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Availability and financing of CAR-T cell therapies: A cross-country comparative analysis
Chimeric antigen receptor T-cell therapies (CAR-T therapies) are a type of advanced therapy medicinal product (ATMP) that belong to a new generation of personalised cancer immunotherapies. This paper compares the approval, availability and financing of CAR-T cell therapies in ten countries. It also examines the implementation of this type of ATMP within the health care system, describing the organizational elements of CAR-T therapy delivery and the challenges of ensuring equitable access to all those in need, taking a more systems-oriented view. It finds that the availability of CAR-T therapies varies across countries, reflecting the heterogeneity in the organization and financing of specialised care, particularly oncology care. Countries have been cautious in designing reimbursement models for CAR-T cell therapies, establishing limited managed entry arrangements under public payers, either based on outcomes or as an evidence development scheme to allow for the study of real-world therapeutic efficacy. The delivery model of CAR-T therapies is concentrated around existing experienced cancer centres and highlights the need for high networking and referral capacity. Some countries have transparent and systematic eligibility criteria to help ensure more equitable access to therapies. Overall, as with other pharmaceuticals, there is limited transparency in pricing, eligibility criteria and budgeting decisions in this therapeutic area.
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Thirteen Nonpharmacological Interventions for Increasing the Quality of Life in Patients with Advanced Cancer: A Network Meta-analysis
Background: A variety of nonpharmacological interventions that improve the quality of life of patients with advanced cancer have been difficult for medical staff to select through randomized controlled trials or traditional meta-analyses. Thus, a network meta-analysis is necessary. Objective: This study used network meta-analysis to analyze the effect of 13 different nonpharmacological interventions on improving the living quality of patients with advanced cancer. Methods: Five English databases were searched up to January 2019. The search strategy only included terms relating to or describing the intervention. Results: The study included 13 different nonpharmacological interventions. The overall efficacy was summarized through a holistic study of quality of life. The study found that the combined effect sizes of 13 nonpharmacological interventions crossed the invalid line (weighted mean difference, -13 [95% confidence interval, -33 to 8.5] to 1.7 [95% confidence interval, -18 to 22]), indicating that none of the intervention was significantly different from each other. By evaluating the heterogeneity of this outcome, no significant evidence of heterogeneity ( P > .05) was observed. Probability ranking according to the surface under the cumulative ranking curve showed that there was a great possibility for the CanWalk intervention and structured multidisciplinary intervention to improve outcomes for cancer patients. Conclusions: Thirteen nonpharmacological interventions did not significantly impact quality of life. Regarding the probability rank, CanWalk intervention may be the most promising way that advanced cancer patients can help themselves to a better life. Because of the limitations of the current studies, the conclusion needs further evidence. Implications for practice: Nurses should consider recommending moderate physical activity for patients with advanced cancer.
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Association of soft drinks and 100% fruit juice consumption with risk of cancer: a systematic review and dose-response meta-analysis of prospective cohort studies
BackgroundStudies of the associations between soft drinks and the risk of cancer showed inconsistent results. No previous published systematic reviews and meta-analysis has investigated a dose-response association between exposure dose and cancer risk or assessed the certainty of currently available evidence. Therefore, we aim to demonstrate the associations and assessed the certainty of the evidence to show our confidence in the associations.MethodsWe searched Embase, PubMed, Web of Science, and the Cochrane Library from inception to Jun 2022, to include relevant prospective cohort studies. We used a restricted cubic spline model to conduct a dose-response meta-analysis and calculated the absolute effect estimates to present the results. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of the evidence.ResultsForty-two articles including on 37 cohorts enrolled 4,518,547 participants were included. With low certainty evidence, increased consumption of sugar-sweetened beverages (SSBs) per 250 mL/day was significantly associated with a 17% greater risk of breast cancer, a 10% greater risk of colorectal cancer, a 30% greater risk of biliary tract cancer, and a 10% greater risk of prostate cancer; increased consumption of artificially sweetened beverages (ASBs)re per 250 mL/day was significantly associated with a 16% greater risk of leukemia; increased consumption of 100% fruit juice per 250 mL/day was significantly associated with a 31% greater risk of overall cancer, 22% greater risk of melanoma, 2% greater risk of squamous cell carcinoma, and 29% greater risk of thyroid cancer. The associations with other specific cancer were no significant. We found linear dose-response associations between consumption of SSBs and the risk of breast and kidney cancer, and between consumption of ASBs and 100% fruit juices and the risk of pancreatic cancer.ConclusionsAn increment in consumption of SSBs of 250 mL/day was positively associated with increased risk of breast, colorectal, and biliary tract cancer. Fruit juices consumption was also positively associated with the risk of overall cancer, thyroid cancer, and melanoma. The magnitude of absolute effects, however, was small and mainly based on low or very low certainty of evidence. The association of ASBs consumption with specific cancer risk was uncertain.
