Association between depression risk and polycystic ovarian syndrome in young women: a retrospective nationwide population-based cohort study (1998-2013).

STUDY QUESTION: Is polycystic ovarian syndrome (PCOS) in women associated with the increasing incidence of depression in an East Asian population? SUMMARY ANSWER: Younger PCOS patients (aged 15-29 years), but not middle-aged patients, have an increased risk of depression in Taiwan. WHAT IS KNOWN ALREADY: During reproductive age, 6-10% of women have PCOS. Among them, ~40% experience depression, mostly at young ages. STUDY DESIGN, SIZE, DURATION: This is a retrospective population-based cohort study analysing depression risk in Taiwanese women using data from a nationwide database containing 1998-2013 data of nearly 1 million people. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 15- to 50-year-old women newly diagnosed with PCOS during 1998-2013 from the Taiwan National Health Insurance Research Database as the PCOS cohort (n = 7684) and then randomly matched them 4 : 1 by sex, age and index year with women without PCOS as the comparison cohort (n = 30 736). We used multivariable Cox proportional hazard regression analysis to determine the association between PCOS and depression risk [hazard ratio (HR) with 95% confidence interval (CI)]. MAIN RESULTS AND THE ROLE OF CHANCE: The incidence of depression was higher in the PCOS group than in the comparison group (6.67 vs. 4.82 per 1000 person-years; adjusted HR = 1.28, 95% CI = 1.12-1.46). PCOS patients aged 15-29 years had a significantly higher depression risk (adjusted HR = 1.39, 95% CI = 1.18-1.65); no such significant association was noted among patients aged 30-39 years and 40-50 years. LIMITATIONS, REASONS FOR CAUTION: A history of malignancy, which may increase depression, could not be obtained for our study patients. Moreover, we could not obtain a family history of depression, a relevant risk factor for depression. Finally, the database has no records of body mass index, which may influence depression outcome. WIDER IMPLICATIONS OF THE FINDINGS: In Taiwan, younger PCOS patients (15-29 years), but not the middle-aged patients, have an increased risk of depression. Our findings provide vital information to patients, clinicians, the Taiwan Government and other developing Asian countries to improve the PCOS treatment strategies in the future. Routine screening for depression in PCOS patients may be implemented into the health practice. STUDY FUNDING/COMPETING INTEREST(S): This study was supported in part by the Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW108-TDU-B-212-133 004), China Medical University Hospital, Academia Sinica Stroke Biosignature Project (BM10701010021), MOST Clinical Trial Consortium for Stroke (MOST 107-2321-B-039 -004-), Tseng-Lien Lin Foundation, Taichung, Taiwan and Katsuzo and Kiyo Aoshima Memorial Funds, Japan. No competing interest existed. TRIAL REGISTRATION NUMBER: N/A.

Prevalence of suicide attempts and their risk factors in school-aged patients with epilepsy: a population-based study.

Suicide prevention is a critical issue for young people. However, no large body of representative data on the risk of suicide attempts in school-aged patients with epilepsy in Taiwan or other developing countries is available. Patients aged ≤ 18 years who received a diagnosis of epilepsy between 2000 and 2012 were included in the epilepsy cohort (N = 9801). The comparison cohort was matched to the epilepsy cohort at a ratio of 4:1. We calculated the adjusted hazard ratio and 95% confidence intervals (CIs) for suicide attempts after adjustment for age, sex, urbanization level, parental occupation category, comorbidities, and follow-up time. Further analysis was performed to assess the dose-response effect on the risk of attempting suicide based on the average frequency of medical visits for epilepsy. The overall incidence rates of suicide attempts in the epilepsy and comparison cohorts were 15.7 and 5.89 per 100,000 people per year, respectively. The epilepsy cohort had a 2.34-fold higher risk of suicide being attempted (95% CI 2.17-2.52) than did the comparison cohort. Male sex, over 12 years of age, and parental occupation of office work were found to be the major risk factors for suicide attempts. Epilepsy might be an independent factor predisposing school-aged patients to suicide attempts. The results of this study could provide clinicians and governments with vital information on suicide prevention for young people with epilepsy in Taiwan and other developing countries.

