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Aim: Patients with bipolar disorder (BD) tend to have poorer outcomes after pneumonia and could have a higher risk for recurrence of pneumonia. We aimed to investigate the incidence and risk factors of recurrent pneumonia in patients with BD. Methods: In a nationwide cohort of BD patients (derived from the National Health Insurance Research Database in Taiwan) who were hospitalized for pneumonia between 1996 and 2012, we identified 188 patients who developed recurrent pneumonia after a baseline pneumonia episode. Applying risk‐set sampling at a 1:2 ratio, 353 matched controls were selected from the study cohort. We used multivariate conditional logistic regression analysis to explore the association between recurrent pneumonia and physical illness, concomitant medications, and psychotropic drugs. Results: The findings showed that the incidence of recurrent pneumonia in BD was 6.60 cases per 100 person‐years, which was higher than that in the general population. About 10% (9.24%) of cases with recurrent pneumonia died within 30 days of hospitalization. Patients had increased risk of recurrent pneumonia if they had hypertension, diabetes mellitus, cancer, or asthma. Conversely, psychotropic drugs, both first‐ and second‐generation antipsychotics, which are known to increase susceptibility to baseline pneumonia, were not associated with risk of pneumonia recurrence. Conclusion: We found an excess incidence of recurring pneumonia in patients with BD, and this risk was associated with pre‐existing medical conditions but not psychotropic agents. Physicians should carefully consider the comorbid medical conditions of patients with BD that could lead to recurrent pneumonia. [ABSTRACT FROM AUTHOR]

Aim We attempted to determine risk factors, particularly pathophysiological changes, for early cardiovascular mortality in bipolar disorder (BD). Methods A total of 5416 inpatients with bipolar I disorder were retrospectively followed through record linkage for cause of death. A total of 35 patients dying from cardiovascular disease (CVD; ICD 9: 401-443) before the age of 65 years were identified. Two living BD patients and two mentally healthy adults were matched with each deceased patient as control subjects according to age (±2 years), sex, and date (±3 years) of the final/index admission or the date of general health screening. Data were obtained through medical record reviews. Results Eighty percent of CVD deaths occurred within 10 years following the index admission. Conditional logistic regression revealed that the variables most strongly associated with CVD mortality were the leukocyte count and heart rate on the first day of the index hospitalization, as the deceased BD patients were compared with the living BD controls. Systolic pressure on the first day of the index hospitalization can be substituted for heart rate as another risk factor for CVD mortality. Conclusion It is suggested that systemic inflammation and sympathetic overactivity during the acute phase of BD may be risk factors for early CVD mortality. [ABSTRACT FROM AUTHOR]

Background: The association between antipsychotic use and the risk of stroke in schizophrenic patients is controversial. We sought to study the association in a nationwide cohort with schizophrenia. Methods: Using a retrospective cohort of patients with schizophrenia (N = 31,976) derived from the Taiwan National Health Insurance Research Database, 802 new-onset cases of stroke were identified within 10 years of follow-up (from 2000 through 2010). We designed a case-crossover study using 14-day windows to explore the risk factors of stroke and the association between antipsychotic drugs and the risk of stroke. We analyzed the risks of individual antipsychotics on various subgroups of stroke including ischemic, hemorrhagic, and other strokes, and the risks based on the antipsychotic receptor-binding profile of each drug. Results: Use of any second-generation antipsychotic was associated with an increased risk of stroke (adjusted risk ratio = 1.45, P = .009) within 14 days while the use of any first-generation antipsychotic was not. Intriguingly, the use of any second-generation antipsychotic was associated with ischemic stroke but not hemorrhagic stroke. The antipsychotic receptor-binding profile analysis showed that the antihistamine 1 receptor was significantly associated with ischemic stroke (adjusted risk ratio = 1.72, P = .037), and the sensitivity analysis based on the 7-day window of exposure validated the association (adjusted risk ratio = 1.87, P = .015). Conclusions: Use of second-generation antipsychotic drugs appeared to be associated with an increased risk of ischemic stroke in the patients studied, possibly mediated by high affinity for histamine-1 receptor blockade. Further research regarding the underlying biological mechanism and drug safety is suggested. [ABSTRACT FROM AUTHOR]

