Drug-Related Problems of Children With Chronic Diseases in a Chinese Primary Health Care Institution: A Cross-Sectional Study.

Introduction: Drug-related problems (DRPs) refer to events or circumstances involving drug therapy that actually or potentially interfere with desired health outcomes. DRPs might be severe for children with chronic diseases managed at primary health care institutions, but the relevant research is scarce. Objective: In this cross-sectional study, we aimed to explore the prevalence, types, causes, and influencing factors of DRPs in children with chronic diseases in a Chinese primary health care institution. Methods: We recruited children with chronic diseases who visited the pediatric outpatient department in a primary health care institution from July 1 to 12 October 2021. Clinical pharmacists identified DRPs through medication therapy reviews, classified the types and causes of DRPs, and distinguished the manifested DRPs that affected the outcome and potential DRPs that were going to affect the outcome. Results: A total of 188 children with chronic diseases was included, and 584 DRPs were identified in 89.89% of participants. The most common type of DRPs was "treatment effectiveness" (a manifested problem or potential problem with the effect of the pharmacotherapy; 83.56%), of which 67.29% were potential DRPs. The second common type was "treatment safety" (patient suffers or could suffer from an adverse drug event; 14.21%), of which 89.16% were potential DRPs. The most common cause of DRPs was related to the process of use (42.24%), such as "patient uses/takes less drug than prescribed or does not take the drug at all," "patient stores drug inappropriately," and "patient administers/uses the drug in a wrong way." The second common cause was related to the process of dispensing (29.83%), such as "necessary information not provided or incorrect advice provided" and "prescribed drug is not available." The third common cause was related to the process of prescribing (26.21%), such as "drug dose is too low" and "no or incomplete drug treatment despite an existing indication." The number of combined medications was an influencing factor for the frequency of DRPs (p < 0.05). Conclusion: This cross-sectional study showed that the current situation regarding DRPs among children with chronic diseases managed in the primary health care institution was serious. The types of DRPs were mainly related to treatment effectiveness, and improper usage of medications was one of the main causes of DRPs. The number of combined drugs was the influencing factor for the frequency of DRPs. In the future, pharmacists should consider formulating pharmaceutical intervention strategies for this specific group according to the characteristics of DRPs.

Effectiveness of azithromycin mass drug administration on trachoma: a systematic review.

BACKGROUNDS: Azithromycin mass drug administration (MDA) is a key part of the strategy for controlling trachoma. This systematic review aimed to comprehensively summarize the present studies of azithromycin MDA on trachoma; provide an overview of the impact of azithromycin MDA on trachoma in different districts; and explore the possible methods to enhance the effectiveness of azithromycin MDA in hyperendemic districts. METHODS: PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov were searched up to February 2021 with no language restriction. Studies reporting the effect of azithromycin MDA on trachoma were included. Mathematical modeling studies, animal studies, case reports, and reviews were excluded. The trachomatous inflammation-follicular (TF) <5.0% was used to judge the effect of azithromycin MDA on eliminating trachoma as a public health problem. Two researchers independently conducted the selection process and risk of bias assessment. RESULTS: A total of 1543 studies were screened, of which 67 studies including 13 cluster-randomized controlled trials and 54 non-randomized studies were included. The effect of azithromycin MDA on trachoma was closely related to the baseline prevalence in districts. For the districts with baseline prevalence between 5.0% and 9.9%, a single round of MDA achieved a TF <5.0%. For the districts with baseline between 10.0% and 29.9%, annual MDA for 3 to 5 years reduced TF <5.0%. However, for the districts with high level of baseline prevalence (TF >30.0%), especially with baseline TF >50.0%, annual MDA was unable to achieve the TF <5.0% even after 5 to 7 years of treatment. Quarterly MDA is more effective in controlling trachoma in these hyperendemic districts. CONCLUSIONS: Azithromycin MDA for controlling trachoma depends on the baseline prevalence. The recommendation by the World Health Organization that annual MDA for 3 to 5 years in the districts with TF baseline >10.0% is not appropriate for all eligible districts.

