Cost-effectiveness analysis of niraparib maintenance therapy in Chinese patients with platinum-sensitive recurrent ovarian cancer.

OBJECTIVES: This study aimed to evaluate the cost-effectiveness of niraparib versus routine surveillance as maintenance therapy for patients with platinum-sensitive recurrent ovarian cancer in China. METHOD: A three-state partitioned survival model that adopted a lifetime horizon with a 4-week cycle length was developed. Efficacy data were derived from the NORA study. Cost and utility data were obtained from published studies and online databases. The cost and health outcomes were discounted at an annual rate of 5%. In this analysis, the primary outcomes included quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio (ICER). The willingness-to-pay (WTP) thresholds were set at 1 to 3 times the gross domestic product per capita of China in 2022 ($12,741 to $38,233/QALY). Sensitivity analyses were conducted to verify the robustness of the model results. RESULTS: In the base-case analysis, niraparib was not found to be cost-effective, with an ICER of $42,888/QALY compared with routine surveillance at the WTP thresholds. One-way deterministic sensitivity analyses indicated that the ICER value was most sensitive to the cost of subsequent treatment in placebo group. The probabilistic sensitivity analysis suggested that at the WTP thresholds, the probability of niraparib being cost-effective was 2.9% to 50.1%. CONCLUSIONS: Niraparib improves the survival benefit of platinum-sensitive recurrent ovarian cancer patients. However, it seems to be less cost-effective, as it has higher costs than routine surveillance at the WTP thresholds. Reasonable dose reduction according to the patient's actual situation or lowering the price of niraparib can improve its cost-effectiveness.

Exploration of an alternative reconstructed individual patient data-based approach for budget impact analysis of anticancer drugs.

BACKGROUND: The duration of treatment (DOT) of the initial intervention and subsequent treatment is the key to determining the accuracy of anticancer-drug budget impact analysis (BIA) calculations. However, existing studies only use simple assumptions as a proxy for DOT, resulting in a high degree of bias. OBJECTIVES: To enhance the accuracy and reliability of anticancer-drug BIA and solve the problem regarding DOT, we propose an alternative individual patient data (IPD)-based approach that reconstructs IPD from the published Kaplan Meier survival curves to estimate DOT. METHODS: We developed a four-step methodological framework for this new approach, taking the use of pembrolizumab in treating microsatellite-instability-high (MSI-H) advanced colorectal cancer as an example: (1) reconstructing the IPD; (2) calculating the total DOT of the initial intervention and subsequent treatment for each patient; (3) assigning a randomized time and DOT; and (4) multiple replacement sampling and calculation of the mean value. RESULTS: Using this approach, the average DOT for the initial intervention and subsequent treatment in each year of the BIA time horizon can be calculated and used to calculate the resources consumed and costs in each year. In our example, the average DOT for the initial intervention with pembrolizumab from the first to the fourth year was 4.90, 6.60, 5.24, and 5.06 months, respectively, while the average DOT for subsequent treatment was 0.75, 2.84, 2.99, and 2.50 months, respectively. CONCLUSIONS: The reconstructed IPD-based approach can improve the accuracy and reliability of anticancer-drug BIA compared with conventional methods, and can be widely used, especially for anticancer drugs with excellent efficacy.

Intraoperative venous congestion rather than hypotension is associated with acute adverse kidney events after cardiac surgery: a retrospective cohort study.

BACKGROUND: The pathophysiological mechanisms by which venous congestion and hypotension lead to acute adverse kidney events after cardiac surgery with cardiopulmonary bypass have not been elucidated. We tested the hypothesis that intraoperative hypotension and venous congestion are associated with acute kidney injury and acute kidney disease. METHODS: Primary exposures were venous congestion and intraoperative hypotension defined by central venous pressure ≥12, 16, or 20 mm Hg or mean arterial pressure ≤55, 65, or 75 mm Hg. The primary outcomes were acute kidney injury and acute kidney disease. Multivariable logistic regression and Cox proportional hazard models were used, adjusted for relevant confounding factors and multiple comparisons. RESULTS: Of 5127 eligible subjects, 1070 (20.9%) and 327 (7.2%) developed acute kidney injury and acute kidney disease, respectively. The occurrence of acute kidney injury was statistically associated with both venous congestion and intraoperative hypotension. The cumulative incidence rate for new onset acute kidney disease was 1.34 (95% confidence interval [CI], 1.21-1.60) per 100 person-days. Acute kidney disease was significantly associated with each 10 min epoch of central venous pressure ≥12 mm Hg (hazard ratio [HR]=1.03; 99% CI, 1.01-1.06; P<0.001), ≥16 mm Hg (HR=1.04; 99% CI, 1.01-1.07; P<0.001), and ≥20 mm Hg (HR=1.07; 99% CI, 1.02-1.13; P<0.001). Venous congestion was associated with an 8-17% increased risk for de novo renal replacement therapy. In contrast, intraoperative hypotension was not associated with development of acute kidney disease. CONCLUSION: Although both venous congestion and intraoperative hypotension are associated with acute kidney injury, only venous congestion correlates with acute kidney disease among patients undergoing cardiac surgery requiring cardiopulmonary bypass. The reported associations are suggestive of a pathophysiological role of venous congestion in acute kidney disease.

Cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar compared with lenvatinib as the first-line treatment of unresectable or metastatic hepatocellular carcinoma.

BACKGROUND: In recent years, programmed cell death protein-1 inhibitors, including sintilimab, have significantly prolonged the overall survival time of patients with unresectable or metastatic hepatocellular carcinoma (HCC); however, the cost-effectiveness of sintilimab is unclear. The aim of this study was to assess the cost-effectiveness of sintilimab plus bevacizumab biosimilar compared with lenvatinib as first-line treatment in patients with unresectable or metastatic HCC. METHODS: A lifetime partitioned survival model was developed to conduct a cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar vs. lenvatinib for advanced HCC from a Chinese healthcare system perspective. The clinical and safety data were derived from two recent randomized clinical trials, the ORIENT-32 and REFLECT studies. Utility data were obtained from previous studies. Long-term direct medical costs and quality-adjusted life-years (QALYs) were predicted. Deterministic and probabilistic sensitivity analyses were performed to verify the robustness of the model. RESULTS: Compared with lenvatinib, combination therapy with sintilimab and bevacizumab biosimilar yielded an additional 0.493 QALYs at a higher cost ($33,102 vs. $21,037) (2021 US dollars). This resulted in a deterministic incremental cost-effectiveness ratio (ICER) of $24,462 per QALY in the base-case analysis. The ICERs were sensitive to the utility of post-progression and the cost of bevacizumab biosimilar. A lower ICER was estimated when the dose of bevacizumab biosimilar decreased from 15 mg to 7.5 mg per kilogram in the scenario analysis. In the probabilistic sensitivity analysis, the probability of being cost-effective for sintilimab treatment at willingness-to-pay (WTP) thresholds of one ($12,516) and three times the gross domestic product per capita in China ($37,547) were 11.6% and 88.6%, respectively. CONCLUSION: Sintilimab plus bevacizumab biosimilar is likely to be a cost-effective treatment option as a first-line treatment for unresectable or metastatic HCC in China when WTP threshold is over $23,650.

Establishment and application of information-based training and assessment platform for clinical nursing operation technology.

BACKGROUND: The paper version of the training assessment was time-consuming and labor-consuming. It is an inevitable trend to change the appraisal method utilizing information technology. This study aimed to realize convenient and rapid management of the whole process of clinical nursing operation technology through information-based training and assessment platform. METHODS: Combined with the operation mode of clinical nursing operation skills and set the basic functions of the information platform of clinical nursing operation training and assessment, the information-based training and evaluation platform for clinical nursing operation skills was established. The platform was officially operated in a tertiary level A general hospital in Shandong Province in 2018. RESULTS: The information-based training and assessment platform is composed of Management Center (Computer Terminal) and a client terminal (APP terminal). The computer terminal contains 11 modules, and the APP terminal contains 8 modules. By December 2020, a total of 12,619 nurses had completed the training in nursing operation skills, and a total of 11,986 nurses had completed the examination. The examination results of nursing operation skills of the same nurses in 2018 were significantly higher than those in 2017(P < 0.05), and the error rate was significantly lower (P < 0.05). From 2016 to 2020, the scores of nasal feeding, CPR, and respiratory airbag of N1 level nurses significantly increased after using the information-based training and Assessment Platform (P < 0.05). CONCLUSION: Based on the information terminal training assessment can realize the management of the whole process of clinical nursing operation technology training and assessment, which is better than the traditional method, and is a very practical and convenient clinical training and assessment method.

