Effectiveness of inactivated influenza vaccine against laboratory-confirmed influenza among Chinese elderly: a test-negative design.

BACKGROUND: Evidence on the effectiveness of influenza vaccination in the elderly is limited, and results are controversial. There are also few reports from China. METHODS: We conducted a test-negative case-control study design to estimate influenza vaccine effectiveness (VE) against laboratory-confirmed influenza-associated visits among elderly (aged ≥ 60 years) across four influenza seasons in Ningbo, China, from 2018 to 19 to 2021-22. Influenza-positive cases and negative controls were randomly matched in a 1:1 ratio according to age, sex, hospital, and date of influenza testing. We used logistic regression models to compare vaccination odds ratios (ORs) in cases to controls. We calculated the VE as [100% × (1-adjusted OR)] and calculated the 95% confidence interval (CI) around the estimate. RESULTS: A total of 30,630 elderly patients tested for influenza with virus nucleic acid or antigen during the study period. After exclusions, we included 1 825 influenza-positive cases and 1 825 influenza-negative controls. Overall, the adjusted VE for influenza-related visits was 63.5% (95% CI, 56.3-69.5%), but varied by season. Influenza VE was 59.8% (95% CI, 51.5-66.7%) for influenza A and 89.6% (95% CI, 77.1-95.3%) for influenza B. The VE for ages 60-69 and 70-79 was 65.2% (95% CI, 55.4-72.9%) and 69.8% (95% CI, 58.7-77.9%), respectively, but only 45.4% (95% CI, 6.2-68.2%) for ages 80 and over. CONCLUSIONS: Standard-dose inactivated influenza vaccine has shown good protection in the elderly in China. However, protection may not be satisfactory in people aged 80 years and older.

Global smoking-related deaths averted due to MPOWER policies implemented at the highest level between 2007 and 2020.

BACKGROUND: In response to the harm caused by tobacco use worldwide, the World Health Organization (WHO) World Health Assembly actioned the WHO Framework Convention on Tobacco Control (FCTC) in 2005. To help countries meet their FCTC obligations, the WHO introduced in 2008 the MPOWER policy package and by 2020 the FCTC had been ratified by 182 parties. The package consists of six evidence-based demand reduction smoking cessation policies to assist countries to achieve best practice. We used published evaluation results and replicated the published model to estimate current policy achievement and demonstrate the impact and equity of the MPOWER policy package in reducing the global number of smokers and smoking-attributable deaths (SADs) between 2007 and 2020. METHODS: We replicated an evaluation model (the Abridged SimSmoke model) used previously for country impact assessments and validated our replicated reduction in SADs for policies between 2014 and 2016 against the published results. The replicated model was then applied to report on the country level SADs averted from achieving the highest level of implementation, that is best practice in MPOWER policies, between 2016 and 2020. The latest results were then combined with past published results to estimate the reduction in SADs since the commencement of the MPOWER policy package. Country level income status was used to investigate the equity in the uptake of MPOWER policies worldwide. RESULTS: Identical estimates for SADs in 41 out of 56 MPOWER policies implemented in 43 countries suggested good agreement in the model replication. The replicated model overestimated the reduction in SADs by 159,800 (1.5%) out of a total of 10.5 million SADs with three countries contributing to the majority of this replication discrepancy. Updated analysis estimated a reduction of 8.57 million smokers and 3.37 million SADs between 2016 and 2020. Between 2007 and 2020, 136 countries had adopted and maintained at least one MPOWER policy at the highest level which was associated with a reduction in 81.0 million smokers and 28.3 million SADs. Seventy five percent of this reduction was in middle income countries, 20% in high income and less than 5% in low income countries. CONCLUSIONS: Considerable progress has been made by MPOWER policies to reduce the prevalence of smokers globally. However, there is inequality in the implementation and maintenance, reach and influence, and the number of SADs averted. Future research to modify the model could provide a more comprehensive evaluation of past and future progress in tobacco control policies, worldwide.

Design and rationale of the Botswana Smoking Abstinence Reinforcement Trial: a protocol for a stepped-wedge cluster randomized trial.

