BackgroundIn pediatric intensive care units, pain, sedation, delirium, and iatrogenic withdrawal syndrome (IWS) must be managed as interrelated conditions. Although clinical practice guidelines (CPGs) exist, new evidence needs to be incorporated, gaps in recommendations addressed, and recommendations adapted to the European context. ObjectiveThis protocol describes the development of the first patient- and family-informed European guideline for managing pain, sedation, delirium, and IWS by the European Society of Paediatric and Neonatal Intensive Care. MethodsThis guideline will follow the Grading of Recommendations Assessment, Development, and Evaluation ADOLOPMENT approach across seven phases: (1) setup—establish 3 groups, namely a steering committee, development panel (experts and patient and family partners), and patient and family partner advisory panel, to define guideline scope through voting and consensus; (2) preparation—vote on 30 summary recommendations compiled from existing CPGs of medium quality or above; prioritize new research questions; update the search for CPGs to match new research questions with recommendations using population, intervention, comparator, and outcome elements; prioritize outcomes for effectiveness questions using a 9-point Likert scale; with validation from patient and family partners; (3) evidence identification, analysis, and data extraction—develop individualized search strategies for each research question (2 independent appraisers will select and appraise studies and conduct data extraction); (4) evidence synthesis—expert pairs will summarize findings in evidence profiles and evidence-to-decision (EtD) frameworks (in the absence of evidence, the expert panel will be surveyed to assess current practices); (5) guideline development—expert pairs will draft recommendations, then topic-specific subgroups will reach consensus before full development panel voting (>80% approval needed; subgroups will determine the need for additional supporting content); (6) review—conduct internal, society-level, and external international expert reviews using surveys with Likert scales and open-ended comments; and (7) issue and update—publish the guideline and monitor literature to assess the need for updates before 5 years. ResultsIn phase 1, a total of 21 clinical experts and 17 patient and family partners were recruited, and the guideline scope was finalized with 80% to 100% agreement. In phase 2, a total of 23 summary recommendations and 17 new research questions (total=40) were selected. The updated CPG search identified 2 low-quality CPGs, which were excluded from recommendation matching. Of the 17 new research questions, 4 matched existing recommendations. Of the 3 effectiveness questions, one had 7 prioritized outcomes, whereas two had 9 outcomes for inclusion in EtD frameworks. The final CPG is expected by spring 2026, with search strategies, EtD frameworks, and recommendations included. ConclusionsThis protocol ensures a transparent Grading of Recommendations Assessment, Development, and Evaluation–based development process, leading to a trustworthy and credible guideline tailored to the European context for managing pain, sedation, delirium, and IWS in children who are critically ill. International Registered Report Identifier (IRRID)DERR1-10.2196/67930

OBJECTIVE:This scoping review will examine the characteristics of the development, implementation, and/or evaluation of a professional practice model (PPM) for pediatric nursing in Westernized countries. INTRODUCTION:PPMs in nursing are designed to improve excellence in nursing practice and have been shown to improve the work environment. Despite the comprehensive insights from the literature on this topic, it predominantly focuses on adult care settings, leaving a gap in the literature regarding pediatric-specific PPMs. ELIGIBILITY CRITERIA:This review will consider evidence sources that include PPMs developed, implemented, or evaluated in at least 1 inpatient pediatric unit admitting children aged from birth to 18 years in Westernized countries. This review will exclude PPMs established solely in adult care contexts and PPMs developed for specific nursing roles. METHODS:This review will follow the JBI methodology for scoping reviews. Evidence sources using any study design published from 2015 up to the date of the search in any language will be considered. A 3-step search strategy will be used to search CINAHL (EBSCOhost), Embase, PubMed, Web of Science Core Collection, ProQuest ABI/inform collection, Business Source Premier (EBSCOhost), ProQuest Dissertations and Theses, and BASE. Complementary searches will be conducted in Google Scholar, and backward and forward citation searching of included evidence sources will be performed. Two reviewers will independently perform study selection and data extraction, and any disagreements will be resolved with a third reviewer. Data extraction and analysis will be performed using a chart to compare patterns, trends, and gaps in the literature. REVIEW REGISTRATION:OSF https://osf.io/g3jxz/overview.

