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The clinical, laboratory, and radiological features at presentation of 16 children (<12 years) with severe acute respiratory syndrome (SARS) and pneumonia were compared with 32 age matched patients with community acquired pneumonia for determination of predictive factors that could allow early differentiation of the two conditions. A definitive contact history was the most important predictor for SARS. Raised serum lactate dehydrogenase concentration in the presence of low neutrophil count and serum creatine phosphokinase level at presentation also indicated an increased likelihood of SARS-coronavirus infection in young children. [ABSTRACT FROM AUTHOR]

Competing Interests: Conflict of interest: none declared.

Resistance to glucocorticoids (GC), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-offunction experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GC-resistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GC against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL.

Background: Interprofessional education (IPE) has the potential to shape students' collaboration perception and interprofessional identity but remains understudied. This study aims to understand the effects of the IPE program as a contextual trigger to promote collaboration perception change and interprofessional identity formation among healthcare professional students., Methods: Using concurrent triangulation mixed-methods, we examined the relationship between collaboration perception and interprofessional identity change among health profession students (N = 263), and explored their perspectives on how their IPE experiences influenced their perception and identity. Participants completed the Interdisciplinary Education Perception Scale and Extended Professional Identity Scale and responded to open-ended questions before and after the IPE intervention. Pearson's correlation, t-tests, regression (quantitative), and thematic analysis (qualitative) were conducted., Results: Teams with initially lower collaboration perception (M = 3.59) and lower interprofessional identity (M = 3.59) showed a significant increase in collaboration perception (M = 3.76, t = 2.63; p = .02) and interprofessional identity (M = 3.97, t = 4.86; p < .001) after participating in IPE. The positive relationship between collaboration perception and interprofessional identity strengthened after participating in IPE, as evident from the correlation (Time 1: r = .69; p < .001; Time 2: r = .79; p < .001). Furthermore, collaboration perception in Time 1 significantly predicted the variance in interprofessional identity at Time 2 (β = 0.347, p < .001). Qualitative findings indicated that 85.2% of students expressed that IPE played a role in promoting their interprofessional identity and collaboration attitudes., Conclusions: Incorporating the IPE program into the curriculum can effectively enhance students' collaboration perception and interprofessional identity, ultimately preparing them for collaborative practice in the healthcare system. By engaging students in interprofessional teamwork, communication, and joint decision-making processes, the IPE program provides a valuable context for students to develop a sense of belonging and commitment to interprofessional collaboration., (© 2024. The Author(s).)

Importance: Among patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate, a treatment sequence initiated with biosimilar disease-modifying antirheumatic drugs (DMARDs) provides better clinical efficacy compared with conventional synthetic DMARDs recommended by current treatment guidelines; but its cost-effectiveness evidence remains unclear., Objective: To evaluate the cost-effectiveness of the treatment sequence initiated with biosimilar DMARDs after failure with methotrexate vs leflunomide and inform formulary listing decisions., Design, Setting, and Participants: This economic evaluation's cost-effectiveness analysis was performed at a Hong Kong public institution using the Markov disease transition model to simulate the lifetime disease progression and cost for patients with RA, using monetary value in 2022. Scenario and sensitivity analyses were performed to test the internal validity of the modeling conclusion. Participants included patients diagnosed with RA from 2000 to 2021 who were retrieved retrospectively from local electronic medical records to generate model input parameters. Statistical analysis was performed from January 2023 to March 2024., Interventions: The model assesses 3 competing treatment sequences initiated with biosimilar infliximab (CT-P13), biosimilar adalimumab (ABP-501), and leflunomide; all used in combination with methotrexate., Main Outcomes and Measures: Lifetime health care cost and quality-adjusted life-years (QALYs) of the simulated cohort., Results: In total, 25 099 patients with RA were identified (mean [SD] age, 56 [17] years; 19 469 [72.7%] women). In the base-case analysis, the lifetime health care cost and QALYs for the treatment sequence initiated with leflunomide were US $154 632 and 14.82 QALYs, respectively; for biosimilar infliximab, they were US $152 326 and 15.35 QALYs, respectively; and for biosimilar adalimumab, they were US $145 419 and 15.55 QALYs, respectively. Both biosimilar sequences presented lower costs and greater QALYs than the leflunomide sequence. In the deterministic sensitivity analysis, the incremental cost-effectiveness ratio (US$/QALY) comparing biosimilar infliximab sequence vs leflunomide sequence and biosimilar adalimumab sequence vs leflunomide sequence ranged from -15 797 to -8615 and -9088 to 10 238, respectively, all below the predefined willingness-to-pay threshold (US $48 555/QALY gain). In the probabilistic sensitivity analysis, the probability of treatment sequence initiated with leflunomide, biosimilar infliximab, and biosmilar adalimumab being cost-effective out of 10 000 iterations was 0%, 9%, and 91%, respectively., Conclusions and Relevance: In this economic evaluation study, the treatment sequences initiated with biosimilar DMARDs were cost-effective compared with the treatment sequence initiated with leflunomide in managing patients with RA who experienced failure with the initial methotrexate treatment. These results suggest the need to update clinical treatment guidelines for initiating biosimilars immediately after the failure of methotrexate for patients with RA.

Objective: The evidence of thyroid dysfunction in the post-acute phase of SARS-CoV-2 infection is limited. This study aimed to evaluate the risk of incident thyroid dysfunction in the post-acute phase of COVID-19., Methods: This retrospective, propensity-score matched, population-based study included COVID-19 patients and non-COVID-19 individuals between January 2020 and March 2022, identified from the electronic medical records of the Hong Kong Hospital Authority. The cohort was followed up until the occurrence of outcomes, death, or 31 January 2023, whichever came first. Patients with COVID-19 were 1:1 matched to controls based on various variables. The primary outcome was a composite of thyroid dysfunction (hyperthyroidism, hypothyroidism, initiation of antithyroid drug or levothyroxine, and thyroiditis). Cox regression was employed to evaluate the risk of incident thyroid dysfunction during the post-acute phase., Results: A total of 84 034 COVID-19 survivors and 84 034 matched controls were identified. Upon a median follow-up of 303 days, there was no significant increase in the risk of diagnosed thyroid dysfunction in the post-acute phase of COVID-19 (hazard ratio [HR] 1.058, 95% confidence interval 0.979-1.144, P = .154). Regarding the secondary outcomes, patients with COVID-19 did not have increased risk of hyperthyroidism (HR 1.061, P = .345), hypothyroidism (HR 1.062, P = .255), initiation of antithyroid drug (HR 1.302, P = .070), initiation of levothyroxine (HR 1.086, P = .426), or thyroiditis (P = .252). Subgroup and sensitivity analyses were largely consistent with the main analyses., Conclusion: Our population-based cohort study provided important reassuring data that COVID-19 was unlikely to be associated with persistent effects on thyroid function., Competing Interests: Disclosure F.T.T.L has been supported by the RGC Postdoctoral Fellowship under the Hong Kong Research Grants Council. X.L has received research grants from the Health Bureau of the Government of the Hong Kong SAR, research and educational grants from Janssen and Pfizer; internal funding from University of Hong Kong; consultancy fee from Merck Sharp & Dohme, unrelated to this work. E.Y.F.W has received research grants from the Health Bureau of the Government of the Hong Kong SAR, and the Hong Kong Research Grants Council, outside the submitted work. C.S.L.C has received grants from the Health Bureau of the Hong Kong Government, Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, and Amgen; personal fee from Primevigilance Ltd.; outside the submitted work. E.W.Y.C reports honorarium from Hospital Authority, grants from Research Grants Council (RGC, Hong Kong), grants from Research Fund Secretariat of the Health Bureau, grants from National Natural Science Fund of China, grants from Wellcome Trust, grants from Bayer, grants from Bristol-Myers Squibb, grants from Pfizer, grants from Janssen, grants from Amgen, grants from Takeda, grants from Narcotics Division of the Security Bureau of HKSAR, outside the submitted work. C.K.H.W reports receipt of research funding from the EuroQoL Group Research Foundation, the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund; AstraZeneca and Boehringer Ingelheim, unrelated to this work. I.C.K.W reports research funding outside the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong RGC, and the Hong Kong Health and Medical Research Fund, National Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia, and also received speaker fees from Janssen and Medice in the previous 3 years. All other authors declare no competing interests., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Population-based epidemiological studies on post-acute phase coronavirus 2019 (COVID-19)-related fractures in older adults are lacking. This study aims to examine the risk of incident major osteoporotic fractures following SARS-CoV-2 infection among individuals aged ≥50, compared to individuals without COVID-19. It was a retrospective, propensity-score matched, population-based cohort study of COVID-19 patients and non-COVID individuals identified from the electronic database of the Hong Kong Hospital Authority from January 2020 to March 2022. The primary outcome was a composite of major osteoporotic fractures (hip, clinical vertebral, and upper limb). COVID-19 patients were 1:1 matched to controls using propensity-score according to age, sex, vaccination status, medical comorbidities and baseline medications. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. A total of 429 459 COVID-19 patients were included, 1:1 matched to non-COVID individuals. Upon median follow-up of 11 months, COVID-19 patients had higher risks of major osteoporotic fractures (5.08 vs 3.95 per 1000 persons; HR 1.22 95%CI [1.15-1.31]), hip fractures (2.71 vs 1.94; 1.33 [1.22-1.46]), clinical vertebral fractures (0.42 vs 0.31; 1.29 [1.03-1.62]), and falls (13.83 vs 10.36; 1.28 [1.23-1.33]). Subgroup analyses revealed no significant interaction. In acute (within 30 days) and post-acute phases (beyond 30 days) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we consistently observed a significant increase in fractures and falls risks. Our study demonstrated increased risk of major osteoporotic fractures after SARS-CoV-2 infection in both acute and post-acute phases in older adults, partly due to increased fall risk. Clinicians should be aware of musculoskeletal health of COVID-19 survivors., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: X.L. reports consultancy fee from Merck Sharp & Dohme, unrelated to this work; research grants from Research Fund Secretariat of the Health Bureau, Health and Medical Research Fund (HMRF, HKSAR), Research Grants Council Early Career Scheme (RGC/ECS, HKSAR), Research Grants Council Research Impact Fund (RGC/RIF, HKSAR), educational and investigator initiate research fund from Janssen and Pfizer; and internal funding from the University of Hong Kong, unrelated to this work. S.C.W.T. reports consultancy for Eledon Pharmaceuticals and Travere Therapeutics, Inc.; honoraria from AstraZeneca, Bayer, Boehringer Ingelheim and Novartis; role on the Editorial Boards of American Journal of Nephrology, Clinical Journal of the American Society of Nephrology, Journal of Nephrology and Kidney Diseases and Kidney International; advisory or leadership role as Associate Editor of Glomerular Diseases and Theme and Subspecialties Editor of Nephrology Dialysis Transplantation; advisory or leadership role on KDIGO Executive Committee; speakers bureau for AstraZeneca; and other interests or relationships as President of Asian Pacific Society of Nephrology. I.C.K.W. reports research funding outside the submitted work from Amgen, Bayer, Bristol-Myers Squibb, European Commission, GSK, Janssen, Novartis, Pfizer, National Health and Medical Research Council in Australia, National Institute for Health Research in England, and the Hong Kong RGC; speaker fees from Janssen and Medice in the previous 3 years; and advisory or leadership role as an independent non-executive director of Jacobson Medical in Hong Kong. All remaining authors have nothing to disclose.

