Impact of mobile phone use on accidental falls risk in young adult pedestrians.

Background: Mobile phone use is known to be a distraction to pedestrians, increasing their likelihood of crossing into oncoming traffic or colliding with other people. However, the effect of using a mobile phone to text while walking on gait stability and accidental falls in young adults remains inconclusive. This study uses a 70 cm low friction slip hazard and the threat of hazard to investigate the effects of texting while walking on gait stability, the ability to recover balance after a slip hazard and accidental falls. Methods: Fifty healthy young adults performed six walking tasks, and one seated texting task in random order. The walks were conducted over a 10-m walkway. Four progressive hazard levels were used: 1) Seated; 2) Normal Walk (walking across the walkway with no threat of a slip); 3) Threat (walking with the threat of a slip); and 4) Slip (walking with an actual 70 cm slip hazard). The three walking conditions were repeated twice with and without the mobile phone texting dual-task. Gait kinematics and trunk posture were recorded using wearable sensors attached to the head, trunk, pelvis and feet. Study outcomes were analyzed using repeated measures analysis of variance with significance set to P≤.05. Results: Mobile phone use significantly impaired postural balance recovery when slipping, as demonstrated by increased trunk sway. Mobile phone use negatively impacted gait stability as demonstrated by increased step time variability and decreased harmonic ratios. Increased hazard levels also led to reduced texting accuracy. Conclusions: Using a mobile phone to text while walking may compete with locomotor tasks, threat assessment and postural balance control mechanisms, which leads to an increased risk of accidental falls in young adults. Pedestrians should therefore be discouraged through new educational and technology-based initiatives (for example a "texting lock" on detection of walking) from texting while walking on roadside footpaths and other environments where substantial hazards to safety exist.

Peptide Nucleic Acids Containing Cationic/Amino-Alkyl Modified Bases Promote Enhanced Hybridization Kinetics and Thermodynamics with Single-Strand DNA.

Peptide nucleic acids (PNAs) are antisense molecules with excellent polynucleotide hybridization properties; they are resistant to nuclease degradation but often have poor cell permeability leading to moderate cellular activity and limited clinical results. The addition of cationic substitutions (positive charges) to PNA molecules greatly increases cell permeability. In this report, we describe the synthesis and polynucleotide hybridization properties of a novel cationic/amino-alkyl nucleotide base-modified PNA (OPNA). This study was designed to quantitate the effect the cationic/amino-alkyl nucleotide base modification had on the kinetic and thermodynamic properties of OPNA-DNA hybridization using surface plasmon resonance and UV thermal melt studies. Kinetic studies reveal a favorable 10-30 fold increase in affinity for a single cationic modification on the base of an adenine, cytosine, or guanidine OPNA sequence compared to the nonmodified PNA strand. The increase in affinity is correlated directly with a favorable decrease in the dissociation rate constant and increase in the association rate constant. Introducing additional amino-alkyl base modifications further favors a decrease in the dissociation rate (3-10-fold per amino-alkyl). The thermodynamics driving the OPNA hybridization is promoted by an additional favorable -80 kJ/mol enthalpy of binding for a single amino-alkyl modification compared to the PNA strand. This increase in enthalpy is consistent with an ion-ion interaction with the DNA strand. These kinetic and thermodynamic hybridization studies reveal for the first time that this type of cationic/amino-alkyl base-modified PNA has favorable hybridization properties suitable for development as an antisense oligomer.

Current status of cardiopulmonary resuscitation training and automatic external defibrillator availability in high schools in Halifax, Nova Scotia, Canada.

