Management in non-traumatic arm, neck and shoulder complaints: differences between diagnostic groups

Arm, neck and/or shoulder complaints are common in western societies. In the Netherlands, general practice guidelines are issued on shoulder pain and epicondylitis only. Little is known about actual management of the total range of diagnoses. The objectives of the study are: to determine management in patients consulting the GP with a new episode of non-traumatic arm neck and shoulder complaints up to 6 months after the first consultation. To evaluate differences in management between patients with specific diagnoses versus non-specific diagnoses and between specific diagnostic groups. In a prospective cohort study in general practice. We recruited 682 eligible patients. Data on diagnosis, management, patient- and complaint-characteristics were collected. Co-occurrence of treatment options was presented in scaled rectangles. After 6 months, additional diagnostic tests had been performed in 18% of the patients, mainly radiographic examination (14%). Further, 49% had been referred for physiotherapy and 12% to the medical specialist. Patients with specific diagnoses were more frequently referred for specialist treatment, and patients with non-specific diagnoses for physiotherapy. Corticosteroid injections (17%) were mainly applied specific diagnoses (e.g. impingement syndrome, frozen shoulder, carpal tunnel and M. Quervain). Frequencies of prescribed medication (51%) did not differ between specific and non-specific

Summary of the DREAM8 Parameter Estimation Challenge: Toward Parameter Identification for Whole-Cell Models

Whole-cell models that explicitly represent all cellular components at the molecular level have the potential to predict phenotype from genotype. However, even for simple bacteria, whole-cell models will contain thousands of parameters, many of which are poorly characterized or unknown. New algorithms are needed to estimate these parameters and enable researchers to build increasingly comprehensive models. We organized the Dialogue for Reverse Engineering Assessments and Methods (DREAM) 8 Whole-Cell Parameter Estimation Challenge to develop new parameter estimation algorithms for whole-cell models. We asked participants to identify a subset of parameters of a whole-cell model given the model’s structure and in silico “experimental” data. Here we describe the challenge, the best performing methods, and new insights into the identifiability of whole-cell models. We also describe several valuable lessons we learned toward improving future challenges. Going forward, we believe that collaborative efforts supported by inexpensive cloud computing have the potential to solve whole-cell model parameter estimation

A Cost-Utility Analysis of Prostate Cancer Screening in Australia

Background and Objectives: The Göteborg randomised population-based prostate cancer screening trial demonstrated that Prostate Specific Antigen (PSA) based screening reduces prostate cancer deaths compared with an age matched control group. Utilising the prostate cancer detection rates from this study we have investigated the clinical and cost-effectiveness of a similar PSA-based screening strategy for an Australian population of men aged 50-69 years. Methods: A decision model that incorporated Markov processes was developed from a health system perspective.The base case scenario compared a population-based screening programme with current opportunistic screening practices. Costs, utility values, treatment patterns and background mortality rates were derived from Australian data. All costs were adjusted to reflect July 2015 Australian dollars. An alternative scenario compared systematic with opportunistic screening but with optimisation of active surveillance (AS) uptake in both groups. A discount rate of 5% for costs and benefits was utilised. Univariate and probabilistic sensitivity analyses were performed to assess the effect of variable uncertainty on model outcomes. Results: Our model very closely replicated the number of deaths from both prostate cancer and background mortality in the Göteborg study. The incremental cost per quality-adjusted life-year (QALY) for PSA screening was $AU147,528. However, for years of life gained (LYGs) PSA based screening ($AU45,890/LYG) appeared more favourable. Our alternative scenario with optimised AS improved cost-utility to $AU45,881/QALY, with screening becoming cost-effective at a 92$AU50,000/QALY. It appears more cost-effective if LYGs are used as the relevant outcome, and is more cost effective than the established Australian breast cancer screening programme on this basis. Optimised utilisation of AS increases the cost-effectiveness of prostate cancer screening dramatically

Linguistic validation, validity and reliability of the British English versions of the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and QuickDASH in people with rheumatoid arthritis