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Dietary Vitamin A Intake and Circulating Vitamin A Concentrations and the Risk of Three Common Cancers in Women: A Meta-Analysis
Background. According to relevant clinical research, dietary and circulating antioxidants vitamin A are connected with the risk of breast, cervical, and cancer women. However, there was inconsistency between the findings. We completed this meta-analysis at the right moment to address this contradiction of the problem. Methods. Web of Science, Embase, and PubMed databases were searched using the proposed search strategy and filtered using the inclusion and exclusion criteria as well as the NOS quality score. As of May 2022, low intake or low concentration was used as a control, and odds ratio (OR) or relative risk (RR) and ninety-five percent confidence intervals (95% CI) were extracted for high intake. Stata 12.0 was used to process the data. Results. Our meta-analysis included a total of 49 studies, 29 on breast cancer, 10 on ovarian cancer, and 10 on cervical cancer. There were 38 case-control studies included, with 25,363 cases and 42,281 controls; there were 11 cohort studies included, 1,334,176 individuals were followed up, and finally 9496 obtained cancer. The pooled OR value results were as follows: diet or supplements (OR=0.83, 95% CI 0.76-0.90, I2=56.1%) and serum or plasma (OR=0.96, 95% CI 0.86-1.09, I2=29.5%). Subgroup analyses were performed according to cancer type, diet or supplements, serum or plasma, study type, and geographic regions. Conclusions. In North American and Asian populations, high dietary consumption of vitamin A or supplements decreases the incidence of three cancers in women, with breast and ovarian cancers being more significant. However, high circulating vitamin A concentrations were not significantly connected with the risk of the three malignancies.
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Factors associated with cervical cancer screening utilisation by people with physical disabilities: A systematic review
Background Previous studies showed that cervical cancer screening uptake among people with physical disabilities is low. A better understanding of the factors affecting their screening uptake is needed to devise strategies to address this issue. Objective This review explores the factors that impede or enhance cervical cancer screening utilisation by people with physical disabilities, such as mobility, visual and hearing impairments. Methods Five electronic databases were searched, resulting in the inclusion of nine studies focusing on people with physical disabilities and their utilisation of cervical cancer screening services. Extracted data from these studies were summarised narratively. Their methodological quality was assessed using the Mixed Methods Appraisal Tool, Version 2018. Results Three major impeding factors were reported: 1) lack of knowledge of cervical cancer screening and how it can be accessed; 2) difficulties and inconveniences in accessing cancer screening providers and undergoing the screening procedures; and 3) uncomfortable experiences during the screening procedures. The availability of attendant services and wheelchair-accessible facilities and a longer duration of screening procedures enhanced screening utilisation by the subjects. Conclusions This review highlights the need to provide training for healthcare professionals on working with people with physical disabilities, enhance supportive services to allow them to access cervical cancer screening and educate them on the importance of screening.
