Safety and effectiveness of lurasidone in the treatment of Chinese schizophrenia patients: An interim analysis of post-marketing surveillance.

BACKGROUND: Schizophrenia is a psychiatric disorder characterized by chronic or recurrent symptoms. Lurasidone was licensed in China in 2019 for the treatment of adult schizophrenia in adults with a maximum dose of 80 mg/d. However, post-market surveillance (PMS) with an adequate sample size is required for further validation of the drug's safety profile and effectiveness. AIM: To conduct PMS in real-world clinical settings and evaluate the safety and effectiveness of lurasidone in the Chinese population. METHODS: A prospective, multicenter, open-label, 12-wk surveillance was conducted in mainland China. All patients with schizophrenia from 10 sites who had begun medication with lurasidone between September 2019 and August 2022 were eligible for enrollment. Safety assessments included adverse events (AEs), adverse drug reactions (ADRs), extrapyramidal symptoms (EPS), akathisia, use of EPS drugs, weight gain, and laboratory values as metabolic parameters and the QTc interval. The effectiveness was assessed using the brief psychiatric rating scale (BPRS) from baseline to the end of treatment. RESULTS: A total of 965 patients were enrolled in the full analysis set and 894 in the safety set in this interim analysis. The average daily dose was 61.7 ± 19.08 mg (mean ± SD) during the treatment. AEs and ADRs were experienced by 101 patients (11.3%) and 78 patients (8.7%), respectively, which were mostly mild. EPS occurred in 25 individuals with a 2.8% incidence, including akathisia in 20 individuals (2.2%). Moreover, 59 patients received drugs for treating EPS during the treatment, with an incidence of 6.6% which dropped to 5.4% at the end of the treatment. The average weight change was 0.20 ± 2.36 kg (P = 0.01687) with 0.8% of patients showing a weight gain of ≥ 7% at week 12 compared with that at the baseline. The mean values of metabolic parameters and the QTc interval at baseline and week 12 were within normal ranges. The mean changes in total BPRS scores were -8.9 ± 9.76 (n = 959), -13.5 ± 12.29 (n = 959), and -16.8 ± 13.97 (n = 959) after 2/4, 6/8, and 12 wk, respectively (P < 0.001 for each visit compared with the baseline) using the last-observation-carried-forward method. CONCLUSION: The interim analysis of the PMS of adult patients with schizophrenia demonstrate the safety and effectiveness of lurasidone in the Chinese population. No new safety or efficacy concerns were identified.

Analysis of 27 ß-Blockers and Metabolites in Milk Powder by High Performance Liquid Chromatography Coupled to Quadrupole Orbitrap High-Resolution Mass Spectrometry.

This paper presents an application of high performance liquid chromatography coupled with quadrupole orbitrap high-resolution mass spectrometry (HPLC-Q-Orbitrap HRMS) for the analysis of 27 ß-blockers and metabolites in milk powder. Homogenized milk power samples were extracted by acetonitrile and purified by using Oasis PRiME HLB solid-phase extraction cartridges. The Ascentis® C8 chromatographic column was used to separate the analytes. The quantification was achieved by using matrix-matched standard calibration curves with carazolol-d7 and propranolol-d7 as the internal standards. The results show an exceptional linear relationship with the concentrations of analytes over wide concentration ranges (0.5⁻500 µg kg-1) as all the fitting coefficients of determination r² are > 0.995. All the limits of detection (LODs) and quantitation (LOQs) values were within the respective range of 0.2⁻1.5 µg kg-1 and 0.5⁻5.0 µg kg-1. Overall average recoveries were able to reach 66.1⁻100.4% with the intra- and inter-day variability under 10%. This method has been successfully applied to the screening of ß-blockers and metabolites in commercial milk powders. At the same time, the corresponding characteristic fragmentation behavior of the 27 compounds was explored. The characteristic product ions were determined and applied to the actual samples screening.

Lack of any prognostic value of body mass index for patients undergoing chemoradiotherapy for esophageal squamous cell carcinoma.

