Risk factors of involuntary referral by police to ER psychiatric services for patients with a severe mental illness: A GEE analysis.

This study aimed to identify risk factors for involuntary referral by police to emergency room (ER) psychiatric services for community-based patients with a mental illness via a generalized estimating equation (GEE) analysis. The analysis was based on data from the Management Information System of Psychiatric Care (MISPC) system for patients with a severe mental illness in Taipei, Taiwan and registered referral records of the police. Data on 6378 patients aged ≥20 years were used in this study, including 164 patients who were involuntarily referred to the ER by the police and 6214 patients who were not during the period of January 1, 2018 to December 31, 2020. GEEs were utilized to explore possible risk factors of repeated involuntary referral to ER psychiatric services for patients with a severe mental illness. The logistic regressions indicated that patients defined as "severe" according to the Mental Health Act of Taiwan (crude odds ratio (OR): 3.840, 95 % confidence interval (CI): 2.407-6.126), with a disability (crude OR: 3.567, 95 % CI: 1.339-9.501), with two or more family members with a psychiatric disorder (crude OR: 1.598, 95 % CI: 1.002-2.548), with a history of a suicide attempt (crude OR: 25.582, 95 % CI: 17.608-37.167), and with a history of domestic violence (crude OR: 16.141, 95 % CI: 11.539-22.579) were positively associated with involuntary referral to ER psychiatric services. However, age (crude OR: 0.971, 95 % CI: 0.960-0.983) and the MISPC score (crude OR: 0.834, 95 % CI: 0.800-0.869) were inversely associated with involuntary referral to ER psychiatric services. After adjusting for demographics and potential confounders, we found that patients defined as "severe" (Exp (ß): 3.236), with a disability (Exp (ß): 3.715), with a history of a suicide attempt (Exp (ß): 8.706), and with a history of domestic violence (Exp (ß): 8.826), as well as age (Exp (ß): 0.986) and the MISPC score (Exp (ß): 0.902) remained significantly associated with repeated involuntary referral to ER psychiatric services. In conclusion, community-based mentally ill patients with a history of a suicide attempt, with a history of domestic violence, with a severe illness, and with a profound level of disability were highly associated with involuntary referral to ER psychiatric services. We suggest that community mental health case managers identify significant factors associated with involuntary referral to ER psychiatric services to accordingly arrange case management plans.

Contralateral exploration and repair of occult inguinal hernias during laparoscopic inguinal hernia repair: systematic review and Markov decision process.

BACKGROUND: Contralateral clinically occult hernias are frequently noted at the time of laparoscopic unilateral inguinal hernia repair. There is no consensus on the role of contralateral exploration and repair. This systematic review assessed the safety and efficacy of operative repair of occult contralateral inguinal hernias found during unilateral repair. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to February 2020. Adults diagnosed with a unilateral inguinal hernia undergoing laparoscopic repair were included. The primary outcome was the incidence of occult contralateral hernias. Summative outcomes of operative and expectant management were reported along with development of a Markov decision process. RESULTS: Thirteen studies (1 randomized trial, 12 observational cohorts) with 5000 patients were included. The incidence of occult contralateral inguinal hernias was 14.6 (range 7.3-50.1) per cent. Among patients who underwent repair, 10.5 (4.3-17.0) per cent experienced a postoperative complication. Of patients managed expectantly, 29 per cent later required elective repair for symptoms. Mean follow-up was 36 (range 2-218) months. Using a Markov decision process, it was calculated that, for every 1000 patients undergoing unilateral inguinal hernia repair, contralateral exploration would identify 150 patients with an occult hernia. Repair would result in 15 patients developing a postoperative complication and 105 undergoing unnecessary repair. Alternatively, expectant management would result in 45 patients requiring subsequent repair. CONCLUSION: Contralateral repair is not warranted in patients with occult hernias diagnosed at the time of elective hernia repair. The evidence is largely based on observational studies at high risk of bias.

Importance of the physical exam: double-blind randomized controlled trial of radiologic interpretation of ventral hernias after selective clinical information.

