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  1. Schmidt JA, Fensom GK, Rinaldi S, Scalbert A, Appleby PN, Achaintre D, et al.
    Int J Cancer, 2020 Feb 01;146(3):720-730.
    PMID: 30951192 DOI: 10.1002/ijc.32314
    Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR1SD ) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR1SD  = 0.77, 95% confidence interval 0.66-0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR1SD  = 0.72, 0.57-0.90), or lysophosphatidylcholines (OR1SD  = 0.81, 0.69-0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR1SD  = 0.77, 0.61-0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.
  2. Perez-Cornago A, Huybrechts I, Appleby PN, Schmidt JA, Crowe FL, Overvad K, et al.
    Int J Cancer, 2020 Jan 01;146(1):44-57.
    PMID: 30807653 DOI: 10.1002/ijc.32233
    The associations of individual dietary fatty acids with prostate cancer risk have not been examined comprehensively. We examined the prospective association of individual dietary fatty acids with prostate cancer risk overall, by tumor subtypes, and prostate cancer death. 142,239 men from the European Prospective Investigation into Cancer and Nutrition who were free from cancer at recruitment were included. Dietary intakes of individual fatty acids were estimated using center-specific validated dietary questionnaires at baseline and calibrated with 24-h recalls. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average follow-up of 13.9 years, 7,036 prostate cancer cases and 936 prostate cancer deaths were ascertained. Intakes of individual fatty acids were not related to overall prostate cancer risk. There was evidence of heterogeneity in the association of some short chain saturated fatty acids with prostate cancer risk by tumor stage (pheterogeneity
  3. Yoshino T, Cervantes A, Bando H, Martinelli E, Oki E, Xu RH, et al.
    ESMO Open, 2023 Jun;8(3):101558.
    PMID: 37236086 DOI: 10.1016/j.esmoop.2023.101558
    The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer (mCRC), published in late 2022, were adapted in December 2022, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with mCRC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with mCRC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian countries. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with mCRC across the different countries of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation, coupled with a disparity in the drug approvals and reimbursement strategies, between the different countries.
  4. Snider CJ, Boualam L, Tallis G, Takashima Y, Abeyasinghe R, Lo YR, et al.
    Vaccine, 2023 Apr 06;41 Suppl 1:A58-A69.
    PMID: 35337673 DOI: 10.1016/j.vaccine.2022.02.022
    Concurrent outbreaks of circulating vaccine-derived poliovirus serotypes 1 and 2 (cVDPV1, cVDPV2) were confirmed in the Republic of the Philippines in September 2019 and were subsequently confirmed in Malaysia by early 2020. There is continuous population subgroup movement in specific geographies between the two countries. Outbreak response efforts focused on sequential supplemental immunization activities with monovalent Sabin strain oral poliovirus vaccine type 2 (mOPV2) and bivalent oral poliovirus vaccines (bOPV, containing Sabin strain types 1 and 3) as well as activities to enhance poliovirus surveillance sensitivity to detect virus circulation. A total of six cVDPV1 cases, 13 cVDPV2 cases, and one immunodeficiency-associated vaccine-derived poliovirus type 2 case were detected, and there were 35 cVDPV1 and 31 cVDPV2 isolates from environmental surveillance sewage collection sites. No further cVDPV1 or cVDPV2 have been detected in either country since March 2020. Response efforts in both countries encountered challenges, particularly those caused by the global COVID-19 pandemic. Important lessons were identified and could be useful for other countries that experience outbreaks of concurrent cVDPV serotypes.
  5. Washif JA, Pyne DB, Sandbakk Ø, Trabelsi K, Aziz AR, Beaven CM, et al.
