Multinational Studies Research Articles

Stroke Risk Following Nonarteritic Anterior Ischemic Optic Neuropathy.

The association between nonarteritic anterior ischemic optic neuropathy (NAION) and an increased risk of stroke has been a subject of debate. However, multinational studies on this topic are scarce. To evaluate the short-term and long-term stroke risk after NAION compared with a matched control group. This global, retrospective, population-based cohort study used aggregated electronic health records from January 1, 2004, through March 19, 2024, sourced from the Global Collaborative Network of TriNetX, which includes data from over 152 million patients across 17 countries. Patients in the study were followed up for a maximum duration of 10 years. Patients with NAION and age-related cataract were included in the analysis. Those with stroke before the diagnosis of NAION and age-related cataract were excluded. Propensity score matching was applied to balance age, sex, race, ethnicity, comorbidities, and medication use. International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis code for NAION or age-related cataract. The primary outcome was the relative risk (RR) of stroke (ICD-10 code I60-63) in the NAION cohort vs the matched controls. Multivariable logistic regression analyses were applied to identify potential clinical factors associated with stroke within the NAION cohort. A total of 89 811 patients were identified in both the NAION (mean [SD] age, 57.2 [18.5] years; 38 678 men [43.1%]) and control (mean [SD] age, 57.0 [17.9] years; 40 014 men [44.6%]) cohorts after matching. The NAION cohort demonstrated a significantly higher all-stroke risk at all time points: 1 month (RR, 5.04; 95% CI, 4.41-5.78), 3 months (RR, 3.79; 95% CI, 3.40-4.21), 1 year (RR, 2.50; 95% CI, 2.32-2.70), 5 years (RR, 1.54; 95% CI, 1.45-1.63), and 10 years (RR, 1.33; 95% CI, 1.23-1.43). Sensitivity analysis in patients without comorbidities similarly revealed a significantly increased all-stroke risk across all intervals: 1 month (RR, 7.55; 95% CI, 4.74-12.03), 3 months (RR, 6.70; 95% CI, 4.48-10.04), 1 year (RR, 3.96; 95% CI, 2.94-5.34), 5 years (RR, 2.85; 95% CI, 2.18-3.72), and 10 years (RR, 1.68; 95% CI, 1.25-2.26). Among all the clinical factors of interest, only hypertension was consistently associated with all subtypes of stroke following NAION. This cohort study of patients with NAION found a significantly elevated risk of stroke compared with matched controls, independently of comorbidities. These findings underscore the importance of regular stroke workups following the onset of NAION.

An explainable longitudinal multi-modal fusion model for predicting neoadjuvant therapy response in women with breast cancer

Multi-modal image analysis using deep learning (DL) lays the foundation for neoadjuvant treatment (NAT) response monitoring. However, existing methods prioritize extracting multi-modal features to enhance predictive performance, with limited consideration on real-world clinical applicability, particularly in longitudinal NAT scenarios with multi-modal data. Here, we propose the Multi-modal Response Prediction (MRP) system, designed to mimic real-world physician assessments of NAT responses in breast cancer. To enhance feasibility, MRP integrates cross-modal knowledge mining and temporal information embedding strategy to handle missing modalities and remain less affected by different NAT settings. We validated MRP through multi-center studies and multinational reader studies. MRP exhibited comparable robustness to breast radiologists, outperforming humans in predicting pathological complete response in the Pre-NAT phase (ΔAUROC 14% and 10% on in-house and external datasets, respectively). Furthermore, we assessed MRP’s clinical utility impact on treatment decision-making. MRP may have profound implications for enrolment into NAT trials and determining surgery extensiveness.

Effectiveness, Safety, and Patterns of Real-World Isavuconazole Use in Europe (2015-2019).

Real-world data from multinational observational studies are required to better understand the role and performance of isavuconazole in real-world practice in Europe. A retrospective medical record review was conducted at 16 sites in Europe (France, Germany, Italy, Spain, and the United Kingdom). Eligible records were from patients aged ≥ 18years at the time of isavuconazole initiation and received at least one dose of isavuconazole for suspected or confirmed invasive aspergillosis (IA) or invasive mucormycosis (IM) during the eligibility period (October 15, 2015 to June 30, 2019). Data were descriptively analysed. Success rates, overall survival, and times to these events were descriptively analysed. Data were abstracted from 218 patients (201, IA; 17, IM) who received isavuconazole as monotherapy (initiated as infusion, 52%; oral, 46%). Isavuconazole was initiated as primary therapy in 92 patients (42.2%) and salvage therapy in 121 patients (55.5%) (unknown for five patients). Mean (standard deviation) age was 56.8 (15.6) years, 66% were men and 62% had at least three comorbidities, most frequently haematologic malignancy (62%). Estimated clinical response rate at week 24 was 54.5% (95% confidence interval [CI], 38.2-66.5%) for primary treatment and 73.5% (95% CI, 62.7-81.1%) for salvage therapy. Overall, 45 patients (21%) experienced at least one adverse event (AE). Serious AEs were experienced by 37 patients (17%), with seven related to isavuconazole; five patients (2.3%) discontinued isavuconazole monotherapy due to the serious AE. A total of 137 patients (63%) died, with 17 deaths (12.4%) related to their invasive fungal infection, 11 of whom initiated isavuconazole as salvage therapy. This study adds to the growing body of evidence that whether used as first-line therapy or after the failure of other antifungal therapies, isavuconazole appears to have a promising clinical response and a good safety profile as an antifungal agent in patients with varied underlying conditions.

