Developing a Cost-Effective Surgical Scheduling System Applying Lean Thinking and Toyota's Methods for Surgery-Related Big Data for Improved Data Use in Hospitals: User-Centered Design Approach.

BACKGROUND: Surgical scheduling is pivotal in managing daily surgical sequences, impacting patient experience and hospital resources significantly. With operating rooms costing approximately US $36 per minute, efficient scheduling is vital. However, global practices in surgical scheduling vary, largely due to challenges in predicting individual surgeon times for diverse patient conditions. Inspired by the Toyota Production System's efficiency in addressing similar logistical challenges, we applied its principles as detailed in the book "Lean Thinking" by Womack and Jones, which identifies processes that do not meet customer needs as wasteful. This insight is critical in health care, where waste can compromise patient safety and medical quality. OBJECTIVE: This study aims to use lean thinking and Toyota methods to develop a more efficient surgical scheduling system that better aligns with user needs without additional financial burdens. METHODS: We implemented the 5 principles of the Toyota system: specifying value, identifying the value stream, enabling flow, establishing pull, and pursuing perfection. Value was defined in terms of meeting the customer's needs, which in this context involved developing a responsive and efficient scheduling system. Our approach included 2 subsystems: one handling presurgery patient data and another for intraoperative and postoperative data. We identified inefficiencies in the presurgery data subsystem and responded by creating a comprehensive value stream map of the surgical process. We developed 2 Excel (Microsoft Corporation) macros using Visual Basic for Applications. The first calculated average surgery times from intra- or postoperative historic data, while the second estimated surgery durations and generated concise, visually engaging scheduling reports from presurgery data. We assessed the effectiveness of the new system by comparing task completion times and user satisfaction between the old and new systems. RESULTS: The implementation of the revised scheduling system significantly reduced the overall scheduling time from 301 seconds to 261 seconds (P=.02), with significant time reductions in the revised process from 99 seconds to 62 seconds (P<.001). Despite these improvements, approximately 21% of nurses preferred the older system for its familiarity. The new system protects patient data privacy and streamlines schedule dissemination through a secure LINE group (LY Corp), ensuring seamless flow. The design of the system allows for real-time updates and has been effectively monitoring surgical durations daily for over 3 years. The "pull" principle was demonstrated when an unplanned software issue prompted immediate, user-led troubleshooting, enhancing system reliability. Continuous improvement efforts are ongoing, except for the preoperative patient confirmation step, which requires further enhancement to ensure optimal patient safety. CONCLUSIONS: Lean principles and Toyota's methods, combined with computer programming, can revitalize surgical scheduling processes. They offer effective solutions for surgical scheduling challenges and enable the creation of a novel surgical scheduling system without incurring additional costs.

Efficacy of Personalized Postoperative Epilepsy Management in Patients with Glioblastoma Utilizing IDH1 Gene Assessment.

Objective: We explored the correlation between the presence of isocitrate dehydrogenase-1 (IDH1) mutations and the incidence of postoperative epilepsy in patients with glioblastoma, as well as assessed the efficacy of preemptive administration of antiepileptic medications in mitigating the occurrence of postoperative epilepsy. Methods: Fifty-three patients who received a postoperative pathological diagnosis of glioblastoma, were enrolled in this study. Tumor specimens were subjected to IDH1 gene analysis. The patient cohort was stratified based on their IDH1 mutation status and the administration of prophylactic antiepileptic drugs during the postoperative phase. We subsequently conducted a comparative analysis of postoperative epileptic complications within each patient subgroup. Results: In the cohort of 53 patients under study, the occurrence of epilepsy was observed in 10 out of 21 patients carrying IDH1 mutations, while 5 out of 32 patients with wild-type IDH1 also experienced epilepsy, revealing a statistically significant difference (P < 0.05). Among the 27 patients who received prophylactic antiepileptic drugs, 6 of them developed epilepsy, whereas 9 out of 26 patients who did not receive prophylactic antiepileptic drugs exhibited concurrent epilepsy, with no statistically significant difference (P > 0.05). However, when performing a subgroup analysis, it was found that 3 out of 12 patients with IDH1 mutations who received prophylactic antiepileptic drugs experienced epilepsy, whereas 7 out of 9 patients who did not receive prophylactic antiepileptic drugs developed epilepsy, demonstrating a statistically significant difference (P < 0.05). Furthermore, within the group of 15 patients with wild-type IDH1, 3 patients who received prophylactic antiepileptic drugs developed epilepsy, while 2 cases of epilepsy occurred among the 17 patients who did not receive prophylactic antiepileptic drugs, with no statistically significant difference (P > 0.05). Conclusion: In individuals with IDH1 mutant glioblastoma who have undergone surgical resection, the implementation of preventive antiepileptic therapy demonstrates a potential to diminish the occurrence of postoperative epilepsy.

