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Advancements in medical science and technology, medicine and public health coupled with increased consciousness about nutrition and environmental and personal hygiene have paved the way for the dramatic increase in life expectancy globally in the past several decades. However, increased life expectancy has given rise to an increasing aging population, thus jeopardizing the socio-economic structure of many countries in terms of costs associated with elderly healthcare and wellbeing. In order to cope with the growing need for elderly healthcare services, it is essential to develop affordable, unobtrusive and easy-to-use healthcare solutions. Smart homes, which incorporate environmental and wearable medical sensors, actuators, and modern communication and information technologies, can enable continuous and remote monitoring of elderly health and wellbeing at a low cost. Smart homes may allow the elderly to stay in their comfortable home environments instead of expensive and limited healthcare facilities. Healthcare personnel can also keep track of the overall health condition of the elderly in real-time and provide feedback and support from distant facilities. In this paper, we have presented a comprehensive review on the state-of-the-art research and development in smart home based remote healthcare technologies.

The world’s population is aging: the expansion of the older adult population with multiple physical and health issues is now a huge socio-economic concern worldwide. Among these issues, the loss of mobility among older adults due to musculoskeletal disorders is especially serious as it has severe social, mental and physical consequences. Human body joint monitoring and early diagnosis of these disorders will be a strong and effective solution to this problem. A smart joint monitoring system can identify and record important musculoskeletal-related parameters. Such devices can be utilized for continuous monitoring of joint movements during the normal daily activities of older adults and the healing process of joints (hips, knees or ankles) during the post-surgery period. A viable monitoring system can be developed by combining miniaturized, durable, low-cost and compact sensors with the advanced communication technologies and data processing techniques. In this study, we have presented and compared different joint monitoring methods and sensing technologies recently reported. A discussion on sensors’ data processing, interpretation, and analysis techniques is also presented. Finally, current research focus, as well as future prospects and development challenges in joint monitoring systems are discussed.

Objective Kawasaki disease (KD) is a childhood vasculitis with conflicting reported North American trends in incidence and patient characteristics. Objectives: (1) determine KD incidence between 1995 and 2017; (2) compare patient characteristics by era and age group; (3) determine complication and cardiovascular follow-up rates. Methods We used population-based health administrative data to identify children (0–18 yr) hospitalized with KD in Ontario, Canada between 1995 and 2017. We excluded children with prior KD diagnosis or incomplete records. We determined the annualized incidence and follow-up trends. Results KD was diagnosed in 4,346 children between 1995 and 2017. Annual KD incidence was 22.0 (<5 yr), 6.1 (5–9 yr), and 0.6 (10–18 yr) per 100,000 children. KD incidence increased significantly for all age groups, including from 18.4 to 25.0 cases per 100,000 children <5 yr. Ninety-day mortality occurred in ≤5 children (≤0.1%). Coronary artery aneurysm (CAA) occurred in 106 children (2.4%, 95% confidence interval 2.0–2.9) during admission and 151 (3.5%, 95% confidence interval 3.0–4.1) during 11-year median follow-up. Children 10–18 yr had longer hospitalizations (4.3 vs. 3.5 days, p  = 0.003) and more CAA (7.4% vs. 3.4%, p  = 0.007). By 1-year post-diagnosis, 3970 (91.3%) and 2576 (59.3%) children had echocardiography and cardiology follow-up, respectively. Conclusions KD incidence is increasing in Ontario, with greater healthcare utilization from hospitalizations and subsequent follow-up. Impact 4346 children were hospitalized for Kawasaki disease over 22 years in Ontario, and Kawasaki disease incidence increased significantly for all age groups, males and females. Older children (10–18 years) had longer hospital length of stay, more PICU admissions and more frequent coronary artery aneurysms. Nearly all children with Kawasaki disease had follow-up echocardiography within 1 year.