Systemic Innate Immune System Restoration as a Therapeutic Approach for Neurodegenerative Disease: Effects of NP001 on Amyotrophic Lateral Sclerosis (ALS) Progression.

Amyotrophic lateral sclerosis (ALS) is a diagnosis that incorporates a heterogeneous set of neurodegenerative processes into a single progressive and uniformly fatal disease making the development of a uniformly applicable therapeutic difficult. Recent multinational ALS natural history incidence studies have identified systemic chronic activation of the innate immune system as a major risk factor for developing ALS. Persistent immune activation in patients with ALS leads to loss of muscle and lowering of serum creatinine. The goal of the current study was to test whether the slowing of nerve and muscle destruction in NP001-treated ALS patients compared with controls in phase 2 studies would lead to extension of survival. Phase 2 clinical studies with NP001, an intravenously administered form of the innate immune system regulator NaClO2, are now reporting long-term survival benefits for drug recipients vs. placebo controls after only six months of intermittent treatment. As a prodrug, NP001 is converted by macrophages to taurine chloramine, a long-lived regulator of inflammation. We performed a pooled analysis of all patients who had completed the studies in two six-month NP001 phase 2 trials. Changes in respiratory vital capacity and the muscle mass product, creatinine, defined treated patients who, compared to placebo, had up to a year of extended survival. The observed longer survival in ALS patients with the greatest inflammation-associated muscle loss provides further evidence that ALS is a disease of ongoing innate immune dysfunction and that NP001 is a disease-modifying drug with sustained clinical activity.

Lifetime exposure to smoking and substance abuse may be associated with late-onset multiple sclerosis: a population-based case-control study

BackgroundLate-onset multiple sclerosis (LOMS), defined as the development of MS after the age of 50, has shown a substantial surge in incidence rates and is associated with more rapid progression of disability. Besides, studies have linked tobacco smoking to a higher chance of MS progression. However, the role of smoking on the risk of developing LOMS remains unclear. This study aims to evaluate the possible association between lifetime exposure to cigarette and waterpipe smoking, drug abuse, and alcohol consumption and the risk of LOMS.MethodsThis population-based case-control study involved LOMS cases and healthy sex and age-matched controls from the general population in Tehran, Iran. The primary data for confirmed LOMS cases were obtained from the nationwide MS registry of Iran (NMSRI), while supplementary data were collected through telephone and on-site interviews. Predesigned questionnaire for multinational case-control studies of MS environmental risk factors was used to evaluate the LOMS risk factors. The study employed Likelihood ratio chi-square test to compare qualitative variables between the two groups and utilized two independent sample t-test to compare quantitative data. Adjusted odds ratio (AOR) for age along with 95% confidence intervals (CI) were calculated using matched logistic regression analysis in SPSS 23.ResultsTotally, 83 LOMS cases and 207 controls were included in the analysis. The female to male ratio in the cases was 1.5: 1. The mean ± SD age of 83 cases and 207 controls was 61.14 ± 5.38) and 61.51 ± 7.67 years, respectively. The mean ± SD expanded disability status scale (EDSS) score was 3.68 ± 2.1. Although the results of waterpipe exposure had no significant effect on LOMS development (P-value: 0.066), ever cigarette-smoked participants had a significantly higher risk of developing LOMS than those who never smoked (AOR: 2.57, 95% CI: 1.44–4.60). Furthermore, people with a history of smoking for more than 20 years had 3.45 times the odds of developing MS than non-smokers. Drug and alcohol abuse were both associated with LOMS in our study; of which opioids (AOR: 5.67, 95% CI: 2.05–15.7), wine (AOR: 3.30, 95% CI: 1.41–7.71), and beer (AOR: 3.12, 95% CI: 1.45–6.69) were found to pose the greatest risk of LOMS, respectively.ConclusionFor the first time, we identified smoking, drug, and alcohol use as potential risk factors for LOMS development. According to the global increase in cigarette smoking and alcohol use, these findings highlight the importance of conducting interventional approaches for prevention.

