The development, use, and challenges of electromechanical tissue stimulation systems.

BACKGROUND: Tissue stimulations greatly affect cell growth, phenotype, and function, and they play an important role in modeling tissue physiology. With the goal of understanding the cellular mechanisms underlying the response of tissues to external stimulations, in vitro models of tissue stimulation have been developed in hopes of recapitulating in vivo tissue function. METHODS: Herein we review the efforts to create and validate tissue stimulators responsive to electrical or mechanical stimulation including tensile, compression, torsion, and shear. RESULTS: Engineered tissue platforms have been designed to allow tissues to be subjected to selected types of mechanical stimulation from simple uniaxial to humanoid robotic stain through equal-biaxial strain. Similarly, electrical stimulators have been developed to apply selected electrical signal shapes, amplitudes, and load cycles to tissues, lending to usage in stem cell-derived tissue development, tissue maturation, and tissue functional regeneration. Some stimulators also allow for the observation of tissue morphology in real-time while cells undergo stimulation. Discussion on the challenges and limitations of tissue simulator development is provided. CONCLUSIONS: Despite advances in the development of useful tissue stimulators, opportunities for improvement remain to better reproduce physiological functions by accounting for complex loading cycles, electrical and mechanical induction coupled with biological stimuli, and changes in strain affected by applied inputs.

A case for genetic testing: Arrhythmogenic cardiomyopathy presenting as myocarditis.

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy associated with fibrofatty tissue replacement of the ventricular tissue. The disease can cause ventricular dysfunction and arrhythmias and can increase the risk of sudden cardiac death. This cardiomyopathy can have variable clinical presentations, especially in the pediatric and young adult populations. In this report, we describe the case of an 18-year-old female with myocarditis as the initial presentation of ACM. She presented following a resuscitated cardiac arrest due to ventricular arrhythmia. On arrival, myocardial edema and delayed gadolinium enhancement were present on cardiac magnetic resonance imaging, with no ventricular changes observed, making the diagnosis consistent with myocarditis. Genetic testing revealed a pathogenic mutation in the desmoplakin gene consistent with ACM. Given the unconventional initial presentation of this patient's disease, early consideration of genetic testing may be beneficial to aid in the early diagnosis and management of ACM in young patients.

A life cycle analysis of the environmental impact of procurement, waste and water in the dental practice.

Background Health care is a significant contributor to climate change. Global pressure for a change towards a more sustainable way of providing dental health care has resulted in the creation of the Green Impact Toolkit, which is comprised of a list of suggested changes that dental practices can make to become more sustainable in a number of categories, such as procurement, waste and water.Aims To compare the effectiveness of changes suggested by the Green Impact Toolkit.Materials and methods A comparative life cycle assessment (LCA) was conducted using the Ecoinvent database v3.8 and these data were processed using OpenLCA v1.10.3 software.Results The carbon footprint per patient was significantly reduced after the recommendations were implemented. For instance, using water from a rainwater collection tank instead of the mains supply saved 30 g CO2eq (carbon dioxide equivalents) per patient, a 90% reduction in carbon footprint.Discussion This comparative LCA identified some effective changes which can be easily made by a dental practice. Nevertheless, some actions require some initial financial investment and may be difficult to implement in a busy modern dental practice setting.Conclusion The findings from this study can be used to guide dental practices to making choices which are more sustainable and eco-friendly in the future.

Molecular crosstalk between insulin-like growth factors and follicle-stimulating hormone in the regulation of granulosa cell function.

Background: The last phase of folliculogenesis is driven by follicle-stimulating hormone (FSH) and locally produced insulin-like growth factors (IGFs), both essential for forming preovulatory follicles. Methods: This review discusses the molecular crosstalk of the FSH and IGF signaling pathways in regulating follicular granulosa cells (GCs) during the antral-to-preovulatory phase. Main findings: IGFs were considered co-gonadotropins since they amplify FSH actions in GCs. However, this view is not compatible with data showing that FSH requires IGFs to stimulate GCs, that FSH renders GCs sensitive to IGFs, and that FSH signaling interacts with factors downstream of AKT to stimulate GCs. New evidence suggests that FSH and IGF signaling pathways intersect at several levels to regulate gene expression and GC function. Conclusion: FSH and locally produced IGFs form a positive feedback loop essential for preovulatory follicle formation in all species. Understanding the mechanisms by which FSH and IGFs interact to control GC function will help design new interventions to optimize follicle maturation, perfect treatment of ovulatory defects, improve in vitro fertilization, and develop new contraceptive approaches.

