Risk factors of hyperprolactinemia induced by risperidone and olanzapine and their correlations with plasma glucose and lipids

Background Hyperprolactinemia is a common adverse reaction in patients with schizophrenia who take antipsychotic drugs;it often leads to treatment noncompliance in patients and has an adverse effect on their prognosis.Aims This study aimed to explore the risk factors of elevated prolactin(PRL)caused by risperidone(RIS)and olanzapine(OLZ)and the relationship between PRL and fasting plasma glucose and lipids.Methods Patients with schizophrenia were divided into two groups:264 patients who were taking RIS and 175 patients who were taking OLZ.These two groups were further divided according to serum PRL levels:an elevated PRL group(>30ng/mL)and a normal PRL group(PRL<30ng/mL).The demographics,medication dosage,fasting plasma glucose,total cholesterol and triglycerides were compared in the two groups.Logistic regression analysis was performed to explore the risk factors of elevated PRL levels.Results Compared with the OLZ group,the RIS group had a greater number of patients with elevated PRL(155/264 vs 58/175).Either the RIS or the OLZ group,the proportion of elevated PRL was greater in female patients(RIS:x^2=6.76,p=0.009;OLZ:x^2=12.98,p<0.001)and with higher doses of the related drugs(RIS:U=-3.73,p<0.001;OLZ:U=-2.31,p=0.021).In patients taking RIS,the elevated PRL subgroup took the drug for a longer period(U=-2.76,p=0.006)and had lower triglyceride levels(U=2.76,p=0.006).In patients taking OLZ,the elevated PRL subgroup had lower fasting plasma glucose levels(U=2.29,p=0.022).Logistic regression analysis showed that gender,dose and fasting glucose levels were significantly associated with elevated PRL levels(RIS:p=0.001,OLZ:p<0.001;RIS:p<0.001;OLZ:p=0.003;RIS:p=0.020,OLZ:p=0.001,respectively).Conclusion Compared with OLZ,RIS had a greater effect on PRL in patients with schizophrenia,and in patients with schizophrenia taking RIS or OLZ,gender and dose were significantly correlated with the PRL value.Moreover,the plasma glucose level of the group with elevated PRL was lower than that of the group with normal PRL.The results also showed that high serum PRL may be associated with a favourable glucose metabolic profile in patients with schizophrenia taking RIS or OLZ.Further studies are warranted to confirm this association.

Study on risk factors of extrapyramidal symptoms induced by antipsychotics and its correlation with symptoms of schizophrenia

Background Extrapyramidal symptoms (EPS) are one of the most common and neglected side effects during the treatment of schizophrenia. The risk factors of EPS in Chinese patients with schizophrenia and its relationship with psychiatric symptoms and mood symptoms of schizophrenia remain unknown. Aims The main objective of this study is to explore the risk factors of EPS caused by antipsychotics and the relationship between EPS and psychotic symptoms and mood symptoms of schizophrenia. Method This study included 679 patients with schizophrenia who have met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition. Patients were divided into the EPS group and the non-EPS group according to the scale rating criteria and whether the anticholinergics have been used. The differences between demographic data and characters of drug intake were compared between the two groups, and the risk factors of EPS were selected between those factors. Correlation analysis was performed on the severity of schizophrenia (Positive and Negative Symptoms Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS) score) and EPS scale (Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), Abnormal Involuntary Movement Scale (AIMS) score) in 679 patients. The differences between the PANSS subscale score and the CDSS score between the EPS grong and the non-EPS group were compared. Result Compared with the non-EPS group, the EPS group patients are older, and they have a longer duration since first prescribed antipsychotics. The EPS group patients have higher frequency of atypical antipsychotics polytherapy and typical and atypical antipsychotics polytherapy or combined treatments with mood stabilisers. Logistic regression analysis shows that antipsychotics with high D2 receptor antagonistic effect and illness duration are the risk factors of EPS. The SAS score was significantly correlated with PANSS negative score, PANSS general psychopathological score and PANSS total score. The BARS scale score was significantly correlated with PANSS positive score, PANSS general psychopathological score, PANSS total score and CDSS total score. The AIMS scale score was significantly correlated with PANSS negative score. Compared with the non-EPS group, the EPS group patients have significantly higher PANSS negative score, PANSS general psychopathological score, PANSS total score and CDSS total score.

