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Objectives: Recent multicenter trials suggest that higher protein delivery may result in worse outcomes in critically ill patients, but uncertainty remains. An updated Bayesian meta-analysis of recent evidence was conducted to estimate the probabilities of beneficial and harmful treatment effects., Data Sources: An updated systematic search was performed in three databases until September 4, 2024. The study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and the protocol was preregistered in PROSPERO (CRD42024546387)., Study Selection: Randomized controlled trials that studied adult critically ill patients comparing protein doses delivered enterally and/or parenterally with similar energy delivery between groups were included., Data Extraction: Data extraction was performed by two authors independently, using a predefined worksheet. The primary outcome was mortality. Posterior probabilities of any benefit (relative risk [RR] < 1.00) or harm (RR > 1.00) and other important beneficial and harmful effect size thresholds were estimated. Risk of bias assessment was performed using the risk of bias 2.0 tool. All analyses were performed using a Bayesian hierarchical random-effects models, under vague priors., Data Synthesis: Twenty-two randomized trials (n = 4164 patients) were included. The mean protein delivery in the higher and lower protein groups was 1.5 ± 0.6 vs. 0.9 ± 0.4 g/kg/d. The median RR for mortality was 1.01 (95% credible interval, 0.84-1.16). The posterior probability of any mortality benefit from higher protein delivery was 43.6%, while the probability of any harm was 56.4%. The probabilities of a 1% (RR < 0.99) and 5% (RR < 0.95) mortality reduction by higher protein delivery were 38.7% and 22.9%, respectively. Conversely, the probabilities of a 1% (RR > 1.01) and 5% (RR > 1.05) mortality increase were 51.5% and 32.4%, respectively., Conclusions: There is a considerable probability of an increased mortality risk with higher protein delivery in critically ill patients, although a clinically beneficial effect cannot be completely eliminated based on the current data., Competing Interests: Dr. Deane is employed by an institution that has received lecture fees from Baxter Healthcare for his time. Dr. van de Poll received in kind support from Nutricia Research for the PRotEin provision in Critical IllneSs (PRECISe) trial and speaker and travel fees from Nutricia Research. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objective: Data on the impact of COVID-19 in people living with HIV (PWH) are lacking in resource-constrained settings. We utilised existingrandomised clinical trials (RCTs) on antiretroviral therapies (ART) in HIV-1 infection to conduct a SARS-CoV-2 serosurvey, between January and March 2021, while characterising participants' features., Design: Cross-sectional serosurvey., Methods: Demographic characteristics, medical history and a serum sample were collected from consenting PWH. Samples were analysed centrally for immunoglobulin G antibodies to recombinant nucleocapsid and spike proteins derived from SARS-CoV-2 using a Luminex based assay., Results: The 549participants recruited in 9 sites across Africa had a median age of 40 years (IQR [34-45]); 63.0% (346) were female. All were on ART; 81.8% (449) had an HIV-1 viral load <50 copies/mL, with CD4 count median at 478/mm 3 (IQR [320-677]). None had received vaccination against SARS-CoV-2. Forty participants (7.3%) had a prior SARS-CoV-2 PCR testing, of whom 10 were positive (1.8%). Crude SARS-CoV-2 seroprevalence was 36.2% (; 95%CI [32.2-40.4]). In the explorative multivariable analysis, comparison of the characteristics of PWH with a positive SARS-CoV-2 serology with those with a negative or indeterminate serology: PWH with a body mass index (BMI)≥30 kg/m 2 were more likely to have a positive serology than those with a BMI≤25 (aOR = 2.39 [1.48-3.86], p < 0.001); and PWH living in Cameroon were less likely to have a positive serology., Conclusion: This study demonstrates a substantial seroprevalence level of SARS-CoV-2 in PWH in the first quarter of 2021, with a marked disparity with the number of COVID-19 PCR tests reported positive., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared with intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients., Methods: We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass. Between September 17, 2019, and November 28, 2023, a total of 3242 patients from 16 hospitals in 6 countries were randomly assigned (1:1 ratio) to receive either intravenous tranexamic acid (control) through surgery or topical tranexamic acid (treatment) at the end of surgery. The primary outcome was seizure, and the secondary outcome was red blood cell transfusion. After the last planned interim analysis, when 75% of anticipated participants had completed follow up, the data and safety monitoring board recommended to terminate the trial, and upon unblinding, the operations committee stopped the trial for safety., Results: Among 3242 randomized patients (mean age, 66.0 years; 77.7% male), in-hospital seizure occurred in 4 of 1624 patients (0.2%) in the topical group, and 11 of 1628 patients (0.7%) in the intravenous group (absolute risk difference, -0.5% [95% CI, -0.9 to 0.03]; P =0.07). Red blood cell transfusion occurred in 570 patients (35.1%) in the topical group and in 433 (26.8%) in the intravenous group (absolute risk difference, 8.3% [95% CI, 5.2-11.5]; P =0.007). The absolute risk difference in transfusion of ≥4 units of red blood cells in the topical group compared with the intravenous group was 8.2% (95% CI, 3.4-12.9)., Conclusions: Among patients undergoing cardiac surgery, topical administration of tranexamic acid resulted in an 8.3% absolute increase in transfusion without reducing the incidence of seizure, compared with intravenous tranexamic acid., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03954314., Competing Interests: Dr Devereaux is employed as a professor at McMaster University. Dr Spence is employed as an anesthesiologist and intensivist at Hamilton Health Sciences and reports consultant fees from AOP Pharmaceuticals and PhaseBio outside the submitted work. Dr Whitlock reports grants from Abbott Canada during the conduct of the study and consultant fees from AtriCure Inc and Cytosorbents outside the submitted work. Dr Belley-Côté reports grants from Abbott Laboratories, Bayer, Bristol-Myers Squibb, Pfizer, and Roche Diagnostics Corporation during the conduct of the study and consultant fees from Trimedic Therapeutics outside the submitted work. Dr Arora reports other funding from Bioporto, Edwards Lifesciences, HLS Therapeutics Inc, and Renibus Therapeutics Inc outside the submitted work. The other authors report no conflicts.

