Ways to improve surgical outcomes in low- and middle-income countries.

Global surgery initiatives such as the Lancet Commission on Global Surgery have highlighted the need for increased investment to enhance surgical capacity in low- and middle-income countries. A neglected issue, however, is surgery-related rehabilitation, which is known to optimize functional outcomes after surgery. Increased investment to enhance surgical capacity therefore needs to be complemented by promotion of rehabilitation interventions. We make the case for strengthening surgery-related rehabilitation in lower-resource countries, outlining the challenges but also potential solutions and policy directions. Proposed solutions include greater leadership and awareness, augmented by recent global efforts around the World Health Organization's Rehabilitation 2030 initiative, and professionalization of the rehabilitation workforce. More research on rehabilitation is needed in low- and middle-income countries, along with support for system approaches, notably on strengthening and integrating rehabilitation within the health systems. Finally, we outline a set of policy implications and recommendations, aligned to the components of the national surgical plan proposed by the Lancet Commission: infrastructure, workforce, service delivery, financing, and information management. Collaboration and sustained efforts to embed rehabilitation within national surgical plans is key to optimize health outcomes for patients with surgical conditions and ensure progress towards sustainable development goal 3: health and well-being for all.

À l'instar de la Commission Lancet sur la chirurgie mondiale, des initiatives internationales consacrées à ce sujet ont mis en évidence le besoin d'investir davantage dans le renforcement des capacités chirurgicales dans les pays à revenu faible et intermédiaire. Néanmoins, la réadaptation post-chirurgicale, connue pour améliorer les résultats fonctionnels après une intervention, reste un enjeu largement ignoré. Ces investissements accrus visant à renforcer les capacités chirurgicales doivent donc aller de pair avec une promotion des services de réadaptation. Dans le présent document, nous plaidons pour le développement d'une réadaptation post-chirurgicale dans les pays à revenu faible et intermédiaire, en identifiant les défis mais aussi les orientations politiques et les solutions possibles. Parmi elles, un meilleur leadership et une prise de conscience, favorisée par les récents efforts mondiaux qui ont entouré l'initiative Réadaptation 2030 de l'Organisation mondiale de la Santé, ainsi qu'une professionnalisation du personnel dédié à la réadaptation. D'autres recherches sur la réadaptation sont nécessaires dans les pays à revenu faible et intermédiaire, tout comme l'apport d'un soutien aux approches systémiques, en particulier pour consolider et intégrer de telles pratiques dans les systèmes de santé. Enfin, nous dégageons une série de recommandations et d'implications politiques inspirés des éléments du plan chirurgical national proposé par la Commission Lancet: infrastructures, main-d'œuvre, prestations de services, financement et gestion des informations. La collaboration et la poursuite des efforts en vue d'inclure la réadaptation dans les plans chirurgicaux nationaux jouent un rôle crucial dans l'amélioration des résultats cliniques chez les patients souffrant de complications post-opératoires. En outre, elles permettront de progresser vers le troisième objectif de développement durable: santé et bien-être pour tous à tout âge.

Las iniciativas de cirugía a nivel mundial, como la Comisión Lancet sobre Cirugía Mundial, han destacado la necesidad de aumentar la inversión para mejorar la capacidad quirúrgica en los países de ingresos bajos y medios. Sin embargo, se ha descuidado la rehabilitación relacionada con la cirugía, que se sabe que optimiza los resultados funcionales después de la intervención. Por lo tanto, el incremento de la inversión para mejorar la capacidad quirúrgica se debe complementar con la promoción de intervenciones de rehabilitación. En este artículo se defiende la necesidad de reforzar la rehabilitación relacionada con la cirugía en los países con menos recursos, y se exponen los desafíos, pero también las posibles soluciones y orientaciones políticas. Las soluciones propuestas incluyen un mayor liderazgo y concienciación, potenciados por los recientes esfuerzos mundiales en torno a la iniciativa Rehabilitación 2030 de la Organización Mundial de la Salud, y la profesionalización del personal de rehabilitación. Se necesita más investigación sobre la rehabilitación en los países de ingresos bajos y medios, junto con el apoyo a los enfoques sistémicos, en particular sobre el fortalecimiento y la integración de la rehabilitación dentro de los sistemas sanitarios. Por último, se expone un conjunto de implicaciones y recomendaciones políticas, alineadas con los componentes del plan quirúrgico nacional que propone la Comisión Lancet: infraestructura, personal, prestación de servicios, financiación y gestión de la información. La colaboración y los esfuerzos sostenidos para integrar la rehabilitación en los planes quirúrgicos nacionales son fundamentales para optimizar los resultados sanitarios de los pacientes con afecciones quirúrgicas y asegurar el progreso hacia el tercer objetivo de desarrollo sostenible: salud y bienestar para todos.

