Late mortality among 5-year survivors of childhood cancer: A systematic review and meta-analysis.

BACKGROUND: Childhood cancer survivors are at increased risk of late mortality (death ≥5 years after diagnosis) from cancer recurrence and treatment-related late effects. The authors conducted a systematic review and meta-analysis to provide comprehensive estimates of late mortality risk among survivors internationally and to investigate differences in risk across world regions. METHODS: Health sciences databases were searched for cohort studies comprised of 5-year childhood cancer survivors in which the risk of mortality was evaluated across multiple cancer types. Eligible studies assessed all-cause mortality risk in survivors relative to the general population using the standardized mortality ratio (SMR). The absolute excess risk (AER) was assessed as a secondary measure to examine excess deaths. Cause-specific mortality risk was also assessed, if reported. SMRs from nonoverlapping cohorts were combined in subgroup meta-analysis, and the effect of world region was tested in univariate meta-regression. RESULTS: Nineteen studies were included, and cohort sizes ranged from 314 to 77,423 survivors. Throughout survivorship, SMRs for all-cause mortality generally declined, whereas AERs increased after 15-20 years from diagnosis in several cohorts. All-cause SMRs were significantly lower overall in North American studies than in European studies (relative SMR, 0.63; 95% confidence interval, 0.49-0.80). SMRs for subsequent malignant neoplasms and for cardiovascular, respiratory, and external causes did not vary significantly between world regions. CONCLUSIONS: The current findings suggest that late mortality risk may differ significantly between world regions, but these conclusions are based on a limited number of studies with considerable heterogeneity. Reasons for regional differences remain unclear but may be better elucidated through future analyses of individual-level data.

Safety and immunogenicity of the live-attenuated varicella vaccine in pediatric solid organ transplant recipients: A systematic review and meta-analysis.

This study aimed to synthesize the available evidence on the immunogenicity, safety, and effectiveness of live-attenuated varicella vaccine in solid organ transplant recipients. Medline and EMBASE were searched using predefined search terms to identify relevant studies. The included articles reported varicella vaccine administration in the posttransplant period in children and adults. A pooled proportion of transplant recipients who seroconverted and who developed vaccine-strain varicella and varicella disease was generated. Eighteen articles (14 observational studies and 4 case reports) were included, reporting on 711 transplant recipients who received the varicella vaccine. The pooled proportion was 88.2% (95% confidence interval 78.0%-96.0%, 13 studies) for vaccinees who seroconverted, 0% (0%-1.2%, 13 studies) for vaccine-strain varicella, and 0.8% (0%-4.9%, 9 studies) for varicella disease. Most studies followed clinical guidelines for administering live-attenuated vaccines, with criteria that could include being at least 1 year posttransplant, 2 months postrejection episode, and on low-dose immunosuppressive medications. Varicella vaccination in transplant recipients was overall safe in the included studies, with few cases of vaccine-strain-induced varicella or vaccine failure, and although it was immunogenic, the proportion of recipients who seroconverted was lower than that seen in the general population. Our data support varicella vaccination in select pediatric solid organ transplant recipients.

Long-term Outcomes of Pediatric Living Versus Deceased Donor Liver Transplantation Recipients: A Systematic Review and Meta-analysis.

