Using Artificial Intelligence to Predict Heart Failure Risk from Single-lead Electrocardiographic Signals: A Multinational Assessment.

Importance: Despite the availability of disease-modifying therapies, scalable strategies for heart failure (HF) risk stratification remain elusive. Portable devices capable of recording single-lead electrocardiograms (ECGs) can enable large-scale community-based risk assessment. Objective: To evaluate an artificial intelligence (AI) algorithm to predict HF risk from noisy single-lead ECGs. Design: Multicohort study. Setting: Retrospective cohort of individuals with outpatient ECGs in the integrated Yale New Haven Health System (YNHHS) and prospective population-based cohorts of UK Biobank (UKB) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Participants: Individuals without HF at baseline. Exposures: AI-ECG-defined risk of left ventricular systolic dysfunction (LVSD). Main Outcomes and Measures: Among individuals with ECGs, we isolated lead I ECGs and deployed a noise-adapted AI-ECG model trained to identify LVSD. We evaluated the association of the model probability with new-onset HF, defined as the first HF hospitalization. We compared the discrimination of AI-ECG against the pooled cohort equations to prevent HF (PCP-HF) score for new-onset HF using Harrel's C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Results: There were 194,340 YNHHS patients (age 56 years [IQR, 41-69], 112,082 women [58%]), 42,741 UKB participants (65 years [59-71], 21,795 women [52%]), and 13,454 ELSA-Brasil participants (56 years [41-69], 7,348 women [55%]) with baseline ECGs. A total of 3,929 developed HF in YNHHS over 4.5 years (2.6-6.6), 46 in UKB over 3.1 years (2.1-4.5), and 31 in ELSA-Brasil over 4.2 years (3.7-4.5). A positive AI-ECG screen was associated with a 3- to 7-fold higher risk for HF, and each 0.1 increment in the model probability portended a 27-65% higher hazard across cohorts, independent of age, sex, comorbidities, and competing risk of death. AI-ECG's discrimination for new-onset HF was 0.725 in YNHHS, 0.792 in UKB, and 0.833 in ELSA-Brasil. Across cohorts, incorporating AI-ECG predictions in addition to PCP-HF resulted in improved Harrel's C-statistic (Δ=0.112-0.114), with an IDI of 0.078-0.238 and an NRI of 20.1%-48.8% for AI-ECG vs. PCP-HF. Conclusions and Relevance: Across multinational cohorts, a noise-adapted AI model with lead I ECGs as the sole input defined HF risk, representing a scalable portable and wearable device-based HF risk-stratification strategy.

Clinician-Created Video Education for Patients With AF: A Randomized Clinical Trial.

Importance: Patient education is a critical aspect of atrial fibrillation (AF) management. However, there is limited time to provide effective patient education during routine care, and resources available online are of variable quality. Objective: To determine whether clinician-led creation of video-based AF education is feasible and improves knowledge of AF. Design, Setting, and Participants: This single-center randomized clinical trial was conducted between 2020 and 2022. Outcomes were assessed prior to their clinic visit and 2 and 90 days after the visit by blinded assessors. Participants included adults with AF and congestive heart failure, hypertension, age at least 75 years (doubled), diabetes, prior stroke or transient ischemic attack or thromboembolism (doubled), vascular disease, age 65 to 74 years, and sex category scores of 1 or greater presenting for routine care at publicly funded outpatient cardiology clinics within a tertiary teaching hospital. Individuals too unwell to participate or with limited English were excluded. Data were assessed as intention to treat and analyzed from December 2022 to October 2023. Intervention: Intervention participants viewed a series of 4 videos designed and narrated by clinicians that aimed to improve understanding of AF pathophysiology, clinical presentation, diagnosis, and management. After viewing the videos, participants received weekly email links to review the videos. The control group received usual care. Main Outcomes and Measures: The prospectively selected primary outcome was AF knowledge at 90 days, measured by the validated Jessa Atrial Fibrillation Knowledge Questionnaire (JAFKQ). Results: Among 657 individuals screened, 208 adults with AF were randomized (mean [SD] age, 65.0 [12.2] years; 133 [65.2%] male) and included in analysis. Participants were randomized 1-to-1, with 104 participants in the control group and 104 participants in the video intervention group. At 90 days after the baseline clinic visit, intervention participants were more likely to correctly answer JAFKQ questions than control participants (odds ratio [OR], 1.23 [95% CI, 1.01-1.49]). The difference was greater in participants who remotely accessed videos on 3 or more occasions during the study (OR, 1.46 [95% CI, 1.14-1.88]). Conclusions and Relevance: In this randomized clinical trial of patients with AF, remotely delivered, clinician-created video education improved medium-term AF knowledge beyond usual care of standard in-clinic education. The improvement demonstrated in this study provides support for the implementation of clinician-created educational resources across the care continuum. Further work is needed to assess for impact on clinical outcomes. Trial Registration: anzctr.org.au Identifier: ANZCTRN12620000729921.

