Rehabilitation exercises for kidney transplant recipients in an organ transplant ward: a best practice implementation project.

INTRODUCTION AND OBJECTIVES: Kidney transplantation is an effective treatment for end-stage kidney disease. Kidney transplant recipients (KTRs) are prone to experiencing reduced physical function, depression, fatigue, and lack of exercise motivation due to their sedentary lifestyle before surgery. Exercise is an effective intervention for KTRs, but it has not been properly implemented in many practice settings. This project aimed to promote evidence-based exercises as part of KTRs' rehabilitation to improve their health outcomes. METHODS: This project was informed by the JBI Evidence Implementation Framework. The project was conducted in the organ transplant ward of a tertiary comprehensive hospital in Changsha, China. Based on a summary of best evidence, 12 audit criteria were developed for the baseline and follow-up audits involving 30 patients and 20 nursing staff. The JBI Practical Application of Clinical Evidence System (PACES) and Getting Research into Practice (GRiP) tool were used to identify barriers and facilitators and develop targeted strategies to improve issues. RESULTS: Compared with the baseline audit, significant improvements were achieved in most of the criteria in the follow-up audit, with 9 of the 12 criteria reaching 100% compliance. Notably, the 6-minute walk distance test results were significantly higher, while the Self-Rating Depression Scale and Self-Rating Anxiety Scale scores were significantly lower (p < 0.05). CONCLUSIONS: This project demonstrates that evidence-based practice can improve the clinical practice of rehabilitation exercises for KTRs. The GRiP strategies proved to be extremely useful, notably, the formulation of a standardized rehabilitation exercise protocol, training, and enhancement of the exercising environment. Head nurses' leadership and decision-making also played an important role in the success of this project. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A180.

Characterization of tongue coating microbiome from patients with colorectal cancer.

Background: Tongue coating microbiota has aroused particular interest in profiling oral and digestive system cancers. However, little is known on the relationship between tongue coating microbiome and colorectal cancer (CRC). Methods: Metagenomic shotgun sequencing was performed on tongue coating samples collected from 30 patients with CRC, 30 patients with colorectal polyps (CP), and 30 healthy controls (HC). We further validated the potential of the tongue coating microbiota to predict the CRC by a random forest model. Results: We found a greater species diversity in CRC samples, and the nucleoside and nucleotide biosynthesis pathway was more apparent in the CRC group. Importantly, various species across participants jointly shaped three distinguishable fur types.The tongue coating microbiome profiling data gave an area under the receiver operating characteristic curve (AUC) of 0.915 in discriminating CRC patients from control participants; species such as Atopobium rimae, Streptococcus sanguinis, and Prevotella oris aided differentiation of CRC patients from healthy participants. Conclusion: These results elucidate the use of tongue coating microbiome in CRC patients firstly, and the fur-types observed contribute to a better understanding of the microbial community in human. Furthermore, the tongue coating microbiota-based biomarkers provide a valuable reference for CRC prediction and diagnosis.