This cross-sectional study aimed to assess the levels of health literacy and the associated factors among the general population living in 2 schistosomiasis-endemic villages in Jiangxi Province, China. Multistage stratified random sampling was used to select participants, and a face-to-face survey was conducted from July to August 2021 to collect participants' socio-demographic characteristics and levels of overall health literacy (HL) and its 3 subscales: health literacy of basic knowledge and concepts (HL-BKC), health literacy of behavior and lifestyle (HL-BAL), and health literacy of health-related skills (HL-HRS). The Chi-square test and logistic regression models were used to assess the association between socio-demographic characteristics and low HL levels. The prevalence rates of low overall HL, HL-BKC, HL-BAL, and HL-HRS were 84.3%, 61.8%, 82.6%, and 86%, respectively. In addition, no significant differences (P > .05) were noted between the 2 villages regarding overall HL scores and the 3 subscales of health literacy scores. Older age (P < .001), occupation (P < .001), lower educational level (P < .001), and lower annual household income (P < .05) were associated with an increased risk of low HL. Multivariate logistic regression revealed that occupation as a student (OR = 32.289, 95% CI:1.965-530.462, P < .05) and fishermen (OR = 27.902, 95%CI:1.91-407.642, P < .05), lower education level (OR = 0.384, 95%CI:0.149-0.99, P < .05), older age (OR = 5.228, 95%CI:1.458-18.75, P < .001), and lower annual household income (OR = 0.452, 95%CI:0.24-0.851, P < .05) were independently associated with low HL. The prevalence of low HL is high among the population in the schistosomiasis-endemic villages of Jiangxi Province, China. Age, education level, occupation, and annual household income were all independent factors associated with HL levels. Health educational interventions to improve HL should be simultaneously conducted in health promotion work to reduce risky habits., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The number of allogeneic hematopoietic stem cell transplantation (allo-HSCT) survivors is increasing globally. Although qualitative studies in this population are reported, clear understanding of how allo-HSCT survivors experience survivorship is lacking., Objective: This study aimed to identify, appraise, and synthesize evidence from qualitative research on survivorship experience among allo-HSCT survivors., Methods: A qualitative systematic review was conducted. A literature search of 9 databases and OpenGrey, Google Scholar, and Google was performed from inception to February 2023. Two reviewers independently screened and assessed the eligibility of each study. Descriptive information was extracted from the studies by one reviewer and checked by another. Findings were extracted and analyzed using thematic synthesis., Results: Seventeen articles were included. Four themes and 12 subthemes regarding allo-HSCT survivors' experiences emerged: (1) recovery as being a longer process than they thought (influenced by long-term physical symptoms, disturbed by survivorship uncertainty); (2) experiencing a restricted survivorship life (shrunken social world, forced dietary limitations, centered around hospitals); (3) suffering from stigma and discrimination (perceived as a burden, seen differently by others, difficulties establishing and maintaining romantic relationships and marriage, limited opportunities in work); and (4) realizing something positive obtained during survivorship (enriched survivorship self-management skills, enhanced personal growth, developed positive relationships)., Conclusions: The findings reveal the challenges, needs, and growth that allo-HSCT survivors experienced during survivorship. Some understudied areas were identified, which warrant further exploration., Implications for Practice: Targeted survivor-centered care should be provided to allo-HSCT survivors, and interventions to resolve issues experienced during survivorship should be developed., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Across guidelines, protein dosing for critically ill patients with obesity varies considerably. The objective of this analysis was to evaluate whether this population would benefit from higher doses of protein., Design: A post hoc subgroup analysis of the effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): an international, multicenter, pragmatic, registry-based randomized trial., Setting: Eighty-five adult ICUs across 16 countries., Patients: Patients with obesity defined as a body mass index (BMI) greater than or equal to 30 kg/m 2 ( n = 425)., Interventions: In the primary study, patients were randomized into a high-dose (≥ 2.2 g/kg/d) or usual-dose protein group (≤ 1.2 g/kg/d)., Measurements and Main Results: Protein intake was monitored for up to 28 days, and outcomes (time to discharge alive [TTDA], 60-d mortality, days of mechanical ventilation [MV], hospital, and ICU length of stay [LOS]) were recorded until 60 days post-randomization. Of the 1301 patients in the primary study, 425 had a BMI greater than or equal to 30 kg/m 2 . After adjusting for sites and covariates, we observed a nonsignificant slower rate of TTDA with higher protein that ruled out a clinically important benefit (hazard ratio, 0.78; 95% CI, 0.58-1.05; p = 0.10). We found no evidence of difference in TTDA between protein groups when subgroups with different classes of obesity or patients with and without various nutritional and frailty risk variables were examined, even after the removal of patients with baseline acute kidney injury. Overall, 60-day mortality rates were 31.5% and 28.2% in the high protein and usual protein groups, respectively (risk difference, 3.3%; 95% CI, -5.4 to 12.1; p = 0.46). Duration of MV and LOS in hospital and ICU were not significantly different between groups., Conclusions: In critically ill patients with obesity, higher protein doses did not improve clinical outcomes, including those with higher nutritional and frailty risk., Competing Interests: Dr. Bear received funding from Baxter Healthcare (advisory board and speaker fees), Avanos (advisor board fees), and Cardinal Health (speaker fees). Dr. León received funding from B Braun Sharing Expertise. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: College students' physical fitness has declined over the past decades. Taichi Qigong exercise offers numerous health benefits and could serve as a suitable option for them. Traditional programs, however, are time-consuming and necessitate long-term commitments. Therefore, a more cost-effective intervention is needed., Methods: The study enrolled a total of 31 students who actively participated in a 5-week STQE program, consisting of three 60-minute sessions per week. Physical and mental health assessments included the Plank test, vital capacity measurement, 1000/800 m run test, standing jump, and the Zung Self-Rating Scale. Data analysis was performed using SPSS., Results: Following the STQE intervention, participants showed improvement in core strength (28.1 seconds in the Plank test, P = .025) and lower limb explosive force (6.52 cm in the standing jump test, P = .011), accompanied by a decrease in anxiety levels (a reduction of 3.41 in the Zung Self-Rating Scale, P = .039). However, no significant improvements were observed in cardiopulmonary endurance, as evidenced by a non-significant increase of 237.84 mL in vital capacity (P = .134) and a non-significant reduction of 1.6 seconds in the 1000/800 m run test (P = .764)., Conclusion: The study suggests that the STQE program effectively improves core strength, lower limb explosive force, and reduces anxiety levels among university students., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: In previous analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these deaths occurred during the index hospitalization for surgery. The authors set out to describe outcomes after discharge from hospital up to 1 yr after inpatient noncardiac surgery and associations between predischarge complications and postdischarge death up to 1 yr after surgery., Methods: This study was an analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007 to 2013 of patients aged 45 yr or older followed to 1 yr after surgery. The study estimated (1) the cumulative postdischarge incidence of death and other outcomes up to a year after surgery and (2) the adjusted time-varying associations between postdischarge death and predischarge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis., Results: Among 38,898 patients discharged after surgery, the cumulative 1-yr incidence was 5.8% (95% CI, 5.5 to 6.0%) for all-cause death and 24.7% (95% CI, 24.2 to 25.1%) for all-cause hospital readmission. Predischarge complications were associated with 33.7% (95% CI, 27.2 to 40.2%) of deaths up to 30 days after discharge and 15.0% (95% CI, 12.0 to 17.9%) up to 1 yr. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [95% CI, 9.3 to 21.9%] of deaths within 30 days, 6.4% [95% CI, 4.1 to 8.7%] within 1 yr), major bleeding (15.0% [95% CI, 8.3 to 21.7%] within 30 days, 4.7% [95% CI, 2.2 to 7.2%] within 1 yr), and sepsis (5.4% [95% CI, 2.2 to 8.6%] within 30 days, 2.1% [95% CI, 1.0 to 3.1%] within 1 yr)., Conclusions: One in 18 patients 45 yr old or older discharged after inpatient noncardiac surgery died within 1 yr, and one quarter were readmitted to the hospital. The risk of death associated with predischarge perioperative complications persists for weeks to months after discharge., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Objectives: Evidence supporting glutamine supplementation in severe adult burn patients has created a state of uncertainty due to the variability in the treatment effect reported across small and large randomized controlled trials (RCTs). We aimed to systematically review the effect of glutamine supplementation on mortality in severe adult burn patients., Data Sources: MEDLINE, Embase, CINAHL, and Cochrane Central were searched from inception to February 10, 2023., Study Selection: RCTs evaluating the effect of enteral or IV glutamine supplementation alone in severe adult burn patients were included., Data Extraction: Two reviewers independently extracted data on study characteristics, burn injury characteristics, description of the intervention between groups, adverse events, and clinical outcomes., Data Synthesis: Random effects meta-analyses were performed to estimate the pooled risk ratio (RR). Trial sequential analyses (TSA) for mortality and infectious complications were performed. Ten RCTs (1,577 patients) were included. We observed no significant effect of glutamine supplementation on overall mortality (RR, 0.65, 95% CI, 0.33-1.28; p = 0.21), infectious complications (RR, 0.83; 95% CI, 0.63-1.09; p = 0.18), or other secondary outcomes. In subgroup analyses, we observed no significant effects based on administration route or burn severity. We did observe a significant subgroup effect between single and multicenter RCTs in which glutamine significantly reduced mortality and infectious complications in singe-center RCTs but not in multicenter RCTs. However, TSA showed that the pooled results of single-center RCTs were type 1 errors and further trials would be futile., Conclusions: Glutamine supplementation, regardless of administration, does not appear to improve clinical outcomes in severely adult burned patients., Competing Interests: Dr. Hill received funding from Fresenius Kabi; she disclosed that she is currently supported by the Medical Faculty Rheinisch-Westfälische Technische Hochschule Aachen University (“Habilitationsstipendium”). Dr. Jeschke received support for article research from the National Institutes of Health. Dr. Cancio disclosed government work. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Young adult survivors of childhood leukemia have been reported with increased likelihood of age-related comorbidities compared with the general population. We compared the prevalence of frailty in young adult survivors of childhood acute lymphoblastic leukemia (n=58, median age=23 y, median survival time=18 y) with age-matched and sex-matched controls without history of cancer. Frailty phenotypes were determined using Fried frailty model. Association between frailty status and cardiometabolic conditions, systemic inflammation, and T-cell immunophenotype changes were also examined. Frailty and prefrailty were more common among survivors compared with controls (58.6% vs. 34.5%, P =0.019). Physical inactivity (39.7%) was the most frequently observed frailty criterion among the survivors. Prevalence of cardiometabolic conditions was comparable between the robust and frail/prefrail survivors. Robust survivors had a higher level of T-cell activation than the prefrail/frail survivors ( P <0.05), but no significant difference was observed for systemic inflammatory markers (IL-6 and C-reactive protein) and percentage of terminally differentiated T cells. Signs of frailty, especially physical inactivity, was detected in childhood acute lymphoblastic leukemia survivors early in their third decade of life. Survivors who were prefrail/frail also had altered T-cell activation; however, the role of such changes in T-cell phenotype in the etiology of frailty warrant further investigation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