Safety and related factors of treatment with long-term atypical antipsychotic in Chinese patients with schizophrenia:observational study

Background Atypical antipsychotics as first-line drugs have been used in patients with schizophrenia in China and abroad.However,its safety still needs to be evaluated in a large population,especially in Chinese patients.Objective The main objective of this study is to evaluate the safety and related factors of long-term atypical antipsychotic use in patients with schizophrenia in China.The secondary objective includes the long-term efficacy of atypical antipsychotics in these patients,as well as pharmacoeconomic evaluation,population pharmacokinetic studies and pharmacogenomics studies.Methods This study has an observational design.The atypical antipsychotics include quetiapine,olanzapine,risperidone,aripiprazole,ziprasidone,paliperidone,amisulpride,perospirone and clozapine.Visits occur at 0,4,8,13,26,52,78,104,130 and 156 weeks.The efficacy evaluations include symptoms,social function,recurrence rate and hospitalisation.The safety measures include physical examination,vital signs,abdominal circumference,laboratory tests(such as blood cell analysis,blood biochemical tests and serum prolactin/thyroxine levels),12-lead ECG,extrapyramidal syndrome assessment,sexual function evaluation,medication and other adverse events.The secondary measures include the Positive and Negative Syndrome Scale,Clinical Global Impression-Severity of Illness Scale,Calgary Depression Scale for Schizophrenia,Personal and Social Performance Scale,relapse rate,drug consolidation,medical-related expenses,income,drug plasma concentration and genetic information.Results This is a large sample,non-interventional and long-term prospective clinical study designed to truly reflect the specific details of clinical practice,fully respect patients’needs,and understand patients’treatment intentions and actual treatment details.Conclusions This research method details the aims,methods,study design,strengths and limitations of the study.

Correlation of hair risperidone concentration and serum level among patients with schizophrenia

Background Risperidone (RSP) has a rapid onset in vivo, low dosage and high plasma protein binding rate, therefore therapeutic drug monitoring (TDM) is needed to ensure safety in clinical treatment. However, compared with blood, hair is non-invasive, safe, non-infectious and easy to transport and store. Aims This study aims to investigate the correlations among the drug concentrations of RSP in hair and serum, which provides an experimental basis to explore hair as a novel biomaterial to meet the needs of clinical detection. Methods 34 patients with schizophrenia treated with RSP for more than 3 months were enrolled in this study. About 1 cm section of hair near the scalp was taken from the subjects, pretreated and detected by liquid chromatography-mass spectrometry. A correlation analysis was conducted among the drug concentrations in hair, the serum concentrations and the daily dosage. The data were analysed usi叩 SPSS 20.0 software. Results There was significant correlation between the hair concentration of RSP (two-tailed test, r=0.440, p=0.009) with the serum concentration of RSP, and the hair concentration of 9-hydroxyrisperidone (9-HR) with the serum concentration of 9-HR had no significant correlation (two-tailed test, r=-0.217, p=0.217);the total concentration of the RSP and 9-HR had no significant correlation between hair and serum (r=0.227, p=0.196). The dosage had no statistically significant correlation with the concentration of RSP in hair (r=0.207, p=0.241), 9-HR in hair (r=-0.194, p=0.271) and the total concentration of RSP and 9-HR in hair (r=0.188, p=0.288). There was no statistical correlation between the dosage and the concentration of RSP in serum (r=-0.059, p=0.741), but significant correlation between the dosage and 9-HR in serum (r=0.581 p<0.001) was found, and the correlation between the dosage and the total concentration of the two drugs RSP and 9-HR in serum was also significant (r=0.437, p=0.01). Conclusion The correlation analysis showed that the concentration of RSP in hair was statistically significant with the serum RSP concentration. In this study, we provided some experimental basis for hair as a new biomaterial to monitor the therapeutic drug concentration.

A comprehensive review on metallic biomaterials for airway stenosis repair

In recent years,the incidence of airway stenosis in respiratory diseases increases year by year.Among many treatment methods,tracheal stent implantation is a very effective way.Metallic stents have been the first choice for tracheal stent implantation due to their excellent mechanical properties,low rate of migration,and minimal effect on the ciliary movement of the trachea.In this paper,the research progress of metal tracheal stents is introduced in detail from three aspects of mechanical properties,degradation properties,and biocompatibility,including traditional inert metallic tracheal stents and new degradable metallic tracheal stents,and its future research and development are prospected:although the current research on biodegradable metal tracheal stents is still in its infancy,with only some studies of magnesium-based,iron-based,and zinc-based tracheal stents,they are considered as the best material for preparing future metal tracheal scaffolds considering their biodegradability and biocompatibility.