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.

Methodological quality of clinical practice guidelines for genetic testing in children: A systematic assessment using the appraisal of guidelines for research and evaluation II instrument.

Genetic testing of children is faced with numerous problems. High-quality clinical practice guidelines (CPGs) are needed to ensure its safe, and appropriate use. This study aimed to systematically identify the current CPGs for genetic testing in children, and to assess the methodological quality of these CPGs.We searched 6 databases, 3 guideline clearinghouses, and 9 web sites of relevant academic agencies from inception to February 2019. CPGs focused on genetic testing in children were included. Four reviewers independently appraised the quality of the eligible CPGs using the appraisal of guidelines for research, and evaluation (AGREE) II instrument.Seventeen CPGs meeting our inclusion criteria were included. Among them, 16 CPGs were focused on the genetic diagnosis/evaluation of diseases, while only 1 CPG was focused on pharmacogenetics. The median domain scores from highest to lowest were: scope and purpose 80.56% (range: 56.95%-87.50%), clarity of presentation 72.22% (range: 45.83%-88.89%), stakeholder involvement 45.83% (range: 27.78%-55.56%), applicability 31.25% (range: 19.79%-54.17%), rigor of development 21.88%, (range: 13.02%-71.88%), and editorial independence 18.75% (range: 0%-83.33%). According to the overall quality, 6 (35%) CPGs were "not recommended," 8 (47%) CPGs were "recommended with modifications," and only 3 (18%) CPGs were "recommended." The clinical topics of the "recommended" CPGs were warfarin, familial Mediterranean fever, and pediatric pulmonary arterial hypertension.The quality of CPGs for genetic testing in children was generally low, and variable across different CPGs and different AGREE II domains. In future guideline development, more attention should be paid to the aspects of stakeholder involvement, rigor of development, applicability, and editorial independence. Not only will guideline users benefit from our results when determining whether to adopt related CPGs to guide genetic testing in children, but guideline developers could also take into account our results to improve the quality of future CPGs.

Essential medicines lists for children of WHO, India, South Africa, and EML of China: A comparative study.

OBJECTIVE: Comparing the essential medicine lists for children and China national essential medicine list 2012, to provide the evidence for establishing essential medicine list for children in China. METHODS: Search the official websites of WHO and some other countries' ministry of health to get essential medicine lists for children (EMLc) that have already established. Compare the situation of updating, the number and classification of medicines, and the dosage forms in essential medicine lists for children and China national essential medicine list 2012. RESULTS: By December 2013, the WHO, India, and South Africa have established EMLc. The list of China was for people in all ages, so the number of medicines ranked first in four lists. WHO, India, and China classified the medicines by pharmacologic action, South Africa classified by ATC classification. Except for WHO, India, South Africa, and China did not have specific medicines for neonatal care or medicines for diseases of joints. The main administration routes in these four lists were oral administration, injection, and topical application. There were medicine restrictions in lists of WHO and India, but there were no medicine restrictions in the lists of South Africa and China. CONCLUSION: Compared with EMLs for children, the 2012 National Essential Medicine List for China is not suitable for children in China. Development of Chinese EMLc should be based on the burden of diseases for children, and should select applicable dosage forms and specifications.

[Lamotrigine monotherapy in children with epilepsy: a systematic review].