In the market, there are many types and shapes of syringes. One of the groupings of syringe types is based on barrel volume. The shape of the product design affects performance and user perception. The aim of this study is to investigate the effect of barrel volume on its performance and user perception. We performed analysis following international organization for standardization 7886 procedures on syringe with 1 mL, 3 mL, 5 mL, and 10 mL volume. In addition, a user perception test was conducted on 29 respondents using a questionnaire with the Likert chart method. This study indicates that the bigger the syringe volume, the larger the dead space and the force to operate the piston are. A larger syringe volume also raises the volume that changes due to the plunger position increase. Meanwhile, the barrel volume does not affect water and water leakage, as we did not observe any leak during the syringe tests in our experiment. In addition, the user perception test shows that the barrel's length influences the ease of device control during the injection. The volume of the barrel negatively correlated with its effect to the environment. The safety features of all syringes are similar except for the 3 mL syringe, which has a value of 0.1 points difference to other syringes., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives: To investigate CSF findings in relation to clinical and electrodiagnostic subtypes, severity, and outcome of Guillain-Barré syndrome (GBS) based on 1,500 patients in the International GBS Outcome Study., Methods: Albuminocytologic dissociation (ACD) was defined as an increased protein level (>0.45 g/L) in the absence of elevated white cell count (<50 cells/μL). We excluded 124 (8%) patients because of other diagnoses, protocol violation, or insufficient data. The CSF was examined in 1,231 patients (89%)., Results: In 846 (70%) patients, CSF examination showed ACD, which increased with time from weakness onset: ≤4 days 57%, >4 days 84%. High CSF protein levels were associated with a demyelinating subtype, proximal or global muscle weakness, and a reduced likelihood of being able to run at week 2 (odds ratio [OR] 0.42, 95% CI 0.25-0.70; p = 0.001) and week 4 (OR 0.44, 95% CI 0.27-0.72; p = 0.001). Patients with the Miller Fisher syndrome, distal predominant weakness, and normal or equivocal nerve conduction studies were more likely to have lower CSF protein levels. CSF cell count was <5 cells/μL in 1,005 patients (83%), 5-49 cells/μL in 200 patients (16%), and ≥50 cells/μL in 13 patients (1%)., Discussion: ACD is a common finding in GBS, but normal protein levels do not exclude this diagnosis. High CSF protein level is associated with an early severe disease course and a demyelinating subtype. Elevated CSF cell count, rarely ≥50 cells/μL, is compatible with GBS after a thorough exclusion of alternative diagnoses., Classification of Evidence: This study provides Class IV evidence that CSF ACD (defined by the Brighton Collaboration) is common in patients with GBS., (© 2023 American Academy of Neurology.)

Background: The incidence of oral squamous cell carcinoma (OSCC) of the tongue is increasing in the younger population without traditional risk habits that lead researchers to find other related factors such as diet and viruses, especially human papillomavirus (HPV). It is noteworthy that many OSCCs develop from oral potentially malignant disorders (OPMDs). Correct diagnosis and timely management of OPMDs may help to prevent malignant transformation, and therefore it is worth seeing the involvement of HPV in OPMDs and oral cancers, as the preventive and curative measures in HPV-induced cancer types are different from the conventional types of OPMDs and OSCCs. Therefore, the main objective of this study was to identify a relationship between HPV and p16 in OPMDs and compare it with OSCC., Methods: This study was conducted on 83 cases of known OSCCs and OPMDs (oral submucous fibrosis, leukoplakia, and oral lichen planus). Assays, such as polymerized chain reaction (PCR) and reverse transcription-PCR, were carried out for HPV and p16 . The results were compared with clinical information and with the literature. The results were analyzed using SPSS 16.0 for windows., Results: P16 expression was mostly seen in males than in female patients. Out of 21 cases of keratosis with dysplasia, 19% expressed p16 . Of 26 oral lichen planus patients, 29% showed the p16 gene with immunohistochemistry. Interestingly, a high percentage of OSF cases expressed p16 (48.27%). Minimal expression was observed in OSCC (6.25%). HPV DNA was detected in 2.4% of the total sample. Both p16 and HPV were detected in a single case of OSCC. OPMDs expressed a significant amount of the p16 gene by immunohistochemistry and reverse transcription-PCR technique when compared with malignant lesions, suggesting a possible inactivation of the p16 gene. HPV and p16 are mostly negative in our OSCC sample, exhibiting low prevalence., Conclusions: OPMDs expressed a significant amount of the p16 gene when compared with malignant lesions, suggesting a possible inactivation of the p16 gene. Although OSF expressed p16 , HPV was not detected, suggesting that over-expression could be independent of HPV. OSCC shows low HPV prevalence., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

A syringe is used to inject fluid or medicine into the patient's soft tissue. The main components of the syringe were the needle, barrel, and plunger. The use of syringes in the medical world is relatively high, and especially since the COVID-19 pandemic, the use of hypodermic syringes increased sharply due to vaccination. The syringe used must be effective and of good quality, so the International Organization for Standardization (ISO) has published test procedures and minimum specifications for hypodermic syringes. The performance of the syringe can be observed from the dead space, force piston operation, water and air leakage, and fitting position of the plunger in the barrel. This review shows that most researchers use the weighing method to measure the dead space, although some use other methods. The researchers found that most of the products met the minimum specifications of the ISO, and that the dimensions and shape of the syringe affected the dead space. Researchers have not examined other performance measures recommended by the ISO. Researchers have focused more on force injection than force piston operation, leakage after injection or back spray than air and water leakage, and reduction the friction of the plunger without considering the fitting position of the plunger in the barrel., Competing Interests: The authors have no conflicts of interest and funding to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To develop an international core outcome set (COS), a minimal collection of outcomes that should be measured and reported in all future clinical trials evaluating treatments of acute simple appendicitis in children., Summary of Background Data: A previous systematic review identified 115 outcomes in 60 trials and systematic reviews evaluating treatments for children with appendicitis, suggesting the need for a COS., Methods: The development process consisted of 4 phases: (1) an updated systematic review identifying all previously reported outcomes, (2) a 2-stage international Delphi study in which parents with their children and surgeons rated these outcomes for inclusion in the COS, (3) focus groups with young people to identify missing outcomes, and (4) international expert meetings to ratify the final COS., Results: The systematic review identified 129 outcomes which were mapped to 43 unique outcome terms for the Delphi survey. The first-round included 137 parents (8 countries) and 245 surgeons (10 countries), the second-round response rates were 61% and 85% respectively, with 10 outcomes emerging with consensus. After 2 young peoples' focus groups, 2 additional outcomes were added to the final COS (12): mortality, bowel obstruction, intraabdominal abscess, recurrent appendicitis, complicated appendicitis, return to baseline health, readmission, reoperation, unplanned appendectomy, adverse events related to treatment, major and minor complications., Conclusion: An evidence-informed COS based on international consensus, including patients and parents has been developed. This COS is recommended for all future studies evaluating treatment ofsimple appendicitis in children, to reduce heterogeneity between studies and facilitate data synthesis and evidence-based decision-making., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Two trials reported that a high inspiratory oxygen fraction (F io2 ) does not promote myocardial infarction or death. Observational studies can provide larger statistical strength, but associations can be due to unobserved confounding. Therefore, we evaluated the association between intraoperative F io2 and cardiovascular complications in a large international cohort study to see if spurious associations were observed., Methods: We included patients from the Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) study, who were ≥45 years of age, scheduled for overnight hospital admission, and had intraoperative F io2 recorded. The primary outcome was myocardial injury after noncardiac surgery (MINS), and secondary outcomes included mortality and pneumonia, all within 30 postoperative days. Data were analyzed with logistic regression, adjusted for many baseline cardiovascular risk factors, and illustrated in relation to findings from 2 recent controlled trials., Results: We included 6588 patients with mean age of 62 years of whom 49% had hypertension. The median intraoperative F io2 was 0.46 (5%-95% range, 0.32-0.94). There were 808 patients (12%) with MINS. Each 0.10 increase in median F io2 was associated with a confounder-adjusted increase in odds for MINS: odds ratio (OR), 1.17 (95% confidence interval [CI], 1.12-1.23; P < .0001). MINS occurred in contrast with similar frequencies and no significant difference in controlled trials (2240 patients, 194 events), in which patients were given 80% vs 30% oxygen. Mortality was 2.4% and was not significantly associated with a median F io2 (OR, 1.07; 95% CI, 0.97-1.19 per 0.10 increase; P = .18), and 2.9% of patients had pneumonia (OR, 1.05; 95% CI, 0.95-1.15 per 0.10 increase; P = .34)., Conclusions: We observed an association between intraoperative F io2 and risk of myocardial injury within 30 days after noncardiac surgery, which contrasts with recent controlled clinical trials. F io2 was not significantly associated with mortality or pneumonia. Unobserved confounding presumably contributed to the observed association between F io2 and myocardial injury that is not supported by trials., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2022 International Anesthesia Research Society.)

