BACKGROUND:Partial breast irradiation (PBI) is an effective treatment for early-stage breast cancer. However, evidence comparing different PBI modalities is limited. METHODS:This trial emulation uses electronic health records from a multi-state large tertiary health system. Three PBI modalities were compared: proton radiation therapy, photon radiation therapy, and applicator-based brachytherapy. Inverse probability weighting (IPW) was used to balance confounders. The primary outcome was ipsilateral breast recurrence (IBR). RESULTS:Between 2013 and 2023, 1041 women with early-stage breast cancer were treated with PBI. Of these, 1026 patients were included in the analyses. The median age was 66 years; 22.51% had ductal carcinoma in situ (DCIS), and 97.56% were estrogen receptor positive. With median follow-up of 38.2 months, the rate of IBR in the overall group was 3.05% (95% confidence interval [CI] = 1.99% to 4.65%) at 3 years. After IPW, compared with photon PBI, the hazard ratio for IBR for proton PBI was 2.11 (95% CI = 0.70 to 6.33) and for brachytherapy, 3.86 (95% CI = 1.39 to 10.69). Compared with proton PBI, the hazard ratio for IBR for brachytherapy was 1.83 (95% CI = 0.88 to 3.81). IBR risk was similar across PBI modalities for patients with tumor size ≤ 10 mm and in patients treated for DCIS. Among patients with tumor size >10 mm, the hazard ratio for IBR for brachytherapy was 7.64 (95% CI = 1.64 to 35.58) and 3.59 (95% CI = 1.22 to 10.56) relative to photons and protons, respectively. CONCLUSION:PBI with applicator-based brachytherapy was associated with higher IBR than photon or proton PBI in patients with tumor size > 10 mm, suggesting the need for more careful PBI patient selection for this modality.

BACKGROUND:The writing committee from the Society for Vascular Surgery has commissioned this systematic review to support the development of clinical practice guidelines on the management of patients with blunt thoracic aortic injury. METHODS:We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. Pairs of independent reviewers selected and appraised studies addressing seven key questions identified by the Society for Vascular Surgery committee regarding the evaluation and management of patients with blunt thoracic aortic injury. The certainty of evidence was assessed using the GRADE approach. RESULTS:We included 21 studies across seven key clinical questions. For Grade 1 and 2 injuries, thoracic endovascular aortic repair (TEVAR) was associated with higher aortic-related mortality compared with nonoperative management (relative risk [RR], 8.11; 95% confidence interval [CI], 1.25-52.57. Early (<24 hours) TEVAR was associated with higher mortality compared with delayed (>24 hours) intervention (RR, 2.04; 95% CI, 1.45-2.86) with moderate certainty of evidence. There may be an increase in ischemic events when the left subclavian artery is covered and not revascularized, with low certainty of evidence. Intraoperative heparin use during TEVAR was associated with lower mortality (RR, 0.41; 95% CI, 0.23-0.71) with low certainty of evidence. In patients with concurrent traumatic brain injury, early TEVAR (<9 hours) was associated with higher mortality (12.9% vs 6.5%; P = .003) compared with delayed repair with low certainty of evidence. Analysis of imaging surveillance protocols suggested potential benefits of systematic follow-up. For Grade 2 injuries managed nonoperatively, studies demonstrated favorable intermediate-term outcomes with most injuries resolving within 8 weeks. CONCLUSIONS:This systematic review demonstrates a limited evidence base with high uncertainty for numerous patient-important outcomes. The evidence suggests benefits of delayed intervention when feasible, particularly for patients with concurrent injuries. Nonoperative management may be appropriate for lower-grade injuries, whereas the timing of intervention and use of intraoperative anticoagulation may be important factors associated with outcomes in TEVAR. These findings of this evidence synthesis, along with individual patient factors and local expertise, will inform the development of clinical practice guidelines.