Phenethyl Isothiocyanate Inhibits In Vivo Growth of Xenograft Tumors of Human Glioblastoma Cells.

Phenethyl isothiocyanate (PEITC) from cruciferous vegetables can inhibit the growth of various human cancer cells. In previous studies, we determined that PEITC inhibited the in vitro growth of human glioblastoma GBM 8401 cells by inducing apoptosis, inhibiting migration and invasion, and altering gene expression. Nevertheless, there are no further in vivo reports disclosing whether PEITC can suppress the growth of glioblastoma. Therefore, in this study we investigate the anti-tumor effects of PEITC in a xenograft model of glioblastoma in nude mice. Thirty nude mice were inoculated subcutaneously with GBM 8401 cells. Mice with one palpable tumor were divided randomly into three groups: control, PEITC-10, and PEITC-20 groups treated with 0.1% dimethyl sulfoxide (DMSO), and 10 and 20 µmole PEITC/100 µL PBS daily by oral gavage, respectively. PEITC significantly decreased tumor weights and volumes of GBM 8401 cells in mice, but did not affect the total body weights of mice. PEITC diminished the levels of anti-apoptotic proteins MCL-1 (myeloid cell leukemia 1) and XIAP (X-linked inhibitor of apoptosis protein) in GBM 8401 cells. PEITC enhanced the levels of caspase-3 and Bax in GBM 8401 cells. The growth of glioblastoma can be suppressed by the biological properties of PEITC in vivo. These effects might support further investigations into the potential use of PEITC as an anticancer drug for glioblastoma.

Survival outcome and mortality rate in patients with migraine: a population-based cohort study.

BACKGROUND: Whether the patients with migraine have an elevated mortality risk in Taiwan is unclear. METHODS: We analyzed a subset of the National Health Insurance Research Database of Taiwan and enrolled patients (≥20 years old) who received a diagnosis of migraine between 2000 and 2012. The migraine cohort was further divided into the ones ever with status migrainosus (SM) and non-status migraine (NM) subcohort and compared with a 1:4 age-, sex-, comorbidity-, and index date-matched comparison cohort. We calculated the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for subsequent mortality risk after adjustment for age, sex, and comorbidities. RESULTS: Compared with the comparison cohort, the corresponding aHRs for mortality were 0.81 (95% CI = 0.76-0.87), 0.89 (95% CI = 0.80-0.98), and 0.78 (95% CI = 0.72-0.84) in the total migraine, SM, and NM cohorts, respectively. SM, male sex, comorbid alcohol-related illness, depression, and mental disorders were identified as risk factors for subsequent mortality. Comorbid alcohol-related illness significantly increased the mortality risk in patients with migraine. CONCLUSION: Taiwanese patients with migraine require comprehensive and universal medical care. These patients would benefit from controlling their migraines and reducing the subsequent mortality.

Male, old age and low income to predispose epilepsy in migraineurs.

BACKGROUND: This study investigated whether sex, age, income and any comorbidity affect subsequent epilepsy development in migraineurs. MATERIALS AND METHODS: A total of 4915 men diagnosed with migraine who were aged older than 20 years were identified as the study cohort. A total of 4882 female migraineurs were included in the comparison cohort. We calculated the adjusted hazard ratio (aHR) for the risk of epilepsy in the two cohorts after adjustment for age and comorbidity. Kaplan-Meier analysis was used to analyse the cumulative epilepsy incidence, and the log-rank test was used to estimate the differences between the two cumulative incidence curves. RESULTS: The risk of epilepsy was 2·31-fold higher in male migraineurs than in female migraineurs. The income-specific analysis showed that the risk of epilepsy was high in migraineurs with a low monthly income [aHR: 2·73 for 15 000-25 000 new Taiwan dollar (NTD; approximately 500-833 USD) and aHR: 2·71 for < 15 000 NTD]. Among patients with one or more comorbidity, a 2·48-fold (95% confidence interval: 1·65-3·74) high risk of epilepsy was noted in male migraineurs, regardless of the presence of head injury. Additional analyses revealed that male migraineurs aged 65 years or older had the highest risk of epilepsy. CONCLUSION: Migraineurs have an increased risk of subsequent epilepsy. Male sex, old age and low income may interact with migraine and result in a high risk of epilepsy in migraineurs.

Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells.

Glioblastoma is the most common and aggressive primary brain malignancy. Phenethyl isothiocyanate (PEITC), a member of the isothiocyanate family, can induce apoptosis in many human cancer cells. Our previous study disclosed that PEITC induces apoptosis through the extrinsic pathway, dysfunction of mitochondria, reactive oxygen species (ROS)-induced endoplasmic reticulum (ER) stress, and intrinsic (mitochondrial) pathway in human brain glioblastoma multiforme (GBM) 8401 cells. To the best of our knowledge, we first investigated the effects of PEITC on the genetic levels of GBM 8401 cells in vitro. PEITC may induce G0/G1 cell-cycle arrest through affecting the proteins such as cdk2, cyclin E, and p21 in GBM 8401 cells. Many genes associated with cell-cycle regulation of GBM 8401 cells were changed after PEITC treatment: 48 genes were upregulated and 118 were downregulated. The cell-division cycle protein 20 (CDC20), Budding uninhibited by benzimidazole 1 homolog beta (BUB1B), and cyclin B1 were downregulated, and clusterin was upregulated in GBM 8401 cells treated with PEITC. These changes of gene expression can provide the effects of PEITC on the genetic levels and potential biomarkers for glioblastoma. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 176-187, 2017.

Men with nonapnea sleep disorders have a high risk of developing subsequent epilepsy: A nationwide population-based cohort study.

OBJECTIVE: This nationwide population-based cohort study evaluated the effects of nonapnea sleep disorders (NSDs) on the development of epilepsy. METHODS: We identified 63,865 patients aged ≥20years, diagnosed with NSDs (ICD-9-CM: 307.4 or 780.5), and without coding for apnea-related sleep disorders (ICD-9-CM: 780.51, 780.53, or 780.57) during 2000-2003 as the NSD cohort. In addition, we enrolled a comparison cohort of 127,728 patients. We calculated the adjusted hazard ratio (aHR) for developing epilepsy (ICD-9-CM: 345) after adjustment for age, sex, comorbidities, and drug use. A Kaplan-Meier analysis was used to measure the cumulative incidence of epilepsy between the 2 groups until the end of 2011. RESULTS: The cumulative incidence of epilepsy was significantly higher in the NSD cohort than in the comparison cohort. The aHR for developing epilepsy in the NSD cohort was 1.52 (95% CI=1.37-1.69). The risk of developing epilepsy was higher among males (aHR=1.41) than among females. The age-stratified effects of NSDs on developing epilepsy were the highest among patients aged ≥65years. When comorbidities and NSDs coexisted, the risk of epilepsy was specifically increased in patients having an NSD and stroke (aHR: 8.61, 95% CI: 7.43-9.98) in addition to brain tumors (aHR: 7.66, 95% CI: 5.06-11.6). CONCLUSION: This study indicated that patients with NSDs have a higher risk of developing epilepsy and that the risk is much higher among men and older patients. These findings suggest that NSDs constitute a predisposing, possibly independent factor for developing subsequent epilepsy in adulthood.

Higher-dose uses of zolpidem will increase the subsequent risk of developing benign brain tumors.

