For more than six decades, the use of the operating microscope for extremity surgery has led to remarkable advances in the management of orthopedic trauma, tumors, infections, and congenital ...differences. The microsurgical reconstructive ladder ascends from basic microsurgical procedures such as a digital artery or nerve repair to more complex procedures such as autologous tissue transplantation. Functional muscle transfers, toe‐to‐hand transfers, and recently vascularized composite allotransplantation are the highest rungs on this ladder that help restore extremity function. The development of the orthoplastic approach over the last three decades simultaneously integrates the principles and practices of both orthopedic surgery and plastic surgery for optimal care and salvage of extremities. Clinical, anatomic, and basic science research in reconstructive microsurgery has resulted in significant improvements in extremity salvage, reconstruction, and restoration.
Aims/hypothesis The aim of the present study was to estimate the prevalence and healthcare costs of diabetic retinopathy (DR). Methods This population-based study included all residents (n = 251,386) ...in the catchment area of the eye clinic of Linköping University Hospital, Sweden. Among patients with diabetes (n = 12,026), those with and without DR were identified through register data from both the Care Data Warehouse in Östergötland, an administrative healthcare register, and the Swedish National Diabetes Register. Healthcare cost data were elicited by record linkage of these two registers to data for the year 2008 in the Cost Per Patient Database developed by Östergötland County Council. Results The prevalence of any DR was 41.8% (95% CI 38.9-44.6) for patients with type 1 diabetes and 27.9% (27.1-28.7) for patients with type 2 diabetes. Sight-threatening DR was present in 12.1% (10.2-14.0) and 5.0% (4.6-5.4) of the type 1 and type 2 diabetes populations respectively. The annual average healthcare cost of any DR was €72 (€53-91). Stratified into background retinopathy, proliferative DR, maculopathy, and the last two conditions combined, the costs were €26 (€10-42), €257 (€155-359), €216 (€113-318) and €433 (€232-635) respectively. The annual cost for DR was €106 000 per 100,000 inhabitants. Conclusions This study presents new information on the prevalence and costs of DR. Approximately one-third of patients with diabetes have some form of DR. Average healthcare costs increase considerably with the severity of DR, which suggests that preventing progression of DR may lower healthcare costs.
Background
Colorectal cancer screening can decrease morbidity and mortality. However, there are widespread differences in the implementation of programmes and choice of strategy. The primary ...objective of this study was to estimate lifelong costs and health outcomes of two of the currently most preferred methods of screening for colorectal cancer: colonoscopy and sensitive faecal immunochemical test (FIT).
Methods
A cost‐effectiveness analysis of colorectal cancer screening in a Swedish population was performed using a decision analysis model, based on the design of the Screening of Swedish Colons (SCREESCO) study, and data from the published literature and registries. Lifelong cost and effects of colonoscopy once, colonoscopy every 10 years, FIT twice, FIT biennially and no screening were estimated using simulations.
Results
For 1000 individuals invited to screening, it was estimated that screening once with colonoscopy yielded 49 more quality‐adjusted life‐years (QALYs) and a cost saving of €64 800 compared with no screening. Similarly, screening twice with FIT gave 26 more QALYs and a cost saving of €17 600. When the colonoscopic screening was repeated every tenth year, 7 additional QALYs were gained at a cost of €189 400 compared with a single colonoscopy. The additional gain with biennial FIT screening was 25 QALYs at a cost of €154 300 compared with two FITs.
Conclusion
All screening strategies were cost‐effective compared with no screening. Repeated and single screening strategies with colonoscopy were more cost‐effective than FIT when lifelong effects and costs were considered. However, other factors such as patient acceptability of the test and availability of human resources also have to be taken into account.
Colonoscopy more cost effective
Transposable elements (TEs) are major components of eukaryotic genomes. However, the extent of their impact on genome evolution, function, and disease remain a matter of intense interrogation. The ...rise of genomics and large-scale functional assays has shed new light on the multi-faceted activities of TEs and implies that they should no longer be marginalized. Here, we introduce the fundamental properties of TEs and their complex interactions with their cellular environment, which are crucial to understanding their impact and manifold consequences for organismal biology. While we draw examples primarily from mammalian systems, the core concepts outlined here are relevant to a broad range of organisms.
