Prioritising Healthcare Workers for Ebola Treatment: Treating Those at Greatest Risk to Confer Greatest Benefit

The Ebola epidemic in Western Africa has highlighted issues related to weak health systems, the politics of drug and vaccine development and the need for transparent and ethical criteria for use of scarce local and global resources during public health emergency. In this paper we explore two key themes. First, we argue that independent of any use of experimental drugs or vaccine interventions, simultaneous implementation of proven public health principles, community engagement and culturally sensitive communication are critical as these measures represent the most cost‐effective and fair utilization of available resources. Second, we attempt to clarify the ethical issues related to use of scarce experimental drugs or vaccines and explore in detail the most critical ethical question related to Ebola drug or vaccine distribution in the current outbreak: who among those infected or at risk should be prioritized to receive any new experimental drugs or vaccines? We conclude that healthcare workers should be prioritised for these experimental interventions, for a variety of reasons.     

Medical Aspects of Chemical Warfare

The first-aid treatment of mass casualties from nerve gas relies mainly upon the use of drugs, and provision for their self-injection is recommended. Means for giving artificial respiration must also be provided, even though its large-scale use is regarded as impracticable. Prophylactic oxime (2 g. PAM chloride orally) is recommended if the situation permits. Some nerve gases are extremely rapid in action, and following exposure (or suspicion of exposure) 4 mg. of atropine and 2 g. of PAM chloride should be injected intramuscularly without delay. Preferably, atropine should be given intravenously. At the same time any clothing contaminated with liquid nerve gas should be removed and the skin cleansed thoroughly with a suitable fluid. Following this, the casualty should be watched closely for one hour. If poisoning develops despite these measures, or is already established, injection of atropine should be continued at short intervals until improvement occurs.     

Triple co-administration of ivermectin, albendazole and praziquantel in zanzibar: a safety study

Background

Public health interventions based on distribution of anthelminthic drugs against lymphatic filariasis (LF), onchocerciasis, soil-transmitted helminthiasis (STH) and schistosomiasis have been implemented separately to date. A better use of available resources might be facilitated by a more coordinated approach to control such infections, including the possibility of co-administering the three recommended anthelminthic drugs through a single, large-scale intervention.

Methodology/Principal Findings

Ivermectin, albendazole and praziquantel were co-administered to 5,055 children and adults living in areas endemic for LF, STH and schistosomiasis in Zanzibar, United Republic of Tanzania, during a pilot intervention aimed at elucidating and quantifying possible side-effects. Subsequently, these drugs were co-administered to about 700,000 individuals during a countrywide intervention targeting a large part of the total population of Zanzibar. Passive and active surveillance measures carried out during both interventions showed that side-effects attributable to the three drugs given at the same time were mild and self-limiting events.

Conclusions/Significance

Our data suggest that co-administration of ivermectin, albendazole and praziquantel is safe in areas where lymphatic filariasis, soil-transmitted helminthiasis and schistosomiasis are co-endemic and where several rounds of treatment with one or two drugs have been implemented in the past. Passive surveillance measures, however, should be continued and detection, management and reporting of possible side-effects should be considered a key component of any health intervention administering drugs.     

临床用药风险管理常见问题及应对措施

目的：对我院不安全用药行为进行监测与调查,分析临床用药问题中存在的风险因素,探讨医疗机构加强药品风险管理的措施,以减少临床用药的安全隐患。方法：采用调查问卷的方式,对我院部分科室就诊患者的用药情况进行问卷调查;应用“医院用药安全监测与评价”软件对我院医护人员在临床用药管理方面存在的风险因素进行评估,整理并分析调查结果。结果：在本次临床用药风险分析中,各因素所占比例为：医生：30.50%,药师：9.00%,护士：32.00%,患者：28.50%。了解临床用药各环节中存在的临床用药风险的医护人员占83.3%,但只有50.6% 的人员采取基本的防范措施。用药风险警示调查显示：PASS 警示有效率为57.5%;关联因素评价中人员因素的发生率最高55.16%;外界因素次之31.29%;药物因素发生率为26.95%。结论：医疗机构应当加强临床用药管理,识别、分析用药风险因素,强化合理用药意识及知识,努力构建临床用药风险控制系统,为医药护理人员及患者营造良好的医疗安全氛围,从而降低用药风险的发生,保障患者的用药安全。     

