What Determines the Shape of an EQ-5D Index Distribution?

Background. EQ-5D-3L index scores in patient and general populations typically have a nonnormal distribution, divided into 2 distinct groups. It is important to understand to what extent this is determined by the way that the EQ-5D-3L index is constructed rather than by the true distribution of ill health. Objective. This paper examines the determinants of the ‘‘2 groups’’ distribution pattern and the extent to which this pattern is attributable either to the EQ-5D-3L classification system used to create health state profiles or to the weights applied to profiles. Methods. Data from the English NHS PROMs program (hip and knee replacements and varicose vein and hernia repairs) and from a study of 2 chronic conditions (asthma and angina) were used to compare the distributions of EQ5D-3L index scores with distributions from which weights have been stripped; profile data decomposed into their constituent dimensions and levels; a condition-specific index; and using weights from different countries, based on both time tradeoff and visual analogue scale. Results. The EQ-5D-3L classification system generates differences between patients with the same condition in respect of dimensions that are mainly observed at level 2 or 3. The weights commonly used to calculate the index exacerbate this grouping by placing a larger weight on level 3 observations, generating a noticeable gap in index scores between the groups. Conclusions. Analyzing EQ-5D profile data enables a better understanding of the resulting distribution of EQ-5D scores. The distinctive shape observed for these distributions is the result of both the classification system and the weights applied to it

Pattern Rigidity and the Hilbert-Smith Conjecture

In this paper we initiate a study of the topological group $PPQI(G,H)$ of pattern-preserving quasi-isometries for $G$ a hyperbolic Poincare duality group and $H$ an infinite quasiconvex subgroup of infinite index in $G$. Suppose $\partial G$ admits a visual metric $d$ with $dim_H < dim_t +2$, where $dim_H$ is the Hausdorff dimension and $dim_t$ is the topological dimension of $(\partial G,d)$. a) If $Q_u$ is a group of pattern-preserving uniform quasi-isometries (or more generally any locally compact group of pattern-preserving quasi-isometries) containing $G$, then $G$ is of finite index in $Q_u$. b) If instead, $H$ is a codimension one filling subgroup, and $Q$ is any group of pattern-preserving quasi-isometries containing $G$, then $G$ is of finite index in $Q$. Moreover, (Topological Pattern Rigidity) if $L$ is the limit set of $H$, \LL is the collection of translates of $L$ under $G$, and $Q$ is any pattern-preserving group of {\it homeomorphisms} of $\partial G$ preserving \LL and containing $G$, then the index of $G$ in $Q$ is finite. We find analogous results in the realm of relative hyperbolicity, regarding an equivariant collection of horoballs as a symmetric pattern in a {\it hyperbolic} (not relatively hyperbolic) space. Combining our main result with a theorem of Mosher-Sageev-Whyte, we obtain QI rigidity results. An important ingredient of the proof is a version of the Hilbert-Smith conjecture for certain metric measure spaces, which uses the full strength of Yang's theorem on actions of the p-adic integers on homology manifolds. This might be of independent interest.Comment: 32 pages, no figures: final version to appear in Geometry and Topolog

Man Bites Mosquito: Understanding the Contribution of Human Movement to Vector-Borne Disease Dynamics

In metropolitan areas people travel frequently and extensively but often in highly structured commuting patterns. We investigate the role of this type of human movement in the epidemiology of vector-borne pathogens such as dengue. Analysis is based on a metapopulation model where mobile humans connect static mosquito subpopulations. We find that, due to frequency dependent biting, infection incidence in the human and mosquito populations is almost independent of the duration of contact. If the mosquito population is not uniformly distributed between patches the transmission potential of the pathogen at the metapopulation level, as summarized by the basic reproductive number, is determined by the size of the largest subpopulation and reduced by stronger connectivity. Global extinction of the pathogen is less likely when increased human movement enhances the rescue effect but, in contrast to classical theory, it is not minimized at an intermediate level of connectivity. We conclude that hubs and reservoirs of infection can be places people visit frequently but briefly and the relative importance of human and mosquito populations in maintaining the pathogen depends on the distribution of the mosquito population and the variability in human travel patterns. These results offer an insight in to the paradoxical observation of resurgent urban vector-borne disease despite increased investment in vector control and suggest that successful public health intervention may require a dual approach. Prospective studies can be used to identify areas with large mosquito populations that are also visited by a large fraction of the human population. Retrospective studies can be used to map recent movements of infected people, pinpointing the mosquito subpopulation from which they acquired the infection and others to which they may have transmitted it

