Evaluating the impact of COVID-19 on DXA waiting lists and osteoporosis prescription trends in England 2019-2023.

This study uses NHS waiting times and osteoporosis medication community prescription datasets to assess the impact of COVID-19 on DXA waits and osteoporosis medication patterns in England. Results show significant increases in DXA waiting list times and variation in prescription rates. Investment is needed to improve waiting list times. PURPOSE: This study investigates the impact of COVID-19 on DXA scan waiting lists, service recovery and osteoporosis medication prescriptions in the NHS following the March 2020 national lockdowns and staff redeployment. METHODS: Data from March 2019 to June 2023, including NHS digital diagnostics waiting times (DM01) and osteoporosis medication prescriptions from the English Prescribing Dataset (EPD), were analysed. This encompassed total waiting list data across England's seven regions and prescribing patterns for various osteoporosis medications. Analyses included total activity figures and regression analysis to estimate expected activity without COVID-19, using R for all data analysis. RESULTS: In England, DXA waiting lists have grown significantly, with the yearly mean waiting list length increasing from 31,851 in 2019 to 65,757 in 2023. The percentage of patients waiting over 6 weeks for DXA scans rose from 0.9% in 2019 to 40% in 2020, and those waiting over 13 weeks increased from 0.1% in 2019 to 16.7% in 2020. Prescription trends varied, with increases in denosumab, ibandronic acid and risedronate sodium and decreases in alendronic acid, raloxifene hydrochloride and teriparatide. A notable overall prescription decrease occurred in the second quarter of 2020. CONCLUSION: COVID-19 has significantly increased DXA scan waiting lists with ongoing recovery challenges. There is a noticeable disparity in DXA service access across England. Osteoporosis care, indicated by medication prescriptions, also declined during the pandemic. Addressing these issues requires focused investment and effort to improve DXA scan waiting times and overall access to osteoporosis care in England.

A RAC-GEF network critical for early intestinal tumourigenesis.

RAC1 activity is critical for intestinal homeostasis, and is required for hyperproliferation driven by loss of the tumour suppressor gene Apc in the murine intestine. To avoid the impact of direct targeting upon homeostasis, we reasoned that indirect targeting of RAC1 via RAC-GEFs might be effective. Transcriptional profiling of Apc deficient intestinal tissue identified Vav3 and Tiam1 as key targets. Deletion of these indicated that while TIAM1 deficiency could suppress Apc-driven hyperproliferation, it had no impact upon tumourigenesis, while VAV3 deficiency had no effect. Intriguingly, deletion of either gene resulted in upregulation of Vav2, with subsequent targeting of all three (Vav2-/- Vav3-/- Tiam1-/-), profoundly suppressing hyperproliferation, tumourigenesis and RAC1 activity, without impacting normal homeostasis. Critically, the observed RAC-GEF dependency was negated by oncogenic KRAS mutation. Together, these data demonstrate that while targeting RAC-GEF molecules may have therapeutic impact at early stages, this benefit may be lost in late stage disease.

Screening for high hip fracture risk does not impact on falls risk: a post hoc analysis from the SCOOP study.

A reduction in hip fracture incidence following population screening might reflect the effectiveness of anti-osteoporosis therapy, behaviour change to reduce falls, or both. This post hoc analysis demonstrates that identifying high hip fracture risk by FRAX was not associated with any alteration in falls risk. INTRODUCTION: To investigate whether effectiveness of an osteoporosis screening programme to reduce hip fractures was mediated by modification of falls risk in the screening arm. METHODS: The SCOOP study recruited 12,483 women aged 70-85 years, individually randomised to a control (n = 6250) or screening (n = 6233) arm; in the latter, osteoporosis treatment was recommended to women at high risk of hip fracture, while the control arm received usual care. Falls were captured by self-reported questionnaire. We determined the influence of baseline risk factors on future falls, and then examined for differences in falls risk between the randomisation groups, particularly in those at high fracture risk. RESULTS: Women sustaining one or more falls were slightly older at baseline than those remaining falls free during follow-up (mean difference 0.70 years, 95%CI 0.55-0.85, p < 0.001). A higher FRAX 10-year probability of hip fracture was associated with increased likelihood of falling, with fall risk increasing by 1-2% for every 1% increase in hip fracture probability. However, falls risk factors were well balanced between the study arms and, importantly, there was no evidence of a difference in falls occurrence. In particular, there was no evidence of interaction (p = 0.18) between baseline FRAX hip fracture probabilities and falls risk in the two arms, consistent with no impact of screening on falls in women informed to be at high risk of hip fracture. CONCLUSION: Effectiveness of screening for high FRAX hip fracture probability to reduce hip fracture risk was not mediated by a reduction in falls.