PURPOSE: Increasingly, radiologic imaging is obtained as part of the pathway in diagnosing ventral hernias. Often, radiologists receive incomplete or incorrect clinical information from clinicians. OBJECTIVE: The aim of the study is to determine if clinical exam findings alter radiological interpretation of ventral hernias on CT. METHODS: This is a single-institution double-blind, randomized trial. All patients with a recent abdominal/pelvic CT scan seen in various surgical clinics were enrolled. A surgeon blinded to the CT scan findings performed a standardized physical examination and assessed for the presence of a ventral hernia. Seven independent radiologists blinded to the study design reviewed the scans. Each radiologist received one of three types of clinical exam data per CT: accurate (correct), inaccurate (purposely incorrect), or none. Allocation was random and stratified by the presence of clinical hernia. The primary outcome was the proportion of radiologic hernias detected, analyzed by chi square. RESULTS: 115 patients were enrolled for a total of 805 CT scan reads. The proportion of hernias detected differed by up to 25% depending on if accurate, no, or inaccurate clinical information was provided. Inaccurate clinical data in patients with no hernia on physical exam led to a significant difference in the radiologic hernia detection rate (54.3% versus 35.7%, p = 0.007). No clinical data in patients with a hernia on physical exam led to a lower radiologic hernia detection rate (75.0% versus 93.8%, p = 0.001). CONCLUSIONS: The presence and accuracy of clinical information provided to radiologists impacts the diagnosis of abdominal wall hernias in up to 25% of cases. Standardization of both clinical and radiologic examinations for hernias and their reporting are needed. TRIAL REGISTRATION: Clinicaltrials.gov, Number NCT03121131, https://clinicaltrials.gov/ct2/show/NCT03121131.

Increased risk of a herpes zoster attack in patients receiving androgen deprivation therapy for prostate cancer.

This study aimed to examine the association of herpes zoster (HZ) with androgen deprivation therapy (ADT) use among patients with prostate cancer (PC), using a population-based data set. The study sample for this study was retrieved from the Taiwan Longitudinal Health Insurance Database 2005. We selected 877 patients with PC who had received ADT as the study group, while 849 patients with PC who had not received ADT served as the comparison group. Each study patient was individually tracked for a 3-year period to discriminate those who subsequently received a diagnosis of HZ. Of the total 1,726 sampled patients, the incidence rate of HZ per 100 person-years was 1.80 (95% CI: 1.41-2.25) during the 3-year follow-up period. In particular, incidence rates of HZ per 100 person-years were 2.36 (95% CI: 1.75-3.13) and 1.24 (95% CI: 0.81-1.81), respectively, for patients with PC who had and those who had not received ADT. Furthermore, Cox proportional hazard regressions showed that the adjusted hazard ratio for an HZ attack during the 3-year follow-up period for patients with PC who had received ADT was 1.88 (95% CI: 1.13-3.11) than those who had not received ADT. We concluded that patients with PC who had received ADT had an increased risk of HZ.

Association between open-angle glaucoma and neovascular age-related macular degeneration: a case-control study.

PurposeTo investigate the relationship between previously diagnosed open-angle glaucoma (OAG) and neovascular age-related macular degeneration (AMD) using a routine insurance dataset.MethodsThis study retrieved data from the Taiwan Longitudinal Health Insurance Database 2005. We found 3282 patients with neovascular AMD as cases and 13 128 sex- and age-matched subjects without neovascular AMD as controls. Conditional logistic regressions were performed to evaluate the association of neovascular AMD with previously diagnosed OAG among the sampled patients.ResultsOf the 16 410 sampled patients, 2.55% had previously diagnosed OAG, 5.06 and 1.92% for the cases and controls, respectively. The logistic regression analysis showed that the odds ratio (OR) of previously diagnosed OAG for cases was 2.45 (OR: 2.45; 95% confidence interval: 1.99-3.01) compared with the controls after adjusting for potential confounders. In addition, the adjusted ORs for previously diagnosed OAG were similar for patients with AMD in both genders (with an adjusted OR of 2.49 for males and 2.39 for females). Furthermore, it shows that OAG was significantly associated with neovascular AMD regardless of sex even after adjusting for monthly income, geographic region, urbanisation level, and comorbidities (with adjusted ORs of 2.49 for males and 2.39 for females).ConclusionsThis study demonstrated that patients with neovascular AMD had a higher odds of previously diagnosed OAG compared with those patients without neovascular AMD regardless of sex.

Androgen deprivation therapy did not increase the risk of Alzheimer's and Parkinson's disease in patients with prostate cancer.

