Comparative effectiveness of primary tumor resection versus chemotherapy in patients with asymptomatic unresectable metastatic colorectal cancer: a retrospective cohort study using the target trial emulation framework.

Patients who undergo primary tumor resection (PTR) reportedly have significantly higher overall survival (OS) than those who do not undergo this procedure. However, this result is only evident in past retrospective studies, and clinical trial results did not show the same trend. Thus, it remains unclear whether primary tumor resection effectively increases survival in patients with metastatic colorectal cancer (mCRC) across different study designs. We compared the OS of patients with asymptomatic unresectable mCRC who underwent PTR with that of those who did not. This retrospective cohort study was designed to be a target trial emulation of a randomized controlled trial (RCT) that would have compared the effectiveness of PTR versus non-PTR in patients with asymptomatic unresectable mCRC from 2009 to 2017. A systematic review and meta-analysis were conducted to compare the efficacy of PTR and non-PTR in patients with mCRC, and corresponding results were compared. This cohort included 1,132 patients for a per-protocol analysis. The PTR group had non-significantly longer survival (adjusted hazard ratio: 0.70, 95% confidence interval: 0.62-1.01) than the non-PTR group in our cohort. A meta-analysis including five RCTs (1,016 patients) and our cohort found that the PTR group did not have a significantly lower mortality rate than the non-PTR group. The results of this cohort study and previous RCTs suggest that PTR is not associated with improved survival compared to systemic chemotherapy combined with targeted therapy among asymptomatic unresectable mCRC patients. Therefore, routine PTR is not recommended in these patients.

Explanatory Role of Conversion Surgery as a Mediator of the Mortality Risk Difference Between Patients With Unresectable Metastatic Colorectal Cancer Treated With First-Line Anti-EGFR Agents Versus Bevacizumab.

INTRODUCTION: Bevacizumab and antiepidermal growth factor receptor-blocking (anti-EGFR) agents plus chemotherapy are first-line therapies for metastatic colorectal cancer (mCRC). Conversion surgery may improve outcomes; however, the extent to which it explains the difference in mortality rates among treatments is unclear. Herein, we aimed to assess the effects of conversion surgery on survival outcomes of patients with unresectable mCRC treated with bevacizumab and anti-EGFR agents. MATERIALS AND METHODS: This retrospective cohort study included patients with mCRC treated with bevacizumab and anti-EGFR agents as first-line therapy. We estimated the direct and indirect effects of treatments by comparing the mortality risk associated with targeted therapy type. Hazard ratios (HR) and the corresponding confidence intervals (CI) were estimated. Mediation analysis was used to estimate hazard ratio differences, and the proportion mediated. RESULTS: A total of 5,106 patients were included. The natural indirect effect of conversion surgery reduced mortality risk (HR: 0.95; 95% CI, 0.93-0.97), with a mediated proportion of 42% after propensity score adjustment. In subgroup analyses, KRAS wild-type (HR: 0.94; 95% CI: 0.91-0.97), left tumor sidedness (HR: 0.94; 95% CI, 0.91-0.96), and liver resection (HR: 0.95; 95% CI, 0.93-0.98) were associated with reduced risks of mortality. The controlled and total direct effects of targeted therapy were associated with reduced mortality risk in the anti-EGFR-treated group compared to those in the bevacizumab-treated group; however, this effect was not statistically significant. CONCLUSION: Conversion surgery may account for the difference in survival outcomes between users of the anti-EGFR agents and bevacizumab.

Comparative Analysis of Out-of-Hospital Cardiac Arrest Outcomes in Health Clinics, Nursing Homes, and Public Places: Implications for Optimizing Automated External Defibrillator Strategies.