BACKGROUND: With expanded and sustained availability of HIV treatment resulting in substantial improvements in life expectancy, the need to address modifiable risk factors associated with leading causes of death among people living with HIV/AIDS (PLWH), such as tobacco smoking, has increased. Tobacco use is highly prevalent among PLWH, especially in southern Africa, where HIV is heavily concentrated, and many people who smoke would like to quit but are unable to do so without assistance. SBIRT (Screening, Brief Intervention and Referral to Treatment) is a well-established evidence-based approach successful at supporting smoking cessation in a variety of settings. Varenicline is efficacious in supporting smoking cessation. We intend to assess the effectiveness of SBIRT and varenicline on smoking cessation among PLWH in Botswana and the effectiveness of our implementation. METHODS: BSMART (Botswana Smoking Abstinence Reinforcement Trial) is a stepped-wedge, cluster randomized, hybrid Type 2 effectiveness-implementation study guided by the RE-AIM framework, to evaluate the effectiveness and implementation of an SBIRT intervention consisting of the 5As compared to an enhanced standard of care. SBIRT will be delivered by trained lay health workers (LHWs), followed by referral to treatment with varenicline prescribed and monitored by trained nurse prescribers in a network of outpatient HIV care facilities. Seven hundred and fifty people living with HIV who smoke daily and have been receiving HIV care and treatment at one of 15 health facilities will be recruited if they are up to 18 years of age and willing to provide informed consent to participate in the study. DISCUSSION: BSMART tests a scalable approach to achieve and sustain smoking abstinence implemented in a sustainable way. Integrating an evidence-based approach such as SBIRT, into an HIV care system presents an important opportunity to establish and evaluate a modifiable cancer prevention strategy in a middle-income country (MIC) setting where both LHW and non-physician clinicians are widely used. The findings, including the preliminary cost-effectiveness, will provide evidence to guide the Botswanan government and similar countries as they strive to provide affordable smoking cessation support at scale. CLINICAL TRIAL REGISTRATION: NCT05694637 Registered on 7 December 2022 on clinicaltrials.gov, https://clinicaltrials.gov/search?locStr=Botswana&country=Botswana&cond=Smoking%20Cessation&intr=SBIRT.

Cost-effectiveness of population-based screening for chronic obstructive pulmonary disease in China: a simulation modeling study.

Background: China has the highest disease burden of chronic obstructive pulmonary disease (COPD) in the world; however, the diagnosis rate remains low. Screening for COPD in the population may improve early diagnosis and long-term health outcomes for patients with COPD. In this study, we aimed to evaluate the cost-effectiveness of population-based COPD screening policies in China. Methods: We developed a microsimulation model that simulated incidence, natural history, and clinical management of COPD over a lifetime horizon among the general population aged 35-80 years in China. We evaluated population-based screening policies with different screening methods (one-step with COPD Screening Questionnaire or two-step with additional portable spirometer test) and frequencies (one-time or every 1-10 years). We calculated the incremental cost-effectiveness ratio (ICER) of the screening policies compared with the status quo (without screening) and identified the most cost-effective screening policy. Scenario and sensitivity analyses were performed to assess the impact of key parameters and the robustness of model results. Findings: Compared with the status quo, all population-based COPD screening policies were cost-effective with estimated ICERs ranging between $8034 and $13,209 per quality-adjusted-life-year (QALY), all under the willingness-to-pay value of $38,441/QALY (three times China's gross domestic product per capita). A total of 0.39%-8.10% of COPD-related deaths and 0.58%-2.70% of COPD exacerbations were projected to be averted by COPD screening. Among all screening policies, annual two-step screening was the most cost-effective. Improving the linkage from screening to diagnosis and treatment could further increase population health benefits and the cost-effectiveness of COPD screening. Interpretation: Population-based screening for COPD could be cost-effective in China. Offering public programs for COPD screening similar to existing preventive health services for other chronic diseases could be a promising strategy to improve population health outcomes and mitigate the disease burden of COPD in China. Funding: Alexander von Humboldt Foundation, National Natural Science Foundation of China, CAMS Innovation Fund for Medical Science, Chinese Academy of Engineering project, and Horizon Europe.

Comparing the effectiveness of full-vacuum and half-vacuum drainage in reducing seroma after modified radical mastectomy: a meta-analysis.

INTRODUCTION: Owing to limited outpatient support for drain management, delayed discharge after mastectomy is more prevalent in developing countries. Utilising half-vacuum (HV) suction drains for routine drainage after mastectomy could lead to a reduced incidence of seroma and a shorter hospital stay. This systematic review and meta-analysis compared the outcomes of HV against full-vacuum (FV) suction drains in patients who underwent modified radical mastectomy for breast cancer. METHODS: Differences between the two groups in length of hospital stay, total volume of drain effluent and incidence of seroma were assessed. RevMan 5.4 was used to calculate the odds ratio (OR) and relative risk (RR) for dichotomous data, and the mean difference (MD) for continuous data. RESULTS: Nine randomised controlled trials were included in this review. Using HV drains reduced both the mean length of hospital stay (MD: -2.30 days, 95% confidence interval [CI]: -4.10 to -0.49 days, I2=97%) and the mean total volume of effluent (MD: -132.61ml, 95% CI: -207.32ml to -57.91ml, I2=88%) compared with FV drains. However, there was no statistically significant difference in incidence of seroma between the two groups (RR: 0.67, 95% CI: 0.30 to 1.46, I2=65%). Likewise, there was no difference in rate of seroma occurrence on sensitivity analysis (OR: 1.29, 95% CI: 0.72 to 2.33, I2=74%). CONCLUSIONS: There was no difference in the incidence of seroma between HV and FV suction drainage. Conversely, a reduction in the length of hospital stay and the total volume of drain effluent was observed for mastectomy patients with a HV drain.

