Evaluation of a national clinical programme for the management of self-harm in hospital emergency departments: impact on patient outcomes and the provision of care.

BACKGROUND: Emergency departments are important points of intervention, to reduce the risk of further self-harm and suicide. A national programme to standardise the management of people presenting to the emergency department with self-harm and suicidal ideation (NCPSHI) was introduced in Ireland in 2014. The aim of this study was to evaluate the impact of the NCPSHI on patient outcomes and provision of care. METHODS: Data on self-harm presentations were obtained from the National Self-Harm Registry Ireland from 2012 to 2017. The impacts of the NCPSHI on study outcomes (3-month self-harm repetition, biopsychosocial assessment provision, admission, post-discharge referral, and self-discharge) were examined at an individual and aggregate (hospital) level, using a before and after study design and interrupted time series analyses, respectively. The 15 hospitals that implemented the programme by January 2015 (of a total of 24 between 2015 and 2017) were included in the analyses. RESULTS: There were 31,970 self-harm presentations during the study period. In hospitals with no service for self-harm (n = 4), risk of patients not being assessed reduced from 31.8 to 24.7% following the introduction of the NCPSHI. Mental health referral in this hospital group increased from 42.2 to 59.0% and medical admission decreased from 27.5 to 24.3%. Signs of a reduction in self-harm repetition were observed for this hospital group, from 35.1 to 30.4% among individuals with a history of self-harm, but statistical evidence was weak. In hospitals with a pre-existing liaison psychiatry service (n = 7), risk of self-discharge was lower post-NCPSHI (17.8% vs. 14.8%). In hospitals with liaison nurse(s) pre-NCPSHI (n = 4), medical admission reduced (27.5% vs. 24.3%) and there was an increase in self-harm repetition (from 5.2 to 7.8%. for those without a self-harm history). CONCLUSION: The NCPSHI was associated with improvements in the provision of care across hospital groups, particularly those with no prior service for self-harm, highlighting the need to consider pre-existing context in implementation planning. Our evaluation emphasises the need for proper resourcing to support the implementation of clinical guidelines on the provision of care for people presenting to hospital with self-harm.

[Safety and efficacy of transcatheter aortic valve replacement using the "All in One" single artery/vessel technique].

Objective: To explore the safety and efficacy of transcatheter aortic valve replacement (TAVR) using the "All in One" single-artery/vessel technique. Methods: This is a retrospective study. A total of 30 consecutive patients underwent TAVR using the single artery/vascular technique in Beijing Anzhen Hospital from August to December 2021 were included. Baseline clinical data, operative situation, postoperative outcomes, and incidence of adverse events during hospitalization and at one month post TAVR were analyzed. Results: Mean age was (72.6±9.7) years, 16 were male patients, STS score was (4.73±3.12)%. Four patients were diagnosed as isolated aortic regurgitation (all with tricuspid aortic valves), and 26 patients were diagnosed as aortic stenosis (AS), 10 of whom with tricuspid aortic valves and 16 of whom with bicuspid aortic valves. The single-vessel technique was applied in 3 aortic stenosis cases; the single-artery technique was applied in 27 cases. Echocardiography was performed immediately after procedure and results showed no or trace perivalvular leak in 27 cases and small perivalvular leak in 3 cases; the mean aortic transvalvular gradient of 26 AS patients decreased from (50.4±16.0) mmHg (1 mmHg=0.133 kPa) to (9.4±3.2) mmHg (P<0.001). The procedure time was (64.8±18.9) min. There were no intraoperative death, valve displacement, conversion to surgery, coronary artery occlusion in all 30 patients. There were no major cardiac adverse events such as myocardial infarction or stroke occurred during hospitalization or at follow-up. One-month follow-up echocardiography indicated prosthesis works well. The symptoms were significantly alleviated, and the Kansas City Cardiomyopathy Score (KCCQ score) of all patients increased from 48.1±18.4 to 73.5±17.6 (P<0.001). Conclusions: TAVR using the single artery/vessel technique is safe and feasible. This technique is related to reduced access complications and worthy of wide application.

[Analysis of dyslipidemia management status in atrial fibrillation patients with very high and high risk of atherosclerotic cardiovascular disease].