This study identified 37,810 patients with anxiety or sleep disorder (mean age=53.2 years, SD=16.0 years) who had zolpidem prescribed for at least 2 months from January 1, 2000 through December 31, 2009. Another non-zolpidem cohort was selected by 1:1 matching with the zolpidem cohort on the estimated probability (propensity score) of being treated. The zolpidem cohort had a higher incidence of benign brain tumors compared with the non-zolpidem cohort, particularly for elderly patients. The matched propensity score analysis showed that the highest risk of benign brain tumors occurred in participants with zolpidem exposure ≥520 mg/year (hazard ratio=1.85, 95% confidence interval=1.21-2.82) compared with those not taking zolpidem.

Evaluation of subcortical grey matter abnormalities in patients with MRI-negative cortical epilepsy determined through structural and tensor magnetic resonance imaging.

BACKGROUND: Although many studies have found abnormalities in subcortical grey matter (GM) in patients with temporal lobe epilepsy or generalised epilepsies, few studies have examined subcortical GM in focal neocortical seizures. Using structural and tensor magnetic resonance imaging (MRI), we evaluated subcortical GM from patients with extratemporal lobe epilepsy without visible lesion on MRI. Our aims were to determine whether there are structural abnormalities in these patients and to correlate the extent of any observed structural changes with clinical characteristics of disease in these patients. METHODS: Twenty-four people with epilepsy and 29 age-matched normal subjects were imaged with high-resolution structural and diffusion tensor MR scans. The patients were characterised clinically by normal brain MRI scans and seizures that originated in the neocortex and evolved to secondarily generalised convulsions. We first used whole brain voxel-based morphometry (VBM) to detect density changes in subcortical GM. Volumetric data, values of mean diffusivity (MD) and fractional anisotropy (FA) for seven subcortical GM structures (hippocampus, caudate nucleus, putamen, globus pallidus, nucleus accumbens, thalamus and amygdala) were obtained using a model-based segmentation and registration tool. Differences in the volumes and diffusion parameters between patients and controls and correlations with the early onset and progression of epilepsy were estimated. RESULTS: Reduced volumes and altered diffusion parameters of subcortical GM were universally observed in patients in the subcortical regions studied. In the patient-control group comparison of VBM, the right putamen, bilateral nucleus accumbens and right caudate nucleus of epileptic patients exhibited a significantly decreased density Segregated volumetry and diffusion assessment of subcortical GM showed apparent atrophy of the left caudate nucleus, left amygdala and right putamen; reduced FA values for the bilateral nucleus accumbens; and elevated MD values for the left thalamus, right hippocampus and right globus pallidus A decreased volume of the nucleus accumbens consistently related to an early onset of disease. The duration of disease contributed to the shrinkage of the left thalamus. CONCLUSIONS: Patients with neocortical seizures and secondary generalisation had smaller volumes and microstructural anomalies in subcortical GM regions. Subcortical GM atrophy is relevant to the early onset and progression of epilepsy.

Investigation of Subcortical Gray Matter in Patients with Non-lesional Neocortical Focal Epilepsy.

PURPOSE: To investigate whether there is any change in the subcortical gray matter of patients with neocortical focal epilepsy without visible magnetic resonance imaging (MRI) abnormalities. METHODS: MRI morphometric parameter data from 24 patients and 29 neurologically normal controls were analyzed. All of the MRI scans were reported to have no any anomaly. Differences were evaluated by vertex-wise shape analysis. RESULTS: A shape analysis showed significant surface reductions at the anterior-ventral and the posteriordorsal aspects of the bilateral thalami, the global left caudate nucleus, part of the bilateral dorsal putamen and the left hippocampus. CONCLUSION: Patients with focal seizures and secondary generalization had smaller volumes and microstructural anomalies in subcortical gray matter regions.

Characteristics of neurogenic voiding dysfunction in cerebellar stroke: a cross-sectional, retrospective video urodynamic study.