BACKGROUND:Patients with multiple chronic conditions often face a cumulative workload that exceeds their capacity to manage daily life and healthcare. Although there is evidence of the contribution of advanced practice nurses in chronic disease management, no prior synthesis has examined how their interventions specifically address capacity-workload balance as conceptualised in the Cumulative Complexity Model-a framework that explains how the interaction between patients' capacity and treatment workload shapes engagement in care-or how these interventions align with internationally recognised domains of advanced nursing practice. OBJECTIVE:To map and synthesise advanced practice nurse-led interventions that promote patient capacity-workload balance, using the Cumulative Complexity Model and the Advanced Practice Role Delineation tool. DATA SOURCES:Eight databases were searched from inception to 2025. METHODS:A scoping review was conducted following the JBI methodology. Eligible articles included interventions or activities led by clinical nurse specialists, nurse practitioners, or generically titled advanced practice nurses for adults living with at least two chronic conditions. Interventions had to relate to patient capacity, workload, or their balance. Included study designs were quantitative, qualitative, mixed-methods, and review studies. Data were extracted by using a structured framework and analysed descriptively and conceptually. RESULTS:Fifteen articles, most quantitative, were included. Most interventions were delivered at home, individually, face-to-face, and over 12 months. Common components included care coordination, coaching, regular clinical follow-up, and individualised care planning. Although none of the articles explicitly referenced the Cumulative Complexity Model, over half of the interventions aligned with its principles by aiming to support capacity-workload balance. The dominant advanced nursing practice domain for interventions was direct comprehensive care. Interventions encompassing all five domains were described in one article that involved a clinical nurse specialist. Outcomes focused on patient- and system-level indicators such as health improvement, quality of life, healthcare utilisation, and costs. A conceptual framework was developed, providing a retrospective lens on how advanced practice nurses address capacity-workload balance for adults with multiple chronic conditions through key interventions embedded within core domains of advanced practice. CONCLUSIONS:This review highlights how interventions led by advanced practice nurses can support patient capacity-workload balance through core components embedded in recognised domains of advanced practice. A conceptual framework integrating these elements offers insights to guide the development, implementation, and evaluation of advanced nursing roles and interventions tailored to the complex needs of individuals with multiple chronic conditions. REGISTRATION:The protocol was registered in the Open Science Framework on April 22, 2025. SOCIAL MEDIA ABSTRACT:Advanced practice nurses help balance the care workload and capacity for patients with multimorbidity - mapped in a framework.

INTRODUCTION:Intrathecal morphine provides effective postoperative analgesia, but there are concerns about potential pulmonary complications influencing peri-operative management. We aimed to determine whether there is an association between intrathecal morphine administration and pulmonary complications after non-obstetric surgery. We also aimed to determine whether there was a dose-dependent effect on pulmonary complications. METHODS:We searched the literature systematically for randomised controlled trials comparing intrathecal morphine vs. control in patients undergoing any type of non-obstetric surgery under general or spinal anaesthesia. Primary outcomes were rates of postoperative sedation, respiratory depression and hypoxaemia. We performed a meta-analysis and meta-regression for each of our outcomes of interest and conducted trial sequential analysis to assess whether the required information size was achieved. RESULTS:We included 127 trials (7388 patients). Rates of sedation and hypoxaemia were not increased significantly in patients receiving intrathecal morphine (odds ratio 1.00, 95%CI 0.78-1.28, p = 0.98, moderate quality evidence; and 1.22, 95%CI 0.84-1.79, p = 0.30, moderate quality evidence, respectively). There were more episodes of respiratory depression in patients receiving intrathecal morphine than control (odds ratio 1.78, 95%CI 1.19-2.67, p = 0.005, very low-quality evidence), which was no longer significant when morphine doses > 500 μg were not included (odds ratio1.49, 95%CI 0.99-2.23, p = 0.06). Meta-regression revealed associations between dose and rate of sedation, respiratory depression and hypoxaemia, but when doses of > 500 μg were not included, these associations did not persist. Trial sequential analyses suggest that further data may still be required for all outcomes, but statistical significance was reached for respiratory depression. DISCUSSION:There is moderate evidence that intrathecal morphine does not increase rates of sedation or hypoxaemia after non-obstetric surgery. There is very low-quality evidence that intrathecal morphine might increase the rate of respiratory depression.