Objective: To analyze the status of statins use and low-density lipoprotein cholesterol (LDL-C) management in patients with atrial fibrillation (AF) and very high/high risk of atherosclerotic cardiovascular disease (ASCVD) from Chinese Atrial Fibrillation Registry (CAFR). Methods: A total of 9 119 patients with AF were recruited in CAFR between January 1, 2015 to December 31, 2018, patients at very high and high risk of ASCVD were included in this study. Demographics, medical history, cardiovascular risk factors, and laboratory test results were collected. In patients with very high-risk, a threshold of 1.8 mmol/L was used as LDL-C management target and in patients with high risk, a threshold of 2.6 mmol/L was used as LDL-C management target. Statins use and LDL-C compliance rate were analyzed, multiple regression analysis was performed to explore the influencing factors of statins use. Results: 3 833 patients were selected (1 912 (21.0%) in very high risk of ASCVD group and 1 921 (21.1%) in high risk of ASCVD group). The proportion of patients with very high and high risk of ASCVD taking statins was 60.2% (1 151/1 912) and 38.6% (741/1 921), respectively. Attainment rate of LDL-C management target in patients with very high and high risk were 26.7% (511/1 912) and 36.4% (700/1 921), respectively. Conclusion: The proportion of statins use and attainment rate of LDL-C management target are low in AF patients with very high and high risk of ASCVD in this cohort. The comprehensive management in AF patients should be further strengthened, especially the primary prevention of cardiovascular disease in AF patients with very high and high risk of ASCVD.

[Feasibility study of using bridging temporary permanent pacemaker in patients with high-degree atrioventricular block after TAVR].

Objective: To determine the feasibility of using temporary permanent pacemaker (TPPM) in patients with high-degree atrioventricular block (AVB) after transcatheter aortic valve replacement (TAVR) as bridging strategy to reduce avoidable permanent pacemaker implantation. Methods: This is a prospective observational study. Consecutive patients undergoing TAVR at Beijing Anzhen Hospital and the First Affiliated Hospital of Zhengzhou University from August 2021 to February 2022 were screened. Patients with high-degree AVB and TPPM were included. Patients were followed up for 4 weeks with pacemaker interrogation at every week. The endpoint was the success rate of TPPM removal and free from permanent pacemaker at 1 month after TPPM. The criteria of removing TPPM was no indication of permanent pacing and no pacing signal in 12 lead electrocardiogram (EGG) and 24 hours dynamic EGG, meanwhile the last pacemaker interrogation indicated that ventricular pacing rate was 0. Routinely follow-up ECG was extended to 6 months after removal of TPPM. Results: Ten patients met the inclusion criteria for TPPM, aged (77.0±11.1) years, wirh 7 females. There were 7 patients with third-degree AVB, 1 patient with second-degree AVB, 2 patients with first degree AVB with PR interval>240 ms and LBBB with QRS duration>150 ms. TPPM were applied on the 10 patients for (35±7) days. Among 8 patients with high-degree AVB, 3 recovered to sinus rhythm, and 3 recovered to sinus rhythm with bundle branch block. The other 2 patients with persistent third-degree AVB received permanent pacemaker implantation. For the 2 patients with first-degree AVB and LBBB, PR interval shortened to within 200 ms. TPPM was successfully removed in 8 patients (8/10) at 1 month without permanent pacemaker implantation, of which 2 patients recovered within 24 hours after TAVR and 6 patients recovered 24 hours later after TAVR. No aggravation of conduction block or permanent pacemaker indication were observed in 8 patients during follow-up at 6 months. No procedure-related adverse events occurred in all patients. Conclusion: TPPM is reliable and safe to provide certain buffer time to distinguish whether a permanent pacemaker is necessary in patients with high-degree conduction block after TAVR.

[Association among urinary polycyclic aromatic hydrocarbons metabolites, SAHH activity and H19 expression in coke oven workers].