Advancing the National Immunization Program in an era of achieving universal vaccine coverage in China and beyond.

BACKGROUND: Immunization is a cornerstone of public health. Despite great success, China's National Immunization Program (NIP) faces challenges, such as the integration of several World Health Organization-recommended vaccines and other systemic issues. The Innovation Laboratory for Vaccine Delivery Research (VaxLab), supported by the Bill & Melinda Gates Foundation and established in 2021 at Duke Kunshan University, focuses on enhancing China's NIP through research and policy advocacy. This editorial aims to summarize the key findings of the manuscripts published in the collection contributed by VaxLab team and set the future research agenda. KEY FINDINGS: The collection contains eleven manuscripts discussing China's immunization landscape and strategies to improve coverage, particularly for non-NIP vaccines like human papillomavirus vaccine (HPV), pneumococcal conjugate vaccine (PCV), Haemophilus influenzae type b vaccine (Hib), and rotavirus vaccines. Key findings include: (i) The COVID-19 vaccination campaign demonstrated China's capacity for rapid, large-scale immunization efforts, suggesting potential for broader vaccine coverage improvements; (ii) Efforts in combating cervical cancer through the HPV vaccine indicate progress but also highlight challenges like vaccine supply and equitable access; (iii) The lag in adopting higher-valent paediatric combination vaccines in China needs attention to address regulatory and health system hurdles; (iv) Disparities in access to non-NIP vaccines underscore the need for government initiatives to improve vaccine coverage, especially for remote areas and marginalized populations; (v) Original studies emphasize the influence of caregivers' knowledge, health workers' financial incentives, and concerns about vaccine efficacy on immunization rates; (vi) Case studies from the Weifang City of China and Indonesia to introduce PCV offer insights on successful vaccine introduction strategies and the impact of innovative financing and government support. CONCLUSION: The articles emphasize the need for government leadership, strategic policymaking, and public awareness to enhance vaccine coverage and equity. The VaxLab will continue strengthening China's NIP by focusing on vaccine financing, emphasizing diversity, equity, and inclusion, and improving maternal vaccination coverage. Research will extend to Southeast Asian and Western Pacific regions, especially in middle-income countries facing challenges in vaccine financing and delivery. The collective efforts outlined in this collection show a commitment to evolving and adapting immunization strategies to meet global health goals and to provide equitable access to vaccines for all.

Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

Promoting higher-valent pediatric combination vaccines in China: challenges and recommendations for action.