Multiple myeloma (MM) treatment outcomes in developing countries may be impacted by resource constraints. This systematic review and meta-analysis evaluated efficacy outcomes of MM treatments across developing regions. Comprehensive searches in five major databases identified 37 eligible studies from Asia, Africa, Latin America, and Eastern Europe. The Newcastle-Ottawa Scale was used to assess risk of bias. Newer novel agents including daratumumab, carfilzomib, and pomalidomide showed limited use across studies. For patients receiving autologous stem cell transplantation (ASCT), the pooled overall survival rate at longest follow-up (2.5-12.5 years) was 62% (95% CI: 48-75%), with high heterogeneity (I²=92%), while the progression-free survival rate at longest follow-up (3-8 years) was 44% (95% CI: 23-67%). Comparative analyses demonstrated ASCT was associated with significantly superior 5-year survival compared to conventional chemotherapy (RR: 1.59; 95% CI: 1.38-1.82). Bortezomib-based regimens showed better outcomes than thalidomide-based therapies (HR for overall survival (OS) at 4 years: 0.73; 95% CI: 0.53-1.0) and alkylating agent-based regimens (HR: 0.48; 95% CI: 0.28-0.83). Despite resource limitations, ASCT and certain novel agents are associated with improved survival outcomes for MM patients in developing countries. However, substantial heterogeneity in outcomes suggests variability in healthcare infrastructure, treatment accessibility, and clinical expertise across these regions.

Objective: To systematically review hospital length of stay (LOS) associated with falls, pressure ulcers, central line–associated bloodstream infections, and surgical site infections and their potential differences before and after the implementation of the hospital-acquired condition (HAC) reduction program (HACRP). Methods: We searched PubMed, Embase, and Cochrane databases from January 1, 2000, to May 26, 2024, for studies examining LOS and health care costs in patients with any of the 4 HACs. Studies included prospective and retrospective cohorts and case-control designs across various clinical settings. Results: Fifty studies involving 45,080,370 patients admitted for medical and surgical conditions met the inclusion criteria, with 1,939,151 patients experiencing 1 or more HACs. Length of stay increased by an average of 5.2 days for falls, 12.9 days for pressure ulcers, 22.1 days for central line–associated bloodstream infections, and 7.9 days for surgical site infections. After HACRP implementation, LOS for falls increased by 4.9 days, whereas LOS for pressure ulcers decreased by 39.1 days. Conclusion: This systematic review presents detailed data on excess LOS for 4 selected HACs across medical, surgical, intensive care unit, and rehabilitation settings over the past 25 years. The varying impact of HACRP on different HACs highlights the need for targeted prevention strategies.

Objective:The objective of this investigation was to evaluate the agreement rate on judgments made using the Murad tool by different systematic review teams.Introduction:Evaluating the methodological quality of case reports and case series is challenging but some tools do exist for this purpose. We leveraged the presence of studies that have been evaluated by different systematic review teams to assess the inter-consensus agreement among different teams on Murad tool domains.Methods:Using a back-citation method, we identified systematic reviews that used the Murad tool and retrieved all the included primary studies. We selected studies that were assessed by more than 1 systematic review team. We calculated observed agreement and Gwet's agreement coefficient on judgments made about each signaling question.Results:We identified 982 systematic reviews that cited the Murad tool and collectively cited 59,080 references. The final data comprised of 81 duplicated case reports and series assessed by more than 1 systematic review team. Overall, the signaling questions had very high observed agreement with 5 of the 8 questions having agreement over 75%. The signaling questions with the highest agreement addressed the adequacy of the ascertainment of the exposure (coefficient 0.959), ascertainment of the outcome (coefficient 0.829), presence of a dose-response gradient (perfect agreement), and clarity of reporting (coefficient 0.755).Conclusion:The current study demonstrates overall high agreement among different systematic review teams that used the Murad tool for appraisal of the same case series and case reports. Leveraging duplicated studies across systematic reviews is a feasible way to retrospectively assess the reliability of the tool.