Background and Objectives: Infections play a key role in the development of Guillain-Barré syndrome (GBS) and have been associated with specific clinical features and disease severity. The clinical variation of GBS across geographical regions has been suggested to be related to differences in the distribution of preceding infections, but this has not been studied on a large scale., Methods: We analyzed the first 1,000 patients included in the International GBS Outcome Study with available biosamples (n = 768) for the presence of a recent infection with Campylobacter jejuni , hepatitis E virus, Mycoplasma pneumoniae , cytomegalovirus, and Epstein-Barr virus., Results: Serologic evidence of a recent infection with C. jejuni was found in 228 (30%), M. pneumoniae in 77 (10%), hepatitis E virus in 23 (3%), cytomegalovirus in 30 (4%), and Epstein-Barr virus in 7 (1%) patients. Evidence of more than 1 recent infection was found in 49 (6%) of these patients. Symptoms of antecedent infections were reported in 556 patients (72%), and this proportion did not significantly differ between those testing positive or negative for a recent infection. The proportions of infections were similar across continents. The sensorimotor variant and the demyelinating electrophysiologic subtype were most frequent across all infection groups, although proportions were significantly higher in patients with a cytomegalovirus and significantly lower in those with a C. jejuni infection. C. jejuni -positive patients were more severely affected, indicated by a lower Medical Research Council sum score at nadir ( p = 0.004) and a longer time to regain the ability to walk independently ( p = 0.005). The pure motor variant and axonal electrophysiologic subtype were more frequent in Asian compared with American or European C. jejuni -positive patients ( p < 0.001, resp. p = 0.001). Time to nadir was longer in the cytomegalovirus-positive patients ( p = 0.004)., Discussion: Across geographical regions, the distribution of infections was similar, but the association between infection and clinical phenotype differed. A mismatch between symptom reporting and serologic results and the high frequency of coinfections demonstrate the importance of broad serologic testing in identifying the most likely infectious trigger. The association between infections and outcome indicates their value for future prognostic models., (© 2022 American Academy of Neurology.)

Pain control is a major determinant for successful stone clearance in extracorporeal shockwave lithotripsy (ESWL) for urolithiasis. Pain perception during ESWL may be influenced by patient factors like gender, age, body habitus and anxiety level, and stone related factors like size, laterality and location of stone. We investigated in general, the confounding patient and stone factors influencing pain perception during ESWL with importance given to procedural anxiety in first and the subsequent session of ESWL. This was a prospective observational study of all new consecutive patients who underwent ESWL for a period of 1 year at a tertiary Urological Centre. Demographic and stone anthropometry were analyzed. Pre-procedural anxiety was assessed prior to procedure using hospital anxiety and depression score (HADS) and pain was scored using numerical rating scale-11 at baseline, 30-minutes (i.e., during) and 24 hours after ESWL. Univariate and multivariate analysis for confounding factors included HADs were performed for pain perception. A P value < .05 was considered to be statistically significant. For the study duration, 119 patients were recruited and 72 of them returned for a second session. Procedural anxiety was the only independent factor affecting pain score in ESWL for the first session in multivariate analysis. A statistically significant reduction of mean procedural anxiety score from 6.7 ± 4.5 to 3.2 ± 2.7 (P < .05) for the second ESWL session was observed (n = 72). This was in conjunction with statistical reduction of mean pain score 30 minutes after ESWL from 5.2 ± 2.1 to 4.2 ± 2.1 (P < .05). Patients with HADS ≥ 8 had statistically significant higher mean pain score at all 3 intervals in the first ESWL session. This study has shown that pre-procedural anxiety mainly anticipatory, reduces and shows reduction in pain intensity among patients undergoing repeat ESWL. Hence, anxiety reducing methods should be explored in patients undergoing ESWL to avoid unnecessary analgesic use., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Bronchial asthma among children is a common chronic disease that may impact quality of life. Health education is one of the strategies to improve knowledge and quality of life. This study aims to assess the effect of health education via a mobile application in promoting the quality of life among schoolchildren with asthma in urban Malaysia during the COVID-19 era. A quasi-experimental, pre- and post-intervention design was used in this study involving a total of 214 students, randomly assigned into two groups (an intervention group and a control group). The control group received face-to-face health education, whereas the experimental group received health education via a mobile application. The findings showed that the total score of quality of life improved from a mean total score at pre-intervention of 5.31 ± 1.27 to post-intervention of 5.66 ± 1.28 for the control group, compared with the experimental group with a mean total score of quality of life at pre-intervention of 5.01 ± 1.36 and post-intervention of 5.85 ± 1.29. A comparison between the experimental and control groups using an independent t test showed statistically significant differences in their mean quality of life scores. The effect of health education via a mobile application showed a statistically significant improvement in the mean quality of life score from pre- to post-intervention ( F1,288 = 57.46, P < .01). As recommended, the use of mobile technology in health education improved the quality of life of schoolchildren with asthma as compared with the traditional methods of a face-to-face lecture and/or a handbook. Thus, educational modules using mobile applications do improve quality of life., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Concise definitive review of how to read and critically appraise a systematic review., Data Sources: None., Study Selection: Current literature describing the conduct, reporting, and appraisal of systematic reviews and meta-analyses., Data Extraction: Best practices for conducting, reporting, and appraising systematic review were summarized., Data Synthesis: A systematic review is a review of a clearly formulated question that uses systematic and explicit methods to identify, select, and critically appraise relevant original research, and to collect and analyze data from the studies that are included in the review. Critical appraisal methods address both the credibility (quality of conduct) and rate the confidence in the quality of summarized evidence from a systematic review. The A Measurement Tool to Assess Systematic Reviews-2 tool is a widely used practical tool to appraise the conduct of a systematic review. Confidence in estimates of effect is determined by assessing for risk of bias, inconsistency of results, imprecision, indirectness of evidence, and publication bias., Conclusions: Systematic reviews are transparent and reproducible summaries of research and conclusions drawn from them are only as credible and reliable as their development process and the studies which form the systematic review. Applying evidence from a systematic review to patient care considers whether the results can be directly applied, whether all important outcomes have been considered, and if the benefits are worth potential harms and costs., Competing Interests: Dr. Hill’s institution received funding from Fresenius Kabi and the Medical Faculty Rheinisch-Westfälische Technische Hochschule Aachen; she received funding from Fresenius Kabi. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Abstract: Fibromyalgia is a highly heterogeneous condition, but the most common symptoms are widespread pain, fatigue, poor sleep, and low mood. Nonpharmacological interventions are recommended as first-line treatment of fibromyalgia. However which interventions are effective for the different symptoms is not well understood. The objective of this study was to assess the efficacy of nonpharmacological interventions on symptoms and disease-specific quality of life. Seven databases were searched from their inception until June 1, 2020. Randomised controlled trials comparing any nonpharmacological intervention to usual care, waiting list, or placebo in people with fibromyalgia aged >16 years were included without language restriction. Fibromyalgia Impact Questionnaire (FIQ) was the primary outcome measure. Standardised mean difference and 95% confidence interval were calculated using random effects model. The risk of bias was evaluated using the modified Cochrane tool. Of the 16,251 studies identified, 167 randomised controlled trials (n = 11,012) assessing 22 nonpharmacological interventions were included. Exercise, psychological treatments, multidisciplinary modality, balneotherapy, and massage improved FIQ. Subgroup analysis of different exercise interventions found that all forms of exercise improved pain (effect size [ES] -0.72 to -0.96) and depression (ES -0.35 to -1.22) except for flexibility exercise. Mind-body and strengthening exercises improved fatigue (ES -0.77 to -1.00), whereas aerobic and strengthening exercises improved sleep (ES -0.74 to -1.33). Psychological treatments including cognitive behavioural therapy and mindfulness improved FIQ, pain, sleep, and depression (ES -0.35 to -0.55) but not fatigue. The findings of this study suggest that nonpharmacological interventions for fibromyalgia should be individualised according to the predominant symptom., (Copyright © 2021 International Association for the Study of Pain.)