Cost-Effectiveness of Ibrutinib for Chronic Lymphocytic Leukemia Treatment in India: Is Evidence Really at Crossroads?

In recent years, newer drugs, such as ibrutinib, have shown promising improvements in the survival of patients with chronic lymphocytic leukemia (CLL). Despite their effectiveness, concerns about their cost have arisen, prompting the need for an evaluation of their cost-effectiveness. However, recent assessments of ibrutinib's cost-effectiveness for treating CLL in India reveal divergent conclusions. The discord centers on divergent cost-effectiveness thresholds, comparator regimens, cost calculations, and outcome valuation approaches. Such discrepancies affect public health decisions and patient care. The recommendation calls for adherence to methodological guidelines by future studies, fostering consistent findings to empower policy makers and clinicians in leveraging economic evidence for informed decision making in CLL treatment strategies.

Evaluation of the Safer Use of Antipsychotics in Youth Study on Population Level Antipsychotic Initiation: An Interrupted Time Series Analysis.

Background: Antipsychotics carry a higher-risk profile than other psychotropic medications and may be prescribed for youth with conditions in which other first-line treatments are more appropriate. This study aimed to evaluate the population-level effect of the Safer Use of Antipsychotics in Youth (SUAY) trial, which aimed to reduce person-days of antipsychotic use among participants. Methods: We conducted an interrupted time series analysis using segmented regression to measure changes in prescribing trends of antipsychotic initiation rates pre-SUAY and post-SUAY trial at four U.S. health systems between 2013 and 2020. Results: In our overall model, adjusted for age and insurance type, antipsychotic initiation rates decreased by 0.73 (95% confidence interval [CI]: 0.30, 1.16, p = 0.002) prescriptions per 10,000 person-months before the SUAY trial. In the first quarter following the start of the trial, there was an immediate decrease in the rate of antipsychotic initiations of 6.57 (95% CI: 0.99, 12.15) prescriptions per 10,000 person-months. When comparing the posttrial period to the pretrial period, there was an increase of 1.09 (95% CI: 0.32, 1.85) prescriptions per 10,000 person-months, but the increasing rate in the posttrial period alone was not statistically significant (0.36 prescriptions per 10,000 person-months, 95% CI: -0.27, 0.99). Conclusion: The declining trend of antipsychotic initiation seen between 2013 and 2018 (pre-SUAY trial) may have naturally reached a level at which prescribing was clinically warranted and appropriate, resulting in a floor effect. The COVID-19 pandemic, which began in the final three quarters of the posttrial period, may also be related to increased antipsychotic medication initiation.

The value-for money of preventing and managing periodontitis: Opportunities and challenges.

This article gives an overview of the societal and economic aspects of periodontitis and periodontal care. Despite its largely preventable nature, periodontitis is highly prevalent worldwide and imposes a substantial health and economic burden on individuals and society as a whole. The worldwide estimated direct treatment costs and productivity losses due to periodontitis (including for periodontitis-related tooth loss) amounted to US$ 186 billion and US$ 142 billion in 2019, respectively. The burden of periodontitis is particularly evident in low and disadvantaged populations. Smoking, dietary habits, and presence of systemic diseases along with social and commercial determinants are considered as risk factors for the periodontal diseases. The cost-effectiveness of preventing and managing periodontitis has been explored in several studies but it has been highlighted that there is scope for improvement in defining the methodology and quality of reporting of such studies. A recent report by The Economist Intelligence Unit examined the cost-effectiveness of interventions to prevent and manage periodontal diseases, suggesting that prevention of periodontitis through prevention of gingivitis by means of individual home care would be more cost-efficient than four other examined approaches. Future research in this field is recommended to further decipher the economic burden of periodontitis to society and to assess the value for money of alternative approaches to address periodontitis with particular emphasis on public health preventive strategies and intersectoral care approaches that address the common risk factors of periodontitis and other non-communicable diseases simultaneously.

The Mediating Effect of Well-Being, Happiness, and Trust in the Relationship Between Work-Life Balance and Work Effectiveness in Seafarers.