OBJECTIVE:This systematic review and meta-analysis evaluates the current evidence on the management of intermittent claudication (IC), a prevalent manifestation of peripheral arterial disease (PAD). METHODS:We conducted comprehensive searches of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. We addressed six questions developed by a guideline committee from the Society for Vascular Surgery, addressing pharmacological treatments, exercise regimens, endovascular interventions, and predictors of major adverse cardiovascular, limb-related events, and mortality. RESULTS:The search resulted in 5333 citations, from which we included 73 studies (46 randomized trials). In patients with PAD and IC who had one or more high-risk comorbidities, low-dose rivaroxaban and aspirin were associated with lower risk of major adverse limb events and major adverse cardiovascular events than aspirin alone. In patients who have undergone surgical or endovascular interventions for PAD, the addition of low-dose rivaroxaban to aspirin may improve limb outcomes. Of note, rivaroxaban trials excluded patients at high risk of bleeding. Single antiplatelet agents showed no significant efficacy differences head-to-head in ambulatory patients with IC and had a lower bleeding risk compared with combination therapy or anticoagulation. Home exercise programs were feasible and may be an alternative to supervised exercise in ambulatory patients with IC and in those who had revascularization. Several comorbidities increased the risk of adverse outcomes after revascularization for IC, such as advanced age, diabetes, coronary artery disease, chronic obstructive pulmonary disease, previous interventions, congestive heart failure, infrapopliteal artery involvement, and longer lesion lengths. In patients with IC undergoing endovascular intervention for superficial femoral artery disease, plain balloon angioplasty was associated with worse outcomes than drug elution or stent implantation for intermediate or longer lesions (ie, >5 cm). CONCLUSIONS:This systematic review summarizes the current evidence base for the management of IC, offering insights into the relative benefits and risks of various therapeutic strategies. The findings underscore the need for individualized patient care, considering both the potential benefits and risks associated with different interventions.

BACKGROUND:Widespread use of respiratory protection masks has become a critical component of public health response. OBJECTIVES:This systematic review synthesises the evidence on the acute physiological, cognitive and psychological impacts associated with different types of masks and provides an evidence map of research gaps. METHODS:A comprehensive search from 2000 to 2023 was conducted across multiple databases (MEDLINE, EMBASE, Cochrane databases, Scopus and PubMed). An umbrella systematic overview was conducted for physiological outcomes using existing systematic reviews. We conducted de novo systematic reviews for cognitive and psychological outcomes. Pairs of independent reviewers determined eligibility, extracted data and assessed risk of bias. Certainty at an outcome level was appraised using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS:The search resulted in 13 370 potential citations, leading to the inclusion of nine systematic reviews for physiological outcomes (87 primary studies) and 10 primary studies for cognitive and psychological outcomes (3815 participants), with the majority of participants being healthy adults. Studies evaluating physiological outcomes demonstrated that various types of masks have little to no significant difference in heart rate (surgical mask (mean difference (MD): 0.96 (-1.01 to 2.93)), N95 mask (MD: 1.63 (-2.79 to 6.05)) and cloth mask (MD: -0.94 (-6.39 to 4.52))) or respiratory rate during rest or exercise (surgical mask (MD: -1.35 (-3.00 to 0.29)), N95 mask (MD: 0.10 (-3.10 to 3.29)) and cloth mask (MD: -2.57 (-6.44 to 1.29)) (low certainty for most outcomes)). Mask use may be associated with very small changes in minute ventilation (surgical mask (MD: -13.9 (-20.30 to -7.53)) and N95 mask (MD: -16.3 (-28.7 to -3.9))), tidal volume (surgical mask (MD: -0.14 (-0.23 to -0.05)) and N95 mask (MD: -0.10 (-0.33 to 0.13))), oxygen saturation (surgical mask (MD: -0.59% (-0.87 to -0.30)), N95 mask (MD: -0.35% (-0.75 to 0.05)) and cloth mask (MD: -0.50% (-1.23; 0.24))), carbon dioxide partial pressure (surgical mask (standardised MD (SMD): 1.17 (0.70 to 1.64)) and N95 mask (SMD: 0.43 (0.08 to 0.79))) and exercise performance (surgical mask (SMD: -0.12 (-0.39 to 0.15)), N95 mask (SMD: -0.42 (-0.76 to -0.08)) and cloth mask (SMD: -0.26 (-0.54 to 0.02)) (low certainty for most outcomes)). Studies evaluating cognitive outcomes showed mixed results. Some studies reported reduced mental workload, and others showed no significant effect or decreased performance. The impact on attention, errors and reaction time was variable. These studies were small and at moderate to high risk of bias. Evidence was insufficient to estimate the effect of mask use on psychological outcomes (claustrophobia, depression and anxiety) as these studies were small, non-longitudinal and at high risk of bias. CONCLUSION:This evidence map provides a comprehensive insight into the multifaceted impact of respiratory protection mask use, and highlights the limited certainty in the available body of evidence. This evidence map supports the development of future research agenda.

