Pediatric human nose organoids demonstrate greater susceptibility, epithelial responses, and cytotoxicity than adults during RSV infection.

Respiratory syncytial virus (RSV) is a common cause of respiratory infections, causing significant morbidity and mortality, especially in young children. Why RSV infection in children is more severe as compared to healthy adults is not fully understood. In the present study, we infect both pediatric and adult human nose organoid-air liquid interface (HNO-ALIs) cell lines with two contemporary RSV isolates and demonstrate how they differ in virus replication, induction of the epithelial cytokine response, cell injury, and remodeling. Pediatric HNO-ALIs were more susceptible to early RSV replication, elicited a greater overall cytokine response, demonstrated enhanced mucous production, and manifested greater cellular damage compared to their adult counterparts. Adult HNO-ALIs displayed enhanced mucus production and robust cytokine response that was well controlled by superior regulatory cytokine response and possibly resulted in lower cellular damage than in pediatric lines. Taken together, our data suggest substantial differences in how pediatric and adult upper respiratory tract epithelium responds to RSV infection. These differences in epithelial cellular response can lead to poor mucociliary clearance and predispose infants to a worse respiratory outcome of RSV infection.

Infant-derived human nasal organoids exhibit relatively increased susceptibility, epithelial responses, and cytotoxicity during RSV infection.

BACKGROUND: Respiratory syncytial virus (RSV) causes significant morbidity and mortality, especially in young children. Why RSV infection in children is more severe compared to healthy adults is not fully understood. METHODS: We used ex-vivo human nasal organoid platforms from infants and adults to investigate the underlying mechanism of this disease disparity at the initial site of RSV replication, the nasal epithelium. RESULTS: Infant-derived human nasal organoid-air liquid interface (HNO-ALIs) lines were more susceptible to early RSV replication. Moreover, infant-derived HNO-ALIs elicited a statistically significant greater overall cytokine response, enhanced mucous production, and greater cellular damage compared to their adult counterparts. Furthermore, the adult cytokine response was associated with a superior regulatory cytokine response, which could explain less cellular damage than in infant lines. CONCLUSIONS: Our data highlights substantial differences in how infant and adult upper respiratory tract epithelium responds to RSV infection at the cellular level. These differences in epithelial cellular response can lead to impaired mucociliary clearance, a more dysregulated innate immune response predisposing infants to more severe RSV infection compared to adults.

Provision of domiciliary dental care in North and West Belfast.

AIM: To determine the level of domiciliary care currently provided for patients by general dental practitioners (GDPs) and to investigate factors that influence the provision of domiciliary dental care in an area of high socioeconomic deprivation in North and West Belfast. METHOD: A descriptive study, involving a self-administered postal questionnaire sent to GDPs (n=89) in North and West Belfast. RESULTS: A valid response rate of 67% was achieved. Almost 20% of responding GDPs reported that they did not routinely offer domiciliary dental care. Of those who did, prosthetic treatment was undertaken most commonly, and other more time-consuming treatments such as fillings were referred to the Community Dental Services (CDS). Many GDPs reported not having a full range of domiciliary equipment, with only half of the GDPs surveyed carrying emergency drugs. Reasons cited for not providing the service were lack of time, the perception that patients would be too difficult to manage, and not having the appropriate equipment. The majority of responding dentists (85%) felt that domiciliary care should be referred to the community service. CONCLUSION: The rate of domiciliary care provision in North and West Belfast appears to be falling, despite it being an area of high socioeconomic deprivation where the demand for the service is growing. The general perception was that domiciliary care is too time-consuming, that the patients are too difficult to manage, and that there was a lack of appropriate equipment. As a result, the majority of GDPs in North and West Belfast felt that the CDS should care for all domiciliary patients.

Cost description of inpatient treatment for ankle fracture.

BACKGROUND: The study estimated the hospital costs associated with the surgical fixation of ankle fractures by either open reduction internal fixation (ORIF) or external fixation. METHOD: A retrospective review of the clinical records of all 264 patients admitted with an ankle fracture requiring surgical stabilisation between 1 March 2007 and 29 February 2008. Patient records were examined for a minimum of 6 months after primary admission. A mean cost per patient was calculated based on patient-level hospital resource use. This included all procedures received during both their primary hospitalisation and subsequent re-admissions. RESULTS: Approximately equal numbers of males and females (mean age 46.2 years) were admitted, and males were significantly younger than females. The mean length of stay was 10.8 days (SD 9.1); however, ORIF (which was performed in the vast majority of cases, 94.7%) was associated with a much shorter mean length of stay compared with external fixation (10.4 days; SD 8.9 vs. 17.4 days; SD 10.2). The mean total hospital cost per patient including was £4730.28 (SD £2340.73) with a higher mean cost for those who received external fixation as the primary procedure (£9453.92; SD £3391.84) compared with ORIF (£4465.76; SD £1965.10). Patients with severe health problems had significantly higher costs than fit and healthy patients (£5982.65; SD £28 77.74 vs. £4375.00; SD £1957.65). CONCLUSIONS: The results highlight the considerable hospital costs associated with the surgical fixation of an ankle fracture, thus providing valuable information for resource planners. Future research should broaden the perspective of the economic analysis to include rehabilitation costs and assess the cost-effectiveness of potential cost-saving strategies.

A cluster randomized controlled trial of an adapted U.S. model of pharmaceutical care for nursing home residents in Northern Ireland (Fleetwood Northern Ireland study): a cost-effectiveness analysis.

OBJECTIVES: To evaluate the cost-effectiveness of an adapted U.S. model of pharmaceutical care to improve psychoactive prescribing for nursing home residents in Northern Ireland (Fleetwood NI Study). DESIGN: Economic evaluation alongside a cluster randomized controlled trial. SETTING: Nursing homes in NI randomized to intervention (receipt of the adapted model of care; n=11) or control (usual care continued; n=11). PARTICIPANTS: Residents aged 65 and older who provided informed consent (N=253; 128 intervention, 125 control) and who had full resource use data at 12 months. INTERVENTION: Trained pharmacists reviewed intervention home residents' clinical and prescribing information for 12 months, applied an algorithm that guided them in assessing the appropriateness of psychoactive medication, and worked with prescribers (general practitioners) to make changes. The control homes received usual care in which there was no pharmacist intervention. MEASUREMENTS: The proportion of residents prescribed one or more inappropriate psychoactive medications (according to standardized protocols), costs, and a cost-effectiveness acceptability curve. The latter two outcomes are the focus for this article. RESULTS: The proportions of residents receiving inappropriate psychoactive medication at 12 months in the intervention and control group were 19.5% and 50.4%, respectively. The mean cost of healthcare resources used per resident per year was $4,923 (95% confidence interval (CI)=$4,206-5,640) for the intervention group and $5,053 (95% CI=$4,328-5,779) for the control group. The probability of the intervention being cost-effective was high, even at low levels of willingness to pay to avoid a resident receiving inappropriately prescribed psychoactive medication. CONCLUSION: The Fleetwood NI model of care was more cost-effective than usual care.