Voiding dysfunctions are common neurological complications after a stroke, yet there are few urodynamic studies of patients with cerebellar stroke. We report the video urodynamic findings of 15 patients with cerebellar stroke, including eight patients with ischemic and seven with hemorrhagic stroke. Their mean age was 75 ± 13.4 years and the mean interval from stroke to video urodynamic study was 11.2 ± 17.9 months. At urodynamic study, four (50 %) patients with ischemic stroke had urinary incontinence as did two (28 %) patients with hemorrhagic stroke. Detrusor overactivity (DO) was found in eight (53 %) patients, dyssynergic urethral sphincter in six (40 %), and nonrelaxing urethral sphincter in seven (47 %). DO occurred in six (75 %) of patients with ischemic stroke and in two (28.6 %) of patients with hemorrhagic stroke (p = 0.072). While DO was not found in five of the 15 patients within 2 months after the stroke, it was more frequently detected in eight (80 %) of the 10 remaining patients 2 or more months after stroke (p = 0.007). Four (80 %) of the five stroke patients had nonrelaxing sphincter and urinary retention within 2 months after stroke. Two or more months after their strokes, coordinated sphincter function was noted in two (20 %) patients and dyssynergic sphincter was found in six (60 %); two (20 %) remained with nonrelaxing sphincter. Thus, lower urinary tract dysfunction caused by cerebellar stroke may change with time. Knowledge of video urodynamic findings should help us better manage voiding dysfunction in patients with cerebellar stroke.

Comparison of the Cost and Effect of Combined Conditioned Medium and Conventional Medium for Fallopian Tube Organoid Cultures.

Fallopian tube epithelial cells (FTEC) are thought to be the cell of origin of high-grade serous ovarian carcinoma. FTEC organoids can be used as research models for the disease. Nevertheless, culturing organoids requires a medium supplemented with several expensive growth factors. We proposed that a combined conditioned medium based on the composition of the fallopian tubes, including epithelial, stromal, and endothelial cells could enhance FTEC organoid formation. We derived two primary culture cell lines from the fimbria portion of the fallopian tubes. The organoids were split into conventional or combined medium groups based on what medium they were grown in and compared. The number and size of the organoids were evaluated. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were used to evaluate gene and protein expression (PAX8, FOXJ1, beta-catenin, and stemness genes). Enzyme-linked immunosorbent assay was used to measure Wnt3a and RSPO1 in both mediums. DKK1 and LiCl were added to the mediums to evaluate their influence on beta-catenin signaling. The growth factor in the combined medium was evaluated by the growth factor array. We found that the conventional medium was better for organoids regarding proliferation (number and size). In addition, WNT3A and RSPO1 concentrations were too low in the combined medium and needed to be added making the cost equivalent to the conventional medium. However, the organoid formation rate was 100% in both groups. Furthermore, the combined medium group had higher PAX8 and stemness gene expression (OLFM4, SSEA4, LGR5, B3GALT5) when compared with the conventional medium group. Wnt signaling was evident in the organoids grown in the conventional medium but not in the combined medium. PLGF, IGFBP6, VEGF, bFGF, and SCFR were found to be enriched in the combined medium. In conclusion, the combined medium could successfully culture organoids and enhance PAX8 and stemness gene expression. However, the conventional medium was a better medium for organoid proliferation. The expense of both mediums was comparable. The benefit of using a combined medium requires further exploration.

Endometrial Cancer-Infiltrating Mesenchymal Stem Cells Exhibit Immunosuppressive Effects.