Background and Objectives: A care pathway is a structured care plan based on best clinical practice for a particular patient group. It reorganizes a complex process by providing structured, standardized care and supportive multidisciplinary teamwork. Although care pathways are used worldwide, the impact and benefit of a care pathway for coronary care practices have been minimally debated. This preliminary study aimed to examine the effect of a care pathway on the autonomy, teamwork, and burnout levels among coronary care nurses in a tertiary hospital., Methods: A preliminary study was conducted using a pre/posttest one-group quasi-experimental design. A self-administered questionnaire was provided to 37 registered nurses from the cardiac ward of a tertiary hospital. The care pathway was developed on the basis of the current literature, local guidelines, and expert panel advice. The autonomy, teamwork, and burnout levels at the beginning and 4 months after disseminating the care pathway were measured. Implementing the care pathway included educational sessions, training in using the care pathway, and site visits to monitor nursing practices., Results: Most of the respondents were female (94.6%; n = 35), the median age of the respondents was 26.5 years (interquartile range [IQR] = 23-31), and the median length of the clinical experience was 4 years (IQR = 2-8). A statistically significant reduction in the mean burnout score was observed (mean of 58.12 vs 52.69, P < .05). A slight improvement in autonomy level was found, although it was not statistically significant. No statistically significant improvement was found in the teamwork levels., Conclusion: The care pathway was associated with reduced nurse burnout. The results showed a slight improvement in autonomy level among coronary care nurses after implementing the care pathway. From a practical viewpoint, the current study can help policy makers and managers reduce burnout. This study highlights the importance of using care pathways as a tool to reorganize the care process and improve the working environment. Managers must support nursing decisions and provide continuous education to enhance nurses' autonomy, which may increase understanding of respective roles, leading to higher levels of teamwork. However, with a small sample size, caution must be applied, as the findings might not be generalizable., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Although the physiatric community increasingly embraces evidence-based medicine (EBM), the current state of EBM training for trainees in physiatry is unclear. The purposes of this article are to report the results of the Association of Academic Physiatrists' surveys of physiatry residency programs in the United States, to discuss the implications of their findings, and to better delineate the "baseline" upon which sound and clear recommendations for systematic EBM training can be made. The two Association of Academic Physiatrists surveys of US physiatry residency programs reveal that most survey respondents report that they include EBM training in their programs that covers the five recommended steps of EBM core competencies. However, although most respondents reported using traditional pedagogic methods of training such as journal club, very few reported that their EBM training used a structured and systematic approach. Future work is needed to support and facilitate physiatry residency programs interested in adopting structured EBM training curricula that include recommended EBM core competencies and the evaluation of their impact., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: d-Amino acids (d-AAs) have been associated with age-associated conditions in the general population but their relevance in people with HIV (PWH), who experience accentuated/accelerated aging has not been studied. We compared d-AA levels in HIV-infected and uninfected controls and explored their association with markers of immune activation, gut permeability and organ dysfunction., Design: Case-control analysis., Method: Plasma samples from 60 antiretroviral therapy-treated HIV-infected individuals and 59 uninfected controls were analysed. A three-dimensional HPLC system was used to measure d-and l-asparagine, serine, alanine and proline and presented as %d-AA. Additionally, cell-associated and soluble markers of immune activation and senescence were characterized. Kidney and liver functions were expressed as estimated glomerular filtration rate and fibrosis-4 scores, respectively. Mann-Whitney and Spearman rank correlation coefficients were used for statistical analysis., Results: d-Asparagine, d-serine, d-alanine and d-proline were detectable in all plasma samples and correlated with age in HIV-infected and uninfected but not different between groups. Kynurenine/tryptophan ratio was positively correlated with all %d-AAs in PWH and with %d-serine and %d-proline in controls. %d-AAs were not consistently correlated with markers of gut permeability in both groups. All %d-AAs were also correlated with kidney function in both groups whereas age-associated accumulation of %d-asparagine, %d-serine and %d-proline were correlated with liver function and the VACS score in controls., Conclusion: Plasma d-AAs are associated with chronological age and correlated with markers of immune activation and organ decline, though variably, in PWH and controls. Their role in the biology of aging warrants further investigation., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Thyrotoxic periodic paralysis is characterized by recurrent episodes of reversible, severe proximal muscle weakness associated with hypokalemia and hyperthyroidism. Prolonged exercise test is an easy, noninvasive method of demonstrating abnormal muscle membrane excitability in periodic paralyses. Although abnormal in thyrotoxic periodic paralysis patients, the effects thyroid hormone levels in non-thyrotoxic periodic paralysis thyrotoxicosis patients have not been well studied. The study aims to evaluate thyrotoxicosis patients (regardless of thyrotoxic periodic paralysis history) with prolonged exercise test and correlate it with their thyroid status., Methods: This is a prospective, cross-sectional study of consecutive thyrotoxicosis patients seen at the endocrine clinic of a tertiary medical center. Thyroid status was determined biochemically before prolonged exercise test. Compound muscle action potential (CMAP) amplitudes postexercise were compared against pre-exercise amplitudes and recorded as percentage of mean baseline CMAP amplitude. Comparisons of time-dependent postexercise CMAP amplitudes and mean CMAP amplitude decrement were made between hyperthyroid and nonhyperthyroid groups., Results: Seventy-four patients were recruited, 23 (31%) men, 30 (41%) Chinese, and the mean age was 48.5 ± 16.8 years. Of 74 patients, 32 (43%) were hyperthyroid and 42 (57%) were nonhyperthyroid viz. euthyroid and hypothyroid. Time-dependent CMAP amplitudes from 10 to 45 minutes after exercise were significantly lower in hyperthyroid patients compared with nonhyperthyroid patients (P < 0.01). Mean CMAP amplitude decrement postexercise was significantly greater in hyperthyroid than nonhyperthyroid patients (23.4% ± 11.4% vs. 17.3% ± 10.5%; P = 0.02)., Conclusions: Compound muscle action potential amplitude declines on prolonged exercise test were significantly greater in hyperthyroid patients compared with nonhyperthyroid patients. Muscle membrane excitability is highly influenced by thyroid hormone level. Thyrotoxic periodic paralysis occurs from increased levels of thyroid hormone activity in susceptible patients., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 by the American Clinical Neurophysiology Society.)

Objectives: To conduct a systematic review and meta-analysis to evaluate the impact of IV vitamin C on outcomes in critically ill patients., Data Sources: Systematic search of MEDLINE, EMBASE, CINAHL, and the Cochrane Register of Controlled Trials., Study Selection: Randomized controlled trials testing IV vitamin C in critically ill patients., Data Abstraction: Two independent reviewers abstracted patient characteristics, treatment details, and clinical outcomes., Data Synthesis: Fifteen studies involving 2,490 patients were identified. Compared with placebo, IV vitamin C administration is associated with a trend toward reduced overall mortality (relative risk, 0.87; 95% CI, 0.75-1.00; p = 0.06; test for heterogeneity I2 = 6%). High-dose IV vitamin C was associated with a significant reduction in overall mortality (relative risk, 0.70; 95% CI, 0.52-0.96; p = 0.03), whereas low-dose IV vitamin C had no effect (relative risk, 0.94; 95% CI, 0.79-1.07; p = 0.46; test for subgroup differences, p = 0.14). IV vitamin C monotherapy was associated with a significant reduction in overall mortality (relative risk, 0.64; 95% CI, 0.49-0.83; p = 0.006), whereas there was no effect with IV vitamin C combined therapy. No trial reported an increase in adverse events related to IV vitamin C., Conclusions: IV vitamin C administration appears safe and may be associated with a trend toward reduction in overall mortality. High-dose IV vitamin C monotherapy may be associated with improved overall mortality, and further randomized controlled trials are warranted., Competing Interests: Dr. Hill disclosed relations with Woerwag Pharma supplying the investigational product for a study regarding vitamin C in cardiac surgery patients. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background and Objectives: There is a worldwide increase in the incidence of stroke in young adults, with major regional and ethnic differences. Advancing knowledge of ethnic and regional variation in causes and outcomes will be beneficial in implementation of regional health care services. We studied the global distribution of risk factors, causes, and 3-month mortality of young patients with ischemic stroke, by performing a patient data meta-analysis from different cohorts worldwide., Methods: We performed a pooled analysis of individual patient data from cohort studies that included consecutive patients with ischemic stroke aged 18-50 years. We studied differences in prevalence of risk factors and causes of ischemic stroke between different ethnic and racial groups, geographic regions, and countries with different income levels. We investigated differences in 3-month mortality by mixed-effects multivariable logistic regression., Results: We included 17,663 patients from 32 cohorts in 29 countries. Hypertension and diabetes were most prevalent in Black (hypertension, 52.1%; diabetes, 20.7%) and Asian patients (hypertension 46.1%, diabetes, 20.9%). Large vessel atherosclerosis and small vessel disease were more often the cause of stroke in high-income countries (HICs; both p < 0.001), whereas "other determined stroke" and "undetermined stroke" were higher in low and middle-income countries (LMICs; both p < 0.001). Patients in LMICs were younger, had less vascular risk factors, and despite this, more often died within 3 months than those from HICs (odds ratio 2.49; 95% confidence interval 1.42-4.36)., Discussion: Ethnoracial and regional differences in risk factors and causes of stroke at young age provide an understanding of ethnic and racial and regional differences in incidence of ischemic stroke. Our results also highlight the dissimilarities in outcome after stroke in young adults that exist between LMICs and HICs, which should serve as call to action to improve health care facilities in LMICs., (© 2021 American Academy of Neurology.)