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Cognitive behavior therapy for insomnia in cancer patients: a systematic review and network meta-analysis
Objective: The aim of this study was to examine the most effective delivery format of cognitive behavioral therapy for insomnia (CBT-I) on insomnia in cancer patients. Methods: We searched five databases up to February 2021 for randomized clinical trials that compared CBT-I with inactive or active controls for insomnia in cancer patients. Outcomes were insomnia severity, sleep efficiency, sleep onset latency (SOL), wake after sleep onset (WASO), and total sleep time (TST). Pairwise meta-analyses and frequentist network meta-analyses with the random-effects model were applied for data analyses. Results: Sixteen unique trials including 1523 participants met inclusion criteria. Compared with inactive control, CBT-I could significantly reduce insomnia severity (mean differences [MD] = -4.98 points, 95% confidence interval [CI]: -5.82 to -4.14), SOL (MD = -12.29 min, 95%CI: -16.48 to -8.09), and WASO (MD = -16.58 min, 95%CI: -22.00 to -11.15), while increasing sleep efficiency (MD = 7.62%, 95%CI: 5.82% to 9.41%) at postintervention. Compared with active control, CBT-I could significantly reduce insomnia severity (MD = -2.75 points, 95%CI: -4.28 to -1.21), SOL (MD = -13.56 min, 95%CI: -18.93 to -8.18), and WASO (MD = -6.99 min, 95%CI: -11.65 to -2.32) at postintervention. These effects diminished in short-term follow-up and almost disappeared in long-term follow-up. Most of the results were rated as "moderate" to "low" certainty of evidence. Network meta-analysis showed that group CBT-I had an increase in sleep efficiency of 10.61%, an increase in TST of 21.98 min, a reduction in SOL of 14.65 min, and a reduction in WASO of 24.30 min, compared with inactive control at postintervention, with effects sustained at short-term follow-up. Conclusions: CBT-I is effective for the management of insomnia in cancer patients postintervention, with diminished effects in short-term follow-up. Group CBT-I is the preferred choice based on postintervention and short-term effects. The low quality of evidence and limited sample size demonstrate the need for robust evidence from high-quality, large-scale trials providing long-term follow-up data.
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Kanglaite (Coix Seed Extract) as Adjunctive Therapy in Cancer: Evidence Mapping Overview Based on Systematic Reviews With Meta-Analyses
Background: Several quantitative systematic reviews of Kanglaite (KLT), an herb preparation used to treat cancer and malignant pleural effusion, have been published in recent years. However, the clinical evidence reported in these studies has not been pursued further and the methodological quality of these meta-analyses remains unknown. Therefore, an overview was designed to map the evidence landscape based on the published meta-analyses on KLT in cancer treatment. Methods: Two bibliographic databases (PubMed and Embase) were searched from inception to 25 November 2021. Two independent reviewers were involved in study selection, data abstraction, and methodological quality assessment using AMSTAR 2. The principal features of publications and the clinical outcomes of efficacy and safety were synthesized narratively, and results of methodological quality were reported as frequencies and percentages with the corresponding 95% confidence intervals. The evidence map was used to visualize the overall quality. Excel 2016 and Stata 17/SE were used for data analysis. Results: Thirteen meta-analyses published in English were included for in-depth analysis. Among them, the year of publication ranged from 2008 to 2021, and the number of included patients ranged from 488 to 2,964. Regarding the cancer type, seven articles focused on non-small cell lung cancer, two on malignant pleural effusion, and four reviews on digestive system malignancies, such as hepatocellular carcinoma and pancreatic cancer. Almost all included meta-analyses reported that KLT as adjunctive therapy could improve various efficacy outcomes (such as disease response rates, quality of life, immune indicators) and reduce the rate of occurrence of adverse reactions, such as nausea and vomiting, leukopenia, and anemia. In terms of their methodological quality, three meta-analyses were of low quality, whereas 10 studies were critically low in quality. The methodological flaws main involved items 2 ( "predesigned protocol and registration informatio''), 3 ( "rationale of study design for inclusion "), 4 ( "comprehensive search strategy''), 5 ( "literature selection in duplicate''), 7 ( "list of excluded studies with reasons''), 8 ( "adequate information on included studies''), 10 ( "funding support for included primary studies''), and 12 ( "evaluation of the potential impact of risk of bias'') based on the AMSTAR 2 tool. Conclusion: Current evidence reveals that KLT is effective and safe as an adjunctive treatment for non-small cell lung cancer, malignant pleural effusion, and digestive system malignancies (such as hepatocellular carcinoma). However, the results assessed in this overview should be further verified using well-designed and clearly reported clinical trials and meta-analyses of KLT.
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White rice consumption and risk of cardiometabolic and cancer outcomes: A systematic review and dose-response meta-analysis of prospective cohort studies
White rice is the food more than half of the world's population depends on. White rice intake can significantly increase the glycemic load of consumers and bring some adverse health effects. However, the quality of evidence implicating white rice in adverse health outcomes remains unclear. To evaluate the association between white rice consumption and the risk of cardiometabolic and cancer outcomes, a systematic review and dose-response meta-analysis of the relevant publications were performed. Twenty-three articles including 28 unique prospective cohorts with 1,527,198 participants proved eligible after a comprehensive search in four databases. For the risk of type 2 diabetes mellitus (T2DM), the pooled RR was 1.18 (16 more per 1000 persons) for comparing the highest with the lowest category of white rice intake, with moderate certainty evidence. Females presented a higher risk (23 more per 1000 persons) in subgroup analysis. And every additional 150 grams of white rice intake per day was associated with a 6% greater risk of T2DM (5 more per 1000 persons) with a linear positive trend. We found no significant associations between white rice intake and risk of cardiovascular diseases (CVD), CVD mortality, cancer, and metabolic syndrome. In conclusion, moderate certainty evidence demonstrated that white rice intake was associated with T2DM risk, with a linear positive trend. However, low to very low certainty of evidence suggested that no substantial associations were found between white rice intake and other cardiometabolic and cancer outcomes. More cohorts are needed to strength the evidence body.
