Safety of azithromycin in pediatrics: a systematic review and meta-analysis.

PURPOSE: To evaluate the toxicity of azithromycin in neonates, infants, and children. METHODS: A systematic review was performed for relevant studies using Medline (Ovid), PubMed, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, and International Pharmaceutical Abstracts. We calculated the pooled incidence of adverse drug reactions (ADRs) associated with azithromycin based on prospective studies (RCTs and prospective cohort studies) and analyzed the risk difference (RD) of ADRs between azithromycin and placebo or other antibiotics using meta-analysis of RCTs. RESULTS: We included 133 studies with 4243 ADRs reported in 197,675 neonates, infants, and children who received azithromycin. The safety of azithromycin as MDA in pediatrics was poorly monitored. The main ADRs were diarrhea and vomiting. In prospective non-MDA studies, the most common toxicity was gastrointestinal ADRs (938/1967; 47.7%). The most serious toxicities were cardiac (prolonged QT or irregular heart beat) and idiopathic hypertrophic pyloric stenosis (IHPS). Compared with placebo, azithromycin did not show increased risk ADRs based on RCTs (risk difference - 0.17 to 0.07). The incidence of QT prolonged was higher in the medium-dosage group (10-30 mg/kg/day) than that of low-dosage group (≤ 10 mg/kg/day) (82.0% vs 1.2%). CONCLUSION: The safety of azithromycin as MDA needs further evaluation. The most common ADRs are diarrhea and vomiting. The risk of the most serious uncommon ADRs (cardiac-prolonged QT and IHPS) is unknown.

Age and Preoperative Velar Closure Ratio Are Significantly Associated With Surgical Outcome of Furlow Double-Opposing Z-Plasty in Palatal Re-Repair.

PURPOSE: The patient selection criteria for Furlow double-opposing Z-plasty in palatal re-repair remain obscure. This study investigated whether patients' preoperative characteristics significantly affected the surgical outcome of Furlow double-opposing Z-plasty in palatal re-repair. MATERIALS AND METHODS: We designed and implemented a case-control study nested in a cohort, which could be divided into 2 stages. In the first stage, a retrospective cohort study was performed to collect basic information and the preoperative status of the patients who would undergo Furlow double-opposing Z-plasty to correct velopharyngeal insufficiency after primary cleft palate repair. Eight predictor variables were included: age, gender, primary surgical technique, velopharyngeal closure pattern, velar movement, lateral pharyngeal wall movement, levator muscle orientation, and preoperative velar closure ratio. The outcome variable was postoperative velopharyngeal function described as velopharyngeal competence or velopharyngeal insufficiency. In the second stage, a case-control analysis was performed to explore the potential factors affecting the surgical outcome. Univariate and multivariate analyses were applied to examine the relationship between the predictor variables and surgical outcome. RESULTS: The sample was composed of 83 patients and resulted in 54 velopharyngeal competence outcomes and 29 velopharyngeal insufficiency outcomes after surgery. Two predictors showed statistical significance: age and preoperative velar closure ratio. The possibility of postoperative velopharyngeal insufficiency in patients older than 14.5 years was 6 times higher than that in patients younger than 14.5 years. The possibility of postoperative velopharyngeal insufficiency in patients with preoperative velar closure ratios of 0.9 or greater was one fifth that in patients with preoperative velar closure ratios between 0.8 and less than 0.9. CONCLUSIONS: The results of this study suggest that age and preoperative velar closure ratio are significantly associated with postoperative velopharyngeal insufficiency. Age was a risk factor in achieving good surgical outcomes, and the preoperative velar closure ratio remained a protective factor.

Preoperative Blindfold Training Prevents Pediatric Psychological Behavior Disorders During the Anesthesia Recovery Period: A Randomized Controlled Trial.