OBJECTIVE: To investigate the efficacy and safety of lamotrigine monotherapy in children with epilepsy via a systematic review. METHODS: PubMed, Cochrane, CNKI, VIP, CBM, Wanfang Data were searched for randomized controlled trials (RCTs) of lamotrigine monotherapy in children with epilepsy. Literature screening, data extraction, and quality assessment were performed according to the method recommended by Cochrane Collaboration. RevMan 5.2 software was used to conduct the Meta analysis. RESULTS: A total of 9 RCTs involving 1 016 participants were included. Lamotrigine yielded a significantly lower complete control rate of seizure than ethosuximide, but the complete control rate of seizure showed no significant differences between lamotrigine and carbamazepine/sodium valproate. Patients treated with lamotrigine had a significantly lower incidence rate of adverse events than those treated with carbamazepine, but the incidence rate of adverse events showed no significant differences between patients treated with lamotrigine and sodium valproate/carbamazepine. The drop-out rate showed no significant differences between the three treatment groups. CONCLUSIONS: Lamotrigine is an ideal alternative drug for children who do not respond to traditional antiepileptic medication or experience significant adverse reactions; however, more high-quality RCTs with a large sample size and a long follow-up time are needed to confirm these conclusions.

Synthesis of key macrolactone structure of resin glycosides using a Keck macrolactonization method.

We present in this paper the efficient synthesis of three macrocyclic lactone units which are core structures of natural resin glycosides by the use of a Keck macrolactonization approach.

The primary microbial pathogens associated with premature rupture of the membranes in China: a systematic review.

To describe the spectrum of pathogens isolated from Chinese women experiencing premature rupture of the membranes (PROM) and those of their neonates, in order to provide effective management of PROM. We searched Ovid Medline, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and VIP Database for Chinese Technical Periodicals up to April 2012. The quality of studies was assessed utilizing the Strengthening the Reporting of Observational Studies in Epidemiology Statement. Among the included 36 studies, 11 (30.55%) were deemed to be at Level A, 12 (33.33%) at Level B, three (8.33%) at Level C, and 10 (27.78%) at Level D. Staphylococcus and Escherichia coli were the two primary microorganisms isolated from women with PROM and their infants. Subgroup analysis showed the distribution of microorganisms from the six regions of China varied. Staphylococcus bacteria were resistant to penicillins, except oxacillin, but more sensitive to first- and second-generation cephalosporins. Escherichia were sensitive to first- and second-generation cephalosporins and were more sensitive to aztreonam than cephalosporins. The main pathogens derived from women with PROM and their newborns were Staphylococcus and E. coli, which differs from the pathogens in Western countries. Hence, one might infer that the pathogens involved in PROM should be defined in each region to maximize antibiotic effectiveness. In addition, randomized controlled studies are needed to compare prophylactic use of antibiotics versus use of antibiotics after a positive culture for newborn infants with a history of PROM.

Topiramate for Tourette's syndrome in children: a meta-analysis.

OBJECTIVES: To assess the efficacy and safety of topiramate for children with Tourette syndrome. METHODS: Randomized controlled trials evaluating topiramate for children with Tourette syndrome were identified from the Cochrane library, PubMed, Cochrane Central, Embase, CBM, CNKI, VIP, WANG FANG database, and relevant reference lists. Two reviewers independently selected trials, assessed trial quality, and extracted the data. Disagreement was resolved by discussion. Quality assessment referred to the Cochrane Handbook for Systematic Reviews of Interventions (version 5.0.1.). RESULTS: Fourteen trials involving 1003 patients were included, of which 720 cases were male (71.8%). Ages were 2 to 17 years old. The general quality of included randomized controlled trials was poor. All trials were positive drug-controlled (12 randomized controlled trials used haloperidol as control, 2 used tiapride). The follow-up period was from 20 days to 12 months. Meta-analysis of 3 trials (n = 207), in which tics symptoms control was assessed by Yale Global Tic Severity Scale, suggested that there was significant difference in the mean change of Yale Global Tic Severity Scale score during the treatment period (mean difference = -7.74, 95% CI [-10.49, -4.99], I(2) = 0) between topiramate and control groups. Meta-analysis of 9 trials (n = 668) evaluating tics symptoms control ≥ 50% suggested that there was no significant difference in reduction of tics between topiramate and control group during the treatment period (relative ratio = 1.36, 95% CI [0.90, 2.06], I(2) = 0). Adverse events were reported in 13 trials. Drowsiness (3.3-16%), loss of appetite (4-16.7%), cognitive dysfunction (7.89-12.5%), and weight loss (6-10.5%) were common adverse events. CONCLUSIONS: The current evidence is promising but not yet sufficient to support the routine use of topiramate for Tourette syndrome in children due to low quality of the study designs. It deserves to confirm in further high-quality, placebo-controlled trials.