Summary: Lipedema is a chronic disease characterized by the disproportionate and symptomatic accumulation of fat in the lower limbs and arms. Women with lipedema experience heaviness, fatigue and pain, leading to impairments in daily activities and reduced quality of life. Conservative treatment mainly focuses on lifestyle modifications, along with compression therapy and manual lymphatic drainage. Exercise training could also play a pivotal role in the management of lipedema. The aim of this systematic review was to explore the effectiveness of exercise training in women with lipedema. A comprehensive literature search was conducted in Embase, MEDLINE, Cochrane CENTRAL, Web of Science, CINAHL on June 23, 2025. The main outcomes were pain, fatigue and other symptoms, quality of life, anthropometric characteristics, lower limb volumes and/or circumference, and functional performance. The search strategy identified 523 studies, of which six were included in this review. Studies included 115 women with lipedema. Exercise training seems to improve pain and other symptoms, quality of life, limb volumes and/or circumference, and functional performance. The effects seem to be greater when combined with ongoing compression therapy. However, the effects of exercise training on the different outcomes varied among the studies, probably related to the high heterogeneity, different training approaches, and small sample sizes. Exercise training might be a promising therapeutic care option in women with lipedema, and the effects seem to be greater when combined with ongoing compression therapy. Appropriately designed and adequately powered studies are needed to further explore the benefits of exercise in these patients. (PROSPERO Registration No.: CRD42024604164)

Older patients hospitalized in acute care settings are at significant risk of presenting hospital-acquired conditions. Healthcare professionals should consider many factors involved in the development of such conditions, including factors related to the patients, as well as those related to the processes of care and the structure of hospitals. The aim of this study was to describe and identify the factors involved in the development of hospital-acquired conditions in older patients in acute care settings. A scoping review was performed based on a structured search in eight databases in September 2022. Data were extracted with an extraction tool and classified into categories. Mapping and a narrative summary were used to synthetize data. A total of 237 articles were included in the scoping review. Functional decline and delirium were the most frequent hospital-acquired conditions studied. Among all categories, factors related to the patients provided most of the data, whereas factors related to the processes of care and the structure of hospitals were less frequently explored. In most articles, one or two categories of factors were retrieved; fewer articles examined factors among three categories. Personal factors, medications, and the human and work environment were the most frequent subcategories of factors retrieved, whereas social factors, hydration and nutrition, and organizational factors were less common. The development of hospital-acquired conditions in older patients in acute care settings involves many factors related to the patients, as well as to the processes of care and the structure of hospitals. Prevention of hospital-acquired conditions must involve to consider the complexities of older patients and of acute care hospitals. Not considering all categories of factors might affect the implementation of new practices of care and interventions.

OBJECTIVE:The objective of this mixed methods review was to examine the effectiveness and family experiences of interventions promoting partnerships between families and the multidisciplinary health care team in pediatric and neonatal intensive care units. INTRODUCTION:Hospitalization of infants and children in neonatal intensive care units and pediatric intensive care units has a significant effect on their families, including increased stress, anxiety, and depression. Available evidence syntheses focused on specific family-centered care, but not on partnership, which is another aspect that may improve families' outcomes and experiences. INCLUSION CRITERIA:This review considered studies that focused on effectiveness or family experiences of interventions by health professionals in partnership with families of infants or children hospitalized in an intensive care unit. For the quantitative component of the review, the type of intervention was a partnership between the health care team and the family, and focused on outcomes of stress, anxiety, depression, quality of life, attachment, or satisfaction with family-centered care. For the qualitative component, the phenomenon of interest was family experiences of interventions that included collaboration and partnering with the health care team in the pediatric or neonatal intensive care unit. Quantitative, qualitative, and mixed methods studies, published from 2000 to August 2022 in English or French, were eligible for inclusion. METHODS:The JBI methodology for convergent segregated mixed methods systematic reviews was followed using the standardized JBI critical appraisal and data extraction tools. Ten databases were searched in December 2019 and again in August 2022. Study selection, critical appraisal, and data extraction were performed by 2 reviewers independently. Findings of quantitative studies were statistically pooled through meta-analysis and those that could not be pooled were reported narratively. Qualitative studies were pooled through meta-synthesis. RESULTS:This review included 6 qualitative and 42 quantitative studies. The methodological quality varied, and all studies were included regardless of methodological quality. Meta-analyses showed improvements in anxiety, satisfaction with family-centered care, and stress, yet no conclusive effects in attachment and depression. These results should be interpreted with caution due to high heterogeneity. Qualitative analysis resulted in 2 synthesized findings: "Interventions that incorporate partnerships between families and the health care team can improve the family's experience and capacity to care for the child" and "Having a child in intensive care can be an experience of significant impact for families." Integration of quantitative and qualitative evidence revealed some congruence between findings; however, the paucity of qualitative evidence minimized the depth of this integration. CONCLUSIONS:Partnership interventions can have a positive impact on parents of children in intensive care units, with improvements reported in stress, anxiety, and satisfaction with family-centered care. REVIEW REGISTRATION:PROSPERO CRD42019137834. SUPPLEMENTAL DIGITAL CONTENT:A Chinese-language version of the abstract of this review is available at http://links.lww.com/SRX/A50 . A French-language version of the abstract of this review is available at http://links.lww.com/SRX/A51 .

