Impact of COVID-19 pandemic on depression incidence and healthcare service use among patients with depression: an interrupted time-series analysis from a 9-year population-based study.

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.

Risk stratification for early postoperative infection in Pediatric spinal deformity correction: development and validation of the Pediatric scoliosis infection risk score (PSIR score).

BACKGROUND CONTEXT: Postoperative infection after spinal deformity correction in pediatric patients is associated with significant costs. Identifying risk factors associated with postoperative infection would help surgeons identify high-risk patients that may require interventions to minimize infection risk. PURPOSE: To investigate risk factors associated with 30-day postoperative infection in pediatric patients who have received posterior arthrodesis for spinal deformity correction. STUDY DESIGN/SETTING: Retrospective review of prospectively collected data. PATIENT SAMPLE: The National Surgical Quality Improvement Program Pediatric database for years 2016-2021 was used for this study. Patients were included if they received posterior arthrodesis for scoliosis or kyphosis correction (CPT 22,800, 22,802, 22,804). Anterior only approaches were excluded. OUTCOME MEASURES: TThe outcome of interest was 30-day postoperative infection. METHODS: Patient demographics and outcomes were analyzed using descriptive statistics. Multivariable logistic regression analysis using likelihood ratio backward selection method was used to identify significant risk factors for 30-day infection to create the Pediatric Scoliosis Infection Risk Score (PSIR Score). ROC curve analysis, predicted probabilities, and Hosmer Lemeshow goodness-of-fit test were done to assess the scoring system on a validation cohort. RESULTS: A total of 31,742 patients were included in the study. The mean age was 13.8 years and 68.7% were female. The 30-day infection rate was 2.2%. Reoperation rate in patients who had a post-operative infection was 59.4%. Patients who had post-operative infection had a higher likelihood of non-home discharge (X2 = 124.8, p < 0.001). In our multivariable regression analysis, high BMI (OR = 1.01, p < 0.001), presence of open wound (OR = 3.18, p < 0.001), presence of ostomy (OR = 1.51, p < 0.001), neuromuscular etiology (OR = 1.56, p = 0.009), previous operation (OR = 1.74, p < 0.001), increasing ASA class (OR = 1.43, p < 0.001), increasing operation time in hours (OR = 1.11, p < 0.001), and use of only minimally invasive techniques (OR = 4.26, p < 0.001) were associated with increased risk of 30-day post-operative infection. Idiopathic etiology (OR = 0.53, p < 0.001) and intraoperative topical antibiotic use (B = 0.71, p = 0.003) were associated with reduced risk of 30-day postoperative infection. The area under the curve was 0.780 and 0.740 for the derivation cohort and validation cohort, respectively. CONCLUSIONS: To our knowledge, this is the largest study of risk factors for infection in pediatric spinal deformity surgery. We found 5 patient factors (BMI, ASA, osteotomy, etiology, and previous surgery, and 3 surgeon-controlled factors (surgical time, antibiotics, MIS) associated with risk. The Pediatric Scoliosis Infection Risk Score (PSIR) Score can be applied for risk stratification and to investigate implementation of novel protocols to reduce infection rates in high-risk patients.

Autoimmune conditions following mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccination: A descriptive cohort study among 1.1 million vaccinated people in Hong Kong.

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.

Disrupted daily routines mediate the socioeconomic gradient of depression amid public health crises: A repeated cross-sectional study.

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.

Access and Unmet Needs of Orphan Drugs in 194 Countries and 6 Areas: A Global Policy Review With Content Analysis.

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.

Multiple recurrences of spindle cell oncocytoma: A case report and literature review.

Spindle cell oncocytoma (SCO) is a rare tumor originating from pituicytes of the neurohypophysis. It typically occurs in the adult population between 50 and 60 years of age and is often misdiagnosed preoperatively as pituitary adenoma because of similar clinical presentation and neuroimaging features. Diffuse nuclear immunoreactivity for TTF-1 (also known as NK2 homeobox 1 factor) is characteristic of SCO and other tumors of the posterior pituitary. We report a case of SCO in a patient who underwent multiple surgical resections for recurrence. The aim of this case report and literature review is to provide an overview of what is currently known about SCO as well as raise the awareness of this entity to endocrinologists, neurologists, neurosurgeons, and neuropathologists. Our case is also unusual in that the tumor displayed immunoreactivity for neuronal markers, which is a very rare occurrence.

