The patient’s perspectives of safe and routine proactive deprescribing in primary care for older people living with polypharmacy: a qualitative study

BackgroundThe process of identifying and discontinuing medicines in instances in which harms outweigh benefits (deprescribing) can mitigate the negative consequences of problematic polypharmacy. This process should be conducted with a focus on the patient and involve collaborative decision-making. Evidence is needed regarding patients’ views on how deprescribing should be safely and routinely implemented in English primary care to improve its application. This study aimed to identify optimal methods of introducing and actioning deprescribing from the patient’s perspective.MethodsParticipants in England aged 65 and above who were taking five or more medicines and residing in their own homes were recruited through social media and service user groups. An interview guide was created from deprescribing literature and input from patients and the public, guided by the Normalisation Process Theory (NPT). The interviews were held online using Microsoft Teams\uae or via phone, recorded, and then transcribed. The data was analysed using the Framework analysis.ResultsTwenty patients (mean age of 74.5, SD = 6.93), with 75% being female, were enrolled in the study. Three main themes emerged: (1) ‘Why deprescribe now?’ emphasised the significance of explaining the reasons behind deprescribing; (2) ‘Monitoring and follow-up’ underscored the necessity of safety measures during deprescribing and patients’ willingness to self-monitor post-intervention; (3) ‘Roles and relationships’ explored patient perceptions of various healthcare professionals involved in deprescribing and the essential interpersonal skills for fostering therapeutic relationships.ConclusionOptimal methods of introducing deprescribing included communicating a convincing rationale for stopping medicines and preparing patients for deprescribing conversations. Patients required support from a range of healthcare professionals with whom they had an existing therapeutic relationship. Whilst patients were motivated to self-monitor unwanted/unexpected effects post-deprescribing, timely support was required. The nature of such bolstered collective action and cognitive participation within NPT enhances the normalisation potential of deprescribing. These findings highlight the significance of considering the content and process of deprescribing consultations to enhance normalisation and tackle problematic polypharmacy. This provides a deeper understanding of patients’ needs for implementing safe and routine deprescribing in primary care, which should be considered when designing medication review and deprescribing services

A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors

Cancer models; Paediatric cancerModelos de cáncer; Cáncer pediátricoModels de càncer; Càncer pediàtricPediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962). To date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient’s tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Pediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation. This PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and treatments development in advanced pediatric malignancies.This work was supported by grants from Fondation Gustave Roussy; Fédération Enfants Cancers et Santé, Société Française de lutte contre les Cancers et les leucémies de l’Enfant et l’adolescent (SFCE), Association AREMIG and Thibault BRIET; Parrainage médecin-chercheur of Gustave Roussy; INSERM; Canceropôle Ile-de-France; Ligue Nationale Contre le Cancer (Equipe labellisée); Fondation ARC for the European projects ERA-NET on Translational Cancer Research (TRANSCAN 2) Joint Transnational Call 2014 (JTC 2014) ‘Targeting Of Resistance in PEDiatric Oncology (TORPEDO)’, ERA-NET TRANSCAN JTC 2014 (TRAN201501238), and TRANSCAN JTC 2017 (TRANS201801292); Agence Nationale de la Recherche (ANR-10-EQPX-03, Institut Curie Génomique d’Excellence (ICGex); IMI ITCC-P4; The Child Cancer Research Foundation (CCRF), Cancer Council Western Australia (CCWA); PAIR-Pédiatrie/CONECT-AML (INCa-ARC-LIGUE_11905 and Association Laurette Fugain), Ligue contre le cancer (Equipe labellisée, since 2016), OPALE Carnot institute; Dell; Fondation Bristol-Myers Squibb; Association Imagine for Margo; Association Manon Hope; L’Etoile de Martin; La Course de l’Espoir; M la vie avec Lisa; ADAM; Couleur Jade; Dans les pas du Géant; Courir pour Mathieu; Marabout de Ficelle; Olivier Chape; Les Bagouz à Manon; Association Hubert Gouin Enfance et Cancer; Les Amis de Claire; Kurt-und Senta Hermann Stiftung; Holcim Stiftung Wissen; Gertrud-Hagmann-Stiftung für Malignom-Forschung; Heidi Ras Grant Forschungszentrum fürs Kind; Children’s Liver Tumor European Research Network (ChiLTERN) EU H2020 projet (668596); Fundación FERO and the Rotary Clubs Barcelona Eixample, Barcelona Diagonal, Santa Coloma de Gramanet, München-Blutenburg, Sassella-Stiftung, Berger-Janser Stiftung and Krebsliga Zürich, Deutschland Gemeindienst e.V. and others from Barcelona and province, and No Limits Contra el Cáncer Infantil Association

Thinking about Later Life: Insights from the Capability Approach

A major criticism of mainstream gerontological frameworks is the inability of such frameworks to appreciate and incorporate issues of diversity and difference in engaging with experiences of aging. Given the prevailing socially structured nature of inequalities, such differences matter greatly in shaping experiences, as well as social constructions, of aging. I argue that Amartya Sen’s capability approach (2009) potentially offers gerontological scholars a broad conceptual framework that places at its core consideration of human beings (their values) and centrality of human diversity. As well as identifying these key features of the capability approach, I discuss and demonstrate their relevance to thinking about old age and aging. I maintain that in the context of complex and emerging identities in later life that shape and are shaped by shifting people-place and people-people relationships, Sen’s capability approach offers significant possibilities for gerontological research