Many countries have adopted higher-valent pediatric combination vaccines to simplify vaccination schedules and minimize health expenditures and social costs. However, China is conservative in the use of pediatric combination vaccines. By reviewing and synthesizing quantitative and qualitative data, in this commentary we identify gaps and challenges to combination vaccine use and make recommendations for promoting use of higher-valent pediatric combination vaccines in China. Challenges are in four dimensions: (1) legislation and regulation, (2) immunization schedule design, (3) vaccine awareness and price, and (4) research and development capacity. To optimize the use of combination vaccines to reduce vaccine-preventable disease burden, we make recommendations that address key challenges: (1) develop policies and regulations to strengthen enforcement of the Vaccine Administration Law and remove regulatory hurdles that hinder combination vaccine research and development, (2) establish an evidence-informed policy-making mechanism for combination vaccines, (3) resolve immunization schedule conflicts between monovalent and combination vaccines, and (4) implement effective interventions to increase vaccine awareness and reduce price.

Validation of traditional Chinese version of Sheffield Profile for Assessment and Referral for Care Questionnaire in Taiwanese patients.

BACKGROUND: Holistic health care considers all aspects of patient care, namely the physical, psychological, spiritual, and social aspects. To assess which patient needs are unmet, a screening questionnaire covering the four aforementioned aspects is required. Therefore, the Sheffield Profile for Assessment and Referral for Care (SPARC), a multidimensional, self-reported questionnaire designed to screen patients regardless of diagnosis, was developed. This study developed a translated and validated traditional Chinese version of the SPARC for patients in Taiwan. METHODS: The original English version of the SPARC was translated into a traditional Chinese version (SPARC-T) through forward-backward translation. Semistructured debriefing interviews were conducted with participants to evaluate the SPARC-T. The reliability and validity of the SPARC-T were assessed through Cronbach's alpha coefficients and a correlation analysis conducted using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. RESULTS: Fifty-three patients were enrolled from our hospital: 22 had cancer but the majority had nonmalignant chronic conditions. About internal consistency, the Cronbach's alpha values for all domains of the SPARC-T were favorable. A correlation analysis of the SPARC-T and FACT-G revealed significant correlations for the domains of physical symptoms, independence and activity, family and social issues, sleep, and treatment issues; no significant correlation was identified for the "psychological issues" domain. CONCLUSION: This study revealed that the SPARC-T is an effective tool for screening Mandarin-speaking patients. Thus, it can be used in hospitals to holistically screen and identify the needs of patients to ensure they can receive appropriate professional support and holistic health care.

Recommendations and guidelines for endoscope reprocessing: Current position statement of digestive endoscopic society of Taiwan.

Reprocessing of gastrointestinal (GI) endoscopes and accessories is an essential part of patient safety and quality control in GI endoscopy centers. However, current endoscopic reprocessing guidelines or procedures are not adequate to ensure patient-safe endoscopy. Approximately 5.4 % of the clinically used duodenoscopes remain contaminated with high-concern microorganisms. Thus, the Digestive Endoscopy Society of Taiwan (DEST) sets standards for the reprocessing of GI endoscopes and accessories in endoscopy centers. DEST organized a task force working group using the guideline-revision process. These guidelines contain principles and instructions of step-by-step for endoscope reprocessing. The updated guidelines were established after a thorough review of the existing global and local guidelines, systematic reviews, and health technology assessments of clinical effectiveness. This guideline aims to provide detailed recommendations for endoscope reprocessing to ensure adequate quality control in endoscopy centers.

The coverage and challenges of increasing uptake of non-National Immunization Program vaccines in China: a scoping review.