Hai-Honghua medicinal liquor is a reliable remedy for fracture by promotion of osteogenic differentiation via activation of PI3K/Akt pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Hai-Honghua medicinal liquor (HHML), an external Chinese herbal formula preparation, is often applied to treat freshly closed tibia/fibular fractures, ankle fractures, and other bone-related disorders, but the related molecular mechanism is unclear. AIM OF THE STUDY: To evaluate the therapeutic effect of HHML in patients with tibial/fibular and ankle fractures, and to explore its related possible mechanism. METHODS AND MATERIALS: A total of 182 patients with tibia/fibular fractures and 183 patients with ankle fractures were enrolled in this study. A randomized, controlled, unblinded clinical trial was designed to evaluate the therapeutic effect of HHML on tibial/fibular and ankle fractures. The chemical compositions of HHML were analyzed by the HPLC-Q-Extractive MS/MS. Furthermore, a rat tibial fracture model was established to evaluate the therapeutic effects of HHML in promoting fracture healing, and the mouse embryonic osteoblasts cell line of MC3T3-E1 was further carried out to explore the mechanisms of HHML on osteoblast differentiation. RESULTS: In the clinical evaluation, HHML treatment significantly shortened the time for pain and swelling in patients with tibial/fibular fractures (P < 0.01) and ankle fractures (P < 0.01), and the incidence of complications was significantly reduced as well. Subsequently, 116 constituents were identified from HHML via HPLC-Q-TOF-MS/MS analysis. In vivo, no obvious changes in weight were observed in HHML-treated rats. Moreover, the levels of bone formation markers (including osteocalcin (OCN), N-terminal propeptide of type I procollagen (PINP), alkaline phosphatase (ALP), calcium (Ca) and substance P) in rat serum were significantly increased in HHML-treated rats compared with model rats (P < 0.05). Micro-CT analysis showed bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness (Tb.Th) of the HHML-treated rats were significantly increased (P < 0.05, vs. Model) while trabecular separation (Tb.Sp) and structure model index (SMI) values were significantly reduced (P < 0.05, vs. Model). Histological analysis showed that HHML treatment promoted the healing of fractures and cartilage repair, and increased the osteoblasts and collagen fibers. Furthermore, our results also revealed HHML could promote MC3T3-E1 cells proliferation and osteoblast differentiation via regulation of the runt-related transcription factor 2 (RUNX2), bone alkaline phosphatase (BALP), and OCN by activating phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway, which confirmed by adding PI3K chemical inhibitor of LY294002. CONCLUSION: HHML treatment is a reliable remedy for fractures in tibial and ankle by promotion of osteogenic differentiation via activation of PI3K/Akt pathway.

Lenvatinib plus pembrolizumab in the patients with advanced previously treated endometrial cancer: A cost-effectiveness analysis in the United States and in China.

PURPOSE: To investigate the cost-effectiveness of lenvatinib plus pembrolizumab (LP) compared to chemotherapy as a second-line treatment for advanced endometrial cancer (EC) from the United States and Chinese payers' perspective. METHODS: In this economic evaluation, a partitioned survival model was constructed from the perspective of the United States and Chinese payers. The survival data were derived from the clinical trial (309-KEYNOTE-775), while costs and utility values were sourced from databases and published literature. Total costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) were estimated. The robustness of the model was evaluated through sensitivity analyses, and price adjustment scenario analyses was also performed. RESULTS: Base-case analysis indicated that LP wouldn't be cost-effective in the United States at the WTP threshold of $200 000, with improved effectiveness of 0.75 QALYs and an additional cost of $398596.81 (ICER $531392.20). While LP was cost-effective in China, with improved effectiveness of 0.75 QALYs and an increased overall cost of $62270.44 (ICER $83016.29). Sensitivity analyses revealed that the above results were stable. The scenario analyses results indicated that LP was cost-effective in the United States when the prices of lenvatinib and pembrolizumab were simultaneously reduced by 61.95% ($26.5361/mg for lenvatinib and $19.1532/mg for pembrolizumab). CONCLUSION: LP isn't cost-effective in the patients with advanced previously treated endometrial cancer in the United States, whereas it is cost-effective in China. The evidence-based pricing strategy provided by this study could benefit decision-makers in making optimal decisions and clinicians in general clinical practice. More evidence about budget impact and affordability for patients is needed.

SIRT1: An Intermediator of Key Pathways Regulating Pulmonary Diseases.

Silent information regulator type-1 (SIRT1), a nicotinamide adenine dinucleotide+-dependent deacetylase, is a member of the sirtuins family and has unique protein deacetylase activity. SIRT1 participates in physiological as well as pathophysiological processes by targeting a wide range of protein substrates and signalings. In this review, we described the latest progress of SIRT1 in pulmonary diseases. We have introduced the basic information and summarized the prominent role of SIRT1 in several lung diseases, such as acute lung injury, acute respiratory distress syndrome, chronic obstructive pulmonary disease, lung cancer, and aging-related diseases.

Dietary consumption trend and its correlation with global cancer burden: A quantitative and comprehensive analysis from 1990 to 2019.