A simple method to dramatically increase C. elegans germline microinjection efficiency.

Genome manipulation methods in C. elegans require microinjecting DNA or ribonucleoprotein complexes into the microscopic core of the gonadal syncytium. These microinjections are technically demanding and represent a key bottleneck for all genome engineering and transgenic approaches in C. elegans. While there have been steady improvements in the ease and efficiency of genetic methods for C. elegans genome manipulation, there have not been comparable advances in the physical process of microinjection. Here, we report a simple and inexpensive method for handling worms using a paintbrush during the injection process that nearly tripled average microinjection rates compared to traditional worm handling methods. We found that the paintbrush increased injection throughput by substantially increasing both injection speeds and post-injection survival rates. In addition to dramatically and universally increasing injection efficiency for experienced personnel, the paintbrush method also significantly improved the abilities of novice investigators to perform key steps in the microinjection process. We expect that this method will benefit the C. elegans community by increasing the speed at which new strains can be generated and will also make microinjection-based approaches less challenging and more accessible to personnel and labs without extensive experience.

Niche cells regulate primordial germ cell quiescence in response to basement membrane signaling.

Stem cell quiescence, proliferation and differentiation are controlled by interactions with niche cells and a specialized extracellular matrix called basement membrane (BM). Direct interactions with adjacent BM are known to regulate stem cell quiescence; however, it is less clear how niche BM relays signals to stem cells that it does not contact. Here, we examine how niche BM regulates Caenorhabditis elegans primordial germ cells (PGCs). BM regulates PGC quiescence even though PGCs are enwrapped by somatic niche cells and do not contact the BM; this can be demonstrated by depleting laminin, which causes normally quiescent embryonic PGCs to proliferate. We show that following laminin depletion, niche cells relay proliferation-inducing signals from the gonadal BM to PGCs via integrin receptors. Disrupting the BM proteoglycan perlecan blocks PGC proliferation when laminin is depleted, indicating that laminin functions to inhibit a proliferation-inducing signal originating from perlecan. Reducing perlecan levels in fed larvae hampers germline growth, suggesting that BM signals regulate germ cell proliferation under physiological conditions. Our results reveal how BM signals can regulate stem cell quiescence indirectly, by activating niche cell integrin receptors.

Effect of Mobile Phone Text Messaging Self-Management Support for Patients With Diabetes or Coronary Heart Disease in a Chronic Disease Management Program (SupportMe) on Blood Pressure: Pragmatic Randomized Controlled Trial.

