Publicly funded healthcare costs associated with orofacial clefts for children born in Alberta, Canada between 2002 and 2018.

BACKGROUND: Orofacial clefts (OFCs) include cleft palate (CP), cleft lip (CL), and cleft lip with cleft palate (CLP) and require multidisciplinary healthcare services. Alberta, Canada has a publicly funded, universal access healthcare system. This study determined publicly funded healthcare costs for children with an OFC and compared these costs to children without congenital anomalies. METHODS: This retrospective population-based cohort analysis used the Alberta Congenital Anomalies Surveillance System to identify children born between 2002 and 2018 with an isolated OFC. They were matched 1:1 to a reference cohort based on sex and year of birth. The study population included 1614 children, from birth to 17 years of age linked to administrative databases to estimate annual inpatient and outpatient costs. Average annual all-cause costs were compared using two-sample independent t tests. RESULTS: The mean total cleft-related costs per patient were highest for children with CLP ($74,138 CAD, standard deviation (SD) $43,447 CAD), followed by CP ($53,062 CAD, SD $74,366 CAD), and CL ($35,288 CAD, SD $49,720 CAD). The mean total all-cause costs per child were statistically significantly higher (p < .001) in children with an OFC ($56,305 CAD, SD $57,744 CAD) compared to children without a congenital anomaly ($18,600 CAD, SD $61,300 CAD). CONCLUSIONS: Despite public health strategies to mitigate risk factors, the trend for OFCs has remained stable in Alberta, Canada for over 20 years. The costs reported are useful to other jurisdictions for comparison, and to families, healthcare professionals, service planners, and policy makers.

Risk factors for disease severity among children with Covid-19: a clinical prediction model.

BACKGROUND: Children account for a significant proportion of COVID-19 hospitalizations, but data on the predictors of disease severity in children are limited. We aimed to identify risk factors associated with moderate/severe COVID-19 and develop a nomogram for predicting children with moderate/severe COVID-19. METHODS: We identified children ≤ 12 years old hospitalized for COVID-19 across five hospitals in Negeri Sembilan, Malaysia, from 1 January 2021 to 31 December 2021 from the state's pediatric COVID-19 case registration system. The primary outcome was the development of moderate/severe COVID-19 during hospitalization. Multivariate logistic regression was performed to identify independent risk factors for moderate/severe COVID-19. A nomogram was constructed to predict moderate/severe disease. The model performance was evaluated using the area under the curve (AUC), sensitivity, specificity, and accuracy. RESULTS: A total of 1,717 patients were included. After excluding the asymptomatic cases, 1,234 patients (1,023 mild cases and 211 moderate/severe cases) were used to develop the prediction model. Nine independent risk factors were identified, including the presence of at least one comorbidity, shortness of breath, vomiting, diarrhea, rash, seizures, temperature on arrival, chest recessions, and abnormal breath sounds. The nomogram's sensitivity, specificity, accuracy, and AUC for predicting moderate/severe COVID-19 were 58·1%, 80·5%, 76·8%, and 0·86 (95% CI, 0·79 - 0·92) respectively. CONCLUSION: Our nomogram, which incorporated readily available clinical parameters, would be useful to facilitate individualized clinical decisions.

How are the mealtime experiences of people in residential aged care facilities informed by policy and best practice guidelines? A scoping review.

BACKGROUND: Mealtimes are embedded routines of residents living in residential aged care facilities (RACFs) that directly impact their health and quality of life. Little is known about how mealtime experiences are informed and affected by structures such as government and organisational policies and processes. This scoping review used Giddens' (The constitution of society: outline of the theory of structuration, 1984) Structuration Theory to investigate how governance structures related to mealtime practices inform residents' mealtime experiences. METHODS: Using Arksey and O'Malley's (Int J Soc Res Methodol 8:19-32, 2005) scoping review framework, a systematic database, grey literature and policy search was completed in May 2020 and updated in July 2021. From 2725 identified articles, 137 articles were included in data charting and deductive analysis, and 76 additional Australian government policy papers were used interpretatively. RESULTS: Data charting identified that the included studies were prominently situated in Western countries, with a progressive increase in publication rate over the past two decades. Qualitative findings captured structures that guide RACF mealtimes, how these relate to person-centred mealtime practices, and how these facilitate residents to enact choice and control. CONCLUSIONS: Current policies lack specificity to inform the specific structures and practices of RACF mealtimes. Staff, residents, organisational and governance representatives possess different signification, legitimation and domination structures, and lack a shared understanding of policy, and how this influences processes and practices that comprise mealtimes.

