Attention-deficit/hyperactivity disorder and subsequent diagnoses of major psychiatric disorders: a nationwide population-based study.

We evaluated the risk of being diagnosed with various psychiatric disorders after an attention-deficit/hyperactivity disorder (ADHD) diagnosis using data from South Korea's National Health Insurance Service from 2002 to 2019, which covers approximately 97% of the country's population. ADHD and control groups were selected after propensity score matching was performed for individuals diagnosed with ADHD and their age- and sex-matched counterparts from the general population. Comorbid psychiatric disorders included depressive disorder, bipolar disorder, tic disorder, and schizophrenia. The incidence of newly diagnosed psychiatric disorders was compared between the groups. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated and adjusted for ADHD medication prescription. After matching, 353,898 individuals were assigned to each of the two groups. Compared to the control group, the ADHD group showed a significantly higher risk of being subsequently diagnosed with depressive disorder, bipolar disorder, schizophrenia, and tic disorder. The onset age of depressive disorder, bipolar disorder, and schizophrenia in the ADHD group was 16-17 years, approximately 5 years earlier than that in the control group. The risk for depression was the highest in individuals with high income levels, and that for schizophrenia was the highest among rural patients. The median length of the follow-up time until the diagnosis of each comorbid psychiatric disorder was 7.53, 8.43, 8.53, and 8.34 years for depressive disorder, bipolar disorder, schizophrenia, and tic disorder, respectively. Individuals with ADHD had an overall higher risk of being diagnosed with subsequent psychiatric disorders than did the controls. Hence, they should be carefully screened for other psychiatric symptoms from an early age and followed up for an extended duration, along with appropriate interventions for ADHD symptoms, including psychosocial treatments and educational approaches.

Trends in degenerative lumbar spinal surgery during the early COVID-19 pandemic in Republic of Korea: A national study utilizing the national health insurance database.

During the first year of the COVID-19 pandemic, the Republic of Korea (ROK) experienced three epidemic waves in February, August, and November 2020. These waves, combined with the overarching pandemic, significantly influenced trends in spinal surgery. This study aimed to investigate the trends in degenerative lumbar spinal surgery in ROK during the early COVID-19 pandemic, especially in relation to specific epidemic waves. Using the National Health Information Database in ROK, we identified all patients who underwent surgery for degenerative lumbar spinal diseases between January 1, 2019 and December 31, 2020. A joinpoint regression was used to assess temporal trends in spinal surgeries over the first year of the COVID-19 pandemic. The number of surgeries decreased following the first and second epidemic waves (p<0.01 and p = 0.34, respectively), but these were offset by compensatory increases later on (p<0.01 and p = 0.05, respectively). However, the third epidemic wave did not lead to a decrease in surgical volume, and the total number of surgeries remained comparable to the period before the pandemic. When compared to the pre-COVID-19 period, average LOH was reduced by 1 day during the COVID-19 period (p<0.01), while mean hospital costs increased significantly from 3,511 to 4,061 USD (p<0.01). Additionally, the transfer rate and the 30-day readmission rate significantly decreased (both p<0.01), while the reoperation rate remained stable (p = 0.36). Despite the impact of epidemic waves on monthly surgery numbers, a subsequent compensatory increase was observed, indicating that surgical care has adapted to the challenges of the pandemic. This adaptability, along with the stable total number of operations, highlights the potential for healthcare systems to continue elective spine surgery during public health crises with strategic resource allocation and patient triage. Policies should ensure that surgeries for degenerative spinal diseases, particularly those not requiring urgent care but crucial for patient quality of life, are not unnecessarily halted.

Role of HIF-1α in the Responses of Tumors to Radiotherapy and Chemotherapy.

Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and NK cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells (MIDSCs), activation of regulatory T cells (Tregs), inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

Extrahepatic Malignancies and Antiviral Drugs for Chronic Hepatitis B: A Nationwide Cohort Study.

