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Background: Palliative care aims to contribute to pain relief, improvement with regard to symptoms and enhancement of health-related quality of life (HRQoL) of patients with chronic conditions. Most of the palliative care protocols, programmes and units are predominantly focused on patients with cancer and their specific needs. Patients with non-cancer chronic conditions may also have significantly impaired HRQoL and poor survival, but do not yet receive appropriate and holistic care. The traditional focus of palliative care has been at the end-of-life stages instead of the relatively early phases of serious chronic conditions. The 'Patient-centred pathways of early palliative care, supportive ecosystems and appraisal standard' (InAdvance) project implements and evaluates early palliative care in the daily clinical routine addressing patients with complex chronic conditions in the evolution towards advanced stages. The objective of the current study is to evaluate the acceptability, feasibility, effectiveness and cost-effectiveness of this novel model of palliative care in the relatively early phases in patients with chronic conditions., Methods: In this study, a single blind randomised controlled trial design will be employed. A total of 320 participants (80 in each study site and 4 sites in total) will be randomised on a 1:1 basis to the Palliative Care Needs Assessment (PCNA) arm or the Care-as-Usual arm. This study includes a formative evaluation approach as well as a cost-effectiveness analysis with a within-trial horizon. Study outcomes will be assessed at baseline, 6 weeks, 6 months, 12 months and 18 months after the implementation of the interventions. Study outcomes include HRQoL, intensity of symptoms, functional status, emotional distress, caregiving burden, perceived quality of care, adherence to treatment, feasibility, acceptability, and appropriateness of the intervention, intervention costs, other healthcare costs and informal care costs., Discussion: The InAdvance project will evaluate the effect of the implementation of the PCNA intervention on the target population in terms of effectiveness and cost-effectiveness in four European settings. The evidence of the project will provide step-wise guidance to contribute an increased evidence base for policy recommendations and clinical guidelines, in an effort to augment the supportive ecosystem for palliative care., Trial Registration: ISRCTN, ISRCTN24825698 . Registered 17/12/2020., (© 2022. The Author(s).)

Competing Interests: The authors report no conflict of interest.

Background and Aims: EUS-guided biliary drainage has emerged as a technique to enable endobiliary drainage in failed ERCP. A newer model, lumen-apposing metal stents (LAMS), with a cautery-enhanced delivery system became available in the USA in late 2015. This cautery-tipped version may facilitate EUS-guided choledochoduodenostomy (EUS-CD), but data using this model are lacking., Methods: We reviewed outcomes of attempted EUS-CD using cautery-enhanced LAMS from 6, US centers. The following data were collected: patient and procedure details, technical success, adverse events, clinical success (resolution of jaundice or improvement in bilirubin > 50%), and biliary re-interventions., Results: EUS-CD was attempted in 67 patients (mean age 68.8) with malignant obstruction after failed ERCP between September 2015 and April 2018. EUS-CD was technically successful in 64 (95.5%). A plastic or metal stent was inserted through the lumen of the deployed LAMS in 50 of 64 (78.1%) patients to maintain a non-perpendicular LAMS axis into the bile duct. Adverse events occurred in 4 (6.3%) and included: abdominal pain (n = 2), peritonitis that responded to antibiotics (n = 1), and bleeding requiring transfusion (n = 1). Among 40 patients with follow-up of > 4 weeks, clinical success was achieved in 100%. Biliary re-interventions for obstruction were needed in 7(17.5%), in 3 of 6 (50.0%) that underwent EUS-CD with LAMS alone versus 4 of 34 (5%) with LAMS plus an axis-orienting stent (p = 0.02)., Conclusion: EUS-CD using LAMS with cautery-enhanced delivery systems has high technical and clinical success rates, with a low rate of adverse events. Inserting an axis-orienting stent through the lumen of the LAMS may reduce the need for biliary re-interventions.

Recent technological advances in colonoscopy have led to improvements in both image enhancement and procedural performance. However, the utility of these technological advancements remain dependent on the quality of bowel preparation during colonoscopy. Poor bowel preparation has been shown to be associated with lower quality indicators of colonoscopy performance, such as reduced cecal intubation rates, increased patient discomfort and lower adenoma detection. The most popular bowel preparation regimes currently used are based on either Polyethylene glycol-electrolyte, a non-absorbable solution, or aqueous sodium phosphate, a low-volume hyperosmotic solution. Statements from various international societies and several reviews have suggested that the efficacy of bowel preparation regimes based on both purgatives are similar, although patients' compliance with these regimes may differ somewhat. Many studies have now shown that factors other than the type of bowel preparation regime used, can influence the quality of bowel preparation among adult patients undergoing colonoscopy. These factors can be broadly categorized as either patient-related or procedure-related. Studies from both Asia and the West have identified patient-related factors such as an increased age, male gender, presence of co-morbidity and socio-economic status of patients to be associated with poor bowel preparation among adults undergoing routine out-patient colonoscopy. Additionally, procedure-related factors such as adherence to bowel preparation instructions, timing of bowel purgative administration and appointment waiting times for colonoscopy are recognized to influence the quality of colon cleansing. Knowledge of these factors should aid clinicians in modifying bowel preparation regimes accordingly, such that the quality of colonoscopy performance and delivery of service to patients can be optimised.

This article summarizes an extensive review of South American experiences with primary health care since the Declaration of Alma-Ata. It aims to address the following specific questions: What are the enabling and constraining historical and structural conditions for primary health care policies and practices? How has health care reform supported or undermined primary health care? What evidence exists on the effectiveness of primary health care? What strategies are common to best practices? What evidence exists on the roles of citizen participation and intersectoral action? And finally, what are the policy lessons to be learned from these experiences? Narrative synthesis was used to identify and examine patterns in the data consistent with these questions. Conditions that were found to promote successful implementation of primary health care are outlined, together with features of effective primary health care systems that help create more equitable health services and health outcomes.

Two cell lines, RR5.ET-1 and RR1.ET-1, that produce monoclonal antibodies specific for the carboxyl-terminal heptapeptide of endothelin-1 (ET-1) have been cloned and stabilized. An RIA was developed to facilitate the evaluation and characterization of these monoclonal antibodies. The affinity constant of each MAb for ET-1, as determined by Scatchard analysis, was 5.74 x 10(8) M-1 for RR5.ET-1 and 4.15 x 10(7) M-1 for RR1.ET-1. The antibodies reacted specifically with the carboxyl-terminus (ET15-21) and did not cross-react with the amino-terminal amino acids (ET1-16). As expected, the antibodies cross-reacted with endothelin-2 (ET-2) and endothelin-3 (ET-3), and to a lesser extent, with the closely related sarafotoxins. Both MAbs retained about 55% reactivity with the ET-1 terminal sequence of Asp-Ile-Ile-Trp (ET18-21) but had no reactivity with the ET sequence His-Leu-Asp-Ile-Ile-Trp-Val-Asn (ET16-23) nor with Big ET-1 (ET1-39). These data strongly suggest that the terminal four amino acids of ET-1 are included in the MAb binding site. More importantly, the terminal Trp21 must be free, not linked to Val22 to retain reactivity with either of the MAbs.