OBJECTIVE: The aim of this study was to estimate the effect of dietary consumption on cancer burden and formulate an effective solution. METHODS: Dietary consumption, number of cancer deaths, disability-adjusted life years, and corresponding age-standardized rates were extracted from the Global Burden of Disease Study 2019. The annual percentage change was used to quantify the temporal trends in cancer burden and dietary consumption. Age, sex, location, and sociodemographic index were stratified to further analyze the discrepancy in cancer burden attributable to dietary intake. RESULTS: Five cancers (breast, colon and rectal, tracheal, bronchus and lung, esophageal, and stomach) were documented to be associated with dietary consumption in the Global Burden of Disease database. The age-standardized death rate and age-standardized disability-adjusted life years rate in 2019 were 7.56 and 1168.77 per 100 000 population, respectively. For most cancers, the age-standardized death rate and age-standardized disability-adjusted life years rate displayed a decreasing tendency, with annual percentage change varying from -3.60 to -0.29 and from -3.64 to -0.03 from 1990 to 2019, respectively. The age-standardized death rate and age-standardized standardized disability-adjusted life years rate were higher in men than in women (9.68 vs 5.79 and 213.16 vs 129.18, respectively). In addition, the diet-related cancer burden in higher sociodemographic index regions exceeded that in lower sociodemographic index regions. CONCLUSION: Dietary consumption has a considerable influence on cancer burden, among which colon and rectal cancer burden account for the largest proportion. Increasing the intake of whole grains, milk, fiber, calcium, vegetables, and fruits and reducing the consumption of processed meat and sodium are instrumental in lowering the disease burden of cancer. The quantitative analysis of dietary consumption would provide a more detailed reference for diet-related decision makers and raise awareness of healthy dietary habits in diet management departments, food production enterprises, and the general public.

Corrigendum: Epigenetic-mediated downregulation of zinc finger protein 671 (ZNF671) predicts poor prognosis in multiple solid tumors.

[This corrects the article DOI: 10.3389/fonc.2019.00342.].

Long-term trend of future Cancer onset: A model-based prediction of Cancer incidence and onset age by region and gender.

OBJECTIVES: This study provided estimates of cancer incidence rate and onset age by Socio-demographic Index (SDI) regions and gender from 2020 to 2040, aiming to clarify the long-term patterns of future cancer onset. METHOD: Based on the incidence data from the Global Burden of Diseases (GBD) 2019 study, we constructed the Bayesian age-period-cohort model to calculate the age-standardized incidence rates (ASIR) of cancers from 2020 to 2040. Using the average annual percentage change (AAPC) to quantify the trends of ASIR and the onset age. In addition, the incidences in 2019 were fixed to distinguish the age onset changes caused by demographic and incidence from 2020 to 2040. RESULTS: Globally, two-thirds of cancers have escalating trends of incidence rate, and the proportion of cancer weighted average onset age above 60 years old will grow from 62% to 76% between 2020 and 2040. In five SDI regions, the proportion of weighted average onset age above 60 years old will rise above 10% in the next 20 years and increase sequentially with the rise of the SDI level. Preclude sex-specific cancers, the onset age is younger in men than in women in 2040. Rule out the influence of changing demographics, half of cancer's morbidity has a youth-oriented tendency globally, which is concentrated in hormone-related and digestive tract cancer. CONCLUSION: From 2020 to 2040, the incidence and onset age changes demonstrate marked geographic and gender variations in the cancer spectrum. Cancer incidence and onset age are predicted to continuously increase worldwide in the future.

Asarinin attenuates bleomycin-induced pulmonary fibrosis by activating PPARγ.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that lacks effective treatment modalities. Once patients are diagnosed with IPF, their median survival is approximately 3-5 years. PPARγ is an important target for the prevention and treatment of pulmonary fibrosis. Asarinin is a lignan compound that can be extracted from food plant Asarum heterotropoides. In this study, we investigated the therapeutic effects of asarinin in a pulmonary fibrosis model constructed using bleomycin in mice and explored the underlying mechanisms. Intraperitoneal administration of asarinin to mice with pulmonary fibrosis showed that asarinin effectively attenuated pulmonary fibrosis, and this effect was significantly inhibited by the PPARγ inhibitor GW9662. Asarinin inhibited TGF-ß1-induced fibroblast-to-myofibroblast transition in vitro, while GW9662 and PPARγ gene silencing significantly inhibited this effect. In addition, asarinin inhibited not only the canonical Smad pathway of TGF-ß but also the non-canonical AKT and MAPK pathways by activating PPARγ. Our study demonstrates that asarinin can be used as a therapeutic agent for pulmonary fibrosis, and that PPARγ is its key target.