Background/Aims: Chronic hepatitis B (CHB) is related to an increased risk of extrahepatic malignancy (EHM), and antiviral treatment is associated with an incidence of EHM comparable to controls. We compared the risks of EHM and intrahepatic malignancy (IHM) between entecavir (ETV) and tenofovir disoproxil fumarate (TDF) treatment. Methods: Using data from the National Health Insurance Service of Korea, this nationwide cohort study included treatment-naïve CHB patients who initiated ETV (n=24,287) or TDF (n=29,199) therapy between 2012 and 2014. The primary outcome was the development of any primary EHM. Secondary outcomes included overall IHM development. E-value was calculated to assess the robustness of results to unmeasured confounders. Results: The median follow-up duration was 5.9 years, and all baseline characteristics were well balanced after propensity score matching. EHM incidence rate differed significantly between within versus beyond 3 years in both groups (P<0.1, Davies test). During the first 3 years, EHM risk was comparable in the propensity score-matched cohort (5.88 versus 5.84/1,000 person-years; subdistribution hazard ratio [SHR]=1.01, 95% confidence interval [CI]=0.88-1.17, P=0.84). After year 3, however, TDF was associated with a significantly lower EHM incidence compared to ETV (4.92 versus 6.91/1,000 person-years; SHR=0.70, 95% CI=0.60-0.81, P<0.01; E-value for SHR=2.21). Regarding IHM, the superiority of TDF over ETV was maintained both within (17.58 versus 20.19/1,000 person-years; SHR=0.88, 95% CI=0.81-0.95, P<0.01) and after year 3 (11.45 versus 16.20/1,000 person-years; SHR=0.68, 95% CI=0.62-0.75, P<0.01; E-value for SHR=2.30). Conclusions: TDF was associated with approximately 30% lower risks of both EHM and IHM than ETV in CHB patients after 3 years of antiviral therapy.

Prognostic Significance of Bulky Nodal Disease in Anal Cancer Management: A Multi Institutional Study.

Purpose: This study aimed to assess the prognostic significance of bulky nodal involvement in patients with anal squamous cell carcinoma treated with definitive chemoradiotherapy. Materials and Methods: We retrospectively analyzed medical records of patients diagnosed with anal squamous cell carcinoma who underwent definitive chemoradiotherapy at three medical centers between 2004 and 2021. Exclusion criteria included distant metastasis at diagnosis, 2D radiotherapy, and salvage treatment for local relapse. Bulky N+ was defined as nodes with a long diameter of 2 cm or greater. Results: A total of 104 patients were included, comprising 51 with N0, 46 with non-bulky N+, and 7 with bulky N+. The median follow-up duration was 54.0 months (range, 6.4-162.2 months). Estimated 5-year progression-free survival (PFS), loco-regional recurrence-free survival (LRRFS), and overall survival (OS) rates for patients with bulky N+ were 42.9%, 42.9%, and 47.6%, respectively. Bulky N+ was significantly associated with inferior PFS, LRRFS and OS compared to patients without or with non-bulky N+, even after multivariate analysis. We proposed a new staging system incorporating bulky N+ as N2 stage, with estimated 5-year LRRFS, PFS, and OS rates of 81.1%, 80.6%, and 86.2% for stage I, 67.7%, 60.9%, and 93.3% for stage II, and 42.9%, 42.9%, and 47.6% for stage III disease, enhancing the predictability of prognosis. Conclusion: Patients with bulky nodal disease treated with standard chemoradiotherapy experienced poor survival outcomes, indicating the potential necessity for further treatment intensification.

Clinical benefits of surgical ablation during isolated aortic valve replacement: a nationwide study.

OBJECTIVES: To compare the early- and long-term clinical outcomes of concomitant surgical ablation (SA) for atrial fibrillation (AF) during isolated aortic valve replacement (AVR) using data from the Korean National Health Insurance Service Database. METHODS: Of 23,332 adult patients who underwent AVR between 2003 and 2019, those with underlying AF with or without concomitant SA were extracted, and propensity score matching analysis was performed. RESULTS: Overall, 1,741 patients with underlying AF with (n = 445, group A) or without (n = 1,296, group N) concomitant SA during isolated AVR were enrolled, from whom 435 pairs were matched in a 1:1 ratio using propensity score matching analysis. The operative mortality and early postoperative morbidities, including bleeding reoperation, stroke, permanent pacemaker implantation and acute kidney injury were comparable between the groups. The overall survival showed no differences between the groups. However, the cumulative incidence of new-onset late ischaemic stroke was significantly lower in group A than group N in propensity score-matched patients [2.3 vs 3.5 per 100 patient-years, adjusted hazard ratio (95% confidence interval) 0.64 (0.43-0.96), Group A versus Group N, respectively]. The cumulative incidence of other morbidities such as reoperation, permanent pacemaker implantation and progression to chronic renal failure showed no difference between groups. CONCLUSIONS: The incidence of late ischaemic stroke was significantly lower when concomitant SA was performed during isolated AVR in patients with underlying AF. Therefore, concomitant SA should be actively considered in patients with underlying AF undergoing isolated AVR to prevent the occurrence of late ischaemic stroke.