Background: Although the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire is widely used in the UK, no British English version is available. The aim of this study was to linguistically validate the DASH into British English and then test the reliability and validity of the British English DASH, (including the Work and Sport/Music DASH) and QuickDASH, in people with rheumatoid arthritis (RA). Methods: The DASH was forward translated, reviewed by an expert panel and cognitive debriefing interviews undertaken with 31 people with RA. Content validity was evaluated using the ICF Core Set for RA. Participants with RA (n=340) then completed the DASH, Health Assessment Questionnaire (HAQ), Short Form Health Survey v2 (SF36v2) and Measure of Activity Performance of the Hand (MAPHAND). We examined internal consistency and concurrent validity for the DASH, Work and Sport/Music DASH modules and QuickDASH. Participants repeated the DASH to assess test-retest reliability. Results: Minor wording changes were made as required. The DASH addresses a quarter of Body Function and half of Activities and Participation codes in the ICF RA Core Set. Internal consistency for DASH scales were consistent with individual use (Cronbach’s alpha = 0.94-0.98). Concurrent validity was strong with the HAQ (rs = 0.69-0.91), SF36v2 Physical Function (rs = -0.71 - -0.85), Bodily Pain (rs = -0.71 - -0.74) scales and MAPHAND (rs =0.71-0.93). Test-retest reliability was good (rs = 0.74-0.95). Conclusions: British English versions of the DASH, QuickDASH and Work and Sport/Music modules are now available to evaluate upper limb disabilities in the UK. The DASH, QuickDASH, Work and Sport/Music modules are reliable and valid to use in clinical practice and research with British people with RA

Non invasive prenatal testing for single gene disorders:Exploring the ethics

Non-invasive prenatal testing for single gene disorders is now clearly on the horizon. This new technology offers obvious clinical benefits such as safe testing early in pregnancy. Before widespread implementation, it is important to consider the possible ethical implications. Four hypothetical scenarios are presented that highlight how ethical ideals of respect for autonomy, privacy and fairness may come into play when offering non-invasive prenatal testing for single gene disorders. The first scenario illustrates the moral case for using these tests for ‘information only', identifying a potential conflict between larger numbers of women seeking the benefits of the test and the wider social impact of funding tests that do not offer immediate clinical benefit. The second scenario shows how the simplicity and safety of non-invasive prenatal testing could lead to more autonomous decision-making and, conversely, how this could also lead to increased pressure on women to take up testing. In the third scenario we show how, unless strong safeguards are put in place, offering non-invasive prenatal testing could be subject to routinisation with informed consent undermined and that woman who are newly diagnosed as carriers may be particularly vulnerable. The final scenario introduces the possibility of a conflict of the moral rights of a woman and her partner through testing for single gene disorders. This analysis informs our understanding of the potential impacts of non-invasive prenatal testing for single gene disorders on clinical practice and has implications for future policy and guidelines for prenatal care

Scaled momentum distributions for K-S(0) and Λ /̄ Λ in DIS at HERA

Scaled momentum distributions for the strange hadrons K0S and Λ/Λ¯ were measured in deep inelastic ep scattering with the ZEUS detector at HERA using an integrated luminosity of 330 pb−1. The evolution of these distributions with the photon virtuality, Q 2, was studied in the kinematic region 10 < Q 2  < 40000 GeV2 and 0.001 < x < 0.75, where x is the Bjorken scaling variable. Clear scaling violations are observed. Predictions based on different approaches to fragmentation were compared to the measurements. Leading-logarithm parton-shower Monte Carlo calculations interfaced to the Lund string fragmentation model describe the data reasonably well in the whole range measured. Next-to-leading-order QCD calculations based on fragmentation functions, FFs, extracted from e + e − data alone, fail to describe the measurements. The calculations based on FFs extracted from a global analysis including e + e −, ep and pp data give an improved description. The measurements presented in this paper have the potential to further constrain the FFs of quarks, anti-quarks and gluons yielding K0S and Λ/Λ¯ strange hadrons

Rotational strength, range of motion, and function in people with unaffected shoulders from various stages of life

Background: Different measurements are used to assess shoulder function, including range of motion, strength, functional performance and self-report function. To understand disablement, it is necessary to understand the relationship between impairments and function in persons without shoulder problems. This study was conducted to enhance existing comparative data in subjects without upper extremity pathology, and to assess the relationships between impairments (range of motion, strength) and selfreported or measured function/disability. The impact of age, gender and dominance was determined. Methods: Two-hundred ninety-four subjects with unaffected shoulders were recruited. The subjects (mean age: 37 years old) were divided into three subgroups, 18–39, 40–59, and over 60 years of age. During a single session, at least two of the following variables were measured: self-reported function (shoulder disability scales), range of motion, isometric rotational strength, or upper limb functional performance (FIT-HaNSA). Two-way analysis of variance was used to determine, for each variable, the effects of age and gender. The relationship between the outcomes was established using Pearson product correlations. Results: Men were significantly stronger than women for all age categories. There was an age-related decline in strength in men in the over-60 age category. Significant negative correlations between strength and range of motion were demonstrated (-0.22 \u3c -0.32). Women had a significantly higher range of motion than men for external rotation in the 40–59 age category. Furthermore, the subjects in the over- 60 age category experienced a decrease of range of motion. There was minimal disability reported in all age groups on self-report scales. Only the Simple Shoulder Test demonstrated significant decreases in the over-60 age category and correlated with age (r = -0.202). Conclusion: Self-reported disability was low in individuals without upper extremity problems, although recruitment of such individuals was difficult in the older age groups due to the high prevalence of shoulder pathology. A low correlation between self-report disability and strength/range of motion in these unaffected subjects reflects the lack of disability reported by all subjects without pathology despite normal variations in strength and motion

