Long-term economic evaluation of the recombinant Mycobacterium tuberculosis fusion protein (EC) test for the diagnosis of Mycobacterium tuberculosis infection.

Background: Tuberculosis continues to be a significant global burden. Purified protein derivative of tuberculin (TB-PPD) is one type of tuberculin skin test (TST) and is used commonly for the auxiliary diagnosis of tuberculosis. The recombinant Mycobacterium tuberculosis fusion protein (EC) test is a new test developed in China. Objective: Evaluate the long-term economic implications of using the EC test compared with the TB-PPD test to provide a reference for clinical decision-making. Methods: The target population was people at a high risk persons of being infected with Mycobacterium tuberculosis. The outcome indicator was quality-adjusted life years (QALY). A cost-utility analysis was used to evaluate the long-term economic implications of using the EC test compared with the TB-PPD test. We employed a decision tree-Markov model from the perspective of the whole society within 77 years. Results: Compared with the TB-PPD test, the EC test had a lower cost but higher QALY. The incremental cost-utility ratio was -119,800.7381 CNY/QALY. That is, for each additional QALY, the EC test could save 119,800.7381 CNY: the EC test was more economical than the TB-PPD test. Conclusion: Compared with the TB-PPD test, the EC test would be more economical in the long term for the diagnosis of M. tuberculosis infection according our study.

Recombinant mycobacterium tuberculosis fusion protein for diagnosis of mycobacterium tuberculosis infection: a short-term economic evaluation.

Objectives: Recombinant Mycobacterium tuberculosis fusion protein (EC) was anticipated to be used for the scale-up of clinical application for diagnosis of Mycobacterium tuberculosis infection in China, but it lacked a head-to-head economic evaluation based on the Chinese population. This study aimed to estimate the cost-utility and the cost-effectiveness of both EC and tuberculin pure protein derivative (TB-PPD) for diagnosis of Mycobacterium tuberculosis infection in the short term. Methods: From a Chinese societal perspective, both cost-utility analysis and cost-effectiveness analysis were performed to evaluate the economics of EC and TB-PPD for a one-year period based on clinical trials and decision tree model, with quality-adjusted life years (QALYs) as the utility-measured primary outcome and diagnostic performance (including the misdiagnosis rate, the omission diagnostic rate, the number of patients correctly classified, and the number of tuberculosis cases avoided) as the effective-measured secondary outcome. One-way and probabilistic sensitivity analyses were performed to validate the robustness of the base-case analysis, and a scenario analysis was conducted to evaluate the difference in the charging method between EC and TB-PPD. Results: The base-case analysis showed that, compared with TB-PPD, EC was the dominant strategy with an incremental cost-utility ratio (ICUR) of saving 192,043.60 CNY per QALY gained, and with an incremental cost-effectiveness ratio (ICER) of saving 7,263.53 CNY per misdiagnosis rate reduction. In addition, there was no statistical difference in terms of the omission diagnostic rate, the number of patients correctly classified, and the number of tuberculosis cases avoided, and EC was a similar cost-saving strategy with a lower test cost (98.00 CNY) than that of TB-PPD (136.78 CNY). The sensitivity analysis showed the robustness of cost-utility and cost-effectiveness analysis, and the scenario analysis indicated cost-utility in EC and cost-effectiveness in TB-PPD. Conclusion: This economic evaluation from a societal perspective showed that, compared to TB-PPD, EC was likely to be a cost-utility and cost-effective intervention in the short term in China.

[Effect of Interactions Among Obesity-Related Proteins on Breast Cancer Risk: A Preliminary Study].

Objective: To explore the potential interactions among obesity-related proteins in the pathogenic process of breast cancer (BC) in women. Methods: We conducted a case-control study, enrolling 279 primary breast cancer cases and 260 age-frequency-matched healthy women between April 2014 and May 2015. Based on the evidence of previous published literature on obesity-related proteins and BC risks, we selected proteins that received more attention and measured the plasma levels of these proteins by enzyme-linked immunosorbent assay (ELISA). After stratification of the subjects according to their menopausal status, an analytic strategy combining multivariate logistic regression and generalized multifactor dimensionality reduction (GMDR) was used to explore the effect of the possible interactions of these proteins on BC risk. Results: There were marginal high-order interactions among insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), C-reactive protein (CRP), resistin (RETN), soluble leptin receptor (sOB-R), and adiponectin (ADP) in premenopausal women (with the balanced accuracy for the testing set being 59.01%, cross-validation consistency being 10/10, and permutation test P=0.05). There were high-order interactions among leptin (LEP), sOB-R, ADP, CRP, IGFBP3 and visfatin (VF) in postmenopausal women (with the balanced accuracy for the testing set being 67.31%, cross-validation consistency being 10/10, and permutation test P=0.01). Along with an increase in the number of obesity-related proteins to which the subjects were exposed, the risk of developing breast cancer gradually increased in both pre- and postmenopausal women ( OR pre =2.18, 95% CI: 1.69-2.82; OR post =2.41, 95% CI: 1.75-3.32). Conclusions: This preliminary study suggested high-order interactions among obesity-related proteins on BC risk in both pre- and postmenopausal women. In future studies, close attention should be given to these potential interactions when these proteins are used jointly as predictors, as well as in developing a comprehensive risk scoring system for BC.