Stereotactic body radiotherapy for primary renal cell carcinoma: a systematic review and practice guideline from the International Society of Stereotactic Radiosurgery (ISRS).

Surgery is the standard of care for patients with primary renal cell carcinoma. Stereotactic body radiotherapy (SBRT) is a novel alternative for patients who are medically inoperable, technically high risk, or who decline surgery. Evidence for using SBRT in the primary renal cell carcinoma setting is growing, including several rigorously conducted prospective clinical trials. This systematic review was performed to assess the safety and efficacy of SBRT for primary renal cell carcinoma. Review results then formed the basis for the practice guidelines described, on behalf of the International Stereotactic Radiosurgery Society. 3972 publications were screened and 36 studies (822 patients) were included in the analysis. Median local control rate was 94·1% (range 70·0-100), 5-year progression-free survival was 80·5% (95% CI 72-92), and 5-year overall survival was 77·2% (95% CI 65-89). These practice guidelines addressed four key clinical questions. First, the optimal dose fractionation was 25-26 Gy in one fraction, or 42-48 Gy in three fractions for larger tumours. Second, routine post-treatment biopsy is not recommended as it is not predictive of patient outcome. Third, SBRT for primary renal cell carcinoma in a solitary kidney is safe and effective. Finally, guidelines for post-treatment follow-up are described, which include cross-axial imaging of the abdomen including both kidneys, adrenals, and surveillance of the chest initially every 6 months. This systematic review and practice guideline support the practice of SBRT for primary renal cell carcinoma as a safe and effective standard treatment option. Randomised trials with surgery and invasive ablative therapies are needed to further define best practice.

Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines.

This systematic review and meta-analysis reports on outcomes and hepatic toxicity rates after stereotactic body radiation therapy (SBRT) for liver-confined hepatocellular carcinoma (HCC) and presents consensus guidelines regarding appropriate patient management. Using the Preferred Reporting Items for Systemic Review and Meta-Analyses guidelines, a systematic review was performed from articles reporting outcomes at ≥5 years published before October 2022 from the Embase, MEDLINE, Cochrane, and Scopus databases with the following search terms: ("stereotactic body radiotherapy" OR "SBRT" OR "SABR" OR "stereotactic ablative radiotherapy") AND ("hepatocellular carcinoma" OR "HCC"). An aggregated data meta-analysis was conducted to assess overall survival (OS) and local control (LC) using weighted random effects models. In addition, individual patient data analyses incorporating data from 6 institutions were conducted as their own subgroup analyses. Seventeen observational studies, comprising 1889 patients with HCC treated with ≤9 SBRT fractions, between 2003 and 2019, were included in the aggregated data meta-analysis. The 3- and 5-year OS rates after SBRT were 57% (95% confidence interval [CI], 47%-66%) and 40% (95% CI, 29%-51%), respectively. The 3- and 5-year LC rates after SBRT were 84% (95% CI, 77%-90%) and 82% (95% CI, 74%-88%), respectively. Tumor size was the only prognostic factor for LC. Tumor size and region were significantly associated with OS. Five-year LC and OS rates of 79% (95% CI, 0.74-0.84) and 25% (95% CI, 0.20-0.30), respectively, were observed in the individual patient data analyses. Factors prognostic for improved OS were tumor size <3 cm, Eastern region, Child-Pugh score ≤B7, and the Barcelona Clinic Liver Cancer stage of 0 and A. The incidence of severe hepatic toxicity varied according to the criteria applied. SBRT is an effective treatment modality for patients with HCC with mature follow-up. Clinical practice guidelines were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS).

Five-Day Spacing of Two Fractionated Ablative Radiotherapies Enhances Antitumor Immunity.