Nurse-Led Cardiac Rehabilitation Care Coordination Program: Improving Functional Outcomes for Patients Through Automatic Referral and Effective Care Coordination.

PURPOSE: The aim of this investigation was to evaluate the impact of automated cardiac rehabilitation (CR) referral and nurse care coordination on patient and program outcomes. Specifically, the aim was to identify whether differences exist in physical and psychological function at CR Phase 2 enrollment and completion and CR Phase 2 participation and completion for hospitalized patients who receive in-person CR nurse visits versus phone consultation. Using a retrospective pre-/post-intervention descriptive design, a purposive sampling technique was used to select groups with matching clinical attributes. Dates were selected to mitigate the impact of COVID-19 on CR program enrollment and completion. METHODS: Data were abstracted from the patient electronic medical record, telemetry documentation, and CR referral tracking tool. Patient descriptors included age, sex, cardiac diagnosis/procedure (post-coronary artery bypass graft surgery, myocardial infarction, percutaneous coronary intervention, heart failure, and aortic valve repair and replacement) and cardiac risk stratification category. Patient functional outcomes included the 6-min walk test and metabolic equivalents of task levels for functional capacity; psychological function was measured by the Patient Health Questionnaire assessment. Program outcomes included discharge to CR Phase 2 enrollment, CR sessions, and completion. RESULTS: Each group had 52 patients. Age was 64 ± 12 yr, 68% were male. Perhaps indications for CR included coronary artery bypass graft surgery (44%), myocardial infarction (19%), percutaneous coronary intervention (20%), heart failure (10%), aortic valve repair and replacement (8%). Cardiac risk was low in 30%, intermediate in 65%, and high in 5%. The post-intervention group compared with the pre-intervention group had a shorter discharge to CR Phase 2 enrollment (35 ± 18 d vs 41 ± 28 d, P = .078) and significantly fewer sessions required for CR completion. CONCLUSION: Automated CR referral and nurse care coordination visits for hospitalized patients decreased the transition period between CR Phase 1 and 2. Patients were physically and psychologically prepared for earlier CR Phase 2 enrollment and successfully completed the program in fewer days than the pre-intervention group.

Examining age, period and cohort effects in attitude change to childhood vaccinations in a representative New Zealand survey: a multiyear cohort-sequential growth modelling study.

OBJECTIVES: Vaccinations are an important preventative measure in reducing the spread of infectious diseases worldwide. However, concerns of undervaccination during childhood have become increasingly common. The current study aims to investigate changes in attitudes towards childhood vaccinations prior to the COVID-19 pandemic using a national sample from New Zealand. DESIGN: Age-based, period-based, and cohort-based changes were assessed using cohort-sequential latent growth modelling in 11 overlapping birth cohorts, which spanned the ages of 23-79 years. SETTING AND PARTICIPANTS: Data were taken from the New Zealand Attitudes and Values Study where 58 654 adults completed at least one wave across a 7-year period (2013 and 2015-2019). RESULTS: The period-based and cohort-based models fit the data equally well (χ2(282)=8547.93, p<0.001, comparative fit index, CFI=0.894, root mean square error of approximation, (RMSEA)=0.074, standardised root mean square residual, SRMR=0.105; χ2(273)=8514.87, p<0.001, CFI=0.894, RMSEA=0.075, SRMR=0.105, respectively) suggesting societal factors contribute to childhood vaccination attitudes. Additionally, the findings suggest attitudes towards childhood vaccinations were becoming increasingly more positive in all birth cohorts (ps<0.001), with younger and older birth cohorts exhibiting even positive attitudes compared with middle-aged cohorts. CONCLUSION: Overall, both the cohort-based and period-based models reveal changes in vaccination attitudes suggesting that even prior to the COVID-19 pandemic, societal influences had an impact on attitudes towards childhood vaccination.