Planned care for patients with bronchiectasis

Bronchiectasis, for which once only the most elementary palliation could be offered, now often can be cured by operation or well controlled by conservative therapy. Since true bronchiectasis implies irreversible anatomic changes, operation offers the only hope of cure, and it should be undertaken whenever it is not contraindicated by extent of involvement, age of the patient or other factors. Surgical results are excellent and mortality is at a minimum. When operation is prohibited, good results can still be anticipated by conservative measures. Such conservative therapy should combine prolonged use of antimicrobial drugs with adequate drainage of the diseased segments and general supportive measures. Any residual infection can be controlled by moderate use of appropriate antimicrobial agents. It is emphasized, however, that the control of bronchiectasis requires very careful diagnostic studies and a detailed analysis of the patient's condition, and that the therapy itself must be carefully adjusted in terms of the individual situation.     

Approach to drug therapy for hypertension.

Prevention of complications of hypertension requires the lowering of blood pressure. The therapeutic goal is to achieve and maintain a diastolic pressure of less than 90 mm Hg with minimal adverse effects. The treatment of patients with established diastolic blood pressures between 90 and 104 mm Hg (determined from three separate readings) should be individualized; general measures such as weight loss and salt restriction should be tried first as an alternative to drug therapy. Patients with diastolic pressure in excess of 104 mm Hg should be treated with antihypertensive drugs; the first step should be the use of a thiazide diuretic in addition to general measures. Patients with diastolic pressures of 90 to 115 mm Hg may require the addition of a beta-adrenergic-receptor antagonist, methyldopa or clonidine if the therapeutic goal is not achieved; rarely they require the further addition of hydralazine or prazosin. Patients with diastolic pressures of 116 to 129 mm Hg usually require initially both a thiazide diuretic and a beta-blocker, methyldopa or clonidine; if the therapeutic goal is not achieved, hydralazine or prazosin is added, and if a further hypotensive effect is required guanethidine can be added. Patients with severe hypertension (diastolic pressures greater than 130 mm Hg) may require urgent treatment with combinations of drugs of all three levels. Emphasis should be placed on individualized therapy and patient compliance in the assessment of therapeutic failures. These "step-care" guidlines represent a framework for antihypertensive therapy devised from information available in 1977. It is not a rigid scheme and should be adjusted to the individual patient to ensure as normal a life as possible.     

A Report of the James Watson Lecture at Yale University

In March 2012, Nobel Prize winner James Watson gave a seminar at Yale University entitled “Driven by Ideas.” In his lecture, Watson discussed his personal vision for the future of science, specifically addressing how the scientific community should approach developing anticancer agents. He discussed the use of glycolytic inhibitors as anticancer agents due to the Warburg effect, as well as the benefits of metformin and anti-inflammatory drugs to help prevent cancer. He also compared drugs that target cell proliferation instead of targeting cell growth. Additionally, Watson commented on the mechanisms for how research should be conducted in the laboratory.     

A twin study of personality and illicit drug use and abuse/dependence.

Although personality measures such as neuroticism (N), extraversion (E) and novelty-seeking (NS) are associated with the use and abuse/dependence of illicit drugs, little is known about the degree to which these associations are due to genetic or environmental factors. The goal of this analysis was to estimate the extent of genetic and environmental overlap between three dimensions of personality (N, E and NS) and illicit psychoactive substance use and abuse/dependence. Using data from adult male and female twins from the Mid-Atlantic Twin Registry, we used the structural equation modeling package Mx to perform bivariate Cholesky decompositions for personality measures of N, E and NS, individually with cannabis, cocaine, sedatives, stimulants and hallucinogens. This was done separately for use and for a polychotomous diagnosis of abuse and/or dependence. Sex differences were tested. The phenotypic relationship between personality and use and abuse/dependence of illicit drugs were moderate and most of the covariance was explained by genetic factors. Sexes could be equated for N and E but not for NS. For NS, use and abuse/dependence of illicit drugs showed greater phenotypic and genetic overlap in males than females. Of the personality measures, NS and illicit drug use and abuse/dependence were most closely related. NS was most closely related to cannabis use while N showed significant genetic overlap with sedative use. NS in males appears to be a good indicator of risk for cannabis use. This result may be useful for candidate gene studies.     