Systematic screening using FRAX® leads to increased use of, and adherence to, anti-osteoporosis medications: an analysis of the UK SCOOP trial.

In the large community-based SCOOP trial, systematic fracture risk screening using FRAX® led to greater use of AOM and greater adherence, in women at high fracture risk, compared with usual care. INTRODUCTION: In the SCreening of Older wOmen for Prevention of fracture (SCOOP) trial, we investigated the effect of the screening intervention on subsequent long-term self-reported adherence to anti-osteoporosis medications (AOM). METHODS: SCOOP was a primary care-based UK multicentre trial of screening for fracture risk. A total of 12,483 women (70-85 years) were randomised to either usual NHS care, or assessment using the FRAX® tool ± dual-energy X-ray absorptiometry (DXA), with medication recommended for those found to be at high risk of hip fracture. Self-reported AOM use was obtained by postal questionnaires at 6, 12, 24, 36, 48 and 60 months. Analysis was limited to those who initiated AOM during follow-up. Logistic regression was used to explore baseline determinants of adherence (good ≥ 80%; poor < 80%). RESULTS: The mean (SD) age of participants was 75.6 (4.2) years, with 6233 randomised to screening and 6250 to the control group. Of those participants identified at high fracture risk in the screening group, 38.2% of those on treatment at 6 months were still treated at 60 months, whereas the corresponding figure for the control group was 21.6%. Older age was associated with poorer adherence (OR per year increase in age 0.96 [95% CI 0.93, 0.99], p = 0.01), whereas history of parental hip fracture was associated with greater rate adherence (OR 1.67 [95% CI 1.23, 2.26], p < 0.01). CONCLUSIONS: Systematic fracture risk screening using FRAX® leads to greater use of AOM and greater adherence, in women at high fracture risk, compared with usual care.

The cost of treating diabetic ketoacidosis in an adolescent population in the UK: a national survey of hospital resource use.

AIMS: Adolescents with Type 1 diabetes commonly experience episodes of ketoacidosis. In 2014, we conducted a nationwide survey on the management of diabetic ketoacidosis in young people. The survey reported how individual adolescents with diabetes were managed. However, the costs of treating diabetic ketoacidosis were not reported. METHODS: Using this mixed population sample of adolescents, we took a 'bottom-up' approach to cost analysis aiming to determine the total expense associated with treating diabetic ketoacidosis. The data were derived using the information from the national UK survey of 71 individuals, collected via questionnaires sent to specialist paediatric diabetes services in England and Wales. RESULTS: Several assumptions had to be made when analysing the data because the initial survey collection tool was not designed with a health economic model in mind. The mean time to resolution of diabetic ketoacidosis was 15.0 h [95% confidence interval (CI) 13.2, 16.8] and the mean total length of stay was 2.4 days (95% CI 1.9, 3.0). Based on data for individuals and using the British Society of Paediatric Endocrinology and Diabetes (BSPED) guidelines, the cost analysis shows that for this cohort, the average cost for an episode of diabetic ketoacidosis was £1387 (95% CI 1120, 1653). Regression analysis showed a significant cost saving of £762 (95% CI 140, 1574; P = 0.04) among those treated using BSPED guidelines. CONCLUSION: We have used a bottom-up approach to calculate the costs of an episode of diabetic ketoacidosis in adolescents. These data suggest that following treatment guidelines can significantly lower the costs for managing episodes of diabetic ketoacidosis.