DQB1 antigen matching improves rejection-free survival in pediatric heart transplant recipients.

BACKGROUND: Presence of donor-specific antibodies (DSAs), particularly to class II antigens, remains a major challenge in pediatric heart transplantation. Donor-recipient human leukocyte antigen (HLA) matching is a potential strategy to mitigate poor outcomes associated with DSAs. We evaluated the hypothesis that antigen mismatching at the DQB1 locus is associated with worse rejection-free survival. METHODS: Data were collected from Scientific Registry of Transplant Recipients for all pediatric heart transplant recipients 2010-2021. Only transplants with complete HLA typing at the DQB1 locus for recipient and donor were included. Primary outcome was rejection-free graft survival through 5 years. RESULTS: Of 5,115 children, 4,135 had complete DQB1 typing and were included. Of those, 503 (12%) had 0 DQB1 donor-recipient mismatches, 2,203 (53%) had 1, and 1,429 (35%) had 2. Rejection-free survival through 5 years trended higher for children with 0 DQB1 mismatches (68%), compared to those with 1 (62%) or 2 (63%) mismatches (pairwise p = 0.08 for both). In multivariable analysis, 0 DQB1 mismatches remained significantly associated with improved rejection-free graft survival compared to 2 mismatches, while 1 DQB1 mismatch was not. Subgroup analysis showed the strongest effect in non-Hispanic Black children and those undergoing retransplant. CONCLUSIONS: Matching at the DQB1 locus is associated with improved rejection-free survival after pediatric heart transplant, particularly in Black children, and those undergoing retransplant. Assessing high-resolution donor typing at the time of allocation may further corroborate and refine this association. DQB1 matching may improve long-term outcomes in children stabilized either with optimal pharmacotherapy or supported with durable devices able to await ideal donors.

An in vitro comparison of intra-operative isohemagglutinin and human leukocyte antigen removal techniques in pediatric heart transplantation.

BACKGROUND: Highly sensitized pediatric patients awaiting heart transplantation experience longer wait times and thus higher waitlist mortality. Similarly, children less than 2 years of age have increased waitlist times and mortality when compared to their older peers. To improve the likelihood of successful transplantation in these patients, various strategies have been utilized, including peri-operative plasmapheresis. However, limited data exists comparing plasmapheresis techniques for antibody reduction. This study's aim was to compare the in vitro magnitude of isohemagglutinin titers (IT) and human leukocyte antigen (HLA) antibody removal and the time required between membrane-based plasmapheresis (MP) and centrifuge-based plasmapheresis (CP) incorporated into the extracorporeal (EC) circuit. METHODS: Two MP (Prismaflex) and two CP (Spectra Optia, Terumo BCT) circuits were incorporated into four separate EC circuits primed with high titer, highly sensitized type O donor whole blood. Assays were performed to determine baseline IT and anti-HLA antibodies and then at 30-minute increments until completion of the run (two plasma volume exchanges) at two hours. RESULTS: There was a decrease in anti-A and anti-B IgM and IgG titers with both MP and CP. Mean anti-A and anti-B titer reduction was by 4.625 titers (93.7% change) and 4.375 titers (93.8% change) using MP and CP, respectively. At 2 h of apheresis, CP reduced 62.5% of all ITs to ≤ 1:4, while MP reduced 50% of ITs to ≤ 1:4. Additionally, reduction of anti-HLA class II antibody to mean fluorescence intensity (MFI) <3000 was achieved with both MP and CP. At 2 h of apheresis, CP reduced MFI by 2-3.5 fold and MP reduced MFI by 1.7-2.5 fold. Both demonstrated similar hemolytic and thrombotic profiles. CONCLUSIONS: In this in vitro plasmapheresis model of IT and anti-HLA antibody reduction, both MP and CP incorporated into the EC circuit can be used quickly and effectively to reduce circulating antibodies. While CP may have some greater efficiency, further study is necessary to verify this in vivo.

