Predictors of Persistent Post-Surgical Pain Following Total Knee Arthroplasty: A Systematic Review and Meta-Analysis of Observational Studies.

OBJECTIVE: Approximately one in four total knee replacement patients develop persistent pain. Identification of those at higher risk could help inform optimal management. METHODS: We searched MEDLINE, EMBASE, CINAHL, AMED, SPORTDiscus, and PsycINFO for observational studies that explored the association between risk factors and persistent pain (≥3 months) after total knee replacement. We pooled estimates of association for all independent variables reported by >1 study. RESULTS: Thirty studies (26,517 patients) reported the association of 151 independent variables with persistent pain after knee replacement. High certainty evidence demonstrated an increased risk of persistent pain with pain catastrophizing (absolute risk increase [ARI] 23%, 95% confidence interval [CI] 12 to 35), younger age (ARI for every 10-year decrement from age 80, 4%, 95% CI 2 to 6), and moderate-to-severe acute post-operative pain (ARI 30%, 95% CI 20 to 39). Moderate certainty evidence suggested an association with female sex (ARI 7%, 95% CI 3 to 11) and higher pre-operative pain (ARI 35%, 95% CI 7 to 58). Studies did not adjust for both peri-operative pain severity and pain catastrophizing, which are unlikely to be independent. High to moderate certainty evidence demonstrated no association with pre-operative range of motion, body mass index, bilateral or unilateral knee replacement, and American Society of Anesthesiologists score. CONCLUSIONS: Rigorously conducted observational studies are required to establish the relative importance of higher levels of peri-operative pain and pain catastrophizing with persistent pain after knee replacement surgery.

Virtual reality rehabilitation following total knee arthroplasty: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The use of virtual reality (VR) based rehabilitation has increased substantially within orthopedic surgery, particularly in the field of total knee arthroplasty (TKA). The objective of this systematic review and meta-analysis was to compare patient-reported outcomes and cost analyses from randomized controlled trials (RCT) utilizing VR-based rehabilitation in patients following TKA. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched for RCTs involving VR-based rehabilitation following TKA. Quantitative synthesis was conducted for pain scores and functional outcomes. Narrative outcomes were reported for results not amenable to quantitative synthesis. RESULTS: A total of 9 RCTs with 835 patients were included with follow-up ranging from 10 days to 6 months postoperatively. No differences in pain scores were demonstrated between VR-based and traditional rehabilitation at 2 weeks and 3 months postoperatively. VR-based rehabilitation demonstrated improved functional outcomes at 12 weeks (n = 353) postoperatively [mean difference (MD) - 3.32, 95% confidence interval (CI) - 5.20 to - 1.45, moderate certainty evidence] and 6 months (n = 66) postoperatively [MD - 4.75, 95% CI - 6.69 to - 2.81, low certainty evidence], compared to traditional rehabilitation. One trial demonstrated significant cost savings with the use of VR-based rehabilitation. CONCLUSIONS: VR-based rehabilitation for patients undergoing TKA represents an evolving field that may have advantages over traditional therapy for some patients. The current review is limited by the low quality of evidence in the literature. This is a rapidly evolving field with more trials needed to determine the impact of VR-based rehabilitation on patients undergoing TKA. LEVEL OF EVIDENCE: Level I; meta-analysis of randomized controlled trials.

The effect of antiplatelet therapy on survival and cardiac allograft vasculopathy following heart transplantation: A systematic review and meta-analysis.

Cardiac allograft vasculopathy (CAV) is mediated by endothelial inflammation, platelet activation and thrombosis. Antiplatelet therapy may prevent the development of CAV. This systematic review and meta-analysis summarizes and appraises the evidence on the effect of antiplatelet therapy after heart transplantation (HT). CENTRAL(Ovid), MEDLINE(Ovid), Embase(Ovid) were searched from inception until April 30, 2020. Outcomes included CAV, all-cause mortality, and CAV-related mortality. Data were pooled using random-effects models. Seven observational studies including 2023 patients, mean age 52 years, 22% female, 47% with ischemic cardiomyopathy followed over a mean 7.1 years proved eligible. All studies compared acetylsalicylic acid (ASA) to no treatment and were at serious risk of bias. Data from 1911 patients in 6 studies were pooled in the meta-analyses. The evidence is very uncertain about the effect of ASA on all-cause or CAV-related mortality. ASA may reduce the development of CAV (RR 0.75, 95% CI: 0.44-1.29) based on very low certainty evidence. Two studies that conducted propensity-weighted analyses showed further reduction in CAV with ASA (HR 0.31, 95% CI: 0.13-0.74). In conclusion, there is limited evidence that ASA may reduce the development of CAV. Definitive resolution of the impact of antiplatelet therapy on CAV and mortality will require randomized clinical trials.