Effect of Palivizumab Prophylaxis on Respiratory Syncytial Virus Hospitalizations in Preterm Infants Born to 290/7 to 316/7 Weeks of Gestational Age

Abstract Objective In 2020, in-line with the recommendations of the Turkish Neonatal Society, a new palivizumab indication was added for preterm infants with 290/7 to 316/7 weeks of gestational age. This study aimed to determine the risk factors of hospitalizations due to lower respiratory tract infections (LRTIs) and respiratory syncytial virus (RSV) in preterm infants (290/7–316/7 weeks of gestational age) who were or were not within the scope of palivizumab indication during the first two RSV seasons (2018–2019 and 2019–2020) and the next two RSV seasons (2020–2021 and 2021–2022) to evaluate the validity of the new indication of palivizumab reimbursement scope. Methods This study was a two-center retrospective and prospective cohort study and included all preterm infants (290/7–316/7 weeks) aged 90 days and younger during the RSV season (October–March). The primary outcome was to compare the hospitalization rates between patients who received palivizumab and those who did not. The secondary outcome was to identify the risk factors for patients hospitalized due to LRTIs. Results Of the 122 preterm infants included in the study, 48.3% (n = 59) were in the prophylaxis group (Group 1) and 51.7% (n = 63) were in the non-prophylaxis group (Group 2). It was noteworthy that 53.8% (n = 14) of the 26 infants hospitalized due to LRTIs were in Group 1 and 46.2% (n = 12) were in Group 2 (p = 0.682). Of the RSV PCR-positive infants, 62.5%(n = 5) were in Group 1 and 37.5% (n = 3) were in Group 2 (p = 0.30). The median length of hospitalization was similar in the groups (p = 0.123). Conclusion The indication for palivizumab prophylaxis can be determined more clearly for our country in light of national multicenter studies with an increased sample size.

Multinational Drug Survival Study of Omalizumab in Patients With Chronic Urticaria and Potential Predictors for Discontinuation

Treating patients with chronic urticaria using omalizumab has been shown to be safe and effective in randomized clinical trials. Multinational studies on long-term omalizumab performance in chronic urticaria in clinical practice settings are lacking, especially on drug survival. Drug survival, which refers to the length of time that patients are treated with a specific drug, is a comprehensive outcome covering effectiveness, safety, and patient and physician preferences. Furthermore, little is known about the reasons and potential predictors for omalizumab discontinuation. To investigate omalizumab drug survival as well as reasons and potential predictors for discontinuation in a large, diverse population. This international multicenter cohort study was conducted at 14 Urticaria Centers of Reference and Excellence in 10 countries, including all patients with chronic urticaria from these centers who were ever treated with omalizumab. Drug survival analysis was performed to assess time to discontinuation. Patient characteristics and treatment protocols were investigated by Cox regression analysis to identify potential predictors for omalizumab discontinuation. In 2325 patients with chronic urticaria who started omalizumab between June 2009 and July 2022, the mean (SD) age of the cohort was 42 (6) years, and 1650 participants (71%) were female. Overall omalizumab survival rates decreased from 76% to 39% after 1 to 7 years, respectively (median survival time, 3.3 [95 % CI, 2.9-4.0] years), primarily due to discontinuation from well-controlled disease in 576 patients (65%). Ineffectiveness and adverse effects were reasons for discontinuation in a far smaller proportion of patients, totaling 164 patients (18%) and 31 patients (4%), respectively. Fast treatment response was associated with higher rates of omalizumab discontinuation due to well-controlled disease (hazard ratio, 1.45 [95% CI, 1.20-1.75]), and disease duration of more than 2 years was associated with lower rates of discontinuation due to well-controlled disease (HR, 0.81 [95% CI, 0.67-0.98]). Immunosuppressive cotreatment at the start of omalizumab and autoimmune disease was associated with a higher risk for discontinuation due to ineffectiveness (HR, 1.65 [95% CI, 1.12-2.42]). The presence of spontaneous wheals (HR, 0.62 [95% CI, 0.41-0.93]) and access to higher dosages (HR, 0.40 [95% CI, 0.27-0.58) were both associated with a lower risk for discontinuation of omalizumab due to ineffectiveness. This multinational omalizumab drug survival cohort study demonstrated that treatment of chronic urticaria with omalizumab in a clinical setting is effective and safe, and well-controlled disease is the main reason for treatment discontinuation. These findings on omalizumab drug survival rates and reasons and potential predictors for discontinuation may guide patients and physicians in clinical decision-making and expectation management. These results may call for the identification of biomarkers for chronic urticaria remission in complete responders to omalizumab treatment.

