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Background: Most studies on the impact of the COVID-19 pandemic on depression burden focused on the earlier pandemic phase specific to lockdowns, but the longer-term impact of the pandemic is less well-studied. In this population-based cohort study, we examined the short-term and long-term impacts of COVID-19 on depression incidence and healthcare service use among patients with depression., Methods: Using the territory-wide electronic medical records in Hong Kong, we identified all patients aged ≥ 10 years with new diagnoses of depression from 2014 to 2022. We performed an interrupted time-series (ITS) analysis to examine changes in incidence of medically attended depression before and during the pandemic. We then divided all patients into nine cohorts based on year of depression incidence and studied their initial and ongoing service use patterns until the end of 2022. We applied generalized linear modeling to compare the rates of healthcare service use in the year of diagnosis between patients newly diagnosed before and during the pandemic. A separate ITS analysis explored the pandemic impact on the ongoing service use among prevalent patients with depression., Results: We found an immediate increase in depression incidence (RR = 1.21, 95% CI: 1.10-1.33, p < 0.001) in the population after the pandemic began with non-significant slope change, suggesting a sustained effect until the end of 2022. Subgroup analysis showed that the increases in incidence were significant among adults and the older population, but not adolescents. Depression patients newly diagnosed during the pandemic used 11% fewer resources than the pre-pandemic patients in the first diagnosis year. Pre-existing depression patients also had an immediate decrease of 16% in overall all-cause service use since the pandemic, with a positive slope change indicating a gradual rebound over a 3-year period., Conclusions: During the pandemic, service provision for depression was suboptimal in the face of increased demand generated by the increasing depression incidence during the COVID-19 pandemic. Our findings indicate the need to improve mental health resource planning preparedness for future public health crises., (© 2024. The Author(s).)

Background: Based on real-world data, we developed a 10-year prediction model to estimate the burden among patients with depression from the public healthcare system payer's perspective to inform early resource planning in Hong Kong., Methods: We developed a Markov cohort model with yearly cycles specifically capturing the pathway of treatment-resistant depression (TRD) and comorbidity development along the disease course. Projected from 2023 to 2032, primary outcomes included costs of all-cause and psychiatric care, and secondary outcomes were all-cause deaths, years of life lived, and quality-adjusted life-years. Using the territory-wide electronic medical records, we identified 25,190 patients aged ≥10 years with newly diagnosed depression from 2014 to 2016 with follow-up until 2020 to observe the real-world time-to-event pattern, based on which costs and time-varying transition inputs were derived using negative binomial modelling and parametric survival analysis. We applied the model as both closed cohort, which studied a fixed cohort of incident patients in 2023, and open cohort, which introduced incident patients by year from 2014 to 2032. Utilities and annual new patients were from published sources., Findings: With 9217 new patients in 2023, our closed cohort model projected the 10-year cumulative costs of all-cause and psychiatric care to reach US$309.0 million and US$58.3 million, respectively, with 899 deaths (case fatality rate: 9.8%) by 2032. In our open cohort model, 55,849-57,896 active prevalent cases would cost more than US$322.3 million and US$60.7 million, respectively, with more than 943 deaths annually from 2023 to 2032. Fewer than 20% of cases would live with TRD or comorbidities but contribute 31-54% of the costs. The greatest collective burden would occur in women aged above 40, but men aged above 65 and below 25 with medical history would have the highest costs per patient-year. The key cost drivers were relevant to the early disease stages., Interpretation: A limited proportion of patients would develop TRD and comorbidities but contribute to a high proportion of costs, which necessitates appropriate attention and resource allocation. Our projection also demonstrates the application of real-world data to model long-term costs and mortality, which aid policymakers anticipate foreseeable burden and undertake budget planning to prepare for the care need in alternative scenarios., Funding: Research Impact Fund from the University Grants Committee, Research Grants Council with matching fund from the Hong Kong Association of Pharmaceutical Industry (R7007-22)., Competing Interests: X Li received research grants from Hong Kong Health and Medical Research Fund (HMRF, HMRF Fellowship Scheme, HKSAR), Research Grants Council Early Career Scheme (RGC/ECS, HKSAR), Janssen and Pfizer; internal funding from the University of Hong Kong; consultancy fees from Merck Sharp & Dohme