Management of Acute Pain From Non-Low Back, Musculoskeletal Injuries : A Systematic Review and Network Meta-analysis of Randomized Trials.

BACKGROUND: Patients and clinicians can choose from several treatment options to address acute pain from non-low back, musculoskeletal injuries. PURPOSE: To assess the comparative effectiveness of outpatient treatments for acute pain from non-low back, musculoskeletal injuries by performing a network meta-analysis of randomized clinical trials (RCTs). DATA SOURCES: MEDLINE, EMBASE, CINAHL, PEDro (Physiotherapy Evidence Database), and Cochrane Central Register of Controlled Trials to 2 January 2020. STUDY SELECTION: Pairs of reviewers independently identified interventional RCTs that enrolled patients presenting with pain of up to 4 weeks' duration from non-low back, musculoskeletal injuries. DATA EXTRACTION: Pairs of reviewers independently extracted data. Certainty of evidence was evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. DATA SYNTHESIS: The 207 eligible studies included 32 959 participants and evaluated 45 therapies. Ninety-nine trials (48%) enrolled populations with diverse musculoskeletal injuries, 59 (29%) included patients with sprains, 13 (6%) with whiplash, and 11 (5%) with muscle strains; the remaining trials included various injuries ranging from nonsurgical fractures to contusions. Topical nonsteroidal anti-inflammatory agents (NSAIDs) proved to have the greatest net benefit, followed by oral NSAIDs and acetaminophen with or without diclofenac. Effects of these agents on pain were modest (around 1 cm on a 10-cm visual analogue scale, approximating the minimal important difference). Regarding opioids, compared with placebo, acetaminophen plus an opioid improved intermediate pain (1 to 7 days) but not immediate pain (≤2 hours), tramadol was ineffective, and opioids increased the risk for gastrointestinal and neurologic harms (all moderate-certainty evidence). LIMITATIONS: Only English-language studies were included. The number of head-to-head comparisons was limited. CONCLUSION: Topical NSAIDs, followed by oral NSAIDs and acetaminophen with or without diclofenac, showed the most convincing and attractive benefit-harm ratio for patients with acute pain from non-low back, musculoskeletal injuries. No opioid achieved benefit greater than that of NSAIDs, and opioids caused the most harms. PRIMARY FUNDING SOURCE: National Safety Council. (PROSPERO: CRD42018094412).

Patterns of Red and Processed Meat Consumption and Risk for Cardiometabolic and Cancer Outcomes: A Systematic Review and Meta-analysis of Cohort Studies.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Studying dietary patterns may provide insights into the potential effects of red and processed meat on health outcomes. Purpose: To evaluate the effect of dietary patterns, including different amounts of red or processed meat, on all-cause mortality, cardiometabolic outcomes, and cancer incidence and mortality. Data Sources: Systematic search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and ProQuest Dissertations & Theses Global from inception to April 2019 with no restrictions on year or language. Study Selection: Teams of 2 reviewers independently screened search results and included prospective cohort studies with 1000 or more participants that reported on the association between dietary patterns and health outcomes. Data Extraction: Two reviewers independently extracted data, assessed risk of bias, and evaluated the certainty of evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. Data Synthesis: Eligible studies that followed patients for 2 to 34 years revealed low- to very-low-certainty evidence that dietary patterns lower in red and processed meat intake result in very small or possibly small decreases in all-cause mortality, cancer mortality and incidence, cardiovascular mortality, nonfatal coronary heart disease, fatal and nonfatal myocardial infarction, and type 2 diabetes. For all-cause, cancer, and cardiovascular mortality and incidence of some types of cancer, the total sample included more than 400 000 patients; for other outcomes, total samples included 4000 to more than 300 000 patients. Limitation: Observational studies are prone to residual confounding, and these studies provide low- or very-low-certainty evidence according to the GRADE criteria. Conclusion: Low- or very-low-certainty evidence suggests that dietary patterns with less red and processed meat intake may result in very small reductions in adverse cardiometabolic and cancer outcomes. Primary Funding Source: None. (PROSPERO: CRD42017074074).