Background: School-based cardiopulmonary resuscitation (CPR) training and early use of an automated external defibrillator (AED) have proven to increase the survival of victims of sudden cardiac arrest (SCA). This study aimed to determine the status of CPR training, availability of AEDs, and medical emergency response programs (MERPs) in high schools in Halifax Regional Municipality. Method: High school principals were asked to participate in a voluntary online survey comprising questions about demographics, AEDs availability, CPR training for staff and students, the existence of MERPs, and perceived barriers. Three autogenerated reminders followed the initial invitation. Results: Out of 51 schools, 21 (41%) responded, only 10% (2/21) and 33% (7/21) reported providing CPR training to students and staff, respectively. About 35% (7/20) of the schools reported having AEDs, but only 10% (2/20) have MERPs for SCA. All respondents reported in favor of AED availability in schools. The reported barriers to CPR training included limited financial resources (54%), perception of low priority (23%), and time constraints (23%). Respondents reported limited financial resources (85%) and the lack of trained staff to use (30%) as the main reasons for the unavailability of AEDs. Conclusion: This survey showed that all respondents overwhelmingly favour having access to AEDs. However, the availability of CPR and AED training for staff and students in schools remains inadequate. Emergency action plans have not been devised, and few schools have AED devices. More education and awareness are needed to ensure lifesaving equipment and practices in all Halifax Regional Municipality schools.

Increased intracranial pressure in a patient with Congenital Heart Defect and Ectodermal Dysplasia (CHDED): Extension of phenotype and review of literature.

Congenital heart defect (CHD) is a birth defect that affects the structure of the heart. Although CHD is often multifactorial, it can also be inherited as part of a Mendelian disorder such as in congenital heart defect and ectodermal dysplasia (CHDED). This disorder is caused by de novo variants in PRKD1. Here, we describe a patient with a novel de novo variant of PRKD1 with phenotypic features consistent with CHDED. Previously unreported features were noted including high intracranial pressure (ICP), partial anomalous pulmonary venous return (PAPVR), and bifid uvula. We suggest that these features may be associated with CHDED.

Alternative to Body Surface Area as a Solution to Correct Systematic Bias in Pediatric Echocardiography z Scores.

BACKGROUND: Z scores are the method of choice to report dimensions in pediatric echocardiography. Z scores based on body surface area (BSA) have been shown to cause systematic biases in overweight and obese children. Using aortic valve (AoV) diameters as a paradigm, the aims of this study were to assess the magnitude of z score underestimation in children with increased body mass index z score (BMI-z) and to determine if a predicting model with height and weight as independent predictors would minimise this bias. METHODS: In this multicentre, retrospective, cross-sectional study, 15,006 normal echocardiograms in healthy children 1-18 years old were analyzed. Residual associations with body size were assessed for previously published z score. BSA-based and alternate prediction models based on height and weight were developed and validated in separate training and validation samples. RESULTS: Existing BSA-based z scores incompletely adjusted for weight, BSA, and BMI-z and led to an underestimation of > 0.8 z score units in subjects with higher BMI-z compared with lean subjects. BSA-based models led to overestimation of predicted AoV diameters with increasing weight or BMI-z. Models using height and weight as independent predictors improved adjustment with body size, including in children with higher BMI-z. CONCLUSIONS: BSA-based models result in underestimation of z scores in patients with high BMI-z. Prediction models using height and weight as independent predictors minimise residual associations with body size and generate well fitted predicted values that could apply to all children, including those with low or high BMI-z.

Long COVID-19: A Primer for Cardiovascular Health Professionals, on Behalf of the CCS Rapid Response Team.

It is now widely recognized that COVID-19 illness can be associated with significant intermediate and potentially longer-term physical limitations. The term, "long COVID-19" is used to define any patient with persistent symptoms after acute COVID-19 infection (ie, after 4 weeks). It is postulated that cardiac injury might be linked to symptoms that persist after resolution of acute infection, as part of this syndrome. The Canadian Cardiovascular Society Rapid Response Team has generated this document to provide guidance to health care providers on the optimal management of patients with suspected cardiac complications of long COVID-19.

Preparing for CBME: How often are faculty observing residents?