In the contemporary global context, seafarers persist as the uncelebrated heroes of international trade, despite their substantial contributions. The current estimate places the number of STCW- certified officers at 857 540, reflecting a notable increase of 10.8% since 2015. Nevertheless, there is a growing recognition of the imperative to accord specific attention to seafarers' mental and physical well-being. During their tenures aboard ships, seafarers confront various challenges, including psychological well-being, work-life imbalance, dissatisfaction, diminished performance, and a sense of mistrust toward the organizational framework. The primary objective of this research is to scrutinize the nexus between work-life balance and work effectiveness, exploring the mediating roles of psychological well-being, organizational happiness, and organizational trust. A questionnaire-based survey is meticulously crafted to achieve this, employing a dataset comprising 420 seafarers engaged in diverse vessel types in Turkey, operating under both Turkish and international flags. Methodologically, structural equation modeling and correlation analyses are executed to assess the formulated research hypotheses rigorously. The empirical findings of this research reveal noteworthy mediating roles: psychological well-being exhibits a complete mediation effect, organizational happiness demonstrates a full mediation effect, and organizational trust manifests a partial mediation effect. These outcomes underscore the nuanced interplay between work-life balance and work effectiveness in the seafaring context. The implications of these findings extend significantly to the maritime sector and industry, accentuating the imperative for targeted interventions to enhance the well-being and performance of seafaring professionals.

Analysis of Safety and Efficacy of the Early Initiation of Antithrombotic Secondary Prevention in Patients Treated with Intravenous Thrombolysis for Acute Ischemic Stroke.

Background and Objectives: Current guidelines and the alteplase product insert recommend that antithrombotic therapy be avoided within 24 h of intravenous thrombolytic therapy with rt-PA in acute ischemic stroke. Therefore, the rate of stroke recurrence is unclear in terms of early neurological deterioration, which we could prevent with the early administration of antithrombotic therapy. We do not know the effect of early antithrombotic therapy after intravenous thrombolysis with rt-PA in acute stroke on the outcome in patients after 90 days either. Design: Prospective monocentric observational cohort study. Methods: Data were collected from consecutive patients treated with alteplase for acute ischemic stroke between January 2015 and January 2023. We examined functional outcome at 90 days, including the risk of symptomatic intracranial hemorrhage and mortality rate as safety indicators and stroke recurrence events in both early and standard antithrombotic therapy at 24 h after intravenous thrombolysis. Results: A total of 489 patients were included, of which 278 (56.9%) were men. Of these, 407 (83.2%) patients received early antithrombotic therapy. No symptomatic intracranial hemorrhage occurred in any participants. There was a significantly higher number of patients with an excellent outcome (mRS 0-1) in early antithrombotic treatment (211 (53.1%) versus 28 (34.6%) in standard antithrombotic treatment (p = 0.002, OR 0.47, 95% CI: 0.28-0.76). Conclusions: Early antithrombotic treatment after intravenous therapy in patients with acute ischemic stroke revealed no safety concerns compared with standard antithrombotic therapy and resulted in a significantly higher proportion of patients with an excellent functional outcome.

Entrectinib as first-line vs. second-line therapy in ROS1 fusion-positive non-small cell lung cancer: a cost-effectiveness analysis.

Background: The concept of cost-effectiveness is crucial for the optimal allocation of scarce healthcare resources. However, the cost-effectiveness of entrectinib in ROS1 fusion-positive non-small cell lung cancer (NSCLC) has not been evaluated. We aim to evaluate the cost-effectiveness of entrectinib as a first-line treatment compared to its reservation for second-line therapy or the exclusive use of chemotherapy in ROS1 fusion-positive advanced NSCLC. Methods: A Markov model was created to assess the clinical outcomes and healthcare costs associated with these three treatment approaches. Cost and utility values were obtained from established literature and cost databases. To test model robustness, probabilistic and univariate sensitivity analyses were conducted. Results: In the first-line setting, where entrectinib was administered as the initial therapy, it yielded an extra 0.07 quality-adjusted life years (QALYs) at an incremental cost of $73,453, leading to an incremental cost-effectiveness ratio (ICER) of $1,090,594.30 per QALY compared to chemotherapy. Conversely, in the second-line setting, when entrectinib was used as a second-line therapy following chemotherapy, it provided an extra 0.11 QALYs at an incremental cost of $53,480, resulting in an ICER of $494,290.39 per QALY compared to chemotherapy. Furthermore, the analysis revealed that the cost of entrectinib and utility values of progressed disease were the most influential factors for the ICER. Conclusions: Considering the current pricing of entrectinib, it is not deemed cost-effective as a first-line or second-line therapy for patients with ROS1 fusion-positive advanced NSCLC when compared to chemotherapy. Alternatively, reserving entrectinib exclusively for second-line therapy might strike a balance between healthcare expenditures and patient outcomes.

Environmental education in Ethiopia: History, mainstreaming in curriculum, governmental structure, and its effectiveness: A systematic review.