Objective: To investigate the relationship of polycyclic aromatic hydrocarbons (PAHs) exposure, S-adenosylhomocysteine hydrolase (SAHH) activity and long noncoding RNA H19 gene expression in the urine of coke oven workers. Methods: In September 2019, in a coking plant in Taiyuan City, 146 male workers who had worked in coke oven operations for one year were selected through a completely random sampling method, and their basic personal information was collected by questionnaire survey, and blood and urine samples were collected. The levels of 4 PAHs metabolites 2-hydroxfluorene (2-FLU), 2- hydroxynaphthalene (2-NAP), 9-hydroxyphenanthren (9-PHE), and 1-hydroxypyrene (1-OHP) in urine were detected by high performance liquid chromatography (HPLC) -fluorescence detection method. HPLC-UV detection method was used to detect the content of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in plasma, and the SAHH activity value was obtained by calculating the ratio. Reverse transcription PCR method was used to determine the H19 gene expression level. Urine levels of 2-FLU, 2-NAP, 9-PHE, and 1-OHP were divided into Q(1), Q(2), Q(3), and Q(4) groups according to quartiles (P(25), P(50), P(75)). Regression, trend test and restricted cubic splines were used to analyze the relationship among PAHs metabolites, SAHH activity, H19 gene expression and their dose-response. Results: The median age of coke oven workers was 39.60 years old, the median length of service was 20.38 years, and the urinary levels of 2-FLU, 2-NAP, 9- PHE, and 1-OHP were 0.29, 0.74, 0.09, and 0.06 µg/mmol Cr, respectively. The levels of 2-FLU, 2-NAP and 9-PHE in the urine of workers were significantly different between groups with different 1-OHP levels (P<0.05). After adjusting for age, length of service, smoking, drinking, and levels of 2-FLU, 2-NAP and 9-PHE, SAHH activity decreased with the increase of urinary 1-OHP level (OR=0.63, 95%CI: 0.41-0.98, P=0.038), showing a nonlinear relationship (P(nonlinear)= 0.030). H19 gene expression increased with the increase of urinary 1- OHP level (OR=1.51, 95%CI: 1.03-2.19, P=0.033), there was a linear relationship (P(trend)= 0.058). The relationship between the other three metabolites in urine and SAHH activity and H19 gene expression was not statistically significant (P>0.05) . Conclusion: Urinary 1-OHP level may be a risk factor for decreased SAHH activity and increased H19 gene expression in coke oven workers.

[Association between duration of digoxin use and adverse outcomes among Chinese patients with atrial fibrillation].

Objective: We aimed to explore the impact of digoxin use on outcomes in Chinese patients with atrial fibrillation (AF). Methods: We used the dataset from the Chinese Atrial Fibrillation Registry, a prospective, multicenter, hospital-based registry study. According to the inclusion and exclusion criteria, 10 472 eligible patients enrolled from August 2011 to December 2016 were included in this ancillary study. The patients were classified into three groups according to the status of digoxin use at study enrollment, patients already receiving digoxin before registry were represented as continuous group, patients initiated on digoxin for the first time were represented as newly group, and patients without digoxin prescription at enrollment were represented as control group. Patients were followed by telephone or outpatient service every 6 months. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to investigate the association of digoxin use with adverse outcomes (all-cause death, cardiovascular death and cardiovascular hospitalization). Results: In the overall study population, men accounted for 42.8%, and the average age was (66.9±11.8) years. There were 777（7.42%）patients in continuous group, 375 (3.58%) patients in newly group, and 9 320 (89.00%) patients in control group. Compared with the control group, the patients in the newly group and the continuous group were older, had faster heart rate, lower estimated glomerular filtration rate, higher proportion of persistent atrial fibrillation, heart failure, renal insufficiency, diabetes mellitus, ischemic stroke, coronary heart disease, vascular disease and bleeding history. At the same time, the patients in the newly group and the continuous group were treated more often with anticoagulants, antiplatelet drugs, ACE inhibitors or angiotensin receptor blockers, beta-receptor blockers while the proportion of antiarrhythmic drugs was lower as compared to control group (P<0.05). During a median follow-up of 36 months (interquartile range: 18-48 month), risk of all-cause mortality was significantly higher in newly group compared to control group (7.3% vs. 4.7%, P<0.05), the rates of all-cause mortality, cardiovascular death and cardiovascular hospitalization were all higher in continuous group than in control group (8.0% vs. 4.7%; 4.7% vs. 3.0%; 16.7% vs. 11.8%; P all<0.05). After adjustment for age, male, body mass index, blood pressure, heart rate, renal function, AF type, history of stroke, heart failure, diabetes, coronary artery disease and other drugs treatment, the association between newly group and adverse outcomes was not significant, however, digoxin use was associated with increased all-cause mortality (HR 1.26; 95%CI 1.04-1.56; P=0.019), cardiovascular death (HR 1.38; 95%CI 1.08-1.77, P =0.01), and cardiovascular hospitalization (HR 1.10; 95%CI 1.06-1.52, P=0.02) in continuous group. Conclusion: Continuous digoxin use is associated with a significant increase in adverse outcomes among Chinese patients with atrial fibrillation.

