Emerging drugs for the treatment of cocaine use disorder: a review of neurobiological targets and pharmacotherapy

Introduction: Cocaine use is a global public health concern of significant magnitude, negatively impacting both the individual as well as larger society. Despite numerous trials, the discovery of an effective medication for treatment of cocaine use disorder remains elusive.

Areas covered: This article reviews the emerging pharmacotherapies for treatment of cocaine use disorder, focusing on those medications that are currently in Phase II or III human clinical trials. Articles reviewed were obtained through searches of PubMed, Ovid MEDLINE, Clinicaltrials.gov and the Pharmaprojects database.

Expert opinion: Research into cocaine pharmacotherapy must continue to show innovation. Given that medications targeting single neurotransmitter systems have demonstrated little efficacy in treatment of cocaine use disorder, the recent focus on pharmacotherapeutic agents with multiple neurobiochemical targets represents an exciting shift in trial design and approach. Additionally, consideration of pharmacogenetics may be helpful in identification of subpopulations of cocaine-dependent individuals who may preferentially respond to medications.     

Emerging drugs for the treatment of perennial allergic rhinitis

Introduction: Allergic rhinitis is a worldwide health problem, currently affecting up to 40% of the general population, and characterized by the following symptoms in a variable degree of severity and duration: nasal congestion/obstruction, rhinorrhea, itchy nose and/or eyes, and/or sneezing. General symptoms like fatigue, reduced quality of sleep, impaired concentration and reduced productivity, if left untreated, may significantly affect quality of life. In addition, of being associated to various comorbidities, allergic rhinitis is also an independent risk factor for the development and worsening of asthma. Perennial allergic rhinitis is caused by allergens present around the year.

Areas covered: Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines currently recommend a stepwise therapeutic approach that combines patient education with specific allergen avoidance, symptomatic pharmacotherapy and allergen immunotherapy. The available treatment strategies provide suboptimal symptom relief in patients with moderate-to-severe disease who continue to experience symptoms while treated, even on multiple therapies.

Expert opinion: New insights into current therapy have been provided with the development of new symptomatic drugs with improved pharmacokinetics and safety. However, the ultimate research goal is beyond symptomatic treatment, and is mainly directed at modifying the immune response to allergens and prevent the progression of allergic rhinitis towards asthma. In this direction, promising advances are expected in the fields of allergen immunotherapy and biological drugs, such as omalizumab. Finally, significant research efforts are also focused on the growing number of new specific molecular targets involved in the Th₂ pathway inflammation of allergic diseases.     

结核病疫苗研究现状

此文介绍了自2015年实施《WHO终止结核病策略（2016—2035）》以来的全球结核病状况,结核病疫苗研究的挑战和建议,以及结核病疫苗技术、临床前研究和临床试验的最新进展。     

Challenges of using new and repurposed drugs for the treatment of multidrug-resistant tuberculosis in children

Introduction: New and repurposed antituberculosis drugs are urgently needed to more safely and effectively treat multidrug-resistant (MDR) tuberculosis (TB) in children. Multiple challenges limit timely access to new MDR-TB treatments in children.

Areas covered: Diagnosis of MDR-TB in children remains a barrier, with few children with MDR-TB diagnosed and treated. Other barriers to timely access to new and repurposed drugs are discussed, and include delayed initiation of paediatric trials, limited funding for paediatric drug development, fragmented regulatory systems and operational challenges. The status of access to current repurposed and novel drugs is presented.

Expert commentary: More timely initiation of paediatric trials is needed and paediatric work should happen and be funded in parallel with each phase of adult trials. Better quality data, increased regulator resources and expertise, harmonization of regulatory requirements across borders/organisations and registration fee waivers would improve registration timelines. Improved diagnosis, recording and reporting will establish better demand. Improved systems for procurement and supply chain management would reduce in-country operational barriers to getting medications to children. The challenges must be addressed to ensure timely and equitable access to new drugs and regimens that are urgently needed for effective, safe and shorter treatment of children with MDR-TB.     

