Flowchart of study subject selection.

<p>In the 3% sample data of national health insurance claims database, 51,671 were diagnosed with osteoporosis and 26,881 were prescribed with bisphosphonate or raloxifene among them.</p

Sub-group analysis of the risk of ischemic stroke with quetiapine, olanzapine, haloperidol, and chlorpromazine compared with risperidone according to the age group, gender, the presence and type of dementia, and comorbidity.

<p>Adjusted for age, gender, presence or absence of dementia (F00-F03, G30, G31.8), depression (F32–33, F34.1, F41.2), dyslipidemia (E78.0), coronary heart disease (I21-I25), COPD (J40-J44, J47), and the use of antidepressants, benzodiazepine, anticoagulants, or antithrombotic agents during the follow-up period.</p><p>The estimated HRs were finally accepted as the SMR weighted and multivariable adjusted HR after exclusion of the patients whose propensity score is > 99.99 in quetiapine, < 0.05 in olanzapine, > 0.90 in haloperidol, and < 0.05 in chlorpromazine</p><p>* Could not be estimated.</p><p>† P for trend was calculated using likelihood ratio test.</p><p>Sub-group analysis of the risk of ischemic stroke with quetiapine, olanzapine, haloperidol, and chlorpromazine compared with risperidone according to the age group, gender, the presence and type of dementia, and comorbidity.</p

The frequency and proportion of osteoporosis patients by age, comorbidities, fracture by site, concurrent medication, and medical insurance type in Korea in 2010.

<p>SD, Standard deviation GERD, Gastroesophageal reflux disease</p><p>^a Cochran–Armitage test for trend analysis</p><p>^b Fisher’s exact test</p><p>^c Vertebra (M48.4, M48.5, S22.0, S22.1, S32.0), Hip (S72.0, S72.1), Distal radius (S52.5, S52.6), Humerus (S42.2, S42.3)</p><p>The frequency and proportion of osteoporosis patients by age, comorbidities, fracture by site, concurrent medication, and medical insurance type in Korea in 2010.</p

Regional distribution of proportion of raloxifene prescription standardized in DDDs/1,000 patients/day.

<p>The Seoul metropolitan area had higher proportion of raloxifene prescriptions among Korean osteoporosis female patients. (The map came from the official site of Statistics Korea, <a href="https://sgis.kostat.go.kr/statbd/statbd_03.vw" target="_blank">https://sgis.kostat.go.kr/statbd/statbd_03.vw</a>)</p

Dose-response relationship and time-varying risks of ischemic stroke of quetiapine, olanzapine, haloperidol, and chlorpromazine compared with risperidone.

<p>(Mean PDD, mean Prescribed Daily Dose)</p><p>*Adjusted for age, gender, presence or absence of dementia (F00-F03, G30, G31.8), depression (F32–33, F34.1, F41.2), dyslipidemia (E78.0), coronary heart disease (I21-I25), COPD (J40-J44, J47), and the use of antidepressants, benzodiazepine, anticoagulants, or antithrombotic agents during the follow-up period.</p><p>The estimated HRs were finally accepted as the SMR weighted and multivariable adjusted HR after exclusion of the patients whose propensity score is > 99.99 in quetiapine, < 0.05 in olanzapine, >0.90 in haloperidol, and < 0.05 in chlorpromazine</p><p>†Could not be estimated.</p><p>‡P for trend was calculated using the likelihood ratio test.</p><p>§Short- and long-term periods were distinguished by the cross-point using a log-log survival curve.</p><p>Dose-response relationship and time-varying risks of ischemic stroke of quetiapine, olanzapine, haloperidol, and chlorpromazine compared with risperidone.</p

Risk of Ischemic Stroke Associated with the Use of Antipsychotic Drugs in Elderly Patients: A Retrospective Cohort Study in Korea

<div><p>Objective</p><p>Strong concerns have been raised about whether the risk of ischemic stroke differs between conventional antipsychotics (CAPs) and atypical antipsychotics (AAPs). This study compared the risk of ischemic stroke in elderly patients taking CAPs and AAPs.</p><p>Method</p><p>We conducted a retrospective cohort study of 71,584 elderly patients who were newly prescribed the CAPs (haloperidol or chlorpromazine) and those prescribed the AAPs (risperidone, quetiapine, or olanzapine). We used the National Claims Database from the Health Insurance Review and Assessment Service (HIRA) from January 1, 2006 to December 31, 2009. Incident cases for ischemic stroke (ICD-10, I63) were identified. The hazard ratios (HR) for AAPs, CAPs, and for each antipsychotic were calculated using multivariable Cox regression models, with risperidone as a reference.</p><p>Results</p><p>Among a total of 71,584 patients, 24,668 patients were on risperidone, 15,860 patients on quetiapine, 3,888 patients on olanzapine, 19,564 patients on haloperidol, and 7,604 patients on chlorpromazine. A substantially higher risk was observed with chlorpromazine (HR = 3.47, 95% CI, 1.97–5.38), which was followed by haloperidol (HR = 2.43, 95% CI, 1.18–3.14), quetiapine (HR = 1.23, 95% CI, 0.78–2.12), and olanzapine (HR = 1.12, 95% CI, 0.59–2.75). Patients who were prescribed chlorpromazine for longer than 150 days showed a higher risk (HR = 3.60, 95% CI, 1.83–6.02) than those who took it for a shorter period of time.</p><p>Conclusions</p><p>A much greater risk of ischemic stroke was observed in patients who used chlorpromazine and haloperidol compared to risperidone. The evidence suggested that there is a strong need to exercise caution while prescribing these agents to the elderly in light of severe adverse events with atypical antipsychotics.</p></div

General characteristics of new users of conventional and atypical antipsychotic medications.

<p>* The P value was calculated by using the Mantel-Haenszel chi-squared test.</p><p>† The P value was calculated by using an ANOVA test with the Bonferroni correction.</p><p>General characteristics of new users of conventional and atypical antipsychotic medications.</p

Age- and sex-standardized prevalence ratios and 95% confidence intervals of the extraintestinal manifestations using a random sample of the entire Korean population as the reference population.

<p>Age- and sex-standardized prevalence ratios and 95% confidence intervals of the extraintestinal manifestations using a random sample of the entire Korean population as the reference population.</p

Number of individuals with extraintestinal manifestations among Crohn disease patients, ulcerative colitis patients, and the general population.

<p>Number of individuals with extraintestinal manifestations among Crohn disease patients, ulcerative colitis patients, and the general population.</p

Additional file 1: of M1 macrophage recruitment correlates with worse outcome in SHH Medulloblastomas

Figure S1. Macrophage recruitment in human tonsil FFPE tissue. Figure S2. Expression heatmap of 22 subgroup-specific signature genes in 48 study patients by the nanoString nCounter System. Figure S3. TAM recruitment and prognostic outcomes in the whole patient cohort. Figure S4. TAM recruitment and prognostic outcomes in SHH MB from Yonsei University. (PPTX 3883 kb