Prior to initiation of therapy, an ECG performed to exclude prolonged QT interval reveals a corrected QTc of 400msec and an electrolyte panel was found to be entirely within normal range. Of the articles excluded, three were concerned with the use of domperidone as a galactagogue agent in lactating mothers; two were case reports: one reporting a prolonged QT interval secondary to domperidone therapy and one in which an excessive dose of a liquid domperidone formulation was followed by a supraventricular tachycardia; one systematic review published in Spanish was excluded—however, all studies from this review were included. Table 1 Summary of included studies examining the QTc prolonging and arrhythmogenic effects of domperidone in infants treated for GORD Citation Population/groups/setting Study type/level of evidence Outcomes Key results Comments Djeddi et al 7 Population: 31 infants with GORD divided into three groups by GA with intended treatment with domperidone Groups: A: 40 weeks (n=13) B: 33 weeks (n=7) C: 28 weeks (n=11) Dose: 0.7–1.3 mg/kg/day Setting: Neonatology unit, France Prospective Cohort Study Level 2b ECG assessment (QTc and arrhythmia) prior to and roughly 2 days after commencing domperidone Routine bloods (serum K+, Ca2+, Mg2+) were drawn and assessed for their relationship to QTc prolongation through multivariate analysis QTc calculated manually by Bazett’s formula The combined data revealed that domperidone prolonged the QTc in all groups from the baseline 373.2±4.8 msec to 387.2±5.1 msec (14 msec prolongation of the QTc interval in total dataset) Almost half of patients (48.4%) experienced QTc interval prolongation of more than 12 msec Prolongation1 of the QTc interval in the particular groups was as follows: A: 19.1±23.7 msec B: 26±14.4 msec C: −2.9±20.4 msec Serum K+ was found to be independently associated with QTc interval prolongation No arrhythmias or atrioventricular conduction issues were identified Despite the fact that the domperidone treatment prolonged the QTc interval overall and in infants with a GA of 40 weeks and 33 weeks, it did not prolong to an overtly arrhythmogenic degree In fact, as domperidone did not increase the QTc of 28-week GA infants at all, the authors suggest that the domperidone may in fact be safer than the alternative, cisapride, which they say has been found to alter cardiac conduction and QTc in this demographic No placebo group Hegar et al 10 Population: 20 roughly 5-month-old infants with GORD Groups: A: Cisapride Rx (n=10) Dose: 0.8 mg/kg/day Setting: Paediatric unit, Indonesia RCT Investigator-blinded Level 2b ECG assessment (QTc and arrhythmia) prior to and 3–5 days after commencing domperidone or cisapride Abnormal serum electrolytes, Ca2+ or Mg2+ were applied as exclusion criteria QTc calculated manually by Bazett’s formula On average, infants in the domperidone group displayed a QTc of 404±18 msec prior to therapy and 402±20 msec after commencing therapy (△QTc=-2msec) On average, infants in the cisapride group displayed a QTc of 430±27 msec prior to therapy and 404±26 msec after commencing domperidone therapy (△QTc=-26msec) One infant with a normal QTc at baseline who was subsequently randomised to receive cisapride developed a prolonged QTc (475 msec) following domperidone treatment commencement No arrhythmias or atrioventricular conduction issues were identified This study was not powered particularly well, but appears to have been well conducted With regard to QTc prolongation and arrhythmia, domperidone failed to elicit either in this cohort of infants with GORD No placebo group Gunelemez et al 12 Population: 40 premature infants (24–33 weeks GA; mean GA of 28 weeks) with GORD requiring domperidone treatment Groups: All participants were grouped as one (n=40) Dose: 0.25 mg/kg/day Setting: Neonatology unit, Turkey Prospective Cohort Study Level 2b ECG assessment (QTc and arrhythmia) prior to and 3, 7 and 14 days after commencing domperidone Serum electrolyte abnormalities, and other conditions or use of drugs known to impact QTc interval, were applied as exclusion criteria QTc calculated manually by Bazett’s formula Absolutely no change in QTc was detected from baseline (370±30 msec) to 3 (380±30 msec), 7 (370±40 msec) or 14 days (370±30 msec) post-commencement of domperidone therapy Domperidone increased the QTc interval to >450 msec in two infants (GA 26 and 30 weeks) at day 7 No arrhythmias or atrioventricular conduction issues were identified Although the results indicate that domperidone did not consistently prolong the QTc interval in most infants or promote arrhythmias, it was associated with prolongation in two infants The authors are suitably modest in their interpretation No placebo group Vieira et al 13 Population: 45 infants (35.5–42 weeks GA; mean GA of 38.6 weeks) with GORD requiring domperidone treatment Groups: All participants were grouped as one (n=45) Dose: 0.5–1.0 mg⁄kg⁄dose, 3–4 times/day Setting: Three paediatric units, Belgium Prospective Cohort Study Level 2b ECG assessment (QTc and arrhythmia) prior to and 2 hours after commencing domperidone Serum electrolyte abnormalities, and other conditions or use of drugs known to impact QTc interval, were applied as exclusion criteria QTc calculated manually by Bazett’s formula The QTc at 2 hours following domperidone administration (397±310 msec) was not significantly prolonged when compared with baseline (389±20 msec) When divided by sex, there was no alteration in female QTc interval, although there was a near significant prolongation following domperidone therapy in males (p=0.051) Two infant males (GA 38 and 39.5 weeks) displayed clinically significant QTc prolongation (>460 msec), but did not develop arrhythmia There was no relationship identified between QTc prolongation and domperidone dose or infant age No arrhythmias or atrioventricular conduction issues were identified The authors chose 2 hours for follow-up ECG as they say that the formulation of domperidone used peaks in effect at 1–2 hours Although the results indicate that domperidone did not consistently prolong the QTc interval in most infants or promote arrhythmias, it was associated with prolongation in two male infants Therefore, the authors warn caution in the use of the drug No placebo group Ngoenmak et al 14 Population: 22 paediatric patients with a mean age of 8.5 months (range of 1–24 months) who were suffering from GORD requiring domperidone treatment Groups: All participants were grouped as one (n=22) Dose: 0.3 mg/kg/day Setting: Paediatric unit, Thailand Prospective Cohort Study Level 2b ECG assessment (QTc, Tpeak to Tend interval, QTc/(Tpeak to Tend interval) and arrhythmia) prior to and after at least 1 week of domperidone therapy Factors such as age, dosage, pre-existing disease and concomitant medicines were assessed for their relationship to QTc interval QTc calculated manually by Bazett’s formula The QTc at 1 week following domperidone administration was 410 msec (range 320–450 m), which was not significantly prolonged when compared with the baseline of 410 msec (range 350-450 msec) One patient had a baseline QTc >450 msec, which reduced following administration of domperidone The QTc increased nominally in eight (36%) patients, but only two patients displayed a QTc ≥450 msec following treatment (baseline QTc intervals of 440 and 420 msec) None of the assessed factors were found to be associated with prolonged QTc interval Median Tpeak to Tend interval and (Tpeak to Tend interval)/QTc were significantly reduced after taking domperidone No arrhythmias or atrioventricular conduction issues were identified The authors suggest that ECG assessment may not be entirely necessary prior to and after commencing domperidone in a similar population Despite this, they suggest that higher-powered clinical studies are required to confirm this hypothesis No placebo group GA, Gestational age; GORD, Gastro-eosophageal reflux disease; NICU, Neonatal intensive care unit; RCT, Randomised controlled trial.