and Pfizer; she is also a non-executive director of Advanced Data Analytics for Medical Science (ADAMS) Limited Hong Kong, all are unrelated to this work; H Luo received research grants Research Grants Council Early Career Scheme (RGC/ECS, HKSAR) unrelated to this work. EWY Chan reports grants from Research Grants Council, Research Fund Secretariat of the Food and Health Bureau, National Natural Science Fund of China, Wellcome Trust, Bayer, Amgen, Bristol-Myers Squibb, Janssen, Takeda, Narcotics Division of the Security Bureau of Hong Kong, honorarium from Hospital Authority, outside the submitted work; ICK Wong received research funding outside the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, Takeda, 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, The European Union's Seventh Framework Programme for research technological development, and has also received consulting fees from IQVIA, the WHO and expert testimony for Appeal Court in Hong Kong over the past three years. He is also a non-executive director of Jacobson Medical Hong Kong, and founder and director of Therakind Limited (United Kingdom), Advanced Data Analytics for Medical Science (ADAMS) Limited (Hong Kong), Asia Medicine Regulatory Affairs (AMERA) Services Limited and OCUS Innovation Limited (Hong Kong, Ireland and United Kingdom)., (© 2024 The Authors.)

Background: Recommendations around the use of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13) seldom focus on potential benefits of vaccine on comorbidities. We aimed to investigate whether sequential vaccination with PCV13 and PPSV23 among older adults would provide protection against cardiovascular diseases (CVD) compared with using a single pneumococcal vaccine., Methods: We conducted a Hong Kong-wide retrospective cohort study between 2012 and 2020. Adults aged ≥65 years were identified as receiving either a single or sequential dual vaccination and followed up until the earliest CVD occurrence, death or study end. To minimize confounding, we matched each person receiving a single vaccination to a person receiving sequential vaccination according to their propensity scores. We estimated the hazard ratio (HR) of CVD risk using Cox regression and applied structural equation modelling to test whether the effect of sequential dual vaccination on CVD was mediated via the reduction in pneumonia., Results: After matching, 69 390 people remained in each group and the median (interquartile range) follow-up time was 1.89 (1.55) years. Compared with those receiving a single vaccine, those receiving sequential dual vaccination had a lower risk of CVD [HR (95% CI): 0.75 (0.71, 0.80), P < 0.001]. Post-hoc mediation analysis showed strong evidence that the decreased CVD risk was mediated by the reduction in all-cause pneumonia., Conclusions: Sequential dual pneumococcal vaccination was associated with lower risk of CVD compared with single-dose PCV13 or PPSV23 in older adults. Such additional CVD benefits should be considered when making decisions about pneumococcal vaccination., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Lumbar microdiscectomy is the most frequent surgical intervention used in the treatment of sciatica from herniated lumbar discs. Many discectomy trials have been plagued with an excessive number of crossovers that have rendered results inconclusive., Methods: We review the design and results of influential lumbar microdiscectomy trials. We also discuss the various strategies that have been used to decrease the number of crossovers or to mitigate the effects of crossovers on analyses., Results: Randomized trials on lumbar discectomy were affected by crossover rates of 8% to 42%. Various strategies that have been used to decrease that number or to mitigate the effects on results include: patient selection, blinding (placebo-controlled trials), an immediate access to surgery for the surgical group (but limited access to surgery for the conservative group), shortening the follow-up period necessary to reach the primary outcome measure, postponing crossovers to surgery after determination of the primary outcome, and modifying the primary outcome measure to include treatment failures. Crossovers should be anticipated and compensated for by increasing the number of participants., Conclusion: Non-adherence to randomly allocated management options can deprive trials of the statistical power needed to inform clinical care. Crossovers and ways to mitigate related problems should be anticipated at the time of trial design., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Formulating a pertinent research question is of the utmost importance in clinical research. An ill-conceived question may lead to an erroneous trial design, which may adversely affect the care of patients and provide uninformative or even misleading results., Methods: We review the research question of a randomized trial on the timing of lumbar discectomy. We compare the resulting design with other trials, real or hypothetical, that would have been more appropriate., Results: The RCT we examine randomly allocated patients to early or delayed surgery to answer a theoretical question of the effect of time on the efficacy of surgery. The