[Value of left ventricular myocardial strain derived from cardiac magnetic resonance tissue tracking on differentiating constrictive pericarditis from restrictive cardiomyopathy].

Objective: To compare left ventricular myocardial mechanics detected by cardiac magnetic resonance tissue tracking(CMR-TT) between patients with constrictive pericarditis(CP) and restrictive cardiomyopathy(RCM),and see if those can be used to differentiate CP from RCM patients. Methods: A total of 23 patients with CP, 20 patients with RCM, who hospitalized in Beijing Anzhen Hospital from January 2014 to April 2019 were included in this study and 25 healthy subjects served as control group, all subjects underwent cardiac magnetic resonance examination. Myocardial mechanics were evaluated by 2-dimensional(2D) and 3-dimensional(3D) CMR-TT in terms of global longitudinal strain(GLS), circumferential strain(GCS), radial strain(GRS) and the lateral wall strain to septal wall strain ratio(lateral/septal ratio) of basal, mid-cavity and apical. The diagnostic area under the receiver operating characteristic curve (ROC) was evaluated for differentiating CP from RCM. Results: Age, sex and heart rate were similar between CP and RCM patients(all P>0.05). 2D-GLS, 3D-GLS, GCS and GRS in CP and RCM groups were significantly lower than those in normal control group(all P<0.05).3D-GLS value was significantly lower in RCM patients than in CP patients(P<0.05), the area under the curve (AUC)=0.787(sensitivity 80%, specificity 78%). 3D-GCS was significantly lower in CP group than in RCM group(P<0.05), the AUC=0.737(sensitivity 80%, specificity 65%). However, there was no significant difference between CP and RCM in 3D-GRS(P>0.05). Compared with RCM, the circumferential and radial lateral/septal ratios of the basal were significantly lower in CP group than in RCM group(both P<0.05), AUC=0.737(sensitivity 70%, specificity 83%) and 0.737 (sensitivity 60%, specificity 87%), respectively. The left ventricular myocardial mechanics strain curve of the CP,RCM and normal control were different. The CP patients presented as " rapidly down-a platform" form, the RCM presented as "slowly down" form, and normal control presented as "rapidly down" form. Conclusion: Evaluating the differences in the diastolic process of left ventricular myocardium and left ventricular myocardial mechanics strain curve is helpful to differentiate CP from RCM patients.

Comparative effect of antipsychotics on risk of self-harm among patients with schizophrenia.

OBJECTIVE: To investigate the association of different antipsychotic treatments with hospitalization due to self-harm among patients with schizophrenia. METHOD: This retrospective cohort study was based on Taiwan's universal health insurance database. Patients aged 15-45 years with a newly diagnosed schizophrenic disorder in 2001-2012 were included. The study outcome was the first hospitalization due to self-harm or undetermined injury after the diagnosis of schizophrenic disorders. The exposure status of antipsychotics was modeled as a time-dependent variable. The analyses were stratified by antipsychotic dosage based on defined daily dose (DDD). RESULTS: Among 70 380 patients with a follow-up of 500 355 person-years, 2272 self-harm hospitalization episodes were identified. Compared with none or former use, current use of several second-generation antipsychotics with a dose of one DDD or above, including amisulpride, aripiprazole, clozapine, risperidone, and sulpiride, was associated with decreased risk of self-harm hospitalization, with clozapine showing the strongest effect (adjusted rate ratio = 0.26, 95% confidence interval 0.15-0.47). CONCLUSION: The protective effect on self-harm may vary across different antipsychotics. Further studies are needed to replicate the findings.

Use of antipsychotics increases the risk of fracture: a systematic review and meta-analysis.