Left atrial enlargement (LAE) is a marker for diastolic cardiac dysfunction. Echocardiograms are considered the gold-standard for diagnosis, but given their wider access and lower economic cost, electrocardiograms (ECGs) may be useful in identifying patients who would benefit from further investigation. This study investigates the utility of ECG criteria to diagnose LAE in pediatric patients. A retrospective chart review (n = 492) was conducted in patients whose echocardiograms demonstrated LAE by left atrial indexed diameter z-score ≥2.0 and/or increased left atrial to aortic root ratio at various cutoffs (≥1.4, ≥1.6, ≥1.8). ECG criteria studied included: (1) P wave ≥110 msec, (2) P mitrale ≥40 msec, in LII (3) terminal negative P wave deflection in lead V1 > 40 msec, and (4) P/PR segment >1.6 in lead II. Sensitivity, specificity, Cohen’s Kappa coefficient (κ), and ROC curves were calculated. A combination of P mitrale ≥40 msec and terminal negative P wave deflection in lead V1 > 40 msec yielded the greatest agreement (κ = 0.221, 95%CI 0.060–0.382), but all ECG criteria used to diagnose LAE had poor diagnostic value (AUC < 0.60). The present ECG criteria should not be used to diagnose LAE in the absence of an echocardiogram and findings should be considered in the context of clinical symptoms.

Background Congenital heart disease (CHD) is the most common congenital anomaly. Almost 90% of isolated cases have an unexplained genetic etiology after clinical testing. Non-canonical splice variants that disrupt mRNA splicing through the loss or creation of exon boundaries are not routinely captured and/or evaluated by standard clinical genetic tests. Recent computational algorithms such as SpliceAI have shown an ability to predict such variants, but are not specific to cardiac-expressed genes and transcriptional isoforms. Methods We used genome sequencing (GS) ( n  = 1101 CHD probands) and myocardial RNA-Sequencing (RNA-Seq) ( n  = 154 CHD and n  = 43 cardiomyopathy probands) to identify and validate splice disrupting variants, and to develop a heart-specific model for canonical and non-canonical splice variants that can be applied to patients with CHD and cardiomyopathy. Two thousand five hundred seventy GS samples from the Medical Genome Reference Bank were analyzed as healthy controls. Results Of 8583 rare DNA splice-disrupting variants initially identified using SpliceAI, 100 were associated with altered splice junctions in the corresponding patient myocardium affecting 95 genes. Using strength of myocardial gene expression and genome-wide DNA variant features that were confirmed to affect splicing in myocardial RNA, we trained a machine learning model for predicting cardiac-specific splice-disrupting variants (AUC 0.86 on internal validation). In a validation set of 48 CHD probands, the cardiac-specific model outperformed a SpliceAI model alone (AUC 0.94 vs 0.67 respectively). Application of this model to an additional 947 CHD probands with only GS data identified 1% patients with canonical and 11% patients with non-canonical splice-disrupting variants in CHD genes. Forty-nine percent of predicted splice-disrupting variants were intronic and > 10 bp from existing splice junctions. The burden of high-confidence splice-disrupting variants in CHD genes was 1.28-fold higher in CHD cases compared with healthy controls. Conclusions A new cardiac-specific in silico model was developed using complementary GS and RNA-Seq data that improved genetic yield by identifying a significant burden of non-canonical splice variants associated with CHD that would not be detectable through panel or exome sequencing.