BACKGROUND: Non-National Immunization Program (NIP) vaccines have played an important role in controlling vaccine-preventable diseases (VPDs) in China. However, these vaccines are paid out of pocket and there is room to increase their coverage. We focused on four selected non-NIP vaccines in this study, namely Haemophilus influenzae type b (Hib) vaccine, human papillomavirus (HPV) vaccine, pneumococcal conjugate vaccine (PCV), and rotavirus vaccine. We aimed to conduct a scoping review of their vaccination rates and the major barriers faced by health systems, providers, and caregivers to increase coverage. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). We searched five English databases (PubMed, Web of Science, EMBASE, Scopus, and WHO IRIS) and four Chinese databases using the search strategy developed by the study team. Two independent reviewers screened, selected studies, and examined their quality. We summarized the non-NIP vaccine coverage data by vaccine and applied the 5A framework (Access, Affordability, Acceptance, Awareness, Activation) to chart and analyze barriers to increasing coverage. RESULTS: A total of 28 articles were included in the analysis (nine pertaining to vaccine coverage, and another 19 reporting challenges of increasing uptake). Among the four selected vaccines, coverage for the Hib vaccine was the highest (54.9-55.9% for 1 dose or more from two meta-analyses) in 2016, while the coverage of the other three vaccines was lower than 30%. Eight of the nine included articles mentioned the regional disparity of coverage, which was lower in under-developing regions. For example, the three-dose Hib vaccination rate in eastern provinces was 38.1%, whereas the rate in central and western provinces was 34.3% and 26.2%, respectively in 2017. Within the 5A framework, acceptance, awareness, and affordability stood out as the most prominent themes. Among the 12 identified sub-themes, high prices, low vaccine awareness, concerns about vaccine safety and efficacy were the most cited barriers to increasing the uptake. CONCLUSIONS: There is an urgent need to increase coverage of non-NIP vaccines and reduce disparities in access to these vaccines across regions. Concerted efforts from the government, the public, and society are required to tackle the barriers and challenges identified in this study, both on the demand and supply side, to ensure everybody has equal access to life-saving vaccines in China. Particularly, the government should take a prudent approach to gradually incorporate non-NIP vaccines into the NIP step by step, and make a prioritizing strategy based on key factors such as disease burden, financial resources, and market readiness, with special attention to high-risk populations and underdeveloped regions.

Efficacy, safety and cost of emicizumab prophylaxis in haemophilia A patients with inhibitors: A nationwide observational study in Taiwan.

INTRODUCTION: Emicizumab mimicking the cofactor function of activated factor VIII (FVIII) restores haemostasis. METHODS: This nationwide observational study aimed to retrospectively investigate efficacy, safety, and cost in 1 year before and up to 3 years after emicizumab prophylaxis for haemophilia A (HA) patients with FVIII inhibitors. RESULTS AND DISCUSSION: A total of 39 severe HA patients with a median age of 23.0 years were enrolled. The median historical peak FVIII inhibitor titre was 174.2 BU/mL with an interquartile range of 56.5-578.8 BU/mL. The median annualized bleeding rate reduced from 24 to 0 events in the first year after emicizumab prophylaxis (p < .01) and sustained in the second and third years. The median annualized joint bleeding rate reduced to 0 and maintained up to 3 years (p < .01). Twenty-seven patients (69.2%) had target joints before emicizumab prophylaxis and only seven patients (17.9%) of them had target joints after prophylaxis. Medical costs, including cost of haemostatic therapy, frequency of outpatient department visits, emergency room visits and hospital admission, were significantly reduced after emicizumab prophylaxis (p < .01). FVIII inhibitor titre decreased after emicizumab prophylaxis. Overall, three (7.7%) patients experienced 202 grade 1 drug-related adverse events after emicizumab prophylaxis. No serious adverse events were reported during emicizumab prophylaxis period. The adherence to emicizumab prophylaxis was 100% up to 3 years. CONCLUSIONS: HA patients with FVIII inhibitors treated with emicizumab prophylaxis resulted in a significant reduction in treated bleeds and associated costs. No new safety events were observed.

Smarca2 genetic ablation is phenotypically benign in a safety assessment of tamoxifen-inducible conditional knockout rats.

