Postoperative cognitive dysfunction (POCD) is commonly observed in perioperative care following major surgery and general anesthesia in elderly individuals. No preventive or interventional agents ...have been established so far. Although the role of interleukin-1β (IL-1β)-mediated neuroinflammation following surgery and anesthesia is strongly implicated in POCD, the exact mechanism of action remains to be explored. Growing evidence has shown that mitochondria-derived reactive oxygen species (mtROS) are closely linked to IL-1β expression through a redox sensor known as the nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. Therefore, we hypothesize that the mechanisms underlying POCD involve the mtROS/NLRP3 inflammasome/IL-1β signaling pathway. Furthermore, we speculate that cholinergic anti-inflammatory pathway induced by α7 nicotinic acetylcholine receptor (a7nAChR) may be the potential upstream of mtROS/NLRP3 inflammasome/IL-1β signaling pathway in POCD. For validating the hypotheses, we provide experimental plan involving different paradigms namely; microglial cells and behavioral studies. The link between mtROS, the NLRP3 inflammasome, and IL-1β within and between these different stages in combination with mtROS and NLRP3 inflammasome agonists and inhibitors could be explored using techniques, such as knockout mice, small interference ribonucleic acid, flow cytometry, co-immunoprecipitation, and the Morris Water Maze test. We conclude that the NLRP3 inflammasome is a new preventive and therapeutic target for POCD.
There is limited evidence of comparative results among different treatments regarding impacts of Health-Related Quality of Life (HRQoL) for patients with metastatic colorectal cancer (mCRC). We aimed ...to compare efficacy of systemic treatments on HRQoL among patients with mCRC.
We collected randomized controlled trials (RCTs) reported in English up until July 2023, from databases including PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and prominent conference databases, for this Bayesian network meta-analysis. Phase 2 or 3 trials that evaluated at least two therapeutic regimens were included. Primary outcomes were short-term and long-term mean changes in EORTC QLQ-C30 global health status/quality of life (GHS/QoL) scores. Secondary outcome was mean change in EQ-5D health utility scores. Mean differences (MDs) with 95% confidence intervals (CIs) were used as effect size. Subgroup analysis was performed based on whether patients received systemic treatments before. We conducted various sensitivity analyses, including differentiating between chemotherapy types, and analyzed patient cohorts with non-specified gene expression levels as well as those with target KRAS expression statuses. The current systematic review protocol was registered on PROSPERO (CRD42023453315 and CRD42023420498).
Immunotherapy and targeted therapy significantly improved HRQoL over chemotherapy, with MDs of 9.27 (95% CI: 3.96 to 14.6) and 4.04 (95% CI: 0.11 to 7.94), respectively. Monotherapy significantly outperformed both combination therapy (MD 5.71, 95%CI 0.78 to 10.63) and no active treatment (MD 3.7, 95%CI 1.41 to 6.01) regarding GHS/QoL in the short-term. Combining targeted therapy with chemotherapy did not improve HRQoL. Focusing on HRQoL, cetuximab excelled when gene expression baselines were unspecified. Subgroup and sensitivity analyses upheld these robust findings, unaffected by model or patient baseline characteristics. Evidence from clinical trials without specific gene level data suggested that monotherapies, especially targeted therapies such as cetuximab, demonstrated superiority in HRQoL. For KRAS wild-type patients, no significant HRQoL differences emerged between chemotherapy, targeted therapy, or their combination..
Targeted therapies and immunotherapy demonstrate superior HRQoL benefits, monotherapy such as cetuximab is associated with significant improvements as compared to combination therapy. However, tailoring these results to individual gene expression profiles requires more evidence.
The COVID-19 pandemic has led nucleic acid collection and detection became a measure to ensure normal life in China. Considering the huge detection demand, it has emerged that robots replace manual ...sample collection. However, the cost-effectiveness of nucleic acid collection by robots instead of humans remain unknown. This study was approved by the Ethics Committee of the Shenzhen Luohu District People's Hospital, number 2021-LHQRMYY-KYLL-031a. All participants signed the written informed consent of this study. 273 volunteers were recruited on December 1.sup.st 2021 from Shenzhen and divided into six groups: one group to be sampled by robots and the others to be sampled manually with varying specifications for swab rotation and insertion time. Questionnaires were distributed to the robot group to ask them sampling feeling. The effectiveness and safety of sampling were evaluated through the sampling efficiency, adverse events and sampling feeling of different groups. The economics of the different methods were judged by comparing the sampling cost for each. The sampling efficiency of the robot group was 96.9%, and there was no statistically significant difference between the other five manually sampled groups (p = 0.586). There were no serious adverse events in any of the six groups, but nasal soreness and tearing did occur in all group. Of the volunteers who underwent robotic sampling, 85.94% reported that the experience was either no different or more comfortable than the manual sampling. In economic terms, a single robot used to replace medical staff for sample collection becomes economically advantageous when the working time is greater than or equal to 455 days. If multiple robots are used to replace twice the number of manual collections, it becomes more economical at 137 days and remains so as long as the robot is used. It appears safe and effective for robots to replace manual sampling method. Implementation of robotic sampling is economical and feasible, and can significantly save costs when working over a long term.