BACKGROUND: The relationship between body mass index(BMI) and outcomes after chemoradiotherapy(CRT) has not been systematically addressed. The purpose of this study was to evaluate the effect of BMI on survival in patients with esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Sixty ESCC cases were retrospectively reviewed in this study. Patient overall survival(OS) and disease-free survival (DFS) were compared between two groups (BMI<24.00 kg/m2 and BMI≥24.00 kg/m2). RESULTS: There were 41 patients in the low/normal BMI group (BMI<24.00 kg/m2) and 19 in the high BMI group (BMI≥24.00 kg/m2). No significant differences were observed in patient characteristics between these. We found no difference in 2-year OS and DFS associated with BMI (p=0.763 for OS; p=0.818 for DFS) using the Kaplan-Meier method. Univariate analysis revealed that higher clinical stage was prognostic for worse 2-year OS and DFS, metastasis for 2-year OS, lymph node status for 2-year DFS, while age, gender, smoking, drinking, tumor location and BMI were not prognostic. There were no differences in the 2-year OS (hazard ratio=1.117; p=0.789) and DFS(hazard ratio=1.161; p=0.708) between BMI groups in multivariate analysis, whereas we found statistical differences in the 2-year OS and DFS associated with clinical stage, gender and tumor infiltration (p<0.04), independent of age, smoking, drinking, tumor location, the status of lymph node metastases and BMI. CONCLUSIONS: BMI was not associated with survival in patients with ESCC treated with CRT as primary therapy. BMI should not be considered a prognostic factor for patients undergoing CRT for ESCC.

Arterial stiffness in patients with chronic kidney disease.

INTRODUCTION: Brachial-ankle pulse wave velocity (baPWV) was a marker of arterial stiffness, and increased baPWV was associated with renal function progression in patients with chronic kidney disease (CKD). However, there was no study to evaluate the longitudinal change of baPWV in patients with CKD. The aims of this study were to assess whether there was a longitudinal change in baPWV and to find out the determinants of this change in patients with CKD. METHODS: This study enrolled 52 patients with CKD stages 3 to 5 from outpatient Department of Internal Medicine. The values of baPWV were measured by an ankle-brachial index-form device at baseline and at 2-year follow-up. Changes of parameters (Δ) were used to evaluate the relationship between biological markers, blood pressures, medications and baPWV. RESULTS: The values of baPWV decreased during the 2-year follow-up (2108.4 ± 893.9 and 1897.1 ± 472.4; P = 0.016). There were also significant reductions in systolic and diastolic blood pressures during the 2-year follow-up, and Δsystolic blood pressure and baseline baPWV were the major determinants of ΔbaPWV. CONCLUSIONS: The present longitudinal study showed that the values of baPWV decreased during the 2-year follow-up, and the major determinants of ΔbaPWV were Δsystolic blood pressure and baseline baPWV in patients with CKD. Good control of systolic blood pressure may be associated with the regression of baPWV in patients with CKD.

Iatrogenic rupture of the ureter during kidney biopsy.

Perirenal hematoma, hematuria, and abdominal pain are common complications of kidney biopsy, but ureter rupture is relatively less frequent. Here we report a patient who experienced severe abdominal pain and gross hematuria following a non-smooth procedure of ultrasound-guided kidney biopsy. Computed tomography showed rupture of the left upper third of the ureter. We implanted a curled double-J catheter between the renal pelvis and urinary bladder. Abdominal pain and gross hematuria improved. After 2 months, the double-J catheter was removed and the patient had no further clinical symptoms. The possibility of ureter rupture, although rare, should be considered in the presence of abdominal pain and gross hematuria in patients after receiving a kidney biopsy.

Outcome of physical therapy intervention on ventilator weaning and functional status.