Cross-sectional and longitudinal construct validity of two rotator cuff disease-specific outcome measures

BACKGROUND: Disease-specific Quality Of Life (QOL) measures are devised to assess the impact of a specific disease across a spectrum of important domains of life. The purpose of this study was to examine the cross-sectional and longitudinal construct validity (sensitivity to change) of two rotator cuff disease-specific measures, the Rotator Cuff-Quality Of Life (RC-QOL) and the Western Ontario Rotator Cuff (WORC) index, in relation to one another and to other joint and limb specific measures in the same population of the patients suffering from rotator cuff pathology. METHODS: Participants enrolled were consecutive patients who received physical therapy for management of impingement syndrome or received treatment following rotator cuff repair, acromioplasty or decompression surgeries. All subjects received physical therapy treatment and completed four outcome measures at 3 single points (initial, interim, and final). Cross-sectional convergent validity was assessed at each of the 3 time-points by correlating the WORC and RC-QOL's scores to each other and to two alternative scales; a joint-specific scale, the American Shoulder and Elbow Surgeons (ASES) standardized shoulder assessment form and a limb-specific measure, the Upper Extremity Functional Index (UEFI). Non-parametric statistics (Spearman's rho and Wilcoxon-Mann-Whitney tests) examined the construct validity. The standardized response mean (SRM) was used to examine sensitivity to change. RESULTS: Forty-one participants entered the study and their scores were compared at 3 cross sectional single points. The correlation coefficients among the 4 measures varied from 0.60 to 0.91. Correlation between corresponding domains of the WORC and RC-QOL varied from 0.45 to 0.85. The known group validity was not significantly different among individual sub-scores and total scores. The final SRMs were (1.42), (1.43), (1.44), and (1.54) for the ASES, RCQOL, WORC, and UEFI respectively. CONCLUSION: The WORC and RC-QOL exhibit similar cross-sectional convergent validity in patients suffering from rotator cuff pathology. The sensitivity to change was very close among all scores, with the UEFI having the highest sensitivity. Further research is needed to examine the extent to which each physical or emotional domain contributes to prognostic or therapeutic decision-making

Whole inactivated virus influenza vaccine is superior to subunit vaccine in inducing immune responses and secretion of proinflammatory cytokines by DCs

Background For protection against (re-) infection by influenza virus not only the magnitude of the immune response but also its quality in terms of antibody subclass and T helper profile is important. Information about the type of immune response elicited by vaccination is therefore urgently needed. Objectives The aim of the study was to evaluate in detail the immune response elicited by three current influenza vaccine formulations and to shed light on vaccine characteristics which determine this response. Methods Mice were immunized with whole inactivated virus (WIV), virosomes (VS) or subunit vaccine (SU). Following subsequent infection with live virus, serum antibody titers and Th cell responses were measured. The effects of the vaccines on cytokine production by conventional and plasmacytoid dendritic cells were investigated in vitro. Results and conclusions In Balb/c mice (Th2 prone) as well as in C57Bl/6 mice (Th1 prone), WIV induced consistently higher hemagglutination-inhibition titers and virus-neutralizing antibody titers than VS or SU. In contrast to VS and SU, WIV stimulated the production of the antibody subclasses IgG2a (Balb/c) and IgG2c (C57BL/6), considered to be particularly important for viral clearance, and activation of IFN-gamma-producing T cells. Similar to live virus, WIV stimulated the production of proinflammatory cytokines by conventional dendritic cells and IFN-alpha by plasmacytoid cells, while VS and SU had little effect on cytokine synthesis by either cell type. We conclude that vaccination with WIV in contrast to VS or SU results in the desired Th1 response presumably by induction of type I interferon and other proinflammatory cytokines