Background: This study assessed the risk of developing acute coronary syndrome requiring hospitalization in association with the use of certain antipsychotic medications in schizophrenia patients. Methods: A nationwide cohort of 31,177 inpatients with schizophrenia between the ages of 18 and 65 years whose records were enrolled in the National Health Insurance Research Database in Taiwan from 2000 to 2008 and were studied after encrypting the identifications. Cases (n = 147) were patients with subsequent acute coronary syndrome requiring hospitalization after their first psychiatric admission. Based on a nested case-control design, each case was matched with 20 controls for age, sex and the year of first psychiatric admission using risk-set sampling. The effects of antipsychotic agents on the development of acute coronary syndrome were assessed using multiple conditional logistic regression and sensitivity analyses to confirm any association. Results: We found that current use of aripiprazole (adjusted risk ratio [RR] = 3.68, 95% CI: 1.27–10.64, p<0.05) and chlorpromazine (adjusted RR = 2.96, 95% CI: 1.40–6.24, p<0.001) were associated with a dose-dependent increase in the risk of developing acute coronary syndrome. Although haloperidol was associated with an increased risk (adjusted RR = 2.03, 95% CI: 1.20–3.44, p<0.01), there was no clear dose-dependent relationship. These three antipsychotic agents were also associated with an increased risk in the first 30 days of use, and the risk decreased as the duration of therapy increased. Sensitivity analyses using propensity score-adjusted modeling showed that the results were similar to those of multiple regression analysis. Conclusions: Patients with schizophrenia who received aripiprazole, chlorpromazine, or haloperidol could have a potentially elevated risk of developing acute coronary syndrome, particularly at the start of therapy. [ABSTRACT FROM AUTHOR]

Introduction: Patients with schizophrenia suffer from excessive premature mortality, and sudden cardiac death (SCD) is receiving growing attention as a potential cause.Aim: The present study investigated the incidence of SCD and its risk factors in a large schizophrenia cohort.Methods: We enrolled a consecutive series of 8264 patients diagnosed with schizophrenia (according to DSM-III-R and DSM-IV criteria) who were admitted to a psychiatric center in northern Taiwan from January 1, 1985 through December 31, 2008. By linking with national mortality database, 64 cases of SCD were identified. The standardized mortality ratio (SMR) for SCD was estimated. The cases were matched with controls randomly selected using risk-set sampling in a 1:2 ratio. A standardized chart review process was used to collect socio-demographic and clinical characteristics and the prescribed drugs for each study subject. Multivariate conditional logistic regression analysis was used to identify correlates of SCD at the index admission and the latest admission.Results: The SMR for SCD was 4.5. For the clinical profiles at the index admission, physical disease (adjusted risk ratio [aRR]=2.91, P<.01) and aggressive behaviors (aRR=3.99, P<.01) were associated with the risk of SCD. Regarding the latest admission, electrocardiographic abnormalities (aRR=5.46, P<.05) and administration of first-generation antipsychotics (aRR=5.13, P<.01) elevated the risk for SCD. Consistently, aggressive behaviors (aRR=3.26, P<.05) were associated with increased risk as well.Conclusions: Apart from cardiovascular profiles and antipsychotics, physical aggression is a crucial risk factor that deserves ongoing work for clarifying the mechanisms mediating SCD in schizophrenia. [ABSTRACT FROM AUTHOR]

Background Excessive alcohol consumption causes a broad range of health problems, including premature mortality and sudden cardiac death ( SCD). We identified potential clinical characteristics and laboratory indices associated with SCD among patients with alcohol dependence. Methods Patients with alcohol dependence ( n = 2,793) admitted to a psychiatric center in northern Taiwan between 1985 and 2008 were linked with a national mortality database for causes of death. Of the 2,793 patients in the cohort, 67 cases died of SCD. The standardized mortality ratio ( SMR) of SCD relative to the general population was calculated. Based on a nested case-control design, we selected a set of sex-, age-, and year-of-admission-matched two control subjects for each case derived from the cohort. We collated the clinical information through a standardized review of patients' medical records. Conditional logistic regressions were then conducted to explore potential exposures associated with SCD. Results The sample had substantially higher SCD mortality ( SMR 12.8) compared to the general population. After adjustments in the multivariate analyses for the clinical profiles at the index (earliest) admission, both abnormal electrocardiography ( ECG) (adjusted risk ratio = 16.97, 95% confidence interval ( CI) 1.60 to 179.58, p = 0.019) and elevated aspartate aminotransferase levels ( adjusted risk ratio = 1.01, 95% CI 1.00 to 1.02, p = 0.046) were significantly associated with SCD. Conclusions This study raises the question of whether intensive follow-up of patients with elevated AST and abnormal ECG findings should be evaluated as a strategy to prevent SCD in patients with alcohol dependence. [ABSTRACT FROM AUTHOR]

