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BACKGROUND: There has been a significant increase in the incidence of cardiovascular disease (CVD) in Malaysia. It is important to identify the group at high risk of CVD. This study aimed to assess the population distribution and factors associated with 10-year CVD risk among adults aged 40 to 74 years in Malaysia. METHODS: This study used secondary data from the NHMS 2019, a nationally representative cross-sectional population study. The following measurements were collected: anthropometric, systolic blood pressure, fasting blood glucose, total cholesterol, smoking, and sociodemographic. The 2019 WHO Southeast Asia laboratory-based charts were used to estimate individuals' CVD risk. These charts predict significant cardiovascular events over ten years. Multiple logistic regression analysis was employed to ascertain the factors that are linked to elevated or extremely elevated risk of CVD. RESULTS: A total of 5,503 respondents were included in the analysis. Less than one-quarter of the respondents were current smokers and obese. Approximately 41.7%, 30.9%, and 22.5% of the participants had extremely low risk (less than 5%), low risk (between 5% and less than 10%), and moderate risk (between 10% and less than 20%), respectively. A total of 4.9% of the participants were categorised as having high (20% to < 30%) or very high (CVD) risk (≥ 30%). This classification was more prevalent among males (7.3%) than among females (2.5%; p < 0.001). The factors associated with high/very high CVD risk were unemployment (aOR = 1.88, 95% CI = 1.47-2.40), those with non-formal and primary education level (aOR = 2.36, 95% CI = 1.36 - 4.12 and aOR = 3.28, 95% CI = 2.10 - 5.12, respectively), and being physically inactive with obesity (aOR = 2.19, 95% CI = 1.18 - 4.08). CONCLUSIONS: This study revealed that almost 5% of the population in Malaysia has a high 10-year CVD risk. These findings highlight Malaysia's urgent need for comprehensive CVD prevention efforts.

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BACKGROUND: Point-of-care testing (POCT) is commonly used in epidemiological surveys due to its various advantages, such as portability and immediate test results. The CardioChek® PA analyser 3-in-1 lipid panel measures total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol. This study tested the reliability and diagnostic accuracy of the CardioChek® PA analyser using a 3-in-1 lipid panel. METHODS: A cross-sectional study design with quota sampling was used. A total of 203 respondents aged 18 years and above from a research centre in the Ministry of Health, Malaysia, were recruited. Venous blood was sent to the laboratory and tested with Siemens Atellica CH, while a POCT analyser was used for capillary blood measurements. Intraclass coefficient correlation (ICC) analysis was employed to determine the agreement between capillary and venous blood parameters. The diagnostic performance of the evaluated tests was evaluated using STATA version 12. RESULTS: The agreement between capillary and laboratory venous blood was moderate (0.64-0.67) for TC and HDL, good (0.75) for LDL and excellent (0.91) for TG). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were as follows: TC, 57.1%, 94.3%, 92.3% and 64.8%; TG, 76.0%, 100%, 100%, and 96.6%; HDL, 96.2%, 83.2%, 47.2% and 99.3%; and LDL, 81.0%, 100%, 100% and 68.3%, respectively. CONCLUSIONS: The CardioChek® PA analyser showed acceptable diagnostic accuracy for screening high-risk individuals more often in places where laboratories are inaccessible. It could also be used in clinical settings where patients would benefit from swift treatment decisions.

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BACKGROUND: Hypertensive disorders of pregnancy (HDP) pose a substantial public health concern, ranking among the primary contributors to maternal and perinatal morbidity and mortality, impacting around 5-10% of pregnancies. This study aimed to determine the prevalence of HDP and its associated factors among mothers aged 15-49 who recently gave birth within the last two years, throughout Malaysia, informing effective public health and primary care interventions. METHODS: This study was a part of the national survey on maternal and child health (MCH) also known as the National Health and Morbidity Survey (NHMS) 2022: MCH. This was a cross-sectional study using two stage stratified random sampling design. Data of mothers aged 15-49 years old who recently gave birth within the last two years were selected in this study. This survey utilised a set of structured validated questionnaires administered via face-to-face interviews (using a mobile device). Multiple logistic regression analysis was employed to identify the associated factors for hypertension. RESULTS: Among 6 335 participants recruited for this study with an estimated population of 782, 550, the prevalence of HDP among Malaysian mothers aged 15-49 years old who recently gave birth within the last two years was 6.5% (95% CI: 5.76, 7.37). Multiple logistic regression showed that maternal age and ethnicity were significantly associated with hypertension. Advanced maternal age had higher odds of hypertension, with an aOR of 2.18 (95% CI = 1.75, 2.71). In addition, Other Bumiputera had higher odds of hypertension (aOR = 2.71, 95% CI = 1.25, 5.87). CONCLUSION: This study reveals the prevalence of HDP among Malaysian women with children under 2 years old, emphasizing advanced maternal age (above 35) and ethnicity as notable risk factors. It improves understanding of the epidemiology of HDP in Malaysia, offering valuable insights for the development of effective public health strategies and clinical interventions that can help with the control of HDP.