PURPOSE: To identify the effectiveness and feasibility of blindfold training on preventing pediatric psychological behavior disorders during the anesthesia recovery period. DESIGN: This study investigated the effect of blindfold training through the assessment of anxiety, delirium, and pain in children during the anesthesia recovery period. METHODS: This study was a prospective, randomized, controlled trial. Pediatric patients were randomized into either a control (routine practice) or blindfold training group (routine practice + blindfold training). Anxiety, delirium, and pain levels of children were assessed by the modified Yale Preoperative Anxiety Scale, Pediatric Anesthesia Emergence Delirium scale, and the Face, Legs, Activity, Cry, Consolability scale. FINDINGS: The blindfold training group had significantly lower scores for emergence delirium, anxiety, and pain during the anesthesia recovery period and a lower incidence of anesthesia complications (all P's < .05). CONCLUSIONS: Preoperative blindfold training was able to reduce anxiety, pain, and the incidence of delirium during the anesthesia recovery period in pediatric patients.

[Cognitive Impairments and Associated Factors in Community-dwelling Elderly in Chengdu, Sichuan].

OBJECTIVE: To determine the prevalence and associated factors of cognitive impairments in the community-dwelling elderly aged 60 years or older in Chengdu of Sichuan province. METHODS: A random cluster sampling strategy was adopted to select 621 community-dwelling elderly. Face-to-face interviews were conducted to assess the cognitive status of the participants. 2 tests and logistic regression analyses were performed to identify factors associated with cognitive impairments. RESULTS: About 40.9% of the participants had cognitive impairments. Those attended primary schools had a lower risk of cognitive impairments [odds ratio OR)=0.369, P<0.001] compared with the illiterate ones. Older age OR=1.505 for 70-79 years, P=0.042; OR=3.069 for ≥80 years, P<0.001), cerebrovascular disease OR=2.159, P=0.003) and smoking OR=2.388, P<0.001) were risk factors of cognitive impairments. Men had lower risk OR=0.489, P=0.005) of cognitive impairments than women. CONCLUSION: The prevalence of cognitive impairments in community-dwelling elderly in Chengdu is high in comparison with those in other cities. Illiteracy, older age (over 70 years), women, smoking, and cerebrovascular disease are risk factors of cognitive impairments.

Proposed clinical model for predicting speech outcomes in patients undergoing Furlow palatoplasty for velopharyngeal insufficiency after primary palatoplasty.

This study aimed to validate the predictors of speech outcomes following Furlow palatoplasty in patients with velopharyngeal insufficiency (VPI) after primary palatoplasty and to propose and validate a model to predict the risk of persistent VPI. The study included patients with VPI after primary palatoplasty who underwent Furlow palatoplasty as a secondary surgery. Eleven variables were included: velar length, pharyngeal cavity depth, velopharyngeal gap, velopharyngeal closure pattern, sex, presence of cleft lip, existence of palatal fistula, surgeon, age at primary palatoplasty, age at secondary surgery, and time interval between primary palatoplasty and secondary surgery. Postoperative speech outcomes were assessed at least 1 year after the secondary surgery and classified as velopharyngeal competence (VPC) or VPI. Variables were analyzed using multivariate logistic regression analysis, and the area under the curve (AUC) was used to validate model accuracy. The study sample comprised 101 patients. Of the patients, 62 had VPC and 39 had VPI after secondary surgery. The results showed a younger age at secondary surgery, a smaller velopharyngeal gap, being female, having a coronal velopharyngeal closure pattern and a velopharyngeal closure ratio of 90% or greater produced a greater probability of VPC. Given the constraints of this study, it appears that the Furlow palatoplasty should be prioritized when the clinical model predicts a substantial likelihood of VPC post-surgery.

Osteochondroplasty with or without labral repair is more cost-effective than arthroscopic lavage with or without labral repair for treatment of young adults with femoroacetabular impingement: A cost-utility analysis based on data from a randomized controlled trial.

