Antipsychotic treatment and risk of discontinuation and hospitalization in first-episode schizophrenia: a nationwide population-based study.

BACKGROUND: Current evidence on antipsychotic treatment and risk of psychiatric hospitalization in first-episode schizophrenia (FES) is largely based on the findings from randomized clinical trials (RCTs). However, the generalization of the findings to real-world patients is limited due to inherent caveats of the RCT. We aimed to investigate the treatment discontinuation and risk of psychiatric hospitalization using a nationwide population database. METHODS: The Health Insurance Review Agency database in South Korea was obtained, and the observation period started from 1 January 2009 to 31 December 2016. We defined the maintenance period as the period from 6-month after the diagnosis of schizophrenia, which is utilized for the main results. For a total of 44 396 patients with FES, a within-individual Cox regression model was used to compare the risk of the treatment discontinuation and psychiatric hospitalization. RESULTS: In group comparison, a long-acting injectable (LAI) antipsychotic group was associated with the lowest risk of the treatment discontinuation (0.64, 0.55-0.75) and psychiatric hospitalization (0.29, 0.22-0.38) in comparison with a typical antipsychotic group and no use, respectively. Among individual antipsychotics, the lowest risk of the treatment discontinuation was observed in LAI paliperidone (0.46, 0.37-0.66) compared to olanzapine. Clozapine was found to be the most effective antipsychotic in lowering the risk of psychiatric hospitalization as monotherapy compared to no use (0.23, 0.18-0.31). CONCLUSIONS: In real-world patients with FES, LAI paliperidone and clozapine were associated with low treatment discontinuation and better effectiveness in lowering the risk of psychiatric hospitalization.

Impact of the early phase of the COVID-19 pandemic on the use of mental health services in South Korea: a nationwide, health insurance data-based study.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has profoundly affected the utilization of mental health services. Existing evidence investigating this issue at the nationwide level is lacking, and it is uncertain whether the effects of the COVID-19 pandemic on the use of psychiatric services differs based on psychiatric diagnosis. METHODS: Data from the claims database between October 2015 and August 2020 was obtained from the Health Insurance Review and Assessment agency in South Korea. Based on the main diagnostic codes, psychiatric patients were identified and categorized into diagnostic groups (anxiety disorders, bipolar and related disorders, depressive disorders, and schizophrenia spectrum disorders). We calculated the number of psychiatric inpatients and outpatients and the medication adherence of patients for each month. We compared the actual and predicted values of outcomes during the COVID-19 pandemic and performed interrupted time-series analyses to test the statistical significance of the impact of the pandemic. RESULTS: During the COVID-19 pandemic, the number of inpatients and admissions to psychiatric hospitals decreased for bipolar and related disorders and depressive disorders. In addition, the number of patients admitted to psychiatric hospitals for schizophrenia spectrum disorders decreased. The number of psychiatric outpatients showed no significant change in all diagnostic groups. Increased medication adherence was observed for depressive, schizophrenia spectrum, and bipolar and related disorders. CONCLUSIONS: In the early phase of the COVID-19 pandemic, there was a trend of a decreasing number of psychiatric inpatients and increasing medication adherence; however, the number of psychiatric outpatients remained unaltered.

Structural impairment in superficial and deep white matter in schizophrenia.

OBJECTIVE: Although disconnectivity among brain regions has been one of the main hypotheses for schizophrenia, the superficial white matter (SWM) has received less attention in schizophrenia research than the deep white matter (DWM) owing to the challenge of consistent reconstruction across subjects. METHODS: We obtained the diffusion magnetic resonance imaging (dMRI) data of 223 healthy controls and 143 patients with schizophrenia. After harmonising the raw dMRIs from three different studies, we performed whole-brain two-tensor tractography and fibre clustering on the tractography data. We compared the fractional anisotropy (FA) of white matter tracts between healthy controls and patients with schizophrenia. Spearman's rho was adopted for the associations with clinical symptoms measured by the Positive and Negative Syndrome Scale (PANSS). The Bonferroni correction was used to adjust multiple testing. RESULTS: Among the 33 DWM and 8 SWM tracts, patients with schizophrenia had a lower FA in 14 DWM and 4 SWM tracts than healthy controls, with small effect sizes. In the patient group, the FA deviations of the corticospinal and superficial-occipital tracts were negatively correlated with the PANSS negative score; however, this correlation was not evident after adjusting for multiple testing. CONCLUSION: We observed the structural impairments of both the DWM and SWM tracts in patients with schizophrenia. The SWM could be a potential target of interest in future research on neural biomarkers for schizophrenia.