Surgical management of broad-based sessile vocal cord polyps: Transnasal vocal fold polypectomy versus microlaryngoscopic surgery: Our experience in 159 cases.

OBJECTIVES: In this study, we retrospectively reviewed and compared the treatment outcomes and complications of office transnasal vocal fold polypectomy (TVFP) with those of microplarygoscopic surgery (MLS) for different clinical and histopathological features of broad-based sessile vocal fold polyps. METHODS: We retrospectively reviewed the records of 159 consecutive patients with broad-based sessile vocal fold polyps treated by TVFP or MLS. The differences in efficacy and complication between these two surgical techniques were compared according to the different types of vocal fold polyps. RESULTS: Satisfactory outcomes of both TVFP and MLS treatments were reported in patients with oedematous, gelatinous and vascular types of vocal fold polyps (p > .05). The efficacy of TVFP was slightly worse than MLS in fibrous polyps group (p < .05). The TVFP-treated patients did not exhibit obvious complications, whereas several MLS-treated patients had suffered different complications. CONCLUSION: The therapeutic effects of both TVFP and MLS on the treatment of broad-based sessile vocal cord polyps are related to their clinical characteristics and histological types. Satisfactory outcomes are achieved in oedematous, gelatinous, and vascular types of polyps after either surgical procedure. TVFP has fewer surgical complications than MLS which can be a preferred option for the treatment of broad-based sessile vocal cord polyps at outpatient setting. TVFP also can be an alternative surgery option for patients who could not tolerate general anaesthesia or laryngeal suspension. In contrast, MLS has proven to be a particularly advantageous treatment in patients who have fibrous type of polyps.

Cost-effectiveness analysis of an orphan drug tebentafusp in patients with metastatic uveal melanoma and a call for value-based pricing.

The normative regimens recommendations for treating metastatic uveal melanoma (mUM) are absent in the US. Recently, a phase III randomized clinical trial revealed that tebentafusp yielded a conspicuously longer overall survival than the control group. Based on the prominent efficacy, this study aimed to assess whether tebentafusp is cost-effective compared to the control group in patients with untreated mUM. A three-state partitioned survival model was developed to assess the costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) from the perspective of US payers. Scenario analyses and sensitivity analyses were conducted to explore the conclusion uncertainty. Compared with control group, tebentafusp therapy yielded an additional 0.47 QALYs (1.19 vs. 0.72 QALYs) and an incremental cost of $444 280 ($633 822 vs. $189 542). The resultant ICER of $953 230/QALY far outweighed the willingness-to-pay threshold of $200 000/QALY. The ICER was always more than $750 000/QALY in all the univariable and probabilistic sensitivity analyses. Scenario analyses indicated that reducing the unit price of tebentafusp to $33.768/µg was associated with a favorable result of tebentafusp being cost-effective. For treatment-naive patients with mUM, the cost of tebentafusp therapy was not worth the improvement in survival benefits at the current price compared to the investigator's choice of therapy. The cost-effectiveness of tebentafusp could be promoted using value-based pricing.

Cross-Image Dependency Modeling for Breast Ultrasound Segmentation.

We present a novel deep network (namely BUSSeg) equipped with both within- and cross-image long-range dependency modeling for automated lesions segmentation from breast ultrasound images, which is a quite daunting task due to (1) the large variation of breast lesions, (2) the ambiguous lesion boundaries, and (3) the existence of speckle noise and artifacts in ultrasound images. Our work is motivated by the fact that most existing methods only focus on modeling the within-image dependencies while neglecting the cross-image dependencies, which are essential for this task under limited training data and noise. We first propose a novel cross-image dependency module (CDM) with a cross-image contextual modeling scheme and a cross-image dependency loss (CDL) to capture more consistent feature expression and alleviate noise interference. Compared with existing cross-image methods, the proposed CDM has two merits. First, we utilize more complete spatial features instead of commonly used discrete pixel vectors to capture the semantic dependencies between images, mitigating the negative effects of speckle noise and making the acquired features more representative. Second, the proposed CDM includes both intra- and inter-class contextual modeling rather than just extracting homogeneous contextual dependencies. Furthermore, we develop a parallel bi-encoder architecture (PBA) to tame a Transformer and a convolutional neural network to enhance BUSSeg's capability in capturing within-image long-range dependencies and hence offer richer features for CDM. We conducted extensive experiments on two representative public breast ultrasound datasets, and the results demonstrate that the proposed BUSSeg consistently outperforms state-of-the-art approaches in most metrics.