Direct comparative effectiveness and safety between non-vitamin K antagonist oral anticoagulants for stroke prevention in nonvalvular atrial fibrillation: a systematic review and meta-analysis of observational studies.

The non-vitamin K antagonist oral anticoagulants (NOACs) have been increasingly prescribed in clinical practice for stroke prevention in patients with nonvalvular atrial fibrillation (AF). Direct comparisons between NOACs in trials are lacking, leaving an important clinical decision-making gap. We aimed to perform a systematic review and meta-analysis to summarize the evidence of observational studies for direct comparative effectiveness and safety amongst NOACs in patients with AF. Conference proceedings and electronic databases including MEDLINE, CINAHL, EMBASE and PUBMED were systematically searched. We included observational studies directly comparing individual NOACs in patients with nonvalvular AF who were aged ≥ 18 years for stroke prevention. Primary outcome included effectiveness outcome (stroke or systemic embolism) and safety outcome (major bleeding). Data were extracted in duplicated by two reviewers independently. A random-effects meta-analysis was conducted to synthesize the data from included observational studies. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to rate the overall quality of evidence for each outcome. Fifteen studies were included for qualitative synthesis, twelve studies for meta-analyses. It was found that rivaroxaban and dabigatran were similar with regard to risk of stroke or systemic embolism (Hazard ratio [HR] = 1.00, 95% CI 0.91-1.10; evidence quality: low), but rivaroxaban was associated with higher risk of major bleeding (HR = 1.39, 95% CI 1.28-1.50; evidence quality: moderate). Compared with apixaban, a significantly higher risk of major bleeding was observed with rivaroxaban (HR = 1.71, 95% CI 1.51-1.94; evidence quality: low). Apixaban was associated with lower risk of major bleeding, in comparison with dabigatran (HR = 0.80, 95% CI 0.68-0.95; evidence quality: low). No differences in risk of stroke or systemic embolism was observed between rivaroxaban versus apixaban, and apixaban versus dabigatran. In this study, apixaban was found to have the most favorable safety profile amongst the three NOACs. No significant difference was observed in risk of stroke or systemic embolism between the NOACs. Such findings may provide some decision-making support for physicians regarding their choices amongst NOACs in patients with AF.Registration PROSPERO (identifier: CRD42016052908).

A systematic review of comparisons between protocols or registrations and full reports in primary biomedical research.

BACKGROUND: Prospective study protocols and registrations can play a significant role in reducing incomplete or selective reporting of primary biomedical research, because they are pre-specified blueprints which are available for the evaluation of, and comparison with, full reports. However, inconsistencies between protocols or registrations and full reports have been frequently documented. In this systematic review, which forms part of our series on the state of reporting of primary biomedical, we aimed to survey the existing evidence of inconsistencies between protocols or registrations (i.e., what was planned to be done and/or what was actually done) and full reports (i.e., what was reported in the literature); this was based on findings from systematic reviews and surveys in the literature. METHODS: Electronic databases, including CINAHL, MEDLINE, Web of Science, and EMBASE, were searched to identify eligible surveys and systematic reviews. Our primary outcome was the level of inconsistency (expressed as a percentage, with higher percentages indicating greater inconsistency) between protocols or registration and full reports. We summarized the findings from the included systematic reviews and surveys qualitatively. RESULTS: There were 37 studies (33 surveys and 4 systematic reviews) included in our analyses. Most studies (n = 36) compared protocols or registrations with full reports in clinical trials, while a single survey focused on primary studies of clinical trials and observational research. High inconsistency levels were found in outcome reporting (ranging from 14% to 100%), subgroup reporting (from 12% to 100%), statistical analyses (from 9% to 47%), and other measure comparisons. Some factors, such as outcomes with significant results, sponsorship, type of outcome and disease speciality were reported to be significantly related to inconsistent reporting. CONCLUSIONS: We found that inconsistent reporting between protocols or registrations and full reports of primary biomedical research is frequent, prevalent and suboptimal. We also identified methodological issues such as the need for consensus on measuring inconsistency across sources for trial reports, and more studies evaluating transparency and reproducibility in reporting all aspects of study design and analysis. A joint effort involving authors, journals, sponsors, regulators and research ethics committees is required to solve this problem.