Mastectomy or Margin Re-excision? A Nomogram for Close/Positive Margins After Lumpectomy for DCIS.

BACKGROUND: Anatomic extent of ductal carcinoma in situ (DCIS) may be uncertain in spite of clinical, pathologic, and imaging data. Consequently close/positive margins are common with lumpectomy for DCIS and often lead to a challenge in deciding whether to perform a re-excision or mastectomy. PATIENTS AND METHODS: From a single health system, we identified cases of lumpectomy for DCIS with close/positive margins who underwent re-excision for the purpose of constructing a nomogram. In total, 289 patients were available for analysis. The patients were randomly divided into two sets allocating 70% to the modeling and 30% to the validation set. A multivariable logistic regression model was used to estimate the probability of overall positive margin status using multiple clinicopathologic predictors. Nomogram validation included internal tenfold cross-validation, internal bootstrap validation, and external validation for which a concordance index was calculated to assess the external validity. RESULTS: Significant predictors of persistent positive margins from regression modeling included necrosis at diagnosis (non-comedo or comedo); DCIS not associated with calcifications on core biopsy; high-grade DCIS; progesterone receptor positivity; and number of positive margins at initial surgery. When subjected to internal validation, the nomogram achieved an uncorrected concordance index of 0.7332, a tenfold cross-validation concordance index of 0.6795, and a bootstrap-corrected concordance index of 0.6881. External validation yielded an estimated concordance index of 0.7095. CONCLUSION: Using clinical and pathologic variables from initial diagnosis and surgery for DCIS, this nomogram predicts persistent positive margins with margin re-excision, and may be a valuable tool in surgical decision-making.

Impact of Screening Mammography on Treatment in Young Women Diagnosed with Breast Cancer.

BACKGROUND: There is little data exploring the impact of screening mammography on subsequent treatment in the 40-49-year age group with breast cancer. We sought to assess the association between frequency of mammography in young women and extent of surgery and chemotherapy required. METHODS: An IRB-approved retrospective review was performed of patients diagnosed with breast cancer between ages 40 and 49 years from 1 January 2010 to 19 November 2018 within a single health system. Patients were grouped based on last screening 1-24 months prior to diagnosis (1-24 group), > 25 months prior to diagnosis (> 25 group), never screened, and > 25+ never screened (combination group). Multivariate logistic regression models were used to assess for associations between screening intervals and tumor and nodal stage, chemotherapy use, and extent of surgery. RESULTS: Of 869 patients included for analysis, 20% were never screened, 60% screened 1-24 months, and 19% screened > 25 months prior to diagnosis. Compared with the 1-24 months group, the never-screened group, > 25 months group, and combined group were more likely to receive chemotherapy. The never-screened and combined groups were more likely to undergo mastectomy and/or axillary lymph node dissection. Of patients undergoing upfront surgery, the > 25 months and combined groups were more likely to receive adjuvant chemotherapy, while the never-screened and combined groups were more likely to have nodal disease. CONCLUSION: Our findings support the initiation of screening mammography at age 40 years to reduce the risk of aggressive treatments for newly diagnosed breast cancers in this group.

Delay in psychiatric hospitalization from the diagnosis of first-episode schizophrenia and its association with clinical outcomes and direct medical costs: a nationwide, health insurance data-based study.