Can Antiviral Drugs Contain Pandemic Influenza Transmission?

Antiviral drugs dispensed during the 2009 influenza pandemic generally failed to contain transmission. This poses the question of whether preparedness for a future pandemic should include plans to use antiviral drugs to mitigate transmission.Simulations using a standard transmission model that allows for infected arrivals and delayed vaccination show that attempts to contain transmission require relatively few antiviral doses. In contrast, persistent use of antiviral drugs when the reproduction number remains above 1 use very many doses and are unlikely to reduce the eventual attack rate appreciably unless the stockpile is very large. A second model, in which the community has a household structure, shows that the effectiveness of a strategy of dispensing antiviral drugs to infected households decreases rapidly with time delays in dispensing the antivirals. Using characteristics of past pandemics it is estimated that at least 80% of primary household cases must present upon show of symptoms to have a chance of containing transmission by dispensing antiviral drugs to households. To determine data needs, household outbreaks were simulated with 50% receiving antiviral drugs early and 50% receiving antiviral drugs late. A test to compare the size of household outbreaks indicates that at least 100-200 household outbreaks need to be monitored to find evidence that antiviral drugs can mitigate transmission of the newly emerged virus.Use of antiviral drugs in an early attempt to contain transmission should be part of preparedness plans for a future influenza pandemic. Data on the incidence of the first 350 cases and the eventual attack rates of the first 200 hundred household outbreaks should be used to estimate the initial reproduction number R and the effectiveness of antiviral drugs to mitigate transmission. Use of antiviral drugs to mitigate general transmission should cease if these estimates indicate that containment of transmission is unlikely.     

Review: Assessment of dairy cow welfare at pasture: measures available,gaps to address,and pathways to development of ad-hoc protocols

Pasture is generally perceived as positive for dairy cow welfare, but it nevertheless exposes cows to heat, parasites, and other challenges. This review is intended for people ready to design comprehensive protocols for assessing the welfare of dairy cows at pasture. We provide an overview of the benefits and risks of pasture for cows, and then go on to identify the available and feasible measures for assessing cow welfare at pasture and the gaps that need to be addressed to develop specific welfare measures. Some of the measures from on-farm welfare assessment protocols designed for indoor use (e.g. Welfare Quality®) are relevant for cows at pasture (e.g. lameness scoring). However, the timing, location and/or method for certain measures (e.g. observation of social behaviour) need to be adapted to the pasture context, as cows at pasture can roam over a large area. Measures to address specific pasture-related risks (e.g. heat stress, biosecurity) or benefits (e.g. expression of a wide range of behaviours) should be implemented in order to capture all dimensions of cow welfare at pasture. Furthermore, cow welfare is liable to vary over the grazing season due to changes in weather conditions, grass quality and pasture plots that induce variations in lying surface conditions, food availability, distance to walk to the milking parlour, and so on. It is therefore important to investigate the variability in different welfare measures across the pasture season to check whether they hold stable over time and, if not, to determine solutions that can give an overview across the grazing season. Sensors offer a promising complement to animal and environment observations, as they can capture long-term animal monitoring data, which is simply not possible for a one-day welfare-check visit. We conclude that some measures validated for indoor situations can already be used in pasture-based systems, while others need to be validated for their fitness for purpose and/or use in pasture conditions. Furthermore, thresholds should probably be determined for measures to fit with pasture contexts. If all measures can be made adaptable to all situations encountered on farms or variants of the measures can at least be proposed for each criterion, then it should be possible to produce a comprehensive welfare assessment protocol suitable for large-scale use in near future.     