Cost-effectiveness and Value-based Pricing of Trastuzumab Deruxtecan in Metastatic Breast Cancer With Low HER2 Expression.

BACKGROUND: Recently, the DESTINY-Breast04 trial revealed that trastuzumab deruxtecan (T-DXd) significantly prolonged overall survival in patients with human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer (MBC). Considering the extraexpensive price of the new drug, a cost-effectiveness analysis of T-DXd is necessary to perform in the United States. In addition, because T-DXd has not been marketed in China, the pricing is a very important driver for the cost-effectiveness of T-DXd. The range of drug costs for which T-DXd could be considered cost-effective from a Chinese healthcare system perspective was explored. METHODS: We developed a Markov model to evaluate the cost-effectiveness of T-DXd versus physician's choice of chemotherapy (PCC). The simulation time horizon for this model was the life-time of patients. Transition probabilities were based on data from the DESTINY-Breast04 trial. Health utility data were derived from published studies. Outcome measures were costs (in 2022 US$), life-years (LYs), quality-adjusted LYs (QALYs), and the incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses assessed the uncertainty of key model parameters and their joint impact on the base-case results. RESULTS: The model predicted that T-DXd provided an improvement of 0.84 LYs and 0.58 QALYs compared to PCC, with an ICER of $259,452.05 per QALY in the United States and $87,646.40 per QALY in China. The one-way sensitivity analysis demonstrated that the price of T-DXd had the greatest impact on ICERs. Probabilistic sensitivity analysis predicted that the probabilities of T-DXd being cost-effective compared to PCC were 7.2% and 0% at a willingness-to-pay of $150,000 per QALY in the United States and $36,475 per QALY (3 times the per capita gross domestic product) in China, respectively. Subgroup analyses showed that T-DXd was more effective for patients without visceral disease at baseline, followed by patients with Asian ethnic, patients without prior CDK 4/6 inhibitors therapy, and patients with HER2-1+ (IHC detection) status. CONCLUSION: T-DXd was unlikely to offer a reasonable value for the money spent compared to PCC for patients with HER2-low MBC in the United States. A value-based price for T-DXd was reduced by 51% in the United States and less than $1950 per cycle in China.

Cost-effectiveness analysis of ovarian function preservation with GnRH agonist during chemotherapy in premenopausal women with early breast cancer.