Biomechanical testing of fixed and adjustable femoral cortical suspension devices for ACL reconstruction under high loads and extended cyclic loading

Purpose: To compare loop elongation after 5000 cycles, loop-elongation at failure, and load at failure of the fixed-loop G-Lok device and three adjustable-loop devices (UltraButton, RigidLoop Adjustable and ProCinch RT), during testing over extended cycles under high loading. Methods: Five devices of each type were tested on a custom-built rig fixed to an Instron machine. The testing protocol had four stages: preloading, cyclic preconditioning, incremental cyclic loading and pull-to-failure. Outcome measures were loop elongation after 5000 cycles, loop-elongation at failure, and load at failure. Results: The loop elongation after 5000 cycles for G-Lok was 1.46 ± 0.25 mm, which was comparable to that of RigidLoop (1.51 ± 0.16 mm, p = 1.000) and ProCinch (1.60 ± 0.09 mm, p = 1.000). In comparison, the loop elongation for UltraButton was 2.66 ± 0.28 mm, which was significantly larger than all other devices (p = 0.048). The failure load for all devices ranged between 1455 and 2178 N. G-Lok was significantly stronger than all adjustable-loop devices (p = 0.048). The elongation at failure was largest for UltraButton (4.20 ± 0.33 mm), which was significantly greater than G-Lok (3.17 ± 0.33 mm, p = 0.048), RigidLoop (2.88 ± 0.20 mm, p = 0.048) and ProCinch (2.78 ± 0.08 mm, p = 0.048). There was no significant difference in elongation at failure for the rest of the devices. Conclusions: Our study has shown that the G-Lok fixed-loop device and the three adjustable-loop devices (UltraButton, RigidLoop Adjustable and ProCinch RT) all elongated less than 3 mm during testing over an extended number of cycles at high loads, nonetheless, the fixed loop device performed best in terms of least elongation and highest load at failure.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.published version, accepted versio

Antimicrobial Peptides and Skin: A Paradigm of Translational Medicine

Antimicrobial peptides (AMPs) are small, cationic, amphiphilic peptides with broad-spectrum microbicidal activity against both bacteria and fungi. In mammals, AMPs form the first line of host defense against infections and generally play an important role as effector agents of the innate immune system. The AMP era was born more than 6 decades ago when the first cationic cyclic peptide antibiotics, namely polymyxins and tyrothricin, found their way into clinical use. Due to the good clinical experience in the treatment of, for example, infections of mucus membranes as well as the subsequent understanding of mode of action, AMPs are now considered for treatment of inflammatory skin diseases and for improving healing of infected wounds. Based on the preclinical findings, including pathobiochemistry and molecular medicine, targeted therapy strategies are developed and first results indicate that AMPs influence processes of diseased skin. Importantly, in contrast to other antibiotics, AMPs do not seem to propagate the development of antibiotic-resistant micro-organisms. Therefore, AMPs should be tested in clinical trials for their efficacy and tolerability in inflammatory skin diseases and chronic wounds. Apart from possible fields of application, these peptides appear suited as an example of the paradigm of translational medicine for skin diseases which is today seen as a `two-way road' - from bench to bedside and backwards from bedside to bench. Copyright (c) 2012 S. Karger AG, Base

Health-related quality of life and a cost-utility simulation of adults in the UK with osteogenesis imperfecta, X-linked hypophosphatemia and fibrous dysplasia.