An overview of graphene-based hydroxyapatite composites for orthopedic applications

Hydroxyapatite(HA)is an attractive bioceramic for hard tissue repair and regeneration due to its physicochemical similarities to natural apatite.However,its low fracture toughness,poor tensile strength and weak wear resistance become major obstacles for potential clinical applications.One promising method to tackle with these problems is exploiting graphene and its derivatives(graphene oxide and reduced graphene oxide)as nanoscale reinforcement fillers to fabricate graphene-based hydroxyapatite composites in the form of powders,coatings and scaffolds.The last few years witnessed increasing numbers of studies on the preparation,mechanical and biological evaluations of these novel materials.Herein,various preparation techniques,mechanical behaviors and toughen mechanism,the in vitro/in vivo biocompatible analysis,antibacterial properties of the graphene-based HA composites are presented in this review.

Efficacy of Huadananshen mistura on insomnia: a randomized, double-blind, placebo-controlled, and multi-center clinical trial

OBJECTIVE: To evaluate the effect of Huadananshen mistura in clinical treatment of Chinese patients with insomnia. METHODS: In this randomized, double-blind, placebo-controlled, multi-center study, 244 patients with insomnia were randomly assigned to a placebo group, a low-dose (10 mL/day), or a high-dose (20 mL/day) mistura group. Efficacy was assessed by using the sleep dysfunction rating scale (SDRS) and Clinical Global Impression-Improvement (CGI-I) scores. Safety and tolerability assessments included emergent adverse events, laboratory tests, and electrocardiograms. RESULTS: Total SDRS scores decreased in all three groups, and there were significant differences between the placebo group and the lowand high-dose mistura groups (P=0.000). CGI-I ratings in the lowand high-dose mistura groups were sig-nificantly better than that of the placebo group (P= 0.000). Incidences of rebound insomnia were similar in all three groups (placebo group: 6.94% , low-dose mistura group: 12.99% , and high-dose mistura group: 10.96% ; P=0.475). The efficacy of Huadananshen mistura in the lowor high-dose group was significantly better than that of the placebo group (P=0.000), but with no significant difference found between the lowand high-dose mistura groups (P=0.887). The rates of adverse events were similar in the three groups (placebo 2.44% , low-dose mistura 0%, and high-dose mistura 5%; P=0.088). CONCLUSION: Huadananshen mistura is an effective and generally well-tolerated hypnotic medicine for the treatment of Chinese patients with insomnia.

Fatigue and corrosion fatigue behaviors of biodegradable Zn-Li and Zn-Cu-Li under physiological conditions

Zinc(Zn)alloys are emerging as a new class of biodegradable metallic materials due to their good biocompatibility,suitable biodegradability,and nontoxicity.However,the dynamic loading in the human body,along with the corrosive physiological environment,brings great challenges to the application of biodegradable Zn alloys.At present,there are few reports on the fatigue and corrosion fatigue properties of Zn alloys in simulated body fluid(SBF).In the present work,extruded Zn-0.8Li and Zn-2Cu-0.8Li alloys were selected in order to systematically evaluate their fatigue and corrosion fatigue behaviors both in air at ambient temperature and in SBF at 37℃.Results revealed that the fatigue limits of the extruded Zn-0.8Li and Zn-2Cu-0.8Li alloys were about 135 and 180 MPa,respectively,in air at ambient temperature.However,the fatigue limits of the two alloys decreased to 65 and 80 MPa,respectively,in SBF at 37℃and showed a linear relationship between the corrosion fatigue life and the stress amplitude.The sources of fatigue cracks in air were internal microstructural defects or weak mechanical properties of the material,while the initiation of corrosion pits on the surface was the main reason for the source of the formation of fatigue cracks in SBF.The fracture mode of the extruded Zn-0.8Li and Zn-2Cu-0.8Li alloys was quasi-cleavage fracturing.Compared to static immersion testing,cyclic loading significantly increased the corrosion rates of the two experimental alloys in a corrosion fatigue environment.

Synthesis and in vitro evaluation of Ca-P coating on biodegradable Zn alloys

The burst release of Zn 2+from the naked pure Zn and Zn-based alloys could induce local and sys-temic toxicity,which limits their clinical applications as biodegradable implants.In order to inhibit the explosive release of zinc ions,a protective Ca-P coating was synthesized on biodegradable Zn al-loy.The microstructure,corrosion resistance,antibacterial activity,and biosafety of the Ca-P coating are systematically investigated.Electrochemical tests revealed that Ca-P protective layer has enhanced the anti-corrosion behavior of Zn alloy.Furthermore,Ca-P protective layer showed good biocompatibility,as demonstrated by significantly increased cell viability,good attachment,and spreading at a higher cell density.Besides,the Ca-P coating could also retain the antibacterial ability and inhibit the bacterial ad-hesion.The Ca-P protective layer synthesized on biodegradable Zn alloy can be considered and applied in future biomedical applications.