Summary Widespread adoption of intrathecal morphine into clinical practice is hampered by concerns about its potential side‐effects. We undertook a systematic review, meta‐analysis and trial sequential analysis with the primary objective of determining the efficacy and safety of intrathecal morphine. Our secondary objective was to determine the dose associated with greatest efficacy and safety. We also assessed the impact of intrathecal morphine on respiratory depression. We systematically searched the literature for trials comparing intrathecal morphine with a control group in patients undergoing hip or knee arthroplasty under spinal anaesthesia. Our primary efficacy outcome was rest pain score (0–10) at 8–12 hours; our primary safety outcome was the rate of postoperative nausea and vomiting within 24 hours. Twenty‐nine trials including 1814 patients were identified. Rest pain score at 8–12 hours was significantly reduced in the intrathecal morphine group, with a mean difference (95%CI) of −1.7 (−2.0 to −1.3), p < 0.0001 (19 trials; 1420 patients; high‐quality evidence), without sub‐group differences between doses (p = 0.35). Intrathecal morphine increased postoperative nausea and vomiting, with a risk ratio (95%CI) of 1.4 (1.3–1.6), p < 0.0001 (24 trials; 1603 patients; high‐quality evidence). However, a sub‐group analysis by dose revealed that rates of postoperative nausea and vomiting within 24 hours were similar between groups at a dose of 100 µg, while the risk significantly increased with larger doses (p value for sub‐group difference = 0.02). Patients receiving intrathecal morphine were no more likely to have respiratory depression, the risk ratio (95%CI) being 0.9 (0.5–1.7), p = 0.78 (16 trials; 1173 patients; high‐quality evidence). In conclusion, there is good evidence that intrathecal morphine provides effective analgesia after lower limb arthroplasty, without an increased risk of respiratory depression, but at the expense of an increased rate of postoperative nausea and vomiting. A dose of 100 µg is a ‘ceiling’ dose for analgesia and a threshold dose for increased rate of postoperative nausea and vomiting.

STUDY OBJECTIVE:Neuraxial hydromorphone provides postoperative pain relief. However, the magnitude of this effect and the optimal dose remain unknown. The objective of this study is to clarify these uncertainties. DESIGN:Systematic review and meta-analysis with trial sequential analysis. SETTING:Postoperative recovery area and ward, up to 24 h. PATIENTS:Any patient undergoing any type of surgery or being in labor. INTERVENTIONS:Neuraxial hydromorphone versus control. MEASUREMENTS:Our primary outcome was rest pain score (analogue scale, 0-10) at 24 h according to route of administration (epidural versus spinal) and type of surgery (orthopedic versus other). Secondary outcomes included rest pain score at 0-4 and 8-12 h; rates of postoperative nausea and vomiting, and pruritus at 24 h. MAIN RESULTS:Six trials, including 436 patients, were identified. Rest pain score at 24 postoperative hours was significantly reduced in the hydromorphone group, with a mean difference (95 %CI) of -0.4 (-0.8 to -0.1), I2 = 74 %, p = 0.01. Neuraxial hydromorphone did not increase postoperative nausea and vomiting (risk ratio [95 %CI]: 1.2 [0.8-1.8], I2 = 27 %, p = 0.47), but increases pruritus (risk ratio [95 %CI]: 3.1 [1.6-5.9], I2 = 0 %, p = 0.0005). The quality of evidence was very low for our primary and secondary outcomes. In conclusion, there is very low level of evidence that neuraxial hydromorphone provides effective analgesia after surgery or labor, at the expense of an increased rate of pruritus. The improvement in pain scores appears to be clinically insignificant. With only six trials published over a period of 30 years, we were unable to perform a meta-regression. CONCLUSIONS:If neuraxial hydromorphone is to be used regularly, trials focusing on the optimal dose and side-effects should be performed before widely administering this medication into the neuraxial space. More trials focusing on the optimal dose and side-effects should be performed before widely administering this medication into the neuraxial space.