Objective: Patients with bipolar disorder are at a high risk for comorbid alcohol use disorder, and both disorders are associated with poor outcomes and multiple morbidities. This study aimed to explore not only the psychosocial functioning and psychopathological outcomes but also the medical morbidity of patients with bipolar disorder with and without alcohol use disorder. Methods: Outpatients with bipolar I disorder (DSM-IV) were recruited from a psychiatric teaching hospital in Taiwan (N = 393). Data on psychiatric symptoms, psychosocial functioning, and physical health were obtained through interviews with patients and collaterals, patient self-report, and medical record reviews. Results: Participants had a mean age of 41.1 years (SD = 11.9) and were mostly female (n = 255, 64.9%). Fewer than 10% (n = 34, 8.7%) met criteria for alcohol use disorder, and these participants were more likely to be male, to smoke, and to have a history of rapid cycling, higher mean body mass index, and higher incidences of gastrointestinal and hepatobiliary morbidities. A multiple logistic regression analysis revealed that patients with, versus those without, alcohol use disorder were more prone to gastrointestinal diseases (adjusted OR = 4.25, 95% CI [1.44–12.53], p <.01), hepatobiliary diseases (adjusted OR = 3.14, 95% CI [1.20–8.25], p <.025), and history of rapid cycling (adjusted OR = 2.53, 95% CI [0.91–7.01], p <.075). Conclusions: Comorbid alcohol use disorders may have a stronger impact on physical health than on psychosocial or psychopathological outcomes of patients with bipolar disorder. [ABSTRACT FROM AUTHOR]

Background: The Chinese version of the Activities of Daily Living Rating Scale III (ADLRS-III), which has 10 domains, is commonly used for assessing activities of daily living (ADL) in patients with schizophrenia. However, construct validity (i.e., unidimensionality) for each domain of the ADLRS-III is unknown, limiting the explanations of the test results. Purpose: This main purpose of this study was to examine unidimensionality of each domain in the ADLRS-III. We also examined internal consistency and ceiling/floor effects in patients with schizophrenia. Methods: From occupational therapy records, we obtained 304 self-report data of the ADLRS-III. Confirmatory factor analysis (CFA) was conducted to examine the 10 one-factor structures. If a domain showed an insufficient model fit, exploratory factor analysis (EFA) was performed to investigate the factor structure and choose one factor representing the original construct. Internal consistency was examined using Cronbach’s alpha (α). Ceiling and floor effects were determined by the percentage of patients with the maximum and minimum scores in each domain, respectively. Results: CFA analyses showed that 4 domains (i.e., leisure, picture recognition, literacy ability, communication tools use) had sufficient model fits. These 4 domains had acceptable internal consistency (α = 0.79-0.87) and no ceiling/floor effects, except the leisure domain which had a ceiling effect. The other 6 domains showed insufficient model fits. The EFA results showed that these 6 domains were two-factor structures. Conclusion: The results supported unidimensional constructs of the leisure, picture recognition, literacy ability, and communication tool uses domains. The sum scores of these 4 domains can be used to represent their respective domain-specific functions. Regarding the 6 domains with insufficient model fits, we have explained the two factors of each domain and chosen one factor to represent its original construct. Future users may use the items from the chosen factors to assess domain-specific functions in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Objective A proinflammatory phase with various immunomodulatory mechanisms has been noted in bipolar mania and major depression. Weight gain and increased production of leptin may be associated with immunomodulation and insulin resistance in bipolar disorder. However, immunomodulation and its linkage with leptin and insulin in the depressive episode of bipolar disorder remain unclear. We investigated alterations in inflammatory markers and their relationship with leptin and insulin levels in patients with phases of bipolar disorder from acute depression to full remission. Methods Thirty-two physically healthy bipolar I depressed patients aged <45 years and age- and sex-matched healthy controls participated in this study. We measured their circulating levels of leptin, insulin, high-sensitivity C-reactive protein (hs-CRP), soluble interleukin-2 receptor ( sIL-2R), soluble interleukin-6 receptor ( sIL-6R), soluble tumor necrosis factor receptor 1 ( sTNF-R1), and interleukin-1 receptor antagonist (IL-1Ra) in three phases, i.e., acute depression, subsequent partial remission, and full remission. Results In acute depression, subsequent partial remission, and full remission, patients with bipolar disorder had significantly higher mean levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R compared with control subjects. The IL-1Ra and sTNF-R1 levels in various affective phases were significantly correlated to body mass index, leptin level, circulating lipids, and medication status. The sIL-2R levels in the three affective phases were all independent of other inflammatory markers and clinical and laboratory variables. Patients showed no alteration of sIL-6R levels through the depressive episode. Conclusions Patients with bipolar disorder in depressive episodes may exhibit persistent inflammation with elevated levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R but not sIL-6R from the acute phases to full remission. Only sIL-2R production seems to be tightly linked with the pathophysiology of bipolar depression and is independent of insulin and leptin levels. [ABSTRACT FROM AUTHOR]