联用左氧氟沙星治疗涂阳重度肺结核病的疗效分析

目的分析新型抗结核药物左氧氟沙星联合其他抗结核药物治疗重度肺结核患者的治疗效果和安全性。方法对100例重症肺结核患者采用1∶1随机、平行对照的方法,分为左氧氟沙星治疗组(治疗组)和常规治疗组(对照组),完成6个月疗程后,随访2年,进行统计分析。结果治疗组和对照组的痰菌阴转情况、药物不良反应情况差异无统计学意义;胸部X线显示病灶吸收率治疗组和对照组的差异有统计学意义,治疗2月末为72%和46%,(χ2=9.24,P<0.01);治疗6月末为78%和52%,(χ2=7.428,P<0.01)。结论初治涂阳的重症肺结核患者可考虑联用左氧氟沙星抗结核治疗,提高治疗效果。     

Emerging drugs and drug targets against tuberculosis

Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, uses various tactics to resist on antibiotics and evade host immunity. To control tuberculosis, antibiotics with novel mechanisms of action are urgently needed. Emerging new antibiotics and underlying novel drug targets are summarized in this paper.     

Genetic immunisation and treatment of disease

Alternative approaches to the more traditional treatments of cancer, allergies and autoimmune diseases are being pursued. In addition, new modes of vaccination are under development. DNA delivery (genetic immunisation) is among the new technologies being investigated. This technique of injecting DNA induces both cellular and humoral responses, can lead to active protein production in vivo and is highly adaptable to the requirements of the condition being targeted. The genes can be delivered such that the immune responses can be polarised to either a Th1 or Th2 phenotype. The manipulation of the immune response can be accomplished by a variety of methods including mode of delivery and use of cytokine genes. Delivery of DNA directly to a host has a great deal of potential with regard to therapy and vaccine development. This potential is apparent based on the extensive number of patents which have been awarded over the past three years.     

Emerging drugs in migraine treatment

Ergot alkaloids have been the mainstay of acute migraine therapy for most of the 20th century. They have been supplanted by sumatriptan-like drugs (‘triptans’), which, while keeping some of the ergots’ mechanisms of action, show improved safety profiles due to their increased receptor selectivity. However, triptans are still far from being perfect drugs: they can constrict human coronary arteries at therapeutic doses and, therefore, are contra-indicated in the presence of cardiovascular disease. Another problem with these agents is recurrence of moderate-to-severe pain within 24 h of initial headache relief. While mechanism-driven drug design has led to the development of various novel, albeit still imperfect, acute antimigraine medications, only a few new prophylactic agents have been made available to migraine clinicians. The efficacy of most, if not all of them has been discovered serendipitously. This is probably due to the fact that, while the pathophysiology of a migraine attack is now reasonably understood, the mechanisms leading to an attack are still mostly unknown. This update analyses the profile of some antimigraine drugs in clinical trials, their mode of action and their potential advantages or drawbacks over already available agents.     

南京市结核病流行病学调查分析

目的 调查2000年－2001年南京市人群结核病患病率、儿童结核免疫水平、死亡率；并对近年来南京市结核病防制规划执行情况和结核病项目实施效果进行评价；了解南京市结核病的流行状况和人群危害程度，为制订未来几年南京市结核病预防控制规划提供科学依据。方法 采用分层整群随机抽样方法，在南京市江宁区农村、溧水县农村、鼓楼区、六合县农村、哺口区城郊共抽样调查8051人。结果 南京市结核病患病率为522．4／10万；肺结核患病率为509．6／10万，男女比为2．33：1，涂阳患病率为216．6／10万，菌阳患病率为293．0／10万，空洞性患病率为63．7／10万；儿童结核菌素试验（PPD）阴性反应为69．2％，强阳性反应为12．8％；死亡率为12．2／10万；62．5％的肺结核病人为本次流调新发现，已知肺结核病人的治理管理率为53．3％。结论 本次调查初步了解了南京市结核病的流行情况，有关资料及其研究分析结果为政府制订控制结核病流行的决策和相关研究提供了科学依据。     

Investigational drugs in phase II clinical trials for the treatment of neuroblastoma

Introduction: Neuroblastoma (NB) is an embryonal tumor originating from undifferentiated neural crest cell, highly heterogeneous ranging from spontaneous regression to progression despite multimodal treatments. Approximately, 20% of patients are refractory to frontline therapy and 50% will relapse/progress after an initial response. The overall five year survival for high-risk neuroblastoma ranges from 35–45%. Despite enhanced understanding of NB biology and the addition of myeloablative chemotherapy, isotretinoin and immunotherapy, survival for high risk NB remains less than 50%.

