The Pain Divide: a cross-sectional analysis of chronic pain prevalence, pain intensity and opioid utilisation in England

Objectives: Our central research question was, in England, are geographical inequalities in opioid use driven by health need (pain)? To answer this question, our study examined: (1) if there are regional inequalities in rates of chronic pain prevalence, pain intensity and opioid utilisation in England; (2) if opioid use and chronic pain are associated after adjusting for individual-level and area-level confounders. Design: Cross-sectional study design using data from the Health Survey for England 2011. Setting England. Primary and secondary outcome measures: Chronic pain prevalence, pain intensity and opioid utilisation. Participants: Participant data relating to chronic pain prevalence, pain intensity and opioid usage data were obtained at local authority level from the Health Survey for England 2011; in total, 5711 respondents were included in our analysis. Methods: Regional and local authority data were mapped, and a generalised linear model was then used to explore the relationships between the data. The model was adjusted to account for area-level and individual-level variables. Results: There were geographical variations in chronic pain prevalence, pain intensity and opioid utilisation across the English regions—with evidence of a ‘pain divide’ between the North and the South, whereby people in the North of England more likely to have ‘severely limiting’ or ‘moderately limiting’ chronic pain. The intensity of chronic pain was significantly and positively associated with the use of opioid analgesics. Conclusions: There are geographical differences in chronic pain prevalence, pain intensity and opioid utilisation across England—with evidence of a ‘pain divide’. Given the public health concerns associated with the long-term use of opioid analgesics—and their questionable activity in the management of chronic pain—more guidance is needed to support prescribers in the management of chronic pain, so the initiation of opioids can be avoided

Landmark detection in 2D bioimages for geometric morphometrics: a multi-resolution tree-based approach

The detection of anatomical landmarks in bioimages is a necessary but tedious step for geometric morphometrics studies in many research domains. We propose variants of a multi-resolution tree-based approach to speed-up the detection of landmarks in bioimages. We extensively evaluate our method variants on three different datasets (cephalometric, zebrafish, and drosophila images). We identify the key method parameters (notably the multi-resolution) and report results with respect to human ground truths and existing methods. Our method achieves recognition performances competitive with current existing approaches while being generic and fast. The algorithms are integrated in the open-source Cytomine software and we provide parameter configuration guidelines so that they can be easily exploited by end-users. Finally, datasets are readily available through a Cytomine server to foster future research

Role of Histamine H4 Receptor ligands in Bleomycin-induced pulmonary fibrosis

Fibrosis of lung tissue is a disease where a chronic inflammatory process determines a pathological remodelling of lung parenchyma. The animal model obtained by intra-tracheal administration of bleomycin in C57BL/6 mice is one of the most validated murine model. Bleomycin stimulates oxidative stress and the production of pro-inflammatory mediators. Histamine H4R have recently been implicated in inflammation and immune diseases. This study was focused to investigate the effects of H4R ligands in the modulation of inflammation and in the reduction of lung fibrosis in C57BL/6 mice treated with bleomycin. C57BL/6 mice were treated with vehicle, JNJ7777120 (JNJ, selective H4R antagonist) or ST-1006 (partial H4R agonist), ST-994 (H4R neutral antagonist) and ST-1012 (inverse H4R agonist) at equimolar doses, released by micro-osmotic pumps for 21 days. Airway resistance to inflation was assayed and lung samples were processed to measure malondialdehyde (TBARS); 8-hydroxy-2'-deoxyguanosine (8OHdG); myeloperoxidase (MPO); COX-2 expression and activity as markers of oxidative stress and inflammation. Fibrosis and airway remodelling were evaluated throughout transforming growth factor-β (TGF-β), percentage of positive Goblet cells, smooth muscle layer thickness determination. Our results indicated that JNJ, ST-994 and ST-1012 decreased inflammation and oxidative stress markers, i.e. the number of infiltrating leukocytes evaluated as lung tissue MPO, COX-2 expression and activity, TBARS and 8OHdG production. They also reduced the level of TGF-β, a pro-fibrotic cytokine, collagen deposition, thickness of smooth muscle layer, Goblet cells hyperplasia; resulting in a decrease of airway functional impairment. The results here reported clearly demonstrated that H4R ligands have a beneficial effect in a model of lung fibrosis in the mouse, thus indicating that H4R antagonists or inverse agonists could be a novel therapeutic strategy for lung inflammatory diseases