Our study aimed to understand the characteristics of ventilator dependence in patients at a respiratory care center and the potential effects of physical therapy on ventilator weaning and patients' functional status. Prospective data collection consisted of the following: (1) demographic data, including name, gender, age, diagnosis, the Acute Physiology and Chronic Health Evaluation as a severity of the disease, modified Glasgow Coma Scale, mobility at the time of admission, and days of hospitalization; (2) Rapid shallow breathing index (RSBI) as a predictive indicator of ventilator weaning, including indicators of ventilator weaning were collected from the respiratory flow sheet; and (3) Barthel index. Between July 1 and December 31, 2007, 126 patients were admitted to the respiratory care center, and those who required mechanical ventilation for more than 14 days were enrolled. Fifty-five subjects received physical therapy. The RSBI in patients who received physical therapy was 75.7 +/- 37.9 before therapy and 80.0 +/- 48.5 afterwards, while the Barthel index increased from 0.8 +/- 1.4 to 1.9 +/- 2.5 (p < 0.05). The RSBI decreased as time of physical therapy lengthened, but not significantly (r = 0.12, p = 0.44). The success rate of ventilator weaning in patients receiving physical therapy intervention versus non-physical therapy intervention was 58.2% and 40.9%, respectively. The results indicated that lengthening the physical therapy intervention time enhanced the ventilator weaning success rate while mobility was not affected (r = -0.11, p = 0.41). Physical therapy may be offered to ventilator-dependent patients in line with their individual needs to improve or maintain basic mobility.

Ankle brachial index as a predictor for mortality in patients with chronic kidney disease and undergoing haemodialysis.

AIM: The ankle brachial index (ABI) is a marker for peripheral artery disease and can predict mortality in advanced chronic kidney disease (CKD) and haemodialysis patients, respectively. However, it is seldom studied in Taiwan, an area with high prevalence of CKD and end-stage renal disease. The aim of this study was to investigate the predictors for mortality by using ABI value in patients with CKD and undergoing haemodialysis in Taiwan. METHODS: One hundred and sixty-nine patients with CKD stage 3-5 and 231 haemodialysis patients were enrolled in one regional hospital. The mean follow-up period was 23.3 + or - 3.3 months. Patients were stratified into three groups according to ABI value (<0.9, > or = 0.9 to < 1.3, and > or = 1.3). The relative mortality risk was analyzed by Cox-regression methods. RESULTS: In multivariate analysis, an ABI of 1.3 or more (hazard ratio, 3.846; P = 0.043) and coronary artery disease (P = 0.012) were positively associated with overall mortality, and serum low-density lipoprotein cholesterol level (P = 0.042) was negatively associated with overall mortality. In addition, an ABI of less than 0.9 (P = 0.049), an ABI of 1.3 or more (P = 0.033), coronary artery disease (P = 0.024) and haemodialysis treatment (P = 0.043) were strong predictors for cardiovascular mortality. CONCLUSION: Our findings show that an ABI of 1.3 or more predicts for both overall and cardiovascular mortality, and an ABI of less than 0.9 predicts for cardiovascular mortality in CKD and haemodialysis patients. Screening patients with chronic renal failure by means of ABI may help to identify a high-risk group for increased mortality.

Antiproliferative and antitumorigenic activity of Toona sinensis leaf extracts in lung adenocarcinoma.

Toona sinensis is a traditional Chinese herb, and the extracts of T. sinensis leaf possess a variety of biological functions. This study attempted to test the antiproliferative effect of TSL-1 (a bioactive fraction of T. sinensis) in H441 cells (lung adenocarcinoma). The data showed that the antiproliferative effect of TSL-1 on H441 cells is prominent using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. TSL-1-induced apoptosis was confirmed by cell morphology, sub-G(1) peak accumulation, cleavage of poly(ADP)-ribose polymerase, and propidium iodide-annexin V double staining. Furthermore, decreased Bcl-2 accompanied by increased Bax (in western blotting) was found with TSL-1 treatment of H441 cells. TSL-1 treatment-induced G(1) arrest was concurrent with the down-regulation of protein levels of cyclin D1 and cyclin-dependent kinase 4 in H441 cells. Peroral and intraperitoneal administrations of TSL-1 were performed to evaluate the therapeutic efficacy, and peroral administration of TSL-1 was also used to elucidate the therapeutic efficacy in the H441 cell xenograft model in vivo. The data revealed that TSL-1 treatment inhibited H441 tumor growth in both therapeutic and preventive experiments. Taken together, these results demonstrate that TSL-1 possesses the capability of preventing and alleviating lung cancer proliferation in vitro and in vivo with proven nephrological and hepatic safety and has the potential to be developed as an anti-lung cancer drug.

