Early psychiatric referral after attempted suicide helps prevent suicide reattempts: A longitudinal national cohort study in South Korea.

Introduction: Although people who attempted suicide tend to repeat suicide attempts, there is a lack of evidence on the association between psychiatric service factors and suicide reattempt among them. Methods: We used a nationwide, population-based medical record database of South Korea to investigate the use of psychiatric services before and after the index suicide attempt and the association between psychiatric service factors after the index suicide attempt with the risk of suicide reattempt. Results: Among 5,874 people who had attempted suicide, the all-cause mortality within 3 months after the suicide attempt was 11.6%. Among all subjects who attempted suicide, 30.6% of them had used psychiatric services within 6 months before the suicide attempt; 43.7% of them had used psychiatric services within 3 months after the suicide attempt. Among individuals who had visited clinics following attempted suicide, the cumulative incidence of suicide reattempt over a mean follow-up period of 5.1 years was 3.4%. About half of suicide reattempts occurred within 1 year after the index suicide attempt. Referral to psychiatric services within 7 days was associated with a decreased risk of suicide reattempt (adjusted hazard ratio, 0.51; 95% confidence intervals, 0.29-0.89). Conclusion: An early psychiatric referral within 1 week after a suicide attempt was associated with a decreased risk of suicide reattempt.

Treatment Patterns and Clinical Outcomes in Korean Cancer Patients With Venous Thromboembolism: A Retrospective Cohort Study.

This study assessed epidemiologic data and clinical outcomes, including venous thromboembolism (VTE) recurrence and bleeding events, in patients with cancer-associated VTE, and assessed factors associated with clinical outcomes. Data were extracted from retrospective medical-chart review of adult patients diagnosed with cancer-associated deep vein thrombosis or pulmonary embolism who received anticoagulation treatment for ≥3 months. Patients were classified by: low-molecular-weight heparin (LMWH), direct oral anticoagulants (DOACs), and other anticoagulants. First VTE recurrence and bleeding events, and factors associated with their occurrence, were assessed during the initial 6 months of treatment. Overall, 623 patients (age: 63.7 ± 11.3 years, 49.3% male) were included (119, 132, and 372 patients in LMWH, DOACs and other anticoagulants groups, respectively). The cumulative 6-month incidence of VTE recurrence was 16.6% (total), 8.3% (LMWH), 16.7% (DOACs), and 20.7% (other); respective bleeding events were 22.5%, 11.0%, 12.3%, and 30.7%). VTE recurrence and bleeding rates differed only between LMWH and other anticoagulants (HR 2.4, 95% CI: 1.2-5.0 and 3.6, 1.9-6.8, respectively). These results highlight the importance of initial VTE treatment choice for preventing VTE recurrence and bleeding events. LMWH or DOACs for ≥3 months can be considered for effective VTE management in cancer patients.

Validation of the Korean Version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale.

BACKGROUND AND PURPOSE: Impulse-control disorder is an important nonmotor symptom of Parkinson's disease (PD) that can lead to financial and social problems, and be related to a poor quality of life. A nationwide multicenter prospective study was performed with the aim of validating the Korean Version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (K-QUIP-RS). METHODS: The K-QUIP-RS was constructed using forward and backward translation, and pretesting of the prefinal version. PD patients on stable medical condition were recruited from 27 movement-disorder clinics. Participants were assessed using the K-QUIP-RS and evaluated for parkinsonian motor and nonmotor statuses and for PD-related quality of life using a predefined evaluation battery. The test-retest reliability of the K-QUIP-RS was assessed over an interval of 10-14 days, and correlations between the KQUIP-RS and other clinical scales were analyzed. RESULTS: This study enrolled 136 patients. The internal consistency of the K-QUIP-RS was indicated by a Cronbach's α coefficient of 0.846, as was the test-retest reliability by a Guttman split-half coefficient of 0.808. The total K-QUIP-RS score was positively correlated with the scores for depression and motivation items on the Unified PD Rating Scale (UPDRS), Montgomery-Asberg Depression Scale, and Rapid-Eye-Movement Sleep-Behavior-Disorders Questionnaire. The total K-QUIP-RS score was also correlated with the scores on part II of the UPDRS and the PD Quality of Life-39 questionnaire, and the dopaminergic medication dose. CONCLUSIONS: The K-QUIP-RS appears to be a reliable assessment tool for impulse-control and related behavioral disturbances in the Korean PD population.