BACKGROUND: Health-related quality of life of adults with osteogenesis imperfecta (OI), fibrous dysplasia (FD) and X-linked hypophosphatemia (XLH) remains poorly described. The aim of this study was to describe the HRQoL of adults with osteogenesis imperfecta, fibrous dysplasia and X-linked hypophophataemia and perform a cost-utility simulation to calculate the maximum cost that a health care system would be willing to pay for a hypothetical treatment of a rare bone disease. RESULTS: Participants completed the EQ-5D-5 L questionnaire between September 2014 and March 2016. For the economic simulation, we considered a hypothetical treatment that would be applied to OI participants in the lower tertile of the health utility score. A total of 109 study participants fully completed the EQ-5D-5 L questionnaire (response rate 63%). Pain/discomfort was the most problematic domain for participants with all three diseases (FD 31%, XLH 25%, OI 16%). The economic simulation identified an expected treatment impact of +2.5 QALYs gained per person during the 10-year period, which led to a willing to pay of £14,355 annually for a health care system willing to pay up to £50,000 for each additional QALY gained by an intervention. CONCLUSIONS: This is the first study to quantitatively measure and compare the HRQoL of adults with OI, FD and XLH and the first to use such data to conduct an economic simulation leading to healthcare system willingness-to-pay estimates for treatment of musculoskeletal rare diseases at various cost-effectiveness thresholds

Are sedatives and hypnotics associated with increased suicide risk of suicide in the elderly?

<p>Abstract</p> <p>Background</p> <p>While antidepressant-induced suicidality is a concern in younger age groups, there is mounting evidence that these drugs may reduce suicidality in the elderly. Regarding a possible association between other types of psychoactive drugs and suicide, results are inconclusive. Sedatives and hypnotics are widely prescribed to elderly persons with symptoms of depression, anxiety, and sleep disturbance. The aim of this case-control study was to determine whether specific types of psychoactive drugs were associated with suicide risk in late life, after controlling for appropriate indications.</p> <p>Methods</p> <p>The study area included the city of Gothenburg and two adjacent counties (total 65+ population 210 703 at the start of the study). A case controlled study of elderly (65+) suicides was performed and close informants for 85 suicide cases (46 men, 39 women mean age 75 years) were interviewed by a psychiatrist. A population based comparison group (n = 153) was created and interviewed face-to-face. Primary care and psychiatric records were reviewed for both suicide cases and comparison subjects. All available information was used to determine past-month mental disorders in accordance with DSM-IV.</p> <p>Results</p> <p>Antidepressants, antipsychotics, sedatives and hypnotics were associated with increased suicide risk in the crude analysis. After adjustment for affective and anxiety disorders neither antidepressants in general nor SSRIs showed an association with suicide. Antipsychotics had no association with suicide after adjustment for psychotic disorders. Sedative treatment was associated with an almost fourteen-fold increase of suicide risk in the crude analyses and remained an independent risk factor for suicide even after adjustment for any DSM-IV disorder. Having a current prescription for a hypnotic was associated with a four-fold increase in suicide risk in the adjusted model.</p> <p>Conclusion</p> <p>Sedatives and hypnotics were both associated with increased risk for suicide after adjustment for appropriate indications. Given the extremely high prescription rates, a careful evaluation of the suicide risk should always precede prescribing a sedative or hypnotic to an elderly individual.</p

High tie versus low tie of the inferior mesenteric artery: a protocol for a systematic review

In anterior resection of rectum, the section level of inferior mesenteric artery is still subject of controversy between the advocates of high and low tie. The low tie is the division and ligation to the branching of the left colic artery and the high tie is the division and ligation at its origin at the aorta. We intend to assess current scientific evidence in literature and to establish the differences comparing technique, anatomy and physiology. The aim of this protocol is to achieve a meta-analysis that tests safety and feasibility of the two procedures with several types of outcome measures