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Background/Aims Worldwide, many people who would benefit from osteoporosis treatment are not offered or receiving them, resulting in an osteoporosis care gap. Adherence with bisphosphonates is particularly low. This study aimed to identify stakeholder research priorities relating to bisphosphonate regimens for the treatment of osteoporosis. Methods A three-step approach based on the James Lind Alliance methodology for identification and prioritisation of research questions was used. Research uncertainties were gathered (Step 1) from recent published international clinical guidelines and a large programme of related research studies about bisphosphonate regimens: the ‘Bisphosphonate aLternAtive regimenS for the prevenTion of Osteoporotic Fragility Fractures’ (Blast Off) study, which consisted of six discrete individual research studies conducted between May 2019 and February 2022, relating to the experience, effectiveness and cost-effectiveness of different bisphosphonate regimens. Clinical and public stakeholders refined the list of uncertainties into research questions (step 2) and then prioritised the questions using a modified nominal group technique (step 3) in two, day-long online workshops. Results In total, 34 draft uncertainties were finalised into 33 research questions by stakeholders. Twenty nine stakeholders were involved in refining uncertainties and prioritisation, including 16 public contributors, 2 Allied Health Professionals, 3 GPs and 8 Consultants. The top 10 questions are shown in Table 1. Conclusion This study reports, for the first time, topics of importance to stakeholders in the research of bisphosphonate osteoporosis treatment regimens. The priorities address how to better implement guidelines to address the care gap, understanding patient factors influencing treatment selection and effectiveness, and how to optimise long-term care. These findings have implications for research into implementation to address the care gap and education of healthcare professionals in the treatment of osteoporosis. Disclosure Z. Paskins: None. A. Moult: None. N. Corp: None. A. Bastounis: None. S. Davis: Grants/research support; Grant from Roche Diagnostics to her employing insitution to fund research into the cost-effectiveness of using a biomarker to monitor response to treatment with antifracture medication. M. Narayanasamy: None. J. Griffin: None. N. Gittoes: None. J. Leonardi-Bee: None. T. Langley: None. S. Bishop: None. O. Sahota: None.

Objectives Despite established standards and guidelines, substantial variation remains in the delivery of hip fracture care across the United Kingdom. We aimed to determine which hospital-level organisational factors predict adverse patient outcomes in the months following hip fracture. Methods We examined a national record-linkage cohort of 178,757 patients aged ≥60 years who sustained a hip fracture in England and Wales in 2016–19. Patient-level hospital admissions datasets, National Hip Fracture Database and mortality data were linked to metrics from 18 hospital-level organisational-level audits and reports. Multilevel models identified organisational factors, independent of patient case-mix, associated with three patient outcomes: length of hospital stay (LOS), 30-day all-cause mortality and emergency 30-day readmission. Results Across hospitals mean LOS ranged from 12 to 41.9 days, mean 30-day mortality from 3.7 to 10.4% and mean readmission rates from 3.7 to 30.3%, overall means were 21.4 days, 7.3% and 15.3%, respectively. In all, 22 organisational factors were independently associated with LOS; e.g. a hospital’s ability to mobilise >90% of patients promptly after surgery predicted a 2-day shorter LOS (95% confidence interval [CI]: 1.2–2.6). Ten organisational factors were independently associated with 30-day mortality; e.g. discussion of patient experience feedback at clinical governance meetings and provision of prompt surgery to >80% of patients were each associated with 10% lower mortality (95%CI: 5–15%). Nine organisational factors were independently associated with readmissions; e.g. readmissions were 17% lower if hospitals reported how soon community therapy would start after discharge (95%CI: 9–24%). Conclusions Receipt of hip fracture care should be reliable and equitable across the country. We have identified multiple, potentially modifiable, organisational factors associated with important patient outcomes following hip fracture.

This article gives a broad sense of existing debate about Global Citizenship Education (GCE) to help situate and contextualize a novel case study. Scholars for Syria originated at a small university in southern Indiana. This grassroots response to the turmoil in Syria bridges the gap between a seemingly distant crisis and a midwestern city in the United States. The unique pedagogical and curricular dimensions of the case study work as a helpful framing device for facilitating exploration of debates about the shape of GCE, as well as providing new ways in which to imagine GCE curriculum, pedagogy, and embedding ethics into wider university initiatives.