Background The COVID-19 pandemic has led nucleic acid collection and detection became a measure to ensure normal life in China. Considering the huge detection demand, it has emerged that robots ...replace manual sample collection. However, the cost-effectiveness of nucleic acid collection by robots instead of humans remain unknown. Methods This study was approved by the Ethics Committee of the Shenzhen Luohu District People’s Hospital, number 2021-LHQRMYY-KYLL-031a. All participants signed the written informed consent of this study. 273 volunteers were recruited on December 1st 2021 from Shenzhen and divided into six groups: one group to be sampled by robots and the others to be sampled manually with varying specifications for swab rotation and insertion time. Questionnaires were distributed to the robot group to ask them sampling feeling. The effectiveness and safety of sampling were evaluated through the sampling efficiency, adverse events and sampling feeling of different groups. The economics of the different methods were judged by comparing the sampling cost for each. Results The sampling efficiency of the robot group was 96.9%, and there was no statistically significant difference between the other five manually sampled groups (p = 0.586). There were no serious adverse events in any of the six groups, but nasal soreness and tearing did occur in all group. Of the volunteers who underwent robotic sampling, 85.94% reported that the experience was either no different or more comfortable than the manual sampling. In economic terms, a single robot used to replace medical staff for sample collection becomes economically advantageous when the working time is ≥ 455 days. If multiple robots are used to replace twice the number of manual collections, it becomes more economical at 137 days and remains so as long as the robot is used. Conclusions It appears safe and effective for robots to replace manual sampling method. Implementation of robotic sampling is economical and feasible, and can significantly save costs when working over a long term.
To compare the efficacy, safety and effects on quality of life of different ALK-inhibitors for global and Asian patients with advanced ALK-positive non-small-cell lung cancer (NSCLC).
The included ...RCTs were identified through a systematic search of PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and major cancer conferences. The assessment of progression-free survival (PFS), intracranial PFS, overall survival (OS), and patient-reported outcomes (PROs) was carried out using restricted mean survival time (RMST) model, fractional polynomial model and Royston-Parmar model. Time-invariant hazard ratio (HR) models were also used to validate and supplement the primary analysis. Objective response rate (ORR) and adverse events with any grade, grade 3-5 were assessed through a Bayesian network meta-analysis. The primary measures for OS, PFS, and PROs were HR and RMST. The odds ratio was the metric for evaluating safety, ORR, 12-month PFS rate, 24-month OS rate, and the 12-month non-deterioration rate of PROs. Subgroup analyses based on patient characteristics were performed.
A total of fourteen studies (ten for first-line, four for second-line) consisting of nine treatments (chemotherapy, crizotinib, alectinib 600mg BID, low-dose alectinib 300mg BID, brigatinib, ceritinib, ensartinib, envonalkib, and lorlatinib) were included. In the first-line setting, alectinib showed a significant advantage over crizotinib and had the longest OS among all ALK-inhibitors. Compared to crizotinib, lorlatinib had the best efficacy regarding PFS for global patients, followed closely by alectinib and brigatinib. For Asian patients, alectinib significantly improved PFS compared to other treatments. In second-line, alectinib had the highest PFS for patients pretreated with crizotinib, followed by brigatinib, ceritinib and chemotherapy. Alectinib, irrespective of the dose, was the safest first-line option, whereas lorlatinib, brigatinib, and ceritinib showed poorer safety profiles. Alectinib was also the safest ALK-inhibitor for crizotinib-resistant patients. Brigatinib had the best performance in terms of PROs.
Considering both efficacy and safety, alectinib appears to be the preferable treatment in first-line and second-line, particularly for Asian patients.
Results of Orient 15 indicated the health benefits to patients with local advanced or metastatic oesophageal squamous cell carcinoma (OSCC). This study aimed to evaluate the cost-effectiveness of ...sintilimab plus chemotherapy in treating OSCC from the perspective of Chinese healthcare system.