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.

Tools for Identifying Potentially Inappropriate Prescriptions for Children and Their Applicability in Clinical Practices: A Systematic Review.

Background: Drug use safety in children is a global public health problem. The potentially inappropriate prescription screening tools are expected to reduce adverse drug reactions and promote rational drug use. Objectives: To systematically evaluate children's potentially inappropriate prescription screening tools and validation studies on these tools. Methods: We systematically searched six databases PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang Data. Two reviewers independently selected articles by the eligible criteria and extracted data. Then we evaluated the coverage of diseases or drugs in these tools and the consistency of items between tools. Results: Five children's potentially inappropriate prescription screening tools were identified, most tools were formed by Delphi expert consensus and focused on respiratory system drugs, anti-infective drugs, and gastrointestinal drugs. The coincidence rates of items between the POPI and the POPI Int, the POPI and the POPI United Kingdom, the POPI United Kingdom and the POPI int, and the POPI United Kingdom and the PIPc were 82.0, 55.1, 51.0 and 2.2% respectively, and the KIDs List did not overlap other four tools. Only the POPI tool developed by French experts was comprehensively validated by studies and most tools have not been validated. Conclusion: The development of screening tools for potentially inappropriate prescribing in children is a neglected field and most tools lack studies to validate clinical applicability. More researchers need to form their national potentially inappropriate prescription screening tools for children based on the best available clinical evidence and the actual clinical situation in their countries.

Safety and Effectiveness of Inhaling Different Dosage Recombinant Human Interferon α1B for Bronchiolitis in Children: a Systematic Review and Meta-Analysis.

Purpose: To systematically evaluate the safety and effectiveness of different dosages of recombinant human interferon α1b (IFNα1b) inhaled for bronchiolitis in children. Methods: 7 databases, including PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang Database, and VIP, were searched. The search time was from their inception dates to March 28, 2022. A randomized controlled trial (RCT) of 2 µg/kg IFNα1b (low dosage group) monotherapy or in combination with other drugs vs. 4 µg/kg IFNα1b (high dosage group) monotherapy or in combination with the other drugs was included. The risk of bias 2.0 evaluated the RCT's quality, and the grading of recommendations assessment, development and evaluation (GRADE) tool was used for evaluating the overall quality of the evidence. Then, a meta-analysis was performed by RevMan 5.4. Results: A total of 13 RCTs with 1719 children were included. The meta-analysis results showed that the high dosage group was significantly shorter than the low dosage group of the duration of hospital stays (MD = -0.40, 95%CI (-0.73, -0.07), P = 0.02) (low quality), three depressions sign disappearing time (MD = -0.60, 95%CI (-1.05, -0.14), P = 0.010) (low quality), and wheeze disappearing time (MD = -0.62, 95%CI (-1.17, -0.06), = 0.03) (low quality). There was no significant difference between the two groups in coughing disappearing time, pulmonary rales disappearing time, wheezing sound disappearing time, or adverse event rates. Conclusions: Compared with low dosage IFNα1b, high dosage IFNα1b reduces the duration of hospital stays, the disappearance time of the three depression signs, and the disappearance time of wheeze in the treatment of bronchiolitis in children. Limited by the low quality of the evidence, the conclusions still need to be supported by high-quality studies.

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.

The efficacy and safety of azithromycin in treatment for childhood asthma: A systematic review and meta-analysis.

