Public Health Outcomes as a Measure of Efficacy of Syringe Exchange Programs

Introduction. A syringe exchange is a public health intervention that offers nonjudgmental services to intravenous drug users (IVDU), providing clean syringes in exchange for used syringes. While prior studies demonstrated that syringe exchanges can reduce transmission of HIV, hepatitis C, and other blood-borne pathogens, other measures of health improvements have been less studied. Methods. 91 members of Vermont CARES syringe exchange program were surveyed on their healthcare practices. New members were defined asprogram. Results. Long-term members tended to have a primary care provider (PCP). Lack of insurance and fear of judgment were commonly cited reasons for not having a PCP. Long-term members were significantly less likely (p=0.04) to use costly emergency department (ED) services and less likely to reuse their own or another person\u27s needles. Long-term members were more likely to be in addiction treatment and reported a greater desire to abstain from drug use. New members were more likely to obtain hepatitis C and HIV testing in the past year. Discussion. Subjects responded positively to the possibility of accessing PCP services through VT CARES, offering a continuation of the nonjudgmental healthcare environment. Decreased ED visits significantly correlated with longer membership, reflecting the positive impact of the syringe exchange education services on reducing healthcare costs. Decreased testing among long-term members may reflect prior knowledge of their status. Long-term members were less likely to reuse their own needles or ones used by another person, suggesting the distribution of clean syringes encourages safer injection practices.https://scholarworks.uvm.edu/comphp_gallery/1247/thumbnail.jp

Progression free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometry

Deeper responses are associated with improved survival in patients being treated for myeloma. However, the sensitivity of the current blood-based assays is limited. Historical studies suggested that normalisation of the serum free light chain (FLC) ratio in patients who were negative by immunofixation electrophoresis (IFE) was associated with improved outcomes. However, recently this has been called into question. Mass spectrometry (MS)-based FLC assessments may offer a superior methodology for the detection of monoclonal FLC due to greater sensitivity. To test this hypothesis, all available samples from patients who were IFE negative after treatment with carfilzomib and lenalidomide-based induction and autologous stem cell transplantation (ASCT) in the Myeloma XI trial underwent FLC-MS testing. FLC-MS response assessments from post-induction, day+100 post-ASCT and six months post-maintenance randomisation were compared to serum FLC assay results. Almost 40% of patients had discordant results and 28.7% of patients with a normal FLC ratio had residual monoclonal FLC detectable by FLC-MS. FLC-MS positivity was associated with reduced progression-free survival (PFS) but an abnormal FLC ratio was not. This study demonstrates that FLC-MS provides a superior methodology for the detection of residual monoclonal FLC with FLC-MS positivity identifying IFE-negative patients who are at higher risk of early progression

Programme evaluation training for health professionals in francophone Africa: process, competence acquisition and use

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Investigating the use of 3-D full-waveform inversion to characterize the host rock at a geological disposal site

The U.K. government has a policy to dispose of higher activity radioactive waste in a geological disposal facility (GDF), which will have multiple protective barriers to keep the waste isolated and to ensure no harmful quantities of radioactivity are able to reach the surface. Currently no specific GDF site in the United Kingdom has been chosen but, once it has, the site is likely to be investigated using seismic methods. In this study, we explore whether 3-D full-waveform inversion (FWI) of seismic data can be used to map changes in physical properties caused by the construction of the site, specifically tunnel-induced fracturing. We have built a synthetic model for a GDF located in granite at 1000 m depth below the surface, since granite is one of the candidate host rocks due to its high strength and low permeability and the GDF could be located at such a depth. We use an effective medium model to predict changes in P-wave velocity associated with tunnel-induced fracturing, within the spatial limits of an excavated disturbed zone (EdZ), modelled here as an increase in fracture density around the tunnel. We then generate synthetic seismic data using a number of different experimental geometries to investigate how they affect the performance of FWI in recovering subsurface P-wave velocity structure. We find that the location and velocity of the EdZ are recovered well, especially when data recorded on tunnel receivers are included in the inversion. Our findings show that 3-D FWI could be a useful tool for characterizing the subsurface and changes in fracture properties caused during construction, and make a suite of suggestions on how to proceed once a potential GDF site has been identified and the geological setting is known

Transforming data by calculation

Thispaperaddressesthefoundationsofdata-modeltransformation.A catalog of data mappings is presented which includes abstraction and representa- tion relations and associated constraints. These are justified in an algebraic style via the pointfree-transform, a technique whereby predicates are lifted to binary relation terms (of the algebra of programming) in a two-level style encompassing both data and operations. This approach to data calculation, which also includes transformation of recursive data models into “flat” database schemes, is offered as alternative to standard database design from abstract models. The calculus is also used to establish a link between the proposed transformational style and bidi- rectional lenses developed in the context of the classical view-update problem.Fundação para a Ciência e a Tecnologia (FCT