Salt-inducible kinases regulate androgen synthesis in theca cells by enhancing CREB signaling.

Ovulation is the pinnacle of folliculogenesis, a process that requires an interplay between the oocyte, the granulosa cells, and the theca cells (TCs). TCs are the only source of ovarian androgens, which play a vital role in female fertility. However, abnormally elevated androgen levels reduce fertility. Therefore, uncovering novel mechanisms regulating androgen synthesis in TCs is of great significance. We have shown that salt-inducible kinases (SIKs) regulate granulosa cell steroidogenesis. Here, we investigated whether SIKs regulate androgen production in TCs. SIK2 and SIK3 were detected in the TCs of mouse ovaries and isolated TCs. Next, TCs in culture were treated with luteinizing hormone (LH) in the presence or absence of a highly specific SIK inhibitor. SIK inhibition enhanced the stimulatory effect of LH on steroidogenic gene expression and androgen production in a concentration-dependent manner. SIK inhibition alone stimulated the expression of steroidogenic genes and increased androgen production. Activation of adenylyl cyclase with forskolin or emulation of increased intracellular cyclic AMP levels stimulated steroidogenesis, an effect that was enhanced by the inhibition of SIK activity. The stimulatory effect of downstream targets of cyclic AMP was also significantly augmented by SIK inhibition, suggesting that SIKs control targets downstream cyclic AMP. Finally, it is shown that SIK2 knockout mice have higher circulating testosterone than controls. This evidence shows that TCs express SIKs and reveal novel roles for SIKs in the regulation of TC function and androgen production. This information could contribute to uncovering therapeutic targets to treat hyperandrogenic diseases.

Epitope Lability of Phosphorylated Biomarkers of the DNA Damage Response Pathway Results in Increased Vulnerability to Effects of Delayed or Incomplete Formalin Fixation.

Phosphorylated biomarkers are crucial for our understanding of drug mechanism of action and dose selection during clinical trials, particularly for drugs that target protein kinases, such as DNA-damage-response (DDR) inhibitors. However, tissue fixation conditions needed to preserve DDR-specific phospho-biomarkers have not been previously investigated. Using xenograft tissues and tightly controlled formalin fixation conditions, we assessed how preanalytical factors affect phosphorylated DDR biomarkers pRAD50(Ser635), ɣH2AX(Ser139), pKAP1(Ser824), and non-phosphorylated biomarkers cMYC and ATM. Cold ischemia times ranged from 15 min to 6 hr, and the fixation duration ranged from 24 hr to 4 weeks. Epitopes pRAD50 and pKAP1 appeared the most labile assessed with staining loss after just 15 min of cold ischemia time, while ATM was more robust showing consistent expression up to 1 hr of cold ischemia. Notably, ɣH2AX expression was lost with formalin fixation over 48 hr. The use of core needle biopsies where possible and novel fixation methods such as the 2-step temperature-controlled formalin approach may improve phosphorylated biomarker preservation; however, practical challenges may affect wider clinical application. The most essential tissue-processing step when downstream analysis includes DDR phosphorylated biomarkers is immediate tissue submersion in formalin, without delay, upon excision from the patient, followed by room temperature fixation for 24 hr.

Adherence to Sedation Targets With Weight-Based Propofol and Dexmedetomidine in Patients With Morbid Obesity.

