Effect of perioperative intravenous ibuprofen versus acetaminophen on postoperative opioid consumption and pain after general anesthesia: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

Background: Ibuprofen and acetaminophen are widely used as adjuvant analgesics for postoperative pain. This meta-analysis compared the effects of intravenous (IV) ibuprofen and acetaminophen on postoperative opioid consumption and pain intensity after general anesthesia. Methods: PubMed/MEDLINE, EMBASE, and Cochrane Library databases were searched to identify relevant studies published up to May 2023. Randomized controlled trials (RCTs) comparing the effects of perioperative IV ibuprofen and acetaminophen on postoperative opioid consumption and pain after general anesthesia were included in the meta-analysis and trial sequential analysis (TSA). Results: Eight studies with 494 participants were included. Compared to IV acetaminophen, IV ibuprofen significantly reduced 24 h opioid consumption, presented as morphine equivalents (mean difference [MD]: -6.01 mg, 95% CI [-8.60, -3.42], P < 0.00001, I2 = 55%), and pain scores (on a scale of 0-10) at 4-6 h (MD: -0.83, 95% CI [-1.29, -0.37], P = 0.0004, I2 = 65%) and 12 h (MD: -0.38, 95% CI [-0.68, -0.08], P = 0.01, I2 = 11%) postoperatively. These results were statistically significant in TSA. Pain scores at 24 h postoperatively and side effects were not significantly different between the two groups in the meta-analysis, and TSA revealed that the sample size was too small to adequately evaluate the effects, requiring further studies for conclusive results. Conclusions: Perioperative IV ibuprofen reduced 24 h opioid consumption and pain severity up to 12 h postoperatively compared to acetaminophen. Additional research is required to assess pain intensity beyond 12 h and side effects.

Replacing Mercury Sphygmomanometers With Mercury-Free Sphygmomanometers for the National Health Survey in Children: Direct Comparisons Applying Two Types of Mercury-Free Sphygmomanometer.

BACKGROUND AND OBJECTIVES: Blood pressure (BP) measurement using an auscultatory sphygmomanometer is recommended for diagnosing hypertension in children. As mercury sphygmomanometers (MSs) are banned owing to environmental concerns, it is crucial to determine the accuracy of mercury-free sphygmomanometers to replace them. We analyzed the accuracy of these devices to guide the National Survey selection. METHODS: BP was measured thrice each with MS, auscultatory device (AD), and oscillometric device (OD) in 104 participants aged 10-18 using the National Survey data. The difference in BP was defined as the difference between MS and other devices. The BP differences, correlations, and influencing factors were analyzed. The frequencies of hypertension were also compared. RESULTS: Systolic BP (SBP) and diastolic BP (DBP) differences between MS and AD were 0.88±3.36 mmHg and 0.63±3.95 mmHg, and those between MS and OD were 0.43±5.83 mmHg and 4.57±6.89 mmHg, respectively. The absolute error of <10 mmHg for DBP between MS and OD was 76%. The concordance correlation coefficient between MS and AD was 0.94 for SBP and 0.90 for DBP, and 0.81 and 0.67, respectively for MS and OD. Arm circumference negatively correlated with BP differences except for SBP between the MS and OD. The frequency of hypertension was not different between MS and AD but was underestimated by OD. CONCLUSIONS: AD correlated well with MS, while OD did not, especially for DBP. The superiority of AD over OD suggests AD as a possible alternative for MS in the National Survey.

Accelerating Progress Towards the 2030 Neglected Tropical Diseases Targets: How Can Quantitative Modeling Support Programmatic Decisions?

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021-2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.

Newly Developed Sex-Specific Z Score Model for Coronary Artery Diameter in a Pediatric Population.