PURPOSE: This study aimed to enhance tumor control and abscopal effects by applying diverse stereotactic ablative radiation therapy (SABR) schedules. METHODS AND MATERIALS: FSaII, CT-26, and 4T1 cells were used for tumor growth delay and lung metastases analysis after 1- or 5-day intervals radiation therapy (RT) with 40, 20, and 20 Gy, respectively. Immunodeficient BALB/c-nude, immunocompetent C3H, and BALB/c mouse models were used. For immune monitoring, FSaII tumors were analyzed using flow cytometry, immunofluorescence staining, and real-time quantitative reverse transcription polymerase chain reaction. The spleens were used for the ELISpot assay and flow cytometry to determine effector CD8 T cells. For abscopal effect analysis in CT-26 tumors, the volume of the nonirradiated secondary tumors was measured after primary tumors were irradiated with 1-day or 5-day intervals. RESULTS: Contrary to the high-dose 1-day interval RT, the 5-day interval RT significantly delayed tumor growth in immunocompetent mice, which was not observed in immunodeficient mice. In addition, the 5-day interval RT significantly reduced the number of lung metastases in FSaII and CT-26 tumors. Five-day spacing was more effective than 1-day interval in enhancing the antitumor immunity via increasing the secretion of tumor-specific IFN-γ, activating the CD8 T cells, and suppressing the monocytic myeloid-derived suppressor cells. The 5-day spacing inhibited nonirradiated secondary tumor growth more effectively than did the 1-day interval. CONCLUSIONS: Compared with the 1-day interval RT, the 5-day interval RT scheme demonstrated enhanced antitumor immunity of CD8 T cells associated with inhibition of myeloid-derived suppressor cells. Enhancing antitumor immunity leads to significant improvements in both primary tumor control and the abscopal effect.

Incidence trend and epidemiology of tic disorders among youths and adults in Korea from 2003 to 2020: A national population-based study.

Tic disorder is a highly prevalent neurodevelopmental disorder; however, research on its incidence trends is still rare. We aimed to investigate its annual incidence rates and the characteristics of incident cases in the general Korean population using data from the National Health Insurance Service-National Health Information Database as a proxy measurement for true incidence in the community. The total number of incident cases and incidence rates of tic disorders from 2003 to 2020 were compared between youths and adults. Both the number of incident cases and the annual incidence rates of tic disorders significantly increased from 2003 to 2020. The overall increasing trend in the incidence rates was significantly greater in youths than in adults; however, the incidence rates in adults showed a relatively recent increase. The male predominance regarding the newly diagnosed case number in youths was no longer observed in adults. Tic disorders occurred more commonly in the low-income group than in the high-income group. Neurodevelopmental comorbidities in youths and mood or anxiety disorders and schizophrenia in adults were more frequently observed. Antipsychotic medication adherence was higher in youths than in adults. Efforts are required to raise awareness and promote expert education for adult patients with tic disorders.

Influence of Procedural Volume on the Outcome of Gastric Endoscopic Submucosal Dissection: A Nationwide Population-Based Study Using Administrative Data.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is a well-established treatment modality for gastric neoplasms. We aimed to investigate the effect of procedural volume on the outcome of ESD for gastric cancer or adenoma. METHODS: In this population-based cohort study, patients who underwent ESD for gastric cancer or adenoma from November 2011 to December 2017 were identified using the Korean National Health Insurance Service database. Operational definitions to identify the target population and post-procedural complications were created using diagnosis and procedure codes and were validated using hospital medical record data. Outcomes included hemorrhage, perforation, pneumonia, 30-day mortality, a composite outcome comprising all of these adverse outcomes, and additional resection. Hospital volume was categorized into 3 groups based on the results of the threshold analysis: high-, medium-, low-volume centers (HVCs, MVCs, and LVCs, respectively). Inverse probability of treatment weighting analysis was applied to enhance comparability across the volume groups. RESULTS: There were 94,246 procedures performed in 88,687 patients during the study period. There were 5886 composite events including 4925 hemorrhage, 447 perforation, and 703 pneumonia cases. There were significant differences in ESD-related adverse outcomes among the 3 hospital volume categories, showing that HVCs and MVCs were associated with a lower risk of a composite outcome than LVCs (inverse probability of treatment-weighted odds ratio [OR], 0.651; 95% CI, 0.521-0.814; inverse probability of treatment-weighted OR, 0.641; 95% CI, 0.534-0.769). Similar tendencies were also shown for hemorrhage, perforation, and pneumonia; however, these were not evident for additional resection. CONCLUSIONS: Procedural volume was closely associated with clinical outcome in patients undergoing ESD for gastric cancer or adenoma.

Risk of lymphadenopathy from SARS-CoV-2 vaccination in Korea: a self-controlled case series analysis.