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Treatment intensification is essential to ensure guideline targets are attained in diabetes patients. The failure to intensify treatment when the targets are not achieved is therapeutic inertia. This study aimed to determine the proportions and factors associated with treatment intensification and therapeutic inertia of antihypertensive therapy in type 2 diabetes patients with uncontrolled hypertension in Malaysia. A retrospective cohort analysis was conducted utilising registry data. Diabetes hypertensive patients with uncontrolled baseline systolic or diastolic blood pressure were included. Treatment intensification was the increase in the number of antihypertensive agents from the index treatment. Therapeutic inertia was the absence of treatment intensification when the second blood pressure reading was still uncontrolled. About 6956 patients were followed up over 2.5 ± 1.1 person-years. Treatment intensification was observed in 29.8% of patients, while 38.6% had therapeutic inertia. Chinese, Indian, and 'others' ethnic groups, retinopathy, more antihypertensive agents, and higher systolic blood pressure were associated with therapeutic inertia. Underweight, overweight patients and those with dyslipidaemia had lower risks for therapeutic inertia. The results indicate suboptimal quality of care in public health clinics in Malaysia. Further studies are needed to determine the underlying causes to formulate precise interventions to tackle the problem in Malaysia.

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The actual prevalence of diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D) in Malaysia is unknown. We aimed to determine the prevalence of DKD and its associated risk factors among T2D patients in Malaysia. An analytical cross-sectional study was conducted using the year 2022 clinical audit dataset from the National Diabetes Registry. DKD was defined as albuminuria, a decreased glomerular filtration rate, or both. Among 80,360 patients, 62.2% were female, 68.4% were Malay, and the mean age was 61.4 years. A total of 56.7% (95% CI 56.4-57.1%) of patients were found to have DKD. Increasing age, male sex, Malay ethnicity, longer duration of diabetes, overweight, obesity, hypertension, diabetic retinopathy, diabetic foot ulcer, nontraumatic lower-extremity amputation, ischaemic heart disease, stroke, insulin, higher numbers of antihypertensive agents, antiplatelet agents, poorer HbA1c control, higher systolic blood pressure, non-achievement of triglyceride target, and non-attainment of HDL-cholesterol goal were independent risk factors associated with DKD. Clinicians, program managers, and health policymakers should target modifiable factors to manage DKD and prevent its progression to end-stage kidney disease in Malaysia.

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Background: The prevalence of diabetes in Malaysia is increasing, and identifying patients with higher risk of complications is crucial for effective management. The use of machine learning (ML) to develop prediction models has been shown to outperform non-ML models. This study aims to develop predictive models for Type 2 Diabetes (T2D) complications in Malaysia using ML techniques. Design and methods: This 10-year retrospective cohort study uses clinical audit datasets from Malaysian National Diabetes Registry from 2011 to 2021. T2D patients who received treatment in public health clinics in the southern region of Malaysia with at least two data points in 10 years are included. Patients with diabetes complications at baseline are excluded to ensure temporality between predictors and the target variable. Appropriate methods are used to address issues related to data cleaning, missing data imputation, data splitting, feature selection, and class imbalance. The study uses 7 ML algorithms, including logistic regression, support vector machine, k-nearest neighbours, decision tree, random forest, extreme gradient boosting, and light gradient boosting machine, to develop predictive models for four target variables: nephropathy, retinopathy, ischaemic heart disease, and stroke. Hyperparameter tuning is performed for each algorithm. The model training is performed using a stratified k-fold cross-validation technique. The best model for each algorithm is evaluated on a hold-out dataset using multiple metrics. Expected impact of the study on public health: The prediction model may be a valuable tool for diabetes management and secondary prevention by enabling earlier interventions and optimal resource allocation, leading to better health outcomes.