Integrative multi-omics landscape of fluoxetine action across 27 brain regions reveals global increase in energy metabolism and region-specific chromatin remodelling.

Depression and anxiety are major global health burdens. Although SSRIs targeting the serotonergic system are prescribed over 200 million times annually, they have variable therapeutic efficacy and side effects, and mechanisms of action remain incompletely understood. Here, we comprehensively characterise the molecular landscape of gene regulatory changes associated with fluoxetine, a widely-used SSRI. We performed multimodal analysis of SSRI response in 27 mammalian brain regions using 310 bulk RNA-seq and H3K27ac ChIP-seq datasets, followed by in-depth characterisation of two hippocampal regions using single-cell RNA-seq (20 datasets). Remarkably, fluoxetine induced profound region-specific shifts in gene expression and chromatin state, including in the nucleus accumbens shell, locus coeruleus and septal areas, as well as in more well-studied regions such as the raphe and hippocampal dentate gyrus. Expression changes were strongly enriched at GWAS loci for depression and antidepressant drug response, stressing the relevance to human phenotypes. We observed differential expression at dozens of signalling receptors and pathways, many of which are previously unknown. Single-cell analysis revealed stark differences in fluoxetine response between the dorsal and ventral hippocampal dentate gyri, particularly in oligodendrocytes, mossy cells and inhibitory neurons. Across diverse brain regions, integrative omics analysis consistently suggested increased energy metabolism via oxidative phosphorylation and mitochondrial changes, which we corroborated in vitro; this may thus constitute a shared mechanism of action of fluoxetine. Similarly, we observed pervasive chromatin remodelling signatures across the brain. Our study reveals unexpected regional and cell type-specific heterogeneity in SSRI action, highlights under-studied brain regions that may play a major role in antidepressant response, and provides a rich resource of candidate cell types, genes, gene regulatory elements and pathways for mechanistic analysis and identifying new therapeutic targets for depression and anxiety.

Comparison of Severe Viral Pneumonia Caused by SARS-CoV-2 and Other Respiratory Viruses Among Malaysian Children During the COVID-19 Pandemic.

Objectives: We described the etiology of severe pneumonia in children during the height of the COVID-19 pandemic in Malaysia and compared the clinical features of severe SARS-CoV-2 to other respiratory viruses. Methods: This retrospective study included all children aged 12 years and below hospitalized with severe pneumonia in Negeri Sembilan, Malaysia, between 1 April 2021 and 31 October 2021. We extracted demographic and clinical data and used logistic regression to examine risk factors associated with severe SARS-CoV-2 or other viral pneumonia. Results: A total of 111 children were included. The median age was 15 months. Human rhinovirus/enterovirus, SARS-CoV-2 and respiratory syncytial virus were the most common etiology of severe pneumonia. Codetection of >1 viral pathogen was present in 14 (12.6%) patients. Children with severe COVID-19 presented early in the course of illness and had lower rates of pediatric intensive care admission. The presence of sick contact with an adult was a predictor for SARS-CoV-2, whereas adventitious breath sounds were predictive of other respiratory viruses. Conclusions: The etiology of severe pneumonia in children evolved with the epidemic curve of COVID-19 and school closures. Children with severe pneumonia due to SARS-CoV-2 experienced a milder clinical course when compared to other respiratory viruses.

The associations between lifestyle factors and mental well-being in baccalaureate nursing students: An observational study.