Background: Since the late 1990s, methamphetamine use has become a considerable public health concern. Despite high suicide rates among methamphetamine users, studies exploring medical utilization and psychiatric and physical comorbidities before suicide are scant. We aim to examine the pattern of medical utilization and distribution of comorbidities shortly before suicide in methamphetamine users who died of suicide and compared these data with those of living methamphetamine users.Methods: From Taiwan's National Health Insurance Research Database, we identified the cohort with methamphetamine use disorder (n = 23,248) between January 1, 2001, and December 31, 2005. We identified 5972 deceased patients (of whom 745 died of suicide) by linking each patient with the national mortality database during the study period. By conducting a nested case-control study with risk-set sampling, from the methamphetamine cohort, we selected four age- and sex-matched controls for each patient who died of suicide (cases). We applied conditional logistic regression to investigate differences in medical utilization and physical and psychiatric comorbidities between cases and controls.Results: Cases had higher medical utilization within 3 months before suicide, particularly in the departments of psychiatry, internal medicine, emergency, and family practice. Cases had higher risks of physical comorbidities, including pneumonia and renal disease, and psychiatric comorbidities, including depressive disorder, sleep disorder, drug-induced mental disorder, schizophrenia, and bipolar disorder.Conclusions: The findings of increased medical utilization and the higher risks of physical and psychiatric comorbidities in cases are crucial for developing specific interventions to prevent suicide in this patient population. [ABSTRACT FROM AUTHOR]

Abstract: This study aimed at estimating the protective effect of suicide precautions and clinical risk factors for inpatient suicides. A standardized precaution system was implemented in a large psychiatric center on January 1, 1996. A consecutive series of 33,121 admissions from 1998 to 2008 constituted the post-implementation cohort and 13,515 admissions from 1985 to 1995 constituted the pre-implementation cohort as comparison group. Inpatient suicides were identified via record linkage with national mortality database. For each of 41 inpatient suicides, four controls were randomly selected based on a nested case–control study. A standardized chart review process was employed to collate clinical information for each study subject. Risk and protective factors for inpatient suicides was estimated by conditional logistic regression. The findings showed that, among subjects with shorter lengths of stay, those admitted in post-implementation era had a significantly lower adjusted risk ratio (0.157, p=0.048) for inpatient suicides. Three depression-related symptoms elevated the risk for inpatient suicides: depressed mood (adjusted risk ratio=2.11, P=0.002), loss of energy (adjusted risk ratio=1.99, P=0.018), and psychomotor retardation (adjusted risk ratio=1.67, P=0.066; with marginal statistical significance). Suicide precautions have protective effect against inpatient suicides. A better assessment and prevention efforts is needed, particularly for those with depression-related symptoms. [Copyright &y& Elsevier]

