Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

A cost minimisation analysis in teledermatology: model-based approach

<p>Abstract</p> <p>Background</p> <p>Although store-and-forward teledermatology is increasingly becoming popular, evidence on its effects on efficiency and costs is lacking. The aim of this study, performed in addition to a clustered randomised trial, was to investigate to what extent and under which conditions store-and-forward teledermatology can reduce costs from a societal perspective.</p> <p>Methods</p> <p>A cost minimisation study design (a model based approach) was applied to compare teledermatology and conventional process costs per dermatology patient care episode. Regarding the societal perspective, total mean costs of investment, general practitioner, dermatologists, out-of-pocket expenses and employer costs were calculated. Uncertainty analysis was performed using Monte Carlo simulation with 31 distributions in the used cost model. Scenario analysis was performed using one-way and two-way sensitivity analyses with the following variables: the patient travel distance to physician and dermatologist, the duration of teleconsultation activities, and the proportion of preventable consultations.</p> <p>Results</p> <p>Total mean costs of teledermatology process were €387 (95%CI, 281 to 502.5), while the total mean costs of conventional process costs were €354.0 (95%CI, 228.0 to 484.0). The total mean difference between the processes was €32.5 (95%CI, -29.0 to 74.7). Savings by teledermatology can be achieved if the distance to a dermatologist is larger (> = 75 km) or when more consultations (> = 37%) can be prevented due to teledermatology.</p> <p>Conclusions</p> <p>Teledermatology, when applied to all dermatology referrals, has a probability of 0.11 of being cost saving to society.</p> <p>In order to achieve cost savings by teledermatology, teledermatology should be applied in only those cases with a reasonable probability that a live consultation can be prevented.</p> <p>Trail Registration</p> <p>This study is performed partially based on PERFECT D Trial (Current Controlled Trials No.ISRCTN57478950).</p

Cost-effectiveness of an integrated 'fast track' rehabilitation service for multi-trauma patients involving dedicated early rehabilitation intervention programs: design of a prospective, multi-centre, non-randomised clinical trial

Contains fulltext : 79649.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: In conventional multi-trauma care service (CTCS), patients are admitted to hospital via the accident & emergency room. After surgery they are transferred to the IC-unit followed by the general surgery ward. Ensuing treatment takes place in a hospital's outpatient clinic, a rehabilitation centre, a nursing home or the community. Typically, each of the CTCS partners may have its own more or less autonomous treatment perspective. Clinical evidence, however, suggests that an integrated multi-trauma rehabilitation approach ('Supported Fast-track multi-Trauma Rehabilitation Service': SFTRS), featuring: 1) earlier transfer to a specialised trauma rehabilitation unit; 2) earlier start of 'non-weight-bearing' training and multidisciplinary treatment; 3) well-documented treatment protocols; 4) early individual goal-setting; 5) co-ordination of treatment between trauma surgeon and physiatrist, and 6) shorter lengths-of-stay, may be more (cost-)effective.This paper describes the design of a prospective cohort study evaluating the (cost-) effectiveness of SFTRS relative to CTCS. METHODS/DESIGN: The study population includes multi-trauma patients, admitted to one of the participating hospitals, with an Injury Severity Scale score > = 16, complex multiple injuries in several extremities or complex pelvic and/or acetabulum fractures. In a prospective cohort study CTCS and SFTRS will be contrasted. The inclusion period is 19 months. The duration of follow-up is 12 months, with measurements taken at baseline, and at 3,6,9 and 12 months post-injury.Primary outcome measures are 'quality of life' (SF-36) and 'functional health status' (Functional Independence Measure). Secondary outcome measures are the Hospital Anxiety & Depression Scale, the Mini-Mental State Examination as an indicator of cognitive functioning, and the Canadian Occupational Performance Measure measuring the extent to which individual ADL treatment goals are met. Costs will be assessed using the PROductivity and DISease Questionnaire and a cost questionnaire. DISCUSSION: The study will yield results on the efficiency of an adapted care service for multi-trauma patients (SFTRS) featuring earlier (and condensed) involvement of specialised rehabilitation treatment. Results will show whether improved SFTRS logistics, combined with shorter stays in hospital and rehabilitation clinic and specialised early rehabilitation training modules are more (cost-) effective, relative to CTCS. TRIAL REGISTRATION: Current Controlled Trials register (ISRCTN68246661) and Netherlands Trial Register (NTR139)