BACKGROUND: This study aimed to generate a Z score calculation model for coronary artery diameter of normal children and adolescents to be adopted as the standard calculation method with consensus in clinical practice. METHODS: This study was a retrospective, multicenter study that collected data from multiple institutions across South Korea. Data were analyzed to determine the model that best fit the relationship between the diameter of coronary arteries and independent demographic parameters. Linear, power, logarithmic, exponential, and square root polynomial models were tested for best fit. RESULTS: Data of 2,030 subjects were collected from 16 institutions. Separate calculation models for each sex were developed because the impact of demographic variables on the diameter of coronary arteries differs according to sex. The final model was the polynomial formula with an exponential relationship between the diameter of coronary arteries and body surface area using the DuBois formula. CONCLUSION: A new coronary artery diameter Z score model was developed and is anticipated to be applicable in clinical practice. The new model will help establish a consensus-based Z score model.

Standardized protocol of blood pressure measurement and quality control program for the Korea National Health and Nutrition Examination Survey.

Accurate blood pressure (BP) measurement is crucial for hypertension detection and management. The Korea National Health and Nutrition Examination Survey (KNHANES) assesses the health of Koreans using representative cross-sectional data. BP measurements were historically done with mercury sphygmomanometers for participants aged ≥10 years. However, KNHANES transitioned to Greenlight 300TM (mercury-free auscultatory device) in 2020 for participants aged ≥6 years and used dual devices (Microlife WatchBP Office AFIB and Greenlight) in 2021-2022. To ensure consistency, KNHANES will adopt Microlife as the unified BP device with Greenlight for device validation from 2023. Under the new protocol, participants aged ≥6 years will have their BP measured three times at 30-second intervals after a 5-minute rest under ambient temperature (20-25℃) and noise ≤65 dB. The average of the 2nd and 3rd readings will be used as the representative BP value. The quality control (QC) program involves four trained examiners passing the "quality control and assurance of BP measurement program" three times annually, and undergoing "video monitoring of weekly calibration process" once a year. Additionally, the QC team will conduct "on-site evaluations of BP measurement" at mobile examination centers three times a year. A Five-Step QC process for BP devices was also developed. This document outlines the standardized BP measurement protocol and rigorous QC program in KNHANES, aiming to ensure accurate and reliable BP data for epidemiological research and public health policymaking in South Korea.

Prostaglandin F2α requires activation of calcium-dependent signalling to trigger inflammation in human myometrium.

Introduction: Preterm birth is one of the major causes of neonatal morbidity and mortality across the world. Both term and preterm labour are preceded by inflammatory activation in uterine tissues. This includes increased leukocyte infiltration, and subsequent increase in chemokine and cytokine levels, activation of pro-inflammatory transcription factors as NF-κB and increased prostaglandin synthesis. Prostaglandin F2α (PGF2α) is one of the myometrial activators and stimulators. Methods: Here we investigated the role of PGF2α in pro-inflammatory signalling pathways in human myometrial cells isolated from term non-labouring uterine tissue. Primary myometrial cells were treated with G protein inhibitors, calcium chelators and/or PGF2α. Nuclear extracts were analysed by TranSignal cAMP/Calcium Protein/DNA Array. Whole cell protein lysates were analysed by Western blotting. mRNA levels of target genes were analysed by RT-PCR. Results: The results show that PGF2α increases inflammation in myometrial cells through increased activation of NF-κB and MAP kinases and increased expression of COX-2. PGF2α was found to activate several calcium/cAMP-dependent transcription factors, such as CREB and C/EBP-ß. mRNA levels of NF-κB-regulated cytokines and chemokines were also elevated with PGF2α stimulation. We have shown that the increase in PGF2α-mediated COX-2 expression in myometrial cells requires coupling of the FP receptor to both Gαq and Gαi proteins. Additionally, PGF2α-induced calcium response was also mediated through Gαq and Gαi coupling. Discussion: In summary, our findings suggest that PGF2α-induced inflammation in myometrial cells involves activation of several transcription factors - NF-κB, MAP kinases, CREB and C/EBP-ß. Our results indicate that the FP receptor signals via Gαq and Gαi coupling in myometrium. This work provides insight into PGF2α pro-inflammatory signalling in term myometrium prior to the onset of labour and suggests that PGF2α signalling pathways could be a potential target for management of preterm labour.

Serological Evidence of Severe Fever with Thrombocytopenia Syndrome Virus and IgM Positivity Were Identified in Healthy Residents in Vietnam.

Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne viral disease, is prevalent in East Asia and has also been reported in Southeast Asia since 2019. SFTS patients in Vietnam were first reported in 2019. However, the seroprevalence of severe fever with thrombocytopenia syndrome virus (SFTSV) in Vietnam has not been reported. To investigate the seroprevalence of SFTSV in Vietnam, we collected serum samples from 714 healthy residents in Thua Thien Hue and Quang Nam Province, Vietnam, and the seroprevalence of SFTSV was assessed using immunofluorescence antibody assay (IFA), Enzyme-Linked Immunosorbent Assays (ELISAs) and the 50% focus reduction neutralization test (FRNT50) assay. The seroprevalence of anti-SFTSV IgM or IgG was observed to be 3.64% (26/714), high IgM positivity was >80 (0.28%, 2/714) and the titer of neutralizing antibodies against SFTSV ranged from 15.5 to 55.9. In Pakistan, SFTSV infection confirmed using a microneutralization test (MNT) assay (prevalence is 2.5%) and ELISAs showed a high seroprevalence (46.7%) of SFTSV. Hence, the seroprevalence rate in Vietnam is similar to that in Pakistan and the number of SFTS patients could increase in Vietnam.

Functional rewiring of G protein-coupled receptor signaling in human labor.

Current strategies to manage preterm labor center around inhibition of uterine myometrial contractions, yet do not improve neonatal outcomes as they do not address activation of inflammation. Here, we identify that during human labor, activated oxytocin receptor (OTR) reprograms the prostaglandin E2 receptor, EP2, in the pregnant myometrium to suppress relaxatory/Gαs-cAMP signaling and promote pro-labor/inflammatory responses via altered coupling of EP2 from Gαq/11 to Gαi/o. The ability of EP2 to signal via Gαi/o is recapitulated with in vitro OT and only following OTR activation, suggesting direct EP2-OTR crosstalk. Super-resolution imaging with computational modeling reveals OT-dependent reorganization of EP2-OTR complexes to favor conformations for Gαi over Gαs activation. A selective EP2 ligand, PGN9856i, activates the relaxatory/Gαs-cAMP pathway but not the pro-labor/inflammatory responses in term-pregnant myometrium, even following OT. Our study reveals a mechanism, and provides a potential therapeutic solution, whereby EP2-OTR functional associations could be exploited to delay preterm labor.

The compatibility of new blood pressure reference values for Korean children and adolescents with the US reference: the Korean Working Group of Pediatric Hypertension.

BACKGROUND: Childhood hypertension is associated with hypertension and metabolic syndrome in adulthood. Since the definition of childhood hypertension is based on the distribution of normative blood pressure (BP), a reference range is essential to create hypertension guidelines for children. We aimed to investigate the compatibility of the new Korean BP reference with the United States (US) BP reference based on the 2017 Clinical Practice Guideline. METHODS: We compared the new Korean reference BP values for children and adolescents aged 10 to 17 years with those in the 2017 Clinical Practice Guidelines. We also analyzed the differences in the prevalence of hypertension in Korean children and adolescents when reference value was applied. Considering Korean and US BP references together, linear trend lines were sought. RESULTS: Systolic BP (SBP) and diastolic BP (DBP) values in 95th percentiles showed no significant differences between the two BP references. Applying the two reference values, there was no significant difference in the prevalence of elevated BP and a combination of elevated BP and hypertension. Combining the Korean and US BP values and plotting them against age, approximate lines for the 90th and 95th SBP and DBP percentiles were observed. CONCLUSIONS: The BP values of the new Korean BP reference were similar to those of the US BP reference; they were reliable and interchangeable.

Integrated serological surveillance of acute febrile illness in the context of a lymphatic filariasis survey in Timor-Leste: a pilot study using dried blood spots.