BACKGROUND: Azithromycin (AZI) is increasingly used for childhood asthma despite limited and inconsistent data. We aimed to evaluate the efficacy and safety of AZI in childhood asthma. METHODS: We searched seven databases to include randomized controlled trials (RCTs) of AZI in the treatment of childhood asthma. Four reviewers independently screened the records. Risk of Bias 2 was used to assess the quality of RCTs. Risk ratios with 95% confidence interval (CI) from dichotomous outcomes, and mean difference (MD) with 95% CI from continuous outcomes were pooled. RESULTS: We included 19 eligible reports from 17 studies. The prevalence of exacerbations in AZI + budesonide (BUD) + ß2 agonist (BA) group was lower than BUD + BA group (four [13%] vs. 19 [63%], p < 0.05) in 6- 14 years old children with chronic persistent asthma. AZI plus antiasthma drugs (AADs) could improve the posttreatment childhood asthma control test score (MD = 2.97; 95% CI, 2.39-3.54) compared to AADs alone in children with chronic persistent asthma. AZI plus AADs could improve posttreatment forced expiratory volume in 1 s of predicted value/forced vital capacity % (MD = 10.24%; 95% CI, 6.44%-14.03%) and posttreatment peak expiratory flow % of predicted value (MD = 7.00%; 95% CI, 2.53%-11.47%) compared to AADs alone in children with chronic persistent asthma. The most common adverse reactions of AZI combined with other drugs were gastrointestinal reactions. CONCLUSIONS: AZI may be beneficial in improving some clinical symptoms and lung functions in older asthma children (over 6 years old) with persistent asthma. But it still requires further research.

[Population-based Study of the Effects of Adiponectin, Leptin and Soluble Leptin Receptor on Risks for Breast Cancer].

OBJECTIVE: To explore the individual or combined effects of adiponectin, leptin, and soluble leptin receptor (sOB-R) on risks for premenopausal and postmenopausal breast cancer, and to provide evidence for revealing the molecular mechanism between obesity and breast cancer. METHODS: 469 newly-diagnosed breast cancer cases were sequentially recruited for the study and 469 age-frequency-matched healthy women were enrolled as the controls over the same period of time. The participant baseline information was collected with questionnaires, and plasmic levels of adiponectin, leptin and sOB-R were checked with ELISA. Multivariate unconditional logistic regression was conducted and the analyses were further stratified according to waist-to-hip ratio (WHR) and body mass index (BMI) to explore the effect of the indicators on the risks for premenopausal and postmenopausal breast cancer. RESULTS: A total of 480 premenopausal and 458 postmenopausal women were included in the study. Among the premenopausal subjects, 249 were breast cancer patients and 231 were controls. The median BMI was 22.9 kg/m 2and 23.2 kg /m 2, respectively, and the median WHR was 0.80 and 0.83, respectively. Among the postmenopausal subjects, 220 were breast cancer patients and 238 were controls. The median BMI was 23.4 kg/m 2 and 23.7 kg/m 2, respectively, and the median WHR was 0.82 and 0.86, respectively. Multivariate logistic regression analysis showed that before and after model adjustment, the increase in sOB-R and adiponectin levels was correlated to reduced risks of premenopausal and postmenopausal breast cancer ( P<0.05), while the increase in the leptin/sOB-R ratio (also known as free leptin index, FLI) and leptin/adiponectin (L/A) ratio was only correlated to increased risks of postmenopausal breast cancer. After further stratification by WHR and BMI, the association between adiponectin, FLI and postmenopausal breast cancer remained statistically significant in all subgroups. Among subjects with normal-BMI central obesity (18.5 kg/m 2≤BMI<24 kg/m 2 & WHR≥0.85) , higher L/A ratio was associated with an increased risk of postmenopausal breast cancer. No clear association between leptin and premenopausal and risks for postmenopausal breast cancer was found in the study. CONCLUSION: Postmenopausal women with decreased levels of sOB-R and adiponectin, and increased FLI and L/A, and premenopausal women with decreased levels of sOB-R and adiponectin were found to be at high risks for breast cancer.

Obesity-related proteins score as a potential marker of breast cancer risk.

There is strong evidence to suggest that obesity-related proteins play a key role in pathways that are related to breast cancer. In this study, we aimed to establish a robust obesity-related protein score (ORPS) that could be used to assess breast cancer risk. Based on evidence from high-quality systematic reviews and population studies, we selected nine such proteins that are stable in vitro, and measured their circulating concentrations by ELISA in a case-control study conducted in Chengdu, Sichuan, China, with 279 breast cancer cases and 260 healthy controls. Two obesity-related protein scores (ORPS) were calculated using a three-step method, with linear-weighted summation, and the one with a larger area under the curve was chosen for further evaluation. As a result, ORPS (PS5pre or PS4post) was positively correlated with breast cancer risk (premenopausal: OR≤63 VS >63 3.696, 95% CI 2.025-6.747; postmenopausal: OR≤38 VS >38 7.100, 95% CI 3.134-16.084), and represented a better risk predictor among obese women compared to non-obese in pre- and postmenopausal women. Among different molecular subtypes, ORPS was positively correlated with Luminal breast cancer, with additionally positive association with triple-negative breast cancer in premenopausal women. The ORPS might be a potential marker of breast cancer risk among Chinese women.

Predicting Breast Cancer in Chinese Women Using Machine Learning Techniques: Algorithm Development.