Purpose: Various factors, such as event location and response time, influence the outcomes of out-of-hospital cardiac arrest (OHCA). Very few studies have explored the delivery of basic life support (BLS) to patients having OHCA at health clinics or nursing homes-settings with professional BLS providers. Thus, in this study, we compared prognostic and survival outcomes between health clinics, nursing homes, and other public places (eg, workplaces and sports facilities/recreational areas) to offer insights for optimizing OHCA outcomes. Patients: This study included adults who had nontraumatic OHCA in Taoyuan City between January 2017 and December 2022. Methods: We collected data on patient characteristics, emergency medical service parameters, onsite patient management, automated external defibrillator (AED) locations, OHCA prognosis, and survival outcomes. Multivariate analyses were performed to predict survival to discharge (primary outcome) and neurological outcomes at discharge (secondary outcome). Results: During the study period, the numbers of OHCA events at health clinics, nursing homes, and other public places were 158, 208, and 1986, respectively. The mean age of OHCA in health medical clinics, nursing home and other public places were 63.4, 81.5 and 64.7, respectively (P value<0.001). The proportion of witnessed events, rate of bystander resuscitation, and frequency of AED utilization were the highest for health clinics (53.2% (84/158), 83.4% (132/158), and 13.3% (21/158), respectively, P value<0.001). The average AED-scene distances and response times were the lowest for health clinics (388.8 m and 5.4 min, respectively). In initial shockable rhythm group, the probabilities of survival to discharge at discharge were the highest for health clinics (aOR=1.41, 95% CI=1.04-1.81, P value=0.041)) and lowest for nursing homes (aOR=0.84, 95% CI=0.76-0.93, P value=0.024). Conclusion: Our research shows that OHCA patients at medical health clinics have higher rates of witnessing and bystander CPR and AED usage than other public places. However, while survival rates for patients with shockable rhythms are slightly better at health clinics, the neurological outcomes are not significantly different. The AED-scene distances are too far to be used effectively.

Assessing the effectiveness of targeted agents in adjuvant therapy for patients with metastatic colorectal cancer undergoing surgical resection: a retrospective cohort study.

Background: Primary tumor resection and metastasectomy may be beneficial for many patients with metastatic colorectal cancer (mCRC). Objective: To assess the differences in postoperative survival outcomes between adjuvant therapy with chemotherapy alone and chemotherapy plus targeted agents (TAs). Design: Retrospective cohort study. Methods: Patients with mCRC who underwent surgical resection for primary colorectal tumor and distant metastases and received adjuvant therapy from 1 January 2010 to 31 December 2017 were enrolled in the Taiwan Cancer Registry. We analyzed the overall survival of patients with resectable or initially unresectable mCRC who received adjuvant chemotherapy alone and chemotherapy plus TAs. Results: We enrolled 1124 and 542 patients with resectable and initially unresectable mCRC, respectively. Adjuvant chemotherapy plus TAs and chemotherapy alone resulted in similar mortality rates among patients with resectable mCRC [adjusted hazard ratio (aHR) = 1.13; 95% confidence interval (CI), 0.93-1.36]; however, it marginally reduced the mortality rate among patients with initially unresectable mCRC who underwent conversion surgery after neoadjuvant therapy (aHR = 0.81; 95% CI, 0.62-1.06). The subgroup analysis of patients who received more than nine cycles of TAs preoperatively and anti-epidermal growth factor receptor agents revealed aHRs of 0.48 (95% CI, 0.27-0.87) and 0.33 (95% CI, 0.18-0.60), respectively. Conclusion: Adjuvant chemotherapy plus TAs may improve survival in patients with initially unresectable tumors who underwent conversion surgery following neoadjuvant therapy with TAs, especially in those who respond well to the targeted therapy. Our study underscores the importance of stratifying patients with mCRC based on tumor resectability when selecting the adjuvant therapy regimen.

Comparative Effectiveness of Adjuvant Therapy on Survival in Patients With Metastatic Colorectal Cancer.