急性单纯性阑尾炎住院临床路径遵循情况分析

利用2010年全国城镇基本医疗保险参保住院患者医疗服务利用调查数据,对急性单纯性阑尾炎住院手术患者临床诊疗措施的实际使用情况与该病的标准临床路径进行对比分析。平均住院日比临床路径要求的7天约高出1天,其中41.9%手术病例住院天数超出了标准住院日;约47.5%患者未在入院当天急诊手术;18个平均使用率在40%以上的检查项目中,有7个项目不在临床路径规定范围内;99.8%病例在手术中使用过全身抗感染类药,且67%的患者同时使用了2种及2种以上抗菌素。急性单纯性阑尾炎的实际诊疗措施和标准临床路径存在着较大的差异,住院流程有待于进一步优化,住院检查检验项目和抗菌药物的使用需要制订更为细致且可操作的指导原则,并强化监管。     

The prevention of HIV/AIDS among injection narcotics users in the city of Odessa

Since August 1996 the realization of the first Ukrainian Project "HIV/AIDS Preventive Maintenance among Injecting Drug Users", based on the strategy of harm reduction, has been started in Odessa with a view to the effective counteraction to the spread of HIV/AIDS among injecting drug users (IDU). The project is being realized with the advisory and financial support of UNAIDS, UNICEF and USAID. The basic organization for the realization of the Project is the Public Movement "Faith, Hope, Love". The Project is aimed at decreasing the rate of the spread of HIV infection in cases of the non-medical use of narcotic drugs by the elaboration and adoption of measures conductive to changes in hazardous behavior. The realization of the project includes the following stages: the rapid evaluation of the situation with the injecting use of drugs in Odessa, the elaboration and adoption of preventive measures.     

Comparing healthcare systems: outcomes, ethical principles, and social values

The question of how healthcare should be structured has been at the forefront of public debate for quite some time. In particular, debate has raged over the acceptability of socialized and rights-oriented approaches to healthcare as opposed to privatized and commodity-oriented approaches. The present discussion looks at the underlying logic of the debate and at the use of outcome measures as a primary determinant. It suggests that outcome measures are of limited use in deciding the issue because they ignore important variables and further suggests that outcome measures are inappropriate tools when comparing distinct healthcare systems because they ignore valuational components that are integral to deciding whether a healthcare system is consistent with a society's principles and values.     

Use of substances of animal origin in pharmaceutics and compliance with the TSE-risk guideline -- a market survey.

The risk of infection with transmissible spongiform encephalopathy (TSE) from the use of animal-derived substances in drug manufacturing was assessed [Swissmedic. TSE guideline to the ordinance. 2001; http://www.swissmedic.ch/files/pdf/Anleitung_TSE.pdf; The European Directorate for the Quality of Medicines. Minimising the risk of transmitting animal spongiform encephalopathy agents via medicinal products. In: European Pharmacopoeia 2002; General chapter 5.2.8. http://www.pheur.org/medias/download/50208E.pdf]. In addition, the compliance of the Swiss Market Authorisation holders to implement the Swissmedic TSE guidelines was examined. To assess the compliance with the TSE guideline for products on the Swiss market a representative number of drugs were selected based on a statistical approach. The documents for the biological, anatomical and geographical origin of the animal substances used for drug manufacturing as well as for the manufacturing processes were requested to be provided within a short response period and were subsequently reviewed. A total of 438 drugs with 655 substances of animal origin were assessed during the survey. The documentation provided by the Market Authorisation holders showed, that in general the measures described in the TSE guidelines were implemented well. Therefore, the risk of these pharmaceutics to transmit TSE was considered minimized. However, the TSE documentation provided by drug companies was incomplete for approximately two-third of the drugs at the beginning of the survey. In particular for those containing excipients such as tallow derivatives or gelatine, numerous clarifications were needed prior assessment. The efforts of the drug companies to correspond to regulatory actions and to implement authoritative guidelines should be improved.     