    Biol Sport, 2022 Oct;39(4):1103-1115.
    PMID: 36247962 DOI: 10.5114/biolsport.2022.117576
    Ramadan intermittent fasting during the COVID-19 lockdown (RIFL) may present unique demands. We investigated training practices (i.e., training load and training times) of athletes, using pre-defined survey criteria/questions, during the 'first' COVID-19 lockdown, comparing RIFL to lockdown-alone (LD) in Muslim athletes. Specifically, a within-subject, survey-based study saw athletes (n = 5,529; from 110 countries/territories) training practices (comparing RIFL to LD) explored by comparative variables of: sex; age; continent; athlete classification (e.g., world-class); sport classification (e.g., endurance); athlete status (e.g., professional); and level of training knowledge and beliefs/attitudes (ranked as: good/moderate/poor). During RIFL (compared to LD), athlete perceptions (ranges presented given variety of comparative variables) of their training load decreased (46-62%), were maintained (31-48%) or increased (2-13%). Decreases (≥ 5%, p < 0.05) affected more athletes aged 30-39 years than those 18-29 years (60 vs 55%); more national than international athletes (59 vs 51%); more team sports than precision sports (59 vs 46%); more North American than European athletes (62 vs 53%); more semi-professional than professional athletes (60 vs 54%); more athletes who rated their beliefs/attitudes 'good' compared to 'poor' and 'moderate' (61 vs 54 and 53%, respectively); and more athletes with 'moderate' than 'poor' knowledge (58 vs 53%). During RIFL, athletes had different strategies for training times, with 13-29% training twice a day (i.e., afternoon and night), 12-26% at night only, and 18-36% in the afternoon only, with ranges depending on the comparative variables. Training loads and activities were altered negatively during RIFL compared to LD. It would be prudent for decision-makers responsible for RIFL athletes to develop programs to support athletes during such challenges.
  6. Hassoun-Kheir N, Guedes M, Arieti F, Pezzani MD, Gladstone BP, Robotham JV, et al.
    Euro Surveill, 2024 Nov;29(47).
    PMID: 39574390 DOI: 10.2807/1560-7917.ES.2024.29.47.2400212
    To reduce antimicrobial resistance (AMR), pathogen-specific AMR burden data are crucial to guide target selection for research and development of vaccines and monoclonal antibodies (mAbs). We identified knowledge gaps through previously conducted systematic reviews, which informed a Delphi expert consultation on future AMR research priorities and harmonisation strategies to support data-driven decision-making. Consensus (≥80% agreement) on importance and feasibility of research topics was achieved in two rounds, involving 24 of 39 and 19 of 24 invited experts, respectively. Priority pathogens and resistance profiles for future research were identified: third generation cephalosporin-resistant Klebsiella pneumoniae and Escherichia coli, for bloodstream and urinary tract infections, respectively, and meticillin-resistant Staphylococcus aureus for surgical-site infections. Prioritised high-risk populations included surgical, haemato-oncological and transplant patients. Mortality and resource use were prioritised as health-economic outcomes. The importance of age-stratified data and inclusion of a non-infected comparator group were highlighted. This agenda provides guidance for future research to fill knowledge gaps and support data-driven selection of target pathogens and populations for new preventive and treatment strategies, specifically vaccines and mAbs, to effectively address the AMR burden in Europe. These research priorities are also relevant to improve the evidence base for future AMR burden estimates.
  7. Marwali EM, Kekalih A, Yuliarto S, Wati DK, Rayhan M, Valerie IC, et al.
    BMJ Paediatr Open, 2022 Oct;6(1).
    PMID: 36645791 DOI: 10.1136/bmjpo-2022-001657
    BACKGROUND: The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.

