Treatment of Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review of Economic Evaluations

The management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been significantly modified by the availability of innovative but expensive treatments, increasing the economic burden of prostate cancer. Here, we aimed to systematically identify and review published economic evaluations (EEs) related to the treatment of mHSPC and assess their quality. A systematic search was performed of the PubMed and Cochrane databases. Three reviewers independently selected EEs by defined inclusion and exclusion criteria. They extracted all data from each EE (general information, study population, data about the EE, interventions and comparators, and outcomes). They also assessed the quality of the selected EEs according to Drummond's checklist. Fourteen EEs published between 2016 and 2021 were eligible for the systematic review. The EEs found ADT + docetaxel to be the most cost-effective of all available treatments as a first-line strategy for mHSPC (abiraterone acetate plus prednisone, enzalutamide, and apalutamide). Five EEs showed that a simple price reduction of abiraterone acetate of 50% to 75% could change the results to render this treatment also cost-effective relative to that with docetaxel. Twelve EEs were of high quality, with a Drummond score ≥ 7. Analysis of the 14 EEs identified by our systematic review, amongst which 78.6% met high quality standards, showed that ADT + docetaxel tends to be the most cost-effective alternative for mHSPC. These results were assessed by sensitivity analysis. The data provided by this systematic review help to provide a better understanding of these treatments and the better use of healthcare resources.     

European Rabbits as Reservoir for Coxiella burnetii

We studied the role of European rabbits (Oryctolagus cuniculus) as a reservoir for Coxiella burnetii in the Iberian region. High individual and population seroprevalences observed in wild and farmed rabbits, evidence of systemic infections, and vaginal shedding support the reservoir role of the European rabbit for C. burnetii.     

Detecting clinically related content in online patient posts

Patients with chronic health conditions use online health communities to seek support and information to help manage their condition. For clinically related topics, patients can benefit from getting opinions from clinical experts, and many are concerned about misinformation and biased information being spread online. However, a large volume of community posts makes it challenging for moderators and clinical experts, if there are any, to provide necessary information. Automatically identifying forum posts that need validated clinical resources can help online health communities efficiently manage content exchange. This automation can also assist patients in need of clinical expertise by getting proper help. We present our results on testing text classification models that efficiently and accurately identify community posts containing clinical topics. We annotated 1817 posts comprised of 4966 sentences of an existing online diabetes community. We found that our classifier performed the best (F-measure: 0.83, Precision: 0.79, Recall:0.86) when using Naïve Bayes algorithm, unigrams, bigrams, trigrams, and MetaMap Symantic Types. Training took 5 s. The classification process took a fraction of 1 s. We applied our classifier to another online diabetes community, and the results were: F-measure: 0.63, Precision: 0.57, Recall: 0.71. Our results show our model is feasible to scale to other forums on identifying posts containing clinical topic with common errors properly addressed.     

Modulation of cardiac impulse generation and conduction by nifedipine and verapamil analyzed by a refined surface ECG technique in Langendorff perfused guinea pig hearts

Summary Using a modified Langendorff system, a special ECG recording technique and appropriate placement of two silver wire electrodes, early atrial and His bundle activity can be detected continuously from the surface of intact and spontaneously beating guinea pig hearts. This new method was applied to measure the direct and inhibitory effects of nifedipine and verapamil on impulse generation and conduction in isolated and perfused guinea pig hearts. Depression of sinoatrial conduction was the most prominent effect of nifedipine. In all concentrations applied (10^–7 M, 10^–6 M, 10^–5 M) nifedipine predominantly led to sinoatrial blocks of different degrees. Heart rate decreased slightly in a dosedependent manner. PQ and HV duration remained essentially constant. In the highest concentration of nifedipine (10^–5 M), sinus node activity was so depressed that AV dissociation or ventricular rhythm developed. Only in one out of eight experiments with cumulative increase of nifedipine concentrations to 10^–5 M was the AV node affected by nifedipine and a second-degree AV block developed (10^–6 M).Verapamil's inhibitory effects on the rate of impulse initiation in the sinus node were more pronounced than those of nifedipine, but the inhibition of sinoatrial conduction by verapamil was less marked. At 10^–6 M verapamil, the incidence of sinoatrial blocks and of ventricular rhythm was similar to the incidence of first degree AV blocks. PQ time (+14%) but also HV time (+12%) were prolonged under the influence of this concentration of verapamil. At the highest concentration of verapamil (10^–5 M) applied for 10 min, ventricular rhythm developed in five out of eight experiments, as well as one second and two third-degree AV blocks.The results confirm that the simultaneous measurement of sinus node activity of sinoatrial and atrioventricular conduction and of HV duration is feasible with this ECG technique, to evaluate the inhibitory effects of Ca-antagonists on sinus and AV node activity in the intact heart.Research scholarship of the Ministry for Science and ResearchPreliminary results were published at the Jahrestagung der Dt. Gesellschaft für Pharmakologie und Toxikologie (Naunyn-Schmiedeberg's Archives of Pharmacology)Supported by a grant of the Ministry for Science and Research, Program for the Reduction of Animal Experiments, Austria     

Evaluation of PyroMark Q24 pyrosequencing as a method for the identification of mycobacteria