BACKGROUND: Early intervention is essential for improving the prognosis in patients with first-episode schizophrenia (FES). The Mental Health Act limits involuntary hospitalization in South Korea to cases where an individual exhibits both a mental disorder and a potential for harming themselves or others, which could result in a delay in the required treatment in FES. We investigated the effect of delay in the first psychiatric hospitalization on clinical outcomes in FES. METHODS: The South Korean Health Insurance Review Agency database (2012-2019) was used. We identified 15,994 patients with FES who had a record of at least one psychiatric hospitalization within 1 year from their diagnosis. A multivariate linear regression model and a generalized linear model with a gamma distribution and log link were used to examine associations between the duration from the diagnosis to the first psychiatric admission and clinical outcomes as well as direct medical costs after 2 and 5 years. RESULTS: Within both the 2-year and the 5-year period, longer durations from the diagnosis to the first psychiatric admission were associated with an increase in the number of psychiatric hospitalizations (2-y: B = 0.003, p = 0.003, 5-y: B = 0.007, p = 0.001) and an increase in direct medical costs (total: 2-y: B = 0.005, p < 0.001, 5-y: B = 0.004, p = 0.005; inpatient care: 2-y: B = 0.005, p < 0.001, 5-y: B = 0.004, p = 0.017). CONCLUSIONS: Earlier psychiatric admission from the diagnosis is associated with a decrease in the number of psychiatric admissions as well as in direct medical costs in patients with FES.

Risk of treatment discontinuation and psychiatric hospitalization associated with early dose reduction of antipsychotic treatment in first-episode schizophrenia: A nationwide, health insurance data-based study.

AIM: We investigated the impact of early dose reduction of antipsychotic treatment on the risk of treatment discontinuation and psychiatric hospitalization in patients with first-episode schizophrenia (FES). METHODS: The Health Insurance Review Agency database in South Korea was used to include 16 153 patients with FES. At 6 months from their diagnosis, the patients were categorized by the magnitude of dose reduction (no reduction, 0%-50%, and >50%). With a reference of no reduction, the risk of treatment discontinuation and psychiatric hospitalization associated with dose reduction in the 1-year follow-up period after the first 6 months was examined with a Cox proportional hazard ratio model stratified by the mean daily olanzapine-equivalent dose in the first 3 months (<10, 10 to 20, >20 mg/day). RESULTS: A >50% dose reduction was associated with an increased risk of treatment discontinuation in all subgroups (<10 mg/day: hazard ratio [HR] =1.44, 95% confidence interval [CI] =1.24-1.67 [P <0.01]; 10-20 mg/day: HR =1.60, 95% CI =1.37-1.86 [P <0.01]; and >20 mg/day: HR =1.62, 95% CI =1.37-1.91 [P <0.01]). In the subgroup taking <10 mg/day, an association of 0%-50% dose reduction with an increased risk of treatment discontinuation was observed (HR =1.20, 95% CI =1.09-1.31; P <0.01). A > 50% dose reduction was associated with increased risk of psychiatric hospitalization only in the subgroup taking <10 mg/day (HR =1.48, 95% CI =1.21-1.80; P <0.01). CONCLUSIONS: Our results suggest that an above certain dose of antipsychotic drugs is required to prevent psychiatric hospitalization, and extensive dose reduction of antipsychotic drugs could result in a higher risk of treatment discontinuation.

Trends in neoadjuvant chemotherapy versus surgery-first in stage I HER2-positive breast cancer patients in the National Cancer DataBase (NCDB).

BACKGROUND: Neoadjuvant chemotherapy (NAC) is the standard of care for locally advanced HER2 + breast cancer (BC). Optimal sequencing of treatment (NAC vs. surgery first) is less clear cut in stage I (T1N0) HER2 + BC, where information from surgical pathology could impact adjuvant treatment decisions. Utilizing the NCDB, we evaluated the trend of NAC use compared to upfront surgery in patients with small HER2 + BC. METHODS: We identified NCDB female patients diagnosed with T1 N0 HER2 + BC from 2010 through 2015. Prevalence ratios (PR) using multivariable robust Poisson regression models were calculated to measure the association between baseline characteristics and the receipt of NAC. Analysis of trends over time was denoted by annual percent change (APC) of NAC versus surgery upfront. RESULTS: Of the 14,949 that received chemotherapy and anti-HER2 therapy during the study period, overall 1281 (8.6%) received NAC and 13,668 (91.4%) received adjuvant treatment. Patients receiving NAC increased annually from 4.2% in 2010 to 17.3% in 2015, with the most rapid increase occurring between years 2013 (8.5%) and 2014 (14.2%). The greatest increase was seen in patients with cT1c tumors with an APC of 37.8% over the study period (95% CI 29.0, 47.3%, p < 0.01), although a significant trend was likewise seen in patients with cT1a (APC = 26.1%,95% CI 1.59, 56.6%), and cT1b (APC = 27.4%, 95% CI 18.0, 37.7%) tumors. Predictors of neoadjuvant therapy receipt were age younger than 50 (PR = 1.69, 95% CI 1.52, 1.89), Mountain/Pacific area (PR = 1.24, 95% CI 1.05, 1.46), and estrogen receptor negativity (ER- PR + : PR = 2.01, 95% CI 1.51, 2.68; ER- PR- : PR = 1.49, 95% CI 1.32, 1.69). CONCLUSIONS: Neoadjuvant therapy for T1 N0 HER2 + BC increased over the study period and was mostly due increased use in clinical T1c tumors. This may be consistent with secular change in Pertuzumab treatment following FDA approval in 2013.