Background Assess process, uptake, validity and resource needs for return of actionable research findings to biobank participants. Methods Participants were prospectively enrolled in a multicenter biorepository of childhood onset heart disease. Clinically actionable research findings were reviewed by a Return of Research Results Committee (RRR) and returned to the physician or disclosed directly to the participant through a research genetic counselor. Action taken following receipt of this information was reviewed. Results Genetic data was generated in 1963 of 7408 participants. Fifty-nine new findings were presented to the RRR committee; 20 (34%) were deemed reportable. Twelve were returned to the physician, of which 7 were disclosed to participants (median time to disclosure, 192 days). Seven findings were returned to the research genetic counselor; all have been disclosed (median time to disclosure, 19 days). Twelve families (86%) opted for referral to clinical genetics after disclosure of findings; 7 results have been validated, 5 results are pending. Average cost of return and disclosure per reportable finding incurred by the research program was $750 when utilizing a research genetic counselor; clinical costs associated with return were not included. Conclusions Return of actionable research findings was faster if disclosed directly to the participant by a research genetic counselor. There was a high acceptability amongst participants for receiving the findings, for referral to clinical genetics, and for clinical validation of research findings, with all referred cases being clinically confirmed.

Background: The stage 1 Norwood procedure and its variants represent the first step of palliation for hypoplastic left heart syndrome. Although appropriate postoperative thromboprophylaxis is integral, significant variance remains across institutional practices. The purpose of this systematic review is to estimate the incidence of thrombosis and thromboembolism following the Norwood or modified Blalock-Taussig shunt procedure and examine current thromboprophylaxis regimens. Methods: Ovid MEDLINE and Embase were searched from January 2000 to June 2016 for primary studies explicitly reporting incidence of thrombosis, thromboembolism (strokes and pulmonary embolisms), or shunt occlusion in neonates, infants, and children undergoing the Norwood procedure or any variant. All-cause mortality was a secondary outcome of interest. Results: Of 887 identified articles, 15 cohort studies were deemed eligible, the majority including modified Blalock-Taussig shunt patients. Reported incidence of thrombosis ranged from 0% to 40%; thromboembolic events were rarely reported. Overall mortality ranged from 4.5% to 31.3% across studies. Although most studies involved the long-term acetylsalicylic acid use, thromboprophylaxis strategies varied across studies. Due to substantial variability in event rates, no correlation was identified with thrombotic complications. Discussion: Clinical practice guidelines recommend that patients receive intraoperative unfractionated heparin therapy and either aspirin or no antithrombotic therapy postoperatively. Our findings suggest a substantial risk of thrombosis and thromboembolism and demonstrate substantial variation in thromboprophylaxis practices. Conclusion: Although postoperative thromboprophylaxis seems optimal, it remains controversial whether the long-term aspirin use is most effective. Our findings highlight the lack of a gold-standard thromboprophylaxis strategy and emphasize the need for more consistency.

Geometric programming is a well-known optimization tool for dealing with a wide range of nonlinear optimization and engineering problems. In general, it is assumed that the parameters of a geometric programming problem are deterministic and accurate. However, in the real-world geometric programming problem, the parameters are frequently inaccurate and ambiguous. To tackle the ambiguity, this paper investigates the geometric programming problem in an uncertain environment, with the coefficients as triangular and trapezoidal twofold uncertain variables. In this paper, we introduce uncertain measures in a generalized version and focus on more complicated twofold uncertainties to propose triangular and trapezoidal twofold uncertain variables within the context of uncertainty theory. We develop three reduction methods to convert triangular and trapezoidal twofold uncertain variables into singlefold uncertain variables using optimistic, pessimistic, and expected value criteria. Reduction methods are used to convert the geometric programming problem with twofold uncertainty into the geometric programming problem with singlefold uncertainty. Furthermore, the chance-constrained uncertain-based framework is used to solve the reduced singlefold uncertain geometric programming problem. Finally, a numerical example is provided to demonstrate the effectiveness of the procedures.

We report a case of a fetus with hypoplastic left heart syndrome in addition to an anomalous vessel extending from the descending thoracic aorta to the basal segments of the lower left lung without sequestration. The concurrence of these 2 congenital abnormalities is extremely rare and unreported in the existing literature. The anomalous vessel to the left lung may cause increased pulmonary vascular resistance, which has implications for the long-term management of hypoplastic left heart syndrome via the Fontan procedure.