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has posed increased risks of hospitalization and mortality in patients with underlying CKD. Current data on vaccine effectiveness of COVID-19 vaccines are limited to patients with CKD on dialysis and seroconversion in the non-dialysis population., Methods: A case-control study was conducted of adults with CKD using data extracted from the electronic health record database in Hong Kong. Adults with CKD and COVID-19 confirmed by PCR were included in the study. Each case was matched with up to ten controls attending Hospital Authority services without a diagnosis of COVID-19 on the basis of age, sex, and index date (within three calendar days). The vaccine effectiveness of BNT162b2 and CoronaVac in preventing COVID-19 infection, hospitalizations, and all-cause mortality was estimated using conditional logistic regression adjusted by patients' comorbidities and medication history during the outbreak from January to March 2022., Results: A total of 20,570 COVID-19 cases, 6604 COVID-19-related hospitalizations, and 2267 all-cause mortality were matched to 81,092, 62,803, and 21,348 controls, respectively. Compared with the unvaccinated group, three doses of BNT162b2 or CoronaVac were associated with a reduced risk of infection (BNT162b2: 64% [95% confidence interval (CI), 60 to 67], CoronaVac: 42% [95% CI, 38 to 47]), hospitalization (BNT162b2: 82% [95% CI, 77 to 85], CoronaVac: 80% [95% CI, 76 to 84]), and mortality (BNT162b2: 94% [95% CI, 88 to 97], CoronaVac: 93% [95% CI, 88 to 96]). Vaccines were less effective in preventing infection and hospitalization in the eGFR <15 and 15-29 ml/min per 1.73 m 2 subgroups as compared with higher GFR subgroups. However, receipt of vaccine, even for one dose, was effective in preventing all-cause mortality, with estimates similar to the higher eGFR subgroups, as compared with unvaccinated., Conclusions: A dose-response relationship was observed between the number of BNT162b2 or CoronaVac doses and the effectiveness against COVID-19 infection and related comorbidity in the CKD population., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

Multimorbidity entails a higher risk of SARS-CoV-2 infection and COVID-19 complications. We examined vaccine effectiveness (VE) stratified by multimorbidity using a case-control study of territory-wide electronic health records in Hong Kong. Cases of infection (testing positive), hospitalization, and mortality were identified from January to March 2022. Controls were matched by age, sex, outpatient attendance/hospitalization date, and Charlson Comorbidity Index. We demonstrated a consistently good VE among people with increased multimorbidity burden; even more so than among those with minimal such burden. There was also a significantly greater VE after a third dose of BNT162b2 or CoronaVac against infection. The difference in VE between those with multimorbidity and those without was less pronounced for hospitalization, and such difference for COVID-19-related mortality was negligible. In conclusion, VE of both examined vaccines against SARS-CoV-2 infection among people with more complex multimorbidity burden is significant. Further vaccine roll-out should prioritize people with multimorbidity., Competing Interests: F.T.T.L. has been supported by the RGC Postdoctoral Fellowship under the Hong Kong Research Grants Council and has received research grants from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, outside the submitted work. E.Y.F.W. has received research grants from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, the Hong Kong Research Grants Council, and the National Natural Science Foundation of China outside the submitted work. C.S.L.C. has received grants from the Food and Health Bureau of the Hong Kong Government, Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, and Amgen; and personal fees from PrimeVigilance; outside the submitted work. X.L. has received research grants from the Research Grants Council Early Career Scheme (RGC/ECS, HKSAR); the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region (HMRF, HKSAR); research and educational grants from Janssen and Pfizer; internal funding from the University of Hong Kong; and consultancy fees from Merck Sharp & Dohme and Pfizer, unrelated to this work. I.C.K.W. receives research funding outside the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong Research Grants Council, the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, National Institute for Health Research in England, European Commission, and the National Health and Medical Research Council in Australia; has received speaker fees from Janssen and Medice in the previous 3 years; and is an independent non-executive director of Jacobson Medical in Hong Kong. E.W.Y.C. reports grants from Research Grants Council of Hong Kong and Research Fund Secretariat of the Food and Health Bureau of Hong Kong, National Natural Science Fund of China, Wellcome Trust, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, and Narcotics Division of the Security Bureau of Hong Kong; honorarium from Hospital Authority; outside the submitted work. All other authors declare no competing interests., (© 2024 The Authors.)