A comparison of self-reported and proxy-reported health utilities in children: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to conduct a systematic review and meta-analysis to compare differences in health utilities (HUs) assessed by self and proxy respondents in children, as well as to evaluate the effects of health conditions, valuation methods, and proxy types on the differences. METHODS: Eligible studies published in PubMed, Embase, Web of Science, and Cochrane Library up to December 2019 were identified according to PRISMA guidelines. Meta-analyses were performed to calculate the weighted mean differences (WMDs) in HUs between proxy- versus self-reports. Mixed-effects meta-regressions were applied to explore differences in WMDs among each health condition, valuation method and proxy type. RESULTS: A total of 30 studies were finally included, comprising 211 pairs of HUs assessed by 15,294 children and 16,103 proxies. This study identified 34 health conditions, 10 valuation methods, and 3 proxy types. In general, proxy-reported HUs were significantly different from those assessed by children themselves, while the direction and magnitude of these differences were inconsistent regarding health conditions, valuation methods, and proxy types. Meta-regression demonstrated that WMDs were significantly different in patients with ear diseases relative to the general population; in those measured by EQ-5D, Health utility index 2 (HUI2), and Pediatric asthma health outcome measure relative to Visual analogue scale method; while were not significantly different in individuals adopting clinician-proxy and caregiver-proxy relative to parent-proxy. CONCLUSION: Divergence existed in HUs between self and proxy-reports. Our findings highlight the importance of selecting appropriate self and/or proxy-reported HUs in health-related quality of life measurement and economic evaluations.

Safety of intraoperative hypothermia for patients: meta-analyses of randomized controlled trials and observational studies.

BACKGROUND: Previous studies have shown that intraoperative hypothermia was associated with higher risks of clinical adverse events, but we found otherwise from recent evidences. This study aims to synthesize the existing evidence evaluating safety of intraoperative hypothermia. METHODS: Articles, reviews, ongoing trials and grey literatures were retrieved from PubMed, The Cochrane Library, Clinical Trails and CNKI (a Chinese national database) till February 2nd, 2019. Both randomized controlled trials and observational studies compared incidences of all sorts of intra- and post-operative consequences between hypothermia and normothermia were included. Researches comparing different warming systems were excluded. We also examined risks of hypothermia using lowered standards (35.5 °C and 35 °C) from a Chinese trial (ChiCTR-IPR-17011099). RESULTS: A total of 9 RCT studies and 11 observational studies were included. RCT-synthesized results showed that intraoperative hypothermia was associated with higher risks of bleeding (MD = 131.90, 95%CI: 117.42, 146.38), surgical site infection (RD = 0.14, 95%CI: 0.06, 0.21) and shivering (RD = 0.32, 95%CI: 0.06, 0.58) but with no significant differences in duration of surgery, hospital stay or mortality. Observational study-synthesized evidences showed that intraoperative hypothermia did not result in higher risks in any of these adverse events. Results didn't change even if the standard of hypothermia was lowered by 0.5-1.0 °C. CONCLUSIONS: The study indicates that the synthesized risks resulted by intra-operative hypothermia might be overestimated and the eligibility of 36 °C to define hypothermia is not sensitive enough. Given body-temperature protection has not been popularized in China, it is still critical to normalize the hypothermia prevention at this stage.

Cyclic Cushing's syndrome caused by neuroendocrine tumor: a case report.

Cushing's syndrome (CS) is a clinical syndrome characterized by hypercortisolemia. Cyclic Cushing's syndrome (CCS), which exhibits a periodic or irregular increasing pattern in cortisol, is a rare type of Cushing's syndrome. A 37-year-old man came to our hospital because of repeated dizzy spells, weakness and hypercortisolemia lasting two weeks. Endocrinological examinations indicated CCS with periodic and intermittent increases in cortisol. Enhanced computed tomography (CT) revealed space occupying lesions on the upper lobe of left lung, and biopsy eventually proved that these were pulmonary carcinoid tumors with ectopic ACTH secretion, which was subsequently manifested a Cushing's syndrome. PET-CT, ultrasound and biopsy of the thyroid gland indicated bilateral thyroid papillary carcinoma. CT scan showed bilateral nodular hyperplasia of the adrenal gland. Enhanced magnetic resonance imaging (MRI) confirmed that the high signal disappeared on the posterior lobe of the pituitary gland and that the pituitary stalk shifted left, which was suspected to be non-functional pituitary microadenoma. The patient underwent surgery involving resection of the left upper pulmonary lobe and the mediastinal lymph node around the hilus pulmonis, which resulted in complete remission of CCS. The patient then chose elective surgery for the thyroid papillary carcinoma. An analysis of the patient's genomic DNA identified a novel mutation in PDE11A: c.2032 (exon 12) G > A, which is associated with primary pigmented nodular adrenocortical disease (PPNAD). This is a novel mutation which has been no previous public clinical report on this mutation as it relates to this disease.