trial was interpreted to have shown that early surgery was associated with better clinical and functional outcomes as compared to delayed surgery. This conclusion is clinically misleading. Valid comparisons between groups should be performed on intent-to-treat analyses and at the same time points after randomization (and not at a fixed follow-up period after surgery). The clinically pertinent comparison is not between the theoretical efficacy of surgery performed at various times, but between surgery and conservative management in patients presenting at various times. Better-designed trials on the clinical benefits of lumbar discectomy, including the treatment of chronic sciatica, have been published., Conclusion: Theoretical research questions inspired from observational data can lead to erroneous trial design. Prospective randomized trials impact practice immediately: they are unique occasions to address clinical problems and optimize care under uncertainty in real time. However, they require the research question to be formulated with great care., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Recent literature indicates that patients with depression had increased immune activation. We hypothesised that treatment-resistant depression (TRD), an indicator of non-responsive depression with long-term dysregulated inflammation, could be an independent risk factor for subsequent autoimmune diseases. We performed a cohort study and a nested case-control study to examine the association between TRD and risk of autoimmune diseases, and to explore potential sex-specific difference. Using electronic medical records in Hong Kong, we identified 24,576 patients with incident depression between 2014 and 2016 without autoimmune history and followed up from diagnosis to death or December 2020 to identify TRD status and autoimmune incidence. TRD was defined as having at least two antidepressant regimens and the third regimen to confirm previous treatment failures. Based on age, sex and year of depression, we matched TRD patients 1:4 to the non-TRD in the cohort analysis using nearest-neighbour matching, and matched cases and controls 1:10 using incidence density sampling in the nested case-control analysis. We conducted survival analyses and conditional logistic regression respectively for risk estimation, adjusting for medical history. Across the study period, 4349 patients without autoimmune history (17.7%) developed TRD. With 71,163 person-years of follow-up, the cumulative incidence of 22 types of autoimmune diseases among the TRD patients was generally higher than the non-TRD (21.5 vs. 14.4 per 10,000 person-years). Cox model suggested a non-significant association (HR:1.48, 95% CI: 0.99-2.24, p = 0.059), whereas conditional logistic model showed a significant association (OR: 1.67, 95% CI: 1.10-2.53, p = 0.017) between TRD status and autoimmune diseases. Subgroup analysis showed that the association was significant in organ-specific diseases but not in systemic diseases. Risk magnitudes were generally higher among men compared to women. In conclusion, our findings provide evidence for an increased risk of autoimmune diseases in patients with TRD. Controlling chronic inflammation in hard-to-treat depression might play a role in preventing subsequent autoimmunity., (© 2023. The Author(s).)

Objective: There is a socioeconomic gradient to depression risks, with more pronounced inequality amid macroenvironmental potential traumatic events. Between mid-2019 and mid-2020, the Hong Kong population experienced drastic societal changes, including the escalating civil unrest and the COVID-19 pandemic. We examined the change of the socioeconomic gradient in depression and the potential intermediary role of daily routine disruptions., Method: We conducted repeated territory-wide telephone surveys in July 2019 and July 2020 with 1112 and 2034 population-representative Cantonese-speaking Hong Kong citizens above 15 years old, respectively. Stratified by year, we examined the association between socioeconomic indicators (education attainment, household income, employment status and marital status) and probable depression (nine-item Patient Health Questionnaire [PHQ-9] ⩾ 10) using logistic regression. Differences in the socioeconomic gradient between 2019 and 2020 were tested. Finally, we performed a path analysis to test for the mediating role of daily routine disruptions., Results: Logistic regression showed that higher education attainment in 2019 and being married in 2020 were protective against probable depression. Interaction analysis showed that the inverse association of higher education attainment with probable depression attenuated in 2020 but that of being married increased. Path analysis showed that the mediated effects through daily routine disruptions accounted for 95.9% of the socioeconomic gradient of probable depression in 2020, compared with 13.1% in 2019., Conclusion: From July 2019 to July 2020, the mediating role of daily routine disruptions in the socioeconomic gradient of depression in Hong Kong increased. It is thus implied that infection control measures should consider the relevant potential mental health impacts accordingly.