Introduction In pediatric intensive care units, pain, sedation, delirium, and iatrogenic withdrawal syndrome must be managed as interrelated conditions. Existing clinical practice guidelines have some methodological limitations and are not readily transferrable to the European context without adaptation. This protocol describes the methods for developing a high-quality, and the first patient- and family-informed European guideline for managing pain, sedation, delirium and iatrogenic withdrawal syndrome. Methods The guideline will be developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) - ADOLOPEMENT approach, engaging clinical experts and patients and families in the development process. It will consist of seven phases: 1) Set-up – establishing three groups for guideline development: i) steering committee, ii) development panel (experts and patient/family partners from across Europe), and iii) patient and family advisory panel, and scoping to determine population, conditions, purpose, and users of the guideline; 2) Preparation – voting on summary recommendations, prioritizing research questions and outcomes, and matching research questions with existing recommendations; 3) Search and retrieval of evidence – using three search approaches to develop search strategies to find evidence, conducting individualized searches for each summary recommendation and new research question, selecting evidence, study appraisal, and initial data extraction; 4) Evidence synthesis – summarizing evidence in evidence profiles and summary of evidence tables, and conducting panel surveys of current practice when evidence is absent; 5) Development – drafting recommendations, voting on and approving them, and developing accompanying materials; 6) Review – conducting internal, society-level, and external international expert reviews; and 7) Issue – publishing the guideline. Discussion This protocol ensures a transparent process follows the GRADE approach for guideline development, leading to a high-quality, trustworthy, and credible guideline for managing pain, sedation, delirium and iatrogenic withdrawal syndrome in critically ill children. Tailored to the European context for healthcare professionals. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial The protocol for developing our CPG was registered in the Practice guideline REgistration for transPAREncy (PREPARE) under registration number PREPARE-2024CN859 ### Funding Statement Yes ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Not applicable I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Not Applicable I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Not Applicable I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Not Applicable not applicable

Purpose: This systematic review aimed to compare the effect of contrast media (CM) dose adjustment based on lean body weight (LBW) method versus other calculation protocols for abdominopelvic CT examinations. Method: Studies published from 2002 onwards were systematically searched in June 2024 across Medline, Embase, CINAHL, Cochrane CENTRAL, Web of Science, Google Scholar and four other grey literature sources, with no language limit. Randomised controlled trials (RCT) and quasi-RCT of abdominopelvic or abdominal CT examinations in adults with contrast media injection for oncological and acute diseases were included. The comparators were other contrast dose calculation methods such as total body weight (TBW), fixed volume (FV), body surface area (BSA), and blood volume. The main outcomes considered were liver and aortic enhancement. Titles, abstracts and full texts were independently screened by two reviewers. Results: Eight studies were included from a total of 2029 articles identified. Liver parenchyma and aorta contrast enhancement did not significantly differ between LBW and TBW protocols (p = 0.07, p = 0.06, respectively). However, the meta-analysis revealed significantly lower contrast volume injected with LBW protocol when compared to TBW protocol (p = 0.003). No statistical differences were found for contrast enhancement and contrast volume between LBW and the other strategies. Conclusion: Calculation of the CM dosage based on LBW allows a reduction in the injected volume for abdominopelvic CT examination, ensuring the same image quality in terms of contrast enhancement.