Confidence of practitioners to support self-management of pain: A multidisciplinary survey

Supplementary Material is available online at: https://journals.sagepub.com/doi/full/10.1177/20494637231212748#supplementary-materials .Copyright © The Author(s) 2023. Background Supported self-management is an important component of management for persistent pain according to current recommendations and guidelines. However, it is unclear whether staff from differing disciplines who may be in early contact with people with established or developing persistent pain are confident to introduce and support self-management for this patient group. Aim To determine the confidence of staff across professional disciplines to introduce and support self-management. Design and Setting Cross-sectional online survey. Methods Charts were constructed to represent information on professional grouping, prior training in self-management and confidence in supporting key components of self-management for persistent pain. Analysis of variance was used to test for differences between groups. Results Overall, 165 practitioners reported confidence to support self-management below the midpoint of a ten-point scale and 93 above. There were few differences between different professions apart from in explaining pain (f = 6.879 p < .001), managing activity levels (f = 6.340 p < .001) and supporting healthy habits (f = 4.700, p = .001) in which physiotherapists expressed higher confidence than other professional groups. There was no difference in confidence expressed between staff who had or had not received previous training in self-management (f = 1.357, p = .233). Conclusions Many front-line staff who might be expected to introduce and deliver self-management support for persistent pain lack the confidence and skills to do so. This is consistent with a known lack of education about pain across disciplinary boundaries in primary and community-based care. In order to meet treatment priorities for persistent pain there is an urgent need to upskill the workforce by providing access to good quality training and resources.Health Education England Long term Conditions and Innovation Fund

What impacts of climate change on surface water in France by 2070? Results of the Explore2070 project in metropolitan France and overseas departments

International audienceLes questions relatives à la disponibilité et à la gestion de l'eau concentreront l'essentiel des mesures d'adaptation qui seront prises dans les décennies à venir pour faire face aux conséquences des changements climatiques. Ces mesures devront également prendre en compte les évolutions socio-économiques, en termes de démographie, d'aménagement du territoire et de politiques publiques (agriculture, énergie, transports, etc.). Il est dès lors primordial pour les décideurs et gestionnaires de quantifier les évolutions socio-économiques possibles, ainsi que le devenir de la ressource en eau et de sa variabilité temporelle et spatiale. C'est dans ce contexte que le projet Explore2070 avait pour objectif d'évaluer les impacts possibles des changements climatiques et socio-économiques futurs sur les grandes masses d'eau (surface, souterrain, littoral) et la biodiversité, en France métropolitaine et sur les départements d'Outre-mer (Guadeloupe, Guyane, Martinique et Réunion). Piloté par le Ministère de l'Ecologie (MEDDTL), ce projet a rassemblé de nombreux bureaux d'études et instituts de recherche pour dresser un panorama général des évolutions à attendre à l'horizon 2070. Par son ampleur et la variété de ses objectifs, ce projet doit permettre de répondre à de nombreuses questions des gestionnaires et de mieux apprécier les enjeux de ces évolutions. Dans la suite, nous présentons les travaux réalisés spécifiquement sur la quantification des évolutions des eaux de surface. Nous détaillerons dans ce qui suit la démarche générale de modélisation proposée, la nature des résultats obtenus, ainsi que la façon dont les incertitudes ont été quantifiées. Ce dernier point est indispensable pour aider à la prise de décision dans un avenir incertain. / Water availability and water management will be the focus of most of the adaptation measures that will be taken in the next decades to face the consequences of climate change. These measures will have to account for the socio-economic evolutions, in terms of population size, town and country planning, as well as public policies (agriculture, energy, transports, etc.). It is therefore essential for decision makers and managers to be able to quantify the possible socio-economic evolutions together with the evolution of water resources and their temporal and spatial variability. In this context, the Explore2070 project aimed at evaluating the possible impacts of future climate and socio-economic changes on water bodies (surface water, groundwater and coastal water) and biodiversity, in metropolitan France and overseas departments (Guadeloupe, Martinique, French Guyana, and Réunion Island). The project was managed by the French Ministry of Ecology (MEDDTL) and gathered several consultancies and research institutes to establish a general overview of the expected evolutions by 2070. Through both the extent and the variety of the project’s objectives, Explore2070 will provide answers to many questions raised by managers and better evaluate the stakes related to these evolutions. In the following, we present the work done specifically to quantify the evolution of surface water. The general modelling approach, the type of results and the way uncertainties were quantified are detailed. Uncertainty quantification is essential to help decision making in an uncertain future