OBJECTIVES: The objective of this study was to conduct a cost-utility analysis of osteochondroplasty with or without labral repair compared to arthroscopic lavage with or without labral repair for femoroacetabular impingement (FAI) from a Canadian public payer perspective. METHODS: A Markov model was constructed to compare the lifetime quality-adjusted life years (QALYs) and costs of the two treatment strategies. The target population was surgical FAI patients aged 36 years. The primary data source was patient-level data from the Femoroacetabular Impingement Randomised Controlled Trial, which evaluated the efficacy of the surgical correction of FAI via arthroscopic osteochondroplasty with or without labral repair compared to arthroscopic lavage with or without labral repair in Canada. Long-term data were extrapolated using a generalized gamma model. The primary outcome was the incremental cost-effectiveness ratio, calculated by dividing the difference in costs by the difference in QALYs between osteochondroplasty and lavage, with or without labral repair. Probabilistic sensitivity analyses and one-way sensitivity analyses were used to characterize uncertainty of model parameters and assumptions. RESULTS: Over a lifetime horizon, osteochondroplasty, with or without labral repair, had a greater expected benefit (0.63 QALYs gained per patient) and lower costs ($955.89 saved per patient), as compared with lavage with or without labral repair. Probabilistic sensitivity analyses demonstrated that the probability of osteochondroplasty, with or without labral repair, being cost-effective was 90.5% at a commonly used willingness-to-pay threshold of $50,000/QALY in Canada. Across all one-way sensitivity analyses, osteochondroplasty with or without labral repair remained a cost-effective option. CONCLUSION: Over a lifetime time horizon, osteochondroplasty, with or without labral repair, is a cost-effective treatment strategy for young adults with FAI. Future research involving real-word data is needed to further validate these findings. LEVEL OF EVIDENCE: III.

Trends and frontiers of research on pharmacoeconomics from 2012-2021: a scientometric analysis.

Background: Research on pharmacoeconomics (PE) promotes the rational allocation of medical resources, which has received attention in the last decade. We conducted a scientometric analysis of PE to determine the current status and frontiers, and promote cooperation and development. Methods: The Web of Science Core Collection-Science Citation Index Expanded was adopted to retrieve publications associated with PE from 2012-2021. After screening publications, CiteSpace 3.8.R3 was used to conduct a scientometric analysis. We analyzed terms, including publications and citations, countries/regions, institutions, journals, authors, keywords, and references. Results: In total, 4,715 documents published from 2012-2021 were included in this study, of which 3,829 were articles and 886 were reviews. The documents were cited 54,596 times, at an average of 11.58 times per document. 121 countries/regions and 410 institutions were involved. The top 3 countries/regions by the number of publications were the United States of America (n=1,790), England (n=601), and China (n=403), while the institution with the most publications was Pfizer. Pharmacoeconomics was the main journal of PE, with 310 publications in all, and the top 3 cited journals were New England Journal of Medicine (citation times =1,620), Value in Health (citation times =1,306), and Lancet (citation times =1,255). Bin Wu was the most productive author (n=16), while World Health Organization was the most influential author (citation times =387). 524 keywords altogether were found, and the top 3 keywords by frequency were therapy (frequency =318), impact (frequency =305), and cost-effectiveness (frequency =296). The keyword "modifying antirheumatic drug" associated with rheumatoid arthritis (RA) has continued bursting from 2016-2021. Guide to the methods of technology appraisal 2013 by the National Institute for Health and Care Excellence, was the most frequently cited publication on PE (citation times =65). Cluster 0 labeled as "cost-effectiveness analysis" (CEA) was the largest and latest cluster, and its citing articles focused on the CEA of first-line treatment for non-small cell lung cancer (NSCLC). Conclusions: The economic analysis of disease-modifying antirheumatic drugs related to RA was a popular topic in the last 6 years, and CEA of NSCLC first-line treatment was at the frontier of PE.

Immunonutrition for traumatic brain injury in children and adolescents: protocol for a systematic review and meta-analysis.