BACKGROUND: Risk-based breast cancer screening is a cost-effective intervention for controlling breast cancer in China, but the successful implementation of such intervention requires an accurate breast cancer prediction model for Chinese women. OBJECTIVE: This study aimed to evaluate and compare the performance of four machine learning algorithms on predicting breast cancer among Chinese women using 10 breast cancer risk factors. METHODS: A dataset consisting of 7127 breast cancer cases and 7127 matched healthy controls was used for model training and testing. We used repeated 5-fold cross-validation and calculated AUC, sensitivity, specificity, and accuracy as the measures of the model performance. RESULTS: The three novel machine-learning algorithms (XGBoost, Random Forest and Deep Neural Network) all achieved significantly higher area under the receiver operating characteristic curves (AUCs), sensitivity, and accuracy than logistic regression. Among the three novel machine learning algorithms, XGBoost (AUC 0.742) outperformed deep neural network (AUC 0.728) and random forest (AUC 0.728). Main residence, number of live births, menopause status, age, and age at first birth were considered as top-ranked variables in the three novel machine learning algorithms. CONCLUSIONS: The novel machine learning algorithms, especially XGBoost, can be used to develop breast cancer prediction models to help identify women at high risk for breast cancer in developing countries.

[Association Between Plasma Adiponectin and Risk of Breast Cancer by Molecular Subtypes].

OBJECTIVE: To explore the relationships between plasma adiponectin levels and risk of breast cancer by molecular subtype. METHODS: A case-control study including 437 histopathologic confirmed primary breast cancer cases and 469 healthy female controls was conducted between April 2014 and May 2015. Basic information of the participants were collected using a structured questionnaire. Blood samples were collected and the plasma adiponectin levels were measured by enzyme-linked immunosorbent assay (ELASA). Analysis of variance (ANOVA) was used to compare the differences of plasma adiponectin levels among the control group and the breast cancer groups with different molecular subtypes. Multinomial logistic regression was used to investigate the association between plasma adiponectin levels and risk of breast cancer by molecular subtypes. All the statistical analyses were stratified by menopausal status. RESULTS: Among the 437 breast cancer cases, there were 310 Luminal breast cancer cases, 83 HER-2-enriched breast cancer cases and 44 basal-like breast cancer cases. The median (P25, P75) of plasma adiponectin level of the controls was 14.85 (9.69, 21.35) µg/mL. The medians (P25, P75) of plasma adiponectin levels of the cases were 11.74 (8.15, 16.14) µg/mL, 12.02(8.43, 16.96) µg/mL and 12.67(8.25, 17.27) µg/mL for Luminal, HER-2-enriched and basal-like subtype respectively, which were statistically different from the controls (P < 0.001). Multinomial logistic regression showed that, after adjustment for the confounders, the higher levels of plasma adiponectin were associated with the lower risks of pre-menopausal Luminal breast cancer (ORpre-menopausal Luminal=0.50, 95%CI: 0.27-0.92, Ptrend=0.001), post-menopausal Luminal breast cancer (ORpost-menopausal Luminal=0.06, 95%CI: 0.02-0.23, Ptrend < 0.001) and post-menopausal HER-2-enriched breast cancer (ORpost-menopausal HER-2-enriched=0.06, 95%CI: 0.01-0.62, Ptrend=0.001). CONCLUSION: Lower levels of plasma adiponectin may increase the risk of pre-menopausal and post-menopausal Luminal breast cancer and post-menopausal HER-2-enriched breast cancer.

Mobile phone applications and self-management of diabetes: A systematic review with meta-analysis, meta-regression of 21 randomized trials and GRADE.

We conducted a systematic review with meta-analysis of randomized controlled trials that evaluated the effect of diabetes mobile phone applications. A total of 1550 participants from 21 studies were included. For type 1 diabetes, a significant 0.49% reduction in HbA1c was seen (95% CI, 0.04-0.94; I2 = 84%), with unexplained heterogeneity and a low GRADE of evidence. For type 2 diabetes, using diabetes apps was associated with a mean reduction of 0.57% (95% CI, 0.32-0.82; I2 = 77%). The results had severe heterogeneity that was explained by the frequency of HCP feedback. In studies with no HCP feedback, low frequency and high frequency HCP feedback, the mean reduction is 0.24% (95% CI, 0.02-0.49; I2 = 0%), 0.33% (95% CI, 0.07-0.59; I2 = 47%) and 1.12% (95% CI, 0.91-1.32; I2 = 0%), respectively, with a high GRADE of evidence. There is evidence that diabetes apps improve glycaemic control in type 1 diabetes patients. A reduction of 0.57% in HbA1c was found in type 2 diabetes patients. However, HCP functionality is important to achieve clinical effectiveness. Future studies are needed to explore the cost-effectiveness of diabetes apps and the optimal intensity of HCP feedback.