Cone rod dystrophies

Cone rod dystrophies (CRDs) (prevalence 1/40,000) are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP), also called the rod cone dystrophies (RCDs) resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7). Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far). The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs), CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs), and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs). It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, and the visual prognosis is poor. Management aims at slowing down the degenerative process, treating the complications and helping patients to cope with the social and psychological impact of blindness

The effect of osteoporotic vertebral fracture on predicted spinal loads in vivo

The aetiology of osteoporotic vertebral fractures is multi-factorial, and cannot be explained solely by low bone mass. After sustaining an initial vertebral fracture, the risk of subsequent fracture increases greatly. Examination of physiologic loads imposed on vertebral bodies may help to explain a mechanism underlying this fracture cascade. This study tested the hypothesis that model-derived segmental vertebral loading is greater in individuals who have sustained an osteoporotic vertebral fracture compared to those with osteoporosis and no history of fracture. Flexion moments, and compression and shear loads were calculated from T2 to L5 in 12 participants with fractures (66.4 ± 6.4 years, 162.2 ± 5.1 cm, 69.1 ± 11.2 kg) and 19 without fractures (62.9 ± 7.9 years, 158.3 ± 4.4 cm, 59.3 ± 8.9 kg) while standing. Static analysis was used to solve gravitational loads while muscle-derived forces were calculated using a detailed trunk muscle model driven by optimization with a cost function set to minimise muscle fatigue. Least squares regression was used to derive polynomial functions to describe normalised load profiles. Regression co-efficients were compared between groups to examine differences in loading profiles. Loading at the fractured level, and at one level above and below, were also compared between groups. The fracture group had significantly greater normalised compression (p = 0.0008) and shear force (p < 0.0001) profiles and a trend for a greater flexion moment profile. At the level of fracture, a significantly greater flexion moment (p = 0.001) and shear force (p < 0.001) was observed in the fracture group. A greater flexion moment (p = 0.003) and compression force (p = 0.007) one level below the fracture, and a greater flexion moment (p = 0.002) and shear force (p = 0.002) one level above the fracture was observed in the fracture group. The differences observed in multi-level spinal loading between the groups may explain a mechanism for increased risk of subsequent vertebral fractures. Interventions aimed at restoring vertebral morphology or reduce thoracic curvature may assist in normalising spine load profiles. © 2006 Springer-Verlag

Toward a Detailed Description of the Thermally Induced Dynamics of the Core Promoter

Establishing the general and promoter-specific mechanistic features of gene transcription initiation requires improved understanding of the sequence-dependent structural/dynamic features of promoter DNA. Experimental data suggest that a spontaneous dsDNA strand separation at the transcriptional start site is likely to be a requirement for transcription initiation in several promoters. Here, we use Langevin molecular dynamic simulations based on the Peyrard-Bishop-Dauxois nonlinear model of DNA (PBD LMD) to analyze the strand separation (bubble) dynamics of 80-bp-long promoter DNA sequences. We derive three dynamic criteria, bubble probability, bubble lifetime, and average strand separation, to characterize bubble formation at the transcriptional start sites of eight mammalian gene promoters. We observe that the most stable dsDNA openings do not necessarily coincide with the most probable openings and the highest average strand displacement, underscoring the advantages of proper molecular dynamic simulations. The dynamic profiles of the tested mammalian promoters differ significantly in overall profile and bubble probability, but the transcriptional start site is often distinguished by large (longer than 10 bp) and long-lived transient openings in the double helix. In support of these results are our experimental transcription data demonstrating that an artificial bubble-containing DNA template is transcribed bidirectionally by human RNA polymerase alone in the absence of any other transcription factors

The individual environment, not the family is the most important influence on preferences for common non-alcoholic beverages in adolescence

Beverage preferences are an important driver of consumption, and strong liking for beverages high in energy (e.g. sugar-sweetened beverages [SSBs]) and dislike for beverages low in energy (e.g. non-nutritive sweetened beverages [NNSBs]) are potentially modifiable risk factors contributing to variation in intake. Twin studies have established that both genes and environment play important roles in shaping food preferences; but the aetiology of variation in non-alcoholic beverage preferences is unknown. 2865 adolescent twins (18–19-years old) from the Twins Early Development Study were used to quantify genetic and environmental influence on variation in liking for seven non-alcoholic beverages: SSBs; NNSBs; fruit cordials, orange juice, milk, coffee, and tea. Maximum Likelihood Structural Equation Modelling established that beverage preferences have a moderate to low genetic basis; from 18% (95% CI: 10%, 25%) for orange juice to 42% (36%, 43%) for fruit cordials. Aspects of the environment that are not shared by twin pairs explained all remaining variance in drink preferences. The sizeable unique environmental influence on beverage preferences highlights the potential for environmental modification. Policies and guidelines to change preferences for unhealthy beverages may therefore be best directed at the wider environment