The quality of life in Chinese population with chronic non-communicable diseases according to EQ-5D-3L: a systematic review.

PURPOSE: Over the past decade, a changing spectrum of disease has turned chronic non-communicable diseases (CNCDs) into the leading cause of death worldwide. During the 2015 in China, there were more than 6.6 million deaths from NCDs, which was the highest rate around the world. In the present study, we performed a systematic review to analyze the health-related quality of life (HRQoL) according to EQ-5D-3L instrument in patients with different kinds of CNCDs in China. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library, VIP, WanFang Data, and CNKI databases up to April 12, 2018, to identify all relevant studies that reported on HRQoL assessed by EQ-5D-3L instrument in Chinese patients with CNCDs. Expert consultation and hand-searching of reference lists from retrieved studies were employed to identify additional references. The variation of mean utility values, EQ-VAS score ranges, and responses for each EQ-5D dimension described in relevant studies were extracted. RESULTS: A total of 5027 English-language articles and 618 Chinese-language articles were identified, among which 38 articles met full inclusion criteria. These 38 studies involved 18 kinds of CNCDs. In this review, the health utility for diabetes mellitus ranged from 0.79 to 0.94 (EQ-5D VAS scores from 61.5 to 78.6), hypertension from 0.78 to 0.93 (70.1-77.4), coronary heart disease from 0.75 to 0.90 (71.0-77.0), chronic obstructive pulmonary disease from 0.64 to 0.80 (55.0-67.0), epilepsy from 0.83 to 0.87 (78.3-79.6), cerebral infarction from 0.51 to 0.75 (49.7-79.0), while children cerebral palsy was 0.44 (27.3). CONCLUSIONS: EQ-5D-3L is widely used in studies of HRQoL associated with CNCDs in China. Our results suggest that many factors may influence the measurement results of health utilities, including age, gender, sample source, comorbidities, rural/urban, and EQ-5D-3L value sets.

Toileting behaviors and overactive bladder in patients with type 2 diabetes: a cross-sectional study in China.

BACKGROUND: Overactive bladder is more prevalent in patients with type 2 diabetes than in those without diabetes. Unhealthy toileting behaviors may be associated with the development and worsening of overactive bladder symptoms. However, little is known about the relationships between toileting behaviors and overactive bladder in patients with diabetes. This study aimed to identify unhealthy toileting behaviors that patients with type 2 diabetes adopted to empty their bladders and investigate the relationships between toileting behaviors and overactive bladder. METHODS: Patients with type 2 diabetes from the endocrinology outpatient department of a hospital in China were recruited. The Toileting Behaviors-Women's Elimination Behavior and Overactive Bladder Symptom Score questionnaires were used to assess the patients' toileting behaviors and overactive bladder symptoms. A multivariate logistic regression model was used to explore the relationships between toileting behaviors and overactive bladder. RESULTS: Almost 14% of patients with diabetes had overactive bladder. The unhealthiest toileting behavior was premature voiding. In the multivariate logistic regression analysis, premature voiding (OR = 1.286, p = 0.016) and straining to void (OR = 1.243, p = 0.026) were associated with overactive bladder. There was a greater likelihood of having overactive bladder when patients engaged in unhealthy toileting behaviors (premature voiding and straining to void). CONCLUSIONS: Overactive bladder in patients with type 2 diabetes was more than twofold higher than that in the general population. Thus, overactive bladder is not just an inconsequential condition for patients with diabetes. Unhealthy toileting behaviors, e.g., premature voiding and straining to void, may contribute to the onset or worsening of overactive bladder in patients with diabetes. Identification and awareness of these modifiable behavioral factors during diabetes care is an essential component of primary prevention, alleviation, and management of overactive bladder symptoms.

Inequalities in health status among rural residents: EQ-5D findings from household survey China.