Effects of comorbid alcohol use disorder on the clinical outcomes of first-episode schizophrenia: a nationwide population-based study.

BACKGROUND: Alcohol use disorder (AUD) is a common psychiatric comorbidity in schizophrenia, associated with poor clinical outcomes and medication noncompliance. Most previous studies on the effect of alcohol use in patients with schizophrenia had limitations of small sample size or a cross-sectional design. Therefore, we used a nationwide population database to investigate the impact of AUD on clinical outcomes of schizophrenia. METHODS: Data from the Health Insurance Review Agency database in South Korea from January 1, 2007 to December 31, 2016 were used. Among 64,442 patients with first-episode schizophrenia, 1598 patients with comorbid AUD were selected based on the diagnostic code F10. We performed between- and within-group analyses to compare the rates of psychiatric admissions and emergency room (ER) visits, and medication possession ratio (MPR) between the patients with comorbid AUD and control patients matched for the onset age, sex, and observation period. RESULTS: The rates of psychiatric admissions and ER visits in both groups decreased after the time point of diagnosis of AUD; however, the decrease was significantly greater in the patients with comorbid AUD compared to the control patients. While the comorbid AUD group showed an increase in MPR after the diagnosis of AUD, MPR decreased in the control group. The rates of psychiatric admissions, ER visits, and MPR were worse in the comorbid AUD group both before and after the diagnosis of AUD. CONCLUSIONS: The results emphasize an importance of psychiatric comorbidities, especially AUD, in first-episode schizophrenia and the necessity of further research for confirmative findings of the association of AUD with clinical outcomes of schizophrenia.

Use of neoadjuvant versus adjuvant chemotherapy for hormone receptor-positive breast cancer: a National Cancer Database (NCDB) study.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is a well-established therapeutic option for patients with locally advanced disease often allowing downstaging and facilitation of breast conserving therapy. With evolution of better targeted treatment regimens and awareness of improved outcomes for significant responders, use of NAC has expanded particularly for triple negative and HER2-positive (HER2+) breast cancer. In this study, we explore utility of neoadjuvant chemotherapy for hormone receptor-positive HER2-negative (HR+ HER2-) patients. METHODS: Patients with HR+ HER2- breast cancer treated with chemotherapy before or after surgery were identified from 2010 to 2015 in the NCDB. Multivariable regression models adjusted for covariates were used to determine associations within these groups. RESULTS: Among 134,574 patients (clinical stage 2A, 64%; 2B, 21%; 3, 15%), 105,324 (78%) had adjuvant chemotherapy (AC) and 29,250 (22%) received NAC. Use of NAC increased over time (2010-2015; 13.2-19.4% and PR = 1.34 for 2015; p < 0.0001). Patients were more likely to receive NAC with cT3, cT4, and cN+ disease. Patients less likely to receive NAC were age ≥ 50, lobular carcinoma, increased Charlson-Deyo score, and government insurance. Complete response (pCR) was noted in 8.3% of NAC patients. Axillary downstaging occurred in 21% of patients, and predictors included age < 50 years, black race, poorly differentiated grade, invasive ductal histology, and either ER or PR negativity. CONCLUSIONS: NAC use among HR+ HER2- breast cancer patients has expanded over time and offers downstaging of disease for some patients, with pCR seen in only a small subset, but downstaging of the axilla in 21%. Further analysis is warranted to determine the subgroup of patients with HR+ HER2- disease who benefit from this approach.