10-year trend in quantity and quality of pediatric randomized controlled trials published in mainland China: 2002-2011.

BACKGROUND: Quality assessment of pediatric randomized controlled trials (RCTs) in China is limited. The aim of this study was to evaluate the quantitative trends and quality indicators of RCTs published in mainland China over a recent 10-year period. METHODS: We individually searched all 17 available pediatric journals published in China from January 1, 2002 to December 30, 2011 to identify RCTs of drug treatment in participants under the age of 18 years. The quality was evaluated according to the Cochrane quality assessment protocol. RESULTS: Of 1287 journal issues containing 44398 articles, a total of 2.4% (1077/44398) articles were included in the analysis. The proportion of RCTs increased from 0.28% in 2002 to 0.32% in 2011. Individual sample sizes ranged from 10 to 905 participants (median 81 participants); 2.3% of the RCTs were multiple center trials; 63.9% evaluated Western medicine, 32.5% evaluated traditional Chinese medicine; 15% used an adequate method of random sequence generation; and 10.4% used a quasi-random method for randomization. Only 1% of the RCTs reported adequate allocation concealment and 0.6% reported the method of blinding. The follow-up period was from 7 days to 96 months, with a median of 7.5 months. There was incomplete outcome data reported in 8.3%, of which 4.5% (4/89) used intention-to-treat analysis. Only 0.4% of the included trials used adequate random sequence allocation, concealment and blinding. The articles published from 2007 to 2011 revealed an improvement in the randomization method compared with articles published from 2002 to 2006 (from 2.7% to 23.6%, p = 0.000). CONCLUSIONS: In mainland China, the quantity of RCTs did not increase in the pediatric population, and the general quality was relatively poor. Quality improvements were suboptimal in the later 5 years.

Side effects of phenobarbital in epilepsy: a systematic review.

AIM: In recent years, phenobarbital, as an antiepileptic drug, has become less popular based on adverse events, especially cognitive and behavioural side effects. Despite the development of better tolerated new generation AEDs, phenobarbital is still widely used particularly in developing countries because of its low cost. The purpose of this review was to: (i) investigate whether phenobarbital can be safely used as an antiepileptic drug and (ii) determine the questions which need to be addressed in order to comprehensively and adequately evaluate the safety of phenobarbital for the treatment of epilepsy. METHODS: The literature was searched using the Cochrane Central Register of randomised controlled trials (1800-2009), Medline (1966-2009), Embase (1966-2009) and three Chinese databases. RESULTS: Twenty studies were finally included in this systematic review. The determination of adverse effects of combined antiepileptic drugs (AEDs) from different studies was complicated by numerous factors including study design, different descriptions of adverse events and a lack of standardised data collection. These factors may also have been responsible for the heterogeneity present in the meta-analysis. The data did not demonstrate any evidence of association between phenobarbital and a higher risk of adverse events. However, phenobarbital appeared to be associated with a higher rate of adverse drug reaction related withdrawal (ADR-related withdraw), compared to carbamazepine, valproic acid and phenytoin. This may have been due to a concern for possible adverse effects of phenobarbital. CONCLUSIONS: Phenobarbital was associated with a higher rate of drug withdrawal although there was no evidence to suggest that phenobarbital caused more adverse events compared to carbamazepine, valproic acid or phenytoin. However, in the case of pregnant women, it is important for clinicians to evaluate the benefits and risks of phenobarbital administration before making a final recommendation. Furthermore, unified scales for the assessment of cognitive function should be applied for future studies particularly in children.