Lifestyle Interventions to Improve Glycemic Control in Adults with Type 2 Diabetes Living in Low-and-Middle Income Countries: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCTs).

Alongside glucose lowering therapy, clinical guidelines recommend lifestyle interventions as cornerstone in the care of people living with type 2 diabetes (T2DM). There is a specific need for an up-to-date review assessing the effectiveness of lifestyle interventions for people with T2DM living in low-and-middle income countries (MICs). Four electronic databases were searched for RCTs published between 1990 and 2020. T2DM, lifestyle interventions, LMICs and their synonyms were used as search terms. Data codebooks were developed and data were extracted. Narrative synthesis and meta-analysis were conducted using random effects models to calculate mean differences (MD) and standardized mean differences (SMD) and 95% confidence intervals (CI). Of 1284 articles identified, 30 RCTs (n = 16,670 participants) met the inclusion criteria. Pooled analysis revealed significant improvement in HBA1c (MD -0.63; CI: -0.86, -0.40), FBG (SMD -0.35; CI: -0.54, -0.16) and BMI (MD -0.5; CI: -0.8, -0.2). In terms of intervention characteristics, those that included promoted self-management using multiple education components (e.g., diet, physical activity, medication adherence, smoking cessation) and were delivered by healthcare professionals in a hospital/clinic setting were deemed most effective. However, when interpreting these results, it is important to consider that most included studies were evaluated as being of low quality and there was a significant amount of intervention characteristics heterogeneity. There is a need for further well-designed studies to inform the evidence base on which lifestyle interventions are most effective for glycemic control in adults with T2DM living in LMICs.

Advanced musculoskeletal physiotherapy practice in Ireland: A National Survey.

BACKGROUND: Since 2011, advanced practice physiotherapists (APPs) have triaged the care of patients awaiting orthopaedic and rheumatology consultant/specialist doctor appointments in Ireland. APP services have evolved across the major hospitals (n = 16) and, after 5 years, profiling and evaluation of APP services was warranted. The present study profiled the national musculoskeletal APP services, focusing on service, clinician and patient outcome factors. METHODS: An online survey of physiotherapists in the allocated APP posts (n = 25) explored: service organization; clinician profile and experience of the advanced role; and patient wait times and outcome measures. Descriptive statistics were used to analyse hospital- and clinician-specific data, and a content analysis was performed to explore APP experiences. RESULTS: A 68% (n = 17) response from 13 sites was achieved, whereby 20 whole-time APP posts existed in services led by 91 consultant doctors. Co-location of APP and consultant clinics at 11 sites facilitated joint medical-APP processes, with between-site differences in autonomy to screen referral letters, and arrange investigations, injections and surgery. Although 83% had postgraduate qualifications, APPs also availed themselves of informal role-specific training. Positive APP experiences related to learning opportunities and clinical support networks but experiences were consultant dependent, with further service developments and formal training required to manage workloads. APPs reported reduced wait times and most commonly chose to capture function/disability in future evaluations. CONCLUSIONS: Variances existed in the organizational design and operating of APP services. Although highly experienced and qualified, APPs welcomed additional formal training and support, due to the complex, more medical nature of APP roles. Further formal evaluation, capturing patient outcomes, is proposed.

Development of PF-06671008, a Highly Potent Anti-P-cadherin/Anti-CD3 Bispecific DART Molecule with Extended Half-Life for the Treatment of Cancer.

Bispecific antibodies offer a promising approach for the treatment of cancer but can be challenging to engineer and manufacture. Here we report the development of PF-06671008, an extended-half-life dual-affinity re-targeting (DART®) bispecific molecule against P-cadherin and CD3 that demonstrates antibody-like properties. Using phage display, we identified anti-P-cadherin single chain Fv (scFv) that were subsequently affinity-optimized to picomolar affinity using stringent phage selection strategies, resulting in low picomolar potency in cytotoxic T lymphocyte (CTL) killing assays in the DART format. The crystal structure of this disulfide-constrained diabody shows that it forms a novel compact structure with the two antigen binding sites separated from each other by approximately 30 Å and facing approximately 90° apart. We show here that introduction of the human Fc domain in PF-06671008 has produced a molecule with an extended half-life (-4.4 days in human FcRn knock-in mice), high stability (Tm1 > 68 °C), high expression (>1 g/L), and robust purification properties (highly pure heterodimer), all with minimal impact on potency. Finally, we demonstrate in vivo anti-tumor efficacy in a human colorectal/human peripheral blood mononuclear cell (PBMC) co-mix xenograft mouse model. These results suggest PF-06671008 is a promising new bispecific for the treatment of patients with solid tumors expressing P-cadherin.