Risks of cutaneous immune-related adverse events in long COVID: Multinational cohort studies in South Korea, Japan, and the UK.

Previous research has not investigated the persistent cutaneous immune-related adverse events (cirAEs) related to long COVID to investigate the long-term sequelae. This multinational study, using a propensity-matched overlap weighting method, utilizes large national claims-based cohorts, using ICD-10 code diagnosis, focusing on patients aged ≥20 years from three countries: South Korean, Japanese, and the British cohorts. To estimate the risk of cirAEs in long COVID, the persistence or emergence of cirAEs occurring 4 weeks after the initial SARS-CoV-2 infection, we employed a Cox proportional hazard regression model. The Korean cohort (n = 5,937,373; mean age 49.2 years [SD: 13.2]), the Japanese cohort (n = 4,307,587; 42.5 years [13.6]), and the UK cohort (n = 395,435; 71.0 years [8.07]) were presented. An increased risk of cirAEs in long COVID was observed (HR, 1.10; 95% CI, 1.06-1.14) in Korean cohort, while a similar association was observed in Japanese and UK cohorts. The long-term risk of cirAEs in long COVID was higher in more severe COVID-19 cases (1.31; 1.22-1.39). Unlike the increased risk of cirAEs in long COVID, COVID-19 vaccination attenuated the risk, especially with two or more doses (1.03; 0.95-1.11) or heterologous regimens (0.98; 0.76-1.27). The time attenuation effect indicated a sustained risk for up to 6 months postinfection (<3 months: 1.13 [1.07-1.19]; 3-6 months: 1.14 [1.06-1.22]). SARS-CoV-2 infection is associated with an increased risk of cirAEs in the aspect of long COVID. Vaccination might reduce this risk, highlighting the need for preventive strategies in long COVID management.

Health-related quality of life in non-alcoholic fatty liver disease: A cross-cultural study between Spain and the United Kingdom.

It is unclear what biopsychosocial factors influence the impact of NAFLD on health-related quality of life (HRQoL), and if these factors are equally important predictors between different nationalities. HRQoL (CLDQ) was measured in both Southern European (Spain, n = 513) and Northern European (United Kingdom -UK-, n = 224) cohorts of patients with NAFLD in this cross-sectional study. For each cohort, participant data were recorded on histological grade of steatohepatitis, stage of fibrosis and biopsychosocial variables. Regression analysis was used to explore which of these variables predicted HRQoL. Moderated mediation models were conducted using SPSS PROCESS v3.5 macro. Participants with severe fibrosis reported more fatigue, systemic symptoms and worry, and lower HRQoL than those with none/mild fibrosis, regardless of place of origin. In addition, body mass index (BMI) and gender were found to be significant predictors of HRQoL in both Spanish and UK participants. Female gender was associated with worse emotional function, higher BMI and more fatigue, which predicted lower participants' HRQoL. UK participants showed more systemic symptoms and worry than Spanish participants, regardless of liver severity. The negative effects of gender on HRQoL through emotional function, BMI and fatigue were reported to a greater degree in UK than in Spanish participants. UK participants showed a greater impairment in HRQoL as compared to Spanish participants. Higher fibrosis stage predicted lower HRQoL, mainly in the Spanish cohort. Factors such as female gender or higher BMI contributed to the impact on HRQoL in both cohorts of patients and should be considered in future multinational intervention studies in NAFLD.

Are Orthopaedic Clinical Trials Linguistically and Culturally Diverse? A Systematic Review.

Underrepresentation and misrepresentation of historically underrepresented populations in randomized controlled trials (RCTs) may have implications for the validity of research results and their application for diverse populations. To evaluate the representation of historically linguistically, racially, and ethnically underrepresented participants in orthopaedic randomized controlled trials (RCTs) and to assess the use of translated and culturally adapted patient reported outcome measures (PROMs). Separate and comprehensive literature searches of PubMed, Web of Science, and Embase databases were performed to identify RCTs utilizing PROMs between the years 2012 - 2022 among the top five highest 5-year impact factor orthopaedic journals according to the 2021 Journal Citation Reports database. The primary outcomes of interest included reporting of linguistic, racial and ethnic demographic characteristics of trial participants and the utilization of translated PROMs. The methodological quality of each clinical trial was assessed using the Jadad Criteria. 230 RCTs met inclusion criteria. The language of participants was reported in 14% of trials and in 17% of trials when searching both the published text and clinical trial registration information. In addition, race and/or ethnicity was reported in 11% of trials, and the use of translated PROMs was reported in 7% of trials. Among the six multinational studies, none reported the language of the study population nor the use of translated PROMs. Notably, four studies (2%) reported utilizing culturally adapted PROMs. The average Jadad score was 3.07. Participant language, race, and ethnicity are infrequently reported in orthopaedic clinical trials, potentially limiting the application and interpretation of study results. Similarly, the linguistic and cultural adaptation of PROMs utilized are often not reported, which also limits interpretations of the validity and generalizability of orthopedic study results. Researchers and journals should promote standard reporting of demographic data and methods of PROM adaptation to ensure results are generalizable to diverse patient populations. III.