BACKGROUND: Maintaining engagement and support for patients with chronic diseases is challenging. SMS text messaging programs have complemented patient care in a variety of situations. However, such programs have not been widely translated into routine care. OBJECTIVE: We aimed to examine the implementation and utility of a customized SMS text message-based support program for patients with type 2 diabetes (T2D), coronary heart disease, or both within a chronic disease integrated care program. METHODS: We conducted a 6-month pragmatic parallel-group, single-blind randomized controlled trial that recruited people with T2D or coronary heart disease. Intervention participants received 4 semipersonalized SMS text messages per week providing self-management support to supplement standard care. Preprogrammed algorithms customized content based on participant characteristics, and the messages were sent at random times of the day and in random order by a fully automated SMS text messaging engine. Control participants received standard care and only administrative SMS text messages. The primary outcome was systolic blood pressure. Evaluations were conducted face to face whenever possible by researchers blinded to randomization. Participants with T2D were evaluated for glycated hemoglobin level. Participant-reported experience measures were evaluated using questionnaires and focus groups and summarized using proportions and thematic analysis. RESULTS: A total of 902 participants were randomized (n=448, 49.7% to the intervention group and n=454, 50.3% to the control group). Primary outcome data were available for 89.5% (807/902) of the participants. At 6 months, there was no difference in systolic blood pressure between the intervention and control arms (adjusted mean difference=0.9 mm Hg, 95% CI -1.1 to 2.1; P=.38). Of 642 participants with T2D, there was no difference in glycated hemoglobin (adjusted mean difference=0.1%, 95% CI -0.1% to 0.3%; P=.35). Self-reported medication adherence was better in the intervention group (relative risk=0.82, 95% CI 0.68-1.00; P=.045). Participants reported that the SMS text messages were useful (298/344, 86.6%) and easily understood (336/344, 97.7%) and motivated change (217/344, 63.1%). The lack of bidirectional messaging was identified as a barrier. CONCLUSIONS: The intervention did not improve blood pressure in this cohort, possibly because of high clinician commitment to improved routine patient care as part of the chronic disease management program as well as favorable baseline metrics. There was high program engagement, acceptability, and perceived value. Feasibility as part of an integrated care program was demonstrated. SMS text messaging programs may supplement chronic disease management and support self-care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616001689460; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371769&isReview=true. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2018-025923.

A simple method to dramatically increase C. elegans germline microinjection efficiency.

Genome manipulation methods in C. elegans require microinjecting DNA or ribonucleoprotein complexes into the microscopic core of the gonadal syncytium. These microinjections are technically demanding and represent a key bottleneck for all genome engineering and transgenic approaches in C. elegans . While there have been steady improvements in the ease and efficiency of genetic methods for C. elegans genome manipulation, there have not been comparable advances in the physical process of microinjection. Here, we report a simple and inexpensive method for handling worms using a paintbrush during the injection process that nearly tripled average microinjection rates compared to traditional worm handling methods. We found that the paintbrush increased injection throughput by substantially increasing both injection speeds and post-injection survival rates. In addition to dramatically and universally increasing injection efficiency for experienced personnel, the paintbrush method also significantly improved the abilities of novice investigators to perform key steps in the microinjection process. We expect that this method will benefit the C. elegans community by increasing the speed at which new strains can be generated and will also make microinjection-based approaches less challenging and more accessible to personnel and labs without extensive experience.

Impact of Socio-demographic Characteristics on Time in Outpatient Cardiology Clinics: A Retrospective Analysis.

Inequitable access to health services influences health outcomes. Some studies have found patients of lower socio-economic status (SES) wait longer for surgery, but little data exist on access to outpatient services. This study analyzed patient-level data from outpatient public cardiology clinics and assessed whether low SES patients spend longer accessing ambulatory services. Retrospective analysis of cardiology clinic encounters across 3 public hospitals between 2014 and 2019 was undertaken. Data were linked to age, gender, Indigenous status, country of birth, language spoken at home, number of comorbidities, and postcode. A cox proportional hazards model was applied adjusting for visit type (new/follow up), clinic, and referral source. Higher hazard ratio (HR) indicates shorter clinic time. Overall, 22 367 patients were included (mean [SD] age 61.4 [15.2], 14 925 (66.7%) male). Only 7823 (35.0%) were born in Australia and 8452 (37.8%) were in the lowest SES quintile. Median total clinic time was 84 min (IQR 58-130). Visit type, clinic, and referral source were associated with clinic time (R2 = 0.23, 0.35, 0.20). After adjusting for these variables, older patients spent longer in clinic (HR 0.94 [0.90-0.97]), though there was no difference according to SES (HR 1.02 [0.99-1.06]) or other variables of interest. Time spent attending an outpatient clinic is substantial, amplifying an already significant time burden faced by patients with chronic health conditions. SES was not associated with longer clinic time in our analysis. Time spent in clinics could be used more productively to optimize care, improve health outcomes and patient experience.