BACKGROUND/AIM: Postoperative survival outcomes are crucial in treatment decision making. This study aimed to compare the efficacy of adjuvant chemotherapy (AC)-alone with that of chemotherapy + targeted agents (CTA) in patients with metastatic colorectal cancer (mCRC) and to investigate the association between neoadjuvant therapy and survival. PATIENTS AND METHODS: Patients who underwent primary tumor excision and metastasectomy were identified in the Taiwan Cancer Registry from 2010 to 2019. The analysis assessed the influence of adjuvant therapy on survival and examined the interactions between adjuvant therapy types (AC-alone and CTA) and patient characteristics with respect to overall survival. RESULTS: Overall, 1,728 and 757 patients received AC alone and CTA, respectively. Compared to AC alone, adjuvant CTA yielded similar mortality after surgery [hazard ratio (HR)=1.03; 95% confidence interval (CI)=0.91-1.17] but resulted in marginally reduced mortality among patients treated with neoadjuvant therapy with targeted agents (HR=0.6; 95%CI=0.34-1.05) after propensity score matching. In patients with mCRC, those who received targeted agents preoperatively and postoperatively in combination with AC had the highest mortality rate (HR=1.75; 95%CI=1.33-2.32). CONCLUSION: Overall survival is comparable between adjuvant CTA and AC alone, but adjuvant CTA may be more beneficial in patients with mCRC who undergo neoadjuvant therapy with targeted agents.

Comparative Effectiveness of Cetuximab Versus Panitumumab in Patients With Metastatic Colorectal Cancer: A Nationwide Database Study.

BACKGROUND/AIM: The study aimed to determine the effectiveness of cetuximab and panitumumab on the survival of patients with metastatic colorectal cancer or those who had undergone conversion surgery and to identify their prognostic factors. PATIENTS AND METHODS: This retrospective cohort study used data from patients with metastatic colorectal cancer who received cetuximab or panitumumab as first-line targeted agent-based therapy. Overall survival and conversion surgery rates were evaluated, and the prognostic factors were determined. RESULTS: A total of 1,749 and 318 patients received cetuximab or panitumumab with chemotherapy, respectively. Overall survival and conversion surgery rates were similar between the cetuximab [hazard ratio (HR)=0.96] and panitumumab groups (HR=1.00). The prognostic factors associated with metastasectomy significantly lowered mortality among patients with metastatic colorectal cancer (HR=0.61). Older age (≥70 years), tumor stage 4B and 4C, right-sided tumors, mucinous adenocarcinoma, primary tumor resection, and the number of positive lymph nodes were associated with higher mortality and lower conversion surgery rates. CONCLUSION: Though panitumumab- and cetuximab-based therapies showed no differences, several factors, such as age over 70 years old, tumor stage 4B and 4C, undifferentiated carcinoma, mucinous carcinoma, right-sided tumor, number of positive lymph nodes, obstruction, and primary tumor resection increased the mortality risk of patients. This study underscores the importance of metastasectomy in current treatment guidelines and future clinical trials.

Risk factors for acute kidney injury after high-dose methotrexate therapy: a single-center study and narrative review.

PURPOSE: To assess the risk factors associated with high-dose methotrexate (HDMTX) (≥ 1 g/m2) treatment-induced acute kidney injury (AKI). METHODS: Patients who received HDMTX from July 2014 to August 2019 in one medical center were enrolled. The patients' demographic, laboratory, and medication data were collected and compared between groups with or without AKI. Risk factors of HDMTX-induced AKI were explored using univariate and multivariate logistic regression analyses. Additionally, we searched and summarized previous studies to identify key correlates of AKI in a narrative review. RESULTS: We enrolled 59 patients who had received 200 HDMTX courses. The incidence of HDMTX-induced nephrotoxicity was 9.5%. Multivariate logistic regression revealed that male sex (odds ratio [OR], 4.20; P = .037), and angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) (OR, 5.18; P = .016) were significantly associated with AKI. Diuretics with urinary acidification, such as loop diuretics, were also a key factor in AKI (OR, 4.91; P = .018). Furthermore, a forest plot identified 21 predictors from nine additional cohort studies showing correlations with the development of AKI. CONCLUSION: Male sex, ACEIs/ARBs, and diuretics with urinary acidification are associated with AKI. Furthermore, laboratory data should be monitored to assess AKI risk before HDMTX therapy, especially in elderly patients with obesity, diabetes, or acute lymphoblastic leukemia.

Mortality of patients with metastatic colorectal cancer who received elective or emergent operation after exposure to bevacizumab: A nationwide database study.