Living donor liver transplantation (LDLT) emerged in the 1980s as a viable alternative to scarce cadaveric organs for pediatric patients. However, pediatric waitlist mortality remains high. Long-term outcomes of living and deceased donor liver transplantation (DDLT) are inconsistently described in the literature. Our aim was to systematically review the safety and efficacy of LDLT after 1 year of transplantation among pediatric patients with all causes of liver failure. We searched the MEDLINE, Medline-in-Process, MEDLINE Epub Ahead of Print, Embase + Embase Classic (OvidSP), and Cochrane (Wiley) from February 1, 1947 to February 26, 2020, without language restrictions. The primary outcomes were patient and graft survival beyond 1 year following transplantation. A meta-analysis of unadjusted and adjusted odds and hazard ratios was performed using a random-effects model. A total of 24 studies with 3677 patients who underwent LDLT and 9098 patients who underwent DDLT were included for analysis. In patients with chronic or combined chronic liver failure and acute liver failure (ALF), 1-year (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.53-0.88), 3-year (OR, 0.73; 95% CI, 0.61-0.89), 5-year (OR, 0.71; 95% CI, 0.57-0.89), and 10-year (OR, 0.42; 95% CI, 0.18-1.00) patient and 1-year (OR, 0.50; 95% CI, 0.35-0.70), 3-year (OR, 0.55; 95% CI, 0.37-0.83), 5-year (OR, 0.5; 95% CI, 0.32-0.76), and 10-year (OR, 0.26; 95% CI, 0.14-0.49) graft survival were consistently better in LDLT recipients compared with those in DDLT recipients. In patients with ALF, no difference was seen between the 2 groups except for 5-year patient survival (OR, 0.60; 95% CI, 0.38-0.95), which favored LDLT. Sensitivity analysis by era showed improved survival in the most recent cohort of patients, consistent with the well-described learning curve for the LDLT technique. LDLT provides superior patient and graft survival outcomes relative to DDLT in pediatric patients with chronic liver failure and ALF. More resources may be needed to develop infrastructures and health care systems to support living liver donation.

Effectiveness of parental education about pain in the neonatal period on knowledge, attitudes, and practices: A systematic review and meta-analysis.

Background: Despite the availability of effective, safe, and feasible pain management strategies, infant pain remains undertreated. Parents can play a key role in advocating for or delivering pain management strategies if they are educated. To date, a quantitative synthesis of the effectiveness of parental education about pain management in the neonatal period has not been performed. Objective: To systematically review the effectiveness of parental education during the neonatal period on pain management in infancy. Methods: MEDLINE, EMBASE, PsycInfo, CINAHL, and the Cochrane Library were searched for relevant randomized controlled trials (RCTs) and non-randomized trials (NRTs) that evaluated parental education with respect to pain management during the neonatal period in any setting from inception to February 2021. Screening of article titles and abstracts and data extraction were performed in duplicate. The risk of bias was assessed using the Cochrane Risk Bias Tool 2.0 and the Risk of Bias in Non-randomized Studies of Interventions for RCTs and NRTs, respectively. As per the GRADE methodology, critically important and important outcomes were identified. Critically important outcomes included utilization of pain management strategies and infant pain. Important outcomes included parental knowledge about pain mitigation strategies, parental attitudes, compliance with painful procedures, procedure outcomes, and safety. Data were combined and presented as relative risk (RR) or mean or standardized mean difference (MD or SMD) with 95% confidence interval (CI). Results: Of the six studies eligible for inclusion, four studies were RCTs and two studies were NRTs. Written information and/or video were used to deliver parental education during the neonatal period in hospital settings in all studies. Four studies (two RCTs and two NRTs) reported on critically important outcomes. The risk of bias was low for the two RCTs and moderate to serious for the two NRTs. Utilization of pain management strategies was assessed for heel lance in the first 48 hours of life in two studies and for vaccine injection at 2 to 6 months of life in two studies. Higher utilization rate for pain management strategies was reported in the pain education group in three studies (RR 1.15, 95% CI 1.04, 1.26; N=2712). There was no difference in the mean number of pain management strategies used in one NRT tracking utilization tracking utilization as continuous data (MD 0.20, 95% CI -0.01, 0.41; N=178). Parent-reported infant pain scores were lower in the pain education group in one RCT (MD -0.16, 95% CI -0.27, -0.06; N=1615). The quality of evidence for the outcome of utilization of pain management strategies was very low while for the outcome of infant pain the quality of evidence was moderate. Five studies (3 RCTs and 2 NRTs) reported on important outcomes. The risk of bias was low for two RCTs and high for one RCT and moderate to serious for the two NRTs. Parental knowledge about pain management strategies (SMD 0.54, 95% CI 0.26, 0.82), parental confidence in their ability to manage pain (SMD 0.24, 95% CI 0.14, 0.34), parental satisfaction with education (MD 1.18, 95% CI 0.84, 1.52) and parental satisfaction with pain management (RR 1.05. 95% CI 1.01, 1.08) were increased in the pain education group. None of the included studies reported on procedural outcomes. No adverse events with the pain education nor the use of pain management interventions were reported in one study. Conclusions: Parental education in the neonatal period was effective in increasing utilization of pain management strategies during painful procedures. Reduction of pain in infants is based on one study of moderate quality. Furthermore, parental education increased parental knowledge about pain management strategies, confidence in their ability to manage infant pain, and satisfaction with the education and pain management. Parental pain education should be incorporated into postnatal care.