The risk of upper gastrointestinal complications associated with nonsteroidal anti-inflammatory drugs, glucocorticoids, acetaminophen, and combinations of these agents

Most anti-inflammatory drugs have been associated with an increased risk of serious upper gastrointestinal complications. Epidemiological studies have estimated the magnitude of the risk for specific anti-inflammatory drugs. The risk of upper gastrointestinal tract bleeding or perforation increases around twofold with use of oral steroids or low dose aspirin, and increases around fourfold with use of nonaspirin nonsteroidal anti-inflammatory drugs. Acetaminophen at daily doses of 2000 mg and higher has also been associated with an increased risk. Overall, the risk is dose dependent and is greater with more than one anti-inflammatory drug taken simultaneously. Hence, whenever possible, anti-inflammatory drugs should be given in monotherapy and at the lowest effective dose in order to reduce the risk of serious upper gastrointestinal complications.     

罕见疾病及孤儿药物研究现状及进展

文中简述了罕见疾病的定义、发病原因、分类,总结了国内外罕见疾病研究和孤儿药物研发的现状,分析了生物技术的研究手段在罕见疾病药物研发方面的应用,进一步阐述了罕见疾病研究和孤儿药物开发的必要性和紧迫性,对推动科学技术的进步和人类健康事业的发展具有深远的意义。     

A cross sectional study of sex differences in self-medication practices among university students in Slovenia

Self-medication patterns in adults depend on sex. Self-medication among students is very common, but little is known about the influence of sex. The aim of the study was to determine the incidence of self-medication college students and to determine the effect of sex on self-medication patterns. A web based incidence study conducted on a sample of Slovenian university students. The main outcome measures were percentages of male and female students reporting the use of self-medication in the past year. A majority of students (92.3%) reported the use of some sort of self-medication in the past year. Most female students (94.1%) and most male students (90.9%) reported the use of self-medication in the past year. The difference was not statistically significant. More female students than male ones (p < 0.05) acquired the drugs for self-medication in pharmacies, used OTC drugs, herbal teas, herbs, vitamins and minerals, remedies for muscle mass gain, antibiotics, benzodiazepines, antacids, acetylsalicylic acid, topical corticosteroids, and nasal decongestives only with the advice of physicians or pharmacists, and thought that increasing drug dosage can be dangerous, that in case of side effects physicians' help must be sought, that no drug can be used during pregnancy, and that self-treatment can mask the symptoms and signs of diseases so the physicians can overlook them easily. Sex appears to be important factor in self-medication patterns even in young adults, such as students. The physicians should actively seek the presence of self-medication in this population. Inappropriate or unsafe use should be properly addressed and managed.     

Impulsivity as a determinant and consequence of drug use: a review of underlying processes

Impulsive behaviors are closely linked to drug use and abuse, both as contributors to use and as consequences of use. Trait impulsivity is an important determinant of drug use during development, and in adults momentary 'state' increases in impulsive behavior may increase the likelihood of drug use, especially in individuals attempting to abstain. Conversely, acute and chronic effects of drug use may increase impulsive behaviors, which may in turn facilitate further drug use. However, these effects depend on the behavioral measure used to assess impulsivity. This article reviews data from controlled studies investigating different measures of impulsive behaviors, including delay discounting, behavioral inhibition and a newly proposed measure of inattention. Our findings support the hypothesis that drugs of abuse alter performance across independent behavioral measures of impulsivity. The findings lay the groundwork for studying the cognitive and neurobiological substrates of impulsivity, and for future studies on the role of impulsive behavior as both facilitator and a result of drug use.     

Protection gonadique contre les effets iatrogènes des traitements anticancéreux: données expérimentales

The cytotoxic agents used in cancer therapy cause serious and long lasting side effects on spermatogenesis in young male patients. In absence of prophylactic measures (cryoconservation of Spermatozoa prior to therapy; lead shields during radiation therapy; drugs less damaging to spermatogenesis), the use of protective agents is necessary. Numerous antioxydants and a variety of hormones have been experimented in attempts to limit the deleterious effects of antimitotic drugs. Major animal studies have been conducted into ?rtain GnRH analogs, FSH steroïds, and in particular the combination of Medroxyprogesterone Acetate + Testosterone, leading to encouraging results. Progress in animal experimentation should, within the near future, allow clinical trials in humans.