The self-management of longer-term depression: learning from the patient, a qualitative study

Background Depression is a common mental health condition now viewed as chronic or long-term. More than 50 % of people will have at least one further episode of depression after their first, and therefore it requires long-term management. However, little is known about the effectiveness of self-management in depression, in particular from the patients’ perspective. This study aimed to understand how people with longer-term depression manage the condition, how services can best support self-management and whether the principles and concepts of the recovery approach would be advantageous. Methods Semi-structured in depth interviews were carried out with 21 participants, recruited from a range of sources using maximum variation sampling. Interpretative Phenomenological Analysis was used by a diverse team comprised of service users, practitioners and academics. Results Four super-ordinate themes were found: experience of depression, the self, the wider environment, self-management strategies. Within these, several prominent sub-themes emerged of importance to the participants. These included how aspects of themselves such as hope, confidence and motivation could be powerful agents; and how engaging in a wide range of chosen activities could contribute to their emotional, mental, physical, social, spiritual and creative wellbeing. Conclusions Services in general were not perceived to be useful in specifically facilitating self-management. Increased choice and control were needed and a greater emphasis on an individualised holistic model. Improved information was needed about how to develop strategies and locate resources, especially during the first episode of depression. These concepts echoed those of the recovery approach, which could therefore be seen as valuable in aiding the self-management of depression. Keywords: Depression; Patients’ perspective; Qualitative research; Recovery; Self-help; Self-managemen

Progressive Focusing and Trustworthiness in Qualitative Research: The Enabling Role of Computer-Assisted Qualitative Data Analysis Software (CAQDAS)

* The business and management community increasingly recognises that qualitative research is a ‘messy’, non-linear and often unpredictable undertaking. Yet, a considerable proportion of the qualitative research published in top journals is still presented as the result of a linear, predictable research process, thus wrongly suggesting deductive reasoning. * In this paper, we focus on a particular type of ‘messiness’ where during fieldwork, the research context is revealed to be more complex than anticipated, forcing the researcher to gradually refine/shift their focus to reflect ‘what really matters’. We adopt Stake’s notion of progressive focusing for this gradual approach. * Progressive focusing is well-suited to qualitative research in international business requiring complex iteration between theory and data, and the truthful yet coherent presentation of the research process. We propose that this dual challenge of complexity and trustworthiness may be addressed by using computer-assisted qualitative data analysis software (CAQDAS). * We present conceptual considerations and guidelines and offer a view on a ‘messy’, non-linear doctoral research project conducted using a progressive focusing approach, to demonstrate how CAQDAS can help to develop and re-negotiate insights from theory and interview data, as well as enhance trustworthiness, transparency and publication potential

Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis

Objective: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.  Methods: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.  Results: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.  Conclusion: Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months

Finding Diagnostically Useful Patterns in Quantitative Phenotypic Data.

Trio-based whole-exome sequence (WES) data have established confident genetic diagnoses in ∼40% of previously undiagnosed individuals recruited to the Deciphering Developmental Disorders (DDD) study. Here we aim to use the breadth of phenotypic information recorded in DDD to augment diagnosis and disease variant discovery in probands. Median Euclidean distances (mEuD) were employed as a simple measure of similarity of quantitative phenotypic data within sets of ≥10 individuals with plausibly causative de novo mutations (DNM) in 28 different developmental disorder genes. 13/28 (46.4%) showed significant similarity for growth or developmental milestone metrics, 10/28 (35.7%) showed similarity in HPO term usage, and 12/28 (43%) showed no phenotypic similarity. Pairwise comparisons of individuals with high-impact inherited variants to the 32 individuals with causative DNM in ANKRD11 using only growth z-scores highlighted 5 likely causative inherited variants and two unrecognized DNM resulting in an 18% diagnostic uplift for this gene. Using an independent approach, naive Bayes classification of growth and developmental data produced reasonably discriminative models for the 24 DNM genes with sufficiently complete data. An unsupervised naive Bayes classification of 6,993 probands with WES data and sufficient phenotypic information defined 23 in silico syndromes (ISSs) and was used to test a "phenotype first" approach to the discovery of causative genotypes using WES variants strictly filtered on allele frequency, mutation consequence, and evidence of constraint in humans. This highlighted heterozygous de novo nonsynonymous variants in SPTBN2 as causative in three DDD probands