BACKGROUND: Acute febrile illnesses (AFIs), including dengue, scrub typhus and leptospirosis, cause significant morbidity and mortality in Southeast Asia. Serological surveillance can be used to investigate the force and distribution of infections. Dried blood spot (DBS) samples are an attractive alternative to serum because they are easier to collect and transport and require less cold storage. We conducted a pilot study to determine the feasibility of integrating serological surveillance for dengue, scrub typhus and leptospirosis into a population-representative lymphatic filariasis seroprevalence survey in Timor-Leste using DBSs. METHODS: A total of 272 DBSs were collected from healthy community participants. DBSs were analysed at the National Health Laboratory using commercially available enzyme-linked immunosorbent assays. To validate assays for DBSs, 20 anonymised serum samples of unknown serostatus were used to create dried serum spots (DSSs). These were analysed with optical densities compared with those of serum. Where low variance was observed (dengue assay) the published kit cut-offs for serum were applied to the analysis of DBSs. For the other assays (scrub typhus and leptospirosis), index values (IVs) were calculated and cut-offs were determined to be at 2 standard deviations (SDs) above the mean. RESULTS: Of the 272 samples analysed, 19 (7.0% [95% confidence interval {CI} 4.3 to 10.7]) were positive for dengue immunoglobulin G (IgG), 11 (4.0% [95% CI 2.1 to 7.1]) were positive for scrub typhus IgG and 16 (5.9% [95% CI 3.4 to 9.4%]) were positive for leptospira IgG. CONCLUSIONS: While dengue seroprevalence was lower than in nearby countries, results represent the first evidence of scrub typhus and leptospirosis transmission in Timor-Leste. Integrated programmes of serological surveillance could greatly improve our understanding of infectious disease epidemiology in remote areas and would incur minimal additional fieldwork costs. However, when planning such studies, the choice of assays, their validation for DBSs and the laboratory infrastructure and technical expertise at the proposed location of analysis must be considered.

Diagnosis of coronary artery abnormalities in Kawasaki disease: recent guidelines and z score systems.

Kawasaki disease, an acute systemic vasculitis affecting children, is the leading cause of acquired heart disease in developed countries. This vasculitis has a predilection for the coronary artery, and coronary artery abnormalities are the main criteria for its diagnosis. The diagnosis of coronary abnormalities has historically been based on dichotomous criteria, but recent guidelines have accepted the body surface area-adjusted z score system to define coronary abnormalities and classify coronary artery aneurysms. Z score systems have improved risk classifications of coronary aneurysms and improved correlations with clinical prognosis. However, the discrepancy of calculated z scores according to the formula has been noticed in the application of the z score system, which is possibly related to the diagnosis of coronary artery abnormalities. This variability was greater in larger coronary aneurysm dimensions. A careful choice of the z score formula and its consistent use is needed in clinical applications.

Control and elimination of lymphatic filariasis in Oceania: Prevalence, geographical distribution, mass drug administration, and surveillance in Samoa, 1998-2017.

Lymphatic filariasis (LF) is a major public health problem globally and in the Pacific Region. The Global Programme to Eliminate LF has made great progress but LF is persistent and resurgent in some Pacific countries and territories. Samoa remains endemic for LF despite elimination efforts through multiple two-drug mass drug administrations (MDA) since 1965, including renewed elimination efforts started in 1999 under the Pacific Programme for Elimination of LF (PacELF). Despite eight rounds of national and two rounds of subnational MDA under PacELF, Samoa failed transmission assessment surveys (TAS) in all three evaluation units in 2017. In 2018, Samoa was the first to distribute countrywide triple-drug MDA using ivermectin, diethylcarbamazine (DEC), and albendazole. This paper provides a review of MDAs and historical survey results from 1998 to 2017 in Samoa and highlights lessons learnt from LF elimination efforts, including challenges and potential ways to overcome them to successfully achieve elimination.

Diagnosis of Coronary Artery Abnormalities in Patients with Kawasaki Disease According to Established Guidelines and Z Score Formulas.