Background: Concerns regarding the autoimmune safety of COVID-19 vaccines may negatively impact vaccine uptake. We aimed to describe the incidence of autoimmune conditions following BNT162b2 and CoronaVac vaccination and compare these with age-standardized incidence rates in non-vaccinated individuals., Methods: This is a descriptive cohort study conducted in public healthcare service settings. Territory-wide longitudinal electronic medical records of Hong Kong Hospital Authority users (≥16 years) were linked with COVID-19 vaccination records between February 23, 2021 and June 30, 2021. We classified participants into first/second dose BNT162b2 groups, first/second dose CoronaVac groups and non-vaccinated individuals for incidence comparison. The study outcomes include hospitalized autoimmune diseases (16 types of immune-mediated diseases across six body systems) within 28 days after first and second dose of vaccination. Age-standardized incidence rate ratios (IRRs) with exact 95% confidence intervals (CIs) were estimated using Poisson distribution., Results: This study included around 3.9 million Hong Kong residents, of which 1,122,793 received at least one dose of vaccine (BNT162b2: 579,998; CoronaVac: 542,795), and 721,588 completed two doses (BNT162b2: 388,881; CoronaVac: 332,707). Within 28 days following vaccination, cumulative incidences for all autoimmune conditions were below 9 per 100,000 persons, for both vaccines and both doses. None of the age-standardized incidence rates were significantly higher than the non-vaccinated individuals, except for an observed increased incidence of hypersomnia following the first dose of BNT162b2 (standardized IRR: 1.47; 95% CI: 1.10-1.94)., Conclusions: Autoimmune conditions requiring hospital care are rare following mRNA and inactivated COVID-19 vaccination with similar incidence to non-vaccinated individuals. The association between first dose BNT162b2 vaccination and immune-related sleeping disorders requires further research. Population-based robust safety surveillance is essential to detect rare and unexpected vaccine safety events., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Depression symptoms are significantly associated with an increased risk of cardiovascular disease (CVD). However, understanding of the magnitude of the association between depression duration and risk of CVD is limited. Therefore, we aimed to assess whether a longer duration of exposure to depression is associated with a higher risk of new-onset CVD., Methods: We conducted a territory-wide retrospective cohort study among patients (≥ 10 years old) with depression diagnosed between January and December 2014 in Hong Kong. The observation period spanned January 1, 2014, to December 31, 2019, and all participants had no CVD at baseline. Incidence of CVD was calculated. We used Cox proportional hazard regression to adjust confounders and estimate hazard ratios of CVD risk., Results: Among 11,651 participants with depression, 1306 (11.2%) individuals developed CVD. Multi-adjusted models showed individuals with depression duration of 2-5 years (Hazard Ratios [HRs]: 1.38 [95% confidence interval (CI): 1.19-1.60]) and ≥6 years (1.45 [1.25-1.68]) had a significantly escalated risk of developing CVD, compared to those with depression within one year. Stratified analyses indicated that the association was prominent in women and those under 65 years old., Limitations: Lack of depression severity information and the small sample size in some subgroup analyses., Conclusions: Longer exposure to depression is associated with significant increased risk of CVD. The interplay between mental and vascular health emphasizes the need for CVD prevention in patients with long-term depression., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: There are few randomized data comparing clipping and coiling for middle cerebral artery (MCA) aneurysms. We analyzed results from patients with MCA aneurysms enrolled in the CURES (Collaborative UnRuptured Endovascular vs. Surgery) and ISAT-2 (International Subarachnoid Aneurysm Trial II) randomized trials., Methods: Both trials are investigator-led parallel-group 1:1 randomized studies. CURES includes patients with 3-mm to 25-mm unruptured intracranial aneurysms (UIAs), and ISAT-2 includes patients with ruptured aneurysms (RA) for whom uncertainty remains after ISAT. The primary outcome measure of CURES is treatment failure: 1) failure to treat the aneurysm, 2) intracranial hemorrhage during follow-up, or 3) residual aneurysm at 1 year. The primary outcome of ISAT-2 is death or dependency (modified Rankin Scale score >2) at 1 year. One-year angiographic outcomes are systematically recorded., Results: There were 100 unruptured and 71 ruptured MCA aneurysms. In CURES, 90 patients with UIA have been treated