Home blood-pressure monitoring in a hypertensive pregnant population: cost-minimization study.

OBJECTIVE: Traditional blood-pressure monitoring in hypertensive pregnant women requires frequent visits to the maternity outpatient services. Home blood-pressure monitoring (HBPM) could offer a cost-saving alternative that is acceptable to patients. The aim of this study was to undertake a health economic analysis of HBPM compared with traditional monitoring in hypertensive pregnant women. METHODS: This was a cost-minimization study of hypertensive pregnant women who had HBPM with or without the adjunct of a smartphone application (App), via a specially designed pathway, and a control group managed according to the local protocol of regular hospital visits for blood-pressure monitoring. Outcome measures were the number of outpatient visits, inpatient bed stays and investigations performed. Maternal, fetal and neonatal adverse outcomes were also recorded. Health economic analysis was performed using direct cost comparison of the study dataset and process scenario modeling. RESULTS: The HBPM group included 108 women, of whom 29 recorded their results on the smartphone App and 79 in their notes. The control group comprised 58 patients. There were significantly more women with chronic hypertension in the HBPM group than in the control group (49.1% vs 25.9%, P = 0.004). The HBPM group had significantly longer duration of monitoring (9 weeks vs 5 weeks, P = 0.004) and started monitoring at an earlier gestational age (30.0 weeks vs 33.6 weeks, P = 0.001) compared with the control group. Despite these differences, the mean saving per week for each patient using HBPM compared with traditional monitoring was £200.69, while for each HBPM patient using the smartphone App, the weekly saving was £286.53 compared with the control group. The process modeling method predicted weekly savings of between £98.32 and £245.80 per patient using HBPM compared with traditional monitoring. CONCLUSION: HBPM in hypertensive pregnancy appears to be cost saving compared with traditional monitoring, without compromising maternal, fetal or neonatal safety. Larger studies are required to confirm these findings. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

The cost of treating diabetic ketoacidosis in the UK: a national survey of hospital resource use.

AIM: Diabetic ketoacidosis is a commonly encountered metabolic emergency. In 2014, a national survey was conducted looking at the management of diabetic ketoacidosis in adult patients across the UK. The survey reported the clinical management of individual patients as well as institutional factors that teams felt were important in helping to deliver that care. However, the costs of treating diabetic ketoacidosis were not reported. METHODS: We used a 'bottom up' approach to cost analysis to determine the total expense associated with treating diabetic ketoacidosis in a mixed population sample. The data were derived from the source data from the national UK survey of 283 individual patients collected via questionnaires sent to hospitals across the country. RESULTS: Because the initial survey collection tool was not designed with a health economic model in mind, several assumptions were made when analysing the data. The mean and median time in hospital was 5.6 and 2.7 days respectively. Based on the individual patient data and using the Joint British Diabetes Societies Inpatient Care Group guidelines, the cost analysis shows that for this cohort, the average cost for an episode of diabetic ketoacidosis was £2064 per patient (95% confidence intervals: 1800, 2563). CONCLUSION: Despite relatively short stays in hospital, costs for managing episodes of diabetic ketoacidosis in adults were relatively high. Assumptions made in the calculations did not consider prolonged hospital stay due to comorbidities or costs incurred as a loss of productivity. Therefore, the actual costs to the healthcare system and society in general are likely to be substantially higher.

Direct costs of pulmonary tuberculosis among patients receiving treatment in Bauchi State, Nigeria.