BACKGROUND: The Royal College of Physicians and Surgeons of Canada officially launched 'Competence by Design' in July 2017, moving from time-based to outcomes-based training. Transitioning to competency-based medical education (CBME) necessitates change in resident assessment. A greater frequency of resident observation will likely be required to adequately assess whether entrustable professional activities have been achieved. PURPOSE: Characterize faculty and resident experiences of direct observation in a single paediatric residency program, pre-CBME implementation. Qualitatively describe participants' perceived barriers and incentives to participating in direct observation. METHODS: Surveys were sent to paediatric residents and faculty asking for demographics, the frequency of resident observation during an average 4-week rotation, perceived ideal frequency of observation, and factors influencing observation frequency. Descriptive data were analyzed. Institutional research ethics board approval was received. RESULTS: The response rate was 54% (34/68 faculty and 16/25 residents). When asked the MAXIMUM frequency FACULTY observed a resident take a history, perform a physical examination, or deliver a plan, the median faculty reply was 1, 2, and 3, for outpatient settings and 0, 1, and 2, for inpatient settings. The median RESIDENT reply was 2, 4, and 10 for outpatient settings and 1, 2, and 20 for inpatient settings. When asked the MINIMUM frequency for each domain, the median FACULTY and RESIDENT reply was 0, except for delivering a plan in the inpatient setting. Faculty reported observing seniors delivering the plan more frequently than junior residents. Faculty and resident median replies for how frequently residents should be observed for each domain were the same, three to four, three to four, and five to six times. Four per cent of faculty reported regularly scheduling observations, and 77% of residents regularly ask to be observed. The most common barriers to observation were too many patients to see and both faculty and residents were seeing patients at the same time. Most faculty and resident responders felt that observation frequency could be improved if scheduled at the start of the rotation; faculty were provided a better tool for assessment; and if residents asked to be observed. CONCLUSIONS: This study provides baseline data on how infrequent faculty observation is occurring and at a frequency lower than what faculty and residents feel is necessary. The time needed for observation competes with clinical service demands, but better scheduling strategies and assessment tools may help.

Female and male perspectives on male partner roles in expanded carrier screening.

PURPOSE: To explore facilitators and barriers for male partner follow through carrier screening (CS) after their female partners were identified as carriers, from both male and female perspectives. METHODS: Participants were either females identified as a carrier through CS (512 participants) or males who had CS (125 participants). Participants were recruited via e-mails with survey links. The survey explored factors surrounding decisions to pursue CS or not. RESULTS: Males who attended the females' CS appointment were more likely to have CS (OR: 2.07). More male partners of females identified as carriers of severe or profound conditions pursued CS (82.0%) than male partners of females who were carriers for moderate conditions (50.0%). Logistic factors were more impactful for males who pursued CS. Females whose male partners did not test endorsed personal belief factors as most impactful, reporting the perceived low risk (75.0%) and his low concern for the specific condition (65.5%) were the top reasons their partners did not test. CONCLUSION: Many factors impact how male partners appraise reproductive risk from CS and make decisions regarding their own screening. Advising that male partners attend CS appointments may increase the likelihood of follow through CS. Thorough and repeated risk counseling is indicated.

Cardiovascular Care Delivery During the Second Wave of COVID-19 in Canada.

Hospitals and ambulatory facilities significantly reduced cardiac care delivery in response to the first wave of the COVID-19 pandemic. The deferral of elective cardiovascular procedures led to a marked reduction in health care delivery with a significant impact on optimal cardiovascular care. International and Canadian data have reported dramatically increased wait times for diagnostic tests and cardiovascular procedures, as well as associated increased cardiovascular morbidity and mortality. In the wake of the demonstrated ability to rapidly create critical care and hospital ward capacity, we advocate a different approach during the second and possible subsequent COVID-19 pandemic waves. We suggest an approach, informed by local data and experience, that balances the need for an expected rise in demand for health care resources to ensure appropriate COVID-19 surge capacity with continued delivery of essential cardiovascular care. Incorporating cardiovascular care leaders into pandemic planning and operations will help health care systems minimise cardiac care delivery disruptions while maintaining critical care and hospital ward surge capacity and continuing measures to reduce transmission risk in health care settings. Specific recommendations targeting the main pillars of cardiovascular care are presented: ambulatory, inpatient, procedural, diagnostic, surgical, and rehabilitation.

