The Outreach Virtual Fracture Clinic - a Pilot Report of the Initial Nine Months.

The virtual fracture clinic (VFC) enables the safe, cost-effective delivery of high-quality patient-centred fracture care, whilst reducing hospital footfall. Within our institution, an Outreach VFC was launched, accepting a pre-defined range of trauma referrals from the outreach centre's emergency department (ED). The initial nine months' worth of cases referred to the Outreach VFC were assessed. The injury pattern, time to review, treatment plan and discharge destination of each referred patient were examined. A total of 822 patients were referred to the Outreach VFC during its initial nine months in operation. Owing to COVID-19-related alterations in the patient pathway, 58.1% of patients were referred on to fracture clinic/ED, with 34.4% of patients being referred for physiotherapy input. 44.9% of patients were reviewed at the Outreach VFC within 72 hours of ED presentation, with 88.6% of patients reviewed within 7 days. The Outreach VFC pilot initiative saved the Dublin Midlands Hospitals Group approximately €83,022 over nine months. The Outreach VFC model represents a novel approach to trauma care delivery with advantages for patient and hospital alike. Rural communities serve to benefit from its future implementation and the remote management of orthopaedic trauma. The Outreach VFC model provides a means of delivering safe and timely orthopaedic care whilst maintaining high levels of patient satisfaction.

Real-world resource use and costs of haemophilia A-related bleeding.

INTRODUCTION: Prophylaxis treatment is recommended for haemophilia patients, but associated real-world economic costs and potential cost-savings associated with improved disease management are not fully known. This study aimed to assess haemophilia A-related resource use and cost by treatment type (prophylaxis versus non-prophylaxis) and any associated cost-savings. METHODS: Truven MarketScan Commercial claims data (2004-2012) were used to identify haemophilia A-related healthcare utilization, healthcare costs and patterns of prophylaxis and non-prophylaxis treatment among 6- to 64-year-old males. We estimated bleeding-related resource utilization and costs in three age groups (6-18, 19-44, 45-64) by treatment types and assessed the extent to which early initiation of prophylactic treatment can mitigate them. T-tests and ordinary least squares regressions were used to compare unadjusted and demographics-adjusted cost estimates. RESULTS: Among children, overall haemophilia- and bleeding-related non-pharmacy costs were substantially lower for patients receiving prophylaxis (haemophilia-related: $15,864 vs. $53,408; P < 0.001; bleeding-related: $696 vs. $2013, respectively; P = 0.04). Among younger adults (19-44), haemophilia-related non-pharmacy costs were lower for patients receiving prophylaxis ($22,028 vs. $56,311, respectively; P = 0.001). Among children, these savings fully offset the incremental pharmacy cost due to prophylaxis. Among younger adults, the savings offset approximately 34% of the incremental pharmacy cost. No differences were found for older adults (45-64). CONCLUSION: These results suggest that initiating prophylaxis earlier in life may reduce the healthcare costs of bleeding events and their long-term complications. Future studies should strive to collect more detailed information on disease severity and treatment protocols to improve estimates of disease burden.

Self-reported prevalence, description and management of pain in adults with haemophilia: methods, demographics and results from the Pain, Functional Impairment, and Quality of life (P-FiQ) study.

INTRODUCTION: Haemophilia is characterized by frequent haemarthrosis, leading to acute/chronic joint pain. AIM: To assess self-reported prevalence, description and management of pain in adult males with mild-to-severe haemophilia and history of joint pain/bleeding. METHODS: Participants completed a pain survey and five patient-reported outcome instruments assessing pain, functional impairment and health-related quality of life (HRQoL). RESULTS: Of 381 participants enrolled, median age was 34 years; 77% had haemophilia A, 71% had severe disease and 65% were overweight/obese. Many (56%) were not receiving routine infusions; 30% never received routine infusions. During the prior 6 months, 20% experienced acute pain, 34% chronic pain and 32% both acute/chronic pain. Subjects with both acute/chronic pain (vs. none, acute or chronic) were more likely to be depressed (30% vs. 0-15%), obese (35% vs. 20-29%) and have lower HRQoL (mean EQ-5D visual analog scale, 69 vs. 83-86) and function (median overall Hemophilia Activities List, 60 vs. 88-99). Most common analgesics used for acute/chronic pain during the prior 6 months were acetaminophen (62%/55%) and non-steroidal anti-inflammatory drugs (34%/49%); most common non-pharmacologic strategies were ice (65%/33%) and rest (51%/33%). Hydrocodone-acetaminophen was the most common opioid for both acute/chronic pain (30%); other long-acting opioids were infrequently used specifically for chronic but not acute pain (morphine, 7%; methadone, 6%; fentanyl patch, 2%). CONCLUSION: Patients with chronic pain, particularly those with both acute/chronic pain, frequently experience psychological issues, functional disability and reduced HRQoL. Treatment strategies for acute pain (e.g. routine infusions to prevent bleeding) and for chronic pain (e.g. long-acting opioids) may be underused.

Common themes and challenges in hemophilia care: a multinational perspective.