Background: Chronic liver disease (CLD) was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Aim: To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma (HCC) among patients with CLD., Methods: A retrospective, territory-wide cohort of CLD patients was identified from an electronic health database in Hong Kong. Patients with confirmed SARS-CoV-2 infection [coronavirus disease 2019 (COVID-19)+CLD] between January 1, 2020 and October 25, 2022 were identified and matched 1:1 by propensity-score with those without (COVID-19-CLD). Each patient was followed up until death, outcome event, or November 15, 2022. Primary outcome was incidence of HCC. Secondary outcomes included all-cause mortality, adverse hepatic outcomes, and different treatment strategies to HCC (curative, non-curative treatment, and palliative care). Analyses were further stratified by acute (within 20 d) and post-acute (21 d or beyond) phases of SARS-CoV-2 infection. Incidence rate ratios (IRRs) were estimated by Poisson regression models., Results: Of 193589 CLD patients (> 95% non-cirrhotic) in the cohort, 55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score matching. Upon 249-d median follow-up, COVID-19+CLD was not associated with increased risk of incident HCC (IRR: 1.19, 95%CI: 0.99-1.42, P = 0.06), but higher risks of receiving palliative care for HCC (IRR: 1.60, 95%CI: 1.46-1.75, P < 0.001), compared to COVID-19-CLD. In both acute and post-acute phases of infection, COVID-19+CLD were associated with increased risks of all-cause mortality (acute: IRR: 7.06, 95%CI: 5.78-8.63, P < 0.001; post-acute: IRR: 1.24, 95%CI: 1.14-1.36, P < 0.001) and adverse hepatic outcomes (acute: IRR: 1.98, 95%CI: 1.79-2.18, P < 0.001; post-acute: IRR: 1.24, 95%CI: 1.13-1.35, P < 0.001), compared to COVID-19-CLD., Conclusion: Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC, they were more likely to receive palliative treatment than those without. The detrimental effects of SARS-CoV-2 infection persisted in post-acute phase., Competing Interests: Conflict-of-interest statement: Lung-Yi Mak is an advisory board member for Gilead Sciences. Xue Li has received research grants from the Health Bureau of the Government of the Hong Kong SAR, research and educational grants from Janssen and Pfizer; internal funding from the University of Hong Kong; consultancy fee from Merck Sharp & Dohme, unrelated to this work. Francisco Tsz Tsun Lai has been supported by the RGC Postdoctoral Fellowship under the Hong Kong Research Grants Council and has received research grants from the Health Bureau of the Government of the Hong Kong SAR, outside the submitted work. Eric Yuk Fai Wan has received research grants from the Health Bureau of the Government of the Hong Kong SAR, and the Hong Kong Research Grants Council, outside the submitted work. Celine Sze Ling Chui has received grants from the Health Bureau of the Hong Kong Government, Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, and Amgen; personal fee from Primevigilance Ltd.; outside the submitted work. Esther Wai Yin Chan reports honorarium from the Hospital Authority, grants from the Research Grants Council (RGC, Hong Kong), Research Fund Secretariat of the Health Bureau, National Natural Science Fund of China, Wellcome Trust, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, and Narcotics Division of the Security Bureau of the Hong Kong SAR, outside the submitted work. Ching Lung Cheung received research grants and honorarium from Amgen, research grant support from HMRF, and honorarium from Abbott. Wai Kay Seto received speaker's fees from AstraZeneca and Mylan, is an advisory board member of CSL Behring, is an advisory board member and received speaker's fees from AbbVie, and is an advisory board member, received speaker's fees, and researching funding from Gilead Sciences. Man-Fung Yuen serves as advisor/consultant for AbbVie, Assembly Biosciences, Aligos Therapeutics, Arbutus Biopharma, Bristol Myer Squibb, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, GlaxoSmithKline, Gilead Sciences, Immunocore, Janssen, Merck Sharp and Dohme, Hoffmann-La Roche, and Springbank Pharmaceuticals, Vir Biotechnology and receives grant/research support from Assembly Biosciences, Aligos Therapeutics, Arrowhead Pharmaceuticals, Bristol Myer Squibb, Fujirebio Incorporation, Gilead Sciences, Immunocore, Merck Sharp and Dohme, Hoffmann-La Roche, Springbank Pharmaceuticals, and Sysmex Corporation, outside the submitted work. Carlos King Ho Wong reports receipt of research funding from the EuroQoL Group Research Foundation, the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund, AstraZeneca and Boehringer Ingelheim, all outside of the submitted work. Ian Chi Kei Wong reports research funding outside the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong RGC, and the Hong Kong Health and Medical Research Fund, National Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia. All other authors declare no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: It is unclear how the coronavirus disease 2019 (Covid-19) pandemic has affected multimorbidity incidence among those with one pre-existing chronic condition, as well as how vaccination could modify this association., Aim: To examine the association of Covid-19 infection with multimorbidity incidence among people with one pre-existing chronic condition, including those with prior vaccination., Design: Nested case-control study., Methods: We conducted a territory-wide nested case-control study with incidence density sampling using Hong Kong electronic health records from public healthcare facilities and mandatory Covid-19 reports. People with one listed chronic condition (based on a list of 30) who developed multimorbidity during 1 January 2020-15 November 2022 were selected as case participants and randomly matched with up to 10 people of the same age, sex and with the same first chronic condition without having developed multimorbidity at that point. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) of multimorbidity., Results: In total, 127 744 case participants were matched with 1 230 636 control participants. Adjusted analysis showed that there were 28%-increased odds of multimorbidity following Covid-19 [confidence interval (CI) 22% to 36%] but only 3% (non-significant) with prior full vaccination with BNT162b2 or CoronaVac (95% CI -2% to 7%). Similar associations were observed in men, women, older people aged 65 or more, and people aged 64 or younger., Conclusions: We found a significantly elevated risk of multimorbidity following a Covid-19 episode among people with one pre-existing chronic condition. Full vaccination significantly reduced this risk increase., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Even with effective vaccines, patients with CKD have a higher risk of hospitalization and death subsequent to COVID-19 infection than those without CKD. Molnupiravir and nirmatrelvir-ritonavir have been approved for emergency use, but their effectiveness for the CKD population is still unknown. This study was conducted to determine the effectiveness of these drugs in reducing mortality and severe COVID-19 in the CKD population., Methods: This was a target trial emulation study using electronic health databases in Hong Kong. Patients with CKD aged 18 years or older who were hospitalized with COVID-19 were included. The per-protocol average treatment effect among COVID-19 oral antiviral initiators, including all-cause mortality, intensive care unit (ICU) admission, and ventilatory support within 28 days, were compared to noninitiators., Results: Antivirals have been found to lower the risk of all-cause mortality, with Molnupiravir at a hazard ratio (HR) of 0.85 (95% confidence interval [CI], 0.77 to 0.95] and nirmatrelvir-ritonavir at an HR of 0.78 [95% CI, 0.60 to 1.00]. However, they do not significantly reduce the risk of ICU admission (molnupiravir: HR, 0.88 [95% CI, 0.59 to 1.30]; nirmatrelvir-ritonavir: HR, 0.86 [95% CI, 0.56 to 1.32]) or ventilatory support (molnupiravir: HR, 1.00 [95% CI, 0.76 to 1.33]; nirmatrelvir-ritonavir: HR, 1.01 [95% CI, 0.74 to 1.37]). There was a greater risk reduction in males and those with higher Charlson Comorbidity Index (CCI). The nirmatrelvir-ritonavir trial also showed reduced risk for those who had antiviral treatment and received 3 or more vaccine doses., Conclusion: Both molnupiravir and nirmatrelvir-ritonavir reduced mortality rates for hospitalized COVID-19 patients with CKD., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: Effectiveness and respiratory adverse events following coronavirus disease-2019 (COVID-19) vaccines have not been well investigated in Chinese patients with chronic obstructive pulmonary disease (COPD) and asthma., Methods: Using electronic health care records in Hong Kong, we included adults with COPD or asthma or both and hospitalised for severe respiratory exacerbation in a self-controlled case series (SCCS) study between 23/02/2021 and 30/11/2022. Conditional Poisson regression models were used to estimate the incidence of outcomes within exposure periods (28 days after each dose) compared with baseline periods. Cox proportional hazard models evaluated vaccine effectiveness (VE) against COVID-related mortality, hospitalisation, and severe complications, including admission to intensive care units or ventilatory support. The VE assessment was based on vaccine types and the number of doses., Results: In the SCCS, 343 CoronaVac recipients and 212 BNT162b2 recipients were included. No increased risk of outcomes was observed within the exposure periods. In the cohort study, 108,423 and 83,323 patients received ≥ 2 doses of CoronaVac and BNT162b2, respectively. The VE (95% CI) against COVID-related mortality, hospitalisation, and severe complications after two-dose CoronaVac was 77% (74-80%), 18% (6-23%), and 29% (12-43%), respectively, while for the two-dose regimen of BNT162b2, it was 92% (91-94%), 33% (30-37%), and 57% (45-66%), respectively. Higher VE against COVID-related mortality, hospitalisation, and severe complications was found for the three-dose regimen of CoronaVac (94%, 40%, and 71%) and BNT162b2 (98%, 65%, and 83%). Administering a fourth dose of either vaccine showed additional reductions in COVID-related outcomes., Conclusions: Among people with COPD and asthma, the COVID-19 vaccines CoronaVac and BNT162b2 did not increase severe exacerbations and achieved moderate-to-high effectiveness against COVID-related outcomes. COVID-19 vaccination remains essential and should be encouraged to protect this vulnerable population in future epidemic waves., (© 2023. The Author(s).)

Severe COVID-19 appears to be disproportionately more common in children and adolescents since the emergence of Omicron. More evidence regarding vaccine effectiveness (VE) is urgently needed to assist policymakers in making decisions and minimize vaccine hesitancy among the public. This was a case-control study in the pediatric population using data extracted from the electronic health records database in Hong Kong. Individuals aged 3-17 with COVID-19 confirmed by polymerase chain reaction were included in the study. Each case was matched with up to 10 controls based on age, gender, and index date (within 3 calendar days). The VE of BNT162b2 and CoronaVac in preventing COVID-19, hospitalizations, and severe outcomes were estimated using conditional logistic regression adjusted by patients' comorbidities and medication history during the outbreak from January to August 2022. A total of 36,434 COVID-19 cases, 2231 COVID-19-related hospitalizations, and 1918 severe COVID-19 cases were matched to 109,004, 21,788, and 18,823 controls, respectively. Compared to the unvaccinated group, three doses of BNT162b2 or CoronaVac was associated with reduced risk of infection [VE: BNT162b2: 56.0% (95% CI: 49.6-61.6), CoronaVac: 39.4% (95% CI: 25.6-50.6)], hospitalization [VE: BNT162b2: 58.9% (95% CI: 36.1-73.6), CoronaVac: 51.7% (11.6-73.6)], and severe outcomes [VE: BNT162b2: 60.2% (95% CI: 33.7-76.1), CoronaVac: 42.2% (95% CI: -6.2-68.6)]. Our findings showed that three doses of BNT162b2 or CoronaVac was effective in preventing COVID-19, hospitalizations, and severe outcomes among the pediatric population during Omicron-dominant pandemic, which was further enhanced after a booster dose.