Androgen deprivation therapy (ADT) has been the standard treatment for advanced prostate cancer for many decades. Although potential adverse effects of ADT have been reported, there are no empirical studies investigating the association between ADT and Alzheimer's disease. Therefore, this retrospective cohort study explored the relationship between the use of ADT and the subsequent risk of Alzheimer's disease in men with prostate cancer using a population-based database. We retrieved data from the "Taiwan Longitudinal Health Insurance Database 2000." The study included 1335 patients with prostate cancer and 4005 age-matched comparison patients without prostate malignancy. We then individually tracked each patient (n = 5340) for a 5-year period to discriminate those who subsequently received a diagnosis of Alzheimer's disease. The Cox proportional hazard regression showed that the hazard ratio (HR) for Alzheimer's disease during the 5-year follow-up period for prostate cancer patients was 1.71 (95% confidence interval (CI) = 0.90~3.25) over that of comparison patients. We further analyzed the hazard ratio for Alzheimer's disease and Parkinson's disease between prostate cancer patients who did and those who did not receive ADT, but we failed to observe a significant difference in the hazard ratio for both diseases during the 5-year follow-up period (adjusted HR = 1.76, 95% CI = 0.55~5.62, and HR = 1.13, 95% CI = 0.58~2.20, respectively). In conclusion, this study demonstrated that the use of androgen deprivation therapy in patients with prostate cancer was not associated with a higher risk of Alzheimer's and Parkinson's disease during the follow-up period.

Sudden sensorineural hearing loss is associated with chronic rhinosinusitis: population-based study.

BACKGROUND: This study aimed to evaluate the association of chronic rhinosinusitis with sudden sensorineural hearing loss using a population-based database. METHODS: Sampled subject data were obtained from the Taiwan Longitudinal Health Insurance Database 2000. A total of 3325 patients with sudden sensorineural hearing loss were identified and 9975 controls were randomly selected. A conditional logistic regression was used to calculate the odds ratio for having been previously diagnosed with chronic rhinosinusitis, for cases and controls. RESULTS AND CONCLUSION: The adjusted odds ratio of having prior chronic rhinosinusitis among cases compared to controls was 1.36 (95 per cent confidence interval = 1.16-1.60). The significant relationship between sudden sensorineural hearing loss and chronic rhinosinusitis was most pronounced among those patients aged 44 years or less (compared to controls) (odds ratio = 2.18; 95 per cent confidence interval = 1.63-2.92). However, the significant relationship between sudden sensorineural hearing loss and prior chronic rhinosinusitis was not sustained for patients older than 60 years compared to controls.

No increased risk of coronary heart disease for patients receiving androgen deprivation therapy for prostate cancer in Chinese/Taiwanese men.

The relationship between androgen deprivation therapy (ADT) and coronary heart disease (CHD) remains controversial. Furthermore, the majority of such studies focused on Caucasian populations, and there is still a paucity of studies among Asian populations. This population-based study aimed to investigate the relationship between ADT and CHD in an ethnic Chinese (i.e., Taiwanese) population. We used data sourced from the Taiwan 'Longitudinal Health Insurance Database'. This study included 1278 patients with prostate cancer in the study group and 1278 subjects without prostate cancer in the comparison group. Each patient was individually tracked for a 3-year period to identify those who had subsequently received a diagnosis of CHD. The results showed that the incidence rate of CHD during the 3-year follow-up period was 4.69 (95% CI: 2.99-5.48) per 100 person-years and 2.67 (95% CI: 2.15-3.27) per 100 person-years for the study and comparison cohort, respectively. The Cox proportional hazard regression showed that the hazard ratio for CHD during the 3-year follow-up period for prostate cancer patients was 1.65 (95% confidence interval (CI) = 1.25-2.16) compared with comparison subjects after adjusting for patients' geographic location, monthly income, urbanization level, hypertension, diabetes, hyperlipidemia, and stroke. However, we failed to find a significant difference in the adjusted hazard of CHD during the 3-year follow-up period between prostate cancer patients who did and those who did not receive ADT (hazard ratio = 1.12, 95% CI = 0.79-1.59). We concluded that prostate cancer but not ADT was significantly associated with CHD. In addition, a common cause of prostate cancer and coronary heart disease could exist.

Statin Use Is Associated with Bladder Pain Syndrome/Interstitial Cystitis: A Population-Based Case-Control Study.