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Background@#Marfan syndrome (MFS) is caused by fibrillin-1 gene (FBN1) variants. Mutational hotspots and/or well-established critical functional domains of FBN1 include cysteine residues, calcium-binding consensus sequences, and amino acids related to interdomain packaging. Previous guidelines for variant interpretation do not reflect the features of genes or related diseases. Using the Clinical Genome Resource (ClinGen) FBN1 variant curation expert panel (VCEP), we re-evaluated FBN1 germline variants reported as variants of uncertain significance (VUSs). @*Methods@#We re-evaluated 26 VUSs in FBN1 reported in 161 patients with MFS. We checked the variants in the Human Genome Mutation Database, ClinVar, and VarSome databases and assessed their allele frequencies using the gnomAD database. Patients’ clinical information was reviewed. @*Results@#Four missense variants affecting cysteines (c.460T > C, c.1006T > C, c.5330G > C, and c.8020T > C) were reclassified as likely pathogenic and were assigned PM1_strong or PM1. Two intronic variants were reclassified as benign by granting BA1 (stand-alone). Four missense variants were reclassified as likely benign. BP5 criteria were applied in cases with an alternate molecular basis for disease, one of which (c.7231G > A) was discovered alongside a pathogenic de novo COL3A1 variant (c.1988G > T, p.Gly633Val). @*Conclusions@#Considering the high penetrance of FBN1 variants and clinical variability of MFS, the detection of pathogenic variants is important. The ClinGen FBN1 VCEP encompasses mutational hotspots and/or well-established critical functional domains and adjusts the criteria specifically for MFS; therefore, it is beneficial not only for identifying pathogenic FBN1 variants but also for distinguishing these variants from those that cause other connective tissue disorders with overlapping clinical features.

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Purpose@#This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). @*Materials and Methods@#Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). @*Results@#In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. @*Conclusion@#Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

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SMARCB1 or SMARCA4-deficient sinonasal carcinoma or thoracic undifferentiated tumor has aggressive nature with a poor prognosis. Patients with this disease were diagnosed by immunohistochemistry or next-generation sequencing. Those who were able to receive a surgery tended to be cured, while the others treated with chemotherapy, radiation therapy, or immune checkpoint inhibitor were often insensitive to these therapies. However, one having CD274 (PD-L1) amplification showed the response to immune checkpoint inhibitor and a good prognosis. We believed that this report could provide promising information for determining the optimal treatment option.

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Purpose@#There have been needs to improve the sensitivity of liquid biopsy. This report aims to report the analytical and clinical validation of a next-generation sequencing (NGS)–based circulating tumor DNA (ctDNA) assay. @*Materials and Methods@#Analytical validation was conducted in vitro by evaluating the limit of detection (LOD), precision, and specificity for various genomic aberrations. The real-world performance in non–small cell lung cancer (NSCLC) was assessed by comparing the results of AlphaLiquid100 to the tissue-based results. @*Results@#The LODs with 30 ng input DNA were 0.11%, 0.11%, 0.06%, 0.21%, and 2.13 copies for detecting single nucleotide variants, insertions, deletions, fusions, and copy number alterations (CNA), respectively. Quantitatively, single nucleotide variants/insertions and deletions, fusions, and CNAs showed a good correlation (R2=0.91, 0.40, and 0.65; y=0.95, 1.06, and 1.19) to the manufacturer’s values, and per-base specificities for all types of variants were near 100%. In real-world NSCLC (n=122), key actionable mutations in NSCLC were detected in 60.7% (74/122) with the ctDNA assay. Comparative analysis against the NGS-based tissue results for all key mutations showed positive percent agreement (PPA) of 85.3%. For individual genes, the PPA was as high as 95.7% for epidermal growth factor receptor (EGFR) mutations and 83.3% for ALK translocations. AlphaLiquid100 detected drug-sensitive EGFR mutation at a variant allele frequency as low as 0.02% and also identified an EGFR mutation in a case where tissue sample missed. Blood samples collected post-targeted therapies revealed additional acquired mutations. @*Conclusion@#The AlphaLiquid100 ctDNA assay demonstrates robust analytical validity, offering clinically important information for NSCLC patients.