Background: In onco-nephrology, data on acute kidney injury (AKI) among children with haematological malignancies are scarce., Methods: A retrospective cohort study of all patients in Hong Kong diagnosed with haematological malignancies from 2019 to 2021 before 18 years of age, was conducted to investigate the epidemiology, risk factors and clinical outcomes of AKI during the first year of treatment. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria., Results: We included 130 children with haematological malignancy at median age of 9.4 years (IQR, 3.9-14.1). Of these patients, 55.4% were acute lymphoblastic leukemia (ALL), 26.9% were lymphoma and 17.7% were acute myeloid leukemia (AML). Thirty-five patients (26.9%) developed 41 AKI episodes during the first year of diagnosis, corresponding to 32 episodes per 100-patient-year. A total of 56.1% and 29.2% of the AKI episodes occurred during induction and consolidation chemotherapy respectively. Septic shock (n = 12, 29.2%) was the leading cause of AKI; 21 episodes (51.2%) were stage 3 AKI; 12 episodes (29.3%) were stage 2 AKI; and 6 patients required continuous kidney replacement therapies. Tumor lysis syndrome and impaired baseline kidney function were significantly associated with AKI on multivariate analysis (P = 0.01). History of AKI was associated with chemotherapy postponement (37.1% vs. 16.8%, P = 0.01), worse 12-month patient survival (77.1% vs. 94.7%, log rank P = 0.002) and lower disease remission rate at 12-month (68.6% vs. 88.4%, P = 0.007), compared to patients without AKI., Conclusion: AKI is a common complication during treatment of haematological malignancies which is associated with worse treatment outcomes. A regular and dedicated surveillance program for at-risk patients should be studied in children with haematological malignancies for prevention and early detection of AKI. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Preclinical evidence suggests that certain antipsychotic medications may inhibit the development of lung cancer. This study aims to investigate the association between incident lung cancer and different cumulative exposure periods of flupentixol or any antipsychotics., Methods: Using electronic health records from the Hospital Authority in Hong Kong, this nested case-control study included case participants aged 18 years or older with newly diagnosed lung cancer after initiating antipsychotics between January 1, 2003, and August 31, 2022. Each case was matched to up to ten controls of the same sex and age, who were also antipsychotic users. Multivariable conditional logistic regression models were conducted to quantify the association between lung cancer and different cumulative exposure times of flupentixol (0-365 days [ref]; 366-1825 days; 1826+ days) and any antipsychotics (1-365 days [ref]; 366-1825 days; 1826+ days), separately., Results: Here we show that among 6435 cases and 64,348 matched controls, 64.06% are males, and 52.98% are aged 65-84 years. Compared to patients with less than 365 days of exposure, those with 366-1825 days of exposure to flupentixol (OR = 0.65 [95% CI, 0.47-0.91]) and any antipsychotics (0.42 [0.38-0.45]) have a lower risk of lung cancer. A decreased risk is observed in patients who have 1826+ days of cumulative use of any antipsychotics (0.54 [0.47-0.60])., Conclusions: A reduced risk of lung cancer is observed in patients with more than one year of exposure to flupentixol or any antipsychotics. Further research on the association between lung cancer and other antipsychotic agents is warranted., (© 2023. The Author(s).)

Accrued epidemiologic data largely support an association of antipsychotic use with breast cancer in women with schizophrenia. No studies have specifically investigated such risks in women with bipolar disorder. This study aims to examine the association between antipsychotics and breast cancer in women with bipolar disorder and compare it against schizophrenia. We conducted a nested case-control study using a territory-wide public healthcare database in Hong Kong examining women aged ≥18 years with bipolar disorder or schizophrenia. Using incidence density sampling, women with a breast cancer diagnosis were matched by up to 10 control participants. In total, 672 case participants (109 with bipolar disorder) and 6,450 control participants (931 with bipolar disorder) were included. Results show a significant association of first-generation antipsychotics with breast cancer in both women with schizophrenia [adjusted odds ratio (aOR) 1.49, 95% confidence interval (CI) 1.17-1.90] or bipolar disorder (aOR 1.80, 95% CI 1.11-2.93). Second-generation antipsychotics was associated with breast cancer only in women with bipolar disorder (aOR 2.49, 95% CI 1.29-4.79), with no significant association found in women with schizophrenia (aOR 1.10, 95% CI 0.88-1.36). In conclusion, further research on breast cancer risks is warranted for women with bipolar disorder on antipsychotics., Competing Interests: Declaration of Competing Interest ICKW receives research funding outside the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong Research Grants Council, the Health Bureau of the Government of the Hong Kong Special Administrative Region, National Institute for Health Research in England, European Commission, and the National Health and Medical Research Council in Australia; has received speaker fees from Janssen and Medice in the previous 3 years; and is an independent non-executive director of Jacobson Medical in Hong Kong. EWC reports grants from Research Grants Council of Hong Kong, Research Fund Secretariat of the Health Bureau of Hong Kong, National Natural Science Fund of China, Wellcome Trust, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, and Narcotics Division of the Security Bureau of Hong Kong; honorarium from Hospital Authority; outside the submitted work. FTTL has been supported by the RGC Postdoctoral Fellowship under the Hong Kong Research Grants Council and has received research grants from the Health Bureau of the Government of the Hong Kong Special Administrative Region, outside the submitted work. All other authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The risk of incident diabetes following Coronavirus Disease 2019 (COVID-19) vaccination remains to be elucidated. Also, it is unclear whether the risk of incident diabetes after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is modified by vaccination status or differs by SARS-CoV-2 variants. We evaluated the incidence of diabetes following mRNA (BNT162b2), inactivated (CoronaVac) COVID-19 vaccines, and after SARS-CoV-2 infection., Methods and Findings: In this population-based cohort study, individuals without known diabetes were identified from an electronic health database in Hong Kong. The first cohort included people who received ≥1 dose of COVID-19 vaccine and those who did not receive any COVID-19 vaccines up to September 2021. The second cohort consisted of confirmed COVID-19 patients and people who were never infected up to March 2022. Both cohorts were followed until August 15, 2022. A total of 325,715 COVID-19 vaccine recipients (CoronaVac: 167,337; BNT162b2: 158,378) and 145,199 COVID-19 patients were 1:1 matched to their respective controls using propensity score for various baseline characteristics. We also adjusted for previous SARS-CoV-2 infection when estimating the conditional probability of receiving vaccinations, and vaccination status when estimating the conditional probability of contracting SARS-CoV-2 infection. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident diabetes were estimated using Cox regression models. In the first cohort, we identified 5,760 and 4,411 diabetes cases after receiving CoronaVac and BNT162b2 vaccines, respectively. Upon a median follow-up of 384 to 386 days, there was no evidence of increased risks of incident diabetes following CoronaVac or BNT162b2 vaccination (CoronaVac: 9.08 versus 9.10 per 100,000 person-days, HR = 0.998 [95% CI 0.962 to 1.035]; BNT162b2: 7.41 versus 8.58, HR = 0.862 [0.828 to 0.897]), regardless of diabetes type. In the second cohort, we observed 2,109 cases of diabetes following SARS-CoV-2 infection. Upon a median follow-up of 164 days, SARS-CoV-2 infection was associated with significantly higher risk of incident diabetes (9.04 versus 7.38, HR = 1.225 [1.150 to 1.305])-mainly type 2 diabetes-regardless of predominant circulating variants, albeit lower with Omicron variants (p for interaction = 0.009). The number needed to harm at 6 months was 406 for 1 additional diabetes case. Subgroup analysis revealed no evidence of increased risk of incident diabetes among fully vaccinated COVID-19 survivors. Main limitations of our study included possible misclassification bias as type 1 diabetes was identified through diagnostic coding and possible residual confounders due to its observational nature., Conclusions: There was no evidence of increased risks of incident diabetes following COVID-19 vaccination. The risk of incident diabetes increased following SARS-CoV-2 infection, mainly type 2 diabetes. The excess risk was lower, but still statistically significant, for Omicron variants. Fully vaccinated individuals might be protected from risks of incident diabetes following SARS-CoV-2 infection., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CKHW reports receipt of research funding from the EuroQoL Group Research Foundation, the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund; AstraZeneca and Boehringer Ingelheim, unrelated to this work. FTTL has been supported by the RGC Postdoctoral Fellowship under the Hong Kong Research Grants Council. EYFW has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, and the Hong Kong Research Grants Council, outside the submitted work. CSLC has received grants from the Food and Health Bureau of the Hong Kong Government, Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, and Amgen; personal fee from Primevigilance Ltd.; outside the submitted work. XL has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, research and educational grants from Janssen and Pfizer; internal funding from University of Hong Kong; consultancy fee from Merck Sharp & Dohme, unrelated to this work. EWYC reports honorarium from Hospital Authority, grants from Research Grants Council (RGC, Hong Kong), grants from Research Fund Secretariat of the Food and Health Bureau, grants from National Natural Science Fund of China, grants from Wellcome Trust, grants from Bayer, grants from Bristol-Myers Squibb, grants from Pfizer, grants from Janssen, grants from Amgen, grants from Takeda, grants from Narcotics Division of the Security Bureau of HKSAR, outside the submitted work. ICKW reports research funding outside the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong RGC, and the Hong Kong Health and Medical Research Fund, National Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia, and also received speaker fees from Janssen and Medice in the previous 3 years. All other authors declare no competing interests., (Copyright: © 2023 Xiong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Large-scale comparative research exploring the risk after the third dose and after inactivated covid-19 vaccination is limited. This study aimed to assess the risk of carditis following three doses of BNT162b2 or CoronaVac., Methods: We conducted a self-controlled case series (SCCS) and a case-control study using electronic health and vaccination records in Hong Kong. Carditis incidents within 28 days of covid-19 vaccination were included as cases. In the case-control study, up to 10 hospitalized controls were selected with stratified probability sampling by age, sex, and hospital admission (±1 day). The incidence rate ratios (IRRs) were reported from conditional Poisson regressions for SCCS, and adjusted odds ratios (ORs) were reported from multivariable logistic regressions., Findings: A total of 8,924,614 doses of BNT162b2 and 6,129,852 doses of CoronaVac were administered from February 2021 to March 2022. The SCCS detected increased carditis risks after BNT162b2: 4.48 (95%confidence interval [CI]:2.99-6.70] in 1-14 days and 2.50 (95%CI:1.43-4.38) in 15-28 days after first dose; 10.81 (95%CI:7.63-15.32) in 1-14 days and 2.95 (95%CI:1.82-4.78) in 15-28 days after second dose; 4.72 (95%CI:1.40-15.97) in 1-14 days after third dose. Consistent results were observed from the case-control study. Risks were specifically found in people aged below 30 years and males. No significant risk increase was observed after CoronaVac in all primary analyses., Interpretations: We detected increased carditis risks within 28 days after all three doses of BNT162b2 but the risk after the third doses were not higher than that of the second dose when compared with baseline period. Continuous monitoring of carditis after both mRNA and inactivated covid-19 vaccines is needed., Funding: : This study was funded by Hong Kong Health Bureau (COVID19F01)., Competing Interests: FTTL has been supported by the RGC Postdoctoral Fellowship under the Hong Kong Research Grants Council and has received research grants from the Health Bureau of the Government of the Hong Kong Special Administrative Region, outside the submitted work. XL has received research grants from the Health Bureau of the Government of the Hong Kong Special Administrative Region; research and educational grants from Janssen and Pfizer; internal funding from the University of Hong Kong; and consultancy fees from Merck Sharp & Dohme, unrelated to this work. EYFW has received research grants from the Health Bureau of the Government of the Hong Kong Special Administrative Region, and the Hong Kong Research Grants Council, outside the submitted work. CKHW reports receipt of research funding from the EuroQoL Group Research Foundation, the Hong Kong Research Grants Council, and the Hong Kong Health and Medical Research Fund; outside of the submitted work. EWYC reports honorarium from Hospital Authority; and grants from Research Grants Council (RGC, Hong Kong), Research Fund Secretariat of the Health Bureau, National Natural Science Fund of China, Wellcome Trust, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, and Narcotics Division of the Security Bureau of the Hong Kong Special Administrative Region, outside the submitted work. CSLC has received grants from the Health Bureau of the Hong Kong Government, Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, MSD, and Amgen; and personal fees from PrimeVigilance; outside the submitted work. ICKW reports research funding outside the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong Research Grants Council, the Health Bureau of the Government of the Hong Kong Special Administrative Region, National Institute for Health Research in England, European Commission, and the National Health and Medical Research Council in Australia; has received speaker fees from Janssen and Medice in the previous 3 years; and is an independent non-executive director of Jacobson Medical in Hong Kong. All other authors declare no competing interests., (© 2023 The Author(s).)