INTRODUCTION: This study analyzed inequalities in health status among different socioeconomic and demographic rural residents covered by the New Rural Cooperative Medical System in China. METHODS: A cross-sectional study was conducted in Lian Yungang City, China. A total of 337 respondents, who were selected by using a multistage stratified systematic random sampling method, completed the surveys. A questionnaire consisting of EQ-5D and demographic and socioeconomic information was adopted for data collection, and was administered by face-to-face interviews. Multiple regression models were employed to examine the differences in the Visual Analogue Scale (VAS) score and the EQ-5D dimensions. RESULTS: Compared with those with lower education attainment, the respondents with higher education levels tended to report a higher VAS score (ß = 2.666, 95% CI: 0.978 to 6.310), and were less likely to suffer from pain/discomfort (OR = 3.968; 95% CI: 1.447 to 10.880). The singles were more likely than the married to report moderate or extreme problems in usual activities (OR = 4.583; 95% CI: 1.188 to 17.676) and mobility (OR = 10.666; 95% CI: 2.464 to 6.171). However, no statistically significant differences were identified between the respondents with different income levels in the VAS score and EQ-5D dimensions. CONCLUSIONS: This study suggests that the singles and the people with lower education levels are high-risk groups for poorer health status in the Chinese rural population. The findings from this study warrant further investigation.

Natural Antioxidants: An Effective Strategy for the Treatment of Alzheimer's Disease at the Early Stage.

The critical role of oxidative stress in Alzheimer's disease (AD) has been recognized by researchers recently, and natural antioxidants have been demonstrated to have anti-AD activity in animal models, such as Ginkgo biloba extract, soy isoflavones, lycopene, and so on. This paper summarized these natural antioxidants and points out that natural antioxidants always have multiple advantages which are help to deal with AD, such as clearing free radicals, regulating signal transduction, protecting mitochondrial function, and synaptic plasticity. Based on the available data, we have created a relatively complete pathway map of reactive oxygen species (ROS) and AD-related targets and concluded that oxidative stress caused by ROS is the core of AD pathogenesis. In the prospect, we introduced the concept of a combined therapeutic strategy, termed "Antioxidant-Promoting Synaptic Remodeling," highlighting the integration of antioxidant interventions with synaptic remodeling approaches as a novel avenue for therapeutic exploration.

Methods for Economic Evaluations of Novel Oral Anticoagulants in Patients with Atrial Fibrillation: A Systematic Review.

BACKGROUND: Atrial fibrillation (AF) is a severe epidemiological and public health concern among the elderly population worldwide, with substantial economic and social burdens. Economic evaluations can play an essential role in optimizing the utilization of scarce resources. In recent years, the number of economic evaluation studies related to AF has increased due to the rising number of AF patients, the continuous updating of clinical data, and the emergence of real-world evidence. However, there are still deficiencies in model settings and parameter sources in relevant studies. OBJECTIVE: This study aims to review the existing economic evaluations of novel oral anticoagulants (NOACs) in patients with AF and summarize the evidence and methods applied. METHODS: A comprehensive and systematic search was conducted on electronic databases, including PubMed, Embase, Web of Science (WOS), and The Cochrane Library, from the date of database creation to November 2022. The reporting quality of included literature was assessed using the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) statement. RESULTS: A total of 102 studies were included in the review, with 200 comparisons between NOACs and vitamin K antagonists (VKAs), as well as 58 comparisons between different NOACs. The healthcare sector and payer perspectives were the most common, and accordingly, the majority of the evaluations considered only direct medical costs. Most studies used Markov cohort models with the number of health states ranging from 4 to 29. Of included studies, 80 (78%) considered event recurrence and complications, and 78 (76%) considered discontinuation and second-line therapy. All of the studies applied uncertainty analysis to explore the robustness of the results. Of all 200 NOACs-VKAs comparisons, 149 (75%) showed that NOACs were more cost-effective; this proportion was 84% (139 out of 165) in high-income countries but decreased to 29% (10 out of 35) in middle- and low-income countries. Most (82%) of the 28 items in the CHEERS 2022 checklist were elucidated in the majority of included studies. A minority (only 39%) of included studies demonstrated high reporting quality. CONCLUSION: NOACs may be more cost-effective than VKAs in patients with AF, but this conclusion applies to high-income countries, whereas VKAs may be more cost-effective in middle- and low-income countries. The reporting quality of included studies was variable, and certain methodological issues were presented. This study highlights the economic evaluation methodology of NOACs in patients with AF and provides recommendations for modeling methods and future studies.