BACKGROUND: The diagnosis of coronary artery abnormalities (CAA), including dilation and aneurysm, in patients with Kawasaki disease is paramount to treatment planning. CAA are defined using various standards, which makes diagnosis difficult. The aims of this study were to determine the variability of CAA prevalence according to existing guidelines and Z score formulas and to examine the discrepancies in widely used Z score formulas. METHODS: Using data from a Korean national survey on Kawasaki disease, 6,889 patients were included and analyzed. The overall prevalence of CAA and the prevalence for subgroups were compared on the basis of aneurysm severity, age, and body surface area. Finally, discrepancies among five Z score formulas were evaluated by comparing two of the formulas in pairs. RESULTS: According to the Japanese criteria, the prevalence of CAA was 18%. According to the American Heart Association criteria, the prevalence of dilation or aneurysm was about 21% to 42%, and that of aneurysm of the left anterior descending artery or right coronary artery was about 8% to 27%. The prevalence of CAA and that of left anterior descending or right coronary artery aneurysm was significantly different, with discrepancies between the Japanese and AHA Z score criteria, as well as among the five Z score formulas. Additionally, misclassification of aneurysm severity was observed for each criterion or Z score formula. There was significant variation among calculated Z scores. The more extreme the Z score values, the more discrepancy was observed. CONCLUSIONS: Different guidelines and Z score formulas yield significantly different prevalence rates and classifications of CAA. In addition, more discrepancies were observed with higher Z score values. As CAA or aneurysm severity could be changed by guidelines or Z score formulas, they should be chosen carefully, and when a particular formula is chosen, consistency is needed.

Whole Blood Holding Time Prior to Plasma Processing Alters microRNA Expression Profile.

MicroRNAs (miRNAs) can exhibit aberrant expression under different physiological and pathological conditions. Therefore, differentially expressed circulating miRNAs have been a focus of biomarker discovery research. However, the use of circulating miRNAs comes with challenges which may hinder the reliability for their clinical application. These include varied sample collection protocols, storage times/conditions, sample processing and analysis methods. This study focused on examining the effect of whole blood holding time on the stability of plasma miRNA expression profiles. Whole blood samples were collected from healthy pregnant women and were held at 4°C for 30 min, 2 h, 6 h or 24 h prior to processing for plasma isolation. Plasma RNA was extracted and the expression of 179 miRNAs were analyzed. Unsupervised principal component analysis demonstrated that whole blood holding time was a major source of variation in miRNA expression profiles with 53 of 179 miRNAs showing significant changes in expression. Levels of specific miRNAs previously reported to be associated with pregnancy-associated complications such as hsa-miR-150-5p, hsa-miR-191-5p, and hsa-miR-29a-3p, as well as commonly used endogenous miRNA controls, hsa-miR-16-5p, hsa-miR-25-3p, and hsa-miR-223-3p were significantly altered with increase in blood holding time. Current protocols for plasma-based miRNA profiling for diagnostics describe major differences in whole blood holding periods ranging from immediately after collection to 26 h after. Our results demonstrate holding time can have dramatic effects on analytical reliability and reproducibility. This highlights the importance of standardization of blood holding time prior to processing for plasma in order to minimize introduction of non-biological variance in miRNA profiles.

PENETRATING OCULAR INJURY WITH RETAINED INTRAOCULAR FOREIGN BODY FROM DRYWALL.

PURPOSE: To present a case of open globe injury and retained intraocular foreign body secondary to drywall. METHODS: Interventional case report. RESULTS: A 21-year-old man presented with corneal laceration, iris defect, and vitreous hemorrhage after hammering drywall. Computed tomography scan was negative for intraocular foreign body, but a drywall intraretinal foreign body was found on 25-gauge vitrectomy. Intraoperative findings and 6-month follow-up are presented. CONCLUSION: Intraocular foreign body must always be suspected in all cases of penetrating ocular trauma. Although magnetic resonance imaging is ideal in diagnosing nonmetallic foreign bodies, computed tomography scan with Hounsfield units should be used in an emergency setting.

Maternal plasma miRNAs as potential biomarkers for detecting risk of small-for-gestational-age births.