Systematic Review of Survival Outcomes of Pregnancy-Associated Breast Cancer in Asian Countries.

Pregnancy-associated breast cancer (PABC) is a rare type of gestational cancer. It poses a significant challenge in diagnosis and management, especially in Asian countries with limited resources. We carried out a systematic literature review and narrative synthesis to identify survival outcomes for women with PABC in Asia. We searched MEDLINE, PubMed, Cochrane Library and the reference lists of the included English language articles for those conducted between January 2010 and August 2022. The search terms were pregnancy-associated breast cancer, breast cancer AND pregnancy, survival of PABC and prognosis of PABC patients. PABC is defined as breast cancer diagnosed either during pregnancy or 1 year-5 years postpartum. This review included observational studies conducted in Asian countries. The final 11 articles met the selection criteria and were analysed. Five of the studies had high quality methods as assessed using the Joanna Briggs Institute (JBI) checklist. We reported study design, year of diagnosis, country, definition of PABC, control group, age of participants, median follow-up time, survival outcomes and pregnancy as prognostic factors. Only five studies reported that PABC patients had a poor overall or disease-free survival rate compared to the control. Pregnancy was a significant independent prognostic factor of breast cancer in only two studies. This review highlights that pregnancy has an unconfirmed association with breast cancer survival in Asia. Most studies that found a non-significant association had small samples, thus there is a need for large-scale multinational epidemiological studies in Asia to establish the survival outcomes in PABC patients.

Landscape review of active vaccine safety surveillance activities for COVID-19 vaccines globally

BackgroundEvidence of COVID-19 vaccine safety relied upon the global vaccine monitoring infrastructure due to shortened clinical development timelines and emergency use licensure. Differences in AVSS capacity between high-income countries (HICs) versus low- and middle-income countries (LMICs) were known prior to the pandemic. ObjectiveTo assess the global landscape of COVID-19 vaccine AVSS activities to identify gaps in safety evidence generation across vaccine products and populations with a focus on LMICs. MethodsA cross-sectional survey was conducted in January 2022 on AVSS activities evaluating adverse events following immunization (AEFI). Data collected included country, targeted population, COVID-19 vaccine product(s), design of surveillance/monitoring activities or study, and AEFIs to be monitored.To supplement these findings, we conducted a literature review of COVID-19 vaccine safety activities published in PubMed through January 2023. Observational activities assessing AEFI, specifically adverse events of special interest (AESI), following routine use of COVID-19 vaccines in medical practice were included; systematic reviews, benefit/risk assessments, clinical trials, and case reports/series were excluded. ResultsThe survey, completed by 34 respondents and compiled with reviews of 7 publicly available Risk Management Plans from five vaccine manufacturers, identified 79 monitoring activities in HICs, 24 in LMICs, and 9 in multiple regions. Most activities in LMICs were planned cohort event monitoring (CEM) studies (n = 18); two multi-national hospital-based sentinel surveillance studies for AESI were ongoing. Activities in LMICs evaluated multiple COVID-19 vaccine products simultaneously and were sponsored by health authorities. The literature review identified 1245 unique citations, of which 379 met inclusion criteria. The majority evaluated vaccines primarily used in high-income countries: Pfizer BioNTech (Comirnaty; n = 303), Moderna (mRNA-1273; n = 164), AstraZeneca (AZD1222; n = 126), and Janssen (Ad26.COV2.S); n = 62); 14 citations assessed vaccines used exclusively in LMICs: Sinovac (CoronaVac), Beijing CNBG (BBIBP-Corv), Bharat (Covaxin), SII (Covashield), and Gamaleya (Gam-Covid-Vac) vaccines. ConclusionsRobust safety evidence for input into benefit/risk assessments is likely unavailable for most COVID-19 vaccines used primarily in LMICs due to emphasis on cohort event monitoring methods. Goals for equitable vaccine access should be coupled with investment and support for building infrastructure and capacity for safety evidence generation to inform policy and regulatory decisions at local levels.