Declining Admission and Mortality Rates for Subarachnoid Hemorrhage in Canada Between 2004 and 2015.

Background and Purpose- The purpose of this study was to assess recent trends in the admission and mortality rates for subarachnoid hemorrhage in Canada. Methods- This retrospective cross-sectional study was based on data retrieved from the Canadian Institute for Health Information for all patients diagnosed with subarachnoid hemorrhage in Canada between 2004 and 2015. Adjusted admission rate, in-hospital mortality rates, and discharge disposition were calculated. Results- A total of 19 765 patients were diagnosed with subarachnoid hemorrhage between 2004 and 2015. The mean age was 58.1 years, and 40.3% were men. The annual hospitalization rate was 6.34 per 100 000 person-years, declining by -0.67% annually. In-hospital mortality rate was 21.5%. Conclusions- The Canadian subarachnoid hemorrhage admission and mortality rates are lower than previously reported, with a declining trend.

Blunt chest trauma: classification and management.

Blunt chest wall injuries are a significant cause of mortality and morbidity in trauma patients. Accurate identification and description of chest wall injuries by the radiologist can aid in guiding proper patient management. The American Association for the Surgery of Trauma (AAST) has devised a classification system based on severity. This article describes the features of each injury grade according to the AAST injury scale and discusses the implications for management. Additionally, common mechanisms of blunt chest trauma and multimodal imaging techniques are discussed.

The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity.

The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens.

Incidence of seizure in adult patients with intracranial metastatic disease.

Seizures have considerable impact on a patient's quality of life. While guidelines have been articulated to direct clinicians in their management of patients with IMD who suffer from seizure, there have been few attempts to identify the seizure rate in IMD and to determine which primary cancers may be associated with an increased seizure incidence. To determine the incidence of seizure in patients with IMD. A systematic review on seizure incidence in patients with IMD from the magnetic resonance imaging (MRI) era was performed. Articles published between January 2000 and July 2014 with thirty or more consecutive adult patients were included in this study. Seizure rate was calculated using a pooled data analysis. Differences between observed and expected seizure rates between primary tumour sites were examined using the Chi square statistic and adjusted standardized residuals. The systematic search produced 18 relevant studies, with a total study population of 2012 patients. 14.6% (n = 294) had seizures. There was a significant association between primary tumour site and seizure rates. The seizure rate in patients with primary melanoma tumours was significantly greater than expected (z = 2.7; p = .006). The seizure rate in patients with primary prostate tumours was significantly lower than expected (z = -2.6; p = .008). Patients with intracranial metastasis are at significant risk for developing seizure, though at a significantly lower incidence than was estimated by studies performed during the CT era. Seizure rates appear to be greater in certain primary tumours, such as melanoma.

Special Needs: Scholastic Disability Accommodations from K-12 and Transitions to Higher Education.

The number of students entering post-secondary education with already diagnosed disabilities is on the rise and mirrors the percentage of children in primary and secondary public schools with registered disabilities. Requirements governed by civil rights laws fundamentally change when comparing the support schools have to provide to students during primary and secondary school with disability access in postsecondary higher education. Psychiatrists may be asked to assist with scholastic disability at any stage of education and need to know about available supports and the parameters of disability in schools. Specifically, special attention should to be made in preparation for transition to postsecondary education when prior accommodations exist.

Teaching a Systematic Approach for Transitioning Patients to College: An Interactive Continuing Medical Education Program.