Objective: We aimed to assess whether the introduction of the first infliximab biosimilar was associated with changes in overall infliximab consumption (originator and biosimilars) and price changes to the originator infliximab., Methods: An interrupted time series analysis using infliximab sales data from 2010 to 2020 from the IQVIA Multinational Integrated Data Analysis System for eight selected regions: Australia, Canada, Hong Kong, Korea, India, Japan, the UK, and the USA. Quarterly measures of infliximab consumption and list prices were respectively defined as the number of standard units (SU)/1000 inhabitants and as 2020 USA dollars (USD)/SU., Results: Following the introduction of infliximab biosimilars, overall infliximab consumption increased in Australia [immediate change: 0.145 SU/1000 inhabitants (P = 0.014); long-term change: 0.022 SU/1000 inhabitants per quarter (P < 0.001)], Canada [immediate change 0.415 (P = 0.008)], the UK [long-term change 0.024 (P < 0.001)], and Hong Kong [immediate change: 0.042 (P < 0.001)]. The list price of originator infliximab also decreased following biosimilar introduction in Australia [immediate change: - 187.84 USD/SU (P < 0.001); long-term change - 6.46 USD/SU per quarter (P = 0.043)], Canada [immediate change: - 145.58 (P < 0.001)], the UK [immediate change: - 34.95 (P = 0.010); long-term change: - 4.77 (P < 0.001)], and Hong Kong [long-term change: - 4.065 (P = 0.046)]. Consumption and price changes were inconsistent in India, Japan, Korea, and the USA., Conclusions: Introduction of the first infliximab biosimilar was not consistently associated with increased consumption across regions. Additional policy and healthcare system interventions to support biosimilar infliximab adoption are needed., (© 2023. The Author(s).)

Background: Avascular necrosis (AVN) of bone is a debilitating complication of pediatric patients with acute lymphoblastic leukemia (ALL). While it is extensively studied and reported in Western population, studies focused on Orientals are limited. This study aims to evaluate the incidence, risk factors, and clinical outcomes of AVN among Chinese children with ALL., Methods: This study is a retrospective, territory-wide population-based cohort study of pediatric patients with ALL enrolled on one of the three consecutive ALL study protocols (ALL-IC-BFM 2002, CCLG-ALL 2008, and CCCG-ALL 2015)., Results: A total of 24 out of 533 pediatric subjects with ALL (4.5%) had symptomatic AVN. Age was the single most important risk factor associated with the development of AVN. Only three patients were below age of 10 at the time of diagnosis of ALL. The incidences of AVN in patients aged above and below 10 years were 18.2% ± 3.6% and 0.8% ± 0.5%, respectively, and were significantly different (p < 0.005). Treatment protocol, immunophenotype, and gender were not predictive of AVN. Among the 24 patients, five required orthopedic interventions in view of progressive and severe disease. For subjects with hip joints involvement, follow-up assessments showed 12 of 22 hip joints had radiological progression over a median duration of 3.63 years. Seventeen of them did not have pain at the latest follow-up and among patients with pain (n = 7), five did not experience any limitation on activities of daily living while two required use of walking aids or wheelchair., Conclusion: The incidence of symptomatic AVN in Chinese ALL patients was comparable to other studies in Western population. Adolescent age more than 10 years old was recognized to be the most important factor for development of AVN. Significant proportion of patients had radiological progression over time with a small percentage of subjects had daily activities affected., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Whether hospitalized patients benefit from COVID-19 oral antivirals is uncertain., Objective: To examine the real-world effectiveness of molnupiravir and nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the Omicron outbreak., Design: Target trial emulation study., Setting: Electronic health databases in Hong Kong., Participants: The molnupiravir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 26 February and 18 July 2022 ( n = 16 495). The nirmatrelvir-ritonavir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 16 March and 18 July 2022 ( n = 7119)., Intervention: Initiation of molnupiravir or nirmatrelvir-ritonavir within 5 days of hospitalization with COVID-19 versus no initiation of molnupiravir or nirmatrelvir-ritonavir., Measurements: Effectiveness against all-cause mortality, intensive care unit (ICU) admission, or use of ventilatory support within 28 days., Results: The use of oral antivirals in hospitalized patients with COVID-19 was associated with a lower risk for all-cause mortality (molnupiravir: hazard ratio [HR], 0.87 [95% CI, 0.81 to 0.93]; nirmatrelvir-ritonavir: HR, 0.77 [CI, 0.66 to 0.90]) but no significant risk reduction in terms of ICU admission (molnupiravir: HR, 1.02 [CI, 0.76 to 1.36]; nirmatrelvir-ritonavir: HR, 1.08 [CI, 0.58 to 2.02]) or the need for ventilatory support (molnupiravir: HR, 1.07 [CI, 0.89 to 1.30]; nirmatrelvir-ritonavir: HR, 1.03 [CI, 0.70 to 1.52]). There was no significant interaction between drug treatment and the number of COVID-19 vaccine doses received, thereby supporting the effectiveness of oral antivirals regardless of vaccination status. No significant interaction between nirmatrelvir-ritonavir treatment and age, sex, or Charlson Comorbidity Index was observed, whereas molnupiravir tended to be more effective in older people., Limitation: The outcome of ICU admission or need for ventilatory support may not capture all severe COVID-19 cases; unmeasured confounders, such as obesity and health behaviors, may exist., Conclusion: Molnupiravir and nirmatrelvir-ritonavir reduced all-cause mortality in both vaccinated and unvaccinated hospitalized patients. No significant reduction in ICU admission or the need for ventilatory support was observed., Primary Funding Source: Health and Medical Research Fund Research on COVID-19, Government of the Hong Kong Special Administrative Region; Research Grants Council, Collaborative Research Fund; and Health Bureau, Government of the Hong Kong Special Administrative Region.

Pediatric acute myeloid leukemia (AML) is an uncommon but aggressive hematological malignancy. The poor outcome is attributed to inadequate prognostic classification and limited treatment options. A thorough understanding on the genetic basis of pediatric AML is important for the development of effective approaches to improve outcomes. Here, by comprehensively profiling fusion genes as well as mutations and copy number changes of 141 myeloid-related genes in 147 pediatric AML patients with subsequent variant functional characterization, we unveil complex mutational patterns of biological relevance and disease mechanisms including MYC deregulation. Also, our findings highlight TP53 alterations as strong adverse prognostic markers in pediatric AML and suggest the core spindle checkpoint kinase BUB1B as a selective dependency in this aggressive subgroup. Collectively, our present study provides detailed genomic characterization revealing not only complexities and mechanistic insights into pediatric AML but also significant risk stratification and therapeutic strategies to tackle the disease., (© 2023. The Author(s).)

