From pipeline to patient: new developments in cystic fibrosis therapeutics

Introduction: Cystic fibrosis (CF) is an inherited rare disease characterised by recurrent pulmonary infection, pancreatic malabsorption and a number of other multisystem effects. In the past few years new drugs specifically designed to treat CF have entered the pipeline, and some are now used in clinical practice.

Areas covered: Clinical trial results from CF trials reported or ongoing within the last 3 years are discussed. A literature and trials registry search of trials and meta-analyses involving patients with CF was conducted, from which the most exciting developments were selected.

Expert opinion: Drugs to address the basic defect in CF have finally come to market, albeit for a limited number of patients with a specific genotype. Traditional areas of CF therapeutics continue to be developed, with modest success, including drugs to modulate the airway surface liquid, new pancreatic supplements, antibiotics and new treatments for endocrine complications of CF.     

The role of particle physico-chemical properties in pulmonary drug delivery for tuberculosis therapy

Abstract

There is increasing interest in the use of inhaled aerosol drug therapy for the treatment of tuberculosis (TB). A number of methods of preparation of particles have been employed including spray drying, solvent evaporation, emulsion and phospholipid methods to create microparticles, macroaggregated nanoparticles, solid lipid nanoparticles and liposomes. Each of these methods involves the use of different proportions of additives to aid in the particle formation or to achieve important physico-chemical properties such as ease of dispersion. While these approaches all have merit their practical value is limited by constraints on dose and means of delivery as an aerosol in order to achieve a therapeutic effect. A review of a number of approaches is presented and placed in the context of the need for effective aerosol delivery systems for the treatment of TB as a guide to selection of appropriate excipients, processes and delivery strategies to support product development activities.     

Evaluating cardiac substructure radiation exposure in breast rotational intensity modulated radiation therapy: Effects of cancer laterality,fractionation and deep inspiration breath-hold

PurposeRotational intensity-modulated radiation therapy currently has a growing role in breast cancer radiation therapy, since this radiation technique reduces cardiac radiation exposure while homogeneously covering target volumes. This study aims to evaluate radiation exposure of cardiac substructures across a broad spectrum of breast cancer cases differing by cancer laterality, fractionation regimen and addition of deep-inspiration breath hold.Materials and methodsCardiac substructures were delineated following guidelines endorsed by the European Society for Radiotherapy and Oncology (ESTRO) for forty-four breast cancer patients having undergone conserving surgery and adjuvant rotational intensity-modulated radiation therapy. Target volumes consisted of the whole breast with a boost, axillary and internal mammary nodes. Patients were treated using free-breathing technique for left-sided or right-sided, normofractionated or hypofractionated helical tomotherapy or volumetric modulated arc therapy, or using deep-inspiration breath hold for left-sided normofractionated volumetric modulated arc therapy. Mean and maximum doses to cardiac substructures were retrieved. Correlations were performed between mean- and maximum radiation doses to cardiac substructures.ResultsLeft-sided and right-sided irradiations were associated with different cardiac substructure exposure patterns despite comparable mean heart dose: 7.21 Gy for left-sided normofractionated regimen, 6.28 Gy for right-sided normofractionated regimen. Deep-inspiration breath hold reduced mean doses to almost all cardiac substructures for left-sided irradiation, but did not decrease maximum doses to coronary arteries. Correlations between mean- and maximum doses to cardiac substructures were usually moderate, but stronger for right-sided irradiation.ConclusionDespite comparable mean heart dose, cardiac substructure radiation exposure patterns with rotational intensity-modulated radiation therapy strongly depend on the breast side, which could trigger clinically different long-term cardiotoxicity events. Deep-inspiration breath hold improves cardiac substructure dosimetry. Mean- and maximum heart dose could probably not be used as surrogate markers for precise cardiac substructure evaluation. In a near future, clinical practice and cardiotoxicity studies could possibly gain by considering cardiac substructure in a more systematic manner, possibly relying on cardiac autosegmentation algorithms.     