INTRODUCTION: Treatment guidelines for colorectal cancer (CRC) indicate that surgical intervention within 4 weeks or 8 weeks after bevacizumab therapy might increase the risk of postoperative complications and mortality, especially in patients who received emergent operation. Therefore, we aimed to assess the association between different surgical timings, emergent or elective surgery, and the risk of postoperative mortality. MATERIALS AND METHODS: Using the Taiwan National Health Insurance Database and Taiwan Cancer Registry, we identified patients with metastatic colorectal cancer (mCRC) who underwent surgery within 1 year of receiving bevacizumab between January 2010 and December 2017. The primary outcomes were 30-day, 60-day, and in-hospital mortality; the secondary outcomes were hospital stay, 30-day readmission rate, and surgical complications. Multivariate analysis was used to adjust for confounders. RESULTS: This study included 2,047 patients. In the multivariate analysis, patients who underwent emergent operation and had higher Charlson scores had a significantly higher mortality rate. Patients with a longer interval to surgery, more cycles of bevacizumab treatment, and distal metastectomy had the opposite result. In subgroup analysis, patients who received emergent operation within 28 days had the highest surgical mortality. CONCLUSIONS: The interval to operation among mCRC patients who receive bevacizumab treatment should exceed 4 weeks to avoid additional risk of mortality whether patients receiving elective or emergent operation. Patients who received emergent operation within 28 days of bevcizumab infusion had the highest risk of mortality.

Revising Vital Signs Criteria for Accurate Triage of Older Adults in the Emergency Department.

Objective: Because of physiologic changes in older adults, their vital signs need to be assessed differently. This study aimed to determine appropriate vital sign cut points for triage designation in older patients presented to the emergency department (ED). Patients and Methods: Data from 78,524 ED visits of patients aged ≥65 years in Linkou Chang Gung Memorial Hospital (LCGMH) between 2016 and 2017 were collected. New cut points for vital signs (systolic blood pressure [SBP], heart rate [HR], body temperature [BT], and Glasgow Coma Scale [GCS]) were determined using the critical event rate (the composite of admission to ICU and mortality in hospital) for each vital sign. The newly proposed triage scale was then validated using two other databases (Chang Gung Research Database [CGRD] and Taipei City Hospital [TPECH] database). The Taiwan Triage and Acuity Scale (TTAS) was used in this study. Results: In the LCGMH derivation group, older patients presenting with SBP < 80 mmHg, HR < 40 or > 140 beats per minute (bpm), BT < 35°C, and GCS score 3-8 had a critical event rate of >20% and were proposed to be uptriaged to TTAS level 1. Following a reclassification, a portion of older patients are uptriaged by the newly proposed TTAS, and increase in the critical event rate in TTAS level 1 and level 2 groups compared to the existing TTAS. The newly proposed TTAS exhibited comparable discriminatory ability for triage in older patients compared to the existing TTAS (the area under the receiver operating characteristics curve: CGRD, 0.76 vs 0.62; TPECH, 0.71 vs 0.59). Conclusion: Revising the vital signs triage criteria for older patients could be a way to improve the identification of patients with critical event outcomes in high TTAS level, thereby improving triage accuracy among older patients visiting the ED.

Comparative Effectiveness of Bevacizumab versus Cetuximab in Metastatic Colorectal Cancer Patients without Primary Tumor Resection.

Primary tumor resection may be unfeasible in metastatic colorectal cancer. We determined the effects of bevacizumab and cetuximab therapies on survival or conversion surgery in patients with metastatic colorectal cancer who did not undergo primary tumor resection. This retrospective cohort study enrolled 8466 patients who underwent first-line bevacizumab- or cetuximab-based therapy. We analyzed the data of both therapies in patients who did not undergo primary tumor resection. Overall survival after targeted therapy plus chemotherapy was assessed. The groups were matched using propensity score matching and weighting. Cetuximab resulted in lower mortality than bevacizumab (hazard ratio (HR) = 0.75); however, it did not have the same effect in patients that underwent primary tumor resection (HR = 0.95) after propensity score weighting. Among patients treated with targeted agents, primary tumor resection was associated with lower mortality among those who received both bevacizumab (HR = 0.60) and cetuximab (HR = 0.75). Among patients that did not undergo primary tumor resection, multivariable analysis for conversion surgery showed that the cetuximab group (HR = 1.82) had a significantly higher metastasectomy rate. In these patients, cetuximab-based therapy was associated with significantly better survival compared with bevacizumab-based therapy. Cetuximab also yielded a higher conversion surgery rate. These findings demonstrate the importance of stratification by primary tumor resection in the application of current treatment guidelines and initiation of future clinical trials.