BACKGROUND AND AIMS:With rapid changes in the management landscape of chronic hepatitis B (CHB), this technical systematic review addresses 4 critical Population, Intervention, Comparator, Outcome (PICO) questions to provide guidance to the formulation of recommendations to the 2025 AASLD practice guideline for management of CHB. APPROACH:The review was reported in accordance with PRISMA guidelines. Outcomes were evaluated across 4 key PICOs: (1) antiviral therapy for prevention of horizontal HBV transmission in high-risk groups, (2) antiviral therapy versus observation for persons in the immune-tolerant phase, (3) discontinuation versus continuation of nucleos(t)ide analogue therapy in HBeAg-negative individuals with undetectable HBV DNA, and (4) hepatocellular carcinoma (HCC) surveillance in non-cirrhotic individuals with HBsAg clearance or co-infections with HCV, HDV, or HIV. RESULTS:For PICO 1, limited evidence suggests antiviral therapy may reduce horizontal transmission risk, though with low certainty. PICO 2 analyses reveal uncertain benefits of treating persons in the immune-tolerant phase, with very low certainty due to heterogeneity and bias. PICO 3 analyses demonstrate that discontinuing antiviral therapy in persons who are HBeAg negative with undetectable HBV DNA increases HBsAg loss rates (OR: 12.65, 95% CI: 1.58-101.51) but carries moderate risks of virologic relapse (OR: 47.17, 95% CI: 2.79-797.35) and clinical flares. PICO 4 analyses on several cohort studies showed that in patients co-infected with HCV, HBV, or HIV, the annual incidence of HCC was higher than the level where screening becomes cost-effective, suggesting that regular liver cancer screening could be beneficial for these patients. CONCLUSIONS:Despite low certainty, the findings support shared decision-making in high-risk horizontal transmission scenarios or in treating individuals in the immune tolerance phase, caution in discontinuing antiviral therapy in virologically suppressed individuals without HBsAg loss, and tailored HCC surveillance for those with co-infection or cirrhosis.

Objective Data extraction from the published literature is the most laborious step in conducting living systematic reviews (LSRs). We aim to build a generalizable, automated data extraction workflow leveraging large language models (LLMs) that mimics the real-world 2-reviewer process.Materials and Methods A dataset of 10 trials (22 publications) from a published LSR was used, focusing on 23 variables related to trial, population, and outcomes data. The dataset was split into prompt development (n = 5) and held-out test sets (n = 17). GPT-4-turbo and Claude-3-Opus were used for data extraction. Responses from the 2 LLMs were considered concordant if they were the same for a given variable. The discordant responses from each LLM were provided to the other LLM for cross-critique. Accuracy, ie, the total number of correct responses divided by the total number of responses, was computed to assess performance.Results In the prompt development set, 110 (96%) responses were concordant, achieving an accuracy of 0.99 against the gold standard. In the test set, 342 (87%) responses were concordant. The accuracy of the concordant responses was 0.94. The accuracy of the discordant responses was 0.41 for GPT-4-turbo and 0.50 for Claude-3-Opus. Of the 49 discordant responses, 25 (51%) became concordant after cross-critique, increasing accuracy to 0.76.Discussion Concordant responses by the LLMs are likely to be accurate. In instances of discordant responses, cross-critique can further increase the accuracy.Conclusion Large language models, when simulated in a collaborative, 2-reviewer workflow, can extract data with reasonable performance, enabling truly "living" systematic reviews.