Patient Values and Preferences Regarding Opioids for Chronic Noncancer Pain: A Systematic Review.

Objective: Shared-care decision-making between patients and clinicians involves making trade-offs between desirable and undesirable consequences of management strategies. Although patient values and preferences should provide the basis for these trade-offs, few guidelines consider the relevant evidence when formulating recommendations. To inform a guideline for use of opioids in patients with chronic noncancer pain, we conducted a systematic review of studies exploring values and preferences of affected patients toward opioid therapy. Methods: We searched MEDLINE, CINAHL, EMBASE, and PsycINFO from the inception of each database through October 2016. We included studies examining patient preferences for alternative approaches to managing chronic noncancer pain and studies that assessed how opioid-using chronic noncancer pain patients value alternative health states and their experiences with treatment. We compiled structured summaries of the results. Results: Pain relief and nausea and vomiting were ranked as highly significant outcomes across studies. When considered, the adverse effect of personality changes was rated as equally important. Constipation was assessed in most studies and was an important outcome, secondary to pain relief and nausea and vomiting. Of only two studies that evaluated addiction, both found it less important to patients than pain relief. No studies examined opioid overdose, death, or diversion. Conclusion: Our findings suggest that the adverse effects of opioids, especially nausea and vomiting, may reduce or eliminate any net benefit of opioid therapy unless pain relief is significant (>2 points on a 10-point scale). Further research should investigate patient values and preferences regarding opioid overdose, diversion, and death.

A scoping review of comparisons between abstracts and full reports in primary biomedical research.

BACKGROUND: Evidence shows that research abstracts are commonly inconsistent with their corresponding full reports, and may mislead readers. In this scoping review, which is part of our series on the state of reporting of primary biomedical research, we summarized the evidence from systematic reviews and surveys, to investigate the current state of inconsistent abstract reporting, and to evaluate factors associated with improved reporting by comparing abstracts and their full reports. METHODS: We searched EMBASE, Web of Science, MEDLINE, and CINAHL from January 1st 1996 to September 30th 2016 to retrieve eligible systematic reviews and surveys. Our primary outcome was the level of inconsistency between abstracts and corresponding full reports, which was expressed as a percentage (with a lower percentage indicating better reporting) or categorized rating (such as major/minor difference, high/medium/low inconsistency), as reported by the authors. We used medians and interquartile ranges to describe the level of inconsistency across studies. No quantitative syntheses were conducted. Data from the included systematic reviews or surveys was summarized qualitatively. RESULTS: Seventeen studies that addressed this topic were included. The level of inconsistency was reported to have a median of 39% (interquartile range: 14% - 54%), and to range from 4% to 78%. In some studies that separated major from minor inconsistency, the level of major inconsistency ranged from 5% to 45% (median: 19%, interquartile range: 7% - 31%), which included discrepancies in specifying the study design or sample size, designating a primary outcome measure, presenting main results, and drawing a conclusion. A longer time interval between conference abstracts and the publication of full reports was found to be the only factor which was marginally or significantly associated with increased likelihood of reporting inconsistencies. CONCLUSIONS: This scoping review revealed that abstracts are frequently inconsistent with full reports, and efforts are needed to improve the consistency of abstract reporting in the primary biomedical community.

Predictors of persistent pain after breast cancer surgery: a systematic review and meta-analysis of observational studies.