SMARCA2 and SMARCA4 are the ATPases of the SWI/SNF chromatin remodeling complex, which play a significant role in regulating transcriptional activity and DNA repair in cells. SMARCA2 has become an appealing synthetic-lethal, therapeutic target in oncology, as mutational loss of SMARCA4 in many cancers leads to a functional dependency on residual SMARCA2 activity. Thus, for therapeutic development, an important step is understanding any potential safety target-associated liabilities of SMARCA2 inhibition. To best mimic a SMARCA2 therapeutic, a tamoxifen-inducible (TAMi) conditional knockout (cKO) rat was developed using CRISPR technology to understand the safety profile of Smarca2 genetic ablation in a model system that avoids potential juvenile and developmental phenotypes. As the rat is the prototypical rodent species utilized in toxicology studies, a comprehensive toxicological and pathological assessment was conducted in both heterozygote and homozygous knockout rats at timepoints up to 28 days, alongside relevant corresponding controls. To our knowledge, this represents the first TAMi cKO rat model utilized for safety assessment evaluations. No significant target-associated phenotypes were observed when Smarca2 was ablated in mature (11- to 15-week-old) rats; however subsequent induction of SMARCA4 was evident that could indicate potential compensatory activity. Similar to mouse models, rat CreERT2-transgene and TAMi toxicities were characterized to avoid confounding study interpretation. In summary, a lack of significant safety findings in Smarca2 cKO rats highlights the potential for therapeutics targeting selective SMARCA2 ATPase activity; such therapies are predicted to be tolerated in patients without eliciting significant on-target toxicities.

Ecological risk assessment of heavy metals in riverine sediments of rural area driven by urbanization.

Rural revitalization denotes the gathering of large populations in rural areas and the subsequent gradual urbanization. Rural environments have been deteriorated by heavy metals (HMs) over the last few years. Without the existence of large-scale industries, the accumulation of HMs in sediments due to population aggregation in rural environments needs to be scientifically confirmed. Therefore, in this study we first understand the sediment pollution in rural environments in China and across the globe, and subsequently investigate HMs in sediments in rural micro water. The study area, Sichuan Province, China, was divided into two areas, namely, sparsely populated areas (SPA) and densely populated areas (DPA). Eight typical HMs (As, Zn, Ni, Hg, Cd, Cr, Cu, and Pb) were selected to target in riverine sediments, and the content and spatial distribution characteristics were analyzed. The results indicate that As, Hg, Cd, and Pb concentrations in sediments were higher than background values (BVs), with high concentration sample sites located in the DPA. In addition, the geo-accumulation index (Igeo), pollution load index (PLI) and potential ecological risk index (RI) were used to quantitatively evaluate the pollution characteristics of HMs in sediments, revealing that the sediments exhibited high As and Hg pollution in the DPA (PLI = 1.09). In general, mild (RI = 48.76) and moderate (RI = 154.92) HM pollution was observed in the sediments of the SPA and DPA, respectively, based on the high PLI (> 1.0) and RI (> 150) values. Correlation analysis and principal component analysis (PCA) indicate that the Cd in the sediment generally originated from geogenic sources, while the other elements (Zn, As, Cu, Cr, Hg, Ni and Pb) were primarily linked to anthropogenic sources. Finally, the results demonstrate that population aggregation will lead to the enrichment of HMs.

"It's Just a Checklist": Examining the Needs of Occupational Health and Safety Training for New Immigrant Workers in Canada.

OBJECTIVES: New immigrant workers (NIWs) are overrepresented in hazardous workplaces. Sufficient Occupational Health and Safety (OH&S) training could minimize workplace injuries. This study aims to identify the current status of OH&S and training for NIWs in Canada. METHODS: Generic qualitative research was conducted. Seven NIWs and nine service providers were interviewed to understand OH&S issues, perceptions on rules and regulations, and expectations for training. Thematic analysis was used for data analysis. RESULTS: Four themes that affect OH&S for NIWs include attitudes toward safety and training, personal barriers, Canadian workplace culture, and macrolevel interconnected systems. Three needs on OH&S training are increasing accessibility, ensuring full understanding, and building confidence. CONCLUSIONS: Current training does not mitigate safety risks in workplaces, and NIWs do not feel empowered to exercise their rights. New training protocols would be beneficial to equip NIWs to enter the workforce.