STUDY QUESTION: Is it economically worthwhile to use GnRH agonist (GnRHa) to prevent menopausal symptoms (MS) and protect fertility in premenopausal women with breast cancer (BC) during chemotherapy from the US perspective? SUMMARY ANSWER: It is cost-effective to administer GnRHa during chemotherapy in order to forefend MS in premenopausal patients with BC when the willingness-to-pay (WTP) threshold is $50 000.00 per quality-adjusted life-year (QALY), and to preserve fertility in young patients with BC who undergo oocyte cryopreservation (OC), or no OC, when the WTP thresholds per live birth are $71 333.33 and $61 920.00, respectively. WHAT IS KNOWN ALREADY: Chemotherapy often results in premature ovarian insufficiency (POI) in premenopausal survivors of BC, causing MS and infertility. Administering GnRHa during chemotherapy has been recommended for ovarian function preservation by international guidelines. STUDY DESIGN, SIZE, DURATION: Two decision-analytic models were developed, respectively, for preventing MS and protecting fertility over a 5-year period, which compared the cost-effectiveness of two strategies: adding GnRHa during chemotherapy (GnRHa plus Chemo) or chemotherapy alone (Chemo). PARTICIPANTS/MATERIALS, SETTING, METHODS: The participants were early premenopausal women with BC aged 18-49 years who were undergoing chemotherapy. Two decision tree models were constructed: one for MS prevention and one for fertility protection from the US perspective. All data were obtained from published literature and official websites. The models' primary outcomes included QALYs and incremental cost-effectiveness ratios (ICERs). The robustness of the models was tested by sensitivity analyses. MAIN RESULTS AND THE ROLE OF CHANCE: In the MS model, GnRHa plus Chemo resulted in an ICER of $17 900.85 per QALY compared with Chemo, which was greater than the WTP threshold of $50 000.00 per QALY; therefore, GnRHa plus Chemo was a cost-effective strategy for premenopausal women with BC in the USA. Probabilistic sensitivity analysis (PSA) results showed an 81.76% probability of cost-effectiveness in the strategy. In the fertility model, adding GnRHa for patients undergoing OC and those who were unable to undergo OC resulted in ICERs of $67 933.50 and $60 209.00 per live birth in the USA, respectively. PSA indicated that GnRHa plus Chemo was more likely to be cost-effective over Chemo when the WTP for an additional live birth exceed $71 333.33 in Context I (adding GnRHa to preserve fertility in young patients with BC after OC) and $61 920.00 in Context II (adding GnRHa to preserve fertility in young patients with BC who cannot accept OC). LIMITATIONS, REASONS FOR CAUTION: The indirect costs, such as disease-related mental impairment and non-medical costs (e.g. transportation cost) were not included. All data were derived from previously published literature and databases, which might yield some differences from the real world. In addition, the POI-induced MS with a lower prevalence and the specific strategy of chemotherapy were not considered in the MS model, and the 5-year time horizon for having a child might not be suitable for all patients in the fertility model. WIDER IMPLICATIONS OF THE FINDINGS: When considering the economic burden of cancer survivors, the results of this study provide an evidence-based reference for clinical decision-making, showing that it is worthwhile to employ GnRHa during chemotherapy to prevent MS and preserve fertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Natural Science Foundation of Fujian Province [2021J02038]; and the Startup Fund for Scientific Research, Fujian Medical University [2021QH1059]. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

The correlation between the costs and clinical benefits of PD-1/PD-L1 inhibitors in malignant tumors: An evaluation based on ASCO and ESMO frameworks.

Background: Life expectancy for patients with malignant tumors has been significantly improved since the presence of the programmed cell death protein-1/programmed cell death protein ligand-1 (PD-1/PD-L1) inhibitors in 2014, but they impose heavy financial burdens for patients, the healthcare system and the nations. The objective of this study was to determine the survival benefits, toxicities, and monetary of programmed cell death protein-1/programmed cell death protein ligand-1 inhibitors and quantify their values. Methods: Randomized controlled trials (RCTs) of PD-1/PD-L1 inhibitors for malignant tumors were identified and clinical benefits were quantified by American Society of Clinical Oncology Value Framework (ASCO-VF) and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). The drug price in Micromedex REDBOOK was used to estimate monthly incremental drug costs (IDCs) and the correlation between clinical benefits and incremental drug costs of experimental and control groups in each randomized controlled trial, and the agreement between two frameworks were calculated. Results: Up to December 2022, 52 randomized controlled trials were included in the quantitative synthesis. All the randomized controlled trials were evaluated by American society of clinical oncology value framework, and 26 (50%) met the American society of clinical oncology value framework "clinical meaningful value." 49 of 52 randomized controlled trials were graded by European society for medical oncology magnitude of clinical benefit scale, and 30 (61.2%) randomized controlled trials achieved European Society for Medical Oncology criteria of meaningful value. p-values of Spearman correlation analyses between monthly incremental drug costs and American society of clinical oncology value framework/European society for medical oncology magnitude of clinical benefit scale scores were 0.9695 and 0.3013, respectively. In addition, agreement between two framework thresholds was fair (κ = 0.417, p = 0.00354). Conclusion: This study suggests that there might be no correlation between the cost and clinical benefit of programmed cell death protein-1/programmed cell death protein ligand-1 inhibitors in malignancy, and the same results were observed in subgroups stratified by drug or indication. The results should be a wake-up call for oncologists, pharmaceutical enterprises and policymakers, and meanwhile advocate the refining of American Society of Clinical Oncology and European Society for Medical Oncology frameworks.

Disease burden of prostate cancer from 2014 to 2019 in the United States: estimation from the Global Burden of Disease Study 2019 and Medical Expenditure Panel Survey.