Introduction: In 2017, breast cancer was the most common cancer and third leading cause of cancer death among women in Hong Kong. Approximately 20% of patients were human epidermal growth factor receptor-2 (HER2)-positive. This study was conducted to investigate cost differences between intravenous and subcutaneous trastuzumab regimens in Hong Kong using medical resources utilisation data from other countries., Methods: A cost-minimisation model was developed to compare the cost of total care, including direct medical cost and full-time equivalent (FTE) hours. The drug acquisition cost was obtained from the manufacturer, whereas the costs for hospitalisation and clinic visits were acquired from the Hong Kong Gazette. Time (in FTE hours) was determined by literature review. All costs were expressed in US dollars (US$1 = HK$7.8). Costs were not discounted because of the short time horizon. One-way deterministic sensitivity analysis was performed to identify the effects of changes in drug acquisition cost, changes in FTE hours (based on confidence intervals reported), and changes in body weight (±20%)., Results: Literature review indicated that 0.18 FTE hour of nursing time (7.9 hours) and 0.14 FTE hour of pharmacist time (6.2 hours) could be saved each week if the subcutaneous formulation was used. Using data in 2017, after 18 cycles of treatment with subcutaneous trastuzumab, the drug acquisition and healthcare professional time costs were reduced by US$9451.28 and US$566.16, respectively, yielding an annual savings of over US$8 million., Conclusion: The subcutaneous formulation of trastuzumab is a potential cost-saving therapy for HER2-positive breast cancer patients in Hong Kong. The drug acquisition cost was the parameter with the greatest effect on the total cost of treatment., Competing Interests: Both authors disclosed no conflicts of interest.

Background: With accruing case reports on de novo or relapsing glomerular diseases (GD) following different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, we evaluated the risk of GD following BNT162b2 and CoronaVac vaccines., Methods: A modified self-controlled case series analysis was conducted using anonymized, territory-wide SARS-CoV-2 vaccination records in Hong Kong. All Hong Kong residents aged 18 years or above with outcomes of interest were included. Outcomes of interest were GD, proteinuria or hematuria within 42 days following each dose of SARS-CoV-2 vaccines. Incidence per 100 000 doses of SARS-CoV-2 vaccines administered was calculated, and incidence rate ratios (IRRs) were estimated using conditional Poisson regression with seasonality adjustment., Results: Between 23 February 2021 and 31 March 2022, 4062 patients had an incident diagnosis of GD, proteinuria or hematuria, with 2873 of them being vaccinated during the observation period. The incidences of the composite events 1-41 days after vaccination were 3.7 (95% CI 3.1-4.4) per 100 000 doses of BNT162b2 administered, and 6.5 (95% CI 5.7-7.5) per 100 000 doses CoronaVac administered. There was no significant increase in the risks of composite events following the first (BNT162b2: IRR = 0.76, 95% CI 0.56-1.03; CoronaVac: IRR = 0.92, 95% CI 0.72-1.19), second (BNT162b2: IRR = 0.92, 95% CI 0.72-1.17; CoronaVac: IRR = 0.88. 95% CI 0.68-1.14) or third (BNT162b2: IRR = 0.39. 95% CI 0.15-1.03; CoronaVac: IRR = 1.18. 95% CI 0.53-2.63) dose of SARS-CoV-2 vaccines., Conclusions: There was no evidence of increased risks of de novo or relapsing GD with either BNT162b2 or CoronaVac vaccines., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Evidence on the effectiveness of COVID-19 vaccines among people who recovered from a previous SARS-CoV-2 infection is warranted to inform vaccination recommendations. Using the territory-wide public healthcare and vaccination records of over 2.5 million individuals in Hong Kong, we examined the potentially differential risk of SARS-CoV-2 infection, hospitalization, and mortality between those receiving two homologous doses of BNT162b2 or CoronaVac versus those with a previous infection receiving only one dose amid the Omicron epidemic. Results show a single dose after a SARS-CoV-2 infection is associated with a lower risk of infection (BNT162b2: adjusted incidence rate ratio [IRR] = 0.475, 95% CI: 0.410-0.550; CoronaVac: adjusted IRR = 0.397, 95% CI: 0.309-0.511) and no significant difference was detected in the risk of COVID-19-related hospitalization or mortality compared with a two-dose vaccination regimen. Findings support clinical recommendations that those with a previous infection could receive a single dose to gain at least similar protection as those who received two doses without a previous infection., (© 2022. The Author(s).)

Despite the expanding portfolio of targeted therapies for adults with acute myeloid leukemia (AML), direct implementation in children is challenging due to inherent differences in underlying genetics. Here we established the pharmacologic profile of pediatric AML by screening myeloblast sensitivity to approved and investigational agents, revealing candidates of immediate clinical relevance. Drug responses ex vivo correlated with patient characteristics, exhibited age-specific alterations, and concorded with activities in xenograft models. Integration with genomic data uncovered new gene-drug associations, suggesting actionable therapeutic vulnerabilities. Transcriptome profiling further identified gene-expression signatures associated with on- and off-target drug responses. We also demonstrated the feasibility of drug screening-guided treatment for children with high-risk AML, with two evaluable cases achieving remission. Collectively, this study offers a high-dimensional gene-drug clinical data set that could be leveraged to research the unique biology of pediatric AML and sets the stage for realizing functional precision medicine for the clinical management of the disease., Significance: We conducted integrated drug and genomic profiling of patient biopsies to build the functional genomic landscape of pediatric AML. Age-specific differences in drug response and new gene-drug interactions were identified. The feasibility of functional precision medicine-guided management of children with high-risk AML was successfully demonstrated in two evaluable clinical cases. This article is highlighted in the In This Issue feature, p. 476., (©2022 The Authors; Published by the American Association for Cancer Research.)

Background & Aims: Case reports of severe acute liver injury (ALI) following COVID-19 vaccination have recently been published. We evaluated the risks of ALI following COVID-19 vaccination (BNT162b2 or CoronaVac)., Methods: We conducted a modified self-controlled case series analysis using the vaccination records in Hong Kong with data linkage to electronic medical records from a territory-wide healthcare database. Incidence rate ratios (IRRs) for ALI outcome in the 56-day period following first and second doses of COVID-19 vaccines in comparison to the non-exposure period were estimated and compared to the ALI risk in patients with SARS-CoV-2 infection., Results: Among 2,343,288 COVID-19 vaccine recipients who were at risk, 4,677 patients developed ALI for the first time between 23 rd February 2021 to 30 th September 2021. The number of ALI cases within 56 days after the first and second dose of vaccination were 307 and 521 (335 and 334 per 100,000 person-years) for BNT162b2, and 304 and 474 (358 and 403 per 100,000 person-years) for CoronaVac, respectively, compared to 32,997 ALI cases per 100,000 person-years among patients within 56 days of SARS-CoV-2 infection. Compared to the non-exposure period, no increased risk was observed in the 56-day risk period for first (IRR 0.800; 95% CI 0.680-0.942) and second (IRR 0.944; 95% CI 0.816-1.091) dose of BNT162b2, or first (IRR 0.689; 95% CI 0.588-0.807) and second (IRR 0.905; 95% CI 0.781-1.048) dose of CoronaVac. There were no severe or fatal cases of ALI following COVID-19 vaccination., Conclusion: There was no evidence of an increased risk of ALI associated with BNT162b2 or CoronaVac vaccination. Based on all current available evidence from previous studies and our study, the benefit of mass vaccination far outweighs the ALI risk from vaccination., Lay Summary: There have been some recent reports that COVID-19 vaccination could be associated with acute liver injury. In our study, we found no evidence that COVID-19 vaccination increased the risk of acute liver injury, which was much more common after SARS-CoV-2 infection than after vaccination. Hence, our study provides further data indicating that the benefits of mass COVID-19 vaccination outweigh the potential risks., Competing Interests: Conflicts of interest Carlos King Ho Wong reports receipt of research funding from the EuroQoL Group Research Foundation, the Hong Kong Research Grants Council, and the Hong Kong Health and Medical Research Fund. Francisco Tsz Tsun Lai has been supported by the RGC Postdoctoral Fellowship under the Hong Kong Research Grants Council. Xue Li has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, research and educational grants from Janssen and Pfizer; internal funding from University of Hong Kong; consultancy fee from Merck Sharp & Dohme, unrelated to this work. Eric Yuk Fai Wan has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, and the Hong Kong Research Grants Council, outside the submitted work. Celine Sze Ling Chui has received grants from the Food and Health Bureau of the Hong Kong Government, Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, and Amgen; personal fee from Primevigilance Ltd.; outside the submitted work. Esther Wai Yin Chan reports honorarium from Hospital Authority, grants from Research Grants Council (RGC, Hong Kong), grants from Research Fund Secretariat of the Food and Health Bureau, grants from National Natural Science Fund of China, grants from Wellcome Trust, grants from Bayer, grants from Bristol-Myers Squibb, grants from Pfizer, grants from Janssen, grants from Amgen, grants from Takeda, grants from Narcotics Division of the Security Bureau of HKSAR, outside the submitted work. MF Yuen is an advisory board member and/or received research funding from AbbVie, Arbutus Biopharma, Assembly Biosciences, Bristol Myer Squibb, Dicerna Pharmaceuticals, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals; and received research funding from Arrowhead Pharmaceuticals, Fujirebio Incorporation and Sysmex Corporation, outside the submitted work. Ian Chi Kei Wong reports research funding outside the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong RGC, and the Hong Kong Health and Medical Research Fund, National Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: In view of accumulating case reports of thyroid dysfunction following COVID-19 vaccination, we evaluated the risks of incident thyroid dysfunction following inactivated (CoronaVac) and mRNA (BNT162b2) COVID-19 vaccines using a population-based dataset., Methods: We identified people who received COVID-19 vaccination between 23 February and 30 September 2021 from a population-based electronic health database in Hong Kong, linked to vaccination records. Thyroid dysfunction encompassed anti-thyroid drug (ATD)/levothyroxine (LT4) initiation, biochemical picture of hyperthyroidism/hypothyroidism, incident Graves' disease (GD), and thyroiditis. A self-controlled case series design was used to estimate the incidence rate ratio (IRR) of thyroid dysfunction in a 56-day post-vaccination period compared to the baseline period (non-exposure period) using conditional Poisson regression., Results: A total of 2,288,239 people received at least one dose of COVID-19 vaccination (57.8% BNT162b2 recipients and 42.2% CoronaVac recipients). 94.3% of BNT162b2 recipients and 92.2% of CoronaVac recipients received the second dose. Following the first dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.864, 95% CI 0.670-1.114; CoronaVac: IRR 0.707, 95% CI 0.549-0.912), LT4 initiation (BNT162b2: IRR 0.911, 95% CI 0.716-1.159; CoronaVac: IRR 0.778, 95% CI 0.618-0.981), biochemical picture of hyperthyroidism (BNT162b2: IRR 0.872, 95% CI 0.744-1.023; CoronaVac: IRR 0.830, 95% CI 0.713-0.967) or hypothyroidism (BNT162b2: IRR 1.002, 95% CI 0.838-1.199; CoronaVac: IRR 0.963, 95% CI 0.807-1.149), GD, and thyroiditis. Similarly, following the second dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.972, 95% CI 0.770-1.227; CoronaVac: IRR 0.879, 95%CI 0.693-1.116), LT4 initiation (BNT162b2: IRR 1.019, 95% CI 0.833-1.246; CoronaVac: IRR 0.768, 95% CI 0.613-0.962), hyperthyroidism (BNT162b2: IRR 1.039, 95% CI 0.899-1.201; CoronaVac: IRR 0.911, 95% CI 0.786-1.055), hypothyroidism (BNT162b2: IRR 0.935, 95% CI 0.794-1.102; CoronaVac: IRR 0.945, 95% CI 0.799-1.119), GD, and thyroiditis. Age- and sex-specific subgroup and sensitivity analyses showed consistent neutral associations between thyroid dysfunction and both types of COVID-19 vaccines., Conclusions: Our population-based study showed no evidence of vaccine-related increase in incident hyperthyroidism or hypothyroidism with both BNT162b2 and CoronaVac., (© 2022. The Author(s).)