The use of positive deviance approach to improve health service delivery and quality of care: a scoping review

BackgroundQuality has been a persistent challenge in the healthcare system, particularly in resource-limited settings. As a result, the utilization of innovative approaches is required to help countries in their efforts to enhance the quality of healthcare. The positive deviance (PD) approach is an innovative approach that can be utilized to improve healthcare quality. The approach assumes that solutions to problems are already available within the community and identifying and sharing those solutions can help others to resolve existing issues. Therefore, this scoping review aimed to synthesize the evidence regarding the use of the PD approach in healthcare system service delivery and quality improvement programs.MethodsArticles were retrieved from six international databases. The last date for article search was June 02, 2023, and no date restriction was applied. All articles were assessed for inclusion through a title and/or abstract read. Then, articles that passed the title and abstract review were screened by reading their full texts. In case of duplication, only the full-text published articles were retained. A descriptive mapping and evidence synthesis was done to present data with the guide of the Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for Scoping Reviews checklist and the results are presented in text, table, and figure formats.ResultsA total of 125 articles were included in this scoping review. More than half, 66 (52.8%), of the articles were from the United States, 11(8.8%) from multinational studies, 10 (8%) from Canada, 8 (6.4%) from the United Kingdom and the remaining, 30 (24%) are from other nations around the world. The scoping review indicates that several types of study designs can be applied in utilizing the PD approach for healthcare service and quality improvement programs. However, although validated performance measures are utilized to identify positive deviants (PDs) in many of the articles, some of the selection criteria utilized by authors lack clarity and are subject to potential bias. In addition, several limitations have been mentioned in the articles including issues in operationalizing PD, focus on leaders and senior managers and limited staff involvement, bias, lack of comparison, limited setting, and issues in generalizability/transferability of results from prospects perspective. Nevertheless, the limitations identified are potentially manageable and can be contextually resolved depending on the nature of the study. Furthermore, PD has been successfully employed in healthcare service and quality improvement programs including in increasing surgical care quality, hand hygiene practice, and reducing healthcare-associated infections.ConclusionThe scoping review findings have indicated that healthcare systems have been able to enhance quality, reduce errors, and improve patient outcomes by identifying lessons from those who exhibit exceptional practices and implementing successful strategies in their practice. All the outcomes of PD-based research, however, are dependent on the first step of identifying true PDs. Hence, it is critical that PDs are identified using objective and validated measures of performance as failure to identify true PDs can subsequently lead to failure in identifying best practices for learning and dissemination to other contextually similar settings.

Ocean economic and cultural benefit perceptions as stakeholders' constraints for supporting conservation policies: A multi-national investigation

Given the vastness and interconnectedness of the ocean, marine conservation requires international treaties, especially after the High Seas Treaty was signed. However, most international marine conservation treaties do not have enforcement mechanisms and leave the fulfillment of obligations to the States’ responsibility. As States’ monitoring, managing, and enforcing capacity is limited, including stakeholders in policy-making and -implementing processes is crucial. Although some multi-national studies have been conducted to examine predictors of stakeholders’ support for conservation management and valuations of ecosystem services, few have focused on how their perceived most crucial economic and cultural benefits of their countries’ oceans are associated with their support level for policies focused on ocean preservation. Thus, the current study aims to fill this gap by employing the Bayesian Mindsponge Framework (BMF) analytics on a dataset of 709 stakeholders from 42 countries, a part of the MaCoBioS project funded by the European Commission H2020. We found that stakeholders’ considerations of the ocean’s provisioning (or economic) and cultural ecosystem services as their countries’ most vital benefits are generally negatively associated with the policy support level. Regarding economic aspects, stakeholders considering transportation and shipping, renewable energy generation, and oil and gas provision as the most crucial benefits their countries’ oceans provide tend to give less support for policies focusing on ocean preservation. For cultural aspects, perceiving recreation and tourism, aesthetic pleasure, mental health and well-being support, and sense of identity provision as the most important benefits provided by the country’s ocean are negatively associated with the policy support level. These findings provide preliminary evidence on the stakeholders’ psychological constraints to support marine conservation-focused policies, which can be insights that might explain why international treaties about environmental and maritime issues mostly failed to produce their intended effects and warn of the risks and challenges to enacting marine protection policies in the high seas effectively. Recommendations for improving the effective management of multi-use marine space and building the eco-surplus among stakeholders are also provided to reduce the perceived competing interests among stakeholders.

Assessing the Effects and Challenges of Total Hip Arthroplasty before Pregnancy and Childbirth: A Systematic Review.