Medullary thyroid carcinoma with poor differentiation and atypical radiographic pattern of metastasis.

A diagnosis of sporadic medullary thyroid carcinoma (MTC) is complicated. On first diagnosis it may present with distant metastasis. There has been inconsistency regarding metastatic MTC tissue expression of calcitonin, its tumor marker. Adding to the difficulty is the fact that the radiographic pattern of pulmonary metastasis from MTC may vary substantially among patients. Herein is reported the case of a 73-year-old man who presented with two ill-defined pulmonary opacities, clinically resembling primary lung carcinoma. MTC was diagnosed on histopathology of tissue obtained from a total thyroidectomy. The pulmonary biopsy specimens were confirmed to be MTC metastasis on positive immunohistochemical staining of chromogranin-A and synaptophysin, even though only a few cells were stained for calcitonin. To the authors' knowledge this is the first reported case of MTC presenting initially as complex pulmonary metastasis with weakened expression of calcitonin in the metastatic lesion.

Mediastinal hematoma caused by central venous catheterization: a rare cause of obscure blood loss.

Gastrointestinal hemorrhage, internal bleeding beyond the gastrointestinal tract and hemolysis are common causes of blood loss in intensive care unit patients. However, mediastinal hematoma is a rare cause of blood loss and is not usually detected. Here, we report a patient who developed a mediastinal hematoma resulting from central venous catheterization who presented with obscure blood loss refractory to blood transfusion. A mediastinal hematoma should be considered in the presence of obscure blood loss in patients with catheter placement.

Pyrogallol induces G2-M arrest in human lung cancer cells and inhibits tumor growth in an animal model.

Pyrogallol, a catechin compound, is an active component of Emblica officinalis extracts and has an anti-proliferative effect on some human cancer cell lines. In our preliminary study, pyrogallol had highly cytotoxic effect on human lung cancer cell lines and less effect on human bronchial epithelium cell line. This study was performed to investigate the beneficial effect of pyrogallol on human lung cancer cell lines - H441 (lung adenocarcinoma) and H520 (lung squamous cell carcinoma). The MTT (cytotoxic) data showed the inhibition growth of lung cancer cells followed pyrogallol treatment. The cell cycle of lung cancer cells was arrested in G2/M phase using flow cytometry. Using Western blot analysis, the cell cycle related proteins - cyclin B1 and Cdc25c were decreased in a time-dependent manner and the phosphorylated Cdc2 (Thr14) was increased within 4h pyrogallol treatment. Moreover, the higher cleavage of poly (ADP)-ribose polymerase (PARP), the increased of Bax concurrent with the decreased of Bcl-2 indicated that pyrogallol treatment resulted in apoptosis of lung cancer cells. The cell apoptosis was also directly demonstrated using Annexin V-FITC and TUNEL stain. Additionally, the tumoricidal effect of pyrogallol was measured using a xenograft nude mice model. After 5 weeks of pyrogallol treatment could cause the regression of tumor. Taken in vitro and in vivo studies together, these results suggest that pyrogallol can be developed as a promising anti-lung cancer drug particular for the non-small cell lung cancer (NSCLC).

Cocaine-related vasculitis causing scrotal gangrene.