    METHODS: The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.

    RESULTS: A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).

    CONCLUSION: Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities.

  8. Işık EB, Brazas MD, Schwartz R, Gaeta B, Palagi PM, van Gelder CWG, et al.
    Nat Biotechnol, 2023 Aug;41(8):1171-1174.
    PMID: 37568018 DOI: 10.1038/s41587-023-01891-9
  9. Godman B, Haque M, Islam S, Iqbal S, Urmi UL, Kamal ZM, et al.
    Front Public Health, 2020;8:585832.
    PMID: 33381485 DOI: 10.3389/fpubh.2020.585832
    Background: Countries have introduced a variety of measures to prevent and treat COVID-19 with medicines and personal protective equipment (PPE), with some countries adopting preventative strategies earlier than others. However, there has been considerable controversy surrounding some treatments. This includes hydroxychloroquine where the initial hype and misinformation lead to shortages, price rises and suicides. Price rises and shortages have also been seen for PPE. Such activities can have catastrophic effects on patients where there are high co-payment levels and issues of affordability. Consequently, there is a need to investigate this further. Objective: Assess changes in the availability, utilization and prices of relevant medicines and PPE during the pandemic among a range of Asian countries. Our approach: Narrative literature review combined with interviews among community pharmacists to assess changes in consumption, prices and shortages of medicines and PPE from the beginning of March 2020 until end of May 2020. In addition, suggestions on ways to reduce misinformation. Results: 308 pharmacists took part from five Asian countries. There was an appreciable increase in the utilization of antimicrobials in Pakistan (in over 88% of pharmacies), with lower increases or no change in Bangladesh, India, Malaysia and Vietnam. Encouragingly, there was increased use of vitamins/immune boosters and PPE across the countries, as well as limited price rises for antimicrobials in India, Malaysia and Vietnam, although greater price rises seen for analgesics and vitamin C/immune boosters. Appreciable price increases were also seen for PPE across some countries. Conclusion: Encouraging to see increases in utilization of vitamins/immune boosters and PPE. However, increases in the utilization and prices of antimicrobials is a concern that needs addressing alongside misinformation and any unintended consequences from the pandemic. Community pharmacists can play a key role in providing evidence-based advice, helping to moderate prices, as well as helping address some of the unintended consequences of the pandemic.
  10. Quetglas-Llabrés MM, Quispe C, Herrera-Bravo J, Catarino MD, Pereira OR, Cardoso SM, et al.
    Oxid Med Cell Longev, 2022;2022:8615242.
    PMID: 35509838 DOI: 10.1155/2022/8615242
    Bergapten (BP) or 5-methoxypsoralen (5-MOP) is a furocoumarin compound mainly found in bergamot essential oil but also in other citrus essential oils and grapefruit juice. This compound presents antibacterial, anti-inflammatory, hypolipemic, and anticancer effects and is successfully used as a photosensitizing agent. The present review focuses on the research evidence related to the therapeutic properties of bergapten collected in recent years. Many preclinical and in vitro studies have been evidenced the therapeutic action of BP; however, few clinical trials have been carried out to evaluate its efficacy. These clinical trials with BP are mainly focused on patients suffering from skin disorders such as psoriasis or vitiligo. In these trials, the administration of BP (oral or topical) combined with UV irradiation induces relevant lesion clearance rates. In addition, beneficial effects of bergamot extract were also observed in patients with altered serum lipid profiles and in people with nonalcoholic fatty liver. On the contrary, there are no clinical trials that investigate the possible effects on cancer. Although the bioavailability of BP is lower than that of its 8-methoxypsoralen (8-MOP) isomer, it has fewer side effects allowing higher concentrations to be administered. In conclusion, although the use of BP has therapeutic applications on skin disorders as a sensitizing agent and as components of bergamot extract as hypolipemic therapy, more trials are necessary to define the doses and treatment guidelines and its usefulness against other pathologies such as cancer or bacterial infections.
  11. Karupaiah T, Rahman SMM, Zhang J, Kumar N, Jamiyan B, Pokharel RK, et al.
    JMIR Pediatr Parent, 2024 Dec 04;7:e63410.
    PMID: 39630493 DOI: 10.2196/63410
    BACKGROUND: Rising childhood obesity rates in Asia are adding risk for the future adult burden of obesity and noncommunicable diseases. Weak policies across most Asian countries enable unrestricted marketing of obesogenic foods and beverages to children. Television is the common medium for food marketing to reach this audience.