INTRODUCTION: Statin may induce epithelial dysfunction of the bladder urothelium. Epithelial dysfunction was proposed as one of the major potential etiologies for bladder pain syndrome/interstitial cystitis (BPS/IC). In this study, we examined the association between statin use and BPS/IC using a population-based study. SUBJECTS AND METHODS: This case-control study used the Taiwan Longitudinal Health Insurance Database. In total, 815 female subjects with BPS/IC and 4075 randomly selected female controls were included. We used a conditional logistic regression to compute the odds ratio (OR) for having previously used statins between cases and controls. RESULTS: A conditional logistic regression analysis showed that the OR of prior statin users for cases was 1.52 (95% confidence interval (CI): 1.19-1.94) compared to controls after adjusting for diabetes, hypertension, coronary heart disease, obesity, chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraines, sicca syndrome, allergies, endometriosis, and asthma. Furthermore, adjusted ORs of regular and irregular statin use for cases were 1.58 (95% CI: 1.20-2.08) and 1.53 (95% CI: 1.02-2.31), respectively, compared to controls. CONCLUSION: We concluded that there was an association between statin use and BPS/IC.

Use of health care services by patients with psoriasis: a population-based study.

BACKGROUND: Although psoriasis is seldom life threatening, very few studies have compared differences in health care service use between patients with and without psoriasis. OBJECTIVES: To investigate differences in health care service use between patients with and without psoriasis. METHODS: Patient details and data on their use of health services were retrieved from the Taiwan Longitudinal Health Insurance Database 2000. We included 3649 patients with psoriasis and 3649 without it. Each patient was followed for a 1-year period to estimate their utilization of health care resources. Student t-tests were used to compare differences in health care services use between patients with and without psoriasis. RESULTS: For dermatology services, patients with psoriasis had significantly more outpatient visits (3·5 vs. 0·9), and higher outpatient and total costs (US$148·00 vs. US$12·20 and US$581·60 vs. US$347·20, respectively) than those without psoriasis. For nondermatology services, patients with psoriasis had more outpatient visits (21·3 vs. 17·6), and higher outpatient and total costs (US$904·60 vs. US$663·50 and US$1335·50 vs. US$998·30, respectively) than those without psoriasis. For overall health care service use, patients with psoriasis had significantly more outpatient visits (24·8 vs. 18·5; P < 0·01) and greater total costs (US$1917·10 vs. US$1345·60; P < 0·01) than those without psoriasis. This indicates that the total cost was about 1·4-fold greater for patients with psoriasis than those without it. CONCLUSIONS: Patients with psoriasis used health care services significantly more often than those without psoriasis.

Primary skin closure after damage control laparotomy.

BACKGROUND: Damage control laparotomy (DCL) is used widely in the management of patients with traumatic injuries but carries significant morbidity. Surgical-site infection (SSI) also carries potential morbidity, increased costs and prolonged hospital stay. The aim of this study was to determine whether primary skin closure after DCL increases the risk of SSI. METHODS: This was a retrospective institutional review of injured patients undergoing DCL between 2004 and 2012. Outcomes of patients who had primary skin closure at the time of fascial closure were compared with those of patients whose skin wound was left open to heal by secondary intention. The association between skin closure and SSI was evaluated using propensity score-adjusted multivariable logistic regression. RESULTS: Of 510 patients who underwent DCL, primary fascial closure was achieved in 301. Among these, 111 (36.9 per cent) underwent primary skin closure and in 190 (63.1 per cent) the skin wound was left open. Fascial closure at the initial take-back surgery was associated with having skin closure (P < 0.001), and colonic injury was associated with leaving the skin open (P = 0.002). On multivariable analysis, primary skin closure was associated with an increased risk of abdominal SSI (P = 0.020), but not fascial dehiscence (P = 0.446). Of patients receiving skin closure, 85.6 per cent did not develop abdominal SSI and were spared the morbidity of managing an open wound at discharge. CONCLUSION: Primary skin closure after DCL is appropriate but may be associated with an increased risk of SSI.

Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

Oxidative stress/reactive metabolite gene expression signature in rat liver detects idiosyncratic hepatotoxicants.