INTRODUCTION: Traumatic brain injury (TBI) is the leading cause of paediatric trauma death and disability worldwide. The 'Guidelines for the Management of Severe Traumatic Brain Injury (Fourth Edition)' recommend that nutritional goals should be achieved within 5-7 days of injury. Immune-enhancing nutrition or immunonutrition, referring to the addition of specialised nutrients, including glutamine, alanine, omega-3 fatty acids and nucleotides, to standard nutrition formulas, may improve surgical outcomes in the perioperative period. However, the role of immune-enhancing nutritional supplements for patients with paediatric TBI remains unclear. We will conduct a systematic review to determine the efficacy and safety of immunonutrition for patients with paediatric TBI and provide evidence for clinical decision-making. METHODS AND ANALYSIS: Studies reporting immune-enhancing nutrition treatments for patients with paediatric TBI will be included. Outcomes of interest include the length of hospital stay, wound infections, all-cause mortality, non-wound infection, including pneumonia, urinary tract infection and bacteraemia, and the reports adverse events. Duration of follow-up has no restriction. Primary studies consisting of randomised controlled trials (RCTs) and non-RCTs will be eligible for this review, and only studies published in English will be included. We will search the Medline, Embase and Cochrane Library databases from their inception dates to January 2020. We will also search clinicaltrials.gov and the WHO International Clinical Trials Registry Platform for additional information. Two reviewers will independently select studies and extract data. Risk-of-bias will be assessed with tools based on the Cochrane risk-of-bias criteria and Newcastle-Ottawa Quality Assessment Scale. A meta-analysis will be used to pool data when there are sufficient studies with homogeneity. Heterogeneity of the estimates across studies will be assessed; if necessary, a subgroup analysis will be performed to explore the source of heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation method will be applied to assess the level of evidence obtained from this systematic review. ETHICS AND DISSEMINATION: The proposed systematic review and meta-analysis will be based on published data, and thus ethical approval is not required. The results of this review will be published. PROSPERO REGISTRATION NUMBER: CRD42020154814.

The spatial heterogeneity of the associations between relative humidity and pediatric hand, foot and mouth disease: Evidence from a nation-wide multicity study from mainland China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) remains a serious health threat to young children in East and Southeast Asia. The humidity is crucial for the survival of enterovirus, but the evidence of the humidity-HFMD association is inconsistent. In this study we investigated the spatial heterogeneity of humidity-HFMD associations and related effect modifiers. METHODS: We retrieved the daily surveillance data of childhood HFMD counts and meteorological variables from 143 cities in mainland China between 2009 and 2014 and then adopted a three-stage time series analysis. We first fitted a common distributed lag nonlinear model (DLNM) for each of the 143 cities separately to obtain the city-specific estimates of humidity-HFMD association. Then, we pooled the city-specific estimates through multivariate meta-regression with city-level characteristics as potential effect modifiers to study the reasons for heterogeneity. Finally, we applied a region-specific analysis to verify our findings and to better visualize our results. RESULTS: We found that the overall pooled humidity-HFMD relationship was shown as an approximately U-shaped curve with substantial spatial heterogeneity (I2 = 77.8%). Taking the reference relative humidity as 70%, the minimum relative risk (RR) was obtained at 45% with a value of 0.83 (0.79, 0.87), while the maximum RR was found to be at both 20% and over 85% separately with a value of 1.10 (1.05, 1.15). The spatial heterogeneity can be well explained by the climatic, social characteristics and terrains among cities. The modification effects can be roughly classified into two types, including change in the overall slope and the shape of the curve. CONCLUSIONS: Due to substantial spatial heterogeneity, caution should be taken when interpreting the weather-HFMD association in a single-site study and to avoid generalizing its findings to another site. Our study also implied the existence of interactions among meteorological factors given that climatic factors can modify the weather-HFMD association.

Ovary and uterus related adverse events associated with statin use: an analysis of the FDA Adverse Event Reporting System.