BACKGROUND: Persistent pain after breast cancer surgery affects up to 60% of patients. Early identification of those at higher risk could help inform optimal management. We conducted a systematic review and meta-analysis of observational studies to explore factors associated with persistent pain among women who have undergone surgery for breast cancer. METHODS: We searched the MEDLINE, Embase, CINAHL and PsycINFO databases from inception to Mar. 12, 2015, to identify cohort or case-control studies that explored the association between risk factors and persistent pain (lasting ≥ 2 mo) after breast cancer surgery. We pooled estimates of association using random-effects models, when possible, for all independent variables reported by more than 1 study. We reported relative measures of association as pooled odds ratios (ORs) and absolute measures of association as the absolute risk increase. RESULTS: Thirty studies, involving a total of 19 813 patients, reported the association of 77 independent variables with persistent pain. High-quality evidence showed increased odds of persistent pain with younger age (OR for every 10-yr decrement 1.36, 95% confidence interval [CI] 1.24-1.48), radiotherapy (OR 1.35, 95% CI 1.16-1.57), axillary lymph node dissection (OR 2.41, 95% CI 1.73-3.35) and greater acute postoperative pain (OR for every 1 cm on a 10-cm visual analogue scale 1.16, 95% CI 1.03-1.30). Moderate-quality evidence suggested an association with the presence of preoperative pain (OR 1.29, 95% CI 1.01-1.64). Given the 30% risk of pain in the absence of risk factors, the absolute risk increase corresponding to these ORs ranged from 3% (acute postoperative pain) to 21% (axillary lymph node dissection). High-quality evidence showed no association with body mass index, type of breast surgery, chemotherapy or endocrine therapy. INTERPRETATION: Development of persistent pain after breast cancer surgery was associated with younger age, radiotherapy, axillary lymph node dissection, greater acute postoperative pain and preoperative pain. Axillary lymph node dissection provides the only high-yield target for a modifiable risk factor to prevent the development of persistent pain after breast cancer surgery.

[The Computer Competency of Nurses in Long-Term Care Facilities and Related Factors].

BACKGROUND: It is important for nurses who work in long-term care facilities (LTCFs) to have an adequate level of computer competency due to the multidisciplinary and comprehensive nature of long-term care services. Thus, it is important to understand the current computer competency of nursing staff in LTCFs and the factors that relate to this competency. PURPOSE: To explore the computer competency of LTCF nurses and to identify the demographic and computer-usage characteristics that relate significantly to computer competency in the LTCF environment. METHODS: A cross-sectional research design and a self-report questionnaire were used to collect data from 185 nurses working at LTCFs in Taipei. RESULTS: The results found that the variables of the frequency of computer use (ß = .33), age (ß = -.30), type(s) of the software used at work (ß = .28), hours of on-the-job training (ß = -.14), prior work experience at other LTCFs (ß = -.14), and Internet use at home (ß = .12) explain 58.0% of the variance in the computer competency of participants. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The results of the present study suggest that the following measures may help increase the computer competency of LTCF nurses. (1) Nurses should be encouraged to use electronic nursing records rather than handwritten records. (2) On-the-job training programs should emphasize participant competency in the Excel software package in order to maintain efficient and good-quality of LTC services after implementing of the LTC insurance policy.

Resveratrol inhibits NLRP3 inflammasome activation by preserving mitochondrial integrity and augmenting autophagy.

The NLRP3 inflammasome is a caspase-1-containing multi-protein complex that controls the release of IL-1ß and plays important roles in the development of inflammatory disease. Here, we report that resveratrol, a polyphenolic compound naturally produced by plants, inhibits NLRP3 inflammasome-derived IL-1ß secretion and pyroptosis in macrophages. Resveratrol inhibits the activation step of the NLRP3 inflammasome by suppressing mitochondrial damage. Resveratrol also induces autophagy by activating p38, and macrophages treated with an autophagy inhibitor are resistant to the suppressive effects of resveratrol. In addition, resveratrol administration mitigates glomerular proliferation, glomerular sclerosis, and glomerular inflammation in a mouse model of progressive IgA nephropathy. These findings were associated with decreased renal mononuclear leukocyte infiltration, reduced renal superoxide anion levels, and inhibited renal NLRP3 inflammasome activation. Our data indicate that resveratrol suppresses NLRP3 inflammasome activation by preserving mitochondrial integrity and by augmenting autophagy.