The clinical utility of exome and genome sequencing across clinical indications: a systematic review.

Exome sequencing and genome sequencing have the potential to improve clinical utility for patients undergoing genetic investigations. However, evidence of clinical utility is limited to pediatric populations; we aimed to fill this gap by conducting a systematic review of the literature on the clinical utility of exome/genome sequencing across disease indications in pediatric and adult populations. MEDLINE, EMBASE and Cochrane Library were searched between 2016 and 2020. Quantitative studies evaluating diagnostic yield were included; other measures of clinical utility such as changes to clinical management were documented if reported. Two reviewers screened, extracted data, and appraised risk of bias. Fifty studies met our inclusion criteria. All studies reported diagnostic yield, which ranged from 3 to 70%, with higher range of yields reported for neurological indications and acute illness ranging from 22 to 68% and 37-70%, respectively. Diagnoses triggered a range of clinical management changes including surveillance, reproductive-risk counseling, and identifying at-risk relatives in 4-100% of patients, with higher frequencies reported for acute illness ranging from 67 to 95%. The frequency of variants of uncertain significance ranged from 5 to 85% across studies with a potential trend of decreasing frequency over time and higher rates identified in patients of non-European ancestry. This review provides evidence for a higher range of diagnostic yield of exome/genome sequencing compared to standard genetic tests, particularly in neurological and acute indications. However, we identified significant heterogeneity in study procedures and outcomes, precluding a meaningful meta-analysis and certainty in the evidence available for decision-making. Future research that incorporates a comprehensive and consistent approach in capturing clinical utility of exome/genome sequencing across broader ancestral groups is necessary to improve diagnostic accuracy and yield and allow for analysis of trends over time.Prospero registration CRD42019094101.

Clinical and psychological outcomes of receiving a variant of uncertain significance from multigene panel testing or genomic sequencing: a systematic review and meta-analysis.

This study systematically reviewed and synthesized the literature on psychological and clinical outcomes of receiving a variant of uncertain significance (VUS) from multigene panel testing or genomic sequencing. MEDLINE and EMBASE were searched. Two reviewers screened studies and extracted data. Data were synthesized through meta-analysis and meta-aggregation. The search identified 4539 unique studies and 15 were included in the review. Patients with VUS reported higher genetic test-specific concerns on the Multidimensional Impact of Cancer Risk Assessment (MICRA) scale than patients with negative results (mean difference 3.73 [95% CI 0.80 to 6.66] P = 0.0126), and lower than patients with positive results (mean difference -7.01 [95% CI -11.31 to -2.71], P = 0.0014). Patients with VUS and patients with negative results were similarly likely to have a change in their clinical management (OR 1.41 [95% CI 0.90 to 2.21], P = 0.182), and less likely to have a change in management than patients with positive results (OR 0.09 [95% CI 0.05 to 0.19], P < 0.0001). Factors that contributed to how patients responded to their VUS included their interpretation of the result and their health-care provider's counseling and recommendations. Review findings suggest there may be a need for practice guidelines or clinical decision support tools for VUS disclosure and management.

Effect of genetics clinical decision support tools on health-care providers' decision making: a mixed-methods systematic review.