BACKGROUND: To access tuberculosis (TB) services, patients have to bear the costs of out-of-pocket expenditures or direct costs for transport, drugs and other services that are not provided free-of-charge. These costs could represent a barrier to care, especially in a country such as Nigeria, where per capita gross national income is only US$1160 and 46% of the urban population live below the poverty line. OBJECTIVE: To describe the direct costs of TB diagnosis and treatment in Bauchi State, Nigeria, from the patient's perspective. METHODS: A cross-sectional study. A sample size of 255 patients was randomly selected from 27 of 67 facilities in Bauchi State, Nigeria. RESULTS: The median out-of-pocket cost for hospitalised patients was estimated at US$166.11, while ambulatory patients paid an estimated median cost of US$94.16, equivalent to about 9-38% of their average annual income. Female patients spent a higher proportion of their income on diagnosis and treatment than males (P < 0.0001). The median out-of-pocket costs borne by patients before, during and after diagnosis were estimated at respectively US$35.23, US$27.12 and US$23.43 for ambulatory patients, and additional average out-of-pocket spending of US$66.44 for patients hospitalised during their illness. Pre-diagnosis, diagnosis and post-diagnosis out-of-pocket spending did not vary significantly by human immunodeficiency virus status (P > 0.05) and sex (P > 0.05). CONCLUSION: The costs of anti-tuberculosis treatment found in this study are expensive and potentially catastrophic for many patients and their families.

A pragmatic randomised controlled trial of the effectiveness and cost-effectiveness of screening older women for the prevention of fractures: rationale, design and methods for the SCOOP study.

SCOOP is a UK seven-centre, pragmatic, randomised controlled trial with 5-year follow-up, including 11,580 women aged 70 to 85 years, to assess the effectiveness and cost-effectiveness of a community-based screening programme to reduce fractures. It utilises the FRAX algorithm and DXA to assess the 10-year probability of fracture. Introduction Osteoporotic, or low-trauma, fractures present a considerable burden to the National Health Service and have major adverse effects on quality of life, disability and mortality for the individual. Methods Given the availability of efficacious treatments and a risk assessment tool based upon clinical risk factors and bone mineral density, a case exists to undertake a community-based controlled evaluation of screening for subjects at high risk of fracture, under the hypothesis that such a screening programme would reduce fractures in this population. Results This study is a UK seven-centre, unblinded, pragmatic, randomised controlled trial with a 5-year follow-up period. A total of 11,580 women, aged 70 to 85 years and not on prescribed bone protective therapy will be consented to the trial by post via primary care providing 90% power to detect an 18% decrease in fractures. Conclusions Participants will be randomised to either a screening arm or control. Those undergoing screening will have a 10-year fracture probability computed from baseline risk factors together with bone mineral density measured by DXA in selected subjects. Individuals above an age-dependent threshold of fracture probability will be recommended for treatment for the duration of the trial. Subjects in the control arm will receive 'usual care'. Participants will be followed up 6 months after randomisation and annually by postal questionnaires with independent checking of hospital and primary care records. The primary outcome will be the proportion of individuals sustaining fractures in each group. An economic analysis will be carried out to assess cost-effectiveness of screening. A qualitative evaluation will be conducted to examine the acceptability of the process to participants.

The Provider Cost of Treating Tuberculosis in Bauchi State; Nigeria

The study was aimed at assessing the economic cost shouldered by government; as providers; in the provision of free tuberculosis (TB) diagnosis and treatment services in Bauchi State; northern Nigeria. A cost analysis study was designed and questionnaires administered by the principal investigators to officers in charge of 27 randomly sampled government TB services providers across the State of Bauchi. Seventeen of these centers were primary care centers; 9 secondary care providers and one was a tertiary care provider. Data was also collected from personnel and projects records in the State Ministry of Health; of Works as well as the Ministry of Budget and Planning.The cost of buildings; staff and equipment replacement; laboratory; radiology and drugs in facilities were assessed and costs attributable tuberculosis inpatient; outpatient and directly observed therapy (DOT) services were estimated from the total cost based on the proportion of TB cases in the total patient pool accessing those services. The average proportion of TB patients in facilities was 3.4in overall; 3.3among inpatients and 3.1in the outpatient population. The average cost spent to treat a patient with TB was estimated at US $227.14. The cost of inpatient care averaged $16.95/patient; DOT and outpatient services was $133.34/patient; while the overhead cost per patient was $30.89. The overall cost and all computed cost elements; except for DOT services; were highest in the tertiary center and least expensive in the infectious diseases hospital partly due to the higher administrative and other overhead recurrent spending in the tertiary health facility while the lower overhead cost observed in the infectious diseases hospital could be due to the economy of scale as a result of the relative higher number of TB cases seen in the facility operating with relatively same level of resources as other facilities in the state

A systematic review of the clinical, public health and cost-effectiveness of rapid diagnostic tests for the detection and identification of bacterial intestinal pathogens in faeces and food.