Background: Suicide is a leading cause of death in young people and an escalating public health crisis. We aimed to assess the effectiveness and harms of available treatments for suicidal thoughts and behaviors in youths at heightened risk for suicide. We also aimed to examine how social determinants of health, racism, disparities, care delivery methods, and patient demographics affect outcomes. Methods: We conducted a systematic review and searched several databases including MEDLINE®, Embase®, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and others from January 2000 to September 2024. We included randomized clinical trials (RCTs), comparative observational studies, and before-after studies of psychosocial interventions, pharmacological interventions, neurotherapeutics, emerging therapies, and combinations therapies. Eligible patients were youths (aged 5 to 24 years) who had a heightened risk for suicide, including youths who have experienced suicidal ideation, prior attempts, hospital discharge for mental health treatment, or command hallucinations; were identified as high risk on validated questionnaires; or were from other at-risk groups. Pairs of independent reviewers selected and appraised studies. Findings were synthesized narratively. Results: We included 65 studies reporting on 14,534 patients (33 RCTs, 13 comparative observational studies, and 19 before-after studies). Psychosocial interventions identified from the studies comprised psychotherapy interventions (33 studies, Cognitive Behavior Therapy, Dialectical Behavior Therapy, Collaborative Assessment and Management of Suicidality, Dynamic Deconstructive Psychotherapy, Attachment-Based Family Therapy, and Family-Focused Therapy), acute (i.e., 1 to 4 sessions/contacts) psychosocial interventions (19 studies, acute safety planning, family-based crisis management, motivational interviewing crisis interventions, continuity of care following crisis, and brief adjunctive treatments), and school/community-based psychosocial interventions (13 studies, social network interventions, school-based skills interventions, suicide awareness/gatekeeper programs, and community-based, culturally tailored adjunct programs). For most categories of psychotherapies (except DBT), acute interventions, or school/community-based interventions, there was insufficient strength of evidence and uncertainty about suicidal thoughts or attempts. None of the studies evaluated adverse events associated with the interventions. The evidence base on pharmacological treatment for suicidal youths was largely nonexistent at the present time. No eligible study evaluated neurotherapeutics or emerging therapies. Conclusion: The current evidence on available interventions intended for youths at heightened risk of suicide is uncertain. Medication, neurotherapeutics, and emerging therapies remain unstudied in this population. Given that most treatments were adapted from adult protocols that may not fit the developmental and contextual experience of adolescents or younger children, this limited evidence base calls for the development of novel, developmentally and trauma-informed treatments, as well as multilevel interventions to address the rising suicide risk in youths.

AbstractBackgroundRisk of bias (RoB) tools are critical in systematic reviews and affect subsequent decision‐making. RoB tools should have adequate interrater reliability and interconsensus agreement. We present an approach of post hoc evaluation of RoB tools using duplicated studies that overlap systematic reviews.MethodsUsing a back‐citation approach, we identified systematic reviews that used the Risk Of Bias In Nonrandomized Studies‐of Interventions (ROBINS‐I) tool and retrieved all the included primary studies. We selected studies that were appraised by more than one systematic review and calculated observed agreement and unweighted kappa comparing the different systematic reviews' assessments.ResultsWe identified 903 systematic reviews that used the tool with 51,676 cited references, from which we eventually analyzed 171 duplicated studies assessed using ROBINS‐I by different systematic reviewers. The observed agreement on ROBINS‐I domains ranged from 54.9% (missing data domain) to 70.3% (deviations from intended interventions domain), and was 63.0% for overall RoB assessment of the study. Kappa coefficient ranged from 0.131 (measurement of outcome domain) to 0.396 (domains of confounding and deviations from intended interventions), and was 0.404 for overall RoB assessment of the study.ConclusionA post hoc evaluation of RoB tools is feasible by focusing on duplicated studies that overlap systematic review. ROBINS‐I assessments demonstrated considerable variation in interconsensus agreement among various systematic reviewes that assessed the same study and outcome, suggesting the need for more intensive upfront work to calibrate systematic reviewers on how to identify context‐specific information and agree on how to judge it.