Environmental education works to achieve the aims of environmental protection through improving a person's environmental awareness, knowledge, attitudes, skills, active engagement, and drive to better the environment. Through a systematic review of various published and unpublished papers, governmental documents, reports, policies, curriculums, and sample surveys of different governmental sectors, this systematic review aimed to ascertain the mainstreaming of both formal and informal environmental education in the curriculum, governmental structure, its effectiveness, and identify the gap that will need to be filled in Ethiopia. So, the objective of this review is to give a good synopsis of environmental education development, point out any gaps that will need to be filled, and provide insights into its future development. The legal environmental right established in the 1995 Ethiopian constitution served as the driving force behind official environmental education and environmental response. As a result, environmental science has been assigned as a separate or autonomous subject in grades 1-4, as well as in many higher education programs and specializations. On the other hand, in secondary cycle primary school (grades five up to eight) as well as secondary school; environmental education uses a cross-curricula approach in a few natural and social subjects, which is marginalized, and covers only a few topics (titles) of the subjects. Environmental clubs and experts in environmental matters are also available at all levels within the non-formal environmental education system, which spans the federal, regional, district, and other cross-sectional sectors. However, there is a gap due to a lack of professional human resources, monitoring, evaluation, commitment, and expanding best practices, as well as the absence of integration among sectors. As a result, the governmental structure, educational policy, and curriculum demand updates with adequate environmental education experts. Environmental content should be incorporated at the governmental structure and all educational levels with proper implementation, either as standalone subjects or as diffused or integrated on equal footing at every subject level. Additionally, more research on environmental education is required.

Effectiveness of leuprolide acetate administered monthly compared to three-monthly in the treatment of central precocious puberty: evaluation at the end of treatment.

Introduction: Gonadotropin-releasing hormone (GnRH) analogs are the standard treatment for central precocious puberty (CPP). Although there are numerous varieties of GnRH agonists, the effectiveness of 1-monthly compared with 3-monthly Leuprolide acetate is still restricted. The objective of this study was to evaluate the outcomes of CPP treatment with Leuprolide acetate at a 1-monthly dosage of 3.75 mg, in comparison to a dosage of 11.25 mg administered every 3 months. Method: This retrospective cohort study involved 143 girls diagnosed with CPP with 72 of them receiving the monthly treatment regimen and 71 receiving the 3-monthly treatment regimen. Anthropometric measurements were compared at the start and end of the therapy. The rates and level of LH suppression were assessed six months after therapy. Results: The regimen administered every 3 months showed more significant suppression of LH. The 3-monthly group showed lower actual height and degree of bone age advancement at the end of therapy. However, the predicted adult height (PAH) remained comparable in both groups. Conclusion: The 3-monthly treatment showed greater hormonal and growth suppression effects, but there was no significant difference in PAH between the two groups.

Effectiveness of the fourth dose of COVID-19 vaccines against severe COVID-19 among adults 40 years or older in Brazil: a population-based cohort study.

Background: The emergence of COVID-19 variants with immune scape and the waning of primary vaccine schemes effectiveness have prompted many countries to indicate first and second booster COVID-19 vaccine doses to prevent severe COVID-19. However, current available evidence on second booster dose effectiveness are mostly limited to high-income countries, older adults, and mRNA-based vaccination schemes scenarios. We aimed to investigate the relative vaccine effectiveness (rVE) of the fourth dose compared to three doses for severe COVID-19 outcomes in Brazil; and compare the rVE of a fourth dose with an mRNA vaccine compared to adenovirus-based product in the same settings. Methods: We performed a target emulated trial using a population-based cohort of individuals aged 40 years or older who have received a homologous primary scheme of CoronaVac, ChAdOx1, or BNT162b2, and any third dose product and were eligible for the fourth dose in Brazil. The primary outcome was COVID-19 associated hospitalization or death. We built Cohort A matching individuals vaccinated with a fourth dose to individuals who received three doses to estimate the rVE of the fourth dose. We built Cohort B, a subset of Cohort A, matching mRNA-based (mRNA) to adenovirus-based fourth dose vaccinated individuals to compare their relative hazards for severe COVID-19. Findings: 46,693,484 individuals were included in Cohort A and 6,763,016 in Cohort B. 45% of them were aged between 40 and 60 years old, and 48% between 60 and 79 years old. In Cohort A, the most common previous series was a ChAdOx1 two-dose followed by BNT162b2 (44%), and a CoronaVac two-dose followed by a BNT162b2 (36%). Among those fourth dose vaccinated, 36.9% received ChAdOx1, 32.7% Ad26.COV2.S, 25.8% BNT162b2, and 4.7% CoronaVac. In Cohort B, among those who received an adenovirus fourth dose, 53.7% received ChAdOx1 and 46.3% received Ad26.COV2.S. The estimated rVE for the primary outcome of four doses compared to three doses was 44.1% (95% CI 42.3-46.0), with some waning during follow-up (rVE 7-60 days 46.8% [95% CI 44.4-49.1], rVE after 120 days 33.8% [95% CI 18.0-46.6]). Among fourth dose vaccinated individuals, mRNA-based vaccinated individuals had lower hazards for hospitalization or death compared to adenovirus-vaccinated individuals (HR 0.81, 95% CI 0.75-0.87). After 120 days, no difference in hazards between groups was observed (HR 1.35, 95% CI 0.93-1.97). Similar findings were observed for hospitalization and death separately, except no evidence for differences between fourth dose brands for death in Cohort B. Interpretation: In a heterogeneous scenario of primary and first booster vaccination combinations, a fourth dose provided meaningful and durable protection against severe COVID-19 outcomes. Compared to adenovirus-based booster, a fourth dose wild-type mRNA vaccine was associated with immediate lower hazards of hospitalization or death unsustained after 120 days. Funding: None.