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Quality Assessment of Cancer Pain Clinical Practice Guidelines
Introduction: Several clinical practice guidelines (CPGs) for cancer pain have been published; however, the quality of these guidelines has not been evaluated so far. The purpose of this study was to evaluate the quality of CPGs for cancer pain and identify gaps limiting knowledge. Methods: We systematically searched seven databases and 12 websites from their inception to July 20, 2021, to include CPGs related to cancer pain. We used the validated Appraisal of Guidelines for Research and Evaluation Instrument II (AGREE II) and Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist to assess the methodology and reporting quality of eligible CPGs. The overall agreement among reviewers with the intraclass correlation coefficient (ICC) was calculated. The development methods of CPGs, strength of recommendations, and levels of evidence were determined. Results: Eighteen CPGs published from 1996 to 2021 were included. The overall consistency of the reviewers in each domain was acceptable (ICC from 0.76 to 0.95). According to the AGREE II assessment, only four CPGs were determined to be recommended without modifications. For reporting quality, the average reporting rates for all seven domains of CPGs was 57.46%, with the highest domain in domain 3 (evidence, 68.89%) and the lowest domain in domain 5 (review and quality assurance, 33.3%). Conclusion: The methodological quality of cancer pain CPGs fluctuated widely, and the complete reporting rate in some areas is very low. Researchers need to make greater efforts to provide high-quality guidelines in this field to clinical decision-making.
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Chinese Medicine as an Adjunctive Treatment for Gastric Cancer: Methodological Investigation of meta-Analyses and Evidence Map
Background: Many meta-analyses (MAs) on Chinese medicine (CM) as an adjunctive treatment for gastric cancer have been published in recent years. However, the pooled evidence reported in MAs and their methodological quality remain unknown. Therefore, we designed a study to comprehensively evaluate and summarize the current evidence of CMs for gastric cancer in published MAs. Methods: A systematic search on MAs published in English from inception to 1st September 2021 was conducted in PubMed and Embase. The AMSTAR-2 tool was used to evaluate the methodological quality of the included MAs, and the results of the quality assessment were visualized using the evidence mapping method. Stata 17/SE was used for statistical analysis (Registration number: INPLASY202190005). Results: A total of 20 MAs (16 pairwise and 4 network MAs) were included from 118 records. These MAs were published in 14 journals from 2013 to 2021, with the number of patients and trials ranging from 688 to 6,857, and from 10 to 85, respectively. A large number of CMs (e.g., AiDi, FuFangKuShen, and HuaChanSu) in combination with chemotherapy for gastric cancer were identified among the included MAs. According to the pooled results reported in MAs, when compared to chemotherapy alone, CMs in combination with chemotherapy not only improve various outcomes on efficacy (e.g., objective response rate, quality of life) but also reduce various adverse reactions (e.g., leucopenia, nausea and vomiting). Only 2 MAs were low in terms of the overall methodological quality, while the other 18 MAs were all critically low. The methodology was required to be advanced significantly, mainly involving: study protocol and registration, explanation for the inclusion of study design, list of excluded studies with justifications, adequate details of included studies, reporting on funding sources of primary studies, and evaluation of the potential impact of risk of bias. In addition, MAs that received funds support (β = 2.68; 95%CI: 0.40 to 4.96; p = 0.024) or were published in journals with higher impact factor (β = 2.81; 95%CI: 0.69 to 4.92; p = 0.012) had a higher score on the overall methodological quality in the univariate analysis, but the results were not statistically significant according to the multivariate analysis. Conclusion: Combining CMs with chemotherapy can potentially improve clinical outcomes and reduce the relevant adverse effects in patients with gastric cancer. However, the methodological quality of relevant MAs requires significant improvement, and the current evidence needs to be validated through multinational trials that are well-designed and have a large sample size.
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