    OBJECTIVE: This study aimed to assess the extent and nature of television food and nonalcoholic beverage marketing in 9 Asian countries (Bangladesh, China, India, Malaysia, Mongolia, Nepal, the Philippines, Sri Lanka, and Vietnam) with capacity building support from the International Network for Food and Obesity/Non-Communicable Disease Research, Monitoring and Action Support, who enabled harmonization of data collection method and content analyses.

    METHODS: Advertised foods were categorized as permitted or not permitted based on the nutrient profile models established by the World Health Organization regional offices for South-East Asia (SEARO) and the World Health Organization regional offices for Western Pacific (WPRO). Overall rates of food advertisements (advertisements per hour per channel) and persuasive strategy use were analyzed along with comparisons between children's peak viewing time (PVT) and non-PVT.

    RESULTS: Cross-country comparisons, irrespective of country income level, indicated that not permitted food advertising dominated children's popular television channels, especially during PVT with rates as per WPRO or SEARO criteria ranging from 2.40/2.29 (Malaysia) to 9.70/9.41 advertisements per hour per channel (the Philippines). Persuasive strategy rates were also comparatively higher during PVT. Sugar-sweetened beverages, sugar-containing solid foods, and high salt- and fat-containing snacks and fast foods were frequently advertised. Evaluation of the application of WPRO and SEARO nutrient profile models identified inconsistencies due to regional taste and cuisine variations across Asia.

    CONCLUSIONS: This study clearly showed that unhealthy food marketing through popular children's television channels is widely occurring in Asia and is a clear breach of child rights. Evidence outcomes will benefit advocacy toward stronger policy regulations to control unhealthy food marketing and strengthen strategies to promote a healthier food environment for Asia's children.

  12. Mohamed K, Rzymski P, Islam MS, Makuku R, Mushtaq A, Khan A, et al.
    J Med Virol, 2022 Apr;94(4):1336-1349.
    PMID: 34845731 DOI: 10.1002/jmv.27487
    The entire world has been suffering from the coronavirus disease 2019 (COVID-19) pandemic since March 11, 2020. More than a year later, the COVID-19 vaccination brought hope to control this viral pandemic. Here, we review the unknowns of the COVID-19 vaccination, such as its longevity, asymptomatic spread, long-term side effects, and its efficacy on immunocompromised patients. In addition, we discuss challenges associated with the COVID-19 vaccination, such as the global access and distribution of vaccine doses, adherence to hygiene guidelines after vaccination, the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, and vaccine resistance. Despite all these challenges and the fact that the end of the COVID-19 pandemic is still unclear, vaccines have brought great hope for the world, with several reports indicating a significant decline in the risk of COVID19-related infection and hospitalizations.
  13. Dian ND, Muhammad AB, Azman EN, Eddie NA, Azmi NI, Yee VCT, et al.
    Am J Trop Med Hyg, 2023 Nov 01;109(5):1081-1085.
    PMID: 37748768 DOI: 10.4269/ajtmh.23-0184
    Malaysia has maintained zero cases of indigenous human malaria since 2018. However, zoonotic malaria is still prevalent in underdeveloped areas and hard-to-reach populations. This study aimed to determine the prevalence of malaria among remote indigenous communities in Peninsular Malaysia. A cross-sectional survey was conducted in six settlements in Kelantan state, from June to October 2019. Blood samples were tested for malaria using microscopy and nested polymerase chain reaction (nPCR) targeting the Plasmodium cytochrome c oxidase subunit III (cox3) gene. Of the 1,954 individuals who appeared healthy, no malaria parasites were found using microscopy. However, nPCR revealed seven cases of Plasmodium knowlesi mono-infection (0.4%), and six out of seven infections were in the group of 19 to 40 years old (P = 0.026). No human malaria species were detected by nPCR. Analysis of the DNA sequences also showed high similarity that reflects common ancestry to other P. knowlesi isolates. These findings indicate low submicroscopic P. knowlesi infections among indigenous communities in Malaysia, requiring PCR-based surveillance to support malaria control activities in the country.
  14. Bennett A, Basurto X, Virdin J, Lin X, Betances SJ, Smith MD, et al.
    Ambio, 2021 May;50(5):981-989.
    PMID: 33454882 DOI: 10.1007/s13280-020-01451-4
    The international development community is off-track from meeting targets for alleviating global malnutrition. Meanwhile, there is growing consensus across scientific disciplines that fish plays a crucial role in food and nutrition security. However, this 'fish as food' perspective has yet to translate into policy and development funding priorities. We argue that the traditional framing of fish as a natural resource emphasizes economic development and biodiversity conservation objectives, whereas situating fish within a food systems perspective can lead to innovative policies and investments that promote nutrition-sensitive and socially equitable capture fisheries and aquaculture. This paper highlights four pillars of research needs and policy directions toward this end. Ultimately, recognizing and working to enhance the role of fish in alleviating hunger and malnutrition can provide an additional long-term development incentive, beyond revenue generation and biodiversity conservation, for governments, international development organizations, and society more broadly to invest in the sustainability of capture fisheries and aquaculture.
  15. Hunter EC, Fine E, Black K, Henriks J, Tofail F, Morroni C, et al.
    Bull World Health Organ, 2024 Dec 01;102(12):861-872.
    PMID: 39611192 DOI: 10.2471/BLT.23.291162
    OBJECTIVE: To refine a standard questionnaire on sexual practices, experiences and health-related outcomes to improve its cross-cultural applicability and interpretability. We aimed to explore participants' willingness and ability to answer the draft questionnaire items, and determine whether items were interpreted as intended across diverse geographic and cultural environments.