Type effect of inhibitory KT tape on measured vs. perceived maximal grip strength.

This study examined the effects of KT tape (KT) applied in an inhibitory manner on muscle activity, measured maximal grip strength, and perceived maximal grip strength in regular KT-users and non-users. This study was a single-blinded crossover study with sixty participants including 27 kT-users and 33 non-users. Participants underwent maximal grip strength tests with and without inhibitory KT applied across the wrist extensors. Muscle activity and maximal grip strength were measured, while perceived maximal grip strength was rated using a visual analogue scale. No significant interaction effect was found between taping conditions and participant KT-experience for muscle activity (F = 0.825, p = 0.367), measured grip strength (F = 1.018, p = 0.317) or perceived grip strength (F = 0.122, p = 0.728). No significant differences were observed in the EMG activity between taping conditions for either KT-users (p = 0.367) or non-users (p = 0.215). A similar trend was found in the measured grip strength (KT-users: p = 0.317; non-users: p = 0.294) and perceived grip strength (KT-users: p = 0.728; non-users: p = 0.063). KT applied in an inhibitory manner does not impede EMG activity, measured maximal grip strength, or perceived maximal grip strength in adults, regardless of their preconceived notions of KT.

Clinical Utility of Expanded Carrier Screening: Reproductive Behaviors of At-Risk Couples.

Expanded carrier screening (ECS) analyzes dozens or hundreds of recessive genes to determine reproductive risk. Data on the clinical utility of screening conditions beyond professional guidelines are scarce. Individuals underwent ECS for up to 110 genes. Five-hundred thirty-seven at-risk couples (ARC), those in which both partners carry the same recessive disease, were invited to participate in a retrospective IRB-approved survey of their reproductive decision making after receiving ECS results. Sixty-four eligible ARC completed the survey. Of 45 respondents screened preconceptionally, 62% (n = 28) planned IVF with PGD or prenatal diagnosis (PNDx) in future pregnancies. Twenty-nine percent (n = 13) were not planning to alter reproductive decisions. The remaining 9% (n = 4) of responses were unclear. Of 19 pregnant respondents, 42% (n = 8) elected PNDx, 11% (n = 2) planned amniocentesis but miscarried, and 47% (n = 9) considered the condition insufficiently severe to warrant invasive testing. Of the 8 pregnancies that underwent PNDx, 5 were unaffected and 3 were affected. Two of 3 affected pregnancies were terminated. Disease severity was found to have significant association (p = 0.000145) with changes in decision making, whereas guideline status of diseases, controlled for severity, was not (p = 0.284). Most ARC altered reproductive planning, demonstrating the clinical utility of ECS. Severity of conditions factored into decision making.

Systematic design and comparison of expanded carrier screening panels.

PurposeThe recent growth in pan-ethnic expanded carrier screening (ECS) has raised questions about how such panels might be designed and evaluated systematically. Design principles for ECS panels might improve clinical detection of at-risk couples and facilitate objective discussions of panel choice.MethodsGuided by medical-society statements, we propose a method for the design of ECS panels that aims to maximize the aggregate and per-disease sensitivity and specificity across a range of Mendelian disorders considered serious by a systematic classification scheme. We evaluated this method retrospectively using results from 474,644 de-identified carrier screens. We then constructed several idealized panels to highlight strengths and limitations of different ECS methodologies.ResultsBased on modeled fetal risks for "severe" and "profound" diseases, a commercially available ECS panel (Counsyl) is expected to detect 183 affected conceptuses per 100,000 US births. A screen's sensitivity is greatly impacted by two factors: (i) the methodology used (e.g., full-exon sequencing finds more affected conceptuses than targeted genotyping) and (ii) the detection rate of the screen for diseases with high prevalence and complex molecular genetics (e.g., fragile X syndrome).ConclusionThe described approaches enable principled, quantitative evaluation of which diseases and methodologies are appropriate for pan-ethnic expanded carrier screening.

