Oral drug therapy for multiple neglected tropical diseases: a systematic review

Context  The neglected tropical diseases include 13 conditions that occur in areas of extreme poverty and are poverty promoting. The neglected tropical diseases produce a disease burden almost as great as that associated with human immunodeficiency virus/AIDS, tuberculosis, or malaria, yet are virtually unknown by health care workers in North America, because they occur almost exclusively in the poorest regions of the world. Seven of the most prevalent diseases have existing oral drug treatments. Identifying treatments that are effective against more than 1 disease could facilitate efficient and inexpensive treatment. Objectives  To systematically review the evidence for drug treatments and to increase awareness that neglected tropical diseases exist and that treatments are available. Data Sources and Study Selection  Using a MEDLINE search (1966 through June 2007), randomized controlled trials (RCTs) were reviewed that examined simultaneous treatment of 2 or more of the 7 most prevalent neglected tropical diseases using oral drug therapy. Data Synthesis  Twenty-nine RCTs were identified, of which 3 targeted 4 diseases simultaneously, 20 targeted 3 diseases, and 6 targeted 2 diseases. Trials were published between 1972 and 2005 and baseline prevalence of individual diseases varied among RCTs. Albendazole plus diethylcarbamazine significantly reduced prevalence of elephantiasis (16.7% to 5.3%), hookworm (10.3% to 1.9%), roundworm (34.5% to 2.3%), and whipworm (55.5% to 40.3%). Albendazole plus ivermectin significantly reduced prevalence of elephantiasis (12.6% to 4.6%), hookworm (7.8% to 0%), roundworm (33.5% to 6.1%), and whipworm (42.7% to 8.9%). Levamisole plus mebendazole significantly reduced prevalence of hookworm (94.0% to 71.8%), roundworm (62.0% to 1.4%), and whipworm (93.1% to 74.5%). Pyrantel-oxantel significantly reduced hookworm (93.4% to 85.2%), roundworm (22.8% to 1.4%), and whipworm (86.8% to 59.5%), while albendazole alone significantly reduced prevalence of hookworm (8.1% to 1.3%), roundworm (28.4% to 0.9%), and whipworm (51.9% to 31.9%). No RCT examined treatment of river blindness or trachoma as part of an intervention to target 2 or more neglected tropical diseases. Adverse events were generally inadequately reported. Conclusions  At least 2 of the most prevalent neglected tropical diseases can be treated simultaneously with existing oral drug treatments, facilitating effective and efficient treatment. Increasing awareness about neglected tropical diseases, their global impact, and the availability of oral drug treatments is an essential step in controlling these diseases.      

Therapeutic drug monitoring of saquinavir in patients during protease inhibitor therapy with saquinavir alone or in combination with ritonavir or nelfinavir

Therapeutic drug monitoring is essential in HIV-patients undergoing highly active antiretroviral therapy (HAART). Saquinavir (SQV) is used alone or in combination with ritonavir (RTV) or nelfinavir (NLF), respectively, in the context of the HAART drug regimen. The achievable SQV concentration range in clinical practice remains to be elucidated. A non-randomized prospecitve clinical trial 19 patients (group I) receiving SQV (1x600 mg/d Invirase or Fortovase), 29 patients (group II) receiving SQV (2x600 mg/d Fortovase) plus RTV (2x400 mg/d Norvir), and 21 patients (group III) receiving SQV (2x600 mg/d Fortovase) plus NLF (2x750 mg/d Viracept) was conducted to determine SQV plasma concentrations. SQV levels were determined as trough levels during routine outpatient visits. Analysis was performed by HPLC with UV detection. The lowest SQV plasma levels were found in group I (95% CI 89-177 ng/ml). Significantly higher SQV levels were found in group III (combination with NLF) ranging from 242 to 398 ng/ml (95% CI) and in group II (combination with RTV) ranging from 1354 to 1747 ng/ml (95% CI). The IC 50% of 54 ng/ml was not reached in at least one sample during the study (mean duration of study 16+/-10 months) in 14/19 patients of group I, 9/29 patients in group II and 13/21 patients in group III, respectively. A positive correlation between patient compliance, defined by SQV levels in the 95% CI of the used combination, and the HIV RNA plasma level was found. The presented data confirm that therapy with SQV alone may not be effective, since trough levels are near the lower limit of antiretroviral efficacy. Although the combination of SQV with NLF results in higher SQV plasma concentrations in a bid regimen, in more than 60% of the patients SQV concentrations below IC 50 level were detected during the twelve-months study period. The combination of SQV with RTV yields the highest SQV-trough levels. SQV concentrations below the IC 50 were seen in only 31% of patients with the SQV/RTV combination. In conclusion, therapeutic drug monitoring allows an efficient surveillance of patients compliance. In addition, therapeutic drug monitoring represents a valuable tool for management of HAART in patients receiving a complex comedication or suffering from advanced liver disease.     