Primary prevention of cardiovascular disease in women with a Mediterranean diet: systematic review and meta-analysis.

BACKGROUND: Dietary modification is a cornerstone of cardiovascular disease (CVD) prevention. A Mediterranean diet has been associated with a lower risk of CVD but no systematic reviews have evaluated this relationship specifically in women. OBJECTIVE: To determine the association between higher versus lower adherence to a Mediterranean diet and incident CVD and total mortality in women. METHODS: A systematic search of Medline, Embase, CINAHL, Scopus, and Web of Science (2003-21) was performed. Randomised controlled trials and prospective cohort studies with participants without previous CVD were included. Studies were eligible if they reported a Mediterranean diet score and comprised either all female participants or stratified outcomes by sex. The primary outcome was CVD and/or total mortality. A random effects meta-analysis was conducted to calculate pooled hazard ratios (HRs) and confidence intervals (CIs). RESULTS: Sixteen prospective cohort studies were included in the meta-analysis (n=7 22 495 female participants). In women, higher adherence to a Mediterranean diet was associated with a lower CVD incidence (HR 0.76, 95% CI 0.72 to 0.81; I2=39%, p test for heterogeneity=0.07), total mortality (HR 0.77, 95% CI 0.74 to 0.80; I2=21%, p test for heterogeneity=0.28), and coronary heart disease (HR 0.75, 95% CI 0.65 to 0.87; I2=21%, p test for heterogeneity=0.28). Stroke incidence was lower in women with higher Mediterranean diet adherence (HR 0.87, 95% CI 0.76 to 1.01; I2=0%, p test for heterogeneity=0.89), but this result was not statistically significant. CONCLUSION: This study supports a beneficial effect of the Mediterranean diet on primary prevention of CVD and death in women, and is an important step in enabling sex specific guidelines.

Hypertension therapy using fixed-dose polypills that contain at least three medications.

Fixed-dose combination (FDC) therapy may provide a solution to treatment gaps by overcoming reasons for therapeutic inertia. To synthesise and report on available evidence on standard or low-dose combination medicines that combine at least three antihypertensive medicines. A literature search was conducted via Scopus, Embase, PubMed and the Cochrane clinical trials database. Studies were eligible for inclusion if they were randomised clinical trials that included adults (>18 years) and examined the impact of at least three antihypertensive medications on blood pressure (BP). A total of 18 trials (n=14 307) were identified that examined combinations of three or four antihypertensive medicines. Ten trials investigated the effect of a standard dose triple combination polypill, four the effect of a low-dose triple and four the effect of a low-dose quadruple combination polypill. The mean difference (MD) in systolic BP ranged from -10.6 to -41.4 for the standard dose triple combination polypill in comparison with 2.1 to -34.5 for dual combination; -9.8 to -20.6 for a low-dose combination polypill in comparison with a MD of -0.9 to -5.2 for placebo; -9.0 to -29.3 for a low-dose combination polypill compared with -2.0 to -20.6 for monotherapy or usual care. All trials reported similar rates of adverse events. Ten studies reported medication adherence, six reported >95% adherence. Triple and quadruple combination antihypertensive medications are effective. Studies of low-dose triple and quadruple combinations involving treatment naïve populations suggest initiating such combinations are safe and effective as first-line therapy for stage 2 hypertension (BP >140/90 mm Hg).

Engagement and fidelity of a cardiovascular disease prevention-focused digital health intervention in cardiology outpatient waiting rooms: a mixed-methods study.