Life-course inequalities in intrinsic capacity and healthy ageing, China.

Objective: To investigate the contribution of early-life factors on intrinsic capacity of Chinese adults older than 45 years. Methods: We used data on 21 783 participants from waves 1 (2011) and 2 (2013) of the China Health and Retirement Longitudinal Study (CHARLS), who also participated in the 2014 CHARLS Life History Survey to calculate a previously validated measure of intrinsic capacity. We considered 11 early-life factors and investigated their direct association with participants' intrinsic capacity later in life, as well as their indirect association through four current socioeconomic factors. We used multivariable linear regression and the decomposition of the concentration index to investigate the contribution of each determinant to intrinsic capacity inequalities. Findings: Participants with a favourable environment in early life (that is, parental education, childhood health and neighbourhood environment) had a significantly higher intrinsic capacity score in later life. For example, participants with a literate father recorded a 0.040 (95% confidence interval, CI: 0.020 to 0.051) higher intrinsic capacity score than those with an illiterate father. This inequality was greater for cognitive, sensory and psychological capacities than locomotion and vitality. Overall, early-life factors directly explained 13.92% (95% CI: 12.07 to 15.77) of intrinsic capacity inequalities, and a further 28.57% (95% CI: 28.19 to 28.95) of these inequalities through their influence on current socioeconomic inequalities. Conclusion: Unfavourable early-life factors appear to decrease late-life health status in China, particularly cognitive, sensory and psychological capacities, and these effects are exacerbated by cumulative socioeconomic inequalities over a person's life course.

Systematic assessment of plasma biomarkers in spinocerebellar ataxia.

BACKGROUND AND OBJECTIVES: Plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), phosphorylated-tau (p-tau), and ß-amyloid (Aß) have emerged as promising markers in several neurodegenerative disorders, but whether they can be used as biomarkers in spinocerebellar ataxias (SCA) is yet to be determined. This study aimed to identify sensitive plasma markers for SCA and investigate their effectiveness in tracking ataxia severity, cognition, non-motor symptoms, and brain atrophy. METHODS: This observational study recruited consecutive participants from Huashan Hospital and the CABLE study from November 2019. Patients with SCA were genetically diagnosed, grouped according to the ataxia severity, and compared with healthy older individuals and patients with multiple system atrophy type C (MSA-C). Plasma NfL, GFAP, p-tau, and Aß levels were measured by Simoa in all participants. Analysis of covariance, Spearman correlation, and multivariable regression were used to explore candidate markers in SCA. RESULTS: A total of 190 participants (60 SCA, 56 MSA-C, and 74 healthy controls) were enrolled. Plasma NfL level increased early in the pre-ataxic stage of SCA (32.23 ± 3.07 vs. 11.41 ± 6.62 pg/mL in controls), was positively associated with the ataxia severity (r = 0.45, P = 0.005) and CAG repeat length (r = 0.51, P = 0.001), varied among the different SCA subtypes (39.57 ± 13.50 pg/mL in SCA3, which was higher than 28.17 ± 8.02 pg/mL in SCA2, 17.08 ± 6.78 pg/mL in SCA8, and 24.44 ± 18.97 pg/mL in rare SCAs; P < 0.05), and was associated with brainstem atrophy. NfL alone (area under the curve [AUC] 0.867) or combined with p-tau181 and Aß (AUC 0.929), showed excellent performance in discriminating SCA patients from controls. Plasma GFAP distinguished SCA from MSA-C with moderate accuracy (AUC > 0.700) and correlated with cognitive performance and cortical atrophy. Changes in levels of p-tau181 and Aß were observed in SCA patients compared to controls. They were both correlated with cognition, while Aß was also associated with non-motor symptoms, such as anxiety and depression. DISCUSSION: Plasma NfL may serve as a sensitive biomarker for SCA, and its level is elevated in the pre-ataxic stage. The different performance of NfL and GFAP indicates differences in the underlying neuropathology of SCA and MSA-C. Moreover, amyloid markers may be useful for detecting memory dysfunction and other non-motor symptoms in SCA.

