. Mean age was 13.8 ± 4.9 years; 46% were male; 92% had hemoglobin-SS. The IVFs (bolus and/or maintenance) were used in 84% of patients. Eight different types of IVFs were utilized and IVF volume administered varied widely. Mean triage pain scores were similar between groups, but improvement in pain scores from presentation-to-ED-disposition was smaller in the NSB group (2.2 vs 3.0, P = .03), while admission rates were higher (71% vs 59%, P = .01). Use of NSB remained associated with poorer final pain scores and worse change in pain scores in our multivariable model. In conclusion, wide variations in practice utilizing IVFs are common. NSB is given to >50% of children with SCA/VOE, but is associated with poorer pain control; a controlled prospective trial is needed to determine causality.

Symbolic sexism: superficial or serious bias? An investigation into images on patient call bells.

OBJECTIVES: To determine whether gendered symbols on patient call bells are restricted to our hospital or are examples of an international practice that perpetuates gender stereotypes and occupational segregation. SETTING: Multicentre, international study of hospital equipment, 2018. MAIN OUTCOME MEASURE: Types of symbols on patient call bells. RESULTS: We received 56 responses from 43 hospitals in eight countries across five continents: 37 devices included female-specific images, nine included gender-neutral images, and ten did not use imagery (for example, button-only devices). No call bells included male-specific images. CONCLUSION: Female symbols on patient call bells are an international phenomenon. Only female or gender-neutral images are used, indicating bias in their design, manufacture, and selection. Female symbols may reinforce gender stereotypes and contribute to occupational segregation and reduced equity of opportunity. We suggest alternative symbols. Individual action with coloured marker pens may provide a pragmatic short term, albeit provocative, solution. While call bell design has only a minor impact on patients, everyday bias affects all staff and society in general.

Abdominal paracentesis: use of a standardised procedure checklist and equipment kit improves procedural quality and reduces complications.

BACKGROUND: Paracentesis is a common invasive procedure performed by junior doctors. Audit of procedure conduct at two New Zealand hospitals in 2012 revealed poor performance across a range of quality measures, including documentation of informed consent, excessive catheter dwell times and inappropriate albumin prescription. Complication rates were 12.7%, compared with published rates of around 9%. A local procedure protocol did not exist. AIM: To evaluate the effect of a standardised procedure checklist (PC) and equipment kit (EK) on procedural quality and complication rates for abdominal paracentesis. METHODS: After presenting the 2012 audit results to resident doctors, we reviewed the paracentesis literature and developed a local procedure protocol (PC and EK). These tools were made readily available after an education campaign. Paracenteses performed after the intervention were studied to determine the impact on procedural quality and safety. RESULTS: Seventy-four paracenteses (14 diagnostic; 60 therapeutic) were performed in 10 months after the introduction of PC and EK. Significant improvements were observed with the use of PC including documentation of informed consent (97% vs 74%, P = <0.01) and aseptic technique (100% vs 62%, P = <0.01). Catheter dwell times <6 h improved (72% vs 48%, P = 0.02). Inappropriate albumin prescriptions were less frequent (21% vs 66%, P = <0.01). Complication rates decreased from 12.7% to 2.8% (P = <0.01). CONCLUSIONS: The PC and EK improved rates of informed consent, appropriate documentation and protocol adherence. Significantly fewer procedure-related complications occurred after introduction of these tools.

Targeted palliative care day therapy interventions using modified MYMOP2 tool can improve outcomes for patients with non-malignant diseases.

BACKGROUND: There is a paucity of evidence supporting the benefits of palliative care day therapy services for patients with non-malignant diseases. Outcome measures in this setting are also lacking. AIM: To evaluate the use of the modified Measure Yourself Medical Outcome Profile 2 (MYMOP2) tool in tailoring day therapy services toward the needs of patients with non-malignant conditions Method: A single system, 'before and after' design quality improvement study was conducted. Data were collected regarding outcome measures, re-referral rates and mortality. RESULT: After the introduction of the modified MYMOP2 tool, there was an improvement in the mean outcome scores for patients with non-malignant disease. Re-referral rates for these patients dropped by 28% during the follow up period, with no change in mortality. IMPLICATIONS FOR PRACTICE: These findings suggest that using the modified MYMOP2 tool to tailor and measure the outcome of holistic day therapy services results in a more sustained improvement for patients with non-malignant disease.

'The best laid schemes o' mice an' men': a workshop to teach the application of evidence based medicine in low- and middle-income countries.

Background Evidence-Based Medicine (EBM) is often an ideal, with beginnings in positivist science. More recent relativism, rights and ethics have challenged a binary view of EBM. Medical volunteering is a paradigm as GPs and trainees often run EBM projects in low- and middle-income countries (LMICs), which require significant contextual adaptation. We created a workshop to enable GPs and GP trainees to reflect on and plan for the factors important in the application of EBM in LMICs. We describe the first running at the 21st WONCA Europe Conference. Aim To enable GPs/trainees to plan for various factors when applying EBM in LMICs in order to promote mutual gains. Method A 75-min workshop with GPs/trainees was conducted using a variety of methods including didacticism, before and after brainstorming, vignettes, voting, role-play and feedback. Key-points highlighted were ethics, economics, politics, culture and relationships. Results Feedback was positive with recommendations to offer the workshop to all GPs/trainees. Lessons learnt were broad-ranging and important. Conclusion/Recommendation This is an effective workshop. More work is needed to bridge the 'EBM gap' in LMICs from both volunteers and recipients. This workshop should be extended to all high-income countries for all health professionals to undertake before medical placements abroad.

RNA Silencing of Exocyst Genes in the Stigma Impairs the Acceptance of Compatible Pollen in Arabidopsis.

Initial pollen-pistil interactions in the Brassicaceae are regulated by rapid communication between pollen grains and stigmatic papillae and are fundamentally important, as they are the first step toward successful fertilization. The goal of this study was to examine the requirement of exocyst subunits, which function in docking secretory vesicles to sites of polarized secretion, in the context of pollen-pistil interactions. One of the exocyst subunit genes, EXO70A1, was previously identified as an essential factor in the stigma for the acceptance of compatible pollen in Arabidopsis (Arabidopsis thaliana) and Brassica napus. We hypothesized that EXO70A1, along with other exocyst subunits, functions in the Brassicaceae dry stigma to deliver cargo-bearing secretory vesicles to the stigmatic papillar plasma membrane, under the pollen attachment site, for pollen hydration and pollen tube entry. Here, we investigated the functions of exocyst complex genes encoding the remaining seven subunits, SECRETORY3 (SEC3), SEC5, SEC6, SEC8, SEC10, SEC15, and EXO84, in Arabidopsis stigmas following compatible pollinations. Stigma-specific RNA-silencing constructs were used to suppress the expression of each exocyst subunit individually. The early postpollination stages of pollen grain adhesion, pollen hydration, pollen tube penetration, seed set, and overall fertility were analyzed in the transgenic lines to evaluate the requirement of each exocyst subunit. Our findings provide comprehensive evidence that all eight exocyst subunits are necessary in the stigma for the acceptance of compatible pollen. Thus, this work implicates a fully functional exocyst complex as a component of the compatible pollen response pathway to promote pollen acceptance.