BACKGROUND: Propofol and dexmedetomidine are routinely used in intensive care units (ICUs). Both are lipophilic, potentially leading to accumulation in adipose tissue. Limited evidence exists on what body weight to utilize in patients with morbid obesity. OBJECTIVE: The purpose of this research was to evaluate the safety and efficacy of weight-based sedation with propofol and dexmedetomidine in ICU patients with morbid obesity. METHODS: Retrospective review of ICU patients admitted from January 2018 to January 2020 who were sedated for ≥48 hours was performed. The primary outcome was the percentage of time within target sedation during the first 48 hours, stratified by body mass index (BMI) <40 or ≥40 kg/m2. Additional outcomes included adverse events and the infusion rate to achieve target sedation. Data were evaluated using descriptive statistics. RESULTS: A total of 80 patients were analyzed. Patients on propofol with a BMI <40 kg/m2 were in their target Richmond Agitation-Sedation Scale (RASS) 11.7% versus 16.1% with a BMI ≥40 kg/m2 (P = .580). Patients with a BMI <40 kg/m2 on dexmedetomidine were in their target RASS 27.6% versus 10.7% with a BMI ≥40 kg/m2 (P = .053). CONCLUSION AND RELEVANCE: Body mass index did not significantly alter propofol target sedation attainment. However, patients with morbid obesity on dexmedetomidine demonstrated significantly less time in target sedation. An actual body weight dosing strategy of these drugs did not achieve desired target sedation for those with a BMI ≥40 versus BMI <40 kg/m2. These findings support future research on the optimal sedation dosing strategy in this patient population.

An ontology of mechanisms of action in behaviour change interventions.

Background: Behaviour change interventions influence behaviour through causal processes called "mechanisms of action" (MoAs). Reports of such interventions and their evaluations often use inconsistent or ambiguous terminology, creating problems for searching, evidence synthesis and theory development. This inconsistency includes the reporting of MoAs. An ontology can help address these challenges by serving as a classification system that labels and defines MoAs and their relationships. The aim of this study was to develop an ontology of MoAs of behaviour change interventions. Methods: To develop the MoA Ontology, we (1) defined the ontology's scope; (2) identified, labelled and defined the ontology's entities; (3) refined the ontology by annotating (i.e., coding) MoAs in intervention reports; (4) refined the ontology via stakeholder review of the ontology's comprehensiveness and clarity; (5) tested whether researchers could reliably apply the ontology to annotate MoAs in intervention evaluation reports; (6) refined the relationships between entities; (7) reviewed the alignment of the MoA Ontology with other relevant ontologies, (8) reviewed the ontology's alignment with the Theories and Techniques Tool; and (9) published a machine-readable version of the ontology. Results: An MoA was defined as "a process that is causally active in the relationship between a behaviour change intervention scenario and its outcome behaviour". We created an initial MoA Ontology with 261 entities through Steps 2-5. Inter-rater reliability for annotating study reports using these entities was α=0.68 ("acceptable") for researchers familiar with the ontology and α=0.47 for researchers unfamiliar with it. As a result of additional revisions (Steps 6-8), 23 further entities were added to the ontology resulting in 284 entities organised in seven hierarchical levels. Conclusions: The MoA Ontology extensively captures MoAs of behaviour change interventions. The ontology can serve as a controlled vocabulary for MoAs to consistently describe and synthesise evidence about MoAs across diverse sources.

Mindfulness for smoking cessation.