Defining the Need for Imaging and Biopsy After Mastectomy.

BACKGROUND: The proportion of patients eligible for breast-conservation therapy (BCT) yet opting for mastectomy is increasing. This decision is often driven by the desire to eliminate future screening and/or biopsy of the remaining breast or breasts. This study investigated the incidence of post-mastectomy imaging and biopsy. METHODS: A retrospective review of all unilateral mastectomy (UM) and bilateral mastectomy (BM) cases managed at a single institution was undertaken. Post-mastectomy imaging and biopsy rates were determined. RESULTS: Between 2009 and 2015, 185 UM and 200 BM cases managed for breast cancer were identified. The mean follow-up period was 30 months (range 3-75 months). For the patients with UM, imaging studies and biopsies done on the contralateral side were excluded given the standard of care for continued surveillance of the contralateral breast. Of the 185 UM patients, 19 (10%) underwent ipsilateral imaging (all ultrasounds) for physical examination findings, 11 (6%) underwent biopsy, and 2 (1%) had malignant findings. Of the 200 BM patients, 31 (15.5%) required imaging (29 ultrasounds and 2 MRIs), with 76% of the ultrasounds performed on the side with previous cancer. Subsequently, 16 (8%) of the BM patients had biopsy, with 11 (69%) of the 16 biopsies performed on the ipsilateral side. Three (1.5%) of the biopsies done on ipsilateral side demonstrated malignancy, whereas all the contralateral biopsies were benign. CONCLUSIONS: For 10-15.5% of patients who undergo mastectomy, either UM or BM, subsequent imaging is required, whereas 6-8% undergo biopsy. The yield of malignancy is low, approximately 1%. Thus, after mastectomy, the need for imaging and biopsy is not eliminated. This information is critical for patient understanding and expectation related to surgical decision making.

Impact of Screening Mammography on Treatment in Women Diagnosed with Breast Cancer.

BACKGROUND: Screening mammography reduces breast cancer mortality; however, screening recommendations, ordering, and compliance remain suboptimal and controversies regarding the value of screening persist. We evaluated the influence of screening mammography on the extent of breast cancer treatment. METHODS: Patients ≥ 40 years of age diagnosed with breast cancer from September 2008 to May 2016 at a single institution were divided into two groups: those with screening 1-24 months prior to diagnosis, and those with screening at 25+ months, including patients with no prior mammography. The association between the two groups and various clinical factors were assessed using logistic regression models. Subgroup analysis was performed based on age groups. RESULTS: Analysis included 1125 patients, 819 (73%) with screening at 1-24 months, and 306 (27%) with screening at 25+ months, including 65 (6%) who never had mammography. Overall, patients in the 25+ months group were more likely to receive chemotherapy [odds ratio (OR) 1.51, p = 0.0040], undergo mastectomy (OR 1.32, p = 0.0465), and require axillary dissection (AD; OR 1.66, p = 0.0045) than those in 1-24 months group. On subgroup analysis, patients aged 40-49 years with no prior mammography were more likely to have larger tumors (p = 0.0323) and positive nodes (OR 4.52, p = 0.0058), undergo mastectomy (OR 3.44, p = 0.0068), undergo AD (OR 4.64, p = 0.0002), and require chemotherapy (OR 2.52, p = 0.0287) than the 1-24 months group. CONCLUSIONS: Screening mammography is associated with decreased stage at diagnosis and receipt of less-extensive treatment. This was evident in all groups, including the 40-49 years age group, where controversy exists on whether screening is even necessary.

Esophageal bronchogenic cyst and review of the literature.