Application of a CRISPR Sequence-Based Method for a Large-Scale Assessment of Salmonella Serovars in Ontario Poultry Production Environments.

Accurate detection of all Salmonella serovars present in a sample is important in surveillance programs. Current detection protocols are limited to detection of a predominant serovar, missing identification of less abundant serovars in a sample. An alternative method, called CRISPR-SeroSeq, serotyping by sequencing of amplified CRISPR spacers, was employed to detect multiple serovars in a sample without the need of culture isolation. The CRISPR-SeroSeq method successfully detected 34 most frequently reported Salmonella serovars in pure cultures and target serovars at 104 CFU/mL in 27 Salmonella-negative environmental enrichment samples post-spiked with one of 15 different serovars, plus 2 additional serovars at 1 log CFU/mL higher abundance. When the method was applied to 442 naturally contaminated environmental samples collected from 192 poultry farms, 25 different serovars were detected from 430 of the samples. In 73.1% of the samples, 2 to 7 serovars were detected, with Salmonella Kiambu (55.7%), Salmonella Infantis (48.4%), Salmonella Kentucky (27.1%), Salmonella Livingstone (26.6%), and Salmonella Mbandaka/Montevideo (23.4%) being the most prevalent on the farms. Single isolates from 384 samples were also analyzed using a traditional serotyping method, and the same serovar identified by culture was detected by CRISPR-SeroSeq in 96.1% (369/384) of samples, with the former missing detection of additional and sometimes critical serovars. The surveillance data obtained via CRISPR-SeroSeq revealed a significant emergence of Salmonella Kiambu and Salmonella Rissen on poultry farms in Ontario. The results highlight the effectiveness of the CRISPR-SeroSeq approach in detecting multiple Salmonella serovars in poultry environmental samples under applied conditions, providing updated surveillance information on Salmonella serovars on poultry farms in Ontario. IMPORTANCE The CRISPR-SeroSeq method represents an alternative molecular tool to the traditional culture-based serotyping method that can detect multiple Salmonella serovars in a sample and provide rapid serovar results without the need of selective enrichment and culture isolation. The evaluation results can facilitate implementation of the method in routine Salmonella surveillance on poultry farms and in outbreak investigations. The application of the method can increase the accuracy of current serovar prevalence information. The results highlight the effectiveness of the validated method and the need for monitoring Salmonella serovars in poultry environments to improve current surveillance programs. The updated surveillance data provide timely information on emergence of different Salmonella serovars on poultry farms in Ontario and support on-farm risk assessment and risk management of Salmonella.

Quantifying the financial impact of overuse in primary care in China: A standardised patient study.

Overuse of health care is a potential factor in explaining the rapid increase in health care expenditure in many countries; however, it is difficult to measure overuse. This study employed the novel method of using unannounced standardised patients (SPs) to identify overuse, document its patterns and quantify its financial impact on patients in primary care in China. We trained 18 SPs to present consistent cases of two common chronic diseases and recorded 492 physician-patient interactions in 63 public and private primary hospitals in a capital city in western China in 2017 and 2018. Overuse, defined as the provision of unnecessary medical tests and drugs, was identified by a panel of medical experts based on national clinical guidelines. We estimated linear regression models to investigate how hospital, physician and patient characteristics were associated with overuse and to quantify the financial impact of overuse after controlling for a series of fixed effects. We found overuse in 72.15% of the SP visits. The high prevalence of overuse was similar among public and private hospitals, low-competence and high-competence physicians, male and female physicians, junior and senior physicians and male and female patients, but it varied between patients presenting different diseases. Compared to the non-overuse group, overuse significantly increased the total cost by 117.8%, the test cost by 58.8% and the drug cost by 100.3%. The financial impact of overuse was consistent across the aforementioned hospital, physician and patient characteristics. We suggest that the overuse observed in this study is unlikely to be attributable to physician incompetence but rather to the financing framework for primary care in China. These findings illuminate the cost escalation of primary care in China, which is a form of medical inefficiency that should be urgently addressed.