Background Intrathecal morphine provides effective analgesia for a range of operations. However, widespread implementation into clinical practice is hampered by concerns for potential side-effects. We undertook a systematic review, meta-analysis, and meta-regression with the primary objective of determining whether a threshold dose for non-pulmonary complications could be defined and whether an association could be established between dose and complication rates when intrathecal morphine is administered for perioperative or obstetric analgesia. Methods We systematically searched the literature for randomised controlled trials comparing intrathecal morphine vs control in patients undergoing any type of surgery under general or spinal anaesthesia, or women in labour. Primary outcomes were rates of postoperative nausea and vomiting, pruritus, and urinary retention within the first 24 postoperative hours, analysed according to doses (1–100 μg; 101–200 μg; 201–500 μg; >500 μg), type of surgery, and anaesthetic strategy. Trials were excluded if doses were not specified. Results Our analysis included 168 trials with 9917 patients. The rates of postoperative nausea and vomiting, pruritus, and urinary retention were significantly increased in the intrathecal morphine group, with an odds ratio (95% confidence interval) of 1.52 (1.29–1.79), P<0.0001; 6.11 (5.25–7.10), P<0.0001; and 1.73 (1.17–2.56), P=0.005, respectively. Meta-regression could not establish an association between dose and rates of non-pulmonary complications. There was no subgroup difference according to surgery for any outcome. The quality of evidence was low (Grading of Recommendations Assessment, Development, and Evaluation [GRADE] system). Conclusions Intrathecal morphine significantly increased postoperative nausea and vomiting, pruritus, and urinary retention after surgery or labour in a dose-independent manner. Systematic review protocol PROSPERO (CRD42023387838).

Metformin is considered as first-line treatment for type 2 diabetes and an effective treatment for polycystic ovary syndrome (PCOS). However, evidence regarding its safety in pregnancy is limited. We conducted a systematic review and meta-analysis of major congenital malformations (MCMs) risk after first-trimester exposure to metformin in women with PCOS and pregestational diabetes mellitus (PGDM). Randomized controlled trials (RCTs) and observational cohort studies with a control group investigating risk of MCM after first-trimester pregnancy exposure to metformin were searched until December 2021. ORs and 95% CIs were calculated separately according to indications and study type using Mantel-Haenszel method; outcome data were combined using random-effects model. Eleven studies (two RCTs; nine observational cohorts) met the inclusion criteria: four included pregnant women with PCOS, four included those with PGDM and three evaluated both indications separately and were considered in both indication groups. In PCOS group, there were two RCTs (57 exposed, 52 control infants) and five observational studies (472 exposed, 1892 control infants); point estimates for MCM rates in RCTs and observational studies were OR 0.93 (95% CI 0.09 to 9.21) (I-2=0%; Q test=0.31; p value=0.58) and OR 1.35 (95% CI 0.37 to 4.90) (I-2=65%; Q test=9.43; p value=0.05), respectively. In PGDM group, all seven studies were observational (1122 exposed, 1851 control infants); the point estimate for MCM rates was OR 1.05 (95% CI 0.50 to 2.18) (I-2=59%; Q test=16.34; p value=0.01). Metformin use in first-trimester pregnancy in women with PCOS or PGDM do not meaningfully increase the MCM risk overall. However, further studies are needed to characterize residual safety concerns.

OBJECTIVES:The objective of our study was to determine whether, and to what degree, the ethical dimension was present in clinical practice guidelines (CPGs) on palliative sedation, and to identify the ethical issues with respect to the different forms of this practice. The purpose was purely to be descriptive; our aim was not to make any kind of normative judgements on these ethical issues or to develop our own ethical recommendations.METHODS:We performed a systematic review of CPGs on the palliative sedation of adults, focusing our analysis on the ethical dimension of these texts and the ethical issues of this practice. The study protocol is registered on PROSPERO.RESULTS:In total, 36 current CPGs from four continents (and 14 countries) were included in our analysis. Generally, ethics was rarely referred to or absent from the CPGs. Only six texts contained a specific section explicitly related to ethics. Ethical issues were named, conceptualised and presented in heterogeneous, often confusing ways. It was impossible to identify the ethical issues of each form of palliative sedation. Ethics expertise was not involved in the development of most of the CPGs and, if it was, this did not always correlate with the ethical dimension of the document.CONCLUSIONS:Effective cooperation between palliative care clinicians and ethicists should be encouraged, in order to integrate in particular the crucial ethical issues of continuous deep sedation until death when developing or updating CPGs on palliative sedation.