PURPOSE: Patient care involving genetics is challenging for nongenetics health-care providers. Clinical decision support (CDS) tools are a potential solution because they provide patient-specific risk assessments and/or management recommendations. This systematic review synthesized evidence on whether using CDS tools resulted in appropriate changes in genetics-related patient management made by nongenetics health-care providers. METHODS: A comprehensive search in MEDLINE, Embase, and CINAHL yielded 2,239 unique articles. Two independent reviewers screened abstracts and full texts for quantitative, qualitative, and mixed-methods articles on management changes by nongenetics clinicians using a CDS tool as part of patient care. Effect sizes were calculated for quantitative studies and all articles were analyzed together using narrative synthesis. Twenty articles were included. RESULTS: In 12/16 quantitative studies, CDS tools slightly increased appropriate changes in management, but study design appeared to affect the statistical significance of the effect. The qualitative data in the four remaining studies reaffirmed that CDS tools facilitated management decisions but raised questions about their effect on patient outcomes. CONCLUSION: Our review assessed clinical utility of CDS tools, finding that they slightly increase appropriate management changes by nongenetics providers. Future studies on CDS tools should explicitly evaluate decision making and patient outcomes.

Automated movement recognition to predict motor impairment in high-risk infants: a systematic review of diagnostic test accuracy and meta-analysis.

AIM: To assess the sensitivity and specificity of automated movement recognition in predicting motor impairment in high-risk infants. METHOD: We searched MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and Scopus databases and identified additional studies from the references of relevant studies. We included studies that evaluated automated movement recognition in high-risk infants to predict motor impairment, including cerebral palsy (CP) and non-CP motor impairments. Two authors independently assessed studies for inclusion, extracted data, and assessed methodological quality using the Quality Assessment of Diagnostic Accuracy Studies-2. Meta-analyses were performed using hierarchical summary receiver operating characteristic models. RESULTS: Of 6536 articles, 13 articles assessing 59 movement variables in 1248 infants under 5 months corrected age were included. Of these, 143 infants had CP. The overall sensitivity and specificity for motor impairment were 0.73 (95% confidence interval [CI] 0.68-0.77) and 0.70 (95% CI 0.65-0.75) respectively. Comparatively, clinical General Movements Assessment (GMA) was found to have sensitivity and specificity of 98% (95% CI 74-100) and 91% (95% CI 83-93) respectively. Sensor-based technologies had higher specificity (0.88, 95% CI 0.80-0.93). INTERPRETATION: Automated movement recognition technology remains inferior to clinical GMA. The strength of this study is its meta-analysis to summarize performance, although generalizability of these results is limited by study heterogeneity.

An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline: Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome.

BACKGROUND: This document provides evidence-based clinical practice guidelines on the use of mechanical ventilation in adult patients with acute respiratory distress syndrome (ARDS). METHODS: A multidisciplinary panel conducted systematic reviews and metaanalyses of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations. RESULTS: For all patients with ARDS, the recommendation is strong for mechanical ventilation using lower tidal volumes (4-8 ml/kg predicted body weight) and lower inspiratory pressures (plateau pressure < 30 cm H2O) (moderate confidence in effect estimates). For patients with severe ARDS, the recommendation is strong for prone positioning for more than 12 h/d (moderate confidence in effect estimates). For patients with moderate or severe ARDS, the recommendation is strong against routine use of high-frequency oscillatory ventilation (high confidence in effect estimates) and conditional for higher positive end-expiratory pressure (moderate confidence in effect estimates) and recruitment maneuvers (low confidence in effect estimates). Additional evidence is necessary to make a definitive recommendation for or against the use of extracorporeal membrane oxygenation in patients with severe ARDS. CONCLUSIONS: The panel formulated and provided the rationale for recommendations on selected ventilatory interventions for adult patients with ARDS. Clinicians managing patients with ARDS should personalize decisions for their patients, particularly regarding the conditional recommendations in this guideline.

Exposure-based Interventions for the management of individuals with high levels of needle fear across the lifespan: a clinical practice guideline and call for further research.