Enhanced Thermostability of Nattokinase by Computation-Based Rational Redesign of Flexible Regions.

Nattokinase is a nutrient in healthy food natto that has the function of preventing and treating blood thrombus. However, its low thermostability and fibrinolytic activity limit its application in food and pharmaceuticals. In this study, we used bioinformatics analysis to identify two loops (loop10 and loop12) in the flexible region of nattokinase rAprY. Using this basis, we screened the G131S-S161T variant, which showed a 2.38-fold increase in half-life at 55 °C, and the M3 variant, which showed a 2.01-fold increase in activity, by using a thermostability prediction algorithm. Bioinformatics analysis revealed that the enhanced thermostability of the G131S-S161T variant was due to the increased rigidity and structural shrinkage of the overall structure. Additionally, the increased rigidity of the local region surrounding the active center and its mutated sites helps maintain its normal conformation in high-temperature environments. The increased catalytic activity of the M3 variant may be due to its more efficient substrate binding mechanism. We investigated strategies to improve the thermostability and fibrinolytic activity of nattokinase, and the resulting variants show promise for industrial production and application.

Impacts of national volume-based drug procurement policy on the utilization and costs of antihypertensive drugs in a Chinese medicine hospital: an interrupted time series analysis of 5138 patients.

Objectives: The study aimed to estimate the effects of National Volume-based Drug Procurement (NVBP) policy on drug utilization and medical expenditures of hypertension patients in public medical institutions in mainland China. Methods: This study used patient-level data based on electronic health records retrieved from the hospital information system of Nanjing Hospital of Chinese Medicine. Data on patients with hypertension who received care at this institution between 2016 and 2021 was used for analysis. Segmented linear regression models incorporating Interrupted Time Series (ITS) analysis were adopted to examine the effects of NVBP policy on drug utilization and health expenditures of eligible patients. Drug utilization volume and health expenditures were the primary outcomes used to assess the policy effects, and were measured using the prescription proportion of each drug class and the overall per-encounter treatment costs. Results: After the implementation of NVBP policy, the volume of non-winning drugs decreased from 54.42% to 36.25% for outpatient care and from 35.62% to 15.65% for inpatient care. The ITS analysis showed that the volume of bid-winning drugs in outpatient and inpatient settings increased by 9.55% (p < 0.001) and 6.31% (p < 0.001), respectively. The volume changes in non-volume based purchased (non-VBP) drugs differed between outpatients and inpatients. The proportion of non-VBP drugs immediately increased by 5.34% (p = 0.002) overall, and showed an upward trend in the outpatient setting specially (p < 0.001) during the post-intervention period. However, no significant differences were observed in the proportion of non-VBP drugs in inpatient setting (p > 0.05) in term of level change (p > 0.05) or trend change (p > 0.05). The average per-visit expenditures of outpatients across all drug groups exhibited an upward trend (p < 0.05) post policy intervention. In addition, a similar increase in the overall costs for chemical drugs were observed in inpatient settings (coefficient = 2,599.54, p = 0.036), with no statistically significant differences in the regression slope and level (p = 0.814). Conclusion: The usage proportion of bid-winning drugs increased significantly post policy intervention, indicating greater use of bid-winning drugs and the corresponding substitution of non-winning hypertensive drugs. Drug expenditures for outpatients and health expenditures per visit for inpatients also exhibited an upward trend, suggesting the importance of enhanced drug use management in Traditional Chinese Medicine hospital settings.

Prevalence of and risk factors for surgical site infections after pancreaticoduodenectomy: a systematic review and meta-analysis.