Background: Pneumonia is one of most prevalent infectious diseases worldwide and is associated with considerable mortality. In comparison to general population, schizophrenia patients hospitalized for pneumonia have poorer outcomes. We explored the risk factors of short-term mortality in this population because the information is lacking in the literature. Methods: In a nationwide schizophrenia cohort, derived from the National Health Insurance Research Database in Taiwan, that was hospitalized for pneumonia between 2000 and 2008 (n = 1,741), we identified 141 subjects who died during their hospitalizations or shortly after their discharges. Based on risk-set sampling in a 1∶4 ratio, 468 matched controls were selected from the study cohort (i.e., schizophrenia cohort with pneumonia). Physical illnesses were categorized as pre-existing and incident illnesses that developed after pneumonia respectively. Exposures to medications were categorized by type, duration, and defined daily dose. We used stepwise conditional logistic regression to explore the risk factors for short-term mortality. Results: Pre-existing arrhythmia was associated with short-term mortality (adjusted risk ratio [RR] = 4.99, p<0.01). Several variables during hospitalization were associated with increased mortality risk, including incident arrhythmia (RR = 7.44, p<0.01), incident heart failure (RR = 5.49, p = 0.0183) and the use of hypoglycemic drugs (RR = 2.32, p<0.01). Furthermore, individual antipsychotic drugs (such as clozapine) known to induce pneumonia were not significantly associated with the risk. Conclusions: Incident cardiac complications following pneumonia are associated with increased short-term mortality. These findings have broad implications for clinical intervention and future studies are needed to clarify the mechanisms of the risk factors. [ABSTRACT FROM AUTHOR]

Abstract: Background: Weight gain and increased production of leptin may be associated with immuno-modulation and insulin resistance in bipolar disorder. The links among inflammatory markers, leptin, and insulin of bipolar patients from acute mania to full remission remain unclear. Methods: Thirty-three healthy, bipolar I patients under 45years of age were enrolled. We measured the circulating levels of high-sensitivity C-reactive protein (hs-CRP), anti-inflammatory mediators (interleukin-1 receptor antagonist [IL-1Ra] and soluble tumor necrosis factor receptor 1 [sTNF-R1]), leptin, and insulin during acute mania and subsequent partial and full remission. The results were compared with 33 age- and gender-matched healthy subjects. Results: The levels of IL-1Ra and hs-CRP of bipolar patients in both acute mania and partial remission were significantly higher than their levels of control subjects. The hs-CRP level of bipolar patients was also elevated in full remission. The elevation of IL-1Ra and hs-CRP levels in acute mania was independent of each other. They were also independent of the body mass index (BMI) and levels of leptin and insulin measurements. The levels of leptin were all positively associated with insulin levels in the normal subjects and bipolar patients in three phases. However, a significant relationship between leptin and immunoparameter was only seen in full remission with sTNF-R1 (r=0.51). Furthermore, IL-1Ra was inversely correlated with sTNF-R1 (r=−0.37, p<0.05) during partly remission, and while levels of IL-1Ra tended to normalize when patients remitted, levels of hs-CRP and sTNF-R1 showed the opposite trend. Conclusions: Activated inflammation was found in acute mania, as evidenced by high levels of IL-1Ra, hs-CRP, and sTNF-R1. The production of leptin may be more tightly linked to insulin than the immunomodulators. Chronic inflammation may exist in bipolar patients and is reflected by elevations of IL-1Ra and hs-CRP levels in acute mania and persistent higher hs-CRP in full remission. [Copyright &y& Elsevier]

Abstract: Background: Marked increases in the incidence of charcoal burning suicide have contributed to Taiwan''s rising suicide rate in the past decade. To assess possible opportunities for intervention, we have compared survivors of suicide attempts by charcoal burning with people who ingested poisons. Methods: We interviewed a consecutive series of suicide attempters by charcoal burning (n=37) and self-poisoning (n=38) admitted to Taipei Veterans General Hospital (TVGH) between January 2009 and March 2010. Interviews included the Structured Clinical Interview of DSMIV (SCID) and Beck Suicide Intent Scale. Results: Compared to people who ingested medicines/poisons, charcoal burning suicide attempters were less likely to have a pre-existing physical illness or contact with psychiatric services prior to the attempt and more likely to be employed. Charcoal burning suicide attempters had higher levels of suicide intent (mean score 20.1) compared to people ingesting poisons (mean score 13.5) (p<0.001) and were considerably more likely to report that their choice of method was influenced by the media (87% vs. 8%), particularly the portrayal of the method as a peaceful way of dying. Charcoal burning suicides were less impulsive. Limitations: The study sample was limited to a single hospital. Conclusions: Survivors of suicide attempts by charcoal burning have high levels of intent and low levels of psychiatric contact indicating they may be more difficult to prevent than suicides by self-poisoning. Encouraging responsible media reporting of suicide and restricting the availability of charcoal may be the most promising approaches to preventing these deaths. [Copyright &y& Elsevier]