Experimental studies have demonstrated statin-induced toxicity for ovary and uterus. However, the safety of statins on the functions of ovary and uterus in real-world clinical settings remains unknown. The aim of this study was to identify ovary and uterus related adverse events (AEs) associated with statin use by analyzing data from FDA Adverse Event Reporting System (FAERS). We used OpenVigil 2.1 to query FAERS database. Ovary and uterus related AEs were defined by 383 Preferred Terms, which could be classified into ten aspects. Disproportionality analysis was performed to assess the association between AEs and statin use. Our results suggest that statin use may be associated with a series of ovary and uterus related AEs. These AEs are involved in ovarian cysts and neoplasms, uterine neoplasms, cervix neoplasms, uterine disorders (excl neoplasms), cervix disorders (excl neoplasms), endocrine disorders of gonadal function, menstrual cycle and uterine bleeding disorders, menopause related conditions, and sexual function disorders. Moreover, there are variabilities in the types and signal strengths of ovary and uterus related AEs across individual statins. According to our findings, the potential ovary and uterus related AEs of statins should attract enough attention and be closely monitored in future clinical practice.

The temporal trend and distribution characteristics in mortality of Alzheimer's disease and other forms of dementia in China: Based on the National Mortality Surveillance System (NMS) from 2009 to 2015.

BACKGROUND: China is experiencing rapid age, which will lead to increasing burden of age-related diseases, such as Alzheimer disease and other forms of dementia. OBJECTIVES: The aim of this study was to 1) Explore the temporal trend of mortality of Alzheimer disease (AD) and other forms of dementia in China and 2) Analyze its geographic variations and urban-rural differences and calculate the years of life lost (YLLs) from AD and other forms of dementia. DATA AND METHODS: Data were extracted from the National Mortality Surveillance System (NMS). Age-standardized mortalities were calculated with the Western Grade 26 Standard Life List, and the YLLs were calculated using the DALY template provided by the WHO / World Bank global burden of disease (GBD) Working Group. The trends in crude and age-standardized mortality of AD and other forms of dementia were examined using Cochran-Armitage trend test. RESULTS: In China, the crude mortality from AD and other forms of dementia increased from 2009 to 2015, but the age-standardized mortality decreased. The YLLs of AD and other forms of dementia increased during the study period. The age-standardized mortality in the east was higher than those in the west and middle regions, and the age-standardized mortality in rural areas was higher than that in urban areas. CONCLUSION: In China, the age-standardized mortality of AD and other forms of dementia decreased from 2009 to 2015. However, the disease burden from AD and other forms of dementia is becoming heavier due to increasing elderly population. Moreover, there were geographic variations and urban-rural differences in mortality of AD and other forms of dementia in China.

General Anesthesia with the Use of SUPREME Laryngeal Mask Airway for Emergency Cesarean delivery: A Retrospective Analysis of 1039 Parturients.

In comparison to elective cesarean delivery, emergency cesarean delivery under endotracheal intubation is associated with higher risk of life-threatening airway problems. In this retrospective study, we evaluate the efficacy and feasibility of using SUPREME laryngeal mask airway (SLMA) in emergency cesarean delivery under general anesthesia (GA). The study included a total of 1039 paturients undergoing emergency cesarean delivery under GA with SLMA from January 2015 to December 2015 at Quanzhou Children's and Women's Hospital. Outcome measures included incidence of the adverse events related to using SLMA, maternal mortality, and neonatal outcomes. Briefly, no aspiration or regurgitation was noticed; the first attempt was successful in all but 2 subjects, both because of incorrect location, one was detected by decreasing oxygenation and the other by high airway pressure, the second attempt was successful in both cases. No subject was switched to endotracheal intubation. No laryngospasm or bronchospasm was detected. No maternal death occurred. There were 1139 neonates (including 944 single birth, 92 twins, 3 triplets) in this study, 5-min Apgar score was 7-10 in 1092 (96.72%) neonates. Thirty-seven (3.28%) neonates received endotracheal intubation. In conclusion, this retrospective study showed that the SLMA was used successfully in 1039 patients undergoing emergent cesarean delivery without any major complications. Vigilant attention by attending anesthesiologists is warranted.