Our systematic review and meta-analysis of observational studies indicated that the use of antipsychotics was associated with a nearly 1.5-fold increase in the risk of fracture. First-generation antipsychotics (FGAs) appeared to carry a higher risk of fracture than second-generation antipsychotics (SGAs). INTRODUCTION: The risk of fractures associated with the use of antipsychotic medications has inconsistent evidence between different drug classes. A systematic review and meta-analysis was conducted to evaluate whether there is an association between the use of antipsychotic drugs and fractures. METHODS: Searches were conducted through the PubMed and EMBASE databases to identify observational studies that had reported a quantitative estimate of the association between use of antipsychotics and fractures. The summary risk was derived from random effects meta-analysis. RESULTS: The search yielded 19 observational studies (n = 544,811 participants) with 80,835 fracture cases. Compared with nonuse, use of FGAs was associated with a significantly higher risk for hip fractures (OR 1.67, 95% CI, 1.45-1.93), and use of second generation antipsychotics (SGAs) was associated with an attenuated but still significant risk for hip fractures (OR 1.33, 95% CI, 1.11-1.58). The risk of fractures associated with individual classes of antipsychotic users was heterogeneous, and odds ratios ranged from 1.24 to 2.01. Chlorpromazine was associated with the highest risk (OR 2.01, 95% CI 1.43-2.83), while Risperidone was associated with the lowest risk of fracture (OR 1.24, 95% CI 0.95-1.83). CONCLUSIONS: FGA users were at a higher risk of hip fracture than SGA users. Both FGAs and SGAs were associated with an increased risk of fractures, especially among the older population. Therefore, the benefit of the off-label use of antipsychotics in elderly patients should be weighed against any risks for fracture.

Comparative risk of self-harm hospitalization amongst depressive disorder patients using different antidepressants: a population-based cohort study in Taiwan.

BACKGROUND: The aim of the study was to evaluate the comparative risk of self-harm associated with the use of different antidepressants. METHOD: A cohort study was conducted using data from Taiwan's National Health Insurance Research Database from 2001 to 2012. A total of 751 606 new antidepressant users with depressive disorders were included. The study outcome was hospitalization due to self-harm (International Classification of Diseases, Ninth Revision, Clinical Modification codes: E950-E958 and E980-E988). Cox proportional hazards models with stratification of the propensity score deciles were used to estimate the hazard ratios of self-harm hospitalization during the first year following the initiation of antidepressant treatment. RESULTS: There were 1038 hospitalization episodes due to self-harm that occurred during the follow-up of 149 796 person-years, with an overall incidence rate of 6.9 [95% confidence interval (CI) 6.5-7.4] per 1000. Compared with fluoxetine, the risk of self-harm hospitalization was higher for maprotiline [adjusted hazard ratio (aHR) = 3.00, 95% CI 1.40-6.45], milnacipran (aHR = 2.34, 95% CI 1.24-4.43) and mirtazapine (aHR = 1.40, 95% CI 1.06-1.86), lower for bupropion (aHR = 0.51, 95% CI 0.30-0.86), and similar level of risk was found for other selective serotonin reuptake inhibitors (citalopram, escitalopram, fluvoxamine, paroxetine and sertraline). CONCLUSIONS: The risk of self-harm may vary across different antidepressant drugs. It would be of importance to conduct further research to investigate the influence of antidepressant use on self-harm behaviors.

Preadmission statin use improves the outcome of less severe sepsis patients - a population-based propensity score matched cohort study.

BACKGROUND: Randomized controlled trials on the post-admission use of statins in sepsis patients have not shown a survival benefit. Whether preadmission use of statins would confer any beneficial effects in sepsis patients has not been well studied. METHODS: We conducted a population-based cohort study on a national health insurance claims database between 1999 and 2011. Sepsis patients were identified by ICD-9 codes compatible with the third International consensus definitions for sepsis. Use of statin was defined as the cumulative use of any statin for more than 30 days before the indexed sepsis admission. We determined the association between statin use and sepsis outcome by multivariate-adjusted Cox proportional hazard models and propensity score matched analysis. To minimize baseline imbalance between statin users and non-statin users, we matched/adjusted for social economic status, comorbidities, proxies for healthy lifestyle, health care facility utilization, and use of medications. RESULTS: We identified 52 737 sepsis patients, of which 3599 received statin treatment. Statins use was associated with a reduced 30-day mortality after multivariable adjustment (HR 0.86, 95% CI, 0.78-0.94) and propensity score matching (HR, 0.88; 95% CI, 0.78-0.99). On subgroup analysis, the beneficial effects of statins were not significant in patients receiving ventilator support or requiring ICU admission. CONCLUSIONS: In this national cohort study, preadmission statin therapy before sepsis development was associated with a 12% reduction in mortality when compared with patients who never received a statin. There were no consistent beneficial effects of statins in all patient subgroups.