Endometrial cancer is the most common gynecologic cancer with high heterogeneity. However, there are limited treatment options for advanced endometrial carcinoma. In recent years, immunotherapy has broadly been used for the treatment of various cancers. However, the efficacy of immunotherapy against endometrial cancer is limited. The tumor microenvironment, including mesenchymal stem cells (MSCs), may contribute to tumor progression through cancer cells themselves and through cells of the immune system. We successfully isolated endometrial cancer-derived MSCs (EmCaMSCs) from patients and found that the population of MSCs in tumor tissues was approximately 1%-5%. The population of MSCs correlated with the stage of the disease. EmCaMSCs expressed MSC markers and exhibited trilineage differentiation ability. The programmed death ligands PD-L1 and PD-L2 were highly expressed in EmCaMSCs; their expression could be further enhanced by tumor necrosis factor-α and interferon-γ. When cocultured with peripheral blood mononuclear cells (PBMCs), anti-CD3, and anti-CD28, EmCaMSCs inhibited the proliferation of PBMCs, which were partially rescued by treatment with anti-PD-L1 antibodies. From the profile of conditioned medium of EmCaMSCs, we discovered that interleukin (IL)-8 and insulin-like growth factor-binding protein 6 could also rescue the proliferation of PBMCs. Furthermore, EmCaMSCs cocultured with IL-2-induced PBMCs exhibited decreased expression of CD56, CD4, and CD8 and showed decreased cytotoxicity toward K562 cells and endometrial cancer cells. Overall, EmCaMSCs were isolated successfully from endometrial cancer tissues and exhibited immunosuppressive effects and may be targeted for the treatment of endometrial cancer by anti-cytokine and immune checkpoint inhibitors. The percentage of MSCs in tumor stroma might predict the prognosis of endometrial cancer.

The organoid: A research model for ovarian cancer.

Epithelial ovarian cancer (EOC) is a heterogeneous disease with a variety of distinct clinical and molecular characteristics. The currently available and common research models for EOC include tumor cell lines and patient-derived xenografts. However, these models have certain shortcomings: establishing a cell line is time-consuming, loss of genetic traits after long-term culture is a possibility, and investment is required in terms of animal care facilities. Therefore, better research models are required. Organoid technology was originally developed from colorectal cancer. Tumor organoid is a three-dimensional culture system and can help accurately recapture the tumor phenotype from the original tumor. Tumor organoid systems can overcome the above-mentioned shortcomings of the currently available research models. The organoid model can be used for culturing ovarian cancer subtypes, screening drugs, assessing genomes, and establishing biobanks. However, the currently available organoid models can only culture one type of cells, epithelial cells. Therefore, an organoid-on-a-chip device can be developed in the future to provide a microenvironment for cell-cell, cell-matrix, and cell-media interactions. Thus, organoid models can be used in ovarian cancer research and can generate a simulated in vivo system, enabling studies on the heterogeneity of ovarian cancer.

Shikonin impedes type 2 ovarian cancer progression via FasL/caspase-8 and mir-874-3p/XIAP axis and prohibits the properties of stemness.

Ovarian cancer is the most lethal gynecological cancer in women. Shikonin (SHK), derived from Lithospermum eryothrorhizon, can reduce cancer activity; however, its clinical effect on type 2 ovarian cancer cells remains undetermined. Here, we studied the effects of SHK on type 2 ovarian cancer using the KURAMOCHI, OVSAHO, CP70, and ascites E04 cell lines. The proliferation curve and half-maximal inhibitory concentration of SHK for the cell lines were evaluated using the second-generation tetrazolium dye assay and the cell viability were determined by the annexin V/PI as well as TUNEL assay. The caspase dependent pathway was performed by western blotting assay with pan-caspase inhibitor Z-VAD-FMK and SHK induced miR-874-3p expression thus suppressed anti-apoptosis markers XIAP and Bcl-xL. The effect of SHK on type 2 ovarian cancer cell migration and invasion was evaluated using the wound healing and transwell assays. Quantitative RT-PCR and western blot was used to evaluate cancer stem cell (CSC)-related gene/protein (OCT4, SOX2, NANOG, ALDH1, and C-MYC) expressions, sphere formation assay was executed and a xenograft animal model for in vivo antitumor effects of SHK. Taken together, Shikonin suppressed type 2 ovarian cancer cell viability, migration, and invasion abilities; decreased CSC-related markers expression as well as the sphere colony numbers. It also reduced the tumorigenicity of KURAMOCHI ALDH+ cells and induced anti-tumor effect in a xenograft model. Thus, SHK could contribute a potential therapeutic strategy on type 2 ovarian cancer cells via multiple functions.