INTRODUCTION: We delivered a video-based, cardiovascular disease prevention focused intervention in cardiology waiting rooms that increased motivation to improve cardiovascular risk behaviours and satisfaction with clinic services. To better understand the potential generalisability and scalability of such waiting room interventions, this study evaluated the fidelity of intervention delivery and barriers and enablers to implementation. METHODS: Mixed-methods process evaluation conducted among intervention participants in a randomised clinical trial. Data sources included (1) Participant screening logs, (2) Intervention delivery platform data and (3) Semi structured interviews performed with participants. Qualitative data were described using inductive thematic analysis. RESULTS: The tablet-based intervention was delivered to 220 patients (112 (50.9%) male, mean age 54.2 (SD 15.4) years). Of 765 videos opened, 636 (83.1%) were watched to completion. Most videos opened were rated (738/765, 96.5%) and video ratings were predominantly positive (661/738, (89.6%) satisfied or highly satisfied). Younger and more educated participants were more likely to rate videos highly (relative risk (RR) 1.73 (95% CI 1.28 to 2.32) and RR 1.26 (95% CI 1.07 to 1.49)) but less likely to watch videos to completion (younger: RR 0.27 (95% CI 0.17 to 0.43), more educated: RR 0.90 (95% CI 0.85 to 0.96)). Of 39 invited, 21 (53.8%) participated in semistructured interviews. Thematic analysis of responses suggested reported behaviour change post intervention may be due to increased awareness of cardiovascular risk, reduced anxiety and intrinsic motivation from delivery within a cardiology waiting room. Lack of reinforcement and limited personalisation were barriers. CONCLUSION: The current analysis demonstrates that engagement with a digitally delivered clinic waiting room educational intervention was high, providing explanation for its efficacy in improving motivation to change cardiovascular risk behaviours. The high fidelity of delivery demonstrates potential for scaling of such interventions across waiting rooms. Recall bias and low response rate may bias self-reported engagement measures. TRIAL REGISTRATION NUMBER: ANZCTR12618001725257.

Clinician-Created Educational Video Resources for Shared Decision-making in the Outpatient Management of Chronic Disease: Development and Evaluation Study.

BACKGROUND: The provision of reliable patient education is essential for shared decision-making. However, many clinicians are reluctant to use commonly available resources, as they are generic and may contain information of insufficient quality. Clinician-created educational materials, accessed during the waiting time prior to consultation, can potentially benefit clinical practice if developed in a time- and resource-efficient manner. OBJECTIVE: The aim of this study is to evaluate the utility of educational videos in improving patient decision-making, as well as consultation satisfaction and anxiety, within the outpatient management of chronic disease (represented by atrial fibrillation). The approach involves clinicians creating audiovisual patient education in a time- and resource-efficient manner for opportunistic delivery, using mobile smart devices with internet access, during waiting time before consultation. METHODS: We implemented this educational approach in outpatient clinics and collected patient responses through an electronic survey. The educational module was a web-based combination of 4 short videos viewed sequentially, followed by a patient experience survey using 5-point Likert scales and 0-100 visual analogue scales. The clinician developed the audiovisual module over a 2-day span while performing usual clinical tasks, using existing hardware and software resources (laptop and tablet). Patients presenting for the outpatient management of atrial fibrillation accessed the module during waiting time before their consultation using either a URL or Quick Response (QR) code on a provided tablet or their own mobile smart devices. The primary outcome of the study was the module's utility in improving patient decision-making ability, as measured on a 0-100 visual analogue scale. Secondary outcomes were the level of patient satisfaction with the videos, measured with 5-point Likert scales, in addition to the patient's value for clinician narration and the module's utility in improving anxiety and long-term treatment adherence, as represented on 0-100 visual analogue scales. RESULTS: This study enrolled 116 patients presenting for the outpatient management of atrial fibrillation. The proportion of responses that were "very satisfied" with the educational video content across the 4 videos ranged from 93% (86/92) to 96.3% (104/108) and this was between 98% (90/92) and 99.1% (107/108) for "satisfied" or "very satisfied." There were no reports of dissatisfaction for the first 3 videos, and only 1% (1/92) of responders reported dissatisfaction for the fourth video. The median reported scores (on 0-100 visual analogue scales) were 90 (IQR 82.5-97) for improving patient decision-making, 89 (IQR 81-95) for reducing consultation anxiety, 90 (IQR 81-97) for improving treatment adherence, and 82 (IQR 70-90) for the clinician's narration adding benefit to the patient experience. CONCLUSIONS: Clinician-created educational videos for chronic disease management resulted in improvements in patient-reported informed decision-making ability and expected long-term treatment adherence, as well as anxiety reduction. This form of patient education was also time efficient as it used the sunk time cost of waiting time to provide education without requiring additional clinician input.