Heart rate and suicide: findings from two cohorts of 533 000 Taiwanese and 75 000 Norwegian adults.

OBJECTIVE: To investigate the association of resting heart rate with suicide in two large cohorts. METHOD: The MJ cohort (Taiwan) included 532 932 adults from a health check-up programme (1994-2008). The HUNT cohort (Norway) included 74 977 adults in the Nord-Trøndelag County study (1984-1986), followed up to 2004. In both cohorts heart rate was measured at baseline, and suicide was ascertained through linkage to cause-of-death registers. Risk of suicide was estimated using Cox proportional hazards models. RESULTS: There were 569 and 188 suicides (average follow-up period of 8.1 and 16.9 years) in the MJ and HUNT cohorts respectively. Sex- and age-adjusted hazard ratio for every 10 beat increase in heart rate per minute was 1.08 (95% Confidence Interval 1.00-1.16) and 1.24 (1.12-1.38) in the MJ and HUNT cohorts, respectively. In the MJ cohort this association was confined to individuals with a history of heart diseases vs. those without such a history (P for interaction = 0.008). In the HUNT cohort the association did not differ by history of heart diseases and was robust to adjustment for health-related life style, medication use, and symptoms of anxiety and depression. CONCLUSION: Elevated resting heart rate may be a marker of increased suicide risk.

[Situation of long-term use of oral anticoagulation among atrial fibrillation patients with stroke in different level hospital].

OBJECTIVE: To investigate the current situation, time trends and factors associated with long-term use of oral anticoagulation (OAC) among atrial fibrillation (AF) patients with ischemic stroke. METHODS: We used the dataset from the CAFR (Chinese Atrial Fibrillation Registry), a prospective, multicenter, hospital-based registry study involving 20 tertiary and 12 nontertiary hospitals in Beijing. In brief, 380 consecutive AF patients with following ischemic stroke were enrolled from 2003 to 2014.Patients with valvular AF, radiofrequency catheter ablation history or contraindications of OAC were excluded. We divided the patients into two groups according to hospital level, and investigated the rate of OAC use and its change over time in patients who had indication, the factors including patient characteristics and hospital level associated with OAC use were also analyzed. RESULTS: Overall oral anticoagulation use rate was 27.71%, which dropped to 22.11% and 15.26% at 6 months and 12 months, respectively.A total of 298 participates were enrolled from tertiary hospitals (78.42%), and 82 were enrolled from nontertiary hospitals. The status of OAC use in tertiary hospitals was better than nontertiary hospitals (32.66% vs 7.32%, P<0.001). Multivariable analysis showed better oral anticoagulation use was independently associated with higher-level hospitals (odds ratio 1.785, 95% confidence interval 1.026-3.106, P=0.040), and history of heart failure (odds ratio 2.247, 95% confidence interval 1.235-4.090, P=0.008). CONCLUSIONS: These data indicates oral anticoagulation use has improved in atrial fibrillation patients with stroke in Beijing. The use of anticoagulation among the patients from tertiary hospitals is significantly better than those from nontertiary hospitals, and the history of heart failure may have effect on the use of oral anticoagulation.

Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma.

BACKGROUND: To investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC). PATIENTS AND METHODS: A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48). RESULTS: Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005). CONCLUSION: In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH.

Minor physical anomalies and craniofacial measures in patients with treatment-resistant schizophrenia.