Background: Surgical site infections (SSIs) are one of the most common complications after pancreaticoduodenectomy (PD); however, the global prevalence and risk factors for SSIs after PD remain unknown. Objectives: To investigate the prevalence of and risk factors for SSIs after PD. Methods: The PubMed, Embase, Cochrane Library, Web of Science, and Science Direct databases were systematically searched from inception to 1 December 2022. Observational studies reporting adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of risk factors for SSIs in patients undergoing PD were included. Two independent reviewers in teams performed data extraction, risk of bias assessment, and level of evidence analysis. The pooled results were estimated using a random-effects model. The I 2 statistic and Q χ 2 statistic were used to assess heterogeneity. Funnel plots, Egger's regression test, and the trim-and-fill method were used to determine publication bias. The primary outcomes were identifying risk factors for SSIs after PD. The secondary outcomes were the pooled prevalence rates of SSIs. Results: A total of 98 704 patients from 45 studies were included, and 80% of the studies were considered high quality. The estimated pooled prevalence of SSIs was 23% (0.19-0.27, I 2=97%). The prevalence of SSIs was found to be higher in Japan and lower in USA. Preoperative biliary stenting, higher body mass index (BMI), longer operation time, postoperative pancreatic fistula, soft pancreatic texture, perioperative blood transfusion, and cardiac disease were identified as significant risk factors for the development of SSIs after PD. Additionally, broad-spectrum antibiotics were a significant protective factor against SSIs. Subgroup analysis and sensitivity analysis showed that the results were robust. Conclusion and relevance: The prevalence of SSIs remains high and varies widely among regions. It is necessary to take effective preventive measures and carry out more prospective studies to further verify these results.

Cost-effectiveness of anlotinib vs. pembrolizumab and nivolumab as third-line treatment in recurrent small cell lung cancer in China.

BACKGROUND: The study aims to evaluate the cost-effectiveness of anlotinib versus pembrolizumab and nivolumab as the third-line treatment in recurrent small cell lung cancer (SCLC) patients from the Chinese healthcare system perspective. RESEARCH DESIGN AND METHODS: A Markov model was built to simulate the costs and health outcomes in the 4-year horizon. Efficacy and safety data of anlotinib, pembrolizumab, and nivolumab in patients with recurrent SCLC were derived from three studies. Cost and utility values were derived from local charges, the published literature, and related databases. Three scenario analyses and sensitivity analyses were performed to explore the robustness of the results. RESULTS: Compared with anlotinib, pembrolizumab and nivolumab were estimated to gain an additional 0.18 and 0.10 quality-adjusted life years (QALYs) at an incremental cost of $10,446 and $5,182, resulting in an increment cost-utility ratio (ICUR) of $58,221/QALY and $56,733/QALY. The sensitivity analyses showed that the likelihood of anlotinib being cost-effective was 87.5% to 99.9% at a willingness-to-pay (WTP) threshold of $11,144 to $33,431/QALY. The scenario analyses indicated that the results varied in different scenarios. CONCLUSIONS: The findings suggest that anlotinib could be the most cost-effective option versus pembrolizumab and nivolumab in the third-line treatment of recurrent SCLC from the Chinese healthcare system perspective.

The cost-effectiveness analysis of serplulimab versus regorafenib for treating previously treated unresectable or metastatic microsatellite instability-high or deficient mismatch repair colorectal cancer in China.

Objective: The aim of this study was to investigate the cost-effectiveness of serplulimab versus regorafenib in previously treated unresectable or metastatic microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) colorectal cancer in China. Methods: From the perspective of China's health-care system, a Markov model with three health states (progression free, progression, death) was developed for estimating the costs and health outcomes of serplulimab and regorafenib. Data for unanchored matching-adjusted indirect comparison (MAIC), standard parametric survival analysis, the mixed cure model, and transition probabilities calculation were obtained from clinical trials (ASTRUM-010 and CONCUR). Health-care resource utilization and costs were derived from government-published data and expert interviews. Utilities used to calculate quality-adjusted life years (QALYs) were obtained from clinical trials and literature reviews. The primary outcome was the incremental cost-effectiveness ratio (ICER) expressed as cost/QALY gained. Four scenarios were considered in scenario analysis: (a) using original survival data without conducting MAIC; (b) limiting the time horizon to the follow-up time of the clinical trial of serplulimab; (c) adopting a fourfold increase in the risk of death; and (d) applying utilities from two other sources. One-way sensitivity analysis and probabilistic sensitivity analysis were also performed to assess the uncertainty of the results. Results: In the base-case analysis, serplulimab provided 6.00 QALYs at a cost of $68,722, whereas regorafenib provided 0.69 QALYs at a cost of $40,106. Compared with that for treatment with regorafenib, the ICER for treatment with serplulimab was $5,386/QALY, which was significantly lower than the triple GDP per capita of China in 2021 ($30,036), which was the threshold used to define the cost-effectiveness. In the scenario analysis, the ICERs were $6,369/QALY, $20,613/QALY, $6,037/QALY, $4,783/QALY, and $6,167/QALY, respectively. In the probabilistic sensitivity analysis, the probability of serplulimab being cost-effective was 100% at the threshold of $30,036/QALY. Conclusion: Compared with regorafenib, serplulimab is a cost-effective treatment for patients with previously treated unresectable or metastatic MSI-H/dMMR colorectal cancer in China.