Cost-effectiveness analysis of potentially curative and combination treatments for hepatocellular carcinoma with person-level data in a Canadian setting.

Patients with early-stage hepatocellular carcinoma (HCC) are potential candidates for curative treatments such as radiofrequency ablation (RFA), surgical resection (SR), or liver transplantation (LT), which have demonstrated a significant survival benefit. We aimed to estimate the cost-effectiveness of curative and combination treatment strategies among patients diagnosed with HCC during 2002-2010. This study used Ontario Cancer Registry-linked administrative data to estimate effectiveness and costs (2013 USD) of the treatment strategies from the healthcare payer's perspective. Multiple imputation by logistic regression was used to handle missing data. A net benefit regression approach of baseline important covariates and propensity score adjustment were used to calculate incremental net benefit to generate incremental cost-effectiveness ratio (ICER) and uncertainty measures. Among 2,222 patients diagnosed with HCC, 10.5%, 14.1%, and 10.3% received RFA, SR, and LT monotherapy, respectively; 0.5-3.1% dual treatments; and 0.5% triple treatments. Compared with no treatment (53.2%), transarterial chemoembolization (TACE) + RFA (average $2,465, 95% CI: -$20,000-$36,600/quality-adjusted life years [QALY]) or RFA monotherapy ($15,553, 95% CI: $3,500-$28,500/QALY) appears to be the most cost-effective modality with lowest ICER value. The cost-effectiveness acceptability curve showed that if the relevant threshold was $50,000/QALY, RFA monotherapy and TACE+ RFA would have a cost-effectiveness probability of 100%. Strategies using LT delivered the most additional QALYs and became cost-effective at a threshold of $77,000/QALY. Our findings found that TACE+ RFA dual treatment or RFA monotherapy appears to be the most cost-effective curative treatment for patients with potential early stage of HCC in Ontario. These findings highlight the importance of identifying and measuring differential benefits, costs, and cost-effectiveness of alternative HCC curative treatments in order to evaluate whether they are providing good value for money in the real world.

Canadian Cardiovascular Society/Canadian Pediatric Cardiology Association Position Statement on Pulse Oximetry Screening in Newborns to Enhance Detection of Critical Congenital Heart Disease.

Congenital heart disease is the most common congenital malformation and approximately 3 in 1000 newborns have critical congenital heart disease (CCHD). Timely diagnosis affects morbidity, mortality, and disability, and newborn pulse oximetry screening has been studied to enhance detection of CCHD. In this position statement we present an evaluation of the literature for pulse oximetry screening. Current detection strategies including prenatal ultrasound examination and newborn physical examination are limited by low diagnostic sensitivity. Pulse oximetry screening is safe, noninvasive, easy to perform, and widely available with a high specificity (99.9%) and moderately high sensitivity (76.5%). When an abnormal saturation is obtained, the likelihood of having CCHD is 5.5 times greater than when a normal result is obtained. The use of pulse oximetry combined with current strategies has shown sensitivities of up to 92% for detecting CCHD. False positive results can be minimized by screening after 24 hours, and testing the right hand and either foot might further increase sensitivity. Newborns with abnormal screening results should undergo a comprehensive assessment and echocardiography performed if a cardiac cause cannot be excluded. Screening has been studied to be cost neutral to cost effective. We recommend that pulse oximetry screening should be routinely performed in all healthy newborns to enhance the detection of CCHD in Canada.

Pulse oximetry screening in newborns to enhance detection of critical congenital heart disease.

Pulse oximetry screening is safe, noninvasive, easy to perform and proven to enhance detection of critical congenital heart disease in newborns. However, this test has yet to be adopted as routine practice in Canada. The present practice point highlights essential details and recommendations for screening, which research has shown to be highly specific, with low false-positive rates. Optimal screening for critical congenital heart disease should include prenatal ultrasound, physical examination and pulse oximetry screening. Screening should be performed between 24 hours and 36 hours postbirth, using the infant's right hand and either foot to minimize false-positive results. Newborns with abnormal results should undergo a thorough evaluation by the most responsible health care provider. When a cardiac diagnosis cannot be excluded, referral to a paediatric cardiologist for consultation and echocardiogram is advised.