The clock genes Period 2 and Cryptochrome 2 differentially balance bone formation

Background: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology/Principal Findings: We found that Per2Brdm1 mutant mice as well as mice lacking Cry2-/- displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2-/- displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2-/- mutants despite the simultaneous inactivation of Per2. Conclusions/Significance: This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters

Novel geometrical concept of a high-performance brain PET scanner. Principle, design and performance estimates

We present the principle, a possible implementation and performance estimates of a novel geometrical concept for a high-resolution positron emission tomograph. The concept, which can be for example implemented in a brain PET device, promises to lead to an essentially parallax-free 3D image reconstruction with excellent spatial resolution and constrast, uniform over the complete field of view. The key components are matrices of long axially oriented scintillator crystals which are read out at both extremities by segmented Hybrid Photon Detectors. We discuss the relevant design considerations for a 3D axial PET camera module, motivate parameter and material choices, and estimate its performance in terms of spatial and energy resolution. We support these estimates by Monte Carlo simulations and in some cases by first experimental results. From the performance of a camera module, we extrapolate to the reconstruction resolution of a 3D axial PET scanner in a semi-analytical way and compare it to an existing state-of-the art brain PET device. We finally describe a dedicated data acquisition system, capable to fully exploit the advantages of the proposed concept. We conclude that the proposed 3D axial concept and the discussed implementation is a competitive approach for high-resolution brain PET. Excellent energy resolution and Compton enhanced sensitivity are expected to lead to high-quality reconstruction and reduced scanning times

The Calcitonin and Glucocorticoids Combination: Mechanistic Insights into Their Class-Effect Synergy in Experimental Arthritis

PMCID: PMC3564948This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Leadership in strategic information (LSI) building skilled public health capacity in Ethiopia

<p>Abstract</p> <p>Background</p> <p>In many developing countries, including Ethiopia, few have the skills to use data for effective decision making in public health. To address this need, the U.S. Centers for Disease Control and Prevention (CDC), in collaboration with two local Ethiopian organizations, developed a year long Leadership in Strategic Information (LSI) course to train government employees working in HIV to use data from strategic information sources. A process evaluation of the LSI course examined the impact of the training on trainees' skills and the strengths and weaknesses of the course. The evaluation consisted of surveys and focus groups.</p> <p>Findings</p> <p>Trainees' skill sets increased in descriptive and analytic epidemiology, surveillance, and monitoring and evaluation (M and E). Data from the evaluation indicated that the course structure and the M and E module required revision in order to improve outcomes. Additionally, the first cohort had a high attrition rate. Overall, trainees and key stakeholders viewed LSI as important in building skilled capacity in public health in Ethiopia.</p> <p>Conclusion</p> <p>The evaluation provided constructive insight in modifying the course to improve retention and better address trainees' learning needs. Subsequent course attrition rates decreased as a result of changes made based on evaluation findings.</p

Neonatal severe bacterial infection impairment estimates in South Asia, sub-Saharan Africa, and Latin America for 2010.

BACKGROUND: Survivors of neonatal infections are at risk of neurodevelopmental impairment (NDI), a burden not previously systematically quantified and yet important for program priority setting. Systematic reviews and meta-analyses were undertaken and applied in a three-step compartmental model to estimate NDI cases after severe neonatal bacterial infection in South Asia, sub-Saharan Africa, and Latin America in neonates of >32 wk gestation (or >1,500 g). METHODS: We estimated cases of sepsis, meningitis, pneumonia, or no severe bacterial infection from among estimated cases of possible severe bacterial infection ((pSBI) step 1). We applied respective case fatality risks ((CFRs) step 2) and the NDI risk among survivors (step 3). For neonatal tetanus, incidence estimates were based on the estimated deaths, CFRs, and risk of subsequent NDI. RESULTS: For 2010, we estimated 1.7 million (uncertainty range: 1.1-2.4 million) cases of neonatal sepsis, 200,000 (21,000-350,000) cases of meningitis, 510,000 cases (150,000-930,000) of pneumonia, and 79,000 cases (70,000-930,000) of tetanus in neonates >32 wk gestation (or >1,500 g). Among the survivors, we estimated moderate to severe NDI after neonatal meningitis in 23% (95% confidence interval: 19-26%) of survivors, 18,000 (2,700-35,000) cases, and after neonatal tetanus in 16% (6-27%), 4,700 cases (1,700-8,900). CONCLUSION: Data are lacking for impairment after neonatal sepsis and pneumonia, especially among those of >32 wk gestation. Improved recognition and treatment of pSBI will reduce neonatal mortality. Lack of follow-up data for survivors of severe bacterial infections, particularly sepsis, was striking. Given the high incidence of sepsis, even minor NDI would be of major public health importance. Prevention of neonatal infection, improved case management, and support for children with NDI are all important strategies, currently receiving limited policy attention