Combined Computer-Aided Predictors to Improve the Thermostability of Nattokinase.

Food-derived nattokinase has strong thrombolytic activity and few side effects. In the field of medicine, nattokinase has been developed as an adjuvant drug for the treatment of thrombosis, and nattokinase-rich beverages and health foods have also shown great potential in the field of food development. At present, the poor thermostability of nattokinase limits its industrial production and application. In this study, we used several thermostability-prediction algorithms to predict nattokinase from Bacillus mojavensis LY-06 (AprY), and screened two variants S33T and T174V with increased thermostability and fibrinolytic activity. The t1/2 of S33T and T174V were 8.87-fold and 2.51-fold those of the wild type AprY, respectively, and their enzyme activities were also increased (1.17-fold and 1.28-fold, respectively). Although the thermostability of N218L was increased by 2.7 times, the fibrinolytic activity of N218L was only 73.3% of that of wild type AprY. The multiple-point mutation results showed that S33T-N218L and S33T-T174V-N218L variants lost their activity, and the T174V-N218L variant did not show any significant change in catalytic performance, while S33T-T174V increased its thermostability and activity by 21.3% and 24.8%, respectively. Although the S33T-T174V variant did not show the additive effect of thermostability, it combined the excellent transient thermostability of S33T with the better thrombolytic activity of T174V. Bioinformatics analysis showed that the overall structure of S33T and T174V variants tended to be stable, while the structure of S33T-T174V variant was more flexible. Local structure analysis showed that the increased rigidity of the active center region (positions 64-75) and the key loop region (positions 129-130, 155-163, 187-192, 237-241, and 268-270) determined the increased thermostability of all variants. In addition, the enhanced flexibility of S33T-T174V variant in the Ca1 binding region (positions 1-4, 75-82) and the peripheral region of the catalytic pocket (positions 210-216) may account for the inability to superpose its thermostability. We explored the effective strategy to enhance the thermostability of nattokinase, and the resulting variants have potential industrial production and application.

Medication adherence with fixed-dose versus free-equivalent combination therapies: Systematic review and meta-analysis.

Objective: We conducted a large-scale meta-analysis and subgroup analysis to compare the effect of fixed-dose combination (FDC) therapy with that of free-equivalent combination (FEC) therapy on medication adherence. Methods: Studies published in Web of Science, PubMed, Cochrane Library, ScienceDirect, and Embase up to May 2022 were identified according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary assessed outcomes were the medication possession ratio (MPR) and proportion of days covered (PDC). We investigated the probability of being adherent to the prescribed treatment (MPR or PDC ≥80%) or the average estimate of these two parameters. Studies reporting such results were included in this meta-analysis. The summary measures were reported as the risk ratio (RR) and the weighted mean difference (MD) with 95% of confidence interval (CI) using the random-effects model of DerSimonian and Laird. The quality of the cohort studies was assessed using the Newcastle-Ottawa scale. Results: Of the 1,814 screened studies, 61 met the predefined inclusion criteria. The meta-analysis of the results showed that compared to FEC, FDC significantly improved the medication compliance of patients by 1.29 times (95% CI:1.23-1.35, p < 0.00001). I2 of 99% represent high heterogeneity across studies. The mean difference in medication adherence between FDC and FEC was 0.10 (95% CI: 0.06-0.14, p < 0.00001) with an I2 estimate of 100%. Subgroup analyses were performed for studies that reported adherence outcomes according to disease type, period of evaluation and compliance indicators. A sensitivity analysis was conducted to exclude the results of low-quality studies, as well as studies in which there was ambiguity in the method of calculating the estimator. Conclusion: Analysis of the assessed parameters for the intention-to-treat and subgroup populations suggests that FDC can improve adherence to treatment and its advantages over FEC may increase over time. Further research is needed to better understand how medical conditions affect the impact of reduced pill burden on adherence, particularly in diseases other than cardiovascular disease and type 2 diabetes mellitus.