Background and Objectives: The clinical course and outcome of the Guillain-Barré syndrome (GBS) are diverse and vary among regions. The modified Erasmus GBS Outcome Score (mEGOS), developed with data from Dutch patients, is a clinical model that predicts the risk of walking inability in patients with GBS. The study objective was to validate the mEGOS in the International GBS Outcome Study (IGOS) cohort and to improve its performance and region specificity., Methods: We used prospective data from the first 1,500 patients included in IGOS, aged ≥6 years and unable to walk independently. We evaluated whether the mEGOS at entry and week 1 could predict the inability to walk unaided at 4 and 26 weeks in the full cohort and in regional subgroups, using 2 measures for model performance: (1) discrimination: area under the receiver operating characteristic curve (AUC) and (2) calibration: observed vs predicted probability of being unable to walk independently. To improve the model predictions, we recalibrated the model containing the overall mEGOS score, without changing the individual predictive factors. Finally, we assessed the predictive ability of the individual factors., Results: For validation of mEGOS at entry, 809 patients were eligible (Europe/North America [n = 677], Asia [n = 76], other [n = 56]), and 671 for validation of mEGOS at week 1 (Europe/North America [n = 563], Asia [n = 65], other [n = 43]). AUC values were >0.7 in all regional subgroups. In the Europe/North America subgroup, observed outcomes were worse than predicted; in Asia, observed outcomes were better than predicted. Recalibration improved model accuracy and enabled the development of a region-specific version for Europe/North America (mEGOS-Eu/NA). Similar to the original mEGOS, severe limb weakness and higher age were the predominant predictors of poor outcome in the IGOS cohort., Discussion: mEGOS is a validated tool to predict the inability to walk unaided at 4 and 26 weeks in patients with GBS, also in countries outside the Netherlands. We developed a region-specific version of mEGOS for patients from Europe/North America., Classification of Evidence: This study provides Class II evidence that the mEGOS accurately predicts the inability to walk unaided at 4 and 26 weeks in patients with GBS., Trial Registration Information: NCT01582763., (© 2021 American Academy of Neurology.)

Background: Abnormalities in computed tomography myocardial perfusion has been associated with coronary artery disease and major adverse cardiovascular events (MACE). We sought to investigate if subendocardial attenuation using coronary computed tomography angiography predicts MACE 30 days postelective noncardiac surgery., Methods: Using a 17-segment model, coronary computed tomography angiography images were analyzed for subendocardial and transmural attenuation and the corresponding blood pool. The segment with the lowest subendocardial attenuation and transmural attenuation were normalized to the segment with the highest subendocardial and transmural attenuation, respectively (SUB normalized , and TRANS normalized , respectively). We evaluated the independent and incremental value of myocardial attenuation to predict the composite of cardiovascular death or nonfatal myocardial infarction., Results: Of a total of 995 coronary CTA VISION (Coronary Computed Tomographic Angiography and Vascular Events in Noncardiac Surgery Patients Cohort Evaluation Study) patients, 735 had available images and complete data for these analyses. Among these patients, 60 had MACE. Based on Revised Cardiovascular Risk Index, 257, 302, 138, and 38 patients had scores of 0, 1, 2, and ≥3, respectively. On coronary computed tomography angiography, 75 patients had normal coronary arteries, 297 patients had nonobstructive coronary artery disease, 264 patients had obstructive disease, and 99 patients had extensive obstructive coronary artery disease. SUB normalized was an independent and incremental predictor of events in the model that included Revised Cardiovascular Risk Index and coronary artery disease severity. Compared with patients in the highest tertile of SUB normalized , patients in the second and first tertiles had an increased hazards ratio for events (2.23 [95% CI, 1.091-4.551] and 2.36 [95% CI, 1.16-4.81], respectively). TRANS normalized , as a continuous variable, was also found to be a predictor of MACE ( P =0.027)., Conclusions: Our study demonstrates that SUB normalized and TRANS normalized are independent and incremental predictors of MACE 30 days after elective noncardiac surgery. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01635309.

Objectives: Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder that may have normal physical examination, clinical laboratory testing and vestibular evaluation. However, advances in neuroimaging have provided new insights in brain functional connectivity and structure in patients with PPPD. This systematic review was aimed at identifying significant structural or alterations in functional connectivity in patients with PPPD., Databases Reviewed: Science Direct, Pubmed, Embase via Ovid databases, and Cochrane library., Methods: This review following the guidelines of PRISMA, systematically and independently examined papers published up to March 2021 which fulfilled the predetermined criteria. PROSPERO Registration (CRD42020222334)., Results: A total of 15 studies were included (MRI = 4, SPECT = 1, resting state fMRI = 4, task-based fMRI = 5, task-based fMRI + MRI = 1). Significant changes in the gray matter volume, cortical folding, blood flow, and connectivity were seen at different brain regions involved in vestibular, visual, emotion, and motor processing., Conclusion: There is a multisensory dimension to the impairment resulting in chronic compensatory changes in PPPD that is evident by the significant alterations in multiple networks involved in maintaining balance. These changes observed offer some explanation for the symptoms that a PPPD patient may experience.Systematic Review Registration: This study is registered with PROSPERO (CRD42020222334)., Competing Interests: The authors disclose no conflicts of interest, financial, or otherwise., (Copyright © 2021, Otology & Neurotology, Inc.)

Objective: The aim of this study is to examine the association between genetic variations in deleted in liver cancer 1 (DLC1) gene with progression of the hepatitis B virus (HBV) infection., Methods: A total of 623 subjects were included in this study, of whom, 423 were chronic hepatitis B (CHB) patients without liver cirrhosis or hepatocellular carcinoma (HCC), 103 CHB with either liver cirrhosis ± HCC and 97 individuals who had resolved HBV. Two single-nucleotide polymorphisms rs3739298 and rs532841 of DLC1 gene were genotyped using the Sequenom MassARRAY platform., Results: Our results indicated significant differences between the chronic HBV and resolved HBV groups in genotype and allele frequencies of DLC1-rs3739298 [odds ratio (OR) = 2.23; 95% confidence interval (CI): 1.24-3.99; P = 0.007] and (OR = 1.54; 95% CI: 1.07-2.22; P = 0.021), respectively. Moreover, haplotype analysis revealed significant associations between chronicity of HBV with TG and GA haplotypes (P = 0.041 and P = 0.042), respectively., Conclusion: A significant association exists between the rs3739298 variant and susceptibility to CHB infection., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Prospective randomized double-blinded trial., Objective: The objective of this study is to determine the efficacy of high-dose versus low-dose tranexamic acid (TXA) in adolescent idiopathic scoliosis (AIS) corrective surgery., Summary of Background Data: Corrective surgery for AIS is associated with significant blood loss. Evidence on the optimum TXA dose to reduce bleeding in pediatric population is scarce., Methods: A total of 166 AIS patients aged between 10 and 21 years, of American Society of Anesthesiologists (ASA) physical status I and II, preoperative hemoglobin >10 g/dL, platelet count >150,000 cells/L and Cobb angle of >45° scheduled for elective single-stage posterior spinal fusion (PSF) surgery by two attending surgeons were included between March 2017 and November 2018. Patients were randomized into Group A (High Dose, 30 mg/kg TXA loading dose followed by 10 mg/kg/h infusion) and Group B (Low Dose, 10 mg/kg TXA loading dose followed by 1 mg/kg/h infusion). The primary outcome was total surgical blood loss between both groups. Secondary outcomes were transfusion requirement, perioperative changes in hemoglobin and coagulation profiles, adverse events, and factors that influence total blood loss., Results: The mean total surgical blood loss between the two groups was not significant (Group A: 928.8 ± 406.1 mL [range: 348-1857 mL]; Group B: 918.1 ± 406.2 mL [range: 271-2000 mL], P = 0.865). The median duration of surgery was 120 minutes. One patient in each group received allogenic blood transfusion during the perioperative period. There were no significant changes in hemoglobin and coagulation profile at pre-operation, post-operation 0 hour and 48 hours. Sex, number of vertebral levels fused, and duration of surgery were independently associated with total surgical blood loss. No adverse events were observed perioperatively., Conclusion: Low-dose TXA was as efficacious as high-dose TXA in reducing blood loss and allogenic blood transfusion for AIS patients undergoing PSF surgery.Level of Evidence: 1., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The COVID-19 pandemic has rerouted the healthcare ecosystem by accelerating digital health, and rapid adoption of eHealth is partly influenced by eHealth literacy (eHL). This study aims to examine patients' eHL in relation to their "technology readiness"-an innate attitude that is underexplored in clinical research. A total of 276 adult inpatients with hypertension, diabetes mellitus, and coronary heart disease were surveyed cross-sectionally in 2019 using self-reported questionnaires: eHealth Literacy Scale and Technology Readiness Index (2.0). The study found moderate eHL (mean, 27.38) and moderate technology readiness (mean, 3.03) among patients. The hierarchical regression model shows that lower eHL scores were associated with patients of minor ethnicity (Malaysian Chinese), with an unemployed status, and having >1 cardiovascular risk (β = -0.136 to -0.215, R2 = 0.283, Ps < .005). Technology readiness is a strong determinant of eHL (ΔR2 = 0.295, P < .001) with its subdomains (optimism, innovativeness, and discomfort) significantly influencing eHL (|β| = 0.28-0.40, Ps < .001), except for the insecurity subdomain. Deployment of eHealth interventions that incorporate assessment of patients' eHL and technology readiness will enable targeted strategies, especially in resource-limited settings hit hard by the pandemic crisis., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest.