Background: Monoclonal antibody (mAb) and Fc-fusion protein (FcP) are highly effective therapeutic biologics. We aimed to analyse consumption and expenditure trends in 14 Asia-Pacific countries/regions (APAC) and three benchmark countries (the UK, Canada, and the US)., Methods: We analysed 440 mAb and FcP biological products using the IQVIA-MIDAS global sales database. For each year between 2010 and 2020 inclusive, we used standard units (SU) sold per 1000 population and manufacture level price (standardised in 2019 US dollars) to evaluate consumption (accessibility) and expenditure (affordability). Changes of consumption and expenditure were estimated using compound annual growth rate (CAGR). Correlations between consumption, country's economic and health performance indicators were measured using Spearman correlation coefficient., Findings: Between 2010 and 2020, CAGRs of consumption in each region ranged from 7% to 34% and the CAGRs of expenditure ranged from 9% to 31%. The median consumption of biologics was extremely low in lower-middle-income economies (0·29 SU/1000 population) compared with upper-middle-income economies (1·20), high-income economies (40·94) and benchmark countries (109·55), although the median CAGRs of biologics consumption in lower-middle-income economies (31%) was greater than upper-middle-income (14%), high-income economies (13%) and benchmark countries (9%). Consumption was correlated with GDP per capita [Spearman's rank correlation coefficient (r) = 0·75, p < 0·001], health expenditure as a percentage of total (r = 0·83, p < 0·001) and medical doctors' density (r = 0·85, p < 0·001)., Interpretation: There have been significant increases in mAb and FcP biologics consumption and expenditure, however accessibility of biological medicines remains unequal and is largely correlated with country's income level., Funding: This research was funded by NHMRC Project Grant GNT1157506 and GNT1196900; Enhanced Start-up Fund for new academic staff and Internal Research Fund, Department of Medicine, LKS Faculty of Medicine, University of Hong Kong., Competing Interests: XL received research grants from Food and Health Bureau of the Government of the Hong Kong SAR (HMRF, HKSAR), Research Grants Council Early Career Scheme (RGC/ECS, HKSAR), RGC Research Matching Grant Scheme, Janssen, Pfizer and internal funding from the University of Hong Kong; consultancy fee from Merck Sharp & Dohme and Pfizer, unrelated to this work. Nicole L Pratt received research grants from Australian Government. WKL received speaker fees from Ferring, Janssen and Takeda. He also participated Data Safety Advisory Board in Astra Zeneca and Pfizer. All outside the submitted work. CSL reports payment of speaker fees from AbbVie, Astra Zeneca, GSK, Janssen, Pfizer and Roche. He also has participation on Astra Zeneca Data Safety Advisory Board. All outside the submitted work. ICKW reports research funding outside the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong RGC, and the Hong Kong Health and Medical Research Fund, National Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia, and also received speaker fees from Janssen and Medice the previous 3 years. He is also an independent non-executive director of Jacobson Medical in Hong Kong. All other authors have no reports on conflict of interest., (© 2022 The Authors.)

Background: Safety monitoring of coronavirus disease 2019 (COVID-19) vaccines is crucial during mass vaccination rollout to inform the choice of vaccines and reduce vaccine hesitancy. Considering the scant evidence directly comparing the safety profiles of mRNA and inactivated SARS-CoV-2 vaccines, this territory-wide cohort study aims to compare the incidence of various adverse events of special interest (AESIs) and all-cause mortality between CoronaVac (inactivated vaccine) and BNT162b2 (mRNA-based vaccine). Our results can help vaccine recipients make an informed choice., Methods and Findings: A retrospective, population-based cohort of individuals who had received at least 1 dose of BNT162b2 or CoronaVac from 23 February to 9 September 2021 in Hong Kong, and had data linkage to the electronic medical records of the Hong Kong Hospital Authority, were included. Those who had received mixed doses were excluded. Individuals were observed from the date of vaccination (first or second dose) until mortality, second dose vaccination (for first dose analysis), 21 days after vaccination, or 30 September 2021, whichever came first. Baseline characteristics of vaccinated individuals were balanced between groups using propensity score weighting. Outcome events were AESIs and all-cause mortality recorded during 21 days of post-vaccination follow-up after each dose, except anaphylaxis, for which the observation period was restricted to 2 days after each dose. Incidence rate ratios (IRRs) of AESIs and mortality comparing between CoronaVac and BNT162b2 recipients were estimated after each dose using Poisson regression models. Among 2,333,379 vaccinated individuals aged 18 years or above, the first dose analysis included 1,308,820 BNT162b2 and 955,859 CoronaVac recipients, while the second dose analysis included 1,116,677 and 821,560 individuals, respectively. The most frequently reported AESI among CoronaVac and BNT162b2 recipients was thromboembolism (first dose: 431 and 290 per 100,000 person-years; second dose: 385 and 266 per 100,000 person-years). After the first dose, incidence rates of overall AESIs (IRR = 0.98, 95% CI 0.89-1.08, p = 0.703) and mortality (IRR = 0.96, 95% CI 0.63-1.48, p = 0.868) associated with CoronaVac were generally comparable to those for BNT162b2, except for Bell palsy (IRR = 1.95, 95% CI 1.12-3.41, p = 0.018), anaphylaxis (IRR = 0.34, 95% CI 0.14-0.79, p = 0.012), and sleeping disturbance or disorder (IRR = 0.66, 95% CI 0.49-0.89, p = 0.006). After the second dose, incidence rates of overall AESIs (IRR = 0.97, 95% CI 0.87-1.08, p = 0.545) and mortality (IRR = 0.85, 95% CI 0.51-1.40, p = 0.516) were comparable between CoronaVac and BNT162b2 recipients, with no significant differences observed for specific AESIs. The main limitations of this study include residual confounding due to its observational nature, and the possibility of its being underpowered for some AESIs with very low observed incidences., Conclusions: In this study, we observed that the incidences of AESIs (cumulative incidence rate of 0.06%-0.09%) and mortality following the first and second doses of CoronaVac and BNT162b2 vaccination were very low. The safety profiles of the vaccines were generally comparable, except for a significantly higher incidence rate of Bell palsy, but lower incidence rates of anaphylaxis and sleeping disturbance or disorder, following first dose CoronaVac versus BNT162b2 vaccination. Our results could help inform the choice of inactivated COVID-19 vaccines, mainly administered in low- and middle-income countries with large populations, in comparison to the safety of mRNA vaccines. Long-term surveillance on the safety profile of COVID-19 vaccines should continue., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CKHW reports receipt of research funding from the EuroQoL Group Research Foundation, the Hong Kong Research Grants Council, and the Hong Kong Health and Medical Research Fund; FTTL has been supported by the RGC Postdoctoral Fellowship under the Hong Kong Research Grants Council; EYFW has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, and the Hong Kong Research Grants Council, outside the submitted work; CSLC has received grants from the Food and Health Bureau of the Hong Kong Government, Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, and Amgen, personal fee from Primevigilance Ltd., outside the submitted work; XL has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, research and educational grants from Janssen and Pfizer, internal funding from University of Hong Kong, consultancy fee from Merck Sharp & Dohme, unrelated to this work; EWYC reports grants from Research Grants Council (RGC, Hong Kong), grants from Research Fund Secretariat of the Food and Health Bureau, grants from National Natural Science Fund of China, grants from Wellcome Trust, grants from Bayer, grants from Bristol-Myers Squibb, grants from Pfizer, grants from Janssen, grants from Amgen, grants from Takeda, grants from Narcotics Division of the Security Bureau of HKSAR and honorarium from Hospital Authority, outside the submitted work; SCWT reports research funding outside the submitted work from the Hong Kong RGC, and the Hong Kong Health and Medical Research Fund, and National Natural Science Fund of China; ICKW reports research funding outside the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong RGC, and the Hong Kong Health and Medical Research Fund, National Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia, and also received speaker fees from Janssen and Medice in the previous 3 years; KTKL, XX, ICHA, LG, and FWTC report no disclosures relevant to the manuscript. Authors who report research funding or grants from Pfizer outside the submitted work have no financial conflict of interests to the current study.