Needle fear typically begins in childhood and represents an important health-related issue across the lifespan. Individuals who are highly fearful of needles frequently avoid health care. Although guidance exists for managing needle pain and fear during procedures, the most highly fearful may refuse or abstain from such procedures. The purpose of a clinical practice guideline (CPG) is to provide actionable instruction on the management of a particular health concern; this guidance emerges from a systematic process. Using evidence from a rigorous systematic review interpreted by an expert panel, this CPG provides recommendations on exposure-based interventions for high levels of needle fear in children and adults. The AGREE-II, GRADE, and Cochrane methodologies were used. Exposure-based interventions were included. The included evidence was very low quality on average. Strong recommendations include the following. In vivo (live/in person) exposure-based therapy is recommended (vs. no treatment) for children seven years and older and adults with high levels of needle fear. Non-in vivo (imaginal, computer-based) exposure (vs. no treatment) is recommended for individuals (over seven years of age) who are unwilling to undergo in vivo exposure. Although there were no included trials which examined children < 7 years, exposure-based interventions are discussed as good clinical practice. Implementation considerations are discussed and clinical tools are provided. Utilization of these recommended practices may lead to improved health outcomes due to better health care compliance. Research on the understanding and treatment of high levels of needle fear is urgently needed; specific recommendations are provided.

A systematic review of the role of C4d in the diagnosis of acute antibody-mediated rejection.

In this study, we conducted a systematic review of the literature to re-evaluate the role of C4d in the diagnosis of acute antibody-mediated rejection of kidney allografts. Electronic databases were searched until September 2013. Eligible studies allowed derivation of diagnostic tables for the performance of C4d by immunofluorescence or immunohistochemistry with comparison to histopathological features of acute antibody-mediated rejection and/or donor-specific antibody (DSA) assays. Of 3492 unique abstracts, 29 studies encompassing 3485 indication and 868 surveillance biopsies were identified. Assessment of C4d by immunofluorescence and immunohistochemistry exhibited slight to moderate agreement with glomerulitis, peritubular capillaritis, solid-phase DSA assays, DSA with glomerulitis, and DSA with peritubular capillaritis. The sensitivity and specificity of C4d varied as a function of C4d and comparator test thresholds. Prognostically, the presence of C4d was associated with inferior allograft survival compared with DSA or histopathology alone. Thus, our findings support the presence of complement-dependent and -independent phenotypes of acute antibody-mediated rejection. Whether the presence of C4d in combination with histopathology or DSA should be considered for the diagnosis of acute antibody-mediated rejection warrants further study.

Juvenile idiopathic arthritis of the axial joints: a systematic review of the diagnostic accuracy and predictive value of conventional MRI.

OBJECTIVE: Our objective was to evaluate the diagnostic accuracy and reliability of MRI and its ability to depict responsiveness to treatment for the evaluation of the axial joints (temporomandibular joint [TMJ], spinal joints, and sacroiliac joints) in juvenile idiopathic arthritis (JIA). CONCLUSION: There is fair (grade B) evidence that MRI is an accurate diagnostic method for evaluating early and intermediate changes in the TMJ in JIA and insufficient evidence to indicate MRI is an accurate diagnostic method for detecting JIA in the spinal (grade I) and sacroiliac (grade I) joints.

Ondansetron and the risk of cardiac arrhythmias: a systematic review and postmarketing analysis.

STUDY OBJECTIVE: To explore the risk of cardiac arrhythmias associated with ondansetron administration in the context of recent recommendations for identification of high-risk individuals. METHODS: We conducted a postmarketing analysis and systematically reviewed the published literature, grey literature, manufacturer's database, Food and Drug Administration Adverse Events Reporting System, and the World Health Organization Individual Safety Case Reports Database (VigiBase). Eligible cases described a documented (or perceived) arrhythmia within 24 hours of ondansetron administration. The primary outcome was arrhythmia occurrence temporally associated with the administration of a single, oral ondansetron dose. Secondary objectives included identifying all cases associating ondansetron administration (any dose, frequency, or route) to an arrhythmia. RESULTS: Primary: No reports describing an arrhythmia associated with single oral ondansetron dose administration were identified. Secondary: Sixty unique reports were identified. Route of administration was predominantly intravenous (80%). A significant medical history (67%) or concomitant use of a QT-prolonging medication (67%) was identified in 83% of reports. Approximately one third occurred in patients receiving chemotherapeutic agents, many of which are known to prolong the QT interval. An additional third involved administration to prevent postoperative vomiting. CONCLUSION: Current evidence does not support routine ECG and electrolyte screening before single oral ondansetron dose administration to individuals without known risk factors. Screening should be targeted to high-risk patients and those receiving ondansetron intravenously.