We evaluated PyroMark Q24 (QIAGEN) pyrosequencing as a method for the identification of mycobacteria, with potential application in clinical practice. Sequence data from the hypervariable region A of the 16S rRNA gene (43 and 35 bp sequences) were obtained using PyroMark Q24, and a similarity search was performed automatically with PyroMark IdentiFire software. Of the 148 mycobacterial type strains tested, 138 (93.2%) were accurately identified to single or clade species level, including complex level. From the remaining 10 strains, 3 (Mycobacterium gilvum, Mycobacterium goodi, and Mycobacterium thermoresistible) showed poor sequencing quality of homopolymers. For 6 other strains (Mycobacterium cosmeticum, Mycobacterium flavescens, Mycobacterium pallens, Mycobacterium hodleri, Mycobacterium xenopi, and Mycobacterium crocinum), the sequences were unreadable from the middle, and Sanger sequencing indicated biallelic site. Finally, a 40 bp sequence for Mycobacterium gordonae could not be obtained despite repeated attempts. PyroMark Q24 provided accurate identification of multiple mycobacterial strains isolated from common clinical settings, but additional gene sequencing is required to distinguish species identified as a group or complex.     

1例Q热肺炎诊治报告北大核心CSCD

Q热是一种重要的人兽共患病,病原体为贝氏柯克斯体(Coxiella burnetii),其经呼吸道吸入进入体内,引起急性Q热,严重急性Q热可出现肺炎、肝炎或心肌炎并发症。部分患者治疗不彻底转为慢性Q热。慢性Q热为贝氏柯克斯体在机体局部持续感染,常需要外科手术及数年抗感染治疗,其严重危害患者身体健康及加重家庭经济负担;。追其原因是临床医生对该病认识不足,导致延误治疗所致。本文旨在报告1例Q热肺炎的诊治和体会,以提高临床医生对该病认识。     

Q808抗鼠最大电休克发作癫痫活性及其作用机制

目的观察Q808抗鼠癫痫活性及其作用机制。方法选取合格大鼠70只随机等分为7组,分别为模型对照组、托吡酯片20 mg/kg、丙戊酸钠100 mg/kg、苯妥英钠35 mg/kg、Q808高剂量60 mg/kg、Q808中剂量30 mg/kg、Q808低剂量15 mg/kg。灌胃给药1次,体积均为20 ml/kg,模型对照组给予同体积0.5%羧甲基纤维素钠(CMC-Na)。大鼠于给药后1、2、4、6、8、10、12 h各刺激1次。合格小鼠70只随机等分为7组,分别为模型对照组、托吡酯片25 mg/kg、苯妥英钠40 mg/kg、丙戊酸钠150 mg/kg、Q808高剂量80 mg/kg、Q808中剂量40 mg/kg、Q808低剂量20 mg/kg。灌胃给药1次,体积均为20 ml/kg,模型对照组给予同体积0.5%CMC-Na。小鼠于给药后1、2、4、6、8、10、12、24 h各刺激1次。大鼠于给药后1、2、4、6、8、10、12 h各刺激1次。以出现后肢强直性惊厥为观察指标,计算惊厥率。取雄性大鼠15只,分为两组,自发性兴奋性突触后电流(sEPSC)组6只,抑制性突触白电位(sIPSC)组9只。采用大、小鼠最大电休克发作(MES)癫痫模型和戊四唑、3-巯基丙酸诱发小鼠惊厥,观察其抗癫痫活性;采用高效液相色谱(HPLC)法分析大脑不同区域神经递质含量、采用膜片钳技术观察海马脑片CA1区椎体细胞和原代培养神经元上脑内γ氨基丁酯(GABA)电流,探讨其作用机制。结果灌胃给予大鼠60 mg/kg、小鼠80、40 mg/kg Q808后1 h即具有明显的抗MES作用,可持续作用12 h,且无种属差异;同时Q808能明显延长小鼠化学物质诱发惊厥模型的惊厥潜伏期、降低强直率、死亡率及发作级别。HPLC分析表明灌胃大鼠Q80860、30 mg/kg提高了海马GABA含量,降低了丘脑谷氨酸及谷氨酰胺含量,但对皮层神经递质没有明显作用。脑片电生理研究表明,Q808能增强海马脑片CA1区椎体细胞sIPSC频率,而对sIPSC幅值、sEPSC频率及幅值和原代培养神经元上GABA受体介导的电流没有明显影响,提示Q808可能通过提高突触间GABA递质释放频率发挥抗癫痫作用,而不影响GABA受体功能。结论Q808对MES癫痫发作及化学物质诱发的惊厥均具有明显的抗癫痫活性,其作用机制可能与增强脑内海马sIPSC频率和增加GABA含量有关,而与GABA受体功能无关。     

肥厚型心肌病的心电图改变

目的 探讨肥厚型心肌病患者心电图变化及其临床意义。方法 对44例肥厚型心肌病(Ⅰ型前间隔肥大14例，Ⅱ型前间隔、后间隔均肥大18例，Ⅲ型左心室前壁或／和侧壁、后壁肥大7例，Ⅳ型心尖部肥大5例)行常规12导联心电图检查。结果 心电图异常(ST-T改变、异常Q波、心室肥大等)发生率为93．2％。Ⅳ型ST-T改变多见于前侧壁、高侧壁，具有特殊性。其它三型患者异常Q波、ST-T改变发生率及部位差异均无显著性意义。结论 肥厚型心肌病患者大多存在不同程度的心电图异常，但除心尖肥厚型心肌病外，其他各型心电图改变无特异性。