Explorative cost-effectiveness analysis of colorectal cancer recurrence detection with next-generation sequencing liquid biopsy in Spain, France, and Germany.

Background: Next-generation sequencing liquid biopsy (NGS-LB) for colorectal cancer (CRC) detection and surveillance remains an expensive technology as economies of scale have not yet been realized. Nevertheless, the cost of sequencing has decreased while sensitivity has increased, raising the question of whether cost-effectiveness (CE) has already been achieved from the perspective of European healthcare systems. Objectives: This health economic (HE) modeling study explores the CE of NGS-LB for CRC based on direct treatment costs compared to standard care without liquid biopsy in Spain, France, and Germany. Methods: A structured literature search was used to collect evidence from 2009 to 2020 on the stage-dependent quality of life (quality-adjusted life-years, QALY), efficacy, and total direct treatment costs (TDC) of NGS-LB. A decision-analytic Markov model was developed. Over the remaining lifetime, cumulative life expectancy (LE), TDC, and QALYs were calculated for 60-year-old men and women in CRC stage III with different assumed effects of NGS-LB of 1% or 3% on improved survival and reduced stage progression, respectively. Results: The use of NGS-LB increases LE by 0.19 years in Spanish men (France: 0.19 years, Germany: 0.13 years) and by 0.21 years in Spanish women (France: 0.21 years, Germany: 0.14 years), respectively. The 3% discounted cost per QALY gained was 35,571.95 € for Spanish men (France: 31,705.15 €, Germany: 37,537.68 €) and 35,435.71 € for Spanish women (France: 31,295.57 €, Germany: 38,137.08 €) in the scenario with 3% improved survival and reduced disease progression. Compared to the other two countries, Germany has by far the highest TDC, which can amount to >80k euros in the last treatment year. Conclusion: In this explorative HE modeling study, NGS-LB achieves generally accepted CE levels in CRC treatment from the health system perspective in three major European economies under assumptions of small improvements in cancer recurrence and survival. Confirmation of these findings through clinical trials is encouraged.

Is it worthwhile to use next generation liquid biopsy for cancer recurrence detection on patients with colorectal cancer? Colon cancer is common. Worldwide, almost one million people die from it every year. Next Generation Sequencing Liquid Biopsy is a very sensitive technology for detecting cancer cells and their genetic information in the blood. Therefore, it is a good way to detect cancer and to detect early recurrence of a previously treated tumor. This test procedure is not yet used very often. Therefore, it is still expensive. Furthermore, there are still no studies that have demonstrated that and how liquid biopsy can aid doctors and patients after initial treatment. The research team of this study has developed an analytical model to investigate what performance liquid biopsy should have to demonstrate an affordable patient benefit in terms of quality of life, survival and cost per additional quality-adjusted life year gained. To do this, they studied the existing medical literature and many cost studies on colorectal cancer for the countries of Spain, France and Germany to feed their model. Then, they made different assumptions about the performance of liquid biopsy and did calculations. In the process, they also particularly examined the significance of specific influencing factors such as costs or disease progression in so-called sensitivity analyses. As a result, the authors found that there are large differences in treatment costs for colorectal cancer between the three countries Spain, France and Germany. Furthermore, even small improvements in the progression of cancer and the survival of cancer patients lead to the economic efficiency of liquid biopsy for the health care system. However, these are still thought experiments, so the research team of this study says that there should be further clinical trials to assess the impact of liquid biopsy on cancer progression and patient survival by using this technology. By this, one could confirm or contradict the authors' educated assumptions and possibly pave a new way towards medical progress for people with colorectal cancer.

Evaluating the Feasibility, Acceptance, and Beneficial Effects of Online Occupational Therapy for Post-COVID-19 Condition: Protocol for a Randomized Controlled Trial (ErgoLoCo Study).