BACKGROUND: Small-for-gestational-age fetuses (SGA) (birthweight <10th centile) are at high risk for stillbirth or long-term adverse outcomes. Here, we investigate the ability of circulating maternal plasma miRNAs to determine the risk of SGA births. METHODS: Maternal plasma samples from 29 women of whom 16 subsequently delivered normally grown babies and 13 delivered SGA (birthweight <5th centile) were selected from a total of 511 women recruited to form a discovery cohort in which expression data for a total of 800 miRNAs was determined using the Nanostring nCounter miRNA assay. Validation by RT-qPCR was performed in an independent cohort. FINDINGS: Partial least-squares discriminant analysis (PLS-DA) of the Nanostring nCounter miRNA assay initially identified seven miRNAs at 12-14+6 weeks gestation, which discriminated between SGA cases and controls. Four of these were technically validated by RT-qPCR. Differential expression of two miRNA markers; hsa-miR-374a-5p (p = 0•0176) and hsa-let-7d-5p (p = 0•0036), were validated in an independent population of 95 women (SGA n = 12, Control n = 83). In the validation cohort, which was enriched for SGA cases, the ROC AUCs were 0•71 for hsa-miR-374a-5p, and 0•74 for hsa-let-7d-5p, and 0•77 for the two combined. INTERPRETATION: Whilst larger population-wide studies are required to validate their performance, these findings highlight the potential of circulating miRNAs to act as biomarkers for early prediction of SGA births. FUNDING: This work was supported by Genesis Research Trust, March of Dimes, and the National Institute for Health Research Biomedical Research Centre (NIHR BRC) based at Imperial Healthcare NHS Trust and Imperial College London.

Lymphatic filariasis in Fiji: progress towards elimination, 1997-2007.

BACKGROUND: Lymphatic filariasis (LF) is a major public health problem in the Pacific Region, including in Fiji. Through transmission by the mosquito vector Aedes, Fiji has suffered the burden of remaining endemic with LF despite efforts at elimination prior to 1999. In the year 1999, Fiji agreed to take part in the Pacific Programme for Elimination of LF (PacELF) and the Global Programme to Eliminate LF. METHODS: This study reviewed and collated past data on LF in Fiji between 1997 and 2007. Sources included published papers as well as unpublished PacELF and WHO program meeting and survey reports. Records were held at Fiji's Department of Health and Medical Services, James Cook University and the WHO office in Suva, Fiji. RESULTS: Baseline surveys between 1997 and 2002 showed that Fiji was highly endemic for LF with an estimated 16.6% of the population antigen positive and 6.3% microfilaria positive at that time. Five rounds of annual mass drug administration (MDA) using albendazole and diethylcarbamazine commenced in 2002. Programmatic coverage reported was 58-70% per year, but an independent coverage survey in 2006 in Northern Division after the fifth MDA suggested that actual coverage may have been higher. Monitoring of the program consisted of antigen prevalence surveys in all ages with sentinel and spot check surveys carried out in 2002 (pre MDA), 2004, and 2005, together with knowledge, attitude, and practice surveys. The stop-MDA survey (C survey) in 2007 was a nationwide stratified cluster survey of all ages according to PacELF guidelines, designed to sample by administrative division to identify areas still needing MDA. The national antigen prevalence in 2007 was reduced by more than a third to 9.5%, ranging from 0.9% in Western Division to 15.4% in Eastern Division, while microfilaria prevalence was reduced by almost four-fifths to 1.4%. Having not reached the target threshold of 1% prevalence in all ages, Fiji wisely decided to continue MDA after 2007 but to move from nationwide implementation to four (later five) separate evaluation units with independent timelines using global guidelines, building on program experience to put more emphasis on increasing coverage through prioritized communication strategies, community participation, and morbidity alleviation. CONCLUSION: Fiji conducted nationwide MDA for LF annually between 2002 and 2006, monitored by extensive surveys of prevalence, knowledge, and coverage. From a high baseline prevalence in all divisions, large reductions in overall and age-specific prevalence were achieved, especially in the prevalence of microfilariae, but the threshold for stopping MDA was not reached. Fiji has a large rural and geographically widespread population, program management was not consistent over this period, and coverage achieved was likely not optimal in all areas. After learning from these many challenges and activities, Fiji was able to build on the progress achieved and the heterogeneity observed in prevalence to realign towards a more stratified and improved program after 2007. The information presented here will assist the country to progress towards validating elimination in subsequent years.