Introduction: The International Commission for Mountain Emergency Medicine (ICAR MedCom) developed updated recommendations for the management of avalanche victims. Methods: ICAR MedCom created Population Intervention Comparator Outcome (PICO) questions and conducted a scoping review of the literature. We evaluated and graded the evidence using the American College of Chest Physicians system.Results: We included 120 studies including original data in the qualitative synthesis. There were 45 retrospective studies (38%), 44 case reports or case series (37%), and 18 prospective studies on volunteers (15%). The main cause of death from avalanche burial was asphyxia (range of all stud-ies 65-100%). Trauma was the second most common cause of death (5-29%). Hypothermia accounted for few deaths (0-4%).Conclusions and recommendations: For a victim with a burial time < 60 minutes without signs of life, presume asphyxia and provide rescue breaths as soon as possible, regardless of airway patency. For a victim with a burial time > 60 minutes, no signs of life but a patent airway or airway with unknown patency, presume that a primary hypothermic CA has occurred and initiate cardiopulmonary resuscitation (CPR) unless temperature can be measured to rule out hypothermic cardiac arrest. For a victim buried > 60 minutes without signs of life and with an obstructed airway, if core temperature cannot be measured, rescuers can presume asphyxia-induced CA, and should not initiate CPR. If core temperature can be measured, for a victim without signs of life, with a patent airway, and with a core temperature < 30 degrees C attempt resuscitation, regardless of burial duration.

PSTPIP1 (proline-serine-threonine phosphatase-interactive protein 1)-associated myeloid-related proteinemia inflammatory (PAMI) syndrome, previously known as Hyperzincemia/Hypercalprotectinemia (Hz/Hc) syndrome, is a recently described, rare auto-inflammatory disorder caused by specific deleterious variants in the PSTPIP1 gene (p.E250K and p.E257K). The disease is characterized by chronic systemic inflammation, cutaneous and osteoarticular manifestations, hepatosplenomegaly, anemia, and neutropenia. Increased blood levels of MRP 8/14 and zinc distinguish this condition from other PSTPIP1-associated inflammatory diseases (PAID). The aim of this systematic review is to provide a comprehensive overview of the disease phenotype, course, treatment, and outcome based on reported cases. This systematic review adheres to the PRISMA guidelines (2020) for reporting. A literature search was performed in Embase, Medline, and Web of Science on 13 October 2022. The quality of the case reports and case series was assessed using the JBI checklists. Out of the 43 included patients with PAMI syndrome, there were 24 females and 19 males. The median age at onset was 3.9 years. The main clinical manifestations included anemia (100%), neutropenia (98%), cutaneous manifestations (74%), osteoarticular manifestations (72%), splenomegaly (70%), growth failure (57%), fever (51%), hepatomegaly (56%), and lymphadenopathy (39%). Systemic inflammation was described in all patients. Marked elevation of zinc and MRP 8/14 blood levels were observed in all tested patients. Response to treatment varied and no consistently effective therapy was identified. The most common therapeutic options were corticosteroids (N = 30), anakinra (N = 13), cyclosporine A (N = 11), canakinumab (N = 6), and anti-TNF (N = 14). Hematopoietic stem cell transplantation has been recently reported to be successful in five patients. Our review highlights the key characteristics of PAMI syndrome and the importance of considering this disease in the differential diagnosis of patients presenting with early-onset systemic inflammation and cytopenia.

CONTEXT: Entrustable Professional Activities (EPAs) are observable tasks that are regular parts of a physician’s daily clinical work. Before being permitted to accomplish these tasks independently, trainees must gain their supervisors’ trust. Defining the list of EPAs that should be mastered by the end of a residency is critical to setting clear expectations about autonomous practice. OBJECTIVE: To collect all the lists of EPAs defined for residencies in general internal medicine and synthesise them into a reference work useful for developing new lists of EPAs or improving existing ones. METHOD: This systematic review searched five databases and relevant grey literature using keywords related to EPAs and postgraduate education, from 2005, when the first article on EPAs was published, to April 2022. Inclusion criteria were the availability of an EPAs list and a focus on general internal medicine. Two reviewers independently selected the studies, extracted data and performed a quality assessment using QATSDD and AACODS tools. Mean values and inter-rater reliability were calculated. RESULTS: The review yielded 3292 records, with 16 articles meeting the inclusion criteria, mostly from North America. Synthesising their 16 lists generated 395 EPAs. The reviewers then inductively categoried those EPAs, 308 of which fell into 6 domains, 14 themes and 24 subthemes. The domains were: (1) care and management of the general adult population (n = 103 EPAs); (2) care and management of patients with specific needs (n = 67); (3) care coordination and communication (n = 52); (4) management and leadership (N = 21); (5) healthcare quality, education, and research (n = 41); and (6) miscellaneous (n = 24). The remaining 87 EPAs were disease-specific and did not fit into this categorisation. CONCLUSIONS: Categorising EPAs created a unique synthesis of the existing lists of EPAs for educating residents in general internal medicine. This synthesis could be used as a reference for anyone tasked with developing new lists of EPAs or improving existing ones.