2型糖尿病患者血糖监测对药物治疗依从性的影响

目的观察分析2型糖尿病患者血糖监测对药物治疗依从性的影响。方法采用问卷调查法对171例2型糖尿病患者对药物治疗依从性和血糖监测情况进行单因素分析和Logistic回归分析。结果171例2型糖尿病患者对药物治疗依从性佳的病例共63例,占36.84%。通过依从性与相关单因素分析,显示出糖尿病教育、血糖定期测量、提醒服药等3项因素可以提高依从性,P<0.01。年龄、文化程度、并发症、定期复查、家中有血糖仪等5项因素亦可以提高依从性,P<0.05。经Logistic回归分析,依照标准系数绝对值大小,服药依从性取决于:糖尿病教育、提醒服药、定期复查、并发症、血糖定期测量。每周测量多次者,依从性佳的占67.86%,每周测量1次者,依从性佳的占41.30%,每月测量1次,依从性佳的为30.00%,不舒服时测量者,依从性佳的仅为21.28%。依从性与测量次数呈正相关。结论除了糖尿病教育、提醒服药、定期复查、并发症等因素影响药物治疗依从性外,血糖监测也是1个影响药物治疗依从性不可忽视的因素。     

Potential use of a dried saliva spot (DSS) in therapeutic drug monitoring and disease diagnosis

In recent years, scientific researchers have increasingly become interested in noninvasive sampling methods for therapeutic drug monitoring and disease diagnosis. As a result, dried saliva spot (DSS), which is a sampling technique for collecting dried saliva samples, has been widely used as an alternative matrix to serum for the detection of target molecules. Coupling the DSS method with a highly sensitive detection instrument improves the efficiency of the preparation and analysis of biological samples. Furthermore, dried blood spots, dried plasma spots, and dried matrix spots, which are similar to those of the DSS method, are discussed. Compared with alternative biological fluids used in dried spot methods, including serum, tears, urine, and plasma, saliva has the advantage of convenience in terms of sample collection from children or persons with disabilities. This review aims to provide integral strategies and guidelines for dried spot methods to analyze biological samples by illustrating several dried spot methods. Herein, we summarize recent advancements in DSS methods from June 2014 to March 2021 and discuss the advantages and disadvantages of the key aspects of this method, including sample preparation and method validation. Finally, we outline the challenges and prospects of such methods in practical applications.     

Osteoporosis--from hormonal replacement therapy to bisphosphonates and beyond: a review

OBJECTIVE: To review the old, current, and emerging agents in pharmacological treatment of osteoporosis. DATA SOURCES: Published original research work and reviews from 1993 to 31 December 2006 were searched in English on subjects related to epidemiology, pathophysiology, diagnosis, treatment, and prevention of osteoporosis. STUDY DESIGN: Only articles that emphasise on management. Data extraction: Online and manual library searches done. Data synthesis: Data added up and summarised. CONCLUSION: Osteoporosis is a serious public health issue. The past 10 years has seen great advances in our understanding of its epidemiology, pathophysiology, and treatment, and further advances are rapidly being made. Bisphosphonates represent the biggest advance in the treatment of osteoporosis, and will probably remain the mainstay of therapy. At the same time other diagnostic and therapeutic approaches, including biological agents, are likely to become more widespread. Combination therapy is generally not recommended due to paucity of data concerning antifracture effectiveness, and, there is currently no definitive answer on the length of treatment with antiresoptive agents.     

光动力学疗法关于治疗晚期胃癌的疗效

目的前瞻性研究光动力学疗法治疗晚期胃癌的近期疗效和远期疗效。方法对140例病理确诊的绝大多数为晚期胃癌患者进行光动力学疗法。结果近期总有效率为89．3％（P〈O.005）。远期疗效：全部患者已随访半年至17年，已有139例死亡，1例健在，并在继续随访中。结论光动力学疗法治疗晚期胃癌的近期疗效较好，远期疗效不够乐观。     