Thriving on novelty: Chinese students' journey to creative travel in Thailand.

This study explores the intersection of creative travel and flow experiences among foreign students, a topic not extensively explored in tourism research. Specifically, it examines the mediating role of flow experiences in the relationship between students' novelty-seeking behaviors and their intention to engage in creative travel. Additionally, the research investigates how familiarity with a destination moderates this relationship. Employing structural equation modeling, the study analyzes data from 704 Chinese students in Thailand. The findings reveal that flow experiences positively mediate the link between the students' pursuit of novelty and their creative travel intentions. Moreover, the extent of familiarity with the destination was found to modify the relationship between novelty seeking and flow experiences. This research contributes to the theoretical understanding of these dynamics and offers practical insights for stakeholders in creative travel marketing and management.

Examining the influence of organizational commitment on service quality through the lens of job involvement as a mediator and emotional labor and organizational climate as moderators.

This study investigates the impact of organizational commitment and job engagement on service quality, while integrating the influences of organizational climate and emotional labor. Utilizing data from 427 participants, acquired via structured questionnaires, the research employed the Statistical Package for the Social Sciences (SPSS) for analysis. The findings reveal that heightened job engagement and organizational commitment significantly enhance service quality, primarily through reinforcing employees' trust in their organization. A favorable organizational climate is instrumental in strengthening employees' affiliation with their organization, consequently leading to superior service provision. Furthermore, the capability to effectively regulate emotions emerges as a critical factor in both job engagement and the quality of service. The study advocates for augmenting job engagement and organizational commitment, cultivating a supportive workplace atmosphere, and equipping employees with resources for efficient emotional management. These strategies are proposed to substantially improve service quality. The insights derived from this research provide essential directives for managers striving to achieve service excellence.

Effect and safety profile of topical lidocaine on post-surgical neuropathic pain and quality of life: A systematic review and meta-analysis.

STUDY OBJECTIVE: Post-surgical chronic pain with a neuropathic component is usually more severe and leads to worse quality of life. We conducted this systematic review to examine the evidence of topical lidocaine for post-surgical neuropathic pain. DESIGN: Systematic review with meta-analysis. SETTING: Published randomized controlled trials (RCTs) comparing topical lidocaine with placebo or no topical lidocaine for post-surgical neuropathic pain. PATIENTS: Seven RCTs including 585 patients. INTERVENTIONS: We systematically searched databases for randomized controlled trials (RCTs) investigating the effect and safety outcomes of topical lidocaine compared with placebo or no intervention. MEASUREMENTS: We conducted meta-analyses to evaluate the effect of topical lidocaine on pain intensity, adverse events, and quality of life. Standardized mean difference (SMD) and relative risk (RR) with 95% CIs were effect measures for continuous and dichotomous outcomes, respectively. We assessed the risk of bias of included trials and the certainty of evidence for each outcome. MAIN RESULTS: Our review included 7 studies with 585 participants. There is moderate certainty evidence that topical lidocaine may increase the likelihood of global pain relief, with a relative risk (RR) of 1.98 (95% confidence interval (CI): 1.04, 3.76; I2 = 70%, P = 0.04). Low certainty evidence suggested topical lidocaine may lead to more reduction in pain intensity (SMD: -0.70; 95% confidence interval: -1.46, 0.06; I2 = 93%, P = 0.07). High certainty evidence showed that topical lidocaine did not increase the adverse event risk (RR: 1.04; 95% CI: 0.93, 1.16; I2 = 0%, P = 0.51). CONCLUSIONS: Topical lidocaine may lead to pain relief and is safe to use for patient with post-surgical pain, though its impact on quality of life is unclear. This review supports the use of topical lidocaine for patients with post-surgical pain, and reveals the evidence gap in topical lidocaine use. (Registration: PROSPERO CRD42021294100).

Immunomodulatory activity of recombinant Ricin toxin binding Subunit B (RTB).