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Objectives@#. Due to the rarity of olfactory neuroblastoma (ONB), there is ongoing debate about optimal treatment strategies, especially for early-stage or locally advanced cases. Therefore, our study aimed to explore experiences from multiple centers to identify factors that influence the oncological outcomes of ONB. @*Methods@#. We retrospectively analyzed 195 ONB patients treated at nine tertiary hospitals in South Korea between December 1992 and December 2019. Kaplan-Meier survival analysis was used to evaluate oncological outcomes, and a Cox proportional hazards regression model was employed to analyze prognostic factors for survival outcomes. Furthermore, we conducted 1:1 nearest-neighbor matching to investigate differences in clinical outcomes according to the use of neoadjuvant chemotherapy. @*Results@#. In our cohort, the 5-year overall survival (OS) rate was 78.6%, and the 5-year disease-free survival (DFS) rate was 62.4%. The Cox proportional hazards model revealed that the modified Kadish (mKadish) stage and Dulguerov T status were significantly associated with DFS, while the mKadish stage and Hyams grade were identified as prognostic factors for OS. The subgroup analyses indicated a trend toward improved 5-year DFS with dural resection in mKadish A and B cases, even though the result was statistically insignificant. Induction chemotherapy did not provide a survival benefit in this study after matching for the mKadish stage and nodal status. @*Conclusion@#. Clinical staging and pathologic grading are important prognostic factors in ONB. Dural resection in mKadish A and B did not show a significant survival benefit. Similarly, induction chemotherapy also did not show a survival benefit, even after stage matching.

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Exposure-response prevention is an effective approach to treat anxiety disorders. Virtual reality exposure therapy (VRET) is a promising treatment for patients with posttraumatic stress disorder (PTSD). New research has helped refine and update VRET. In this study, we introduce a form of VRET developed for patients suffering from PTSD after a traffic accident, and present two cases treated using this protocol. After 6 weeks of VRET treatment, the two participants not only improved their PTSD symptoms, but also improved their depressed mood, anxiety, and insomnia symptoms. Future studies of VRET for car accident-related PTSD should utilize a controlled design with randomization in order to account for numerous possible confounds.

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Objective@#This study aimed to identify serum biomarkers prospectively associated with remission at 12 weeks in outpatients with depressive disorders receiving stepwise psychopharmacotherapy, according to the main antidepressant used during the treatment period. @*Methods@#This study included 1,024 depressive outpatients initially treated using antidepressant monotherapy, followed by alternating pharmacological strategies during the acute phase (3−12 weeks; 3-week interval). Fourteen serum biomarkers, sociodemographics, and clinical characteristics were evaluated at baseline. Based on the use frequency and mechanism of action, four main antidepressant types were distinguished: escitalopram, other selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. A Hamilton Depression Rating Scale score ≤ 7 was take to indicate remission. @*Results@#Lower high-sensitivity C-reactive protein levels were correlated with remission at 12 weeks for all antidepressant types. Lower interleukin (IL)-6 levels and tumor necrosis factor-alpha levels were associated with remission using escitalopram and other SSRIs respectively. Lower IL-1β and leptin levels, predicted remission in association with SSRIs including escitalopram. For SNRIs, remission at 12 weeks was predicted by lower IL-4 and IL-10 levels. For mirtazapine, remission at 12 weeks was associated with lower leptin levels, and higher serotonin and folate levels. @*Conclusion@#Baseline serum status, as estimated by nine serum markers, may help clinicians determine the most appropriate antidepressant to achieve remission in the acute phase of depression.