    METHODS: We conducted cognitive interviews (n = 645) in three iterative waves of data collection across 19 countries during March 2022-March 2023, with participants of diverse sex, gender, age and geography. Interviewers used a semi-structured field guide to elicit narratives from participants about their questionnaire item interpretation and response processes. Local study teams completed data analysis frameworks, and we conducted joint analysis meetings between data collection waves to identify question failures.

    FINDINGS: Overall, we observed that participants were willing to respond to even the most sensitive questionnaire items on sexual biography and practices. We identified issues with the original questionnaire that (i) affected the willingness (acceptability) and ability (knowledge barriers) of participants to respond fully; and/or (ii) prevented participants from interpreting the questions as intended, including poor wording (source question error), cultural portability and very rarely translation error. Our revisions included adjusting item order and wording, adding preambles and implementation guidance, and removing items with limited cultural portability.

    CONCLUSION: We have demonstrated that a questionnaire exploring sexual practices, experiences and health-related outcomes can be comprehensible and acceptable by the general population in diverse global contexts, and have highlighted the importance of rigorous processes for the translation and cognitive testing of such a questionnaire.

  16. Nasreldein A, Asyraf W, Nguyen TN, Martins S, Lioutas VA, Elbassiouny A, et al.
    Int J Stroke, 2025 Feb 03.
    PMID: 39773209 DOI: 10.1177/17474930251314395
    BACKGROUND: Mechanical thrombectomy (MT) is the standard of care for eligible acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) since 2015.

    AIM: Our aim was to determine the key challenges for MT implementation and access worldwide.

    METHODS: We conducted an international online survey consisting of 37 questions, distributed through the World Stroke Organization network and as invited by co-authors between December 2022 and March 2023. The survey included a preamble outlining its purpose, questions on respondent demographics, imaging availability, MT service availability, MT selection criteria, barriers to MT, and training status in each country.

