Non-pulmonary complications of intrathecal morphine administration: a systematic review and meta-analysis with meta-regression.

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).

Adjustments of iodinated contrast media using lean body weight for abdominopelvic computed tomography: A systematic review and meta-analysis.

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.

Efficacy and safety of intrathecal diamorphine: a systematic review and meta-analysis with meta-regression and trial sequential analysis.

BACKGROUND: Intrathecal diamorphine is believed to provide postoperative analgesia but is associated with adverse effects such as nausea and vomiting. There is little evidence of synthesis regarding intrathecal diamorphine in the contemporary literature. We performed a systematic review, meta-analysis with meta-regression and trial sequential analysis to determine the magnitude of intrathecal diamorphine efficacy and safety. METHODS: We systematically searched the literature for trials comparing intrathecal diamorphine with a control group in patients undergoing all types of surgery. The primary efficacy and safety outcomes were intravenous morphine consumption and incidence of postoperative nausea and vomiting at 24 h following surgery, respectively. RESULTS: Twelve trials were identified, which included data for 712 patients. Intrathecal doses of diamorphine ranged from 100 µg to 2500 µg. Intravenous morphine consumption at 24 h postoperatively was significantly reduced in the intrathecal diamorphine group, with a mean difference (95%CI) of -8 mg (-11 to -6), I2 = 93%, p < 0.001. There was a significant difference between three intrathecal diamorphine dosing subgroups but without correlation: mean differences (95%CI) -1 mg (-3-0), -26 mg (-40 to -11) and -6 mg (-15-4) in patients receiving doses of 0-200 µg, 201-400 µg and > 400 µg, respectively (p = 0.003). Intrathecal diamorphine increased postoperative nausea and vomiting with a risk ratio (95%CI) of 1.37 (1.19-1.58), I2 = 7%, p < 0.001. There were no differences in postoperative nausea and vomiting between the three intrathecal diamorphine dosing subgroups. There was no correlation observed with meta-regression of the primary efficacy and safety outcomes. The quality of evidence for all outcomes was very low. CONCLUSION: There is very low level of evidence that intrathecal diamorphine provides effective analgesia after surgery, while increasing postoperative nausea and vomiting with doses > 200 µg.

Palliative sedation: ethics in clinical practice guidelines - systematic review.

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.

PSTPIP1-Associated Myeloid-Related Proteinemia Inflammatory (PAMI) Syndrome: A Systematic Review.

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.

Major malformations risk following early pregnancy exposure to metformin: a systematic review and meta-analysis.

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) (I2=0%; Q test=0.31; p value=0.58) and OR 1.35 (95% CI 0.37 to 4.90) (I2=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) (I2=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.

Experience of hope in adult patients with advanced chronic disease and their informal caregivers: a qualitative systematic review protocol.

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.

Ethical challenges in palliative sedation of adults: protocol for a systematic review of current clinical practice guidelines.

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.

Assessing the Will to Live: A Scoping Review.

CONTEXT: The will to live (WTL) is an important factor to consider in the context of providing resource-oriented palliative care. Until now, there has been no major review of the existing research on this subject. OBJECTIVES: The primary objective of this study is to summarize the state of research concerning instruments that assess the WTL. The secondary objective is to explore the theoretical models and psychometric properties of these instruments, in studies where these instruments were initially presented. The tertiary objective is to identify, among all studies where these instruments have been used, the intensity of the WTL, and factors associated with it. METHODS: We conducted a scoping review, including studies that were designed to assess the WTL among participants in all settings. Records were systematically searched from seven bibliographic databases with no date limitations up to August 2020. RESULTS: Of the 3078 records screened, 281 were examined in detail and 111 were included in the synthesis. A total of 25 different instruments quantitatively assessing the WTL are presented. Most are single-question tools and rate intensity. The underlying concepts and psychometric properties are incompletely explained. Lack of crossreferencing is apparent. The intensity of the WTL is high, even among people with significant health impairment, and is frequently associated with different factors, such as resilience and quality of life. CONCLUSION: A considerable yet unconnected body of studies assesses the WTL. Its assessment in clinical routine could promote resource-oriented and patient-centered care.

Impact of incarceration on cardiovascular disease risk factors: a systematic review and meta-regression on weight and BMI change.

OBJECTIVE: Cardiovascular disease is an underappreciated issue in prison medicine. Recent studies have revealed a higher prevalence of cardiovascular disease risk factors (CVDRFs) among individuals in prison, but the impact of incarceration on CVDRFs over time is not well understood. This review aimed to assess available literature and quantify the relationship between incarceration and trends in major CVDRFs in high-income countries. DESIGN: Systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Meta-regression on weight change and obesity. DATA SOURCES: Medline, Embase, PubMed, Cochrane Central Wiley and Web of Science. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Longitudinal studies reporting on the incidence of, or trends in any CVDRF among current or former people in prison over time, in high-income countries. DATA EXTRACTION AND SYNTHESIS: Two authors independently screened articles for eligibility, extracted data and assessed quality using an adapted version of the Newcastle-Ottawa Scale. Trends in CVDRFs during and following incarceration were summarised and in those with sufficient data a meta-regression was performed. RESULTS: Twenty-six articles were identified. CVDRFs assessed included obesity, hypertension, diabetes, dyslipidaemia, tobacco use, physical inactivity and unhealthy diet. A meta-regression on change in weight during incarceration found a mean increase of 5.3 kg (95% CI 0.5 to 10.1) and change in body mass index of 1.8 kg/m2 (95% CI -0.9 to 4.6) at 2 years. Weight gain appeared most pronounced right after entering prison and then plateaued at 2 years. Concerning hypertension, the results were inconclusive, despite a trend towards rising blood pressure or prevalence of hypertension during incarceration, and an increased incidence of hypertension following incarceration. Results are contradictory or inconclusive for the other CVDRFs reviewed. CONCLUSION: Possible explanations for the association between incarceration and weight include a sedentary lifestyle, unhealthy diet, forced smoking cessation, psychotropic medication use and high levels of stress. Incarceration may be an independent risk factor for cardiovascular disease.

Experiences of newly diagnosed cancer patients in confronting the finitudes of life: a qualitative systematic review protocol.

REVIEW QUESTION: What is the experience of newly diagnosed patients with cancer when facing the finitude of life and undergoing initial anti-cancer treatment?