Background: The purpose of this study was to determine the incidence, characteristics, impact, and risk factors associated with persistent incisional pain. The hypothesis was that patient demographics and perioperative interventions are associated with persistent pain., Methods: This was a secondary analysis of an international prospective cohort study from 2012 to 2014. This study included patients who were 45 yr of age or older who underwent major inpatient noncardiac surgery. Data were collected perioperatively and at 1 yr after surgery to assess for the development of persistent incisional pain (pain present around incision at 1 yr after surgery)., Results: Among 14,831 patients, 495 (3.3%; 95% CI, 3.1 to 3.6) reported persistent incisional pain at 1 yr, with an average pain intensity of 3.6 ± 2.5 (0 to 10 numeric rating scale), with 35% and 14% reporting moderate and severe pain intensities, respectively. More than half of patients with persistent pain reported needing analgesic medications, and 85% reported interference with daily activities (denominator = 495 in the above proportions). Risk factors for persistent pain included female sex (P = 0.007), Asian ethnicity (P < 0.001), surgery for fracture (P < 0.001), history of chronic pain (P < 0.001), coronary artery disease (P < 0.001), history of tobacco use (P = 0.048), postoperative patient-controlled analgesia (P < 0.001), postoperative continuous nerve block (P = 0.010), insulin initiation within 24 h of surgery (P < 0.001), and withholding nonsteroidal anti-inflammatory medication or cyclooxygenase-2 inhibitors on the day of surgery (P = 0.029 and P < 0.001, respectively). Older age (P < 0.001), endoscopic surgery (P = 0.005), and South Asian (P < 0.001), Native American/Australian (P = 0.004), and Latin/Hispanic ethnicities (P < 0.001) were associated with a lower risk of persistent pain., Conclusions: Persistent incisional pain is a common complication of inpatient noncardiac surgery, occurring in approximately 1 in 30 adults. It results in significant morbidity, interferes with daily living, and is associated with persistent analgesic consumption. Certain demographics, ethnicities, and perioperative practices are associated with increased risk of persistent pain., (Copyright © 2021, the American Society of Anesthesiologists. All Rights Reserved.)

Niemann-Pick disease type C (NP-C) is a severe neurovisceral lipid storage disease that results in the accumulation of unesterified cholesterol in lysosomes or endosomes. The clinical presentations of NP-C are variable which include visceral symptoms, neurologic symptoms and psychiatric symptoms. Psychosis is the most common psychiatric manifestation of NP-C and is indistinguishable from a typical psychosis presentation of schizophrenia. The common psychotic presentations in NP-C include visual hallucinations, delusions, auditory hallucinations and thought disorders. Psychosis symptoms are more common in adult or adolescent-onset forms compared with pediatric-onset forms. The underlying pathophysiology of psychosis in NP-C is most probably due to dysconnectivity particularly between frontotemporal connectivity and subcortical structures. NP-C sometimes is mistaken for schizophrenia which causes delay in treatment due to lack of awareness and literature review. This review aims to summarize the relevant case reports on psychosis symptoms in NP-C and discuss the genetics and pathophysiology underlying the condition., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Poly lactic-co-glycolic acid (PLGA) nanoparticles are intensively studied nanocarriers in drug delivery because of their biodegradability and biochemical characteristics. Polyethylene glycol (PEG) coating for nanocarriers gives them long circulation time in blood and makes them invisible to the reticuloendothelial system. Breast cancer cells have greater uptake of hyaluronic acid compared to normal cells as it binds to their overexpressed CD44 receptors. Since hypoxia plays an important role in cancer metastasis; we formulated PEG-PLGA nanoparticles coated with hyaluronic acid as targeted delivery system for doxorubicin (DOX) using nanoprecipitation method, and characterized them for chemical composition, size, surface charge, shape, and encapsulation efficiency. Then we tested them in vitro on hypoxia-optimized metastatic breast cancer cells. The nanoparticles were spherical with an average size of about 106 ± 53 nm, a negative surface charge (-15 ± 3 mV), and high encapsulation efficiency (73.3 ± 4.1%). In vitro investigation with hypoxia-elevated CD44 MDA-MB-231 cells showed that hyaluronic acid-targeted nanoparticles maintained their efficacy despite hypoxia-induced drug resistance unlike free DOX and nontargeted nanoparticles. In conclusion, this study revealed a simple third generation nanoparticle formulation for targeted treatment of hypoxia-induced drug resistance in breast cancer metastatic cells. Further, optimization is needed including In vivo efficacy and nanoparticle-specific pharmacokinetic studies., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Obstructive sleep apnea (OSA) has been found to be associated with difficult airway, although there is a paucity of prospective studies investigating thresholds of OSA severity with difficult airway outcomes. The aim of this study was to examine the association between OSA and difficult intubation or difficult mask ventilation. We also explored the utility of the Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and Gender (STOP-Bang) score for difficult airway prediction., Methods: The Postoperative Vascular Complications in Unrecognized Obstructive Sleep Apnea (POSA) trial was an international prospective cohort study of surgical patients 45 years or older with one or more cardiac risk factor presenting for noncardiac surgery, with planned secondary analyses of difficult airway outcomes. Multivariable logistic regression analyses tested associations between OSA severity and predictors of difficult airway with difficult intubation or difficult mask ventilation. Overall, 869 patients without prior diagnosis of OSA were screened for OSA risk with the STOP-Bang tool, underwent preoperative sleep study, and had routine perioperative care, including general anesthesia with tracheal intubation. The primary outcome analyzed was difficult intubation, and the secondary outcome was difficult mask ventilation., Results: Based on the sleep studies, 287 (33%), 324 (37%), 169 (20%), and 89 (10%) of the 869 patients had no, mild, moderate, and severe OSA, respectively. One hundred and seventy-two (20%) had a STOP-Bang score of 0-2 (low risk), 483 (55%) had a STOP-Bang score of 3-4 (intermediate risk), and 214 (25%) had a STOP-Bang score 5-8 (high risk). The incidence of difficult intubation was 6.7% (58 of 869), and difficult mask ventilation was 3.7% (32 of 869). Multivariable logistic regression demonstrated that moderate OSA (odds ratio [OR] = 3.26 [95% confidence interval {CI}, 1.37-8.38], adjusted P = .010) and severe OSA (OR = 4.05 [95% CI, 1.51-11.36], adjusted P = .006) but not mild OSA were independently associated with difficult intubation compared to patients without OSA. Relative to scores of 0-2, STOP-Bang scores of 3-4 and 5-8 were associated with increased odds of difficult intubation (OR = 3.01 [95% CI, 1.13-10.40, adjusted P = .046] and 4.38 [95% CI, 1.46-16.36, adjusted P = .014]), respectively. OSA was not associated with difficult mask ventilation, and only increasing neck circumference was found to be associated (adjusted P = .002)., Conclusions: Moderate and severe OSA were associated with difficult intubation, and increasing neck circumference was associated with difficult mask ventilation. A higher STOP-Bang score of 3 or more may be associated with difficult intubation versus STOP-Bang score of 0-2. Anesthesiologists should be vigilant for difficult intubation when managing patients suspected or diagnosed with OSA., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2021 International Anesthesia Research Society.)