BACKGROUND: Post-COVID-19 syndrome (PCS; also known as "long COVID") is a relatively novel disease comprising physical, psychological, and cognitive complaints persisting several weeks to months after acute infection with SARS-CoV-2. Approximately 10% of patients with COVID-19 are affected by long-term symptoms. However, effective treatment strategies are lacking. The ErgoLoCo (Occupational Therapy [Ergotherapie] for Long COVID) study was designed to develop and evaluate a novel occupational therapy (OT) concept of online delivery of therapy for long COVID. OBJECTIVE: The primary study objective is to assess the feasibility of the online OT intervention in PCS. Secondary aims include the evaluation of online OT concerning cognitive problems, occupational performance, and social participation. METHODS: This randomized controlled interventional pilot study involves parallel mixed methods process analyses and a realist evaluation approach. A total of 80 clients with PCS aged at least 16 years will be recruited into two interventional groups. The control cohort (watch and wait) comprises 80 clients with long COVID. Treatment is provided through teletherapy (n=40) or delivery of prerecorded videos (n=40) using the same standardized OT concept twice weekly over 12 weeks. Analyses of quantitative questionnaires and qualitative interviews based on the theoretical framework of acceptability will be performed to assess feasibility. Focus group meetings will be used to assess how acceptable and helpful the intervention was to the participating occupational therapists. Standardized tests will be used to assess the initial efficacy of the intervention on neurocognitive performance; limitations in mobility, self-care, and everyday activities; pain; disabilities; quality of life (QoL); social participation; and anxiety and depression in PCS, and the possible effects of online OT on these complaints. RESULTS: The German Ministry of Education and Research provided funding for this research in March 2022. Data collection took place from October 2022 to August 31, 2023. Data analysis will be completed by the end of April 2024. We anticipate publishing the results in the fall of 2024. CONCLUSIONS: Despite the enormous clinical need, effective and scalable treatment options for OT clients who have PCS remain scarce. The ErgoLoCo study will assess whether online-delivered OT is a feasible treatment approach in PCS. Furthermore, this study will assess the effect of the intervention on cognitive symptoms, QoL, and occupational performance and participation in everyday life. Particular emphasis will be placed on the experiences of clients and occupational therapists with digitally delivered OT. This study will pave the way for novel and effective treatment strategies in PCS. TRIAL REGISTRATION: German Clinical Trial Registry DRKS00029990; https://drks.de/search/de/trial/DRKS00029990. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50230.

Comparison of the Clinical Effectiveness of Telerehabilitation with Traditional Rehabilitation Methods in Multiple Sclerosis Patients: A Systematic Review.

Background: The rehabilitation process for multiple sclerosis (MS) patients is long and complex, which can lead to reduced rehabilitation outcomes and reduced quality improvement. Thus, there is a need to use new methods to boost traditional rehabilitation. Innovations such as telerehabilitation can be helpful to remove the obstacles to treatment, but evidence for their effectiveness is limited. The objective of this work was to compare the clinical effectiveness of telerehabilitation with traditional interventions in MS patients. Methods: Seven bibliographic databases (PubMed, Cochran Library, Scopus, Science Direct, Web of Science, Embase, and ProQuest) were used in this research. The initial search resulted in the extraction of 8,239 articles; after the review of the title, abstract, and full text, 11 articles were selected. In addition, backward reference list checking of the selected studies was conducted. Studies that were related to our objectives were included. Quality assessment was performed using the CONSORT checklist. Then, data extraction was done using the form set by the researcher in Word 2016 software. Results: Overall, telerehabilitation achieved more positive effects compared to traditional rehabilitation on physical (n = 6), cognitive (n = 3), cognitive, and physical outcomes (n = 2), respectively. Synchronous telerehabilitation was more effective than other modalities (n = 8). In four studies, virtual reality-based telerehabilitation was used. Also, telerehabilitation in home offered better clinical outcomes compared to rehabilitation center (n = 9). Conclusions: This review provides evidence for the potential effectiveness of telerehabilitation for the improvement of clinical outcomes in MS patients. However, more robust randomized controlled trials are needed to confirm the observed positive effects.

Estimation of glucose absorption, insulin sensitivity, and glucose effectiveness from the oral glucose tolerance test.