Shared decision-making and patient decision aids in choosing first-line targeted therapy for metastatic colorectal cancer in Taiwan.

INTRODUCTION: In Taiwan, given the discrepancy between current treatment guidelines and reimbursement options, patients might require a tool to support their decision-making process when selecting a regimen for metastatic colorectal cancer, especially therapeutic strategies, and subsequent costs, along with efficacy and safety outcomes. Therefore, we developed a patient decision aid (PDA) to support patients in choosing between treatment options recommended based on the current evidence and those reimbursed by the Taiwanese National Health Insurance. METHODS: By carefully reviewing the updated data and then interpreting the clinical tool, we conducted a needs assessment using a serial questionnaire to test for a step-by-step adjustment of the PDA. RESULTS: Patients, their relatives, and medical team members were most concerned about outcomes, such as overall survival, progression-free survival, objective response rate, tumor shrinkage to resectable status, total medical cost, severe gastrointestinal perforation, and severe skin reaction. After a serial alpha test for quality, we performed quantitative evaluation and beta tests, revealing average scores of more than 4 points (on a scale of 1-5) for both perceptibility and utility. CONCLUSIONS: The present findings suggest that PDAs are useful and supplement the shared decision-making practice, helping patients make decisions about preferences and consider the pros and cons of treatment regimens, along with insurance reimbursement options.

Optimal Sequence and Second-Line Systemic Treatment of Patients with RAS Wild-Type Metastatic Colorectal Cancer: A Meta-Analysis.

Although several sequential therapy options are available for treating patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), the optimal sequence of these therapies is not well established. A systematic review and meta-analysis of 13 randomized controlled trials and 4 observational studies were performed, resulting from a search of the Cochrane Library, PubMed, and Embase databases. Overall survival (OS) did not differ significantly in patients with RAS-WT failure who were administered a second-line regimen of changed chemotherapy (CT) plus anti-epidermal growth factor receptor (EGFR) versus only changed CT, changed CT plus bevacizumab versus changed CT plus anti-EGFR, or changed CT versus maintaining CT plus anti-EGFR after first-line therapy with CT, plus bevacizumab. However, OS was significantly different with a second-line regimen that included changed CT plus bevacizumab, versus only changing CT. Analysis of first-line therapy with CT plus anti-EGFR for treatment of RAS-WT mCRC indicated that second-line therapy of changed CT plus an anti-EGFR agent resulted in better outcomes than changing CT without targeted agents. The pooled data study demonstrated that the optimal choice of second-line treatment for improved OS was an altered CT regimen with retention of bevacizumab after first-line bevacizumab failure. The best sequence for first-to-second-line therapy of patients with RAS-WT mCRC was cetuximab-based therapy, followed by a bevacizumab-based regimen.