BACKGROUND: Mindfulness-based smoking cessation interventions may aid smoking cessation by teaching individuals to pay attention to, and work mindfully with, negative affective states, cravings, and other symptoms of nicotine withdrawal. Types of mindfulness-based interventions include mindfulness training, which involves training in meditation; acceptance and commitment therapy (ACT); distress tolerance training; and yoga. OBJECTIVES: To assess the efficacy of mindfulness-based interventions for smoking cessation among people who smoke, and whether these interventions have an effect on mental health outcomes. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, and trial registries to 15 April 2021. We also employed an automated search strategy, developed as part of the Human Behaviour Change Project, using Microsoft Academic. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster-RCTs that compared a mindfulness-based intervention for smoking cessation with another smoking cessation programme or no treatment, and assessed smoking cessation at six months or longer. We excluded studies that solely recruited pregnant women. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. We measured smoking cessation at the longest time point, using the most rigorous definition available, on an intention-to-treat basis. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for smoking cessation for each study, where possible. We grouped eligible studies according to the type of intervention and type of comparator. We carried out meta-analyses where appropriate, using Mantel-Haenszel random-effects models. We summarised mental health outcomes narratively. MAIN RESULTS: We included 21 studies, with 8186 participants. Most recruited adults from the community, and the majority (15 studies) were conducted in the USA. We judged four of the studies to be at low risk of bias, nine at unclear risk, and eight at high risk. Mindfulness-based interventions varied considerably in design and content, as did comparators, therefore, we pooled small groups of relatively comparable studies. We did not detect a clear benefit or harm of mindfulness training interventions on quit rates compared with intensity-matched smoking cessation treatment (RR 0.99, 95% CI 0.67 to 1.46; I2 = 0%; 3 studies, 542 participants; low-certainty evidence), less intensive smoking cessation treatment (RR 1.19, 95% CI 0.65 to 2.19; I2 = 60%; 5 studies, 813 participants; very low-certainty evidence), or no treatment (RR 0.81, 95% CI 0.43 to 1.53; 1 study, 325 participants; low-certainty evidence). In each comparison, the 95% CI encompassed benefit (i.e. higher quit rates), harm (i.e. lower quit rates) and no difference. In one study of mindfulness-based relapse prevention, we did not detect a clear benefit or harm of the intervention over no treatment (RR 1.43, 95% CI 0.56 to 3.67; 86 participants; very low-certainty evidence). We did not detect a clear benefit or harm of ACT on quit rates compared with less intensive behavioural treatments, including nicotine replacement therapy alone (RR 1.27, 95% CI 0.53 to 3.02; 1 study, 102 participants; low-certainty evidence), brief advice (RR 1.27, 95% CI 0.59 to 2.75; 1 study, 144 participants; very low-certainty evidence), or less intensive ACT (RR 1.00, 95% CI 0.50 to 2.01; 1 study, 100 participants; low-certainty evidence). There was a high level of heterogeneity (I2 = 82%) across studies comparing ACT with intensity-matched smoking cessation treatments, meaning it was not appropriate to report a pooled result. We did not detect a clear benefit or harm of distress tolerance training on quit rates compared with intensity-matched smoking cessation treatment (RR 0.87, 95% CI 0.26 to 2.98; 1 study, 69 participants; low-certainty evidence) or less intensive smoking cessation treatment (RR 1.63, 95% CI 0.33 to 8.08; 1 study, 49 participants; low-certainty evidence). We did not detect a clear benefit or harm of yoga on quit rates compared with intensity-matched smoking cessation treatment (RR 1.44, 95% CI 0.40 to 5.16; 1 study, 55 participants; very low-certainty evidence). Excluding studies at high risk of bias did not substantially alter the results, nor did using complete case data as opposed to using data from all participants randomised. Nine studies reported on changes in mental health and well-being, including depression, anxiety, perceived stress, and negative and positive affect. Variation in measures and methodological differences between studies meant we could not meta-analyse these data. One study found a greater reduction in perceived stress in participants who received a face-to-face mindfulness training programme versus an intensity-matched programme. However, the remaining eight studies found no clinically meaningful differences in mental health and well-being between participants who received mindfulness-based treatments and participants who received another treatment or no treatment (very low-certainty evidence). AUTHORS' CONCLUSIONS: We did not detect a clear benefit of mindfulness-based smoking cessation interventions for increasing smoking quit rates or changing mental health and well-being. This was the case when compared with intensity-matched smoking cessation treatment, less intensive smoking cessation treatment, or no treatment. However, the evidence was of low and very low certainty due to risk of bias, inconsistency, and imprecision, meaning future evidence may very likely change our interpretation of the results. Further RCTs of mindfulness-based interventions for smoking cessation compared with active comparators are needed. There is also a need for more consistent reporting of mental health and well-being outcomes in studies of mindfulness-based interventions for smoking cessation.

Mean differences in maternal body mass index and recurrent pregnancy loss: a systematic review and meta-analysis of observational studies.