IntroductionSubstantial variation in the delivery of hip fracture care, and patient outcomes persists between hospitals, despite established UK national standards and guidelines. Patients’ outcomes are partly explained by patient-level risk factors, but it is hypothesised that organisational-level factors account for the persistence of unwarranted variation in outcomes. The mixed-methods REducing unwarranted variation in the Delivery of high qUality hip fraCture services in England and Wales (REDUCE) study, aims to determine key organisational factors to target to improve patient care.Methods and analysisQuantitative analysis will assess the outcomes of patients treated at 172 hospitals in England and Wales (2016–2019) using National Hip Fracture Database data combined with English Hospital Episodes Statistics; Patient Episode Database for Wales; Civil Registration (deaths) and multiple organisational-level audits to characterise each service provider. Statistical analyses will identify which organisational factors explain variation in patient outcomes, and typify care pathways with high-quality consistent patient outcomes. Documentary analysis of 20 anonymised British Orthopaedic Association hospital-initiated peer-review reports, and qualitative interviews with staff from four diverse UK hospitals providing hip fracture care, will identify barriers and facilitators to care delivery. The COVID-19 pandemic has posed a major challenge to the resilience of services and interviews will explore strategies used to adapt and innovate. This system-wide understanding will inform the development, in partnership with key national stakeholders, of an ‘Implementation Toolkit’ to inform and improve commissioning and delivery of hip fracture services.Ethics and disseminationThis study was approved: quantitative study by London, City and East Research Ethics Committee (20/LO/0101); and qualitative study by Faculty of Health Sciences University of Bristol Research Ethics Committee (Ref: 108284), National Health Service (NHS) Health Research Authority (20/HRA/71) and each NHS Trust provided Research and Development approval. Findings will be disseminated through scientific conferences, peer-reviewed journals and online workshops.

There are little data on the prevalence of reduced bone mineral density (BMD) in young adult patients with coeliac disease; guidelines do not support routine investigation of these patients. We assessed the prevalence of reduced BMD in our patients by age.Prospective observational study of 260 coeliac patients having DXA one year after commencing gluten-free diet. Nonparametric tests and regression were used.Median age was 51years, BMI 24 and 85 (32.7%) were male. Reduced BMD was associated with increasing age (p .001), female sex (p = .005), low BMI (p .001) and previous fracture (p .01); 49% of all patients and all patients under 20 years old had reduced BMD. The median age of patients with BMI20 kgmLow BMD is a common finding in young patients with coeliac disease, yet routine assessment of BMD is not currently supported by national guidelines. Early identification may improve motivation to comply with GFD and allow adequate calcium and vitamin D supplementation to reduce risk of fracture later in life.

To evaluate organisational reporting infrastructure and patient-related reporting data in the diagnosis of vertebral fragility fractures (VFFs) as demonstrated on computed tomography (CT). Organisational and patient-specific questionnaires were developed by consensus between The Royal College of Radiologists, the Royal College of Physicians, and the Royal Osteoporosis Society. The patient-specific component of the audit involved analysis of CT reporting data acquired from 50 consecutive non-traumatic studies including the thoracolumbar spine. Ethical approval for this type of study is not required in the UK. All UK radiology departments with an audit lead (auditor) registered with The Royal College of Radiologists (RCR) were invited to participate in this retrospective audit. In total, 127 out of 202 departments (63%) supplied data to the study, with inclusion of 6357 patients. Overall, 1362/6357 patients (21.4%) had a fracture present on auditor review of the CT imaging. There was a lack of compliance with all audit standards: 79% of reports commented on the vertebrae (target 100%), fracture severity was mentioned in 26.2% (target 100%), the recommended terminology ‘vertebral fracture’ was used in 60.1% (target 100%), and appropriate onward referral was recommended in 2.6% (target 100%). The findings from this study should be used to provide impetus to improve the diagnosis and care for patients with osteoporotic VFFs. Solutions are multifactorial, but radiologist and local osteoporosis/fracture liaison service engagement is fundamental, combined with necessary development of electronic report notification systems and expansion of supporting fracture services. • Early detection and diagnosis of vertebral fragility fractures (VFFs) significantly reduce patient morbidity and mortality. This study describes the results of a retrospective UK-wide audit evaluating current radiology reporting practice in the opportunistic diagnosis of VFFs as demonstrated on computed tomography (CT) studies including the spine. • Key audit standards included comment made on bone integrity in primary report (target 100%), comment made on severity of fractures (90%), report used recommended terminology ‘fracture’ (100%), and report made appropriate recommendations for referral/further assessment (100%). The audit results demonstrated a lack of compliance with all audit standards; lack of compliance was most marked in the use of recommended terminology (achieved 60.3%), in relation to comment on fracture severity (achieved 26.2%) and for recommendation for referral/further assessment (achieved 2.6%). • Solutions are challenging and multifactorial but the opportunity exists for all radiologists to examine their practice and directly improve patient care.