Subtypes of Sleep Disturbance in Parkinson's Disease Based on the Cross-Culturally Validated Korean Version of Parkinson's Disease Sleep Scale-2.

BACKGROUND AND PURPOSE: This study aimed to determine the clinimetric properties of the Korean version of Parkinson's Disease Sleep Scale-2 (K-PDSS-2) and whether distinct subtypes of sleep disturbance can be empirically identified in patients with Parkinson's disease (PD) using the cross-culturally validated K-PDSS-2. METHODS: The internal consistency, test-retest reliability, scale precision, and convergent validity of K-PDSS-2 were assessed in a nationwide, multicenter study of 122 patients with PD. Latent class analysis (LCA) was used to derive subgroups of patients who experienced similar patterns of sleep-related problems and nocturnal disabilities. RESULTS: The total K-PDSS-2 score was 11.67±9.87 (mean±standard deviation) at baseline and 12.61±11.17 at the retest. Cronbach's α coefficients of the total K-PDSS-2 scores at baseline and follow-up were 0.851 and 0.880, respectively. The intraclass correlation coefficients over the 2-week study period ranged from 0.672 to 0.848. The total K-PDSS-2 score was strongly correlated with health-related quality of life measures and other corresponding nonmotor scales. LCA revealed three distinct subtypes of sleep disturbance in the study patients: "less-troubled sleepers," "PD-related nocturnal difficulties," and "disturbed sleepers." CONCLUSIONS: K-PDSS-2 showed good clinimetric attributes in accordance with previous studies that employed the original version of the PDSS-2, therefore confirming the cross-cultural usefulness of the scale. This study has further documented the first application of an LCA approach for identifying subtypes of sleep disturbance in patients with PD.

Safety of bazedoxifene in Korean women with post-menopausal osteoporosis: a post-marketing surveillance study (PMSS).

Objectives: Bazedoxifene was found to be effective and well tolerated for the treatment and prevention of osteoporosis in postmenopausal women. This post-marketing surveillance study (PMSS) examined the safety of bazedoxifene in postmenopausal Korean women with osteoporosis, in a real-world setting. Methods: This PMSS was conducted from 2013 to 2017. A total of 3,423 subjects from 68 centers were enrolled and monitored for about 3 months (± 2 weeks). Bazedoxifene was prescribed at a dose of 20 mg/day. The safety of bazedoxifene was evaluated based on the number and nature of adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs) and serious ADRs (SADRs) in routine medical practice. Results: The mean age of study subjects was 69.51 years. The incidence of AEs and ADRs was 6.11% and 3.86%, respectively, and significantly decreased with increasing age (p= 0.0007). AE and ADR rates with bazedoxifene treatment of 3 months or more were significantly lower than those of less than 3 months (AE, 3.64% vs 30.00%, p < 0.0001; ADR, 1.74% vs 24.38%, p < 0.0001). Conclusion: In this study, bazedoxifene was well tolerated in the management of postmenopausal osteoporosis in Korean women, including those aged 70 years or more.

Validation of the Korean Version of the Scales for Outcomes in Parkinson's Disease-Sleep.

BACKGROUND: Sleep problems commonly occur in patients with Parkinson's disease (PD), and are associated with a lower quality of life. The aim of the current study was to translate the English version of the Scales for Outcomes in Parkinson's Disease-Sleep (SCOPA-S) into the Korean version of SCOPA-S (K-SCOPA-S), and to evaluate its reliability and validity for use by Korean-speaking patients with PD. METHODS: In total, 136 patients with PD from 27 movement disorder centres of university-affiliated hospitals in Korea were enrolled in this study. They were assessed using SCOPA, Hoehn and Yahr Scale (HYS), Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Sleep Scale 2nd version (PDSS-2), Non-motor Symptoms Scale (NMSS), Montgomery Asberg Depression Scale (MADS), 39-item Parkinson's Disease Questionnaire (PDQ39), Neurogenic Orthostatic Hypotension Questionnaire (NOHQ), and Rapid Eye Movement Sleep Behaviour Disorder Questionnaire (RBDQ). The test-retest reliability was assessed over a time interval of 10-14 days. RESULTS: The internal consistency (Cronbach's α-coefficients) of K-SCOPA-S was 0.88 for nighttime sleep (NS) and 0.75 for daytime sleepiness (DS). Test-retest reliability was 0.88 and 0.85 for the NS and DS, respectively. There was a moderate correlation between the NS sub-score and PDSS-2 total score. The NS and DS sub-scores of K-SCOPA-S were correlated with motor scale such as HYS, and non-motor scales such as UPDRS I, UPDRS II, MADS, NMSS, PDQ39, and NOHQ while the DS sub-score was with RBDQ. CONCLUSION: The K-SCOPA-S exhibited good reliability and validity for the assessment of sleep problems in the Korean patients with PD.