A partitioned survival model was constructed to evaluate the cost-effectiveness of sintilimab plus chemotherapy vs. chemotherapy in treating OSCC. Baseline characteristics of patients and key clinical data were extracted from Orient 15. Costs and utilities were collected from published studies and open-access databases. Costs, quality-adjusted life-years (QALYs), life-years gained, and incremental cost-effectiveness ratios (ICER) were chosen as economic outcome indicators. We also performed sensitivity analyses and subgroup analyses to verify the stability of results.
Combination therapy provided additional 0.84 QALYs and 1.46 life-years with an incremental cost of $25,565.48 than chemotherapy, which had an ICER of $30,409.44 per QALY. The probabilistic sensitivity analysis indicated that combination therapy had a 98.8% probability of cost-effectiveness at the willingness-to-pay threshold (WTP) of $38,184 per QALY. Deterministic sensitivity analysis showed that model outcomes were sensitive to the utilities of progression-free survival and progression disease. The subgroup analysis revealed that combination therapy was cost-effective in patients with high expression of PD-L1 and several specific subgroups.
In this economic evaluation, sintilimab plus chemotherapy was likely to be cost-effective compared with chemotherapy in the first-line therapy of advanced OSCC from the perspective of Chinese healthcare system. Our findings may provide evidence for clinicians to make optimal decisions in clinical practice and for decision-makers to evaluate the cost-effectiveness of sintilimab.
Clinical evidence suggests that first-line immune checkpoint inhibitor (ICI) combination therapies can improve survival in patients with advanced non-squamous non-small cell lung cancer (nsq-NSCLC). ...However, the optimal strategy remains unknown without a systematic comparison of their long-term effects.
We performed a systematic review and network meta-analysis by retrieving up-to-date literature from PubMed
(National Library of Medicine, Bethesda, MD, USA), Embase
(Elsevier, Amsterdam, Netherlands), MEDLINE
(National Library of Medicine), ClinicalTrials.gov (National Library of Medicine), and major international conference publications. Published studies and abstracts comparing first-line ICI combination therapies with other treatments for patients with advanced nsq-NSCLC were included. Restricted mean survival time (RMST) was measured over 12 months for progression-free survival (PFS) and 18 months for overall survival (OS), and the Royston-Parmar model was used to extrapolate and compare data for the long-term outcomes.
We included a total of 11 trials involving 12 therapies and 6,130 patients. Pembrolizumab plus chemotherapy exhibited the best overall survival (OS) benefit at both 18 and 60 months RMST = 2.95, 95% confidence interval (CI) 1.96 to 3.97; life-years gained over a 5-year period = 2.18 years. Nivolumab plus bevacizumab plus chemotherapy was found to present the best progression-free survival (PFS) benefit at 12 months (RMST 3.02, 95% CI 2.11 to 3.91), whereas atezolizumab plus bevacizumab plus chemotherapy showed the best PFS benefit at 36 months (life-years gained over 3 years = 1.22 years). Subgroup analyses showed that among patients with programmed death-ligand 1 (PD-L1) expression ≥ 50%, atezolizumab plus chemotherapy and nivolumab plus ipilimumab resulted in superior OS benefits at 18 and 60 months, respectively. Among patients with PD-L1 expression< 1%, pembrolizumab plus chemotherapy was associated with OS benefits at both 18 and 60 months. Sintilimab plus chemotherapy was associated with relatively fewer grade ≥ 3 adverse events than other ICI combination therapies.
Our results show that ICI combination therapies showed better survival benefits than chemotherapy. Pembrolizumab plus chemotherapy could provide the best OS benefits to patients with advanced nsq-NSCLC, whereas atezolizumab plus bevacizumab plus chemotherapy could bring the best PFS benefits. The optimal ICI combination therapy varies depending on PD-L1 expression level.
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=325005, identifier CRD42022325005.
Non-pharmacological interventions (NPIs) could be considered in the early management of prehypertensive population. This study aimed to evaluate the potential cost-effectiveness of NPIs and the ...budget impact of implementing NPIs on prehypertensive population in China and provide evidence of chronic disease management innovation for decision-makers.
Five NPIs including usual care, lifestyle, strengthen exercise, relaxation, and diet therapy were selected based on the practice of hypertension management in China. A nine-state Markov model was constructed to evaluate the lifetime costs and health outcomes of five NPIs and a non-intervention group from the perspective of Chinese healthcare system. The effectiveness of NPIs was obtained from a published study. Parameters including transition probabilities, costs and utilities were extracted or calculated from published literature and open-access databases. Sensitivity analyses were conducted to test the uncertainty of all parameters. The impact of duration of intervention was considered in scenario analyses. A budget impact analysis (BIA) was conducted to evaluate the total cost and the medical cost saving of a hypothetical nationwide implementation of potential cost-effective NPI in prehypertensive people. Management strategies including focusing on patients with specific ages or different CVE risk levels, and different duration of implementation were taken into consideration.