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Objective@#This study aimed to evaluate the unexplored relationship between BDNF methylation, long-term outcomes, and its interaction with suicidal ideation (SI), which is closely associated with both BDNF expression and stroke outcomes. @*Methods@#A total of 278 stroke patients were assessed for BDNF methylation status and SI using suicide-related item in the Montgomery–Åsberg Depression Rating Scale at 2 weeks post-stroke. We investigated the incidence of composite cerebro-cardiovascular events (CCVEs) during an 8−14-year period after the initial stroke as long-term stroke outcome.We conducted Cox regression models adjusted for covariates to evaluate the association between BDNF methylation status and CCVEs, as well as its interaction with post-stroke SI at 2 weeks. @*Results@#Higher methylation status of CpG 1, 3, and 5, but not the average value, predicted a greater number of composite CCVEs during 8−14 years following the stroke. The associations between a higher methylation status of CpGs 1, 3, 5, and 8, as well as the average BDNF methylation value, and a greater number of composite CCVEs, were prominent in patients who had post-stroke SI at 2 weeks. Notably, a significant interaction between methylation status and SI on composite CCVEs was observed only for CpG 8. @*Conclusion@#The significant association between BDNF methylation and poor long-term stroke outcomes, particularly amplified in individuals who had post-stroke SI at 2 weeks, suggested that evaluating the biological marker status of BDNF methylation along with assessing SI during the acute phase of stroke can help predict long-term outcomes.

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Background@#Operative management with intramedullary nail fixation remains the definitive treatment of choice for osteoporotic subtrochanteric (ST) fractures; however, there remains no consensus regarding the proper nail length. We aimed to use 3-dimensional finite element (FE) analysis to determine the optimal nail length for the safe fixation of osteoporotic ST fractures. @*Methods@#Nine modes of FE models were constructed using 9 different lengths of cephalomedullary nails (short nails: 170, 180, and 200 mm; long nails: 280, 300, 320, 340, 360, and 380 mm) from the same company. The interfragmentary motion was analyzed. Additionally, the peak von Mises stress (PVMS) in the cortical bone, cancellous bone of the femoral head, and the nail were measured, and the yielding risk for each subject was investigated. @*Results@#Long nails were associated with less interfragmentary motion. In the cortical bone, the PVMS of short nails was observed at the distal locking screw holes of the femoral medial cortex; however, in long nails, the PVMS was observed at the lag screw holes on the lateral cortex. The mean yielding risk of long nails was 40.1% lower than that of short nails. For the cancellous bone of the femoral head, the PVMS in all 9 FE models was in the same area: at the apex of the femoral head. There was no difference in the yielding risk between short and long nails. For implants, the PVMS was at the distal locking screw hole of the nail body in the short nails and the nail body at the fracture level in the long nails. The mean yielding risk was 74.9% lower for long nails than that for short nails. @*Conclusions@#Compared to short nails, long nails with a length of 320 mm or more showed less interfragmentary motion and lower yielding risk in low-level osteoporotic ST fractures. The FE analysis supports long nails as a safer option than short nails, especially for treating transverse-type low-level osteoporotic ST fractures.

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This review article investigates solid organ transplantation-induced osteoporosis, a critical yet often overlooked issue, emphasizing its significance in post-transplant care. The initial sections provide a comprehensive understanding of the prevalence and multifactorial pathogenesis of transplantation osteoporosis, including factors such as deteriorating post-transplantation health, hormonal changes, and the impact of immunosuppressive medications. Furthermore, the review is dedicated to organ-specific considerations in transplantation osteoporosis, with separate analyses for kidney, liver, heart, and lung transplantations. Each section elucidates the unique challenges and management strategies pertinent to transplantation osteoporosis in relation to each organ type, highlighting the necessity of an organ-specific approach to fully understand the diverse manifestations and implications of transplantation osteoporosis. This review underscores the importance of this topic in transplant medicine, aiming to enhance awareness and knowledge among clinicians and researchers. By comprehensively examining transplantation osteoporosis, this study contributes to the development of improved management and care strategies, ultimately leading to improved patient outcomes in this vulnerable group. This detailed review serves as an essential resource for those involved in the complex multidisciplinary care of transplant recipients.