Lifestyle factors are modifiable habits that shape the way in which individuals live their lives and can influence mental health. This study examined the associations between lifestyle factors and mental well-being among baccalaureate nursing students at one Canadian university. A cross-sectional, observational online survey was distributed at one urban university campus in Ontario, Canada. Baccalaureate nursing students (n = 147) completed the survey containing questions for demographic variables, sleep quality, dietary pattern, alcohol use, physical activity, sitting time, cigarette smoking, depression, anxiety and stress. Linear regression analysis revealed that more sitting time, poor sleep quality, and low dairy consumption were associated with higher scores in depression, anxiety, and psychological stress. In conclusion, poor lifestyle behaviors such as sedentary lifestyle, poor sleep, and low dairy consumption may reduce the mental well-being of baccalaureate nursing students. Future efforts should aim to establish a causal relationship between lifestyle and mental well-being, which would contribute to the development of lifestyle interventions to promote mental health.

Good Quality Care for Cancer Patients Dying in Hospitals, but Information Needs Unmet: Bereaved Relatives' Survey within Seven Countries.

BACKGROUND: Recognized disparities in quality of end-of-life care exist. Our aim was to assess the quality of care for patients dying from cancer, as perceived by bereaved relatives, within hospitals in seven European and South American countries. MATERIALS AND METHODS: A postbereavement survey was conducted by post, interview, or via tablet in Argentina, Brazil, Uruguay, U.K., Germany, Norway, and Poland. Next of kin to cancer patients were asked to complete the international version of the Care Of the Dying Evaluation (i-CODE) questionnaire 6-8 weeks postbereavement. Primary outcomes were (a) how frequently the deceased patient was treated with dignity and respect, and (b) how well the family member was supported in the patient's last days of life. RESULTS: Of 1,683 potential participants, 914 i-CODE questionnaires were completed (response rate, 54%). Approximately 94% reported the doctors treated their family member with dignity and respect "always" or "most of the time"; similar responses were given about nursing staff (94%). Additionally, 89% of participants reported they were adequately supported; this was more likely if the patient died on a specialist palliative care unit (odds ratio, 6.3; 95% confidence interval, 2.3-17.8). Although 87% of participants were told their relative was likely to die, only 63% were informed about what to expect during the dying phase. CONCLUSION: This is the first study assessing quality of care for dying cancer patients from the bereaved relatives' perspective across several countries on two continents. Our findings suggest many elements of good care were practiced but improvement in communication with relatives of imminently dying patients is needed. (ClinicalTrials.gov Identifier: NCT03566732). IMPLICATIONS FOR PRACTICE: Previous studies have shown that bereaved relatives' views represent a valid way to assess care for dying patients in the last days of their life. The Care Of the Dying Evaluation questionnaire is a suitable tool for quality improvement work to help determine areas where care is perceived well and areas where care is perceived as lacking. Health care professionals need to sustain high quality communication into the last phase of the cancer trajectory. In particular, discussions about what to expect when someone is dying and the provision of hydration in the last days of life represent key areas for improvement.

Clinical Pharmacokinetics and Pharmacodynamics of Delafloxacin.

Delafloxacin has recently received approval by the US Food and Drug Administration for the treatment of acute bacterial skin and skin structure infections. This article provides a balanced and comprehensive systematic critique of the literature in order to provide an up-to-date summary of its clinical pharmacology. Oral delafloxacin is rapidly absorbed and exhibits comparable exposure characteristics (300 mg intravenous versus 450 mg oral) between the two formulations, allowing easy transition from intravenous to oral therapy. The bioavailability is high (60-70%) and absorption is not affected by food intake, although further studies are required under clinically relevant conditions. Delafloxacin is primarily excreted renally (thus requiring renal dose adjustment in the setting of renal dysfunction), but also undergoes metabolism by uridine diphosphate-glucuronosyltransferase enzymes in the formation of a conjugated metabolite. Few drug-drug interaction studies have been identified, although more systematic characterizations in vitro and in vivo are warranted. Delafloxacin is a concentration-dependent bactericidal agent that has in vitro susceptibility for gram-positive (notably potent activity against methicillin-resistant Staphylococcus aureus), gram-negative, and anaerobic organisms. In addition to acute bacterial skin and skin structure infections, the clinical utility of delafloxacin has also been studied in community-acquired pneumonia, acute exacerbation of chronic bronchitis, and gonorrhea, with potentially promising findings. Given its mild side effect profile, including an apparent lack of association with clinically important QTc prolongation, delafloxacin is generally well tolerated.

Matching phenotypes to whole genomes: Lessons learned from four iterations of the personal genome project community challenges.