Is basal ultrasensitive measurement of calcitonin capable of substituting for the pentagastrin-stimulation test?

OBJECTIVE: To evaluate a second-generation assay for basal serum calcitonin (CT) measurements compared with the pentagastrin-stimulation test for the diagnosis of inherited medullary thyroid carcinoma (MTC) and the follow-up of patients with MTC after surgery. Recent American Thyroid Association recommendations suggest the use of basal CT alone to diagnose and assess follow-up of MTC as the pentagastrin (Pg) test is unavailable in many countries. DESIGN: Multicentric prospective study. PATIENTS: A total of 162 patients with basal CT &lt;10 ng/l were included: 54 asymptomatic patients harboured noncysteine \u27rearranged during transfection\u27 (RET) proto-oncogene mutations and 108 patients had entered follow-up of MTC after surgery. MEASUREMENT: All patients underwent basal and Pg-stimulated CT measurements using a second-generation assay with 5-ng/l functional sensitivity. RESULTS: Ninety-five per cent of patients with basal CT ≥ 5 ng/l and 25% of patients with basal CT &lt;5 ng/l had a positive Pg-stimulation test (Pg CT &gt;10 ng/l). Compared with the reference Pg test, basal CT ≥ 5 ng/l had 99% specificity, a 95%-positive predictive value but only 35% sensitivity (P &lt; 0.0001). Overall, there were 31% less false-negative results using a 5-ng/l threshold for basal CT instead of the previously used 10-ng/l threshold. CONCLUSION: The ultrasensitive CT assay reduces the false-negative rate of basal CT measurements when diagnosing familial MTC and in postoperative follow-up compared with previously used assays. However, its sensitivity to detect C-cell disease remains lower than that of the Pg-stimulation test

Time Until Partial Response in Metastatic Adrenocortical Carcinoma Long-Term Survivors

A partial response (PR) has been proposed as a surrogate for overall survival in advanced adrenocortical carcinoma (ACC). The primary endpoint of the study was to characterize the time until a PR in patients with metastatic ACC treated with a standard therapy is achieved. Long-term survivors were selected to allow evaluation of delayed tumor response to mitotane. Records from patients with metastatic ACC that survived for &gt; 24 months were retrieved. Tumor response was analyzed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Time until a tumor response, after treatment initiation or therapeutic plasma mitotane level, was analyzed. Sixty-eight patients were analyzed. The first-line systemic therapy was mitotane as a monotherapy (M) (n = 57) or cytotoxic polychemotherapy plus/minus mitotane (PC ± M) (n = 11). The second-line therapy was M (n = 2) or PC ± M (n = 41). Thirty-two PRs occurred in 30/68 patients (44.1%): this was obtained for 13 (40.6%) during M and during PC ± M for 19/32 responders (59.4%). PRs were observed within 6 months of starting M or PC ± M in 76.9 and 94.7% of responses, respectively, within 6 months of therapeutic plasma mitotane being first observed in 88.9% of responses with M and in 53.3% of responses with PC ± M. All PRs (but one) occurred within 1 year after initiating treatment. To conclude, Most patients with metastatic ACC and long survival times had PRs within the first 6 months of standard systemic therapy, and almost all within the first year. The absence of response after that period could be considered as a treatment failure. Maintenance of mitotane therapy in non-responders after 1 year should be questioned in future randomized trials