Efficacy and Safety of Direct Oral Anticoagulants vs Warfarin in Patients with Chronic Kidney Disease and Dialysis Patients: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Systematic reviews and meta-analyses of direct oral anticoagulants (DOACs) for patients with chronic kidney disease (CKD) or dialysis patients are lacking. We aimed to compare the efficacy and safety of DOACs and warfarin in patients with CKD requiring anticoagulation therapy. METHODS: We performed a systematic review and meta-analysis of six randomized controlled trials and 19 observational studies, with the inclusion criteria being a comparative study between DOACs and warfarin in patients with CKD or dialysis patients from database inception until August 2020. The efficacy outcomes were stroke, systemic embolism (SE), or venous thromboembolism (VTE), and the safety outcome was major bleeding. RESULTS: Compared with warfarin, DOACs significantly reduced the risk of stroke/SE/VTE by 22% (hazard ratio [HR] = 0.78, 95% confidence interval [CI] 0.64-0.95) and major bleeding by 17% (HR = 0.83, 95% CI 0.71-0.97). On comparing factor Xa inhibitors and dabigatran with warfarin separately, factor Xa inhibitors significantly reduced the risk of stroke/SE/VTE (HR = 0.78, 95% CI 0.62-0.98) and major bleeding (HR = 0.76, 95% CI 0.64-0.91) overall in patients. Comparing each DOACs with warfarin separately, apixaban was associated with a significantly better risk reduction of stroke/SE/VTE (25% risk reduction) and major bleeding (35% risk reduction) than warfarin. Compared with warfarin, DOACs significantly reduced the risk of stroke, SE, or VTE by 19% (HR = 0.81, 95% CI 0.68-0.97) in patients with CKD stage 3 and significantly lowered the risk of major bleeding by 31% (HR = 0.69, 95% CI 0.56-0.85) in patients with CKD stages 4-5. CONCLUSIONS: In pooled, analyzed randomized controlled trials and observational studies, DOACs were associated with better efficacy in early CKD, as well as similar efficacy and safety outcomes to warfarin in patients with CKD stages 4-5 or dialysis patients. The results of patients with CKD stages 4-5 and dialysis patients were from observational studies. Well-designed randomized controlled trials focused on DOAC use in patients with CKD and dialysis patients are needed. PROSPERO register number: CRD42020150599, 6 February, 2020.

Loading dose and efficacy of continuous or extended infusion of beta-lactams compared with intermittent administration in patients with critical illnesses: A subgroup meta-analysis and meta-regression analysis.

WHAT IS KNOWN AND OBJECTIVE: The role of continuous/extended beta-lactam infusions (CEIs) in improving clinical outcomes among critically ill patients remains controversial. Therefore, we aimed to compare the clinical efficacy of CEI versus intermittent administration (IA) of beta-lactams by performing a systematic review and meta-analysis. METHODS: PubMed, the Cochrane Library and Embase were searched from inception until December 2018 for studies comparing clinical outcomes of CEI versus IA in critically ill patients. The meta-analysis included 18 randomized controlled trials (RCTs) and 13 non-RCTs. RESULTS AND DISCUSSION: For CEI versus IA, the summary relative risk (RR) for overall mortality and clinical cure was 0.82 (95% confidence interval [CI]: 0.72-0.94) and 1.31 (95% CI: 1.15-1.49), respectively. Subgroup and meta-regression analyses of the loading dose revealed a significantly increased clinical cure rate in the loading-dose group (RR: 1.44, 95% CI: 1.22-1.69), which remained significant after adjustments for beta-lactam type, and association between clinical cure and loading dose for clinical cure (RR: 1.47, 95% CI: 1.20-1.80; p = .001). Subgroup analysis of administration type indicated that both groups had low mortality and high clinical cure rates; however, the heterogeneity analysis did not support an association across continuous infusion and extended infusion groups. Subgroup analysis of the Acute Physiology and Chronic Health Evaluation (APACHE) score was conducted; according to APACHE scores ≥ 16, overall mortality and clinical cure significantly differed between CEI and IA. WHAT IS NEW AND CONCLUSION: CEIs with loading-dose treatment may significantly improve the clinical outcomes in critically ill sepsis or septic shock patients.

Tumor sidedness and efficacy of first-line therapy in patients with RAS/BRAF wild-type metastatic colorectal cancer: A network meta-analysis.

We conducted a systemic search of several databases for randomized controlled trials (RCTs) that reported efficacy and safety outcomes of drugs for left-sided and right-sided metastatic colorectal cancer (mCRC), to identify the best available treatment. A network meta-analysis with mixed comparisons was created to interpret the best treatment option using the surface under the cumulative ranking curve. In the left-sided rat sarcoma (RAS) wild-type (WT) mCRC patients, bevacizumab, panitumumab, or cetuximab with chemotherapy groups showed a significantly better objective response rate than the chemotherapy alone group. The progression-free survival (PFS) and overall survival were better with panitumumab or cetuximab with chemotherapy than with chemotherapy alone. In the right-sided RAS WT mCRC patients, PFS for bevacizumab with chemotherapy was significantly better than that for cetuximab with chemotherapy. Cetuximab, closely followed by panitumumab, is the most effective treatment in left-sided RAS WT mCRC. Bevacizumab is more effective in right-sided mCRC.