BACKGROUND: Bronchogenic cysts are rare foregut abnormalities that arise from aberrant budding of the tracheobronchial tree early in embryological development. These cysts predominantly appear in the mediastinum, where they may compress nearby structures. Intra-abdominal bronchogenic cysts are rare. We report an intra-abdominal bronchogenic cyst that was excised laparoscopically. METHODS: A 40-year old female with a history of gastritis presented for evaluation of recurrent abdominal pain. A previous ultrasound showed cholelithiasis and a presumed portal cyst. Physical examination and laboratory findings were unremarkable. A CT scan with pancreatic protocol was performed and an intra-abdominal mass adherent to the esophagus was visualized. A laparascopic enucleation of the mass was performed. A 3-cm myotomy was made after circumferential dissection of the cyst and the decision was made intraoperatively to reapproximate the muscularis layer. A PubMed literature search on surgical management of esophageal bronchogenic cysts was subsequently performed. RESULTS: The literature search performed on the subject of esophageal bronchogenic cysts found one review article focusing on intramural esophageal bronchogenic cysts in the mediastinum and five case reports of esophageal bronchogenic cysts. Of these, only one was both intraabdominal and managed laparascopically with simple closure of the resulting myotomy. The majority of the bronchogenic cysts mentioned in the literature were located mediastinally and were managed via open thoracotomy. Our findings confirm the rarity of this particular presentation and the unique means by which this cyst was surgically excised. CONCLUSION: This case highlights the management of a rare entity and advocates for enucleation of noncommunicating, extraluminal esophageal bronchogenic cysts and closure of the esophageal muscular layers over intact mucosa as a viable surgical approach to this unusual pathology. Other cases of laparascopic enucleation of bronchogenic cysts have shown similarly uneventful postoperative courses and rapid recovery with no apparent return of symptoms.

Differentially hypomethylated cell-free DNA and coronary collateral circulation.

BACKGROUND: The factors affecting cardioprotective collateral circulation are still incompletely understood. Recently, characteristics, such as CpG methylation of cell-free DNA (cfDNA), have been reported as markers with clinical utility. The aim of this study was to evaluate whether cfDNA methylation patterns are associated with the grade of coronary collateral circulation (CCC). RESULT: In this case-control study, clinical and angiographic data were obtained from 143 patients (mean age, 58 years, male 71%) with chronic total coronary occlusion. Enzymatic methyl-sequencing (EM-seq) libraries were prepared using the cfDNA extracted from the plasma. Data were processed to obtain the average methylation fraction (AMF) tables of genomic regions from which blacklisted regions were removed. Unsupervised analysis of the obtained AMF values showed that some of the changes in methylation were due to CCC. Through random forest preparation process, 256 differentially methylated region (DMR) candidates showing strong association with CCC were selected. A random forest classifier was then constructed, and the area under the curve of the receiver operating characteristic curve indicated an appropriate predictive function for CCC. Finally, 20 DMRs were identified to have significantly different AMF values between the good and poor CCC groups. Particularly, the good CCC group exhibited hypomethylated DMRs. Pathway analysis revealed five pathways, including TGF-beta signaling, to be associated with good CCC. CONCLUSION: These data have demonstrated that differential hypomethylation was identified in dozens of cfDNA regions in patients with good CCC. Our results support the clinical utility of noninvasively obtained epigenetic signatures for predicting collateral circulation in patients with vascular diseases.

Comparative effectiveness of antipsychotic monotherapy and polypharmacy in schizophrenia patients with clozapine treatment: A nationwide, health insurance data-based study.

Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia (TRS). However, it remains uncertain whether antipsychotic augmentation to clozapine has the superior effectiveness over clozapine alone and the effect size of clozapine compared to other antipsychotic drugs in TRS. Therefore, we examined the comparative effectiveness of antipsychotic monotherapy and polypharmacy on the risk of psychiatric admission and treatment discontinuation in TRS. Data were collected from the Health Insurance Review Agency database between January 2010 and December 2019 in South Korea. Among prevalent patients with schizophrenia, we defined 22,327 patients with TRS as those who had been prescribed with clozapine at least once during the entire observation period. Stratified Cox proportional hazards regressions were performed using data on all antipsychotic prescriptions of patients with TRS to investigate the risk of psychiatric hospitalization and treatment discontinuation associated with antipsychotic treatment. In individual comparisons, clozapine monotherapy was the most effective for the risk of psychiatric hospitalization compared to no use (hazard ratio [HR] = 0.23, 95% confidence interval [CI] = 0.22-0.25). In group comparisons, clozapine with long-acting injectable (LAI) second-generation antipsychotics (SGA) was superior to clozapine monotherapy for the risk of psychiatric hospitalization (HR = 0.60, 95%CI = 0.41-0.88). Clozapine monotherapy was associated with the lowest risk of treatment discontinuation in the individual and group comparisons. This retrospective observational population-based study reports that clozapine with LAI SGA is more effective in lowering the risk of psychiatric hospitalization in antipsychotic group comparison with the reference of clozapine monotherapy.