OBJECTIVES: To determine the diagnostic accuracy of tests for the rapid diagnosis of bacterial food poisoning in clinical and public health practice and to estimate the cost-effectiveness of these assays in a hypothetical population in order to inform policy on the use of these tests. DATA SOURCES: Studies evaluating diagnostic accuracy of rapid tests were retrieved using electronic databases and handsearching reference lists and key journals. Hospital laboratories and test manufacturers were contacted for cost data, and clinicians involved in the care of patients with food poisoning were invited to discuss the conclusions of this review using the nominal group technique. REVIEW METHODS: A systematic review of the current medical literature on assays used for the rapid diagnosis of bacterial food poisoning was carried out. Specific organisms under review were Salmonella, Campylobacter, Escherichia coli O157, Staphylococcus aureus, Clostridium perfringens and Bacillus cereus. Data extraction was undertaken using standardised data extraction forms. Where a sufficient number of studies evaluating comparable tests were identified, meta-analysis was performed. A decision analytic model was developed, using effectiveness data from the review and cost data from hospitals and manufacturers, which contributed to an assessment of the cost-effectiveness of rapid tests in a hypothetical UK population. Finally, diagnostic accuracy and cost-effectiveness results were presented to a focus group of GPs, microbiologists and consultants in communicable disease control, to assess professional opinion on the use of rapid tests in the diagnosis of food poisoning. RESULTS: Good test performance levels were observed with rapid test methods, especially for polymerase chain reaction (PCR) assays. The estimated levels of diagnostic accuracy using the area under the curve of the summary receiver operating characteristic curve was very high. Indeed, although traditional culture is the natural reference test to use for comparative statistical analysis, on many occasions the rapid test outperforms culture, detecting additional 'truly' positive cases of food-borne illness. The significance of these additional positives requires further investigation. Economic modelling suggests that adoption of rapid tests in combination with routine culture is unlikely to be cost-effective, however, as the cost of rapid technologies decreases; total replacement with rapid technologies may be feasible. CONCLUSIONS: Despite the relatively poor quality of reporting of studies evaluating rapid detection methods, the reviewed evidence shows that PCR for Campylobacter, Salmonella and E. coli O157 is potentially very successful in identifying pathogens, possibly detecting more than the number currently reported using culture. Less is known about the benefits of testing for B. cereus, C. perfringens and S. aureus. Further investigation is needed on how clinical outcomes may be altered if test results are available more quickly and at a greater precision than in the current practice of bacterial culture.

The cost-effectiveness of mycophenolate mofetil as firstline therapy in active lupus nephritis.

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disorder that can affect any system of the body. Involvement of the kidneys, lupus nephritis (LN), affects up to 50% of SLE patients during the course of their disease, and is characterized by periods of active disease (flares) and remission. For more severe nephritis, an induction course of immunosuppressive therapy is recommended. Options include intravenous cyclophosphamide (IVC) or mycophenolate mofetil (MMF), followed by a maintenance course, typically of azathioprine. The objective of this study is to determine which therapy results in better quality of life (QoL) for patients and which represents best value for money for finite health service resources. METHODS: A patient-level simulation model is developed to estimate the costs and quality-adjusted life-years (QALYs) of a patient treated with IVC or MMF for an induction period of six months. Efficacy, QoL, resource use and cost data are extracted from the literature and standard databases and supplemented with expert opinion where necessary. RESULTS: On average, the model predicts MMF to result in improved QoL compared with IVC. MMF is also less expensive than IVC, costing pound 1600 (euro 2400; US$ 3100) less over the period, based on 2005 NHS prices. The major determinant and cost driver of this result is the requirement for a day-case procedure to administer IVC. Sensitivity analysis shows an 81% probability that MMF will be cost-effective compared with IVC at a willingness to pay of pound 30,000 (euro 44,700; US$ 58,500) per QALY gained. CONCLUSION: MMF is likely to result in better QoL and be less expensive than IVC as induction therapy for LN.