The advent of next-generation sequencing has dramatically decreased the cost for whole-genome sequencing and increased the viability for its application in research and clinical care. The Personal Genome Project (PGP) provides unrestricted access to genomes of individuals and their associated phenotypes. This resource enabled the Critical Assessment of Genome Interpretation (CAGI) to create a community challenge to assess the bioinformatics community's ability to predict traits from whole genomes. In the CAGI PGP challenge, researchers were asked to predict whether an individual had a particular trait or profile based on their whole genome. Several approaches were used to assess submissions, including ROC AUC (area under receiver operating characteristic curve), probability rankings, the number of correct predictions, and statistical significance simulations. Overall, we found that prediction of individual traits is difficult, relying on a strong knowledge of trait frequency within the general population, whereas matching genomes to trait profiles relies heavily upon a small number of common traits including ancestry, blood type, and eye color. When a rare genetic disorder is present, profiles can be matched when one or more pathogenic variants are identified. Prediction accuracy has improved substantially over the last 6 years due to improved methodology and a better understanding of features.

Epidemiology, clinical characteristics, laboratory findings and severity of respiratory syncytial virus acute lower respiratory infection in Malaysian children, 2008-2013.

AIM: The aim of this study is to describe epidemiology, clinical features, laboratory data and severity of respiratory syncytial virus (RSV) acute lower respiratory infection (ALRI) in Malaysian children and to determine risk factors associated with prolonged hospital stay, paediatric intensive care unit (PICU) admission and mortality. METHODS: Retrospective data on demographics, clinical presentation, outcomes and laboratory findings of 450 children admitted into Tuanku Jaafar Hospital in Seremban, Malaysia from 2008 to 2013 with documented diagnosis of RSV ALRI were collected and analysed. RESULTS: Most admissions were children below 2 years old (85.8%; 386/450). Commonest symptoms were fever (84.2%; 379/450), cough (97.8%; 440/450) and rhinorrhea (83.6%; 376/450). The median age among febrile patients (n = 379) was 9.0 months with interquartile range (IQR) of 4.0-19.0 months whereas the median age among those who were apyrexial (n = 71) was 2 months with IQR of 1-6 months (P-value <0.001). 15.3% (69/450) needed intensive care and 1.6% (7/450) died. Young age, history of prematurity, chronic comorbidity and thrombocytosis were significantly associated with prolonged hospital stay, PICU admission and mortality. CONCLUSIONS: Infants less than 6 months old with RSV ALRI tend to be afebrile at presentation. Younger age, history of prematurity, chronic comorbidity and thrombocytosis are predictors of severe RSV ALRI among Malaysian children. Case fatality rate for Malaysian children below 5 years of age with RSV ALRI in our centre is higher than what is seen in developed countries, suggesting that there is room for improvement.

The National Health Plan Collaborative to Reduce Disparities and Improve Quality.

BACKGROUND: Despite numerous reports and initiatives, progress in reducing racial/ethnic disparities in health care has been slow. The National Health Plan Collaborative (NHPC), a novel public-private partnership between nine health plans covering approximately 95 million lives, leading learning and research organizations, the Agency for Healthcare Research and Quality, and the Robert Wood Johnson Foundation, was established in December 2004 to address these disparities. PROGRESS TO DATE: The health plans were able to overcame initial challenges in obtaining information on race/ethnicity of their enrollees and examined their diabetes performance measure to assess disparities in care. By February 2006, the initial nine plans that had joined the NHPC progressed from focusing solely on data collection and management issues and were engaged in outreach activities to members, providers, or community or had completed capacity development for disparities work. Five plans had implemented one or more pilot interventions. Plans also addressed unanticipated challenges, such as sorting through large amounts of data to target disparities. CHALLENGES AND LESSONS LEARNED: Because many of the plans are complex national entities with varying regional and departmental structures, simply achieving coordination of disparities activities across the organization has been a major challenge and, in many cases, a major breakthrough. CONCLUSIONS: The NHPC represents a model of shared learning and innovation through which health plans are tackling racial/ethnic disparities. Now that most of the plans have some data on their enrollees with diabetes and have begun targeting disparities, they want to capitalize on their collective industry strength to influence policy on issues related to disparities.