Areas covered: This review summarizes and gives a critical overview of phase II trials investigating therapies for relapsed-refractory and high risk neuroblastoma.

Expert opinion: Several novel molecules have been developed and are currently under investigation for the treatment of NB. The trend of novel targeted agents is one towards individualized, tailored therapy, based on the molecular and biological differences that characterize tumors that seem similar based solely on histological analysis. The task of developing new molecules is particularly difficult for NB, given the recurrent development of new patterns of drug resistance. However, even if current research is focused towards identifying the best treatments for each children and young adult with a NB defined disease, a deeper knowledge of the molecular biology and genetics is needed.     

亚硒酸钠联合抗痨药治疗HBV感染的肺结核病人临床研究

目的 探讨亚硒酸钠联合抗痨药治疗HBV感染的肺结核病人的疗效及对肝功能的影响。方法 将病人随机分为联合抗痨组和单纯抗痨组，定期观察临床症状，体征，胸部影像学改变及痰菌含量变化，并检测肝功能指标。结果 联合抗痨组有效率为91．7％，单纯抗痨组为79．0％（P＜0．05）；联合组肝损害率为11．7％，单纯组为25．8％（P＜0．05）。结论 亚硒酸钠联合抗痨药治疗肺结核优于单纯抗痨药物治疗，且亚硒酸钠具有保肝作用。     

Emerging intravesical drugs for the treatment of non muscle-invasive bladder cancer

Introduction: Bladder cancer (BC) is a severe health burden: and has high recurrence and progression rates. Standard treatment starts with TURB followed by intravesical chemotherapy with Mitomycin C or immunotherapy with BCG. However, successful management still remains a challenge, because approximately 30% of patients have recurrence or progression within 5 years, and treatment has considerable side effects. Anticipating on the upcoming BCG shortage emphasizes, moreover, the necessity to develop and study novel treatments. This review explores emerging and novel salvage treatments as well as approaches of current treatments with decrease side-effects for non muscle-invasive bladder cancer (NMIBC).

Areas covered: In this review, the authors provide an overview of the novel and emerging therapies for NMIBC. They also provide the currently available data and ongoing trials.

Expert opinion: Key findings in the field of research on emerging intravesical drugs for the treatment of NMIBC are the promising results for device assisted treatments, treatment with intravesical immunotherapy, and treatments to expedite the immunotherapy checkpoint inhibitors. Other novel therapies are still in an experimental stage and have to make the transition towards the clinical setting to determine the benefit in terms of reduced side-effects, recurrence and progression rates.     

经纤支镜灌注治疗难治性肺结核

目的探讨经纤支镜灌注治疗难治性肺结核的治疗价值。方法61例难治性肺结核住院患者随机分为治疗组31例及对照组30例。治疗组强化期采用纤支镜灌注治疗加全身化疗,对照组只进行全身化疗。对比观察两组疗效。结果强化期结束时,经纤支镜灌注治疗组症状明显改善93.54%,痰菌阴转率87.09%,病灶显著吸收率64.51%,明显高于单纯化疗组的63.33%、46.66%、36.66%(P<0.01～0.05)。结论经纤支镜灌注治疗难治性肺结核疗效显著,且无并发症及明显毒副反应,值得进一步推广使用。     

Effect of immunotherapy in bronchial asthma: treatment with mite extract adsorbed on tyrosine

Summary

A trial was carried out in 18 asthmatic patients to assess the effectiveness of a vaccine of house dust mite extract (Dermatophagoides pteronyssinus) adsorbed on tyrosine. Patients were initially given 6 graduated doses of the vaccine subcutaneously at 7-day intervals. Maintenance injections were then given at 2-week intervals, the total dose being determined by clinical response.

About 66% of the treated patients showed a significantly beneficial response to immunotherapy as assessed by symptomatic improvements. Seventy-two per cent of the patients required less oral anti-asthmatic therapy and 50% of the patients had a demonstrable increase in blocking antibodies. Local reactions were not severe and occurred infrequently. None of the patients developed systemic reactions to immunotherapy. Clinical response was found to depend to some extent on the dosage of antigen administered and rise in blocking antibodies of the patient's serum.     