The unfolded protein response and its relevance to connective tissue diseases

The unfolded protein response (UPR) has evolved to counter the stresses that occur in the endoplasmic reticulum (ER) as a result of misfolded proteins. This sophisticated quality control system attempts to restore homeostasis through the action of a number of different pathways that are coordinated in the first instance by the ER stress-senor proteins IRE1, ATF6 and PERK. However, prolonged ER-stress-related UPR can have detrimental effects on cell function and, in the longer term, may induce apoptosis. Connective tissue cells such as fibroblasts, osteoblasts and chondrocytes synthesise and secrete large quantities of proteins and mutations in many of these gene products give rise to heritable disorders of connective tissues. Until recently, these mutant gene products were thought to exert their effect through the assembly of a defective extracellular matrix that ultimately disrupted tissue structure and function. However, it is now becoming clear that ER stress and UPR, because of the expression of a mutant gene product, is not only a feature of, but may be a key mediator in the initiation and progression of a whole range of different connective tissue diseases. This review focuses on ER stress and the UPR that characterises an increasing number of connective tissue diseases and highlights novel therapeutic opportunities that may arise

Variation in survival after surgery for peri-ampullary cancer in a regional cancer network

Background: Centralisation of specialist surgical services requires that patients are referred to a regional centre for surgery. This process may disadvantage patients who live far from the regional centre or are referred from other hospitals by making referral less likely and by delaying treatment, thereby allowing tumour progression. The aim of this study is to explore the outcome of surgery for peri-ampullary cancer (PC) with respect to referring hospital and travel distance for treatment within a network served by five hospitals. Methods: Review of a unit database was undertaken of patients undergoing surgery for PC between January 2006 and May 2014. Results: 394 patients were studied. Although both the median travel distance for patients from the five hospitals (10.8, 86, 78.8, 54.7 and 89.2 km) (p < 0.05), and the annual operation rate for PC (2.99, 3.29, 2.13, 3.32 and 3.07 per 100,000) (p = 0.044) were significantly different, no correlation was noted between patient travel distance and population operation rate at each hospital. No difference was noted between patients from each hospital in terms of resection completion rate or pathological stage of the resected tumours. The median survival after diagnosis for patients referred from different hospitals ranged from 1.2 to 1.7 years and regression analysis revealed that increased travel distance to the regional centre was associated with a small survival advantage. Conclusion: Although variation in the provision and outcome of surgery for PC between regional hospitals is noted, this is not adversely affected by geographical isolation from the regional centre

Maternal depressive symptoms, and not anxiety symptoms, are associated with positive mother–child reporting discrepancies of internalizing problems in children: a report on the TRAILS Study

Maternal internalizing problems affect reporting of child’s problem behavior. This study addresses the relative effects of maternal depressive symptoms versus anxiety symptoms and the association with differential reporting of mother and child on child’s internalizing problems. The study sample comprised a cohort of 1,986 10- to 12-year-old children and their mothers from the Dutch general population in a cross sectional setup. Children’s internalizing problems were assessed with the DSM-IV anxiety and affective problem scales of the Child Behavior Checklist (CBCL) and the Youth Self-Report (YSR). Current maternal internalizing problems were assessed with the depressive and anxiety symptom scales of the Depression Anxiety Stress Scale (DASS), while the TRAILS Family History Interview (FHI) measured lifetime maternal depression and anxiety. Results show that current and lifetime maternal depressive symptoms were associated with positive mother–child reporting discrepancies (i.e. mothers reporting more problems than their child). Considering the small amount of variance explained, we conclude that maternal depressive symptoms do not bias maternal reporting on child’s internalizing problems to a serious degree. Studies concerning long term consequences of mother–child reporting discrepancies on child’s internalizing problems are few, but show a risk for adverse outcome. More prognostic research is needed