OBJECTIVES: The aim of this study was to evaluate the disease burden of prostate cancer (PC) and assess key influencing factors associated with the disease expenditures of PC in the United States. METHODS: The total deaths, incidence, prevalence, and disability-adjusted life-years of PC were obtained from the Global Burden of Disease Study 2019. The Medical Expenditure Panel Survey was used to estimate healthcare expenditures and productivity loss and to investigate patterns of payment and use of healthcare resources in the United States. A multivariable logistic regression model was conducted to identify key factors influencing expenditures. RESULTS: For patients aged 50 and older, the burden for all age groups showed a modest increase over the 6-year period. Annual medical expenditures were estimated to range from US$24.8 billion to US$39.2 billion from 2014 to 2019. The annual loss in productivity for patients was approximately US$1,200. The top 3 major components of medical costs were hospital inpatient stays, prescription medicines, and office-based visits. Medicare was the largest source of payments for survivors. In terms of drug consumption, genitourinary tract agents (57.0%) and antineoplastics (18.6%) were the main therapeutic drugs. High medical expenditures were positively associated with age (p=0.005), having private health insurance (p=0.016), more comorbidities, not currently smoking (p=0.001), and patient self-perception of fair/poor health status (p<0.001). CONCLUSIONS: From 2014 to 2019, the national real-world data of PC revealed that the disease burden in the United States continued to increase, which was partly related to patient characteristics.

Adjuvant zoledronic acid therapy for postmenopausal women with early breast cancer in China: a cost-effectiveness analysis.

Combination therapy of zoledronic acid (ZOL) plus aromatase inhibitor (AI) was found to reduce bone metastasis risk and improve overall survival for treatment-naïve postmenopausal women (PMW) with hormone receptor-positive (HR+) early breast cancer (EBC), when compared with AI alone. The objective of this study was to evaluate the cost-effectiveness of adding ZOL to AI in treating PMW with HR+ EBC in China. A 5-state Markov model was constructed to evaluate the cost-effectiveness of adding ZOL to AI for PMW-EBC (HR+) over a lifetime horizon from the perspective of Chinese healthcare provider. Data used were obtained from previous reports and public data. The primary outcomes of this study were direct medical cost, life years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses were performed to examine the robustness of the presented model. Over a lifetime horizon, adding ZOL to AI was projected to yield a gain of 1.286 LYs and 1.099 QALYs compared with AI monotherapy, which yielded ICER $11 140.75 per QALY with an incremental cost of $12 247.36. The one-way sensitivity analysis indicated that the cost of ZOL was the most influential factor in our study. The probability that adding ZOL to AI was cost-effective at a threshold of $30 425 per QALY in China was 91.1%. ZOL is likely to be cost-effective in reducing bone metastasis risk and improving overall survival for PMW-EBC (HR+) in China.

Prophylaxis for Pneumocystis carinii pneumonia in non-Hodgkin's lymphoma undergoing R-CHOP21 in China: a meta-analysis and cost-effectiveness analysis.

OBJECTIVE: Rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone, once every 3 weeks (R-CHOP21) is commonly used in non-Hodgkin's lymphoma (NHL), but accompanied by Pneumocystis carinii pneumonia (PCP) as a fatal treatment complication. This study aims to estimate the specific effectiveness and cost-effectiveness of PCP prophylaxis in NHL undergoing R-CHOP21. DESIGN: A two-part decision analytical model was developed. Prevention effects were determined by systemic review of PubMed, Embase, Cochrane Library and Web of Science from inception to December 2022. Studies reporting results of PCP prophylaxis were included. Enrolled studies were quality assessed with Newcastle-Ottawa Scale. Costs were derived from the Chinese official websites, and clinical outcomes and utilities were obtained from published literature. Uncertainty was evaluated through deterministic and probabilistic sensitivity analyses (DSA and PSA). Willingness-to-pay (WTP) threshold was set as US$31 315.23/quality-adjusted life year (QALY) (threefold the 2021 per capita Chinese gross domestic product). SETTING: Chinese healthcare system perspective. PARTICIPANTS: NHL receiving R-CHOP21. INTERVENTIONS: PCP prophylaxis versus no prophylaxis. MAIN OUTCOME MEASURES: Prevention effects were pooled as relative risk (RR) with 95% CI. QALYs and incremental cost-effectiveness ratio (ICER) were calculated. RESULTS: A total of four retrospective cohort studies with 1796 participants were included. PCP risk was inversely associated with prophylaxis in NHL receiving R-CHOP21 (RR 0.17; 95% CI 0.04 to 0.67; p=0.01). Compared with no prophylaxis, PCP prophylaxis would incur an additional cost of US$527.61, and 0.57 QALYs gained, which yielded an ICER of US$929.25/QALY. DSA indicated that model results were most sensitive to the risk of PCP and preventive effectiveness. In PSA, the probability that prophylaxis was cost-effective at the WTP threshold was 100%. CONCLUSION: Prophylaxis for PCP in NHL receiving R-CHOP21 is highly effective from retrospective studies, and routine chemoprophylaxis against PCP is overwhelmingly cost-effective from Chinese healthcare system perspective. Large sample size and prospective controlled studies are warranted.