Antiviral prophylaxis during chemotherapy or immunosuppressive drug therapy to prevent HBV reactivation in patients with resolved HBV infection: a systematic review and meta-analysis.

BACKGROUND: Until recently, the role of antiviral prophylaxis in preventing hepatitis B virus (HBV) reactivation during immunosuppressive therapy or chemotherapy in patients with resolved HBV infection was unclear. The aim of the study reported here was to compare the efficacy of antiviral prophylaxis versus that of non-prophylaxis in resolved HBV-infected patients undergoing chemotherapy or immunosuppressive therapy. METHODS: PubMed, the Cochrane library, and the ClinicalTrials.gov website were searched from inception until December 2017. Studies comparing reactivation in prophylaxis versus non-prophylaxis in patients undergoing immunosuppressive therapy or chemotherapy were included. The meta-analysis was performed to calculate the relative risk (RR) and the pooled estimates. RESULTS: A meta-analysis was conducted of 13 studies (2 randomized controlled trials [RCTs] and 11 cohort studies). The summary RR for HBV reactivation was 0.47 (95% confidence interval [CI] 0.13-1.69) for antiviral prophylaxis versus non-prophylaxis. Both of the RCTs included in the meta-analysis enrolled patients treated with rituximab. Subgroup analyses showed that the two RCTs ± high-quality cohort studies showed a decreased risk of HBV reactivation among the antiviral prophylaxis groups (RCT 1: RR 0.13, 95% CI 0.02-0.70; P = 0.02; RCT 2: 0.28, 95% CI 0.08-0.98; P = 0.05). Subgroup analyses further showed that the cohort studies did not support an association between the antiviral prophylaxis groups and HBV reactivation (RR 0.62, 95% CI 0.14-2.83; P = 0.54); adjusting for confounding factors, such as detectable anti-HBs antibodies, failed to produce a significant association (RR,0.29, 95% CI 0.07-1.28; P = 0.10). CONCLUSION: Our meta-analyses did not show an association between antiviral prophylaxis use and risk of HBV reactivation. As using only the RCTs ± high-quality cohort studies data rendered this association significant, clinicians can consider providing antiviral prophylaxis to patients with resolved HBV infection who are undergoing rituximab-based therapy.

Hepatitis B virus reactivation in patients with resolved hepatitis B virus infection receiving chemotherapy or immunosuppressive therapy.

BACKGROUND: The role of antiviral prophylaxis before chemotherapy or immunosuppressive therapy to prevent hepatitis B virus (HBV) reactivation in patients with resolved HBV infection [hepatitis B surface antigen (HBsAg) negative, hepatitis B core antibody (anti-HBc) positive] is unclear. This study aimed to evaluate the efficacy of prophylactic antiviral therapy and outcomes of HBsAg-negative, anti-HBc-positive patients who received chemotherapy or immunosuppressive therapy. PATIENTS AND METHODS: We retrospectively evaluated the medical records of HBsAg-negative, anti-HBc-positive patients who underwent chemotherapy or immunosuppressive therapy from January 2013 through November 2016 at a single institute in southern Taiwan. RESULTS: Among 1000 included HBsAg-negative, anti-HBc-positive patients, the rate of hepatitis B surface antibody (anti-HBs) seropositivity before chemotherapy or immunosuppressive therapy was 76.6%. Twenty-six patients received a prophylactic oral antiviral agent (one telbuvudine, two lamivudine, 22 entecavir, and one tenofovir). Seven (0.7%) patients were diagnosed with HBV reactivation during or after chemotherapy courses. In multivariate Cox regression analysis, an rituximab-based regimen (hazard ratio: 11.74; 95% confidence interval: 1.62-84.94; P=0.02) and baseline anti-HBs-positive status (hazard ratio: 0.17; 95% confidence interval: 0.04-0.8; P=0.03) were significant predictive factors for HBV reactivation. Among anti-HBs-negative recipients of rituximab-based chemotherapy, HBV reactivation was observed in zero of nine patients who received prophylactic antiviral therapy and three (33.3%) of nine patients who did not. CONCLUSION: Negative anti-HBs status and rituximab-containing regimens are both important factors for predicting chemotherapy or immunosuppressive therapy-related HBV reactivation in patients with resolved HBV infection. Therefore, antiviral prophylaxis should be considered in this patient population.