OBJECTIVE: To describe a case of possible cocaine-related vasculitis resulting in gangrene of the scrotum and review the literature on cocaine-related vascular complications. CASE SUMMARY: A 22-year-old male presented with fever, painful swelling of the right scrotum, and a blackened ulcerated lesion on the right scrotum 3 hours after smoking crack cocaine. Blood and urine cultures and serologic tests were negative, and the D-dimer level was normal. Echocardiogram showed no evidence of vegetation and results of a chest X-ray were normal. Despite treatment for presumptive orchitis with intravenous levofloxacin 750 mg/day, the ulcerated lesion of the right scrotum progressed the next day. The patient received debridement of the necrotic tissue and pathology revealed some degenerated vessels with fibrinoid deposits and inflammatory infiltrates, suggestive of vasculitis. No further tenderness and swelling of the scrotum occurred and the patient was discharged after 10 days. When he returned for follow-up, the wound had healed completely. DISCUSSIONS: Cocaine-related vascular complications, including ischemic stroke, myocardial infarction, and peripheral occlusive disease, all of which have various possible mechanisms, are of clinical importance. Vasculitis is one of the mechanisms of vascular complications associated with cocaine use. According to the Naranjo probability scale, cocaine was the possible causative agent of the patient's vasculitis, which led to scrotum gangrene. To our knowledge, this is the first report in the literature of scrotum gangrene developing after crack cocaine was smoked. CONCLUSIONS: This case report describes a rare occurrence of gangrene of the scrotum associated with cocaine smoking, which is consistent with cocaine's potent vasoconstrictive activity. Cocaine abuse has the potential to cause clinically significant ischemic events anywhere in the body, independent of the method of administration.

Significant correlation between ankle-brachial index and vascular access failure in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Vascular access failure (VAF) is associated with increased morbidity and mortality in hemodialysis patients. The most common cause of VAF is stenosis at the arteriovenous anastomosis because of abnormal neointimal proliferation and extracellular matrix deposition. These two changes are also observed in the classic atheroma, which means atherosclerotic lesions and venous stenosis in VAF may share some similar pathogenic mechanisms. The ankle-brachial index (ABI) is a reliable marker for atherosclerosis. The aim of this study was to evaluate the relationship between ABI <0.9 and VAF. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All routine hemodialysis patients in one regional hospital were included except for six patients refusing ABI examinations and four patients with atrial fibrillation. Finally, 225 patients formed our study group. The study subjects were observed from arteriovenous access creation until the first episode of VAF. The mean observation period was 42.2 +/- 42.8 mo. The relative VAF risk was analyzed by Cox-regression methods with adjustments for demographic and comorbid conditions. RESULTS: VAF episodes were recorded in 111 patients. In multivariate analysis, ABI <0.9 (hazard ratio, 1.893; P = 0.039), vascular access type of arteriovenous graft (P = 0.004), and serum triglyceride level (P = 0.043) were positively associated with VAF, and serum parathyroid hormone level (P = 0.043) was negatively associated with VAF. CONCLUSIONS: Our findings show that ABI <0.9 is significantly correlated with increased VAF. Screening hemodialysis patients by means of ABI may help to identify a high-risk group for VAF.

Pulmonary embolism after tadalafil ingestion.

Tadalafil is a phosphodiesterase 5 (PDE5) inhibitor that is used to treat male erectile dysfunction. It is currently undergoing clinical trials for the treatment of pulmonary hypertension. Although at present there is no evidence of hypercoagulation states being associated with the use of PDE5 inhibitors, several studies suggest that PDE5 inhibitors may, in rare cases, cause arterial and venous thrombotic or embolic events in the heart, eye, brain, and ear. We report a 54-year-old male patient with reduced plasma levels of protein C who developed pulmonary embolism (PE) just after he started taking tadalafil. The Naranjo probability scale indicates tadalafil as the possible cause of a PE in our patient. To the best of our knowledge, this is the first case report of tadalafil-induced PE in the literature.

Clinical characteristics of pulmonary tuberculosis patients from a southern Taiwan hospital-based survey.