Ricin toxin binding subunit B (RTB) is one of the subunits of the ricin protein. RTB has been used as adjuvant, but little is known about its mechanism. In this study, we found that RTB increased not only nitric oxide (NO) release, but also tumor necrosis factor (TNF)-α and interleukin (IL)-6 production in mouse macrophage cell line RAW264.7 cells. They subsequently exhibited enhanced ConA-induced T-cell and LPS-induced B-cell proliferative responses. We also examined the cytokines that were produced from splenocytes following in vitro RTB administration. Increased levels of IL-2, interferon (IFN)-γ and TNF-α were observed, while IL-4 and IL-5 were unaffected. These results demonstrate that recombinant RTB can act on the immune system and activate T-cells by introducing a Th1 immune response. Th1 cells might be the primary cellular target affected by RTB. Our results suggest that the recombinant RTB can promote the activation of macrophages and has a beneficial effect on immunomodulatory activity.

Quadratus lumborum block for postoperative pain management in patients undergoing total hip arthroplasty: a systematic review and meta-analysis.

BACKGROUND: The use of quadratus lumborum nerve blocks (QLB) for pain control following elective total hip arthroplasty (THA) has increased substantially in recent years. The objective of this systematic review and meta-analysis was to compare outcomes from randomised controlled trials (RCTs) utilising QLBs following elective THA. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched for RCTs perioperative QLBs for THA. Quantitative synthesis was conducted for pain scores, opioid consumption and adverse events. RESULTS: A total of 7 RCTs with 429 patients undergoing THA were included. No differences in pain scores were demonstrated between QLBs and control interventions. Subgroup analysis demonstrated no differences between QLBs and sham procedures or active comparators. No differences in postoperative opioid consumption between QLB and control interventions was found. In trials reporting adverse events, they were rare and similar between groups. Overall, the certainty of the evidence was graded as low or very low. CONCLUSIONS: The current literature suggests that a QLB for THA does not reduce pain or opioid consumption compared to sham or active comparators.

Role of patient selection and trial stimulation for spinal cord stimulation therapy for chronic non-cancer pain: a comprehensive narrative review.

BACKGROUND/IMPORTANCE: Patient selection for spinal cord stimulation (SCS) therapy is crucial and is traditionally performed with clinical selection followed by a screening trial. The factors influencing patient selection and the importance of trialing have not been systematically evaluated. OBJECTIVE: We report a narrative review conducted to synthesize evidence regarding patient selection and the role of SCS trials. EVIDENCE REVIEW: Medline, EMBASE and Cochrane databases were searched for reports (any design) of SCS in adult patients, from their inception until March 30, 2022. Study selection and data extraction were carried out using DistillerSR. Data were organized into tables and narrative summaries, categorized by study design. Importance of patient variables and trialing was considered by looking at their influence on the long-term therapy success. FINDINGS: Among 7321 citations, 201 reports consisting of 60 systematic reviews, 36 randomized controlled trials (RCTs), 41 observational studies (OSs), 51 registry-based reports, and 13 case reports on complications during trialing were included. Based on RCTs and OSs, the median trial success rate was 72% and 82%, and therapy success was 65% and 61% at 12 months, respectively. Although several psychological and non-psychological determinants have been investigated, studies do not report a consistent approach to patient selection. Among psychological factors, untreated depression was associated with poor long-term outcomes, but the effect of others was inconsistent. Most RCTs except for chronic angina involved trialing and only one RCT compared patient selection with or without trial. The median (range) trial duration was 10 (0-30) and 7 (0-56) days among RCTs and OSs, respectively. CONCLUSIONS: Due to lack of a consistent approach to identify responders for SCS therapy, trialing complements patient selection to exclude patients who do not find the therapy helpful and/or intolerant of the SCS system. However, more rigorous and large studies are necessary to better evaluate its role.

Effectiveness, safety, initial optimal dose, and optimal maintenance dose range of basal insulin regimens for type 2 diabetes: A systematic review with meta-analysis.