    RESULTS: We received 526 responses from 89 countries distributed across 7 continents. One hundred and sixteen (22.1%) respondents did not have available MT service, 43 (8.2%) had available MT only during working hours, 362 (68.8%) had 24/7 MT availability. Regarding neuroimaging protocols, 13.5% used non-contrast computed tomography (NCCT) only, 40.1% used NCCT/CT angiography, 37.5% used NCCT/CT angiography/CT perfusion), 0.4% used magnetic resonance imaging (MRI) only, and 7.8% used MRI/MR angiography. The most common reasons for not receiving MT were cost, late presentation, and lack of availability of qualified neurointerventional services within reasonable distance. There were 59.1% of respondents who reported having a well-structured MT training program. Lack of qualified trainers, financial support, support from higher authorities, and lack of collaboration between departments were the most common obstacles against developing a training program.

    CONCLUSION: Our study highlights significant variations in MT availability, accessibility, patient selection criteria, and MT service training programs worldwide. Financial costs and a shortage of trained neurointerventionalists were the main challenges in low- and middle-income countries.

  17. Cappellini MD, Viprakasit V, Georgiev P, Coates TD, Origa R, Khelif A, et al.
    Lancet Haematol, 2025 Feb 10.
    PMID: 39947215 DOI: 10.1016/S2352-3026(24)00376-4
    BACKGROUND: Treatments to reduce red blood cell (RBC) transfusion burden among patients with transfusion-dependent β-thalassaemia remain limited. Here, we report long-term follow-up data from the phase 3 BELIEVE trial of luspatercept for transfusion-dependent β-thalassaemia.

    METHODS: BELIEVE was a phase 3, randomised, double-blind, placebo-controlled study performed at 65 sites in 15 countries. The trial included adults with transfusion-dependent β-thalassaemia or haemoglobin E/β-thalassaemia and Eastern Cooperative Oncology Group score of 0-1. Patients were randomly assigned (2:1) using integrated response technology stratified by region to luspatercept (1·0-1·25 mg/kg) or placebo administered subcutaneously once every 21 days. After study unblinding, patients could receive luspatercept in the open-label extension phase (crossover allowed). The primary endpoint results (proportion of patients with reduction in transfusion burden of ≥33% and ≥2 RBC units during weeks 13-24) are described elsewhere; herein we present an update to the primary endpoint analysis consequent to late-reported transfusion events. We also report long-term efficacy (intention-to-treat population) and safety data (safety population) for patients followed up for approximately 3 years. This trial is registered on ClinicalTrials.gov (NCT02604433) and is completed.

    FINDINGS: Between May 2, 2016, and May 16, 2017, 336 patients were randomly assigned to luspatercept (n=224) or placebo (n=112). The median age of patients was 30 years (IQR 23-40); 195 (58%) were female and 141 (42%) male. As of Jan 5, 2021, the median duration of treatment in the luspatercept group was 153·6 weeks (IQR 81·0-171·0) and median study follow-up was 163·1 weeks (140·5-176·2). Due to the difference in treatment duration between the luspatercept and placebo groups, no comparative analyses between the two groups were performed after week 96. Patients in the luspatercept group showed a sustained reduction in RBC transfusion burden from baseline through week 192, with mean decreases of 6·2 RBC units (SD 5·7) during weeks 97-144 and 6·4 RBC units (4·3) during weeks 145-192. In the luspatercept group, a 33% or greater reduction in transfusion burden from baseline was observed in 173 (77%) patients over any 12-week interval and in 116 (52%) patients over any 24-week interval. The median total duration of 33% or greater transfusion burden reduction response during any period of at least 12 weeks was 586·0 days (IQR 264·0-1010·0). The most common grade 3 or worse treatment-emergent adverse events (TEAEs) among all patients who received luspatercept (n=315, including 92 patients who crossed over after study unblinding) were anaemia (nine [3%]), increased liver iron concentration (seven [2%]), and bone pain (seven [2%]); serious TEAEs occurred in 71 (23%) patients. No treatment-related deaths occurred in any group during the study.