Total hip arthroplasty is indubitably one of the most performed operations worldwide. On the other hand, especially in the western world, the average age that women get pregnant has raised confoundedly. Consequently, a steadily increasing number of women become pregnant after they had hip arthroplasty surgery, with copious potential implications. The amount of knowledge on this particular field is considered inadequate in the existing literature. This paper aims to augment clinicians understanding surrounding this topic. A systematic literature review was conducted in accordance with the PRISMA guidelines. Papers from various computerized databases were scrutinized. Article selection was carried out by three authors independently employing specific pre-determined inclusion and exclusion criteria, while disagreements were elucidated with the contribution of other authors. A patently limited number of research articles were detected from our rigorous literature review, with only 12 papers meeting the inclusion criteria. The vast majority of studies were small-scale and examined confined population groups. Most studies had been performed in Finland, utilizing data from nationwide registries. Women with previous history of total hip arthroplasty feature increased rates of c-section delivery, although vaginal labor can be attempted with certain precautions. Hip implants' survival does not appear to be affected from gestation, which is predominately well-tolerated from these women. Metal ion circulation in mothers' blood has not been proven to trigger substantial complications concerning either mothers or offspring. It can be considered safe for women with such medical history to get pregnant; however, further multinational studies and pertinent research on this field are vital to attain more solid inferences.

The outcome in pediatric acute myeloblastic leukemia; results of the first-line treatment and contribution of hematopoietic stem cell transplantation to survival of relapsed patients.

To analyze the long-term outcome of pediatric patients with acute myeloblastic leukemia. Data from 69 patients 0-18 years of age diagnosed between December 2001 and October 2019 were analyzed in April 2023. Patients received MRC-AML10 chemotherapy (2ADE+MACE+MidAC). No maintenance chemotherapy or preventive cranial radiotherapy was administered. Twelve patients with Down syndrome and 15 patients with promyelocytic leukemia were in the cohort. Patients with Down syndrome received reduced chemotherapy (cumulative anthracycline 420 mg/m2, cytarabine 3.4 g/m2, etoposide 1400 mg/m2). ATRA was added to chemotherapy in promyelocytic leukemia. Four patients (5.8%) died in the induction (two typhlitis, one intracranial hemorrhage, and one resistant disease). The complete remission rate of 66 patients was 87.8%. There was one death due to cardiotoxicity. Total infection-related deaths were 7.2%. Seven patients with high-risk criteria and one with resistant disease underwent hematopoietic stem cell transplantation (HSCT) following the first-line treatment. All seven patients in remission were alive and disease-free. The relapse rate was 34.4% (n = 21). Four patients developing marrow relapse were disease-free in the second remission after salvage and maintenance chemotherapy. Thirteen patients (18.84%) underwent HSCT in the second remission and 8 are alive and disease-free. The mean follow-up period of patients from diagnosis was 185 ± 13 months. Thirty-four patients (49.2%) were alive and disease-free in the first remission whereas another two patients in the first remission developed secondary malignancy. In good, standard, and poor risk groups, event-free survival (EFS) rates were 68.2%, 52.9%, and 10%, and overall survival (OS) rates were 86.4%, 79.4%, and 20%, respectively. Fifteen years of EFS and OS of the whole cohort were 49.3% and 69.6%, respectively. When compared with national data and multicenter studies of developed countries, survival rates were acceptable.

Incident allergic diseases in post-COVID-19 condition: multinational cohort studies from South Korea, Japan and the UK

As mounting evidence suggests a higher incidence of adverse consequences, such as disruption of the immune system, among patients with a history of COVID-19, we aimed to investigate post-COVID-19 conditions on a comprehensive set of allergic diseases including asthma, allergic rhinitis, atopic dermatitis, and food allergy. We used nationwide claims-based cohorts in South Korea (K-CoV-N; n = 836,164; main cohort) and Japan (JMDC; n = 2,541,021; replication cohort A) and the UK Biobank cohort (UKB; n = 325,843; replication cohort B) after 1:5 propensity score matching. Among the 836,164 individuals in the main cohort (mean age, 50.25 years [SD, 13.86]; 372,914 [44.6%] women), 147,824 were infected with SARS-CoV-2 during the follow-up period (2020−2021). The risk of developing allergic diseases, beyond the first 30 days of diagnosis of COVID-19, significantly increased (HR, 1.20; 95% CI, 1.13−1.27), notably in asthma (HR, 2.25; 95% CI, 1.80−2.83) and allergic rhinitis (HR, 1.23; 95% CI, 1.15−1.32). This risk gradually decreased over time, but it persisted throughout the follow-up period (≥6 months). In addition, the risk increased with increasing severity of COVID-19. Notably, COVID-19 vaccination of at least two doses had a protective effect against subsequent allergic diseases (HR, 0.81; 95% CI, 0.68−0.96). Similar findings were reported in the replication cohorts A and B. Although the potential for misclassification of pre-existing allergic conditions as incident diseases remains a limitation, ethnic diversity for evidence of incident allergic diseases in post-COVID-19 condition has been validated by utilizing multinational and independent population-based cohorts.