OBJECTIVE: The purpose of this article is to determine the effectiveness of a hands-on continuing education program for practicing child and adolescent psychiatrists (CAPs) with a focus on best practices in transitioning psychiatric patients to college. The plan was to build on the unique knowledge and skill set of CAPs, use audience and facilitator feedback from prior programs to inform program content, structure, and format, and incorporate findings from the evolving literature. METHODS: A 3-h interactive workshop was designed with an emphasis on audience participation. The workshop was divided into three main segments: didactics, whole group discussion/brainstorming, and small group discussion of illustrative case vignettes. RESULTS: Improvements and changes in knowledge, skills, and attitudes related to transition planning were identified by program participants. Quantitative feedback in the form of course evaluations, pre- and posttests, and a 6-month follow-up questionnaire indicate that the use of interactive teaching techniques is a productive learning experience for practicing CAPs. Qualitative feedback was that the discussion of the case vignettes was the most helpful. DISCUSSION: The use of a workshop format is an effective strategy to engage practicing CAPs in learning about and implementing best practices to support the transition of their patients to college and into young adulthood. Comprehensive and proactive transition planning, facilitated by clinicians, should promote the wellness of college-bound patients and help to reduce the potential risks in the setting of an upcoming transition.

Characterizing antibiotic prophylaxis practices in pediatric deformity spinal surgery and impact on 30-day postoperative infection: an NSQIP pediatric database study.

PURPOSE: The aim of this study was to characterize antibiotic prophylaxis practices in pediatric patients who have received posterior arthrodesis for spinal deformity and understand how these practices impact 30-day postoperative infection rates. METHODS: This was a retrospective cohort study using the National Surgical Quality Improvement Program Pediatric database for year 2021. Patients 18 years of age or younger who received posterior arthrodesis for scoliosis or kyphosis correction were included. The outcome of interest was 30-day postoperative infection. Fisher's exact test and multivariable regression analysis were used to analyze the impact of intravenous antibiotic prophylaxis, intraoperative intravenous antibiotic redosing after 4 h, postoperative antibiotic prophylaxis, intraoperative topical antibiotics on 30-day postoperative infection, and various antibiotic prophylaxis regimens. RESULTS: A total of 6974 patients were included in this study. The 30-day infection rate was 2.9%. Presurgical intravenous antibiotic (11.5% vs. 2.7%, p = 0.005), postoperative antibiotic (5.7% vs. 2.4%, p < 0.01), and intraoperative topical antibiotic (4.0% vs. 2.7%, p = 0.019) were associated with significantly reduced infection rates. There was no significant difference in infection rates between patients that received cefazolin versus vancomycin versus clindamycin. The addition of Gram-negative coverage did not result in significant differences in infection rates. Multivariable regression analysis found postoperative intravenous antibiotics and intraoperative topical antibiotics to reduce infection rates. CONCLUSIONS: We found the use of presurgical intravenous antibiotics, postoperative intravenous antibiotics, and intraoperative topical antibiotics to significantly reduce infection rates. Results from this study can be applied to future research on implementation of standardized infection prevention protocols. LEVEL OF EVIDENCE: Level II.

Navigating the landscape of food allergies: Insights and perspectives from the AMCP Market Insights Program.

AMCP convened a panel of clinical and managed care experts to identify insights regarding the prevalence, clinical manifestations, and management approaches for immunoglobulin E-mediated food allergies. This article aims to summarize expert perspectives on health care system challenges and areas of agreement concerning the management of food allergies, and to advance payers' understanding of their role in supporting health care for patients with food allergies. Food allergy management requires dietary modification and is associated with significant patient and caregiver burdens. Emerging therapies provide hope for those living with food allergies but will likely lead to a rise in health plan pharmacy expenses. In considering the value of new treatments, it is important to consider the total cost of care and the value of preventing anaphylaxis and enhancing the patient's quality of life. Several challenges remain in identifying the appropriate patient population for treatment with newer agents and in optimizing treatment outcomes. Addressing health disparities will require standardized clinical protocols, better access to specialized allergy care, and management of comorbid conditions.

Effects of sequential vs single pneumococcal vaccination on cardiovascular diseases among older adults: a population-based cohort study.

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.

Projecting the 10-year costs of care and mortality burden of depression until 2032: a Markov modelling study developed from real-world data.

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).

Treatment-resistant depression and risk of autoimmune diseases: evidence from a population-based cohort and nested case-control study.

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.