Satellite glia of the adult dorsal root ganglia harbor stem cells that yield glia under physiological conditions and neurons in response to injury

The presence of putative stem/progenitor cells has been suggested in adult peripheral nervous system (PNS) tissue, including the dorsal root ganglion (DRG). To date, their identification and fate in pathophysiological conditions have not been addressed. Combining multiple in vitro and in vivo approaches, we identified the presence of stem cells in the adult DRG satellite glial population, and progenitors were present in the DRGs and sciatic nerve. Cell-specific transgenic mouse lines highlighted the proliferative potential of DRG stem cells and progenitors in vitro. DRG stem cells had gliogenic and neurogenic potentials, whereas progenitors were essentially gliogenic. Lineage tracing showed that, under physiological conditions, adult DRG stem cells maintained DRG homeostasis by supplying satellite glia. Under pathological conditions, adult DRG stem cells replaced DRG neurons lost to injury in addition of renewing the satellite glial pool. These novel findings open new avenues for development of therapeutic strategies targeting DRG stem cells for PNS disorders

Conclusions and recommendations of a who expert consultation meeting on iron supplementation for infants and young children in malaria endemic areas [Conclusions et recommandations à l\u27issue de la consultation de l\u27oms sur la lutte contre la carence martiale chez le nourrisson et le jeune enfant dans les pays d\u27endémie palustre]

This article presents the results of an expert consultation meeting aimed at evaluating the safety and public health implications of administering supplemental iron to infants and young children in malaria-endemic areas. Participants at this meeting that took place in Lyon, France on June 12-14, 2006 reached consensus on several important issues related to iron supplementation for infants and young children in malaria-endemic areas. The conclusions in this report apply specifically to regions where malaria is endemic

p.Ala541Thr variant of MEN1 gene: A non deleterious polymorphism or a pathogenic mutation?

Context Multiple Endocrine Neoplasia Type 1 (MEN1) is an autosomal dominant inherited syndrome, related to mutations in the MEN1 gene. Controversial data suggest that the nonsynonymous p.Ala541Thr variant, usually considered as a non-pathogenic polymorphism, may be associated with an increased risk of MEN1-related lesions in carriers. Objective The aim of this study was to evaluate the pathogenic influence of the p.Ala541Thr variant on clinical and functional outcomes. Patients and methods We analysed a series of 55 index patients carrying the p.Ala541Thr variant. Their clinical profile was compared to that of 117 MEN1 patients. The biological impact of the p.Ala541Thr variant on cell growth was additionally investigated on menin-deficient Leydig cell tumour (LCT)10 cells generated from Men1+/Men1− heterozygous knock-out mice, and compared with wild type (WT). Results The mean age at first appearance of endocrine lesions was similar in both p.Ala541Thr carriers and MEN1 patients, but no p.Ala541Thr patient had more than one cardinal MEN1 lesion at initial diagnosis. A second MEN1 lesion was diagnosed in 13% of MEN1 patients and in 7% of p.Ala541Thr carriers in the year following preliminary diagnosis. Functional studies on LCT10 cells showed that overexpression of the p.Ala541Thr variant did not inhibit cell growth, which is in direct contrast to results obtained from investigation of WT menin protein. Conclusion Taken together, these data raise the question of a potential pathogenicity of the p.Ala541Thr missense variant of menin that commonly occurs within the general population. Additional studies are required to investigate whether it may be involved in a low-penetrance MEN1 phenotype