This study aimed to identify the clinical characteristics of culture-positive pulmonary tuberculosis (TB) patients from a southern Taiwan hospital-based survey between August 1, 2003 and July 31, 2006. Demographics, symptoms, susceptibility patterns, sputum acid-fast bacilli (AFB) stain status and treatment outcomes were recorded. The medical records of 154 patients who presented to the Kaohsiung Municipal Hsiao-Kang Hospital were analyzed retrospectively. The mean age of patients was 59.5 years; 115 patients were male and 39 were female. Diabetes mellitus (48/154; 31.2%) was the most frequent risk factor for pulmonary TB infection. Nearly all patients (139/154; 90.3%) had a cough. Fever was only seen in 27.9% and hemoptysis in 14.9% of patients. The combined resistance rates of Mycobacterium tuberculosis to the tested first-line agents were as follows: isoniazid, 3.2%; rifampin, 7.8%; ethambutol, 5.8%; and streptomycin, 2.6%. The combined resistance rate to any one of four first-line drugs was 12.3%. The combined resistance rate to ofloxacin was 3.9%. The combined resistance rate of multidrug resistant-TB was 1.9%. Sputum AFB stains were positive in 68.2% of cases. Analysis of treatment outcomes showed overall treatment success at 76.6%. The proportions of patients who died, defaulted treatment or in whom treatment failed were 16.2%, 3.9% and 0.0%, respectively. In conclusion, our study showed: (1) a higher frequency of pulmonary TB in male subjects than in other areas of Taiwan; (2) a higher frequency of cough and lower frequency of fever and hemoptysis than previous studies; (3) that the combined resistance rates to isoniazid and streptomycin were lower than both average levels in Taiwan and the global combined drug resistance rate; and (4) a higher proportion of patients responding to treatment and lower proportions of patients suffering mortality, defaulting treatment or not responding to treatment compared with other areas of Taiwan. With regard to resistance rates, the combined resistance rate to ethambutol was similar to the average level in Taiwan and higher than the global combined drug resistance rate. However, the combined resistance rate to rifampin was higher than both the average level in Taiwan and the global combined drug resistance rate. The combined resistance rates to at least any one of four first-line drugs and multidrug resistant-TB were lower than the average levels in Taiwan and higher than the global combined drug resistance rate. Our results may help to identify local variations in the disease and improve the effectiveness of TB infection control programs.

Predictors for identifying the most infectious pulmonary tuberculosis patient.

BACKGROUND/PURPOSE: Clinicians need to decide whether to begin isolation and empiric therapy for patients suspected of having infectious tuberculosis (TB). This study aimed to identify the demographic, clinical and radiographic characteristics of acid-fast bacilli (AFB) smear-positive patients and to create a smear-positive TB prediction rule, which clinicians may use to predict risk. METHODS: This was a retrospective study involving 105 patients with AFB smear-positive TB and 52 patients with AFB smear-negative TB at Kaohsiung Municipal Hsiao-Kang Hospital in southern Taiwan from August 1, 2003 to July 31, 2006. All of the patients had at least one sputum culture that was positive for Mycobacterium tuberculosis. Demographic, clinical and radiographic data of patients with AFB smear-positive TB were compared to those of patients with AFB smear-negative TB. RESULTS: On univariate analysis, young age (p = 0.033), alcoholism (p = 0.036), weight loss (p = 0.003), fever (p = 0.018), consolidation (p = 0.001), infiltration (p = 0.012), cavitary pattern (p = 0.005), right upper lung field (p < 0.001) and left upper lung field (p = 0.001) lesions on chest radiographs were found to be predictive of smear-positive TB patients. In contrast, end-stage renal disease (p = 0.035) and normal chest radiograph (p = 0.006) were predictive of smear-negative TB patients. On multivariate analysis, age less than 65 years (p = 0.004), fever (p = 0.004), right upper lung field (p = 0.044), left upper lung field (p = 0.041), consolidation (p = 0.018) and cavitary (p = 0.049) lesions on chest radiograph were independently associated with an increased risk of an AFB positive smear finding. The smear-positive TB prediction model was created based on the results of the multivariate analysis that had an area of 0.788 under the receiver operating characteristic curve. CONCLUSION: The smear-positive TB prediction model may help clinicians decide if a patient with pending sputum smear results should first be placed in isolation and empiric anti-tuberculous therapy started.