OBJECTIVES: To assess the risk of lymphadenopathy following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. METHODS: A self-controlled case series design was used to determine whether the risk of lymphadenopathy was higher in the 1-day to 42-day risk interval after coronavirus disease 2019 (COVID-19) vaccination compared to the control period. In addition, subgroup analyses were conducted according to baseline characteristics, time since vaccination, and sensitivity analyses adjusted for the length of the risk interval. RESULTS: The risk of developing lymphadenopathy in the risk interval (1-42 days) after COVID-19 vaccination compared to the control period was significantly increased, with a relative incidence (RI) of 1.17 (95% confidence interval [CI], 1.17 to 1.18) when the first, second, and third doses were combined. The RI was greater on the day of vaccination (1.47; 95% CI, 1.44 to 1.50). In subgroup analyses by baseline characteristics, a significantly increased risk or trend toward increased risk was observed in most subgroups except for those aged 70 years and older, with a significant increase in risk in younger individuals, those with a Charlson's comorbidity index <5, and those who received mRNA vaccines (mRNA-1273>BNT162b2). Within the 1-day to 42-day post-dose risk period, the relative risk was highest during the 1-day to 7-day post-dose period (1.59; 95% CI, 1.57 to 1.60) compared to the control period, and then the risk declined. In the sensitivity analysis, we found that the longer the risk window, the smaller the RI. CONCLUSIONS: SARS-CoV-2 vaccination is associated with a statistically significant increase in the risk of lymphadenopathy, and this risk was observed only with mRNA vaccines.

Treatment outcomes of stereotactic body radiation therapy for primary and metastatic sarcoma of the spine.

PURPOSE: This study evaluated the treatment outcomes of spine stereotactic body radiation therapy (SBRT) in sarcoma patients. MATERIALS AND METHODS: A total of 44 sarcoma patients and 75 spinal lesions (6 primary tumors, 69 metastatic tumors) treated with SBRT were retrospectively reviewed between 2006 and 2017. The median radiation dose was 33 Gy (range, 18-45 Gy) in 3 fractions (range, 1-5) prescribed to the 75% isodose line. RESULTS: The median follow-up duration was 18.2 months. The 1-year local control was 76.4%, and patients treated with single vertebral body were identified as a favorable prognostic factor on multivariate analyses. Progression-free survival at 1 year was 31.9%, with the interval between initial diagnosis and SBRT and extent of disease at the time of treatment being significant prognostic factors. The 1-year overall survival was 80.5%, and PTV and visceral metastases were independently associated with inferior overall survival. CONCLUSION: SBRT for spinal sarcoma is effective in achieving local control, particularly when treating a single vertebral level with a limited extent of disease involvement, resulting in an excellent control rate. The extent of disease at the time of SBRT is significantly correlated with survival outcomes and should be considered when treating spine sarcoma.

Association between weight loss agents and elevated liver enzymes: a population-based cross-sectional study.

The widespread use of body weight control agents might be related to liver enzyme elevation, but this potential association has only been documented in a few case reports. This study aimed to investigate the associations between weight loss agents and elevated liver enzymes at the population-level. We conducted a cross-sectional study using Korea National Health and Nutrition Examination Survey (KNHANES) data from 2013 to 2019. This study included 36,259 participants over 20 years of age who completed the questionnaire and had no history of hepatitis, cancer, or renal failure. In these participants, we analyzed associations between weight loss agents and elevated liver enzymes by constructing multiple logistic regression models with adjustment for confounding factors and stratified by sex, age, and body mass index. The use of weight loss agents related to liver enzyme elevation in men (adjusted odds ratio (aOR): 1.36, 95% confidence interval (CI): 1.08-1.71) and participants aged less than 40 years (aOR: 1.44, 95% CI: 1.12-1.87). Using more types of weight loss agents was associated with liver enzyme elevation (aOR: 1.31, 95% CI: 1.03-1.67 for 1 weight loss agent, aOR: 1.93, 95% CI: 0.93-3.99 for ≥ 2 weight loss agents). Elevated liver enzymes were associated with the use of traditional medicines (aOR: 1.96, 95% CI: 1.14-3.34) and dietary supplements (aOR: 1.33, 95% CI: 1.02-1.72) in men. We observed an association between weight loss agents and liver enzyme elevation in men, particularly for traditional herbal medicines and dietary supplements. To confirm the observed associations, studies higher on the evidence hierarchy are needed.

Machine learning approaches that use clinical, laboratory, and electrocardiogram data enhance the prediction of obstructive coronary artery disease.