Previously we reported a gene expression signature in rat liver for detecting a specific type of oxidative stress (OS) related to reactive metabolites (RM). High doses of the drugs disulfiram, ethinyl estradiol and nimesulide were used with another dozen paradigm OS/RM compounds, and three other drugs flutamide, phenacetin and sulindac were identified by this signature. In a second study, antiepileptic drugs were compared for covalent binding and their effects on OS/RM; felbamate, carbamazepine, and phenobarbital produced robust OS/RM gene expression. In the present study, liver RNA samples from drug-treated rats from more recent experiments were examined for statistical fit to the OS/RM signature. Of all 97 drugs examined, in addition to the nine drugs noted above, 19 more were identified as OS/RM-producing compounds-chlorpromazine, clozapine, cyproterone acetate, dantrolene, dipyridamole, glibenclamide, isoniazid, ketoconazole, methapyrilene, naltrexone, nifedipine, sulfamethoxazole, tamoxifen, coumarin, ritonavir, amitriptyline, valproic acid, enalapril, and chloramphenicol. Importantly, all of the OS/RM drugs listed above have been linked to idiosyncratic hepatotoxicity, excepting chloramphenicol, which does not have a package label for hepatotoxicity, but does have a black box warning for idiosyncratic bone marrow suppression. Most of these drugs are not acutely toxic in the rat. The OS/RM signature should be useful to avoid idiosyncratic hepatotoxicity of drug candidates.

Circular closure is associated with the lowest rate of surgical site infection following stoma reversal: a systematic review and multiple treatment meta-analysis.

AIM: Stoma reversal is frequently complicated by surgical site infection (SSI). To reduce SSI, several techniques for skin closure have been studied, with no agreement on which is best. The aim of this study was to identify the skin closure technique associated with the lowest rate of SSI following stoma reversal. METHOD: We systematically searched MEDLINE (PubMed and OvidSP), Scopus and clinical registries from 1 January 1980 to 24 March 2012, and included original reports on adult patients following stoma reversal. A network of treatments was created to map the comparisons between skin closure techniques, including primary closure, primary closure with a drain, secondary closure, delayed primary closure, loose primary closure and circular closure. Pairwise meta-analyses were performed for all available direct comparisons of closure types and heterogeneity was assessed. A multiple-treatments meta-analysis was conducted to estimate relative treatment effects between competing closure types (reported as an odds ratio with 95% credible interval, and a probability that each treatment is best). Several sensitivity analyses were performed. RESULTS: Fifteen studies were identified with a total of 2921 cases of stoma reversal. Overall, study quality was poor with observed low (one study), moderate (seven studies) and high (seven studies) risk of bias. Circular closure was associated with the lowest SSI risk (OR 0.12; 95% CI 0.02-0.40) and was the best of six skin closure techniques (probability of being best = 68.9%). Circular closure remained the best after sensitivity analyses. CONCLUSION: This study showed that circular closure is the best skin closure technique after stoma reversal in terms of SSI rate, but the quality of supporting evidence is limited, precluding definite conclusions.

Antibiotic resistance and molecular typing of Photobacterium damselae subsp. damselae, isolated from seafood.

AIM: The objectives of our study is to determinate the antibiotic susceptibility of this organism to different antibiotics to determine the discriminatory power of the molecular typing methods. METHODS AND RESULTS: In this study, 50 Photobacterium damselae subsp. damselae isolates from Scomber australasicus and Rachycentron canadum were collected in Taiwan and their resistance to 15 different antimicrobial agents was determined. In addition, random amplification of polymorphic DNA (RAPD) and pulsed-field gel electrolysis (PFGE) were performed to study the epidemiology and clonal relationship of P. damselae subsp. damselae. The results showed that the 50 isolates generated 25 typeable profiles with multidrug resistance to 3-7 antimicrobials. The results also indicate that the RAPD and PFGE methods have high discriminatory power for molecular subtyping. CONCLUSION: Photobacterium damselae subsp. damselae isolates from fish to examine for multidrug resistance to antimicrobials. RAPD and PFGE methods revealed the high discriminatory power for molecular subtyping and provided information that could be used for risk assessment of P. damselae subsp. damselae infections. SIGNIFICANCE AND IMPACT OF THE STUDY: These results may help in epidemiological investigations of P. damselae subsp. damselae and may be useful in controlling or treating P. damselae subsp. damselae infections in aquaculture and clinical therapy.

Clinical characteristics of optic neuritis in Taiwanese children.