High performance enzyme kinetics of turnover, activation and inhibition for translational drug discovery.

INTRODUCTION: Enzymes are the macromolecular catalysts of many living processes and represent a sizable proportion of all druggable biological targets. Enzymology has been practiced just over a century during which much progress has been made in both the identification of new enzymes and the development of novel methodologies for enzyme kinetics. Areas covered: This review aims to address several key practical aspects in enzyme kinetics in reference to translational drug discovery research. The authors first define what constitutes a high performance enzyme kinetic assay. The authors then review the best practices for turnover, activation and inhibition kinetics to derive critical parameters guiding drug discovery. Notably, the authors recommend global progress curve analysis of dose/time dependence employing an integrated Michaelis-Menten equation and global curve fitting of dose/dose dependence. Expert opinion: The authors believe that in vivo enzyme and substrate abundance and their dynamics, binding modality, drug binding kinetics and enzyme's position in metabolic networks should be assessed to gauge the translational impact on drug efficacy and safety. Integrating these factors in a systems biology and systems pharmacology model should facilitate translational drug discovery.

Data-driven approach of CUSUM algorithm in temporal aberrant event detection using interactive web applications.

OBJECTIVE: In 2014/2015, Public Health Ontario developed disease-specific, cumulative sum (CUSUM)-based statistical algorithms for detecting aberrant increases in reportable infectious disease incidence in Ontario. The objective of this study was to determine whether the prospective application of these CUSUM algorithms, based on historical patterns, have improved specificity and sensitivity compared to the currently used Early Aberration Reporting System (EARS) algorithm, developed by the US Centers for Disease Control and Prevention. METHOD: A total of seven algorithms were developed for the following diseases: cyclosporiasis, giardiasis, influenza (one each for type A and type B), mumps, pertussis, invasive pneumococcal disease. Historical data were used as baseline to assess known outbreaks. Regression models were used to model seasonality and CUSUM was applied to the difference between observed and expected counts. An interactive web application was developed allowing program staff to directly interact with data and tune the parameters of CUSUM algorithms using their expertise on the epidemiology of each disease. Using these parameters, a CUSUM detection system was applied prospectively and the results were compared to the outputs generated by EARS. The outcome was the detection of outbreaks, or the start of a known seasonal increase and predicting the peak in activity. RESULTS: The CUSUM algorithms detected provincial outbreaks earlier than the EARS algorithm, identified the start of the influenza season in advance of traditional methods, and had fewer false positive alerts. Additionally, having staff involved in the creation of the algorithms improved their understanding of the algorithms and improved use in practice. CONCLUSION: Using interactive web-based technology to tune CUSUM improved the sensitivity and specificity of detection algorithms.

Genetic Counselors in Startup Companies: Redefining the Genetic Counselor Role.

Genetic counselors (GCs) have recently begun moving into non-clinic based roles in increasing numbers. A relatively new role for GCs is working for startup companies. Startups are newly established companies in the phase of developing and researching new scalable businesses. This article explores the experiences of four GCs working at different startup companies and aims to provide resources for GCs interested in learning more about these types of roles. The article describes startup culture, including a relatively flat organizational structure, quick product iterations, and flexibility, among other unique cultural characteristics. Financial considerations are described, including how to understand and evaluate a company's financial status, along with a brief explanation of alternate forms of compensation including stock options and equity. Specifically, the article details the uncertainties and rewards of working in a fast-paced startup environment that affords opportunities to try new roles and use the genetic counseling skill set in new ways. This article aims to aid GCs in determining whether a startup environment would be a good fit, learning how to evaluate a specific startup, and understanding how to market themselves for positions at startups.