Large language models (LLMs) may facilitate and expedite systematic reviews, although the approach to integrate LLMs in the review process is unclear. This study evaluates GPT-4 agreement with human reviewers in assessing the risk of bias using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool and proposes a framework for integrating LLMs into systematic reviews. The case study demonstrated that raw per cent agreement was the highest for the ROBINS-I domain of 'Classification of Intervention'. Kendall agreement coefficient was highest for the domains of 'Participant Selection', 'Missing Data' and 'Measurement of Outcomes', suggesting moderate agreement in these domains. Raw agreement about the overall risk of bias across domains was 61% (Kendall coefficient=0.35). The proposed framework for integrating LLMs into systematic reviews consists of four domains: rationale for LLM use, protocol (task definition, model selection, prompt engineering, data entry methods, human role and success metrics), execution (iterative revisions to the protocol) and reporting. We identify five basic task types relevant to systematic reviews: selection, extraction, judgement, analysis and narration. Considering the agreement level with a human reviewer in the case study, pairing artificial intelligence with an independent human reviewer remains required.

Background and Aims: Transient elastography (TE), shear wave elastography, and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F). Approach and Results: A comprehensive search for studies assessing LSM by TE, shear wave elastography, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), using histopathology as the standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV coinfection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults. Conclusions: LSM from TE, shear wave elastography, and MRE shows acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.

Assessing the methodological quality of case reports and case series is challenging due to human judgment variability and time constraints. We evaluated the agreement in judgments between human reviewers and GPT-4 when applying a standard methodological quality assessment tool designed for case reports and series. We searched Scopus for systematic reviews published in 2023–2024 that cited the appraisal tool by Murad et al. A GPT-4 based agent was developed to assess the methodological quality using the 8 signaling questions of the tool. Observed agreement and agreement coefficient were estimated comparing published judgments of human reviewers to GPT-4 assessment. We included 797 case reports and series. The observed agreement ranged between 41.91

BACKGROUND AND AIMS:Blood-based biomarkers have been proposed as an alternative to liver biopsy for noninvasive liver disease assessment in chronic liver disease. Our aims for this systematic review were to evaluate the diagnostic utility of selected blood-based tests either alone, or in combination, for identifying significant fibrosis (F2-4), advanced fibrosis (F3-4), and cirrhosis (F4), as compared to biopsy in chronic liver disease. APPROACH AND RESULTS:We included a comprehensive search of databases including Ovid MEDLINE(R), EMBASE, Cochrane Database, and Scopus through to April 2022. Two independent reviewers selected 286 studies with 103,162 patients. The most frequently identified studies included the simple aspartate aminotransferase-to-platelet ratio index and fibrosis (FIB)-4 markers (with low-to-moderate risk of bias) in HBV and HCV, HIV-HCV/HBV coinfection, and NAFLD. Positive (LR+) and negative (LR-) likelihood ratios across direct and indirect biomarker tests for HCV and HBV for F2-4, F3-4, or F4 were 1.66-6.25 and 0.23-0.80, 1.89-5.24 and 0.12-0.64, and 1.32-7.15 and 0.15-0.86, respectively; LR+ and LR- for NAFLD F2-4, F3-4, and F4 were 2.65-3.37 and 0.37-0.39, 2.25-6.76 and 0.07-0.87, and 3.90 and 0.15, respectively. Overall, the proportional odds ratio indicated FIB-4 <1.45 was better than aspartate aminotransferase-to-platelet ratio index <0.5 for F2-4. FIB-4 >3.25 was also better than aspartate aminotransferase-to-platelet ratio index >1.5 for F3-4 and F4. There was limited data for combined tests. CONCLUSIONS:Blood-based biomarkers are associated with small-to-moderate change in pretest probability for diagnosing F2-4, F3-4, and F4 in viral hepatitis, HIV-HCV coinfection, and NAFLD, with limited comparative or combination studies for other chronic liver diseases.