Cost‐effectiveness of maribavir versus conventional antiviral therapies for post‐transplant refractory cytomegalovirus infection with or without genotypic resistance: A US perspective

AbstractThis study evaluated the cost‐effectiveness of maribavir versus investigator‐assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for post‐transplant refractory cytomegalovirus (CMV) infection with or without resistance. A two‐stage Markov model was designed using data from the SOLSTICE trial (NCT02931539), real‐world multinational observational studies, and published literature. Stage 1 (0–78 weeks) comprised clinically significant CMV (csCMV), non‐clinically significant CMV (n‐csCMV), and dead states; stage 2 (78 weeks–lifetime) comprised alive and dead states. Total costs (2022 USD) and quality‐adjusted life years (QALYs) were estimated for the maribavir and IAT cohorts. An incremental cost‐effectiveness ratio was calculated to determine cost‐effectiveness against a willingness‐to‐pay threshold of $100 000/QALY. Compared with IAT, maribavir had lower costs ($139 751 vs $147 949) and greater QALYs (6.04 vs 5.83), making it cost‐saving and more cost‐effective. Maribavir had higher acquisition costs compared with IAT ($80 531 vs $65 285), but lower costs associated with administration/monitoring ($16 493 vs $27 563), adverse events (AEs) ($11 055 vs $16 114), hospitalization ($27 157 vs $33 905), and graft loss ($4516 vs $5081), thus making treatment with maribavir cost‐saving. Maribavir‐treated patients spent more time without CMV compared with IAT‐treated patients (0.85 years vs 0.68 years), leading to lower retreatment costs for maribavir (cost savings: −$42 970.80). Compared with IAT, maribavir was more cost‐effective for transplant recipients with refractory CMV, owing to better clinical efficacy and avoidance of high costs associated with administration, monitoring, AEs, and hospitalizations. These results can inform healthcare decision‐makers on the most effective use of their resources for post‐transplant refractory CMV treatment.

Prognostic factors for resected cases with gallbladder carcinoma: a systematic review and meta-analysis.

Current meta-analysis was performed to systematically evaluate the potential prognostic factors for overall survival among resected cases with gallbladder carcinoma. PubMed, EMBASE, and the Cochrane Library were systematically retrieved and hazard ratio (HR) and its 95% confidence interval were directly extracted from the original study or roughly estimated via Tierney's method. Standard Parmar modifications were used to determine pooled HRs. A total of 36 studies with 11502 cases were identified. Pooled results of univariate analyses indicated that advanced age (HR=1.02, P =0.00020), concurrent gallstone disease (HR=1.22, P =0.00200), elevated preoperative CA199 level (HR=1.93, P <0.00001), advanced T stage (HR=3.09, P <0.00001), lymph node metastasis (HR=2.78, P <0.00001), peri-neural invasion (HR=2.20, P <0.00001), lymph-vascular invasion (HR=2.37, P <0.00001), vascular invasion (HR=2.28, P <0.00001), poorly differentiated tumor (HR=3.22, P <0.00001), hepatic side tumor (HR=1.85, P <0.00001), proximal tumor (neck/cystic duct) (HR=1.78, P <0.00001), combined bile duct resection (HR=1.45, P <0.00001), and positive surgical margin (HR=2.90, P <0.00001) were well-established prognostic factors. Pathological subtypes ( P =0.53000) and postoperative adjuvant chemotherapy ( P =0.70000) were not prognostic factors. Pooled results of multivariate analyses indicated that age, gallstone disease, preoperative CA199, T stage, lymph node metastasis, peri-neural invasion, lymph-vascular invasion, tumor differentiation status, tumor location (peritoneal side vs hepatic side), surgical margin, combined bile duct resection, and postoperative adjuvant chemotherapy were independent prognostic factors. Various prognostic factors have been identified beyond the 8th AJCC staging system. By incorporating these factors into a prognostic model, a more individualized prognostication and treatment regime would be developed. Upcoming multinational studies are required for the further refine and validation.

Transformative capabilities of MedTech organizations in driving circularity in the healthcare industry: Insights from multiple cases

The healthcare industry's significant environmental impact has prompted the urgent need for sustainable practices. MedTech companies play a crucial role in advancing circularity within the sector by adopting sustainable approaches to product design, resource management, and waste reduction. This research aims to explore how MedTech companies initiate and drive transformation towards circular practices and the key factors influencing their successful transition. Using a qualitative approach, four multinational MedTech companies' case studies are conducted, employing semi-structured interviews with 33 managers and healthcare professionals. The results reveal a model grounded in dynamic capabilities, comprising three stages: sensing, seizing, and transforming, guided by adaptability and flexibility. The study extends the understanding of how MedTech companies can proactively respond to environmental challenges and embrace circular economy practices. Furthermore, the model offers practical implications for MedTech companies to foster sustainable practices, optimize resources, and enhance circularity in the healthcare industry.