CONTEXT: Glucose tolerance during an oral glucose tolerance test (OGTT) is affected by variations in glucose effectiveness (GE) and glucose absorption and thus affects minimal model calculations of insulin sensitivity (SI). The widely used OGTT SI by Dalla Man et al. does not account for variances in GE and glucose absorption. OBJECTIVE: To develop a novel model that concurrently assesses SI, GE, and glucose absorption. DESIGN: Cross-sectional. SETTING: Academic Medical Center. PARTICIPANTS: Eighteen subjects without abnormalities on OGTT (controls) and 88 subjects with diabetes. INTERVENTION: All subjects underwent 75-gram 120-minute 6-timepoint OGTT. MAIN OUTCOMES: SI from the Dalla Man model was validated with the novel model Si using Bland Altman limits of agreement methodology. Comparisons of SI, GE, and gastrointestinal glucose half-life (GIGt1/2); a surrogate measure for glucose absorption were made between subjects with diabetes and controls. RESULTS: In controls and diabetes, the novel model SI was higher than the current OGTT model. SI from both controls (ƿ=0.90, p < 0.001) and diabetes (ƿ=0.77, p < 0.001) has high agreement between models. GE was higher in diabetes (median:0.021 1/min, IQR [interquartile range]: 0.020-0.022) compared to controls (median:0.016 1/min, IQR: 0.015-0.017), p = 0.02. GIGt1/2 was shorter in diabetes (median: 48.404 min, IQR: 54.424-39.426) than in controls (median: 55.086 min, IQR: 61.368-48.502) without statistical difference. CONCLUSIONS: Our novel model SI has a good correlation with SI from the widely used Dalla Man's model while concurrently calculating GE and GIGt1/2. Thus, besides estimating SI, our novel model can quantify differences in insulin-independent glucose disposal mechanisms important for diabetes pathophysiology.

The varying clinical effectiveness of single, three and five intraarticular injections of platelet-rich plasma in knee osteoarthritis.

OBJECTIVE: To investigate the variations in clinical effectiveness among patients diagnosed with knee osteoarthritis who underwent intra-articular administration of platelet-rich plasma using single, triple, or quintuple injections. METHODS: One hundred twenty patients with grade I-III knee osteoarthritis were randomly assigned to three groups: PRP1 group, who received a single injection of platelet-rich plasma; PRP3 group, who received three PRP injections one week apart; PRP5 group, who received five PRP injections one week apart. The patients' conditions were evaluated using the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index-VA3.1 version (WOMAC-VA3.1) at baseline and 6, 12, 24, and 52 weeks 52 weeks follow up. RESULTS: Out of the total participants, 106 patients (30 males and 76 females) completed the study. The primary outcome measure, WOMAC pain score, registered significant improvements across all groups when compared to pre-treatment levels. However, the application of 3 and 5 injections of platelet-rich plasma was substantially more effective than that of a single injection in reducing knee pain and stiffness, as well as enhancing physical function in patients with knee osteoarthritis. No statistically discernable difference was observed between PRP3 and PRP5 at all follow-up intervals, and there was no discernable difference between 3 and 5 PRP injections either. Mild side effects occurred in all three groups. CONCLUSIONS: The administration of three or five injections of platelet-rich plasma is safe, substantially more effective than single injections, and leads to remarkable clinical improvement by significantly reducing knee pain, improving joint stiffness, and enhancing physical function in patients with grade I-III knee osteoarthritis. Furthermore, no significant difference was observed in the efficacy of three or five injections. Therefore, we recommend using three injections of PRP in the treatment of patients with knee osteoarthritis of grade I-III.

Long-term outcome of risankizumab in Crohn's disease: a real-world GETAID study.

INTRODUCTION: The aim of this study was to assess the long-term effectiveness and safety of risankizumab maintenance treatment in a large real-world cohort of patients with CD. PATIENTS AND METHODS: From May 2021 to August 2023, all consecutive CD patients treated with risankizumab in 25 GETAID centers have been retrospectively included. The primary endpoint was steroid-free clinical remission (Harvey Bradshaw Index (HBI) <5) at 52 weeks. RESULTS: Of the 174 patients included, 99%, 93%, and 96% had been previously exposed to anti-TNF, vedolizumab, and ustekinumab, respectively. All patients had received ≥3 biologics and 108 (62%) had previous intestinal resection. Median follow-up was 13.7 (10.0-18.1) months. The rates of steroid-free clinical remission and clinical remission at week 26 were 47% (72/152) and 52% (79/152), and 46% (58/125), and 48% (60/125) at week 52, respectively. Risankizumab persistence rates were 94%, 89%, and 79% at weeks 12, 26, and 52, respectively. At the end of follow-up, 45 (45/174, 26%) patients had discontinued risankizumab (loss of response, 42%; primary failure, 37%; intolerance, 13%). Thirty-six patients (36/174, 20.9%) were hospitalized and 22 (22/174, 12.6%) required intestinal resection. Fifty-one (29%) patients had an adverse event including 26 (15%) serious adverse events (CD flare, n=17). One death (myocardial infarction) and one cancer (papillary thyroid carcinoma) were observed. CONCLUSION: This is the first real-life study to report long-term outcomes in patients with refractory CD treated with risankizumab. Half of the patients achieved steroid-free clinical remission after one year, and the safety profile was consistent with the literature.