Study Design: Retrospective study., Objective: To assess the learning curve of a dual attending surgeon strategy in severe adolescent idiopathic scoliosis patients., Summary of Background Data: The advantages of a dual attending surgeon strategy in improving the perioperative outcome in scoliosis surgery had been reported. However, the learning curve of this strategy in severe scoliosis had not been widely studied., Methods: A total of 105 patients with adolescent idiopathic scoliosis with Cobb angle of 90° or greater, who underwent posterior spinal fusion using a dual attending surgeon strategy were recruited. Primary outcomes were operative time, total blood loss, allogeneic blood transfusion requirement, length of hospital stay from time of operation and perioperative complications. Cases were sorted chronologically into group 1: cases 1 to 35, group 2: cases 36 to 70, and group 3: case 71 to 105. Mean operative time (≤193.3 min), total blood loss (≤1612.2 mL), combination of both and allogeneic blood transfusion were the selected criteria for receiver operating characteristic analysis of the learning curve., Results: The mean Cobb angle was 104.5° ± 12.3°. The operative time, total blood loss, and allogeneic blood transfusion requirement reduced significantly for group 1 (220.6 ± 54.8 min; 2011.3 ± 881.8 mL; 12 cases) versus group 2 (183.6 ± 36.7 min; 1481.6 ± 1035.5 mL; 3 cases) and group 1 versus group 3 (175.6 ± 38.4 min; 1343.7 ± 477.8 mL; 3 cases) (P < 0.05). There were six perioperative complications. Fifty-seven cases were required to achieve the preset criteria (mean operative time and mean total blood loss) (area under the curve 0.740; P < 0.001; sensitivity 0.675; specificity 0.662)., Conclusion: There was significant improvement in operative time and total blood loss when comparing group 1 versus group 2 and group 1 versus group 3. The cut-off point for the learning curve was 57 cases when the preset criteria were fulfilled (≤193.3 min operative time and ≤1612.2 mL of total blood loss).Level of Evidence: 4., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Chronic kidney disease (CKD)-associated pruritus (CKD-aP) contributes to poor quality of life, including reduced sleep quality and poor sleep quality is a source of patient stress and is linked to lower health-related quality of life. This study aimed to investigate the effectiveness of zolpidem 10 mg and acupressure therapy on foot acupoints to improve the sleep quality and overall quality of life among hemodialysis patients suffering from CKD-aP., Method: A multicenter, prospective, randomized, parallel-design, open label interventional study to estimate the effectiveness of zolpidem (10 mg) oral tablets versus acupressure on sleep quality and quality of life in patients with CKD-aP on hemodialysis. A total of 58 hemodialysis patients having sleep disturbance due to CKD-aP completed the entire 8-week follow-up. The patients were divided into a control (acupressure) group of 28 patients and an intervention (zolpidem) group of 30 patients., Results: A total of 58 patients having CKD-aP and sleep disturbance were recruited. In the control group there was a reduction in the PSQI score with a mean ± SD from 12.28 ± 3.59 to 9.25 ± 3.99, while in the intervention group the reduction in PSQI score with a mean ± SD was from 14.73 ± 4.14 to 10.03 ± 4.04 from baseline to endpoint. However, the EQ5D index score and EQ-visual analogue scale (VAS) at baseline for the control group with a mean ± SD was 0.49 ± 0.30 and 50.17 ± 8.65, respectively, while for the intervention group the values were 0.62 ± 0.26 and 47.17 ± 5.82, respectively. The mean EQ5D index score in the control group improved from 0.49 ± 0.30 to 0.53 ± 0.30, but in the intervention group there was no statistical improvement in mean EQ5D index score from 0.62 ± 0.26 to 0.62 ± 0.27 from baseline to week 8. The EQ 5D improved in both groups and the EQ-VAS score was 2.67 points higher at week 8 as compared to baseline in the control group, while in the intervention group the score was 3.33 points higher at week 8 as compared to baseline. Comparing with baseline, the PSQI scores were significantly reduced after week 4 and week 8 (P =  < .001). Furthermore, at the end of the study, the PSQI scores were significantly higher in the control as compared to the intervention group (P = .012)., Conclusion: An improvement in sleep quality and quality of life among CKD-aP patients on hemodialysis has been observed in both the control and intervention groups. Zolpidem and acupressure safety profiling showed no severe adverse effect other that drowsiness, nausea and daytime sleeping already reported in literature of zolpidem., Competing Interests: The authors have conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: To evaluate the clinical and imaging findings of papillary breast neoplasm and review the pathologic correlation at a tertiary center.Retrospective study of patients diagnosed with benign and malignant papillary lesions between 2008 to 2018. 147 patients were identified with histology diagnosis of papillary lesions. The clinical, imaging, and pathological characteristics were reviewed.Patient cohort included 147 women diagnosed with papillary lesions (mean age at diagnosis 53.8 years) and were divided into 3 histology groups (benign, atypical, and malignant). Common clinical presentations were breast lump (n = 60) and nipple discharge (n = 29), 48 patients were asymptomatic.Only 37 were detected as a mass lesion on mammogram. The presence of mass lesion on mammogram was the most common feature in all 3 papillary lesion groups, and with the presence of asymmetric density, were the 2 mammographic features significantly associated (P < .05) with malignancy.All lesions were detected on ultrasound. The most common sonographic features for all 3 groups were the presence of a mass and irregular shape. Among all the sonographic features assessed, larger size, presence of vascularity and absence of dilated ducts were significantly associated (P < .05) with malignancy.Feature pattern recognition of the variety of benign, atypical and malignant papillary neoplasm on ultrasound and mammogram, with emphasis on size, presence of vascularity and dilated ducts on ultrasound and presence of mass, and architectural distortion on mammogram, is important in the assessment of patients with suspected ductal lesions to facilitate optimal treatment and surgical care., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To determine whether probiotics are effective for constipation, a common and often difficult-to-treat problem, in Parkinson disease (PD)., Methods: In this double-blind, randomized, placebo-controlled, single-center trial, 280 patients with PD were screened, and 72 eligible patients were block-randomized (1:1) to receive either multistrain probiotics capsules (n = 34) or identical-appearing placebo (n = 38), for 4 weeks. The primary endpoint was the change in the average number of spontaneous bowel movements (SBM) per week during the last 2 weeks of intervention compared with the 2-week preintervention phase, recorded by daily stool diary. Secondary outcome measures included changes in stool consistency, constipation severity score, and quality of life related to constipation. Satisfaction with intervention received was assessed. Change in levels of fecal calprotectin, a marker of intestinal inflammation, was an exploratory outcome., Results: SBM increased by 1.0 ± 1.2 per week after treatment with probiotics and decreased by 0.3 ± 1.0 per week in the placebo group (mean difference 1.3, 95% confidence interval 0.8-1.8, p < 0.001). Significant improvements were also seen for secondary outcomes after correction for multiple comparisons, including stool consistency ( p = 0.009) and quality of life related to constipation ( p = 0.001). In the treatment group, 65.6% reported satisfaction with the intervention vs only 21.6% in the placebo group ( p < 0.001). One patient (2.9%) in the treatment group withdrew due to a nonserious adverse event. Fecal calprotectin did not change significantly during the study., Conclusions: Multistrain probiotics treatment was effective for constipation in PD. Further studies are needed to investigate the long-term efficacy and safety of probiotics in PD, as well as their mechanisms of action., Clinicaltrialsgov Identifier: NCT03377322., Classification of Evidence: This study provides Class I evidence that, for people with PD, multistrain probiotics significantly increased the average number of SBM per week., (© 2020 American Academy of Neurology.)

Purpose of Review: The endoscopic medial maxillectomy (EMM) has remained a relevant procedure for certain sinus diseases and at the same time reemerged as a salvage technique or even as a primary procedure for other diseases. Several mucosal-sparing techniques have also been described and the outcome of the surgeries is available for review., Recent Findings: Modifications of the EMM technique in the last two decades, aimed at mucosal preservation of the inferior turbinate, nasolacrimal duct, and medial maxillary wall have been successful in addressing a multitude of diseases. There are also evidences to support adjunct procedures/methods to improve access, healing, and to address associated dysfunction such as impaired mucociliary clearance. Tailored approaches have shown favourable outcomes with a low rate of adverse effects., Summary: The EMM is appropriate for selected indications, in particular lesions causing medial wall destruction or extensive tumour involving the anterior wall or the prelacrimal recess. As for other maxillary sinus diseases including those identified to a limited site, a modified EMM is a reasonable consideration. The choice is appropriate provided instrument access, visualization, the ability for complete resection, postoperative care, and the requirement for surveillance is not compromised. A tailored approach with or without adjunct procedures is recommended., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)