Background
Patients with moderate‐to‐severe psoriasis require long‐term treatment, yet few trials compare outcomes beyond a short‐term induction period. Quantitative comparisons of long‐term outcomes ...in patients with psoriasis are limited. To our knowledge, no network meta‐analysis (NMA) of such data has been performed.
Objective
To compare novel systemic therapies, both biologic and non‐biologic, approved for moderate‐to‐severe psoriasis by conducting a systematic review (SR) and NMA of Psoriasis Area and Severity Index (PASI) outcomes measured at or around 1 year.
Methods
An SR was conducted to identify studies reporting PASI 75, PASI 90 and PASI 100 responses. Feasibility of an NMA on maintenance phase endpoints was assessed and sources of heterogeneity considered. Data appropriate for analysis were modelled using a Bayesian multinomial likelihood model with probit link. Wherever possible, data corresponding to an intention‐to‐treat approach with non‐responder imputation were used.
Results
Twenty‐four studies reporting outcomes at 40–64 weeks were identified, but heterogeneity in study design allowed synthesis of only 17. Four 52‐week randomized controlled trials (RCTs) comprised the primary analysis, which found brodalumab was significantly more efficacious than secukinumab, ustekinumab and etanercept. Secukinumab was also more efficacious than ustekinumab and both outperformed etanercept. In a secondary analysis, evidence from 13 additional studies and 4 further therapies (adalimumab, apremilast, infliximab and ixekizumab) was included by comparing long‐term outcomes from active interventions to placebo outcomes extrapolated from induction. Results were consistent with the primary analysis: brodalumab was most effective, followed by ixekizumab and secukinumab, then ustekinumab, infliximab and adalimumab. Etanercept and apremilast had the lowest expected long‐term efficacy. Results were similar when studies with low prior exposure to biological therapies were excluded.
Conclusion
Results suggest that brodalumab is associated with a higher likelihood of sustained PASI response, including complete clearance, at week 52 than comparators. Further long‐term active‐comparator RCT data are required to better assess relative efficacy across therapies.
Background: Elevated Epstein–Barr virus (EBV) antibody titers are risk factors for multiple sclerosis (MS), but the strength and consistency of this association are not well characterized.
...Objectives: The objectives of this study were to determine whether this association is confounded by vitamin D or modified by gender or race, and the usefulness of EBV nuclear antigen (EBNA) antibodies as a marker for MS.
Methods: We conducted a prospective study among US military personnel. Antibody titers against EBV antigens were measured in serum samples from 222 individuals who developed MS and 444 age, sex, and race/ethnicity matched controls. Conditional logistic regression was used to estimate relative risks.
Results: MS risk increased with increasing titers of anti-EBNA complex (p < 10−9) and anti-EBNA-1 (p = 5.8 × 10−9) titers. MS risk was 36-fold higher among individuals with anti-EBNA complex IgG titers ≥320 than among those with titers <20 (95% confidence interval CI 9.6–136), and 8-fold higher among those with anti-EBNA-1 ≥320 than among those with anti-EBNA-1 <20 (95% CI 2.6–23). These associations were consistent across gender and race/ethnicity groups and independent from 25-hydroxyvitamin D levels. Areas under the receiver operating characteristic (ROC) curves were 0.67 for EBNA complex and 0.65 for EBNA-1.
Conclusions: Serum titers of pre-onset anti-EBNA antibodies are strong, robust markers of MS risk and could be useful in an MS risk score.
The detection of five new fast radio bursts (FRBs) found in the 1.4-GHz High Time Resolution Universe high-latitude survey at Parkes, is presented. The rate implied is 7
$^{+5}_{-3}\times 10^3$
...(95 per cent) FRBs sky−1 d−1 above a fluence of 0.13 Jy ms for an FRB of 0.128 ms duration to 1.5 Jy ms for 16 ms duration. One of these FRBs has a two-component profile, in which each component is similar to the known population of single component FRBs and the two components are separated by 2.4 ± 0.4 ms. All the FRB components appear to be unresolved following deconvolution with a scattering tail and accounting for intrachannel smearing. The two-component burst, FRB 121002, also has the highest dispersion measure (1629 pc cm−3) of any FRB to-date. Many of the proposed models to explain FRBs use a single high-energy event involving compact objects (such as neutron-star mergers) and therefore cannot easily explain a two-component FRB. Models that are based on extreme versions of flaring, pulsing, or orbital events, however, could produce multiple component profiles. The compatibility of these models and the FRB rate implied by these detections is discussed.
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