Sleepiness and Depression in Parkinson's Disease Patients Treated with Ropinirole and Levodopa.

OBJECTIVE: We aimed to investigate the effect of ropinirole on excessive daytime sleepiness (EDS) and depression in Parkinson's disease (PD) with a large population. METHODS: We conducted a cross-sectional observational study at nine hospitals in Korea between April 24, 2013, and April 22, 2015. We analyzed the demographic and clinical features, other medical history, history of antiparkinsonian medication within 6 months, Hoehn and Yahr stage (HY stage), Unified Parkinson's Disease Rating Scale (UPDRS) part II and III, Epworth Sleepiness Scale (ESS), and 30-item Geriatric Depression Scale (GDS-30). RESULTS: Four-hundred-thirteen patients with PD (mean age: 65.2 ± 9.0 years; men: 227 patients) were analyzed. Multivariate logistic regression analysis showed that age at examination, UPDRS II, and GDS-30 were independent risk factors for EDS and that sex, UPDRS II, and ESS were independent risk factors for depression. CONCLUSION: Our large group study did not find any significant associations of ropinirole with EDS and depression in Korean PD patients.

Validation of the Korean Version of the Scale for Outcomes in Parkinson's Disease-Autonomic.

OBJECTIVE: Autonomic symptoms are commonly observed in patients with Parkinson's disease (PD) and often limit the activities of daily living. The Scale for Outcomes in Parkinson's disease-Autonomic (SCOPA-AUT) was developed to evaluate and quantify autonomic symptoms in PD. The goal of this study was to translate the original SCOPA-AUT, which was written in English, into Korean and to evaluate its reliability and validity for Korean PD patients. METHODS: For the translation, the following processes were performed: forward translation, backward translation, expert review, pretest of the pre-final version and development of the final Korean version of SCOPA-AUT (K-SCOPA-AUT). In total, 127 patients with PD from 31 movement disorder clinics of university-affiliated hospitals in Korea were enrolled in this study. All patients were assessed using the K-SCOPA-AUT and other motor, non-motor, and quality of life scores. Test-retest reliability for the K-SCOPA-AUT was assessed over a time interval of 10-14 days. RESULTS: The internal consistency and reliability of the K-SCOPA-AUT was 0.727 as measured by the mean Cronbach's α-coefficient. The test-retest correlation reliability was 0.859 by the Guttman split-half coefficient. The total K-SCOPA-AUT score showed a positive correlation with other non-motor symptoms [the Korean version of non-motor symptom scale (K-NMSS)], activities of daily living (Unified Parkinson's Disease Rating Scale part II) and quality of life [the Korean version of Parkinson's Disease Quality of Life 39 (K-PDQ39)]. CONCLUSION: The K-SCOPA-AUT had good reliability and validity for the assessment of autonomic dysfunction in Korean PD patients. Autonomic symptom severities were associated with many other motor and non-motor impairments and influenced quality of life.

α-Synuclein in the colon and premotor markers of Parkinson disease in neurologically normal subjects.

Extranigral non-motor signs precede the first motor manifestations of Parkinson's disease by many years in some patients. The presence of α-synuclein deposition within colon tissues in patients with Parkinson's disease can aid in identifying early neuropathological changes prior to disease onset. In the present study, we evaluated the roles of non-motor symptoms and signs and imaging biomarkers of nigral neuronal changes and α-synuclein accumulation in the colon. Twelve subjects undergoing colectomy for primary colon cancer were recruited for this study. Immunohistochemical staining for α-synuclein in normal and phosphorylated forms was performed in normally appearing colonic tissue. We evaluated 16 candidate premotor risk factors in this study cohort. Among them, ten subjects showed positive immunostaining with normal- and phosphorylated-α-synuclein. An accumulation of premotor markers in each subject was accompanied with positive normal- and phosphorylated-α-synuclein immunostaining, ranging from 2 to 7 markers per subject, whereas the absence of Lewy bodies in the colon was associated with relative low numbers of premotor signs. A principal component analysis and a cluster analysis of these premotor markers suggest that urinary symptoms were commonly clustered with deposition of peripheral phosphorylated-α-synuclein. Among other premotor marker, color vision abnormalities were related to non-smoking. This mathematical approach confirmed the clustering of premotor markers in preclinical stage of Parkinson's disease. This is the first report showing that α-synuclein in the colon and other premotor markers are related to each other in neurologically normal subjects.