Strengthen exercise was the most cost-effective intervention with a probability of 78.1% under the given WTP threshold. Our results were sensitive to the cost of interventions, and the utility of prehypertension and hypertension. The duration of implementation had limited impact on the results. BIA results showed that the program cost was hefty and far more than the medical cost saving with the course of simulation time. Applying management strategies which focused on individual characteristics could largely reduce the program cost despite it remained higher than medical cost saving.
Strengthen exercise was a potential NPI that can be considered in priority for early management in prehypertensive population. Although early management can acquire medical cost saving, the related program cost can be quite hefty. Precise strategies which may help reduce the cost of early management should be taken into consideration in program design.
Shenzhen is characterized with the largest scale of migrant children among all the cities in China. Unequal access to health services among migrant and local children greatly affects health equity ...and has a profound impact on the quality of human capital. This study aimed to investigate differences in using community-based healthcare between local and migrant children and to identify the influencing factors in Futian District of Shenzhen.
Households in 12 communities in Futian District of Shenzhen were randomly sampled. Children aged 0-14 years were investigated using self-administered questionnaire - the 2018 Survey of Health Service Needs of Chinese Residents. Differences in healthcare including physical examination, feeding guidance, development guidance, disease prevention guidance, injury prevention guidance, oral health guidance, and mental health guidance, were tested between local and migrant children. Binary logistic regressions were used in identifying potential influencing factors which affected the use in the above healthcare items.
A total of 936 participants from1512 families were sampled and 508 of them were included. Compared with local children, migrant children had less use of development guidance (OR = 0.417, 95% CI: 0.279-0.624) and oral health care guidance (OR = 0.557, 95% CI: 0.381-0.813). Children whose father received higher education level enjoyed a better use of disease prevention guidance as compared to whose father stopped at junior high school education or below (senior high vs junior high and below, OR = 1.286, 95% CI: 0.791-2.090; bachelor and above vs junior high and below, OR = 2.257, 95% CI: 1.417-3.595). Children whose fathers were blue-collar workers had less use of injury prevention guidance (OR = 0.750, 95% CI: 0.334-1.684) and mental health guidance (OR = 0.784, 95% CI: 0.295-2.080) as compared to whose father were white collar workers.
Except feeding guidance, healthcare utilization were lower among migrant children than among local children. Generally, fathers have a stronger influence on children's use of community-based healthcare than mothers do. The potential influence of fathers in promoting children's healthcare use behaviors should be carefully considered, and fathers' attention to children's health should be increased.
General practitioner (GP) system is proved to be effective in over 50 countries worldwide. Guangdong province, as a reform pilot in China, initiated its patient-GP contract service reform in 2014. ...This study is designed to assess the patients' acceptance of General Practitioners Contract (GPC) reform and explore its influencing factors.
This survey interviewed 1010 participants from 16 primary health centers (PHCs) chosen from 4 pilot cities in Guangdong during July and December in 2015. Data were collected through face-to-face interviews. The questionnaire was developed to discover the acceptance of GPC and covered three parts: respondents' socio-demographic characteristics, health service utilization, and the patients' assessment of primary health care centers. A binary logistic regression model was used to measure the influencing factors of respondents' acceptance of GPC policy.
A total of 611(60.5%) participants accepted GPC policy. Compared to patients visited PHCs over 7 times in the previous year, those visited PHCs fewer times reported lower acceptance of GPC policy (OR:0.68, 95% CI:0.49-0.96 for visits ≤3 times and OR:0.57, 95% CI:0.38-0.84 for visits = 4-6 times). Patients' satisfaction with medical service coverage was positively associated with patients' acceptance of GPC (OR: 1.72, 95% CI:1.01-3.98 for the satisfied versus the dissatisfied; OR: 1.38, 95% CI:0.92-3.30 for neutral versus the dissatisfied), and the satisfaction with drug list also positively influenced patients' acceptance of GPC policy (OR: 1.44, 95% CI:1.26-2.73 for the satisfied versus the dissatisfied; OR:1.61, 95% CI:1.36-2.99 for neutral versus the dissatisfied). Meanwhile, age and education had positive impacts on the acceptance of the GPC policy.
This study finds out that patients' satisfaction with medical service coverage and drug list are the influencing factors for the acceptance of GPC policy. Therefore, improvement of medical service accessibility such as better follow-up of patients with chronic diseases and enhanced referral service, as well as the expansion of drug list, will improve patients' acceptance of GPC policy. It also finds that patients using more primary health service are inclined to accept GPC policy, so more attractive and high-quality service should be provided in PHCs.
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