    INTERPRETATION: These long-term results affirm luspatercept's efficacy in addressing key unmet needs of patients with transfusion-dependent β-thalassaemia with a manageable safety profile.

    FUNDING: Celgene and Acceleron Pharma.

  18. Srisurapanont M, Hong JP, Tian-Mei S, Hatim A, Liu CY, Udomratn P, et al.
    Asia Pac Psychiatry, 2013 Dec;5(4):259-67.
    PMID: 24038919 DOI: 10.1111/appy.12104
    The objective of this study was to investigate the clinical features of depression in Asian patients.
  19. Ong-Abdullah M, Ordway JM, Jiang N, Ooi SE, Kok SY, Sarpan N, et al.
    Nature, 2015 Sep 24;525(7570):533-7.
    PMID: 26352475 DOI: 10.1038/nature15365
    Somaclonal variation arises in plants and animals when differentiated somatic cells are induced into a pluripotent state, but the resulting clones differ from each other and from their parents. In agriculture, somaclonal variation has hindered the micropropagation of elite hybrids and genetically modified crops, but the mechanism responsible remains unknown. The oil palm fruit 'mantled' abnormality is a somaclonal variant arising from tissue culture that drastically reduces yield, and has largely halted efforts to clone elite hybrids for oil production. Widely regarded as an epigenetic phenomenon, 'mantling' has defied explanation, but here we identify the MANTLED locus using epigenome-wide association studies of the African oil palm Elaeis guineensis. DNA hypomethylation of a LINE retrotransposon related to rice Karma, in the intron of the homeotic gene DEFICIENS, is common to all mantled clones and is associated with alternative splicing and premature termination. Dense methylation near the Karma splice site (termed the Good Karma epiallele) predicts normal fruit set, whereas hypomethylation (the Bad Karma epiallele) predicts homeotic transformation, parthenocarpy and marked loss of yield. Loss of Karma methylation and of small RNA in tissue culture contributes to the origin of mantled, while restoration in spontaneous revertants accounts for non-Mendelian inheritance. The ability to predict and cull mantling at the plantlet stage will facilitate the introduction of higher performing clones and optimize environmentally sensitive land resources.
  20. Mollica MA, Mayer DK, Oeffinger KC, Kim Y, Buckenmaier SS, Sivaram S, et al.
    JCO Glob Oncol, 2020 09;6:1394-1411.
    PMID: 32955943 DOI: 10.1200/GO.20.00180
    PURPOSE: The purpose of this study was to describe follow-up care for breast and colorectal cancer survivors in countries with varying levels of resources and highlight challenges regarding posttreatment survivorship care.

    METHODS: We surveyed one key stakeholder from each of 27 countries with expertise in survivorship care on questions including the components/structure of follow-up care, delivery of treatment summaries and survivorship care plans, and involvement of primary care in survivorship. Descriptive analyses were performed to characterize results across countries and variations between the WHO income categories (low, middle, high). We also performed a qualitative content analysis of narratives related to survivorship care challenges to identify major themes.

    RESULTS: Seven low- or /lower-middle-income countries (LIC/LMIC), seven upper-middle-income countries (UMIC), and 13 high-income countries (HICs) were included in this study. Results indicate that 44.4% of countries with a National Cancer Control Plan currently address survivorship care. Additional findings indicate that HICs use guidelines more often than those in LICs/LMICs and UMICs. There was great variation among countries regardless of income level. Common challenges include issues with workforce, communication and care coordination, distance/transportation issues, psychosocial support, and lack of focus on follow-up care.

    CONCLUSION: This information can guide researchers, providers, and policy makers in efforts to improve the quality of survivorship care on a national and global basis. As the number of cancer survivors increases globally, countries will need to prioritize their long-term needs. Future efforts should focus on efforts to bridge oncology and primary care, building international partnerships, and implementation of guidelines.

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