Evidence-based outcomes on diagnostic accuracy of quantitative ultrasound for assessment of pediatric osteoporosis - a systematic review.

BACKGROUND: Dual-energy absorptiometry (DXA) is the current reference standard for assessing pediatric osteoporosis; however due to its areal nature, it has limitations. Thus, quantitative ultrasound (QUS), a modality free of ionizing radiation, has been proposed as a potential surrogate for DXA. OBJECTIVE: To semi-quantitatively assess the diagnostic accuracy of QUS for evaluating pediatric osteoporosis according to the U.S. Preventive Services Task Force guidelines. MATERIALS AND METHODS: We retrieved articles on the diagnostic accuracy of quantitative US for assessing abnormal bone quality or quantity in patients of mean age ≤19 years from MEDLINE, EMBASE and Cochrane Library CCTR databases. Evidences were analyzed for reliability, construct and criterion validity, and responsiveness of quantitative US, according to the following questions: (1) How reliable is the acquisition of QUS measurements? (2) Is QUS diagnostically accurate to characterize bone strength and quality in osteoporotic children? (3) Is QUS sensitive to detect changes in bone status over time? (4) Is QUS able to predict future skeletal fractures/degeneration? Three reviewers independently evaluated the quality of reporting and methodological quality using the Standards for Reporting of Diagnostic Accuracy (STARD) and the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tools. RESULTS: Out of 262 retrieved references (215 unique), we included 28 studies (1,963 patients; 807 reported boys and 761 girls, others unspecified; reported mean age, 0-19 years). The mean quality of reporting score was "excellent" in 24/28 (86%) studies; 11/28 (39%) studies had "adequate" research design quality. CONCLUSION: There is no evidence of the diagnostic value of QUS at the present time despite the overall excellent and adequate research design quality of primary studies. Although QUS can produce reliable measurements, insufficient evidence has been reported to support other clinimetric properties of this technique.

Trans health training objectives: A scoping review.

BACKGROUND: Transgender individuals are discriminated against in health care environments and consistently experience poorer health outcomes than their cisgender counterparts. Enhancing physician training in transgender-specific health is critical to closing the transgender health gap. METHODS: We conducted a scoping review to identify transgender health training objectives in Internal Medicine and Internal Medicine Subspecialty residency programmes in Canada and the United States. A systematic search was conducted from 1946 to 15 February 2022. Studies were eligible for inclusion if they were written in English, included transgender training objectives, and were aimed at resident physicians in Internal Medicine or Internal Medicine Subspecialty training programmes in Canada or the United States. FINDINGS: We found 4048 papers, of which 11 were included for analysis. Transgender health training objectives were synthesised into five themes, including (1) terminology, physiology, and gender presentation, (2) gender-affirming care and communication, (3) hormonal and surgical management, (4) routine health management and maintenance, and (5) equity, diversity, and inclusion in clinical care. The majority of objectives pertained to equity, diversity, and inclusion in clinical care, namely, respectful communication and non-judgemental care of transgender patients. DISCUSSION: Our findings provide a comprehensive overview of published transgender health objectives in Canada and the United States and highlight existing gaps in postgraduate medical education for Internal Medicine and Subspecialty programmes. CONCLUSIONS: We argue a need for standardisation of transgender-related residency training and suggest that postgraduate Internal Medicine programmes can utilise this review as a framework to begin enhancing transgender health education for their residents.