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Background@#Parathyroid adenoma (PA) is a common endocrine disease linked to multiple complications, but the pathophysiology of the disease remains incompletely understood. The study aimed to identify the key regulator proteins and pathways of PA according to functionality and volume through quantitative proteomic analyses. @*Methods@#We conducted a retrospective study of 15 formalin-fixed, paraffin-embedded PA samples from tertiary hospitals in South Korea. Proteins were extracted, digested, and the resulting peptides were analyzed using liquid chromatography-tandem mass spectrometry. Pearson correlation analysis was employed to identify proteins significantly correlated with clinical variables. Canonical pathways and transcription factors were analyzed using Ingenuity Pathway Analysis. @*Results@#The median age of the participants was 52 years, and 60.0% were female. Among the 8,153 protein groups analyzed, 496 showed significant positive correlations with adenoma volume, while 431 proteins were significantly correlated with parathyroid hormone (PTH) levels. The proteins SLC12A9, LGALS3, and CARM1 were positively correlated with adenoma volume, while HSP90AB2P, HLA-DRA, and SCD5 showed negative correlations. DCPS, IRF2BPL, and FAM98A were the main proteins that exhibited positive correlations with PTH levels, and SLITRK4, LAP3, and AP4E1 had negative correlations. Canonical pathway analysis demonstrated that the RAN and sirtuin signaling pathways were positively correlated with both PTH levels and adenoma volume, while epithelial adherence junction pathways had negative correlations. @*Conclusion@#Our study identified pivotal proteins and pathways associated with PA, offering potential therapeutic targets. These findings accentuate the importance of proteomics in understanding disease pathophysiology and the need for further research.

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Purpose@#The objective of this study was to evaluate the effect of Polymyxin B hemoperfusion (PMX-HP) on patients with sepsis. @*Methods@#A systematic review and meta-analysis was performed using relevant articles retrieved from 3 databases (PubMed, Cochrane Library, EMBASE). Randomized studies from 1 January 1999 to 28 February 2022 were examined to determine the clinical results of PMX-HP. A meta-analysis was carried out using the random-effects method, meta-regression with clinical variables, and assessment of risk of bias (ROB) tool (Cochrane ROB assessment tool). Mortality was evaluated within 60 days of hospitalization (in-hospital death 28-day, 30-day, and 60-day mortality) and predictors associated with mortality were determined using meta-regression. @*Results@#There were 11 randomized studies with 548 patients included in the meta-analysis. The pooled mortality was 35% (95% CI, 27%-42%, 95% CI 0.53-0.96). Further subgroup analysis was performed according to the duration of PMX-HP. An extension of PMX-HP treatment beyond 2 hours (pooled mortality, 43%; 95% CI, 9%-76%) compared with a 2-hour session (pooled mortality, 33%. 95% CI, 27%-38%) showed an increase in mortality rates. However, this was not statistically significant. Univariate meta-regression showed that patient’s age, the acute physiology and chronic health evaluation score, and the sequential organ failure assessment score did not significantly impact mortality. @*Conclusion@#While PMX-HP is valuable in the management of septic shock, treatment duration should be based on careful assessment of the patient's condition, the risks and benefits of prolonged therapy, and the overall treatment strategy including antimicrobial management and source control.

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Background@#Korea has witnessed significant fluctuations in its suicide rates in recent decades, which may be related to modifications in its death registration system. This study aimed to explore the structural shifts in suicide trends, as well as accidental and ill-defined deaths in Korea, and to analyze the patterns of these changes. @*Methods@#We analyzed age-adjusted death rates for suicides, deaths due to transport accidents, falls, drowning, fire-related incidents, poisonings, other external causes, and ill-defined deaths in Korea from 1997 to 2021. We identified change-points using the ‘breakpoints’ function from the ‘strucchange’ package and conducted interrupted time series analyses to assess trends before and after these change-points. @*Results@#Korea’s suicide rates had three change-points in February 2003, September 2008, and June 2012, characterized by stair-step changes, with level jumps at the 2003 and 2008 change-points and a sharp decline at the 2012 change-point. Notably, the 2003 and 2008 spikes roughly coincided with modifications to the death ascertainment process. The trend in suicide rates showed a downward slope within the 2003–2008 and 2008–2012 periods.Furthermore, ill-defined deaths and most accidental deaths decreased rapidly through several change-points in the early and mid-2000s. @*Conclusion@#The marked fluctuations in Korea’s suicide rate during the 2000s may be largely attributed to improvements in suicide classification, with potential implications beyond socio-economic factors. These findings suggest that the actual prevalence of suicides in Korea in the 2000s might have been considerably higher than officially reported.