OBJECTIVE: To investigate the association of maternal body mass index (BMI) and recurrent pregnancy loss (RPL). DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): A total of 3,833 women with RPL and 4,083 women as controls. INTERVENTION(S): Studies were identified through a search of PubMed, Embase, Scopus, and Cochrane. MAIN OUTCOME MEASURE(S): The primary outcome of interest was RPL using the mean differences in maternal BMI as the predictor variable. The results of the meta-analysis were reported as the mean difference with a 95% confidence interval. RESULT(S): In total, 892 studies were reviewed. Pooled data from 25 studies suggested that the maternal BMI of women with a history of recurrent pregnancy loss was significantly higher than the BMI of controls, mean difference 0.7 kg/m2 [95% confidence interval 0.2-1.3]. CONCLUSION(S): These findings supported an association between maternal BMI and RPL. Large prospective studies are needed to evaluate the influence of maternal BMI on pregnancy outcomes in women with RPL.

Hospitalizations for Respiratory Syncytial Virus and Vaccine Preventable Infections following Pediatric Heart Transplantation.

OBJECTIVE: To determine the risk factors for acquiring a respiratory syncytial virus (RSV) and vaccine-preventable infections (R/VPI) in pediatric heart transplant recipients and the associated morbidity and hospital resource use. STUDY DESIGN: Patients <18 years who underwent heart transplantation from September 2003 to December 2018 at hospitals using the Pediatric Health Information System database were identified. Their transplant hospitalization and subsequent hospitalizations for R/VPI through December 2018 were analyzed. Risk factors for R/VPI hospitalizations were evaluated using negative regression binomial models adjusted for demographic and clinical confounders. Total hospital costs were adjusted for 2018 US$. RESULTS: Of 3815 transplant recipients, 681 (17.9%) had an R/VPI hospitalization during 23 746 available person-years of follow-up. There were 984 R/VPIs diagnosed during 951 hospitalizations, and 440 (44.7%) occurred the first year after transplantation. The most common causes were RSV (n = 380; 38.6%), influenza (n = 265; 26.9%), and pneumococcus (n = 105; 10.7%). In adjusted analyses, there was an increased risk of R/VPI hospitalization in patients requiring mechanical circulatory support before transplantation, patients receiving induction with ≥2 immunosuppressive agents, and patients <2 years in the first year after transplantation. The median length of stay for an R/VPI hospitalization was 4 days (IQR, 2-8 days) with a median total cost of $11 081 (IQR, $6215-$24 322). CONCLUSIONS: Hospitalization for R/VPIs occurred frequently after heart transplantation and were associated with significant costs. Potential strategies to minimize R/VPI include expanding vaccine use through accelerated immunization schedules, further studies of use of palivizumab beyond 2 years of age, and immunogenicity monitoring after vaccination with re-immunization based on guidelines.

A systematic review: The effects of frenotomy on breastfeeding and speech in children with ankyloglossia.

Purpose: The primary objective of this systematic review was to determine if frenotomy for ankyloglossia improves breastfeeding or speech outcomes in infants and children ages birth to 12.Method: Literature selection focussed on the presence of ankyloglossia, reported as either posterior or submucosal, and the impact of surgical treatment. The two populations that were included involve infants who were breastfeeding and children with speech delays. Six search engines were utilised (PubMed, Medline, Cochrane Database, CINHAL Plus, ERIC and PsychINFO). The selected articles critically examined study characteristics, measurement tools, outcome measures, design, and summary of results, and bias.Result: Five articles met the inclusion criteria related to infants who had undergone a frenotomy and who were examining changes in breastfeeding outcomes and two articles met the inclusion criteria for changes in speech production following a frenotomy.Conclusion: Research supports the use of frenotomy in children with ankyloglossia to reduce nipple pain and improve maternal self-efficacy during breastfeeding. The classification of ankyloglossia, assessment tools used, age and timing of frenotomy, in terms of breastfeeding improvements were inconsistent across the studies. Ankyloglossia release for children with speech delays is currently inconclusive due to lack of objective data and research quality. Overall, the review also revealed inconsistent definitions of ankyloglossia severity, standardised outcome measures and research protocols.