How to conduct an annual literature update for top articles relevant to clinical practice in geriatrics: A scoping review.

BACKGROUND: Clinical educators in geriatrics are often tasked with presenting a literature update at annual conferences and scientific meetings, which is a highly regarded continuing medical education (CME) activity. Preparation of an annual literature update cannot rely on bibliometric analysis due to time lag and poor correlation between bibliometrics and expert opinion on clinical relevance. The methodology of how top research articles of the year are selected and presented is not often reported. METHODS: We conducted a scoping review for published reports of a curated selection of recent articles critically appraised for high impact to clinical practice in general geriatrics, published from 2010 to 2022. RESULTS: Six annual literature updates were included for study. Three updates detailed their article sources, ranging from a survey of clinicians, consulting seven individual journals, searching up to four bibliographic databases, scanning social media outlets, and reviewing previous literature updates. One update reported a detailed method of article selection and consensus development. Critical appraisal of articles followed a structured reporting of clinical context, methods, results, and a statement of clinical implication or bottom line. Three of the six updates' results were disseminated in an annual conference update and did not evaluate learning outcomes of the audience. We mapped the results on a four-step framework of article search, selection, critical appraisal, and dissemination of knowledge. CONCLUSIONS: Educators in geriatrics consult numerous article sources spanning multiple journals, databases, social media, and peer suggestions to create an annual literature update. The methodology of article search and selection is inconsistently described. In this exciting area of CME, we encourage educators to develop a framework for conducting annual literature updates in geriatrics and expand its scholarship.

The carbon footprint of critical care: a systematic review.

PURPOSE: The provision of healthcare is a substantial global contributor to greenhouse gas (GHG) emissions. Several medical specialties and national health systems have begun evaluating their carbon emission contributions. The aim of this review is to summarise and describe the carbon footprint resulting from the provision of adult, paediatric and neonatal critical care. METHODS: A systematic search of Embase, Cochrane and Web of Science was performed in January 2023. Studies reporting any assessment of the carbon footprint of critical care were included. No language restrictions were applied. GHG emissions from life cycle assessments (LCA) were reported, in addition to waste, electricity and water use. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was followed. RESULTS: In total, 13 studies assessing and describing the environmental impact of 36 adult or paediatric intensive care units (ICUs) were included. Two studies described full LCAs, seven reported waste only, two provided audits of unused medical supplies, one reported electricity use, and one study described a Material Flow Analysis. The estimated carbon emissions from critical care range between 88 kg CO2e/patient/day and 178 kg CO2e/patient/day. The two predominant sources of carbon emissions in critical care originate from electricity and gas use, as well as consumables. Waste production ranged from 1.1 to 13.7 kg/patient/day in the 6 studies where mean waste could be calculated. CONCLUSION: There is a significant carbon footprint that results from intensive care provision. Consumables and waste constitute important, measurable, and modifiable components of anthropogenic emissions. There remains uncertainty due to a lack of literature, several unstudied areas of carbon emissions from critical care units, and within measured areas, measurement and reporting of carbon emissions are inconsistent.

Is there a role for carboplatin in the treatment of malignant germ cell tumors? A systematic review of adult and pediatric trials.

BACKGROUND: While cisplatin is considered superior to carboplatin for the treatment of malignant germ cell tumors (MGCTs) in adults, pediatric oncology collaborative groups still remain concerned about the late effects of cisplatin in children. METHODS: We performed a literature search to identify randomized controlled trials (RCTs) that used carboplatin for MGCTs in adults. Since no RCTs were available in children, we identified cohort studies of pediatric MGCTs treated with carboplatin. We compared the adult and pediatric studies in terms of characteristics, doses of chemotherapy, and outcomes. RESULTS: Of 2,131 publications retrieved, five RCTs in adults (1,340 patients) and four cohort studies in children (219 patients) met criteria for inclusion. All adult RCTs evaluated carboplatin versus cisplatin regimens in men with good-prognosis metastatic MGCTs. Carboplatin regimens had a higher risk of events (RR 2.51, P < 0.001) and of deaths (RR 2.21, P < 0.001) than cisplatin regimens. Across all five RCTs, 497/654 (76%) of adults who received carboplatin remained event-free. Compared to the adult trials, three pediatric studies used carboplatin at a higher dose, frequency, and number of cycles. Across these three studies, 158/179 (88%) of children remained event-free. CONCLUSIONS: Cisplatin is superior to carboplatin at the studied doses for the treatment of adult metastatic MGCTs. However, we observe that carboplatin is associated with good outcomes for children with MGCT when used at the higher doses. We hypothesize that a risk-adapted approach utilizing both platinum agents may achieve the optimal balance between cure and late effects.