OBJECTIVE This systematic review will evaluate the experience of hope in adult patients with advanced chronic diseases other than cancer, transitioning toward end-of-life. The review will also evaluate the experience of hope in informal caregivers caring for adult patients with advanced chronic diseases other than cancer as they transition toward end-of-life. INTRODUCTION Hope is an important resource that assists patients and informal caregivers to deal with difficult and complex situations, such as living with advanced chronic disease. INCLUSION CRITERIA The review will include studies written in English, French, and Portuguese exploring hope. Qualitative studies focusing on adult patients with advanced chronic diseases other than cancer and/or informal caregivers will be considered. Studies with children as patients or parents as caregivers will be excluded. METHODS The review will search Embase, MEDLINE, CINAHL, PsycINFO, Web of Science, ProQuest Dissertations and Theses, DART-Europe E-theses Portal, and Google Scholar. The search will be conducted without date restrictions. Articles will be assessed against the inclusion criteria by two independent reviewers. Data will be extracted using a standard tool. The extracted findings will be synthesized using the meta-aggregation approach through assembling and categorizing data. SYSTEMATIC REVIEW REGISTRATION NUMBER PROSPERO CRD42021266487.

Introduction This study aims to identify the full spectrum of ethical challenges of all forms of palliative sedation for adults as presented in current clinical practice guidelines (CPGs) and to determine whether CPGs specify ethical challenges of this therapy for patients with cancer and non-cancer and, if so, how exactly they do this. To the best of our knowledge, no studies have yet investigated this topic. The purpose is purely descriptive; our aim is not to make any kind of normative judgements on these challenges. Nor is our aim to assess the quality of the CPGs. Methods and analysis We will perform a systematic review of CPGs on palliative sedation for adults via five electronic databases, grey literature search tools, citation tracking and contact with palliative care experts. Current CPGs accredited by an international, national or regional authority, published in English, German, French, Italian or Polish, from 2000 to the date of the search, will be subjected to content analysis at the textual, linguistic and thematic levels. Ethics and dissemination This is a protocol for a systematic review and no human will be involved in this research. Therefore, ethics approval and consent to participate are not applicable to this context. This study protocol is reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis for Protocols criteria and registered on PROSPERO. Moreover, the integral version of this study protocol is published as a preprint on Research Square. The results of this study will be actively disseminated through peer-reviewed journals and books, international, national and local conference presentations, social media and media in general.

We investigated how nonpain-based exercise therapy intensity (light-to-moderate or vigorous) affects improvements in walking performance and cardiorespiratory fitness of patients with symptomatic lower-extremity peripheral artery disease (PAD). We searched the Embase, MEDLINE, Cochrane, Web of Science, and Google Scholar databases up to April 2021 and included randomized controlled trials reporting training therapies targeting exercise intensity (heart rate, oxygen consumption, or perceived exertion). The main outcomes were walking performance (pain-free [PFWD] and maximal [MWD] walking distance) and cardiorespiratory fitness (V̇O2peak). Secondary subanalyses examined the training modality (walking or other modalities) and the approach (high-intensity interval or moderate-intensity training). A total of 1132 patients were included. Light-to-moderate was superior to vigorous exercise intensity in improving MWD (223 m [95% CI 174 to 271], p < 0.00001; 153 m [95% CI 113 to 193], p < 0.00001; respectively) and PFWD (130 m [95% CI 87 to 173], p < 0.00001; 83 m [95% CI 61 to 104], p < 0.00001; respectively). When training modalities were considered, walking at a vigorous intensity (272 m [95% CI 207 to 337], p < 0.00001) showed the largest improvement in MWD compared to other exercise modalities. A larger increase in V̇O2peak was observed following vigorous (3.0 mL O2·kg−1·min−1 [95% CI 2.4 to 3.6], p < 0.00001) compared to light-to-moderate (1.1 mL O2·kg−1·min−1 [95% CI 0.4 to 1.7], p = 0.001) exercise intensity. These results indicate that vigorous was less effective than light-to-moderate intensity in improving walking performance, whereas it was more effective in improving V̇O2peak. When the training modalities were considered, walking at a vigorous intensity showed the greatest improvement in MWD. (PROSPERO Registration No.: CRD42020199469)