Association between urine protein/creatinine ratio and cognitive dysfunction in Lewy body disorders.

BACKGROUND: Impaired renal function and proteinuria have been associated with cognitive impairment and dementia. Chronic kidney disease is considered to be an independent risk factor for Lewy body spectrum disorders (LBD). However, few studies have mentioned an association between proteinuria and cognition in LBD. We investigated the relationship between proteinuria and cognitive dysfunction in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). METHODS: Among 186 patients with LBD, 53 had PD-normal cognition (PD-NC), 76 had PD-mild cognitive impairment (PD-MCI), 43 had PD-dementia (PDD) and 14 had DLB. The urine protein/creatinine ratio was calculated using the spot urine test and brain magnetic resonance scans was obtained in all patients. RESULTS: The urine protein/creatinine ratio was significantly higher in patients with PDD and DLB than in those with PD-MCI, PD-NC patients and healthy controls, and was correlated with white matter hyperintensities on magnetic resonance imaging. All abnormal neuropsychological test results were associated with increased urine protein/creatinine ratio. After controlling for age, education, symptom duration, diabetes mellitus, hypertension, and parkinsonian motor severity, the urine protein/creatinine ratio was significantly associated with decreased cognition. CONCLUSION: The urine protein/creatinine ratio was associated with cognitive status in LBD. These finding suggests that increased protein excretion is associated with cognitive dysfunction in patients with LBD.

Orthostatic hypotension and cardiac sympathetic denervation in Parkinson disease patients with REM sleep behavioral disorder.

BACKGROUND: Rapid eye movement (REM) sleep behavioral disorder (RBD), orthostatic hypotension (OH), and cardiac sympathetic denervation were commonly observed in PD and are related in both the premotor and motor periods. This study is intended to evaluate if the OH and cardiac sympathetic denervation found in PD are associated with RBD. METHODS: Among 94 non-medicated and mild PD patients, 53 had RBD. Orthostatic vital signs and ambulatory 24-hour blood pressure values were recorded. (123)I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy as obtained in all patients. The association between orthostatic hypotension, supine hypertension, nocturnal hypertension, non-dipping, myocardial MIBG uptake, and RBD was analyzed. RESULTS: RBD was associated with orthostatic hypotension. Patients with RBD had higher systolic blood pressure changes during orthostasis and lower myocardial MIBG uptake than patients without RBD and controls. Patients with OH also had lower mean H/M ratios those in the non-OH group. CONCLUSION: This study showed that RBD was closely associated with OH and cardiac sympathetic denervation in patients with early and mild PD. The result also suggests that impaired cardiac sympathetic innervation could be the mechanism behind OH in PD. This association may be closely correlated with Braak alpha-synuclein pathogenetic sequences, which would account for the clinical spectrum of PD.

Cardiovascular autonomic dysfunctions in elderly patients with essential tremor: comparison with healthy controls.

Questionnaire-based analyses show that patients with essential tremor (ET) may have several autonomic dysfunctions, especially in the cardiovascular and genitourinary domains; yet the laboratory correlates of autonomic dysfunction in ET are unknown and have not been studied. Herein, we explored whether sympathetic and parasympathetic functions differed between control subjects and patients with ET. Seventy-five elderly patients with ET were enrolled in this study, along with 25 age-matched controls. Orthostatic vital signs, ambulatory 24-h blood pressure monitoring and 24-h Holter monitoring values were recorded and metaiodobenzylguanidine (MIBG) uptake was assessed using the heart-to-mediastinum ratio (H/M ratio). The frequencies of orthostatic hypotension, supine hypertension, nocturnal hypertension and non-dipping were not different between the ET patients and the controls, although ET patients had more episodes of orthostatic intolerance. The ET group also had similar heart rate variations as the control group for all the time-domains. The mean H/M ratios for the ET group were not statistically different from that of the control group. This result proves that the autonomic control of the cardiovascular system is normal in ET.

Autonomic Nervous System Dysfunction in Patients With Parkinson Disease Having Depression.