PURPOSE: To document the etiology, clinical presentation, and visual prognosis of optic neuritis in Taiwanese children. METHODS: Retrospectively reviewed children younger than 18 years old with optic neuritis in Chang Gung Memorial Hospital and Chang Gung Children's Hospital from 1998 to 2009. RESULTS: There were 24 children (38 eyes) with optic neuritis in that period. Overall, 14 patients (58.3%) were female and 10 patients (41.7%) were male. In total, 14 patients (58.3%) had bilateral involvement, and 10 patients (41.7%) had unilateral involvement. Out of 38 eyes, 24 (63.2%) had disc swelling. Out of 24 patients, 21 (87.5%) underwent intravenous steroid therapy (10 to 30 mg/kg/day) for 3-5 days, and followed by an oral taper. Out of 24 patients, 20 (83.3%) achieved final visual acuity (VA) of 20/40 or better. However, a poor visual outcome (four patients) (VA<20/40) was correlated with pale disc at presentation (P=0.002, Pearson χ (2)-test) and age older than 10 years (P=0.012, Fisher's exact test). Five patients were diagnosed with acute disseminated encephalomyelitis (ADEM) (21%), and three patients were diagnosed with multiple sclerosis (MS) (12.5%). Patients with ADEM did not have a better visual outcome than patients with MS (P=0.643, Fisher's exact test). CONCLUSIONS: Visual recovery from optic neuritis was favorable in Taiwanese children. A poor visual outcome was correlated with pale disc at presentation and patients' age older than 10 years. ADEM is the most common associated systemic disease; MS is relatively rare.

A longitudinal study of Taiwanese sialidosis type 1: an insight into the concept of cherry-red spot myoclonus syndrome.

BACKGROUND AND PURPOSE: Sialidosis type 1 (ST-1) is a neurodegenerative disorder with limited long-term follow-up report. This study is to document the chronological profile of ST-1. METHODS: We perform serial analysis of 17 Taiwanese patients with ST-1 focusing on evolution of clinical features, electrophysiological findings, genetic studies, and neuroimage examinations. RESULTS: All patients had a mutation at 554A-->G in exon 3 of the NEU1 gene causing Ser182Gly substitution. Fifteen patients were homozygous. Two patients were heterozygous with novel mutations, 956C-->T causing Ala319Val in one and 163C-->T causing Gln55stop codon in the other. The neuraminidase activity was markedly decreased in all 11 available patients. Only three patients (17.6%) manifested the macular cherry-red spot. The majority of patients (82.3%) developed full-blown manifestation of myoclonus, ataxia, and seizures within 5 years. Abnormal somatosensory evoked potentials with giant cortical waves were found in all patients. Prolonged P100 peak latency of the visual evoked potentials (VEPs) were found in 16 patients (94.1%) in the early stage even without visual symptoms. CONCLUSION: ST-1 in Taiwanese population illustrates distinct characteristics of phenotype with infrequent cherry-red spot. We suggest to screen the NEU1 mutations in patients presenting action myoclonus with abnormal VEPs, even without macular cherry-red spots.

Disposition, metabolism, and excretion of [14C]doripenem after a single 500-milligram intravenous infusion in healthy men.

In this open-label, single-center study, eight healthy men each received a single 500-mg dose of [(14)C]doripenem, containing 50 microCi of [(14)C]doripenem, administered as a 1-h intravenous infusion. The concentrations of unchanged doripenem and its primary metabolite (doripenem-M-1) resulting from beta-lactam ring opening were measured in plasma and urine by a validated liquid chromatography method coupled to a tandem mass spectrometry assay. Total radioactivity was measured in blood, plasma, urine, and feces by liquid scintillation counting. Further metabolite profiling was conducted on urine samples using liquid chromatography coupled to radiochemical detection and high-resolution mass spectrometry. Unchanged doripenem and doripenem-M-1 accounted for means of 80.7% and 12.7% of the area under the plasma total-radioactivity-versus-time curve (area under the concentration-time curve extrapolated to infinity) and exhibited elimination half-lives of 1.1 and 2.5 h, respectively. Total clearance of doripenem was 16 liters/h, and renal clearance was 12.5 liters/h. At 7 days after the single dose, 95.3% of total doripenem-related radioactivity was recovered in urine and 0.72% in feces. A total mean of 97.2% of the administered dose was excreted in the urine as unchanged doripenem (78.7% +/- 5.7%) and doripenem-M-1 (18.5% +/- 2.6%). Most of the urinary recovery occurred within 4 h of dosing. Three additional minor metabolites were identified in urine: the glycine and taurine conjugates of doripenem-M-1 and oxidized doripenem-M-1. These results show that doripenem is predominantly eliminated in urine as unchanged drug, with only a fraction metabolized to doripenem-M-1 and other minor metabolites.