Association of heart rate variability with clinical outcome in parkinsonian patients after subthalamic deep brain stimulation: a retrospective cohort study.

BACKGROUND/PURPOSE: Lower sympathetic and parasympathetic function increases the morbidity in Parkinsonian patients. We conducted this retrospective study to elucidate the effect of subthalamic deep brain stimulation (STN-DBS) on autonomic cardiovascular regulation of patients with Parkinson's disease. METHODS: Twelve men and four women with advanced Parkinson's disease (mean age: 63 years) who underwent bilateral STN-DBS were followed up for 9-32 months. Daytime electrocardiography for 5 minutes and rating scores were recorded before and after surgery. Good response was defined as improvement >50% in the Unified Parkinson's Disease Rating Scale (UPDRS), and a fair response as improvement between 10% and 50% after surgery. Digitalized electrocardiography signals such as high-frequency power [HF; 0.15-0.45 Hz, to reflect vagal (parasympathetic) regulation], low-frequency power (LF; 0.04-0.15 Hz, contributed from mixed sympathetic and parasympathetic divisions), and the fraction of LF/(HF + LF) in normalized units (LF%, to reflect sympathetic regulation) were transformed with fast Fourier transformation to power spectrum and heart rate variables. RESULTS: Six male and two female patients were good responders and the others were fair responders. There were no significant differences in height, weight, duration of disease, levadopa equivalent daily dose, preoperative and postoperative UPDRS, and DBS-off and levodopa-off UPDRS between the good and fair response groups. There were no significant differences between the good and fair response groups for preoperative heart rate interval, LF values, LF% values, and HF values. Compared with preoperative values, the good response group showed a significant increase in LF but not in heart rate, LF%, and HF after surgery. In contrast, the fair response group showed no significant change in all heart rate variables postoperatively. CONCLUSION: Our study showed an improvement in autonomic cardiovascular regulation in Parkinsonian patients with >50% improvement in rating scale after STN-DBS, which implied morbidity reduction in nonmotor symptoms among such patients.

The Combination of Clindamycin and Gentamicin Is Adequate for Pelvic Inflammatory Disease: A Retrospective Cohort Study.

Pelvic inflammatory disease (PID) affects 4.4% of women aged 18-44 in the United States, and may cause infertility if it is ineffectively treated. A combination of clindamycin and gentamicin is generally used for the treatment of PID. The benefit of adding metronidazole into the treatment combination still remains unclear, and this study was designed to evaluate its effectiveness. We retrospectively included 107 women who were diagnosed with PID from May 2013 to September 2020 in a single hospital. Based on their used antibiotic regimens, the patients were divided into three groups-those who were treated with clindamycin + gentamicin (group 1, n = 46), those who took regular antibiotics plus metronidazole (group 2, n = 27), and others (group 3, n = 34). Primary outcomes included the rates of taking surgery after failed antibiotics, occurrence/rupture of tubo-ovarian abscesses, and readmission within the following 6 months of first treatment. Secondary outcomes to assess were the length of stay (LOS) and expenditure for PID. There were no significant differences in the surgical rates, readmission rates, LOS and expenditure noted between the three groups. Subgroup analysis showed that visual analogue pain scores being 5 or more would increase the LOS by 3.83 days (p < 0.001), and body temperature > 38.3 °C or more would increase the treatment total expenditure (p < 0.001). Our study results suggest that the combination of clindamycin + gentamicin is a convincible treatment protocol for PID.

Use of bladder antimuscarinics is associated with an increased risk of dementia: a retrospective population-based case-control study.