To freeze or not to freeze: a cost-effectiveness analysis of wart treatment.

BACKGROUND: Several general practitioner (GP)-prescribed and over-the-counter therapies for warts and verrucae are available. However, the cost-effectiveness of these treatments is unknown. OBJECTIVES: To compare the cost-effectiveness of different treatments for cutaneous warts. METHODS: We designed a decision-analytic Markov simulation model based on systematic review evidence to estimate the cost-effectiveness of various treatments. The outcome measures studied are percentage of patients cured, cost of treatment and incremental cost-effectiveness ratio for each treatment, compared with no treatment, after 18 weeks. RESULTS: Duct tape was most cost-effective but published evidence of its effectiveness is sparse. Salicylic acid was the most cost-effective over-the-counter treatment commonly used. Cryotherapy administered by a GP was less cost-effective than GP-prescribed salicylic acid and less cost-effective than cryotherapy administered by a nurse. CONCLUSIONS: Duct tape could be adopted as the primary treatment for cutaneous warts if its effectiveness is verified by further rigorous trials. Nurse-administered cryotherapy is likely to be more cost-effective than GP-administered cryotherapy.

Effectiveness and cost-effectiveness of salicylic acid and cryotherapy for cutaneous warts. An economic decision model.

OBJECTIVES: To estimate the costs of commonly used treatments for cutaneous warts, as well as their health benefits and risk. To create an economic decision model to evaluate the cost-effectiveness of these treatments, and, as a result, assess whether a randomised controlled trial (RCT) would be feasible and cost-effective. DATA SOURCES: Focus groups, structured interviews and observation of practice. Postal survey sent to 723 patients. A recently updated Cochrane systematic review and published cost and prescribing data. REVIEW METHODS: Primary and secondary data collection methods were used to inform the development of an economic decision model. Data from the postal survey provided estimates of the effectiveness of wart treatments in a primary care setting. These estimates were compared with outcomes reported in the Cochrane review of wart treatment, which were largely obtained from RCTs conducted in secondary care. A decision model was developed including a variety of over-the-counter (OTC) and GP-prescribed treatments. The model simulated 10,000 patients and adopted a societal perspective. RESULTS: OTC treatments were used by a substantial number of patients (57%) before attending the GP surgery. By far the most commonly used OTC preparation was salicylic acid (SA). The results of the economic model suggested that of the treatments prescribed by a GP, the most cost-effective treatment was SA, with an incremental cost-effectiveness ratio (ICER) of 2.20 pound/% cured. The ICERs for cryotherapy varied widely (from 1.95 to 7.06 pound/% cured) depending on the frequency of applications and the mode of delivery. The most cost-effective mode of delivery was through nurse-led cryotherapy clinics (ICER = 1.95 pound/% cured) and this could be a cost-effective alternative to GP-prescribed SA. Overall, the OTC therapies were the most cost-effective treatment options. ICERs ranged from 0.22 pound/% cured for OTC duct tape and 0.76 pound/% cured for OTC cryotherapy to 1.12 pound/% cured for OTC SA. However, evidence in support of OTC duct tape and OTC cryotherapy is very limited. Side-effects were commonly reported for both SA and cryotherapy, particularly a burning sensation, pain and blistering. CONCLUSIONS: Cryotherapy delivered by a doctor is an expensive option for the treatment of warts in primary care. Alternative options such as GP-prescribed SA and nurse-led cryotherapy clinics provide more cost-effective alternatives, but are still expensive compared with self-treatment. Given the minor nature of most cutaneous warts, coupled with the fact that the majority spontaneously resolve in time, it may be concluded that a shift towards self-treatment is warranted. Although both duct tape and OTC cryotherapy appear promising new self-treatment options from both a cost and an effectiveness perspective, more research is required to confirm the efficacy of these two methods of wart treatment. If these treatments are shown to be as cost-effective as or more cost-effective than conventional treatments, then a shift in service delivery away from primary care towards more OTC treatment is likely. A public awareness campaign would be useful to educate patients about the self-limiting nature of warts and the possible alternative OTC treatment options available. Two future RCTs are recommended for consideration: a trial of SA compared with nurse-led cryotherapy in primary care, and a trial of home treatments. Greater understanding of the efficacy of these home treatments will give doctors a wider choice of treatment options, and may help to reduce the overall demand for cryotherapy in primary care.