Summary Optimizing diabetes management in patients with complex type 2 diabetes (T2DM) and obesity presents challenges. This study evaluates weight and HbA1c at 12 months (primary outcomes) and blood pressure, lipids, medication and lifestyle changes (secondary outcomes) in patients referred by a diabetes specialist (DSN) to the weight management intervention (Slimming World). Patients attended up to 12 or 24 funded weekly group sessions. The DSN recorded baseline and 12‐month primary and secondary outcome data. A post‐intervention questionnaire explored the lifestyle changes made. 69 patients achieved a mean weight loss of 5.5 (5.16) %, reduction in BMI [37.7(6.11) to 35.9 (6.30) kg/m2, P

Oseltamivir, an orally bioavailable neuraminidase inhibitor, is licensed in the United States for treatment and chemoprophylaxis of influenza in children ≥1 year of age.1 Another neuraminidase inhibitor, zanamivir, also is licensed for use in children ≥7 years of age for treatment and ≥5 years of age for chemoprophylaxis.1 It is delivered via an inhaler device that is difficult for younger children to use. In a prospective, randomized, blinded, placebo-controlled study in influenza-infected children 1 to 12 years of age, a 5-day treatment course of oseltamivir was associated with a median reduction in overall clinical illness of 36 hours and a reduction in fever of 25 hours.2 Additionally, the incidence of acute otitis media was reduced by 44% compared with placebo recipients. A significant decrease in viral shedding was also noted in treated children, with few treated children still shedding virus on day 4 of therapy. The most common adverse drug effect was vomiting (14% of oseltamivir-treated subjects vs. 8% of placebo recipients).2 The safety of oseltamivir therapy in infants younger than 12 months of age is a potential concern. The oseltamivir package insert states that use of oseltamivir in this age group is not indicated,3 based on preclinical findings in juvenile rats.4 A single 1000 mg/kg dose of oseltamivir (about 250 times the recommended dose in children) in 7-day-old rats resulted in excess deaths in association with unusually high exposure to both the active metabolite of oseltamivir and the prodrug. Concentrations of the prodrug in juveniles were approximately 1500 times greater than those seen in adult animals, suggesting that these adverse outcomes may be related to an immature blood-brain barrier or to immaturity of conversion of prodrug to active metabolite in juvenile animals. While the applicability of these rat studies to human infants is questionable due to significant differences in oseltamivir metabolism between the 2 species and the extremely high doses employed in the animal trials, caution is warranted until appropriate pediatric studies can be conducted. Reassuringly, a retrospective study of infants younger than 1 year of age in Japan did not find an association between use of oseltamivir and either mortality or encephalopathy.5 Despite the wording of the package insert, off-label use of oseltamivir in infants less than 12 months of age occurs in the United States, particularly in infants who are seriously ill or considered to be at high risk of complications from influenza infection or in those who present with severe disease. To assess potential neurologic adverse effects of oseltamivir in infants, a retrospective chart review was performed in North America by the National Institute of Allergy and Infectious Diseases (NIAID) Collaborative Antiviral Study Group (CASG) of infants less than 12 months of age who received oseltamivir compared with either of the adamantanes (amantadine or rimantadine).

Congenital cytomegalovirus (CMV) affects 0.6% to 0.7% of live births in industrialized nations. It is the leading viral causeof mental retardation and can also result in sensorineural hearing loss. Accepted treatment for patients with symptomatic congenital CMV involving the central nervous system includes intravenous ganciclovir, but the benefits of intravenous ganciclovir may wane over time. Oral therapy with valganciclovir has also been used in the treatment of congenital CMV, and the benefit of longer therapy was studied in this randomized controlled trial. A total of 40 sites participated in the study, and newborns were eligible if they had symptomatic congenital CMV disease, without or without central nervous system involvement. All patients received valganciclovir for 6 weeks, and 1 group continued the treatment for 4.5 months, whereas the rest received a placebo. Change in hearing in the better ear was measured as the primary end point. From 31 study sites, a total of 96 participants were randomized, with 47 participants receiving 6 months of treatment and 49 receiving placebo. A total of 12 stopped taking the blinded medication before the end of the study, but none did so because of adverse events. At 6 months, hearing in the better ear was similar between the 2 groups, with 2 having improvement in the 6-month group and 3 having improvement in the 6-week group, and 5 and 3, respectively, worsening (P = 0.41). At 12 months, total-ear hearing was more likely to be improved or remain normal in patients in the 6-month group than in the 6-week group (73% vs 57%, P = 0.001). The 6-month group scored better on the Bayley Scales of Infant and Toddler Development than did the 6-week group after 24 months on the receptive-communication scale (P = 0.003) and the language-composite scale (P = 0.004).Grade 3 or 4 neutropenia was not different in the 6-month versus the 6-week group (21% vs 27% after 6 months, P = 0.64).These findings suggest 6 months, compared with 6 weeks, of oral valganciclovir among infants with symptomatic congenital CMV disease modestly improved hearing, not in the short term, but in the long term. The prolonged treatment also appearedto improve developmental outcomes modestly.

Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease.We enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo-controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other. After completing a regimen of 14 to 21 days of parenteral acyclovir, the infants were randomly assigned to immediate acyclovir suppression (300 mg per square meter of body-surface area per dose orally, three times daily for 6 months) or placebo. Cutaneous recurrences were treated with open-label episodic therapy.A total of 74 neonates were enrolled--45 with CNS involvement and 29 with skin, eye, and mouth disease. The Mental Development Index of the Bayley Scales of Infant Development (in which scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62%) at 12 months of age. After adjustment for covariates, infants with CNS involvement who had been randomly assigned to acyclovir suppression had significantly higher mean Bayley mental-development scores at 12 months than did infants randomly assigned to placebo (88.24 vs. 68.12, P=0.046). Overall, there was a trend toward more neutropenia in the acyclovir group than in the placebo group (P=0.09).Infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; CASG 103 and CASG 104 ClinicalTrials.gov numbers, NCT00031460 and NCT00031447, respectively.).

Background. Intravenous ganciclovir administered for 6 weeks improves hearing outcomes in infants with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system. Methods. Twenty-four subjects received antiviral therapy for 6 weeks. Serial pharmacokinetic assessments were performed after administration ofvalganciclovir oral solution and of intravenous ganciclovir. Results. On the basis of a previous pharmacokinetic study of the use of intravenous ganciclovir in this population, a target AUC 12 (area under the concentration-time curve over a 12-h period) of 27 mg X h/L was defined. The median dose of oral valganciclovir administered in the present trial was 16 mg/kg, which produced a geometric mean AUC 12 of 27.4 mg X h/L. The bioavailability of valganciclovir was 41.1%. Of the 18 subjects who had detectable CMV in whole blood at baseline or during therapy, 11 had

Cytomegalovirus (CMV) is the most common viral congenital infection, producing both sensorineural hearing loss and mental retardation. Our objective was to assess the population pharmacokinetics of a research-grade oral valganciclovir solution in neonates with symptomatic congenital CMV disease. Twenty-four neonates received 6 weeks of antiviral therapy. Ganciclovir and valganciclovir were measured by liquid chromatography/tandem mass spectroscopy. NONMEM version VI beta was used for population analyses. All profiles were consistent with a one-compartment model. Postnatal age, body surface area, and gender did not improve the model fit after body weight was taken into account. The typical value of clearance (l/h), distribution volume (l), and bioavailability of ganciclovir were 0.146 x body weight (WT)(1.68), 1.15 x WT, and 53.6%, respectively. Although these results cannot be extrapolated to extemporaneously compounded valganciclovir preparations, they provide the foundation on which a commercial-grade valganciclovir oral solution may be a viable option for administration to neonates.

We describe a case of runaway pacemaker. The differential diagnosis is discussed and a review of the literature is included for the diagnosis and treatment of pacemaker mediated tachycardia and runaway pacemaker.

A LTHOUGH there are many similarities between cisplatin (Platinol) administration in the office and outpatient settings, this discussion is from the perspective of the office oncology nurse. The changing realities of today’s medical environment present physicians and nurses with the opportunity to administer cisplatin in the office setting. Such outpatient administration requires a well-organized office, appropriate patient scheduling, and a qualified nursing staff allocated to perform this function. Although some physicians still regard cisplatin as an agent predominantly for inpatient usage, with proper patient selection and an understanding of associated toxicities and hydration regimens, the drug can be administered safely to patients in the office setting. Overall, the selection of patients for cisplatin administration in the office setting requires planning and collaboration by the physician, nurse, and other office staff. An important benefit to office administration is that the patient with cancer can avoid continuous hospitalization, which can be detrimental psychologically. Decreased hospitalization affords the patient continuation of a normal lifestyle, one that offers privacy. In this way, the patients tend to feel less ill and more in control of the treatment course.