Efficacy of oral iron therapy in improving the developmental outcome of pre-school children with non-anaemic iron deficiency: a systematic review.

OBJECTIVE: To systematically review the efficacy and safety of oral Fe therapy in pre-school children (1­5 years) with non-anaemic Fe deficiency, determined by children's developmental and haematological status and the incidence of reported side-effects. DESIGN: A random-effects model was used to show mean differences with 95% confidence intervals of developmental and haematological scores between Fe-treated and non-treated groups. SETTING: MEDLINE, EMBASE, Cochrane library and bibliographies of identified articles were searched up to September 2011. Randomized and observational studies were assessed by two reviewers independently. Quality of the trials was assessed on the basis of concealment of allocation, method of randomization, masking of outcome assessment and completeness of follow-up. SUBJECTS: From the titles of 743 articles, full text review was completed on forty-six and two randomized trials of acceptable quality met the inclusion criteria. The two trials included a total of sixty-nine children. RESULTS: One study showed a statistically significant difference in the post-treatment Mental Developmental Index score among children who received oral Fe therapy v. no therapy (mean difference56?3, 95% CI 1?5, 11?0, P value not provided). Both studies showed significant improvement in serum ferritin level (mg/l: mean difference551? 1, 95% CI 33?6, 68?6, P,0?01 and mean difference517?1, 95% CI 7?5, 26?6, P value not provided, respectively) in children who received Fe therapy. CONCLUSIONS: Evidence is insufficient to recommend oral Fe therapy to children with non-anaemic Fe deficiency. There is urgent need of conducting adequately powered, randomized trials examining the efficacy of oral Fe therapy in pre-school children with non-anaemic Fe deficiency.

Does this child have bacterial meningitis? A systematic review of clinical prediction rules for children with suspected bacterial meningitis.

BACKGROUND: Acute meningitis is a relatively common phenomenon in children. Identifying which children are most likely to have bacterial meningitis vs. self-limiting aseptic meningitis is important, as these children require investigation and antibiotic treatment. OBJECTIVE: Our aim was to systematically identify and review the quality and performance of published clinical prediction rules (CPRs) for children with suspected bacterial meningitis. METHODS: Medline and Embase were searched for CPRs involving children 0-18 years of age with suspected bacterial meningitis, with cerebral spinal fluid (CSF) culture used as the reference diagnostic standard. CPR quality was assessed using 17 previously published items. CPR performance was evaluated using sensitivity, negative likelihood ratio, and the treatment frequency that would result if the rule was used. RESULTS: Eleven studies involving 6675 children with acute meningitis fulfilled all inclusion criteria and were entered in the study. They all describe the derivation or validation of six unique CPRs. A rigorously developed, high-performing, and well-validated CPR ready for clinical use to guide which children with suspected bacterial meningitis should be hospitalized and treated with intravenous antibiotics and which can be safely discharged home was not identified. Areas for quality improvement for future CPR studies include prospective validation using standardized inclusion criteria, adequate blinding, predictor reproducibility assessment, and meticulous follow-up of outcomes. The Bacterial Meningitis Score had the highest quality and performance and is the best candidate for prospective validation. CONCLUSIONS: Until consistently high methodological quality and diagnostic performance are demonstrated through prospective validation, caution is warranted in the routine clinical use of existing CPRs for children with suspected bacterial meningitis.