Safety Assessment and Probiotic Potential Comparison of Bifidobacterium longum subsp. infantis BLI-02, Lactobacillus plantarum LPL28, Lactobacillus acidophilus TYCA06, and Lactobacillus paracasei ET-66.

Bifidobacterium longum subsp. infantis BLI-02, Lactobacillus paracasei ET-66, Lactobacillus plantarum LPL28, and Lactobacillus acidophilus TYCA06, isolated from healthy breast milk, miso, and the healthy human gut, were assessed for safety in this study. BLI-02, LPL28, TYCA06, and ET-66 exhibited no antibiotic resistance and mutagenic activity in the Ames test at the highest dosage (5000 µg/plate). No genotoxicity was observed in micronucleus and chromosomal aberration assays in rodent spermatogonia at the maximum dosage of 10 g/kg body weight (BW). No acute and sub-chronic toxicity occurred in mice and rats at the maximum tested dosage of 10 g/kg BW and 1.5 g/kg BW, respectively. The lyophilized powder of these strains survived a low pH and high bile salt environment, adhering strongly to Caco-2 cells. Unique antimicrobial activities were noted in these strains, with BLI-02 demonstrating the best growth inhibition against Vibrio parahaemolyticus, LPL28 exhibiting the best growth inhibition against Helicobacter pylori, and ET-66 showing the best growth inhibition against Aggregatibacter actinomycetemcomitans. Based on the present study, the lyophilized powder of these four strains appears to be a safe probiotic supplement at tested dosages. It should be applicable for clinical or healthcare applications.

Disease burden of ageing, sex and regional disparities and health resources allocation: a longitudinal analysis of 31 provinces in Mainland China.

OBJECTIVES: To measure the disease burden of ageing based on age-related diseases (ARDs), the sex and regional disparities and the impact of health resources allocation on the burden in China. DESIGN: A national comparative study based on Global Burden of Diseases Study estimates and China's routine official statistics. SETTING AND PARTICIPANTS: Thirty-one provinces of Mainland China were included for analysis in the study. No individuals were involved. METHODS: We first identified the ARDs and calculated the disability-adjusted life years (DALYs) of ARDs in 2016. We assessed the ARD burden disparities by province and sex and calculated the provincial ARD burden-adjusted age. We assessed historical changes between 1990 and 2016. Fixed effects regression models were adopted to evaluate the impact of health expenditures and health workforce indicators on the ARD burden in 2010-2016. RESULTS: In 2016, China's total burden of ARDs was 15 703.7 DALYs (95% uncertainty intervals: 12 628.5, 18 406.2) per 100 000 population. Non-communicable diseases accounted for 91.9% of the burden. There were significant regional disparities. The leading five youngest provinces were Beijing, Guangdong, Shanghai, Zhejiang and Fujian, located on the east coast of China with an ARD burden-adjusted age below 40 years. After standardising the age structure, western provinces, including Tibet, Qinghai, Guizhou and Xinjiang, had the highest burden of ARDs. Males were disproportionately affected by ARDs. China's overall age-standardised ARD burden has decreased since 1990, and females and eastern provinces experienced the largest decline. Regression results showed that the urban-rural gap in health workforce density was positively associated with the ARD burdens. CONCLUSION: Chronological age alone does not provide a strong enough basis for appropriate ageing resource planning or policymaking. In China, concerted efforts should be made to reduce the ARDs burden and its disparities. Health resources should be deliberately allocated to western provinces facing the greatest health challenges due to future ageing.