Introduction: The outcomes of patients diagnosed with multiple myeloma (MM) have improved significantly with the advent of immunomodulatory drugs, proteasome inhibitors, anti-CD38 monoclonal antibodies, and high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT). Further advancements include immune-based approaches such as bispecific antibodies and chimeric antigen T-cell receptor therapy. However, most of these therapies are predominantly available in developed countries, with limited access globally. Our study aimed to ascertain the landscape of interventions being used in developing countries for MM, and their efficacy. Methods: A comprehensive search was conducted on March 13, 2023, using Embase via Elsevier, PubMed, Scopus, CINAHL, and CENTRAL. We included retrospective and prospective studies that were evaluating interventions for patients with plasma cell dycrasias in the developing country setting. We defined developing country according to the United Nations. For comparative studies, we calculated the risk ratio (RR) for binary outcomes such as overall survival (OS) and progression-free survival (PFS), estimating 95% confidence intervals (CIs) and pooling data using the DerSimonian and Laird random effects model. For non-comparative studies, we calculated overall event rates and transformed them using the Freeman-Tukey double arcsine method, then pooled the data using the same random effects model. All statistical analyses were conducted using R version 4.4.0. Results: A total of 448 records were identified, of which 37 studies met the eligibility criteria. The overall risk of bias was moderate. The included studies evaluated induction treatments using doublet and triplet-based therapies, including TD (thalidomide and dexamethasone), VD (bortezomib and dexamethasone), MP (melphalan and prednisone), CTD (cyclophosphamide, thalidomide, and dexamethasone), VTD (bortezomib, thalidomide, and dexamethasone), and VAD (vincristine, doxorubicin, and dexamethasone). Lenalidomide was notably absent in the induction regimens apart from one non-comparative study reported on the use of RVD (lenalidomide, bortezomib, and dexamethasone). Studies were divided into comparative (n=11) and non-comparative groups (n=26). Comparative studies included: HSCT vs. no HSCT, induction with alkylating agents vs. thalidomide or bortezomib, and thalidomide vs. bortezomib or CTD vs. VTD. Lenalidomide use in comparative studies was reported only post-HSCT, compared against observation. High-dose chemotherapy followed by autologous HSCT was commonly utilized, with most studies reporting outcomes for patients who underwent autologous HSCT. Two comparative studies from 2 countries (Colombia and India) compared the overall survival of autologous HSCT in patients diagnosed with MM (N=130) vs. patients who never received ASCT (N=293). At one year of follow-up, there was no significant difference in overall survival (OS) between patients who received autologous HSCT and those who did not (relative risk [RR] = 1.11, 95% CI: 0.93-1.33). However, a significant improvement in OS was observed at five years post-autologous HSCT (RR = 1.59, 95% CI: 1.38-1.82). The pooled estimate for five-year OS in single-arm studies, which included nine cohorts from seven countries (Pakistan, India, Colombia, Algeria, Sri Lanka, Mexico, and Peru), was 62% (95% CI: 48-75). Progression-free survival (PFS) at five years post-HSCT, reported in three cohorts from three countries (India, Algeria, and Mexico), was 44% (95% CI: 23-67). Conclusions: Most of the recent advancements in MM treatment, including immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies, were not widely utilized globally, particularly in developing countries. This limited access is a major issue, hindering the potential improvement in patient outcomes. However, high-dose chemotherapy followed by autologous HSCT showed good outcomes, demonstrating a significant survival advantage at five years follow-up. The lack of survival benefits at one-year post-HSCT may be due to high toxicity and/or limited resources to manage side effects in developing countries. Addressing the disparity in treatment availability is crucial for improving MM management and patient survival globally.