BACKGROUND AND AIM: Both depression and cardiovascular autonomic dysfunctions, such as orthostatic hypotension, supine hypertension, and the absence of normal nocturnal blood pressure (BP) fall ("nondipping"), occur relatively commonly in Parkinson disease (PD); however, the relationship between depression and cardiovascular autonomic abnormalities has not been established. In this study, we sought to determine whether the cardiovascular autonomic abnormalities found in PD are associated with depression. METHODS: Among 129 nondemented, levodopa-naive patients with mild PD, 44 had depression. Orthostatic vital signs and ambulatory 24-hour BP monitoring were recorded, and geriatric depressive scales were obtained in all patients. Associations between orthostatic hypotension, supine hypertension, nocturnal hypertension, nondipping, and depression were analyzed. The ratio of the standard deviation of 24-hour heart rate to that of systolic BP (SBP) was utilized as an index of baroreflex-cardiovagal function. RESULTS: Depression was associated with orthostatic hypotension, and patients with depression had higher SBP change during orthostasis and attenuated cardiovagal dysfunction as observed during ambulatory BP monitoring. Across individuals, values for orthostatic changes in BP were correlated with values for geriatric depressive scale. CONCLUSION: Depression is associated with neurocirculatory abnormalities-especially orthostatic hypotension-in early PD. Although the association does not imply causation, this result suggests that depression in PD might be associated with functional impairment of the autonomic nervous system and its pathologic substrate.

(123)I-MIBG myocardial scintigraphy and neurocirculatory abnormalities in patients with dementia with Lewy bodies and Alzheimer's disease.

BACKGROUND: Although adoption of new clinical criteria for dementia with Lewy bodies (DLB) leads to an increase in the proportion of patients diagnosed with probable DLB, the sensitivity of clinical diagnostic criteria of DLB is low, and there are no generally accepted clinical or imaging biomarkers to distinguish DLB from other types of dementia. In this study, we investigated whether neurocirculatory abnormalities and cardiac sympathetic denervation differed in controls and patients with subjective memory impairment (SMI), mild cognitive impairment (MCI), Alzheimer's disease (AD), and DLB. We also assessed whether spontaneous features of Parkinsonism might be related to the neurocirculatory abnormalities and cardiac sympathetic denervation found in DLB. METHODS: Twenty-two consecutive patients with probable DLB were enrolled in this study; 25 age-matched controls, 14 SMI, 24 MCI, and 37 AD patients were also evaluated. Metaiodobenzylguanidine (MIBG) uptake was assessed using the ratio of the heart to the upper mediastinum (H/M ratio), and orthostatic vital signs and ambulatory 24-hour blood pressure monitoring values were recorded. RESULTS: The mean H/M ratio was significantly lower and the proportion of orthostatic hypotension was higher in patients with DLB than in controls, SMI, MCI and AD patients. In patients with DLB, spontaneous Parkinsonism was not related to the degree of cardiac sympathetic denervation nor did it influence neurocirculatory abnormalities. CONCLUSION: Our results suggest that MIBG scintigraphy and autonomic function tests may be useful for distinguishing between DLB and AD in clinical practice. Myocardial postganglionic sympathetic denervation and autonomic dysfunctions are present in patients with DLB regardless of spontaneous Parkinsonism.

Subcortical whiter matter hyperintensities within the cholinergic pathways of patients with dementia and parkinsonism.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) in the cholinergic pathways are associated with cognitive performance in Alzheimer's disease (AD) and Parkinson disease dementia (PDD). This study aimed to evaluate the relationship between loss of white matter cholinergic pathways and cognitive function in patients with AD, diffuse Lewy body disease (DLB), and PDD. METHODS: The subjects included 20 patients with AD, 17 with DLB, 21 with PDD, and 20 healthy controls. The extent of WMHs within cholinergic pathways was assessed using the Cholinergic Pathways Hyperintensities Scale (CHIPS) and was compared among the different diseases. RESULTS: The mean CHIPS scores were similar among the three dementia groups (AD vs. DLB vs. PDD = 34.6 ± 17.9 vs. 32.4 ± 14.1 vs. 31.8 ± 14.5, p = 0.781 by ANCOVA) and higher than those of controls (11.5 ± 7.6, p = 0.001 by ANCOVA). CONCLUSIONS: Losses of cholinergic pathways were similar among AD, DLB, and PDD groups, and more severe cognitive dysfunction was associated with elevated WMHs. These findings suggest that interruption of acetylcholine pathways may be related to cognitive dysfunction in these three diseases, even though they have different pathological mechanisms.