三种方法测定地面游离蚤的效果观察

目的比较水盘法、粘蚤纸法及粘蝇板法等三种方法现场测定地面游离蚤的效果。方法选择云南省景洪市景讷乡4个村54户家庭作为研究对象,其中2个村同时布放水盘及粘蚤纸,另外2个村同时放置水盘及粘蝇板测定地面游离蚤,分别计算不同方法对地面游离蚤的捕获率,并进行结果比较。结果同时布放粘蚤纸及水盘的勐混和小寨,粘蚤纸法和水盘法的捕获率分别为44.50%(283/636)和80.85%(494/611),两种方法对地面游离蚤的捕获率差异有统计学意义(χ2=175.33,P0.01);同时布放粘蝇板及水盘的大寨和新寨,粘蝇板法及水盘法捕获率分别为54.06%(353/653)和69.78%(448/642),捕获率测定结果差异有统计学意义(χ2=33.09,P0.01)。不同村寨水盘法的捕获率80.85%(494/611)和69.78%(449/642),与粘蚤纸法和粘蝇板法的捕获率44.50%(283/636)和54.06%(353/653)交叉比较,差异有统计学意义(χ2=83.40,P0.01和χ2=102.48,P0.01)。分别布放在不同村寨的粘蚤纸及粘蝇板对地面游离蚤的捕获率44.50%(283/636)和54.06%(353/653),差异有统计学意义(χ2=11.78,P0.01)。结论水盘法对地面游离蚤的收集效果明显优于粘蚤纸法及粘蝇板法,粘蝇板法虽然捕获率优于粘蚤纸法,但实际应用中存在缺点。水盘法更适合在基层鼠疫监测工作中使用。     

Association of heart rate and diabetes among 0.5 million adults in the China Kadoorie biobank: Results from observational and Mendelian randomization analyses

Background and aimsObservational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults.Methods and resultsThe China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]).ConclusionsThis study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation.     

Development of a neonatal incubator with phototherapy,biometric fingerprint reader,remote monitoring,and heart rate control adapted for developing countries hospitals

This paper aims to develop an automatic neonatal incubator equipped with phototherapy, biometric fingerprint reader, remote monitoring and heart rate control modules for developing countries due to the lack of neonatal incubators. The proposed device consists of an acquisition module that senses temperatures (of the enclosure and the baby) and humidity, a biometric fingerprint reader to identify the user, a remote monitoring module in charge of supervising the temperature and the heart rate of the baby, a video surveillance module which allows filming and transmitting the images to the web server in order to give parents and nurses the possibility of being able to visualize whatever their location the newborn baby, a phototherapy module used to treat newborn jaundice by lowering the bilirubin levels in the baby's blood, a digital control module from a pulse width modulation (PWM) signal generated by a microcontroller of Arduino Nano type for system operation monitoring, and a human machine interface module for setting parameters. The equations describing the energy balance and heat transfer for newborn baby (Ostrowski and Rojczyk, 2018) are taken into account for the implementation of power supply and the choice of the heating resistor. The desired temperature of 37 °C was obtained after only a few minutes inside the incubator.     

耳石复位与药物联合仰卧位摇头法治疗主观性良性阵发性位置性眩晕临床研究

目的:观察耳石复位与药物联合仰卧位摇头法治疗主观性良性阵发性位置性眩晕(S-BPPV)的效果。方法:选取2012年1月至2016年1月期间符合纳入标准的S-BPPV患者186例,采用随机数字表法将患者分为观察组与对照组各93例,对照组采用耳石复位联合药物治疗,观察组在对照组基础上采用仰卧位摇头法治疗。比较两组患者临床疗效、首次治疗成功率、中转手术治疗率、复发率与不良反应发生率的差异。结果:与对照组比较,观察组治疗总有效率、首次治疗成功率明显增高,中转手术治疗率与复发率明显降低,差异具有统计学意义(P0.05);两组中共18例患者经外科手术治疗后症状彻底消失;随访3个月期间,观察组平均复发次数与对照组比较差异具有统计学意义(P0.05);两组患者头晕、恶心呕吐、心律失常、走路不稳与情感障碍等不良反应发生率比较差异无统计学意义(P0.05)。结论:耳石复位与药物联合仰卧位摇头法治疗S-BPPV效果显著,可降低复发率,且未增加不良反应的发生风险。     

鲍曼不动杆菌对多黏菌素类抗菌药物耐药现状及机制研究进展

多黏菌素类抗菌药物是多重耐药鲍曼不动杆菌的最后防线，但随着临床对多黏菌素类药物使用增多，鲍曼不动杆菌对其耐药的报道也陆续出现，相关耐药机制的研究成为热点。本文对近年来国内外鲍曼不动杆菌对多黏菌素类耐药报道以及耐药机制研究进行综述，以期对临床合理应用多黏菌素类抗菌药物、保持其抗菌活性提供参考。