Diagnostic conversion from unipolar to bipolar affective disorder-A population-based study.

OBJECTIVES: It is essential to clinically distinguish bipolar affective disorder from unipolar affective disorders. However, patients previously diagnosed with unipolar affective disorder are sometimes later diagnosed with bipolar affective disorder, known as diagnostic conversion. Here we investigated diagnostic conversion using data from a nationwide population-based register. METHODS: We obtained claims data from 2007 to 2020 in Korea's Health Insurance Review Agency database and identified a cohort of patients who were diagnosed with unipolar depression in 2009 without prior psychiatric diseases within the previous 2 years. We studied the rate of diagnostic conversion and risk factors, especially antidepressants. RESULTS: About 6.5% of patients underwent diagnostic conversion during the observation period. Younger age at disease onset and usage of antidepressants increased the relative risk for diagnostic conversion. Patients using serotonin-norepinephrine reuptake inhibitors (SNRI) showed more than twice the risk compared to no usage of antidepressant. LIMITATION: First, this study was based on the population-based register data. Thus, we defined the patient cohort diagnosed with unipolar depression with strict inclusion criteria. Second, the exposure time differed between different antidepressants. Third, we estimated the relative risk for diagnostic conversion compared to no use of antidepressants. Moreover, we could not rule out the potential influence of antidepressant polypharmacy. CONCLUSION: We confirmed diagnostic conversion in some patients and identified younger age or usage of antidepressants, especially SNRI, as risk factors. Because unipolar and bipolar affective disorders show different disease courses or prognoses and have different treatment strategies, clinicians should be mindful of diagnostic conversion.

One-Year Clinical Outcomes Following Electroconvulsive Therapy for Patients with Schizophrenia: A Nationwide Health Insurance Data-Based Study.

Background: Although the use of electroconvulsive therapy (ECT) in the treatment of schizophrenia has decreased since the advent of antipsychotic drugs, ECT is still implemented in several clinical indications. However, a few population-based studies have examined its real-world effectiveness in schizophrenia. Methods: We used data from 2010 to 2019 from the Health Insurance Review and Assessment Service database in the Republic of Korea. We selected 380 schizophrenia patients having more than six ECT sessions and 1140 patient controls matched for age, sex, calendar year at entry, and the number of psychiatric hospitalizations before the time point of start of psychiatric hospitalization for ECT. Antipsychotic treatment discontinuation, psychiatric hospitalization, and direct medical costs were used as measures of clinical outcomes. Multiple regression analysis was used for any group-by-time interaction effect, and 1-year pre- and post-ECT periods were compared within and between the groups. Results: We found a significantly lower number of antipsychotic treatment discontinuations in the ECT group during the 1-year post-ECT period (t=2.195, p=0.028). A larger decrease was found in the number of psychiatric hospitalizations in the ECT group, with a group-by-time interaction effect (p=0.043). The direct medical costs in the 1-year pre- (t=-8.782, p<0.001) and post-ECT periods (t=-9.107, p<0.001) were higher in the ECT group than in the control group, with no significant change across both periods. Conclusion: We found that the ECT group had a larger decrease in the number of psychiatric hospitalizations in the 1-year post-ECT period than the control group.

Use of olanzapine compared with clozapine for treatment-resistant schizophrenia in a real-world setting: nationwide register-based study.

BACKGROUND: Clozapine is generally considered as the treatment of choice for patients with treatment-resistant schizophrenia (TRS). However, its superiority has recently been questioned because olanzapine has been suggested as non-inferior to clozapine in its effectiveness. AIMS: We aimed to investigate the current status of clozapine prescriptions to identify any disparity between clinical guidelines and real-world practices. METHOD: In this study, we utilised the Health Insurance Review Agency database in the Republic of Korea to investigate the real-world effectiveness of clozapine for patients with TRS. We compared differences in patient variables before and after clozapine administration, and we also performed survival analyses for both psychiatric admissions and emergency room visits among patients who used clozapine or olanzapine. RESULTS: This study investigated an incident cohort of 64 442 patients, and 2338 patients have been prescribed clozapine. Of these, 998 patients had TRS. In survival analysis, clozapine showed a worse survival rate for psychiatric admissions than olanzapine (hazard ratio 0.615). We also identified that clinicians tended to try a number of antipsychotics, as recommended, before starting patients on clozapine. CONCLUSIONS: In conclusion, we found that olanzapine led to higher survival rates for psychiatric admissions than clozapine. Thus, considering the risk of serious adverse effects, clozapine may be used conservatively. Considering several studies advocating superior efficacy of clozapine, further studies with extensive data are recommended.