Abstract Introduction Effective pain and anxiety management during the perioperative phase remains a challenge for patients undergoing surgeries and other invasive procedures. The current standard of care involves prescribing analgesics to treat these conditions; however, there has been recent interest in applying multimodal strategies that limit the use of these medications. One such modality is meditation, which has been shown to be effective in alleviating various physical and psychological symptoms in other settings. This systematic review aims to assess how current meditative practices affect perioperative pain and anxiety. Methods We conducted a systematic review of randomized controlled trials following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. A comprehensive literature search was conducted using PubMed MEDLINE, Embase, PsycINFO, APA PsycINFO, EBM Reviews, Scopus, and Web of Science for all available dates. Our primary outcomes of interest were patient‐reported pain and anxiety scores using the Visual Analog Scale, the Brief Pain Inventory, the Depression Anxiety Stress Scale, the State‐Trait Anxiety Inventory (STAI), and the Hospital Anxiety and Depression Scale (HADS). For the HADS and STAI scales, only the anxiety and anxiety‐state subgroups were reported, respectively. Results The literature search yielded 1746 articles. A total of 286 full‐text articles were screened, and 16 studies were included in this systematic review. A total of eight studies assessed pain scores after invasive procedures; five reported improvements in pain scores, and three reported no change after meditative practices. Ten studies assessed anxiety outcomes after invasive procedures: nine reported a decrease in overall anxiety levels as a result of meditation practices while one study reported no change in anxiety scores. Conclusion Data from this limited literature suggests that different meditation practices could be effective in alleviating pain and anxiety within the perioperative phase for patients undergoing various types of invasive procedures. Future prospective studies are needed to determine whether routine meditation in the perioperative setting is effective in mitigating perioperative pain and anxiety.

BACKGROUND AND AIMS:Portal hypertension is a serious complication of cirrhosis, which leads to life-threatening complications. HVPG, a surrogate of portal pressure, is the reference standard test to assess the severity of portal hypertension. However, since HVPG is limited by its invasiveness and availability, noninvasive liver disease assessments to assess portal pressure, especially clinically significant portal hypertension (CSPH), are needed. APPROACH AND RESULTS:We conducted a systematic review of Ovid MEDLINE(R) Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from each database's inception to April 22, 2022. We included only studies in English that examined ≥50 patients in single liver disease etiologies, which compared noninvasive tests (blood and/or imaging) to HVPG for predicting clinically significant portal hypertension (CSPH; defined as HVPG ≥ 10 mm Hg) in patients with chronic liver disease. Outcomes included measures of diagnostic test accuracy. Additionally, a narrative review of studies not eligible for the systematic review is also provided. Nine studies with 2492 patients met the inclusion criteria. There was substantial heterogeneity with regard to liver disease studied and cutoff values used to detect CSPH. Blood-based tests, including aspartate-to-platelet ratio index (APRI) (56% sensitivity and 68% specificity) and FIB-4 (54% sensitivity and 73% specificity) had low accuracy measures. Imaging-based tests (transient elastography and shear wave elastography detection of liver stiffness measurement [LSM]) had better accuracy but also had substantial variation; at 15 kPa, TE sensitivity was 90%-96% and specificity was 48%-50%, while at 25 kPa, its sensitivity and specificity were 57%-85% and 82%-93%, respectively. The narrative review suggested that imaging-based tests are the best available noninvasive liver disease assessment to detect CSPH; CSPH is highly unlikely to be present at an LSM ≤15 kPa and likely to be present at an LSM ≥25 kPa. CONCLUSIONS:While imaging-based noninvasive liver disease assessment appeared to have higher accuracy than blood-based tests to detect CSPH, only 9 studies fit the a priori established inclusion criteria for the systematic review. In addition, there was substantial study heterogeneity and variation in cutoffs for LSM to detect CSPH, limiting the ability to establish definitive cutoffs to detect CSPH.