Text messages for primary prevention of cardiovascular disease: The TextMe2 randomized clinical trial.

BACKGROUND: Primary prevention guidelines emphasize the importance of lifestyle modification, but many at high-risk have suboptimal cardiovascular risk factor (CVRF) control. Text message support may improve control, but the evidence is sparse. Our objective was to determine the impact of text messages on multiple CVRFs in a moderate-high risk primary prevention cohort. METHODS: This study was a single-blind randomized clinical trial comparing semi-personalized text message-based support to standard care. A random sample of adults with 10-year absolute cardiovascular risk score ≥10% and without coronary heart disease, referred from February 2019 to January 2020, were recruited from an outpatient cardiology clinic in a large tertiary hospital in Sydney, Australia. Patients were randomized 1:1 to intervention or control. Intervention participants received 4 texts per week over 6 months, and standard care, with content covering: diet, physical activity, smoking, general cardiovascular health, and medication adherence. Controls received standard care only. Content was semipersonalized (smoking status, vegetarian or not-vegetarian, physical ability, taking medications or not) and delivered randomly using automated software. The primary outcome was the difference in the proportion of patients who have ≥3 uncontrolled CVRFs (out of: low-density lipoprotein cholesterol >2.0 mmol/L, blood pressure >140/90 mm Hg, body mass index ≥25 kg/m2, physical inactivity, current smoker) at 6 months adjusted for baseline. Secondary outcomes included differences in biomedical and behavioral CVRFs. RESULTS: Among 295 eligible participants, 246 (mean age, 58.6 ± 10.7 years; 39.4% female) were randomized to intervention (n = 124) or control (n = 122). At 6 months, there was no significant difference in the proportion of patients with ≥3 uncontrolled CVRFs (adjusted relative risk [RR] 0.98; 95% confidence interval [CI] 0.75-1.29; P = .88). Intervention participants were less likely to be physically inactive (adjusted RR 0.72; 95% CI 0.57-0.92; P = .01), but there were no significant changes in other single CVRFs. More intervention participants reduced the number of uncontrolled CVRFs at 6-months from baseline than controls (86% vs 75%; RR 1.15; 95% CI 1.00-1.32; P = .04). CONCLUSIONS: In moderate-high cardiovascular risk primary prevention, text message-based support did not significantly reduce the proportion of patients with ≥3 uncontrolled CVRFs. However, the program did motivate behavior change and significantly improved cardiovascular risk factor control overall. Larger multicenter studies are needed.

Education on cardiac risk and CPR in cardiology clinic waiting rooms: a randomised clinical trial.

OBJECTIVE: Waiting time is inevitable during cardiovascular (CV) care. This study examines whether waiting room-based CV education could complement CV care. METHODS: A 2:1 randomised clinical trial of patients in waiting rooms of hospital cardiology clinics. Intervention participants received a series of tablet-delivered CV educational videos and were randomised 1:1 to receive another video on cardiopulmonary resuscitation (CPR) or no extra video. Control received usual care. The primary outcome was the proportion of participants reporting high motivation to improve CV risk-modifying behaviours (physical activity, diet and blood pressure monitoring) post-clinic. SECONDARY OUTCOMES: clinic satisfaction, CV lifestyle risk factors (RFs) and confidence to perform CPR. Assessors were blinded to treatment allocation. RESULTS: Among 514 screened, 330 were randomised (n=220 intervention, n=110 control) between December 2018 and March 2020, mean age 53.8 (SD 15.2), 55.2% male. Post-clinic, more intervention participants reported high motivation to improve CV risk-modifying behaviours: 29.6% (64/216) versus 18.7% (20/107), relative risk (RR) 1.63 (95% CI 1.04 to 2.55). Intervention participants reported higher clinic satisfaction RR: 2.19 (95% CI 1.45 to 3.33). Participants that received the CPR video (n=110) reported greater confidence to perform CPR, RR 1.61 (95% CI 1.20 to 2.16). Overall, the proportion of participants reporting optimal CV RFs increased between baseline and 30-day follow-up (16.1% vs 24.8%, OR=2.44 (95% CI 1.38 to 4.49)), but there was no significant between-group difference at 30 days. CONCLUSION: CV education delivery in the waiting room is a scalable concept and may be beneficial to CV care. Larger studies could explore its impact on clinical outcomes. TRIAL REGISTRATION NUMBER: ANZCTR12618001725257.