Diagnostic Value of Serum Golgi Protein 73 for Liver Fibrosis: A Systematic Review and Meta-Analysis.

BACKGROUND: The assessment of liver fibrosis has been a critical component in the clinical management of liver diseases. We performed a meta-analysis to evaluate serum Golgi protein 73 (GP73) in the diagnosis of liver fibrosis. METHODS: A literature search was performed in eight databases until July 13, 2022. We strictly searched studies according to inclusion and exclusion criteria, extracted data, and then assessed quality. We pooled the sensitivity, specificity, and other diagnostic estimates of serum GP73 to assess liver fibrosis. Moreover, publication bias, threshold analysis, sensitivity analysis, meta-regression, subgroup analysis, and post-test probability were evaluated. RESULTS: Our research integrated 16 articles including 3,676 patients. Potential publication bias and threshold effect were not found. The pooled sensitivity, specificity, and area under the curve of the summary receiver operating characteristic curve were 0.63, 0.79, and 0.818 for significant fibrosis; 0.77, 0.76, and 0.852 for advanced fibrosis; and 0.80, 0.76, and 0.894 for cirrhosis, respectively. The aetiology was one of the important sources of heterogeneity. CONCLUSION: Serum GP73 was a feasible diagnostic marker for liver fibrosis, which is of great significance for the clinical management of liver diseases.

Prognostic Value of Controlling Nutritional Status Score in Advanced Hypopharyngeal Cancer.

OBJECTIVE: The purpose of this study was to investigate the prognostic significance of the preoperative controlling nutritional status (CONUT) score in patients with resectable advanced hypopharyngeal cancer. METHODS: This retrospective study included 113 advanced hypopharyngeal cancer patients who underwent curative resection in our hospital from 2013 to 2017. The association between the CONUT score and clinicopathological variables was evaluated. The association between CONUT score and survival was analyzed using Kaplan-Meier survival curves and Cox regression. The efficacy of the CONUT score and other immune-nutritional markers to predict prognosis was compared using a time-dependent receiver operating characteristic (ROC). RESULTS: Patients were divided into the high-CONUT score group (≥3) and the low-CONUT score group (≤2) according to ROC analysis. The CONUT score was associated with body mass index (p = 0.047), monocyte (p = 0.021), pharyngocutaneous fistula (p = 0.045), flap repairment (p = 0.034), tumor (T) classification (p = 0.034), node (N) classification (p = 0.036), subsite of tumor (p = 0.035), and negative pathologic factors (p < 0.001). Tumor, node, metastasis (TNM) stage, negative pathologic factors, adjuvant radiotherapy, postoperative chemoradiotherapy, and CONUT score were independent prognostic factors for survival. Patients with a higher CONUT score had worse overall survival (OS) (hazard ratio: 2.76, 95% confidence interval [CI]: 1.44-5.29, p = 0.002) and disease-free survival (hazard ratio: 2.51, 95% CI: 1.28-4.91, p = 0.007). The area under the curve of the CONUT score (0.799) to predict 5-year OS was greater than those of Preoperative Nutritional Index (0.769), platelet-to-lymphocyte ratio (0.643), neutrophil-to-lymphocyte ratio (0.565), and lymphocyte-to-monocyte ratio (0.577). CONCLUSION: The CONUT score is a prognostic marker for patients with resectable advanced hypopharyngeal cancer. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2613-2620, 2023.