Purpose : We describe a novel vector system of nonviral gene transfer into the cornea using a dehydrated form of a plasmid expressing basic fibroblast growth factor–polyethylenimine (p-bFGF-PEI) complex to induce angiogenesis. Methods : Corneal neovascularization was evaluated in 48 eyes of Sprague-Dawley rats after implantation of a dehydrated form of PEI containing 1 μ g green fluorescent protein (p-GFP-PEI; control group), or 10 μ g, 1 μ g, or 0.1 μ g of p-bFGF-PEI introduced by spin vacuum at ambient temperature. Neovascularization was observed and quantified from day 1 to day 45. Eighteen kDa bFGF protein expression was analyzed by Western blot and immunohistochemistry. Results : Limbal vessels began to sprout on day 3 in the p-bFGF-PEI groups. The dehydrated form of the p-bFGF-PEI complex induced dose-dependent corneal neovascularization, which reached a maximum on days 24–30 in the 10 μ g bFGF group, days 18–24 in the 1 μ g bFGF group, and days 15–21 in 0.1 μ g bFGF group, and then regressed progressively. No neovascularization was observed in the GFP group. Conclusions : The dehydrated form of the p-bFGF-PEI complex is a novel and precise method for controlling the dose, localizing the reagents, and avoiding loss of liquid form during transfection into corneal tissue. [ABSTRACT FROM AUTHOR]

Background: Sex differences in the development of alcohol dependence (AD) among patients with panic disorder (PD) remain unexplored. The study investigated sex as an effect modifier in the incidence of AD among patients with PD.Method: We included 9480 patients with PD from the Taiwan National Health Insurance Research Database. A total of 169 patients (89 men and 80 women) developed incident AD during the follow-up period. Standardized incidence ratios (SIRs) were used to represent the relative risks of incident AD compared with the general population. Based on a nested case-control study design, 10 controls were selected for each case. Medical utilization and psychiatric comorbidity before diagnosing AD were analyzed using conditional logistic regression.Results: The SIR of incident AD was 3.36 for men and 6.29 for women. Women with PD and incident AD had more visits to the outpatient department than the controls did, whereas men exhibited no significant differences. Women with incident AD were more likely to comorbid with depressive disorder (adjusted risk ratio [aRR] = 2.94), personality disorder (aRR = 5.03), and sleep disorder (aRR = 1.72), whereas men with incident AD were more likely to comorbid with sleep disorder (aRR = 1.85) and other substance use disorders (aRR = 3.08).Conclusion: Patients with PD have an additional risk of developing AD compared with the general population, and that risk is higher in women. Women and men exhibited dissimilar patterns of medical utilization and psychiatric comorbidity before developing AD. Sex differences should be taken into consideration when establishing preventive measures. [ABSTRACT FROM AUTHOR]

Objective: Ascertaining comorbid illnesses and patterns of medical utilization early in the course of psychiatric illness can help identify patients with panic disorder. We investigated how such cases were diagnosed and the comorbidities associated with newly diagnosed panic disorder in a nationwide database.Methods: We enrolled a large representative cohort of the general population in Taiwan (N = 1000,000) and selected 9759 cases of panic disorder from January 1, 2000 to December 31, 2013. The distribution of the departments in which the cases were identified and the medical utilization 12 months before diagnosis were analyzed. Based on a nested case-control study, four controls were randomly selected for each case and matched for sex, age, and incidence year. Conditional logistic regression was used to explore the factors associated with newly-diagnosed panic disorder such as demographic factors, concomitant medications, and physical and psychiatric comorbidities.Results: Most (58.5%) cases of panic disorder were diagnosed in the psychiatry department, whereas only 3.7% were identified in the emergency department. Before diagnosis, the patients frequently visited the departments of internal medicine, family practice, and Chinese herbal medicine. A multivariate analysis revealed a higher number of physical and psychiatric comorbidities before diagnosis in the cases compared with the controls, especially depressive disorder and other anxiety disorders.Conclusions: Individuals with certain comorbidities and patterns of medical utilization are more likely to be diagnosed with panic disorder. We suggest providing more training to general practitioners and emergency physicians for the early diagnosis of panic disorder. [ABSTRACT FROM AUTHOR]