Comparison of prehospital triage and five-level triage system at the emergency department.

OBJECTIVE: There is lack of scientific evidence regarding the effectiveness of prehospital triage systems. This study compared the two-level Taiwan Prehospital Triage System (TPTS) with the five-level Taiwan Triage and Acuity Scale (TTAS) at ED arrival regarding the prediction of patient outcomes and the utilisation of medical resources. DESIGN: This was a retrospective cohort study. Adult patients transported via the emergency medical service (EMS), who arrived at the ED of a medical centre in northern Taiwan during the study period were enrolled. TTAS acuity levels 1-2 were considered comparable to the designation of 'emergent' by the prehospital TPTS system. The outcomes were analysed by comparing TPTS and TTAS by acuity levels. RESULTS: Among 4430 enrolled patients, 25.2% and 74.8% were classified as emergent and non-emergent by TPTS; 44.1% and 55.9% were classified as levels 1-2 and levels 3-5 by TTAS. Of the TPTS emergent patients, 15.2% were classified as TTAS levels 3-5, whereas 30.4% of TPTS non-emergent transports were classified as TTAS levels 1-2 at the ED. TTAS levels 1-2 showed better predictability than TPTS emergent level for hospitalisation rate with a sensitivity of 70.3% (95% CI 68.3% to 72.2%) versus 41.1% (95% CI 39.0% to 43.2%), and a negative predictive value of 74.8% (95% CI 73.4% to 76.0%) versus 62.6% (95% CI 61.7% to 63.5%). CONCLUSION: The current prehospital triage system is insufficient and inappropriate in classifying patients transported to the ED. The present study offers supporting evidence for the introduction of a five-level triage system to prehospital EMS systems.

Is 15 minutes an appropriate resuscitation duration before termination of a traumatic cardiac arrest? A case-control study.

BACKGROUND: Previous guidelines suggest up to 15 minutes of cardiopulmonary resuscitation (CPR) accompanied by other resuscitative interventions before terminating resuscitation of a traumatic cardiac arrest. The current study evaluated the duration of CPR according to outcome using the model of a county-based emergency medical services (EMS) system in Taiwan. METHODS: This study was performed as a prospectively defined retrospective review from EMS records and cardiac arrest registration between June 2011 and November 2012 in Taoyuan, Taiwan. RESULTS: A total of 396 patients were enrolled. Among the blunt injuries, most incidents were traffic accidents (66.5%) followed by falls (31.5%). Bystander CPR was performed in 34 patients (8.6%). Of the patients, 18.4% were sent to intermediate to advanced level traumatic care hospitals. Although 4.8% of patients survived for 24 hours, only 2.3% survived to discharge, and 0.8% achieved cerebral performance category 1 or 2. Among all patients who developed return of spontaneous circulation (ROSC), 14.3% of ROSC was achieved within 15 minutes since CPR. Except for 1, most patients who developed ROSC over 24 hours but did not survive to discharge received CPR more than 15 minutes. Four of 6 patients who survived to discharge achieved ROSC after CPR for more than 15 minutes (16, 18, 22, and 24 minutes). Three patients discharged with cerebral performance category 1 or 2 received CPR for 6, 16, and 18 minutes, respectively. CONCLUSIONS: Fifteen minutes of CPR before terminating resuscitation is inappropriate for patients undergoing traumatic cardiac arrsests, as longer duration resuscitation increases ROSC and survival.