含左氧氟沙星抗结核方案对复治肺结核的治疗研究

目的　探讨左氧氟沙星用于复治肺结核的有效性和安全性。方法　对 6 2例 (31对 )复治肺结核进行了同期对照配对研究。其中治疗组为含左氧氟沙星的抗结核方案。结果　抗结核治疗 2个月 ,治疗组痰菌阴转率 (92 .80 % )显著高于对照组 (4 2 .8% ,P<0 .0 5 ) ,但抗结核治疗 4、6、9个月则无显著差异 (P>0 .0 5 )。抗结核治疗 2、6、9个月 ,治疗组和对照组空洞闭合率、肺部病变明显吸收率均有显著差异 (P<0 .0 5 )。结论　含左氧氟沙星的抗结核方案用于复治肺结核安全有效。     

Emerging strategies in the diagnosis,prevention and treatment of chlamydial infections

Chlamydial infections cause a spectrum of diseases affecting millions of individuals worldwide. Chlamydia trachomatis is the most common sexually transmitted bacterium and the causative agent of trachoma, the leading cause of preventable infectious blindness in the world. The unique intracellular life-cycle and the chronic, persistent nature of chlamydial infections have hindered efforts to develop optimal diagnostic, preventive and treatment strategies for these pathogens. The reported association of C. pneumoniae with atherosclerosis and adult onset asthma suggests that these organisms may play an important role in the aetiology of chronic diseases. Treatment options involving new classes of antibiotics or new versions of existing antibiotics that may provide greater specificity and utility for long-term use against chlamydiae are much needed. In addition, new combinations of therapies are needed to manage existing chronic conditions and at the same time to alleviate any role that chlamydiae could be playing in these conditions. Novel strategies that address these shortcomings are apparent in recent research efforts. This review summarises patent claims of emerging strategies to diagnose, prevent and treat chlamydial infections. In addition, current efforts to develop suitable vaccine candidates are highlighted.     

Emerging drugs in the treatment of pancreatic cancer

Background: Pancreatic cancer is the fourth leading cause of cancer-related death in the US. However, there is a growing belief that novel biological agents could improve survival of patients with this cancer. Gemcitabine-based chemotherapy remains the cornerstone treatment for advanced pancreatic cancers. So far, the current targeted agents that have been used in combination with gemcitabine have failed to improve clinical outcomes. This failure may stem from the heterogeneous molecular pathogenesis of pancreatic cancers, which involves several oncogenic pathways and defined genetic mutations. Objective: The aims of this review are: i) to define the existing treatments available at present for patients with pancreatic cancers in the neo-adjuvant, adjuvant, locally advanced and metastatic settings; ii) to highlight the molecular heterogeneity of the cancers and the rationale for targeting specific oncogenic pathways; iii) to give an overview of targeted agents that may potentially have an impact in the treatment of pancreatic cancers. Conclusions: Molecular pathogenesis of pancreatic cancer involves several pathways and defined genetic mutations. Targeting these complex molecular pathways with a combination of novel biological and chemotherapeutic agents could potentially improve patient outcome.     

黄精汤及制剂治疗肺结核和耐药性肺结核临床研究

目的：观察黄精汤及制剂治疗肺结核和耐药性肺结核的疗效。方法：新诊108例患者随机分为黄精汤及制剂组（治疗组57例）和2ERHZ/4RH化疗组（对照组51例）,45例耐药患者为耐药治疗组（治疗方法同治疗组）,观察3组治疗后肺部病灶、血沉、PPD试验、痰菌检、肝肾功能及主要症状体征的变化和安全性。结果：3组患者治疗后证候积分较之治疗前均明显减少（P〈0.01）。治疗组、耐药治疗组症状疗效、临床疗效与对照组等效性比较差异有统计学意义（P〈0.05）。对照组疗程6~12个月,平均（8.5±2.3）个月,肝肾异常率为25.49%,治疗组、耐药治疗组,疗程均3～5个月,平均（3.5±1.2）个月,肝肾异常率均0,与对照组比较差异均有统计学意义（P〈0.05）。结论：黄精汤及制剂是一组疗程短、安全、有效的治疗肺结核和耐药性肺结核的中药,具2ERHZ/4R化疗等效。