A framework for measuring costs to society of IgE-mediated food allergy.

Both immunoglobulin E (IgE)-mediated food allergy and food intolerance can lead to many changes in personal behaviour and health care resource use which have important economic consequences. These costs will impact directly, indirectly and intangibly on both individuals and society in general. It is important to measure the cost of illness (COI) of food allergy as a first step in developing and evaluating measures to reduce and control the burden of illness. This paper outlines a framework for assessing COI of food allergy from different viewpoints. It offers a structure for identifying the different cost impacts on allergic and nonallergic consumers, food producers and society as a whole, and for scoping, measurement and valuation of relevant costs. Within this structure, the existing literature is reviewed. This review illustrates the lack of information and clear methodology for assessing costs of food allergy. The paper concludes that there is a need for a more structured research programme to generate data essential for future evaluations of procedures and technologies for the diagnosis, treatment and management of food allergy.

Inadequate lung development and bronchial hyperplasia in mice with a targeted deletion in the Dutt1/Robo1 gene.

Chromosome 3 allele loss in preinvasive bronchial abnormalities and carcinogen-exposed, histologically normal bronchial epithelium indicates that it is an early, possibly the first, somatic genetic change in lung tumor development. Candidate tumor suppressor genes have been isolated from within distinct 3p regions implicated by heterozygous and homozygous allele loss. We have proposed that DUTT1, nested within homozygously deleted regions at 3p12-13, is the tumor suppressor gene that deletion-mapping and tumor suppression assays indicate is located in proximal 3p. The same gene, ROBO1 (accession number ), was independently isolated as the human homologue of the Drosophila gene, Roundabout. The gene, coding for a receptor with a domain structure of the neural-cell adhesion molecule family, is widely expressed and has been implicated in the guidance and migration of axons, myoblasts, and leukocytes in vertebrates. A deleted form of the gene, which mimics a naturally occurring, tumor-associated human homozygous deletion of exon 2 of DUTT1/ROBO1, was introduced into the mouse germ line. Mice homozygous for this targeted mutation, which eliminates the first Ig domain of Dutt1/Robo1, frequently die at birth of respiratory failure because of delayed lung maturation. Lungs from these mice have reduced air spaces and increased mesenchyme, features that are present some days before birth. Survivors acquire extensive bronchial epithelial abnormalities including hyperplasia, providing evidence of a functional relationship between a 3p gene and the development of bronchial abnormalities associated with early lung cancer.

Economics of fall prevention programs: evidence and research priorities.

Injurious falls, particularly among the elderly, are a leading cause of morbidity, mortality and health and social care expenditure. Non injurious falls may result in significant quality of life losses through generating a fear of subsequent falls. Falls may be due to intrinsic (age-related physiological changes, diseases or polypharmacy) or extrinsic (environmental hazards and behavior) factors. Although interventions target both of these, much of the focus is upon extrinsic factors, through changes to behavior and the environment. This paper reviews the cost-effectiveness of such interventions in reducing the risk of new falls, or modifying the harm caused in the event of a fall, for the general unselected population of the elderly living independently in the community.