Pretest probability (PTP) for assessing obstructive coronary artery disease (ObCAD) was updated to reduce overestimation. However, standard laboratory findings and electrocardiogram (ECG) raw data as first-line tests have not been evaluated for integration into the PTP estimation. Therefore, this study developed an ensemble model by adopting machine learning (ML) and deep learning (DL) algorithms with clinical, laboratory, and ECG data for the assessment of ObCAD. Data were extracted from the electronic medical records of patients with suspected ObCAD who underwent coronary angiography. With the ML algorithm, 27 clinical and laboratory data were included to identify ObCAD, whereas ECG waveform data were utilized with the DL algorithm. The ensemble method combined the clinical-laboratory and ECG models. We included 7907 patients between 2008 and 2020. The clinical and laboratory model showed an area under the curve (AUC) of 0.747; the ECG model had an AUC of 0.685. The ensemble model demonstrated the highest AUC of 0.767. The sensitivity, specificity, and F1 score of the ensemble model ObCAD were 0.761, 0.625, and 0.696, respectively. It demonstrated good performance and superior prediction over traditional PTP models. This may facilitate personalized decisions for ObCAD assessment and reduce PTP overestimation.

Antidepressants and the Risk of Ischemic Stroke in Older Adults According to the Degree of Serotonin Reuptake Inhibition: A Retrospective Cohort Study.

OBJECTIVE: The effects of serotonin reuptake inhibition induced by antidepressants on ischemic stroke and its pathophysiology remain unclear despite the frequent use of antidepressants and high fatality of ischemic stroke. We estimated the risk of ischemic stroke associated with antidepressant use in older adults according to the degree of serotonin reuptake inhibition. DESIGN: Retrospective cohort study. PARTICIPANTS: The cohort consisted of older adult patients who were treated with antidepressants. MEASUREMENTS: We estimated the risk of ischemic stroke associated with antidepressant use in older adults according to the degree of serotonin reuptake inhibition using Korea's National Health Insurance System-Senior Cohort. Exposure to antidepressants was categorized by type (strong, intermediate, or weak serotonin reuptake inhibitors [SRIs]) and by the mean prescribed dose per day and treatment duration. The risk for the strong and intermediate SRIs group was compared with that of the weak SRIs group using a Cox proportional hazards regression model. RESULTS: Of 97,411 were weak SRIs users, and 107,152 and 18,783 were users of strong and intermediate SRIs. The risk of ischemic stroke was 1.192- and 1.057-fold higher in strong and intermediate SRI users, respectively than in weak SRI users. Hazard ratios were increased in higher dose and shorter duration user groups. The risk increased 1.753-fold in strong SRI users with anticonvulsants and 1.387-fold in intermediate SRI users with PPIs. CONCLUSION: The use of strong and intermediate SRIs should be considered carefully in older adult patients, especially when high-dose antidepressants are prescribed even for a short duration.

Stereotactic body radiotherapy for Ultra-Central lung Tumors: A systematic review and Meta-Analysis and International Stereotactic Radiosurgery Society practice guidelines.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an effective and safe modality for early-stage lung cancer and lung metastases. However, tumors in an ultra-central location pose unique safety considerations. We performed a systematic review and meta-analysis to summarize the current safety and efficacy data and provide practice recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). METHODS: We performed a systematic review using PubMed and EMBASE databases of patients with ultra-central lung tumors treated with SBRT. Studies reporting local control (LC) and/or toxicity were included. Studies with <5 treated lesions, non-English language, re-irradiation, nodal tumors, or mixed outcomes in which ultra-central tumors could not be discerned were excluded. Random-effects meta-analysis was performed for studies reporting relevant endpoints. Meta-regression was conducted to determine the effect of various covariates on the primary outcomes. RESULTS: 602 unique studies were identified of which 27 (one prospective observational, the remainder retrospective) were included, representing 1183 treated targets. All studies defined ultra-central as the planning target volume (PTV) overlapping the proximal bronchial tree (PBT). The most common dose fractionations were 50 Gy/5, 60 Gy/8, and 60 Gy/12 fractions. The pooled 1- and 2-year LC estimates were 92 % and 89 %, respectively. Meta-regression identified biological effective dose (BED10) as a significant predictor of 1-year LC. A total of 109 grade 3-4 toxicity events, with a pooled incidence of 6 %, were reported, most commonly pneumonitis. There were 73 treatment related deaths, with a pooled incidence of 4 %, with the most common being hemoptysis. Anticoagulation, interstitial lung disease, endobronchial tumor, and concomitant targeted therapies were observed risk factors for fatal toxicity events. CONCLUSION: SBRT for ultra-central lung tumors results in acceptable rates of local control, albeit with risks of severe toxicity. Caution should be taken for appropriate patient selection, consideration of concomitant therapies, and radiotherapy plan design.