White matter impairments in patients with schizophrenia: A multisite diffusion MRI study.

There is a lack of convincing and replicative findings regarding white matter abnormalities in schizophrenia. Several multisite diffusion magnetic resonance imaging (dMRI) studies have been conducted to increase statistical power and reveal subtle white matter changes. Data pooling methods are crucial in joint analysis to compensate for the use of different scanners and image acquisition parameters. A harmonization method using raw dMRI data was developed to overcome the limited generalizability of previous data pooling methods. We obtained dMRI data of 242 healthy controls and 190 patients with schizophrenia from four different study sites. After applying the harmonization method to the raw dMRI data, a two-tensor whole-brain tractography was performed, and diffusion measures were compared between the two groups. The correlation of fractional anisotropy (FA) with the positive and negative symptoms was evaluated, and the interaction effect of diagnosis-by-age, age-squared, and sex was examined. The following white matter tracts showed significant group differences in the FA: the right superior longitudinal fascicle (SLF), the left-to-right lateral orbitofrontal commissural tract, pars orbitalis (pOr-pOr) commissural tract, and pars triangularis (pTr-pTr) commissural tract. The FA of the right SLF and pTr-pTr commissural tract were significantly associated with the Positive and Negative Syndrome Scale (PANSS) positive and negative scores. No significant interaction effect was observed. These findings add to the evidence on structural brain abnormalities in schizophrenia and can aid in obtaining a better understanding of the biological foundations of schizophrenia.

Optical Coherence Tomography: A Novel Imaging Method for Post-lumpectomy Breast Margin Assessment-A Multi-reader Study.

RATIONALE AND OBJECTIVES: This study aimed to assess whether different breast cancer subspecialty physicians can be trained to distinguish non-suspicious from suspicious areas of post-lumpectomy specimen margin in patients with breast cancer using optical coherence tomography (OCT) images (a near-infrared based imaging technique) with final histology as the reference standard. MATERIALS AND METHODS: This institutional review board-exempt, Health Insurance Portability and Accountability Act-compliant study was performed on 63 surgically excised breast specimens from 35 female patients, creating a 90-case atlas containing both non-suspicious and suspicious areas for cancer. OCT images of the specimens were performed, providing 6.5-15 µm resolution with tissue visualization 1-2 mm subsurface. From the 90-case atlas, 40 cases were chosen for training and 40 were randomly selected for reader assessment. Three breast imaging radiologists, two pathologists, two breast surgeons, and one non-clinical reader were trained and assessed for ability to distinguish non-suspicious from suspicious findings blinded to clinical data and corresponding histology slides. Duration of training and assessment, sensitivity, specificity, positive predictive value, negative predictive value, and the area under the curve for each reader were calculated as well as averages by subspecialty. RESULTS: The average training time was 3.4 hours (standard deviation, 1.2). The average assessment time was 1.9 hours (standard deviation, 0.7). The overall average reader sensitivity, specificity, and accuracy for detecting suspicious findings with histologic confirmation of cancer at the surgical margin for all eight readers were 80%, 87%, and 87%, respectively. Radiologists demonstrated the highest average among the disciplines, 85%, 93%, and 94%, followed by pathologists, 79%, 90%, and 84%, and surgeons, 76%, 84%, and 82% respectively. CONCLUSIONS: With relatively short training (3.4 hours), readers from different medical specialties were able to distinguish suspicious from non-suspicious OCT imaging findings in ex vivo breast tissue as confirmed by histology. These results support the potential of OCT as a real-time intraoperative tool for post-lumpectomy specimen margin assessment.