Corticosteroid therapy in pulmonary sarcoidosis: a systematic review

Context  Corticosteroids are used in pulmonary sarcoidosis to reduce symptoms and minimize long-term damage. Spontaneous recovery is a common feature. Both the decision to initiate therapy and the treatment response may be influenced by disease severity, so trials need to use a randomized controlled design. Objective  To assess the effect of oral and inhaled corticosteroids on chest radiograph results, symptoms, pulmonary function, and long-term outcome in pulmonary sarcoidosis. Data Sources  MEDLINE, EMBASE, CINAHL, and the Cochrane Controlled Trials Register were searched all years through December 2001. Bibliographies of review articles and retrieved articles were searched, and pharmaceutical companies and authors of identified trials were contacted for other studies. There was no language restriction. Study Selection  Trials were randomized and included a control group. Participants were adults with histologic evidence of pulmonary sarcoidosis. Treatments included the use of oral and inhaled corticosteroids for at least 8 weeks. The search identified 150 studies; 9 met the inclusion criteria, but only 8 provided usable data. Data Extraction  Two reviewers assessed trial quality using the Jadad score, which evaluates the quality of randomization, blinding, and reasons for withdrawal. Data were extracted and sent to primary authors for verification. Data Synthesis  In patients with stage 2 and 3 disease, oral corticosteroids improved findings on the chest radiograph after 6 to 24 months (Peto odds ratio, 2.54; 95% confidence interval [CI], 1.69-3.81; P<.001). Forced vital capacity improved with oral corticosteroids (weighted mean difference [WMD], 4.2% predicted; 95% CI, 0.4%-7.9% predicted) and diffusing capacity also improved (WMD, 5.7% predicted; 95% CI, 1.0%-10.5% predicted). In 2 small studies of inhaled corticosteroids, there was no effect on chest radiograph and inconsistent effects on lung function in one and only a small improvement in symptoms in the other. There were no data following corticosteroid withdrawal to assess any disease-modifying effect. Conclusions  Oral corticosteroids improved results on the chest radiograph following 6 to 24 months of treatment and produced a small improvement in vital capacity and diffusing capacity. Trials of inhaled corticosteroids were small and results too inconsistent to make firm conclusions concerning their efficacy. There are no data to suggest that corticosteroid therapy alters long-term disease progression.      

艾迪注射液治疗非小细胞肺癌系统评价

目的：评价艾迪注射液治疗非小细胞肺癌的有效性和临床研究质量。 方法：检索PubMed（1980～2008年）、Cochrane中心对照试验注册资料库（Cochrane Central Register of Controlled Trials,CENTRAL）2008年第3期、EMBASE（1984～2004年）、CancerLit（1996～2003年）、中国生物医学文献数据库（CBMdisc1980～2008年）、中国学术期刊网专题全文数据库（中国知网1980～2008年）、中文科技期刊全文数据库（重庆维普1980～2008年）、万方数据库（1980～2008年）,并根据文献中的参考文献进行文献追溯。手工检索四川大学医学图书馆部分相关期刊,纳入随机对照试验。使用国际Cochrane中心推荐的方法进行文献质量评价,并用RevMan5．0软件进行统计分析。 结果：共纳入14篇研究,且均为低质量研究。14项研究显示,在改善瘤体变化方面,艾迪注射液联合^60Co与单独应用^60Co比较,差异有统计学意义（P=0．0002）,相对危险度（relative risk,RR）为1．93,95％可信区间（confidence interval,CI）[1．36,2．72];艾迪注射液联合长春瑞滨和顺铂（navelbine and platinol,NP）与单用NP比较,差异亦有统计学意义（P=0．04）,RR=1．18,95％CI[1．00,1．38]。但艾迪注射液联合依托泊苷和顺铂（etoposideand and platinol,EP）、紫杉醇制剂和顺铂（taxinoland and platinol,TP）以及伽玛刀与单用EP、TP和伽玛刀比较,差异均无统计学意义（P=0．60,P=0．16,P=0．34）,其RR和95％CI分别为1．17[0．65,2．09],1．27[0．91,1．78]和1．08[0．92,1．26]。6项研究证实艾迪注射液联合NP或伽玛刀能够改善患者的生活质量。6项研究显示艾迪注射液具有保护骨髓造血功能的作用。3项研究显示可提高免疫功能。3项研究显示艾迪注射液未能提高1年及以上生存率。 结论：艾迪注射液对非小细胞肺癌可能具有一定的辅助治疗作用,但不排除与纳入文献质量较低,各种治疗方案纳入研究数量少和发表偏倚有关,尚需大样本多中心随机对照临床试验进一步证实其临床疗效。     

Gene therapy in head and neck cancer: a review

Gene therapy for cancer is a rapidly evolving field with head and neck squamous cell cancer being one of the more frequently targeted cancer types. The number of clinical trials in the UK is growing and there is already a commercially available agent in China. Various gene therapy strategies along with delivery mechanisms for targeting head and neck cancer are reviewed.     

Epidemiological modelling (including economic modelling) and its role in preventive drug therapy

In contrast to curative therapies, preventive therapies are administered to largely healthy individuals over long periods. The risk-benefit and cost-benefit ratios are more likely to be unfavourable, making treatment decisions difficult. Drug trials provide insufficient information for treatment decisions, as they are conducted on highly selected populations over short durations, estimate only relative benefits of treatment and offer little information on risks and costs. Epidemiological modelling is a method of combining evidence from observational epidemiology and clinical trials to assist in clinical and health policy decision-making. It can estimate absolute benefits, risks and costs of long-term preventive strategies, and thus allow their precise targeting to individuals for whom they are safest and most cost-effective. Epidemiological modelling also allows explicit information about risks and benefits of therapy to be presented to patients, facilitating informed decision-making.