and 10 await treatment. Surgical and endovascular management of unruptured MCA aneurysms led to treatment failure in 3/42 (7%; 95% confidence interval [CI], 0.02-0.19) for clipping and 13/48 (27%; 95% CI, 0.17-0.41) for coiling (P = 0.025). All 71 patients with RA have been treated. In ISAT-2, patients with ruptured MCA aneurysms managed surgically had died or were dependent (modified Rankin Scale score >2) in 7/38 (18%; 95% CI, 0.09-0.33) cases, and 8/33 (24%; 95% CI, 0.13-0.41) for endovascular. One-year imaging results were available in 80 patients with UIA and 62 with RA. Complete aneurysm occlusion was found in 30/40 (75%; 95% CI, 0.60-0.86) patients with UIA allocated clipping, and 14/40 (35%; 95% CI, 0.22-0.50) patients with UIA allocated coiling. Complete aneurysm occlusion was found in 24/34 (71%; 95% CI, 0.54-0.83) patients with RA allocated clipping, and 15/28 (54%; 95% CI, 0.36-0.70) patients with RA allocated coiling., Conclusions: Randomized data from 2 trials show that better efficacy may be obtained with surgical management of patients with MCA aneurysms., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.

Objectives: Three hundred million people living with rare diseases worldwide are disproportionately deprived of in-time diagnosis and treatment compared with other patients. This review provides an overview of global policies that optimize development, licensing, pricing, and reimbursement of orphan drugs., Methods: Pharmaceutical legislation and policies related to access and regulation of orphan drugs were examined from 194 World Health Organization member countries and 6 areas. Orphan drug policies (ODPs) were identified through internet search, emails to national pharmacovigilance centers, and systematic academic literature search. Texts from selected publications were extracted for content analysis., Results: One hundred seventy-two drug regulation documents and 77 academic publications from 162 countries/areas were included. Ninety-two of 200 countries/areas (46.0%) had documentation on ODPs. Thirty-four subthemes from content analysis were categorized into 6 policy themes, namely, orphan drug designation, marketing authorization, safety and efficacy requirements, price regulation, incentives that encourage market availability, and incentives that encourage research and development. Countries/areas with ODPs were statistically wealthier (gross national income per capita = $10 875 vs $3950, P < .001). Country/area income was also positively correlated with the scope of the respective ODP (correlation coefficient = 0.57, P < .001)., Conclusions: Globally, the number of countries with an ODP has grown rapidly since 2013. Nevertheless, disparities in geographical distribution and income levels affect the establishment of ODPs. Furthermore, identified policy gaps in price regulation, incentives that encourage market availability, and incentives that encourage research and development should be addressed to improve access to available and affordable orphan drugs., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

AIntradialytic hypotension (IDH) occurring during hemodialysis (HD) may cause severe complications and can be life-threatening. IDH is a common symptom in patients with end stage renal disease undergoing HD. Currently, no effective predictive models for IDH exist. This study analyzed data on variations in oxygen saturation (SaO 2 ) and heart rate (HR) in 68 patients during their HD sessions by using sequence alignment and Boolean algebra. Three classifiers derived from SaO 2 and HR variation data were developed as predictors for predetermining IDH occurrence within 30 minutes. The accuracy of these classifiers in predicting IDH occurrence was approximately 80%. SaO 2 and HR variations can potentially be used as predictors for developing an alarm system for detecting IDH occurrence., Competing Interests: The author reported no actual or potential conflict of interest in relation to this continuing nursing education activity., (Copyright© by the American Nephrology Nurses Association.)

This study modeled the general relationship between individual Macao adolescents' universal human values, measured by the Schwartz Values Inventory, and their problem/pathological gambling, indicated by the South Oaks Gambling Screen, using parsimonious, quantitative structural equation modeling. Data were collected through 471 questionnaires (261 females and 210 males) in 2010. Of the 10 value types in the Schwartz Values Inventory and derived value subtypes, only the human value subtype "nonfaith tradition" was found to be (negatively) related to problem/pathological gambling in the model. The corresponding factor loading was -0.07 (p = .015). This study was supported by the Education and Youth Affairs Bureau, the Government of Macao.