OBJECTIVE: To identify ways that provision of hemophilia care can be maximized at the local level, irrespective of available resources or cultural or geographic challenges. METHODS: The SHIELD group used its multinational experience to share examples of local initiatives that have been employed to deliver optimal hemophilia care. RESULTS: The examples were reviewed and categorized into four key themes: guidelines and algorithms for delivery of care; collaboration with patients and allied groups for care and education; registries for the monitoring of treatment and outcomes and health care planning and delivery; and opportunities for personalization of care. These themes were then incorporated into a road map for collaborative care in hemophilia that reflected the contribution of best practice. DISCUSSION: Differing healthcare reimbursement systems, budgetary constraints, and geographical and cultural factors make it difficult for any country to fully deliver ideal care for people with hemophilia. The SHIELD approach for collaborative care provides illustrative examples of how four key themes can be used to optimize hemophilia care in any setting. ABBREVIATIONS: AHCDC: Association of Hemophilia Clinic Directors of Canada; AICE: Italian Association of Hemophilia Centres; ATHN: American Thrombosis and Hemostasis Network; EAHAD: European Association for Haemophilia and Allied Disorders; EHC: European Hemophilia Consortium; FIX: Coagulation Factor IX; FVIII: Coagulation Factor VIII; HAL: Haemophilia Activity List; HJHS: Haemophilia Joint Health Score; HTC: Hemophilia Treatment Centre; HTCCNC: Hemophilia Treatment Centre Collaborative Network of China; MASAC: Medical and Scientific Advisory Council; MDT: Multidisciplinary team; NHD: National Haemophilia Database; NHF: National Hemophilia Foundation; PK: Pharmacokinetics; POCUS: Point of care ultrasound; PWH: People with haemophilia; SHIELD: Supporting Hemophilia through International Education, Learning and Development; WFH: World Federation of Hemophilia.

Genotoxicity evaluation of lithium hypochlorite.

Lithium hypochlorite (LiOCl), the pool and spa sanitizer/algicide, was evaluated for genotoxicity in a battery of studies designed to evaluate potential mutagenicity, DNA damage and chromosome aberrations. LiOCl was not mutagenic in the Ames test when tested in Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 or in the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) mutation assay in Chinese hamster ovary (CHO) cells without metabolic activation. LiOCl did not induce DNA damage in the unscheduled DNA synthesis assay using rat primary hepatocytes. Effects on metaphase chromosomes were evaluated in vitro in CHO cells at 12 and 18 h exposure without S9 and at 12 and 22 h following a 2 h exposure with S9. LiOCl induced a statistically significant increase in chromosome aberrations at the high dose only at both harvest times without S9 and at the late harvest time with S9. There were significant increases in chromosome aberrations at the low dose, low-mid and high doses, but not at the high mid-dose at the early harvest time with S9. However, LiOCl did not increase chromosome aberrations when tested orally in rats at maximally tolerated doses. Bone marrow cells, collected 6, 24 and 48 h after a single oral dose of LiOCl to rats (100, 500, 1000 mg/kg in males; 50, 250, 500 mg/kg in females) showed no increase in the incidence of aberrations. In general, the weight of the evidence indicates that LiOCl is not genotoxic.

Respiratory syncytial virus-specific cell-mediated immune responses after vaccination with a purified fusion protein subunit vaccine.

Vaccination with a respiratory syncytial virus (RSV) fusion protein subunit vaccine (PFP-2) was done to determine if this vaccine induced evidence of cell-mediated immunity to RSV and if cell-mediated immunity prevented RSV reinfection. Healthy children 12-18 months old received 50 micrograms of PFP-2 or a saline control. Lymphocyte transformation (LTF) responses were determined before and 1 and 6 months after vaccination. PFP-2 induced positive LTF responses in 5 (83%) of 6 subjects whose prevaccination samples lacked evidence of cell-mediated immunity. Positive LTF responses in prevaccination samples were not boosted but were more persistent in vaccinees than in controls. Positive LTF responses were not associated with protection against subsequent infection. Immunization with PFP-2 induces correlates of cell-mediated immunity, but this immunity does not appear to be a critical component of protection.

Lipid synthesis in macrophages derived from the human cell line THP-1: modulation of the effects of native and oxidized chylomicron-remnant-like particles by oestrogen.

The effects of native and oxidized chylomicron remnants on the synthesis of cholesteryl ester and triacylglycerol in macrophages, and the way that this is influenced by exposure of the cells to oestrogen, was investigated using the human monocyte cell line THP-1 and chylomicron-remnant-like particles containing human apolipoprotein E (CRLPs). Synthesis of the lipids was measured by the incorporation of [(3)H]oleate into cholesteryl ester and triacylglycerol. CRLPs (5-40 microgram of cholesterol/ml) containing either trilinolein or triolein as the triacylglycerol component caused a dose-dependent decrease in cholesteryl ester formation, while triacylglycerol production was unchanged. After oxidation of the CRLPs, the level of thiobarbituric acid-reactive substances was increased by 6.3-fold and 2.2-fold in particles containing trilinolein and triolein respectively. Furthermore, CRLPs containing oxidized trilinolein lost their ability to down-regulate cholesterol esterification, while CRLPs containing oxidized triolein did not. Both types of oxidized CRLPs decreased triacylglycerol synthesis. Treatment of the macrophages with 17beta-oestradiol caused increases of approx. 94% and 34% in the synthesis of cholesteryl ester and triacylglycerol respectively in the absence of CRLPs. The differences between control and oestrogen-treated cells were abolished, however, when CRLPs (40 microgram of cholesterol/ml) were added to the incubations. In addition, in contrast with their lack of effect in control cells, CRLPs containing oxidized trilinolein decreased cholesterol esterification in oestrogen-treated cells by approx. 48%. These findings with CRLPs suggest that chylomicron remnants have significant effects on cholesteryl ester and triacylglycerol synthesis in macrophages, which may be modulated both by the oxidation state of the particles and by oestrogen.