Introduction: Compared with young children who have acute lymphoblastic leukaemia (ALL), adolescents with ALL have unfavourable disease profiles and worse survival. However, limited data are available regarding the characteristics and outcomes of adolescents with ALL who underwent treatment in clinical trials. The aim of this study was to investigate the causes of treatment failure in adolescents with ALL., Methods: We retrospectively analysed the outcomes of 711 children with ALL, aged 1-18 years, who were enrolled in five clinical trials of paediatric ALL treatment between 1993 and 2015., Results: Among the 711 children with ALL, 530 were young children (1-9 years at diagnosis) and 181 were adolescents (including 136 younger adolescents [10-14 years] and 45 older adolescents [15-18 years]). Compared with young children who had ALL, adolescents with ALL were less likely to have favourable genetic features and more likely to demonstrate poor early response to treatment. The 10-year overall survival and event-free survival rates were significantly lower among adolescents than among young children (77.9% vs 87.6%, P=0.0003; 69.7% vs 76.5%, P=0.0117). There were no significant differences in the 10-year cumulative incidence of relapse, but the 10-year cumulative incidence of treatment-related death (TRD) was significantly greater among adolescents (7.2%) than among young children (2.3%; P=0.002). Multivariable analysis showed that both younger and older adolescents (vs young children) had worse survival and greater incidence of TRD., Conclusion: Adolescents with ALL had worse survival because they experienced a greater incidence of TRD. There is a need to investigate optimal treatment adjustments and novel targeted agents to achieve better survival rates (without excessive toxicity) among adolescents with ALL., Competing Interests: All authors have disclosed no conflicts of interest.

Background: Thyroiditis and Graves' disease have been reported after coronavirus disease 2019 (COVID-19) vaccination. We evaluated the risks of adverse events after COVID-19 vaccination among patients treated for hypothyroidism. Methods: In this retrospective population-based cohort study of Hong Kong Hospital Authority electronic health records with the Department of Health vaccination records linkage, levothyroxine (LT4) users were categorized into unvaccinated, vaccinated with BNT162b2 (mRNA vaccine), or CoronaVac (inactivated vaccine) between February 23, 2021, and September 9, 2021. Study outcomes were dosage reduction or escalation in LT4, emergency department (ED) visit, unscheduled hospitalization, adverse events of special interest (AESI) according to the World Health Organization's Global Advisory Committee on Vaccine Safety, and all-cause mortality. Inverse probability of treatment weighting for propensity score was applied to balance baseline patient characteristics among the three groups. Hazard ratios (HR) were estimated using Cox regression models. Patients were observed from the index date until the occurrence of study outcome, death, or censored on September 30, 2021, whichever came first. Results: In total, 47,086 LT4 users were identified (BNT162b2: n  = 12,310; CoronaVac: n  = 11,353; and unvaccinated: n  = 23,423). COVID-19 vaccination was not associated with increased risks of LT4 dosage reduction (BNT162b2: HR = 0.971 [confidence interval; CI 0.892-1.058]; CoronaVac: HR = 0.968 [CI 0.904-1.037]) or escalation (BNT162b2: HR = 0.779 [CI 0.519-1.169]; CoronaVac: HR = 0.715 [CI 0.481-1.062]). Besides, COVID-19 vaccination was not associated with a higher risk of ED visits (BNT162b2: HR = 0.944 [CI 0.700-1.273]; CoronaVac: HR = 0.851 [CI 0.647-1.120]) or unscheduled hospitalization (BNT162b2: HR = 0.905 [CI 0.539-1.520]; CoronaVac: HR = 0.735 [CI 0.448-1.207]). There were two (0.016%) deaths and six (0.062%) AESI recorded for BNT162b2 recipients, and one (0.009%) and three (0.035%) for CoronaVac recipients, respectively. Conclusions: BNT162b2 or CoronaVac vaccination is not associated with unstable thyroid status or an increased risk of adverse outcomes among patients treated for hypothyroidism in general. These reassuring data should encourage them to get vaccinated against COVID-19 for protection from potentially worse COVID-19-related outcomes.

Inter-individual variance in 6-mercaptopurine (6-MP) dose intensity is common in patients with acute lymphoblastic leukemia (ALL). We aimed to evaluate the association of common variants of ABCC4 , ITPA , NUDT15 , and TPMT with 6-MP dose intensity and toxicity in pediatric ALL patients. In this cohort, 13.8% of patients were intolerant to 6-MP with actual dosage less than 50% of scheduled dose. Twenty percent of patients were found to be heterozygous or homozygous mutated with NUDT15 . NUDT15 c.415C > T and the genotype-predicted NUDT15 activity were significantly associated with 6-MP intolerance. TPMT *3C variants were not common in this cohort (2.8%). NUDT15 polymorphisms and genotype predicted NUDT15 activity were significantly associated with 6-MP dose intensity and leukopenia episodes. Combination of ABCC4 and ITPA variants ( ABCC4 c.912G > T and ITPA c.94C > A) also showed significant positive association with 6-MP intolerance in Chinese children with ALL. Further study on pharmacogenetic screening for ALL patients to avoid 6-MP induced toxicity is recommended.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1973628.

Aim: Childhood encephalopathy comprises a wide range of etiologies with distinctive distribution in different age groups. We reviewed the pattern of encephalopathy admitted to the pediatric intensive care unit (PICU) of a tertiary children's hospital., Methods: We reviewed the medical records and reported the etiologies, clinical features, and outcomes of children with encephalopathy., Results: Twenty-four admissions to the PICU between April 2019 and May 2020 were reviewed. The median (interquartile range) age was 10.0 (14.7) years and 62.5% were boys. Confusion (66.7%) was the most common presentation. Adverse effects related to medications (33.3%) and metabolic disease (20.8%) were predominant causes of encephalopathies in our study cohort. Methotrexate was responsible for most of the medication-associated encephalopathy (37.5%), whereas Leigh syndrome, pyruvate dehydrogenase deficiency and Wernicke's encephalopathy accounted for those with metabolic disease. The median Glasgow Coma Scale (GCS) on admission was 12.5 (9.0). Antimicrobials (95.8%) and antiepileptic drugs (60.9%) were the most frequently given treatment. Children aged 2 years or younger were all boys (P = 0.022) and had a higher proportion of primary metabolic disease (P = 0.04). Intoxication or drug reaction only occurred in older children. The mortality was 8.3%, and over half of the survivors had residual neurological disability upon PICU discharge. Primary metabolic disease (P = 0.002), mechanical ventilation (P = 0.019), failure to regain GCS back to baseline level (P = 0.009), and abnormal cognitive function on admission (P = 0.03) were associated with cerebral function impairment on PICU discharge., Conclusions: Primary metabolic encephalopathy was prevalent in younger children, whereas drug-induced toxic encephalopathy was common among older oncology patients. Survivors have significant neurologic morbidity. Failure to regain baseline GCS was a poor prognostic factor for neurological outcomes., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There is no established effective treatment for patients with t(1;22)(p13;q13) acute megakaryoblastic leukemia (AMKL) and hepatic fibrosis., Observation: Here we report the outcomes of 2 t(1;22)(p13;q13) AMKL patients with hepatic fibrosis. One patient died from liver failure despite the control of leukemia. The other patient was successfully treated with reduced-intensity chemotherapy and antifibrosis therapy with tretinoin and α-tocopheryl acetate, the hepatic fibrosis resolved and leukemia was in remission for 3 years., Conclusions: Reduced-intensity chemotherapy plus antifibrosis therapy with tretinoin and α-tocopheryl acetate could be a treatment option for these patients with t(1;22)(p13;q13) AMKL and hepatic fibrosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)