Is there a future for the use of left ventricular assist devices in Duchenne muscular dystrophy?

Duchenne muscular dystrophy (DMD) is the most common form of childhood muscular dystrophy resulting in progressive muscle wasting and weakness. With advancements in respiratory care and the use of glucocorticoids, cardiomyopathy has surpassed respiratory compromise as the leading cause of morbidity and mortality in this patient population. As muscular dystrophy remains a relative contraindication to heart transplantation, end-stage heart failure management represents a major therapeutic challenge. Long-term left ventricular assist device (LVAD) therapy has emerged as a promising management strategy to improve the survival and quality of life in DMD cardiomyopathy. Preoperative planning, optimal patient selection, aggressive postoperative rehabilitation, and continued discussion of goals of care are critical considerations for the appropriate use of LVAD in DMD patients with cardiomyopathy.

Epidemiology of Pediatric Hypertrophic Cardiomyopathy in a 10-Year Medicaid Cohort.

The epidemiologic data for pediatric hypertrophic cardiomyopathy (HCM) needs to be periodically updated as diagnostic techniques and management strategies improve. Herein, the incidence, prevalence, and mortality rates of pediatric HCM in a population-based treatment system are described. Patients aged ≤ 17 years and diagnosed with HCM on service visits over a 10-year period in one state Medicaid database (2007-2016) were analyzed. The cohort included 137 unique patients; 64.2% were male; 40.9% were African American; 42.3% were first diagnosed ≤ 24 months. The accrued 10-year prevalence rate for pediatric HCM was 1.2/1,000,000 and the annual incidence rate (CY 2010) was 1.3/100,000. Cardiac-related mortality was 2.9% in those who died cohort (N = 10); 70.0% of those who died were ≤ 13 months of age. Arrhythmia was diagnosed in 30.7% of the cohort, heart failure in 12.4%, and low birth weight in 8.8%. Inborn errors of metabolism were diagnosed in 8.0% of the cohort; malformation syndromes in 13.1%, and neuromuscular disorders in 2.9%; therefore, 75.9% were classified as idiopathic HCM. Our findings are somewhat higher than extant study estimates but update and augment them in representing a Southeast US statewide service system.

Improving Quality of Care Through a Mandatory Provincial Audit Program: Ontario's Emergency Department Return Visit Quality Program.

The Emergency Department Return Visit Quality Program was launched in Ontario, Canada, to promote a culture of quality. It mandates the province's largest-volume emergency departments (EDs) to audit charts of patients who had a return visit leading to hospital admission, including some of their 72-hour all-cause return visits with admission and all of their 7-day ones with sentinel diagnoses (ie, acute myocardial infarction, subarachnoid hemorrhage, and pediatric sepsis), and submit their findings to a governmental agency. This provides an opportunity to identify possible adverse events and quality issues, which hospitals can then address through quality improvement initiatives. A group of emergency physicians with quality improvement expertise analyzed the submitted audits and accompanying narrative templates, using a general inductive approach to develop a novel classification of recurrent quality themes. Since the Return Visit Quality Program launched in 2016, 125,698 return visits with admission have been identified, representing 0.93% of the 86 participating EDs' 13,559,664 visits. Overall, participating hospitals have conducted 12,852 detailed chart audits, uncovering 3,010 (23.4%) adverse events/quality issues and undertaking hundreds of quality improvement provincewide projects as a result. The inductive analysis revealed 11 recurrent themes, classified into 3 groupings: patient characteristics (ie, patient risk profile and elder care), ED team actions or processes (ie, physician cognitive lapses, documentation, handover/communication between providers, radiology, vital signs, and high-risk medications or medication interactions), and health care system issues (ie, discharge planning/community follow-up, left against medical advice/left without being seen, and imaging/testing availability). The Return Visit Quality Program is the largest mandatory audit program for EDs and provides a novel approach to identify local adverse events/quality issues to target for improved patient safety and quality of care. It provides a blueprint for health system leaders to enable clinicians to develop an approach to organizational quality, as well as for teams to construct an audit system that yields defined issues amenable to improvement.