Acute presentation of a proximal fibular stress fracture after a total knee arthroplasty.

A 67-year-old woman underwent a routine and uneventful elective total knee arthroplasty for osteoarthritis at our centre. No intraoperative nor immediate postoperative complications were noted clinically nor radiologically. At 5 weeks postoperative, she began to notice some new discomfort in her upper calf area, with no preceding history of trauma. A Doppler ultrasound scan ruled out a deep vein thrombus. Only on further re-imaging of her knee with X-rays and CT was there shown to be a fibular fracture of the proximal third with evidence of callus formation. The pain arising from her stress fracture delayed her rehabilitation slightly, going on to require a successful manipulation under anaesthetic (0°-95°). She went on to have excellent function in her knee and the pain from the stress fracture had settled by 5 months.

While you're waiting, a waiting room-based, cardiovascular disease-focused educational program: protocol for a randomised controlled trial.

INTRODUCTION: Patients with cardiovascular disease (CVD) frequently attend outpatient clinics and spend a significant amount of time in waiting rooms. Currently, this time is poorly used. This study aims to investigate whether providing CVD and cardiopulmonary resuscitation (CPR) education to waiting patients in a cardiology clinic of a large referral hospital improves motivation to change health behaviours, CPR knowledge, behaviours and clinic satisfaction post clinic, and whether there is any impact on reported CVD lifestyle behaviours or relevant CPR outcomes at 30 days. METHODS AND ANALYSIS: Randomised controlled trial with parallel design to be conducted among 330 patients in the waiting room of a chest pain clinic in a tertiary referral hospital. Intervention (n=220) participants will receive a tablet-delivered series of educational videos catered to self-reported topics of interest (physical activity, blood pressure, diet, medications, smoking and general health) and level of health knowledge. Control (n=110) participants will receive usual care. In a substudy, intervention participants will be randomised 1:1 to receive an extra video on CPR or no extra video. The primary outcome will be the proportion of intervention and control participants who report high motivation to improve physical activity, diet and blood pressure monitoring at end of clinic. The primary outcome of the CPR study will be confidence to perform CPR post clinic. Secondary analysis will examine impact on clinic satisfaction, lifestyle behaviours, CPR knowledge and willingness to perform CPR post clinic and at 30-day follow-up. ETHICS AND DISSEMINATION: Ethics approval has been received from the Western Sydney Local Health District Human Research Ethics Committee. All patients will provide informed consent via a tablet-based eConsent framework. Study results will be disseminated via the usual channels including peer-reviewed publications and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: ANZCTR12618001725257.

Waiting Time as an Indicator for Health Services Under Strain: A Narrative Review.

As pressure increases on public health systems globally, a potential consequence is that this is transferred to patients in the form of longer waiting times to receive care. In this review, we overview what waiting for health care encompasses, its measurement, and the data available in terms of trends and comparability. We also discuss whether waiting time is equally distributed according to socioeconomic status. Finally, we discuss the policy implications and potential approaches to addressing the burden of waiting time. Waiting time for elective surgery and emergency department care is the best described type of waiting time, and it either increases or remains unchanged across multiple developed countries. There are many challenges in drawing direct comparisons internationally, as definitions for these types of waiting times vary. There are less data on waiting time from other settings, but existing data suggest waiting time presents a significant barrier to health care access for a range of health services. There is also evidence that waiting time is unequally distributed to those of lower socioeconomic status, although this may be improving in some countries. Further work to better clarify definitions, identify driving factors, and understand hidden waiting times and identify opportunities for reducing waiting time or better using waiting time could improve health outcomes of our health services.