AIMS: To investigate the effectiveness, safety, optimal starting dose, optimal maintenance dose range, and target fasting plasma glucose of five basal insulins in insulin-naïve patients with type 2 diabetes mellitus. METHODS: MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched from January 2000 to February 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was adopted. The registration ID is CRD42022319078 in PROSPERO. RESULTS: Among 11 163 citations retrieved, 35 publications met the planned criteria. From meta-analyses and network meta-analyses, we found that when injecting basal insulin regimens at bedtime, the optimal choice in order of most to least effective might be glargine U-300 or degludec U-100, glargine U-100 or detemir, followed by neutral protamine hagedorn (NPH). Injecting glargine U-100 in the morning may be more effective (ie, more patients archiving glycated hemoglobin < 7.0%) and lead to fewer hypoglycemic events than injecting it at bedtime. The optimal starting dose for the initiation of any basal insulins can be 0.10-0.20 U/kg/day. There is no eligible evidence to investigate the optimal maintenance dose for basal insulins. CONCLUSIONS: The five basal insulins are effective for the target population. Glargine U-300, degludec U-100, glargine U-100, and detemir lead to fewer hypoglycemic events than NPH without compromising glycemic control.

Probiotics, Prebiotics, Lactoferrin, and Combination Products for Prevention of Mortality and Morbidity in Preterm Infants: A Systematic Review and Network Meta-Analysis.

Importance: Modulation of intestinal microbiome by administering probiotics, prebiotics, or both may prevent morbidity and mortality in premature infants. Objective: To assess the comparative effectiveness of alternative prophylactic strategies through a network meta-analysis (NMA) of randomized clinical trials. Data Sources: MEDLINE, EMBASE, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, and Google Scholar from inception until May 10, 2023. Study Selection: Eligible trials tested probiotics, prebiotics, lactoferrin, and combination products for prevention of morbidity or mortality in preterm infants. Data Extraction and Synthesis: A frequentist random-effects model was used for the NMA, and the certainty of evidence and inferences regarding relative effectiveness were assessed using the GRADE approach. Main Outcomes and Measures: All-cause mortality, severe necrotizing enterocolitis, culture-proven sepsis, feeding intolerance, time to reach full enteral feeding, and duration of hospitalization. Results: A total of 106 trials involving 25 840 preterm infants were included. Only multiple-strain probiotics were associated with reduced all-cause mortality compared with placebo (risk ratio [RR], 0.69; 95% CI, 0.56 to 0.86; risk difference [RD], -1.7%; 95% CI, -2.4% to -0.8%). Multiple-strain probiotics alone (vs placebo: RR, 0.38; 95% CI, 0.30 to 0.50; RD, -3.7%; 95% CI, -4.1% to -2.9%) or in combination with oligosaccharides (vs placebo: RR, 0.13; 95% CI, 0.05 to 0.37; RD, -5.1%; 95% CI, -5.6% to -3.7%) were among the most effective interventions reducing severe necrotizing enterocolitis. Single-strain probiotics in combination with lactoferrin (vs placebo RR, 0.33; 95% CI, 0.14 to 0.78; RD, -10.7%; 95% CI, -13.7% to -3.5%) were the most effective intervention for reducing sepsis. Multiple-strain probiotics alone (RR, 0.61; 95% CI, 0.46 to 0.80; RD, -10.0%; 95% CI, -13.9% to -5.1%) or in combination with oligosaccharides (RR, 0.45; 95% CI, 0.29 to 0.67; RD, -14.1%; 95% CI, -18.3% to -8.5%) and single-strain probiotics (RR, 0.61; 95% CI, 0.51 to 0.72; RD, -10.0%; 95% CI, -12.6% to -7.2%) proved of best effectiveness in reduction of feeding intolerance vs placebo. Single-strain probiotics (MD, -1.94 days; 95% CI, -2.96 to -0.92) and multistrain probiotics (MD, -2.03 days; 95% CI, -3.04 to -1.02) proved the most effective in reducing the time to reach full enteral feeding compared with placebo. Only single-strain and multistrain probiotics were associated with greater effectiveness compared with placebo in reducing duration of hospitalization (MD, -3.31 days; 95% CI, -5.05 to -1.58; and MD, -2.20 days; 95% CI, -4.08 to -0.31, respectively). Conclusions and Relevance: In this systematic review and NMA, moderate- to high-certainty evidence demonstrated an association between multistrain probiotics and reduction in all-cause mortality; these interventions were also associated with the best effectiveness for other key outcomes. Combination products, including single- and multiple-strain probiotics combined with prebiotics or lactoferrin, were associated with the largest reduction in morbidity and mortality.