BACKGROUND: Schizophrenia patients have higher rates of minor physical anomalies (MPAs) than controls, particularly in the craniofacial region; this difference lends support to the neurodevelopmental model of schizophrenia. Whether MPAs are associated with treatment response in schizophrenia remains unknown. The aim of this case-control study was to investigate whether more MPAs and specific quantitative craniofacial features in patients with schizophrenia are associated with operationally defined treatment resistance. METHOD: A comprehensive scale, consisting of both qualitatively measured MPAs and quantitative measurements of the head and face, was applied in 108 patients with treatment-resistant schizophrenia (TRS) and in 104 non-TRS patients. Treatment resistance was determined according to the criteria proposed by Conley & Kelly (2001; Biological Psychiatry 50, 898-911). RESULTS: Our results revealed that patients with TRS had higher MPA scores in the mouth region than non-TRS patients, and the two groups also differed in four quantitative measurements (facial width, lower facial height, facial height, and length of the philtrum), after controlling for multiple comparisons using the false discovery rate. Among these dysmorphological measurements, three MPA item types (mouth MPA score, facial width, and lower facial height) and earlier disease onset were further demonstrated to have good discriminant validity in distinguishing TRS from non-TRS patients in a multivariable logistic regression analysis, with an area under the curve of 0.84 and a generalized R 2 of 0.32. CONCLUSIONS: These findings suggest that certain MPAs and craniofacial features may serve as useful markers for identifying TRS at early stages of the illness.

Risk of skin ulcerations associated with oral nicorandil therapy: a population-based study.

BACKGROUND: Although healthcare products regulatory agencies have issued warnings on risk of ulceration associated with the use of nicorandil, a population-based study has not been carried out. OBJECTIVES: To determine the relationship between use of nicorandil and skin ulceration. METHODS: We carried out a population-based study using a cohort of 1 million people assembled from Taiwan's national health insurance database. The association between nicorandil use and skin ulcers was estimated by a Cox proportional hazards regression model adjusting for a nicorandil-specific propensity score (PS) comprising of 86 potential predictors (c-statistic = 0·91). RESULTS: The prospective cohort was longitudinally followed from January 2005 to December 2009, during which 1268 new users of nicorandil and 771 136 nonusers were identified. A higher frequency of skin ulcers (29 of 1268; 2·3%) was observed for users of nicorandil compared with nonusers (3231 of 771 136; 0·4%). Compared with nonusers, the crude hazard ratio (HR) associating nicorandil use with skin ulcers was 5·52 [95% confidence interval (CI) 3·82-7·95] and the PS-adjusted HR was 1·85 (95% CI 1·27-2·69). A risk period analysis showed that the risk of skin ulceration among users of nicorandil was greatest in the first year. Subgroup analysis found that the interaction term reached statistical significance (P < 0·05) for age and diabetes. CONCLUSIONS: Use of nicorandil was found to be associated with an increased risk for skin ulceration, especially in the first year after incident exposure. We suggest that regulatory agencies re-evaluate the risk for skin ulceration associated with use of nicorandil.

Risk of osteonecrosis in patients taking bisphosphonates for prevention of osteoporosis: a systematic review and meta-analysis.

SUMMARY: We aimed to systematically review observational studies evaluating use of bisphosphonates (BPs) and risk of osteonecrosis of jaw (ONJ) or other sites among non-cancer patients. INTRODUCTION: PubMed, EMBASE, and Cochrane Library were screened from database inception to Dec 2012. METHODS: Two reviewers independently identified cohort and case-control studies evaluating the use of oral or intravenous (IV) BPs and the risk of ONJ and extracted the characteristics of the studies and risk estimates. Pooled estimates of odds ratios and 95 % confidence intervals (CI) were derived by random effects meta-analysis. Subgroup analyses were carried according to patients' characteristics and route of BP use. RESULTS: We identified 12 studies, including 2,652 cases and 1,571,997 controls. Use of BPs was associated with a significantly increased risk of ONJ or ON of other sites [odds ratio (OR) 2.32; 95 % CI 1.38-3.91; I (2) = 91 %]. The summary OR was 2.91 (95 % CI 1.62-5.22; I (2) = 85.9 %) for adjusted studies. Use of BPs were associated with higher risk on ONJ (OR 2.57; 95 % CI 1.37-4.84; I (2) = 92.2 %) than ON of other sites (OR 1.79; 95 % CI 0.71-4.47; I (2) = 83.3 %). Meta-regression analysis did not find design characteristics or outcome definitions to be significant sources of heterogeneity. CONCLUSION: The available evidence suggests that use of BPs in cancer patients is associated with a substantial risk for ONJ. Patients receiving IV BP are at highest risk.