The association between bladder antimuscarinic use and dementia development is unclear. We used data from the Taiwan National Health Insurance Research Database to determine the association between the exposure dose and duration of bladder antimuscarinics and the subsequent dementia risk. We enrolled participants aged 55 years or more and defined a dementia cohort (International Classification of Diseases, Ninth Revision, Clinical Modification codes 290, 294.1, and 331.0). We used a propensity score matching method, and randomly enrolled two controls without dementia. We evaluated dementia risk with respect to the exposure dose and duration of treatment with seven bladder antimuscarinics (oxybutynin, propiverine, tolterodine, solifenacin, trospium, darifenacin, and fesoterodine) used for at least 1 year before the index date, after adjusting for age, sex, comorbidities, and medications. The dementia risk was 2.46-fold (95% confidence interval: 2.22-2.73) higher in Taiwanese patients who used bladder antimuscarinics for ≥ 1 year than in those who were not exposed to this treatment. The risk proportionally increased with increasing doses of antimuscarinics for less than 4 years. Taiwanese patients aged 55 years or more on bladder antimuscarinics exhibited a higher risk of dementia. Additional studies in other countries are required to determine whether this result is valid worldwide.

Increasing Risks of Suicide Attempt and Suicidal Drug Overdose After Head Trauma in Patients With Sleep-Disordered Breathing: A Population-Based Study.

Objective: To determine the risks of suicide attempt (SA) and suicidal drug overdose (SDO) after head trauma in patients with sleep-disordered breathing (SDB) by using the National Health Insurance Research Database of Taiwan. Methods: We analyzed the data of patients aged ≥20 years who were diagnosed with SDB between 2000 and 2012. We further divided them into two cohorts [with admission for head injury (SBI) and without (SBN)], and we compared them against sex-, age-, comorbidity-, and index-date-matched healthy individuals. The adjusted hazard ratios (aHRs) and 95% confidence intervals of SA and SDO were calculated with adjustment of age, sex, and comorbidities. Results: Approximately 0.61% of patients among the overall 142,063 patients with SDB had SA, with 535 and 335 patients included in the SBN and SBI cohorts, respectively. Compared with patients with SBN, a significantly higher risk of SA was observed in patients with SBI (aHR = 2.22), especially in those aged under 50 years (aHR = 2.48). Notably, a SDO incidence of 1.20% was noted in patients with SDB, and the SBI cohort had a 1.81-fold higher risk for SDO when compared with the SBN cohort. Conclusion: The risks of subsequent SA and SDO are proportionally increased by the effects of head trauma with a moderating role of SDB, especially in those aged <50 years. SDB and head trauma can increase suicide behaviors individually and synergistically.

Suicide Attempt and Suicidal Drug Overdose in Chronic Obstructive Pulmonary Disease Patients With or Without Depression.

BACKGROUND: To determine differences in the incidence and risks of suicide attempt (SA) and suicidal drug overdose (SDO) between chronic obstructive pulmonary disease (COPD) patients with and without comorbid depression by using data from Taiwan's National Health Insurance Research Database. METHODS: We analyzed the data of patients aged ≥20 years who had received a COPD diagnosis between 2000 and 2012. These COPD patients were divided into those with and without depression, and they were compared against a cohort from the general population. We calculated adjusted hazard ratios and the corresponding 95% confidence intervals for SA and SDO in the three cohorts after adjustment for age, sex, and comorbidities. RESULTS: Until the end of 2012, 5.81% of patients with COPD developed depression. The incidence of SA and SDO in COPD patients with and without depression was 29.7 and 4.69 per 10,000 person-years and 71.2 and 20.9 per 10,000 person-years, respectively. COPD patients with depression had 13.6- and 10.0-fold higher risks of SA and SDO, respectively, than did controls. Particularly, an increased risk of SA caused by the enhancement effects of depression on COPD was noted in patients aged less than 50 years. CONCLUSION: SA and SDO risks are extremely high in Taiwanese COPD patients with depression. Our findings suggest that clinicians should be aware that for COPD patients with comorbid depression, prescribing a large amount of medications may be associated with SA risk through SDO.