Niche Cell Wrapping Ensures Primordial Germ Cell Quiescence and Protection from Intercellular Cannibalism.

Niche cells often wrap membrane extensions around stem cell surfaces. Niche wrapping has been proposed to retain stem cells in defined positions and affect signaling [e.g., 1, 2]. To test these hypotheses and uncover additional functions of wrapping, we investigated niche wrapping of primordial germ cells (PGCs) in the C. elegans embryonic gonad primordium. The gonad primordium contains two PGCs that are wrapped individually by two somatic gonad precursor cells (SGPs). SGPs are known to promote PGC survival during embryogenesis and exit from quiescence after hatching, although how they do so is unknown [3]. Here, we identify two distinct functions of SGP wrapping that are critical for PGC quiescence and survival. First, niche cell wrapping templates a laminin-based basement membrane around the gonad primordium. Laminin and the basement membrane receptor dystroglycan function to maintain niche cell wrapping, which is critical for normal gonad development. We find that laminin also preserves PGC quiescence during embryogenesis. Exit from quiescence following laminin depletion requires glp-1/Notch and is accompanied by inappropriate activation of the GLP-1 target sygl-1 in PGCs. Independent of basement membrane, SGP wrapping performs a second, crucial function to ensure PGC survival. Endodermal cells normally engulf and degrade large lobes extended by the PGCs [4]. When SGPs are absent, we show that endodermal cells can inappropriately engulf and cannibalize the PGC cell body. Our findings demonstrate how niche cell wrapping protects germ cells by manipulating their signaling environment and by shielding germ cells from unwanted cellular interactions that can compromise their survival.

Branching out: origins of the sea urchin larval skeleton in development and evolution.

It is a challenge to understand how the information encoded in DNA is used to build a three-dimensional structure. To explore how this works the assembly of a relatively simple skeleton has been examined at multiple control levels. The skeleton of the sea urchin embryo consists of a number of calcite rods produced by 64 skeletogenic cells. The ectoderm supplies spatial cues for patterning, essentially telling the skeletogenic cells where to position themselves and providing the factors for skeletal growth. Here, we describe the information known about how this works. First the ectoderm must be patterned so that the signaling cues are released from precise positions. The skeletogenic cells respond by initiating skeletogenesis immediately beneath two regions (one on the right and the other on the left side). Growth of the skeletal rods requires additional signaling from defined ectodermal locations, and the skeletogenic cells respond to produce a membrane-bound template in which the calcite crystal grows. Important in this process are three signals, fibroblast growth factor, vascular endothelial growth factor, and Wnt5. Each is necessary for explicit tasks in skeleton production.

Hox5 interacts with Plzf to restrict Shh expression in the developing forelimb.

To date, only the five most posterior groups of Hox genes, Hox9-Hox13, have demonstrated loss-of-function roles in limb patterning. Individual paralog groups control proximodistal patterning of the limb skeletal elements. Hox9 genes also initiate the onset of Hand2 expression in the posterior forelimb compartment, and collectively, the posterior HoxA/D genes maintain posterior Sonic Hedgehog (Shh) expression. Here we show that an anterior Hox paralog group, Hox5, is required for forelimb anterior patterning. Deletion of all three Hox5 genes (Hoxa5, Hoxb5, and Hoxc5) leads to anterior forelimb defects resulting from derepression of Shh expression. The phenotype requires the loss of all three Hox5 genes, demonstrating the high level of redundancy in this Hox paralogous group. Further analyses reveal that Hox5 interacts with promyelocytic leukemia zinc finger biochemically and genetically to restrict Shh expression. These findings, along with previous reports showing that point mutations in the Shh limb enhancer lead to similar anterior limb defects, highlight the importance of Shh repression for proper patterning of the vertebrate limb.