Depression and anxiety in individuals with amyotrophic lateral sclerosis: epidemiology and management

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease with no curative treatment. Considering the devastating nature of the disease, a high prevalence of depression and anxiety in affected patients would be expected. A review of the literature shows prevalence rates for depression in ALS patients ranging from 0% to 44%, but studies using the structured interview according to DSM-IV criteria find highly consistent rates of 9-11%. Prevalence rates for anxiety in ALS range from 0% to 30%. Depression and anxiety appear to be not always properly addressed aspects of ALS, as there are only a few references in the literature about psychological and pharmacological interventions. Additionally, pharmacological antidepressant therapy is often not continuously monitored and its effectiveness remains unevaluated. A review of the literature and our own experiences show that there is a lack of psychological care and, to our knowledge, there is no specific psychological intervention method for ALS patients. Concerning pharmacological treatment of depression in patients with ALS, there is broad consensus among clinical experts that SSRIs and TCAs are helpful, but there have been no controlled clinical studies of these medications in ALS patients. TCAs can be prescribed if anticholinergic effects are desired simultaneously for treating pseudohypersalivation or insomnia. Anxiety is usually treated with anxiolytics, but again there have been no systematic studies of these drugs in patients with ALS. For psychological intervention we suggest a cognitive behavioural approach, which has to be integrated into an intervention programme that includes teaching of appropriate coping strategies and reappraisal skills and encourages engagement in activities that are still practicable and pleasant. We propose that the treatment of depression and anxiety should involve both cognitive behavioural therapy and pharmacological intervention. Pharmacological treatment should be strictly monitored for effectiveness. To date, no clinical trials are available that would allow us to recommend pharmacotherapy over psychotherapy or vice versa; however, evidence from other patient groups, such as elderly patients diagnosed with major depressive disorder, suggests that a combination of both therapies has the potential to also improve depression and anxiety in patients with ALS.     

Selecting a pharmacy computer system for the future

Major advances are occurring in the field of computer science that have placed us at the threshold of a significant revolution in the management and application of clinical data. These advances will have a profound effect on the practice of pharmacy and are occurring at a time when many hospital pharmacies are deciding whether to enhance or replace their current systems. To best position your department for the future, it is essential that you are knowledgeable of the advances being made, have a vision for how they will affect your practice, and undergo a well-organized and thorough selection process.     

The use of biological laboratory markers in the diagnosis of alcohol misuse: an evidence-based approach

BACKGROUND: A large number of patients seen in clinical practice have an underlying alcohol problem. There is a pressing need for accurate methods to diagnose alcohol over-consumption objectively. Our aim was to determine how best to use biological markers to objectify alcohol problems in patients with clinical suspicion of alcohol misuse. METHODS: A 6-month longitudinal multicenter trial was conducted, using four study groups (alcohol abusers, alcohol-dependents, healthy controls and consulting controls). CDT, GGT and MCV were measured. Statistical analyses used a computer learning system that created classification systems displayed in decision trees. RESULTS: In 379 subjects the marker that best discriminated those with alcohol problems from controls was CDT. GGT then helped to differentiate between alcohol abuse and alcohol dependence in cases of high CDT. MCV, age and gender provided no extra information. DISCUSSION: We recommend CDT as a first-line biological marker to confirm or disprove suspected alcohol misuse. High CDT plus GGT above normal points to alcohol dependence, while high CDT plus GGT below normal is evidence of alcohol abuse.     

Small- and large-scale biosimulation applied to drug discovery and development

Biosimulation uses mathematics to quantitatively represent the dynamics of biological systems and thereby analyze and predict system behavior. Biosimulations can be classified into two general categories: small-scale models designed to address a specific problem, and large-scale models of detailed regulatory mechanisms used to address a broad scope of questions. Both classes of biosimulations have been applied to problems important for drug discovery and development. Small-scale biosimulations have been particularly useful for interpreting clinical data and developing novel biomarkers. Large-scale biosimulations typically integrate a wide variety of data and can provide insights into how complex biological systems are regulated in both health and disease. Because large-scale biosimulations represent detailed regulatory mechanisms and their interactions, they can predict the overall clinical effect of modulating individual pathways or targets. In this mini-review, we describe several examples of how small- and large-scale biosimulations have been applied to problems important for drug development in diabetes, HIV, heart disease and asthma.     

Fax technology for collecting outcomes data in a computer database.

In this era of cost containment, outcomes research is becoming more prevalent. Therefore, various technologies allowing for flexibility in study design and the capture of specific clinical information need to be examined and used. These technologies include fax data systems, pocket scanners, automated telephone equipment, and hand-held computer devices. Fax data systems convert a fax machine into an automated data-entry system. Data-filled forms are faxed to a computer, the fax is converted, and the data are entered into preset fields in a database. Applications for fax systems include acute care-based and ambulatory care-based drug-use evaluations, drug recall systems, and patient-completed surveys of health status. Pocket scanners are hand-held instruments for rapid data entry and transport. Applications for pocket scanning include patient interview responses, procedure and disease analysis, and procedure coding. Options for automated telephone equipment include surveys with interactive voice-mail responses or keypad data entry, pharmacist-monitored drug information and survey services, fax-back and mail-out services, and patient-generated disease intervention programs. Hand-held computer technology is a source of information on multiple protocols and care pathways. All these technologies improve data collection with respect to accuracy and speed, facilitate data analysis, and promote cost-efficient information sharing. The purpose of this study was to evaluate the use of fax technology in data collection for a prospective, multicenter study of the outcomes and cost-effectiveness of two drugs used in the treatment of cancer. Details for the pharmacoeconomic study can be found elsewhere. Fax technology was selected because of the ease with which those responsible for managing the data collection could be trained to use it, the affordability and efficiency of the technology, the ease with which data could be analyzed, and the accuracy of data collection.     

Laboratory and software applications for clinical trials: the global laboratory environment

The Applied Pharmaceutical Software Meeting is held annually. It is sponsored by The Boston Society, a not-for-profit organization that coordinates a series of meetings within the global pharmaceutical industry. The meeting generally focuses on laboratory applications, but in recent years has expanded to include some software applications for clinical trials. The 2011 meeting emphasized the global laboratory environment. Global clinical trials generate massive amounts of data in many locations that must be centralized and processed for efficient analysis. Thus, the meeting had a strong focus on establishing networks and systems for dealing with the computer infrastructure to support such environments. In addition to the globally installed laboratory information management system, electronic laboratory notebook and other traditional laboratory applications, cloud computing is quickly becoming the answer to provide efficient, inexpensive options for managing the large volumes of data and computing power, and thus it served as a central theme for the meeting.     

Real-time Imaging and Quantification of Brain Delivery of Liposomes

Abstract The surgical delivery of therapeutic agents into the parenchyma of the brain is problematic because it has been virtually impossible to know with any certainty where infused material is going, and how much to infuse. We have started to use liposomes loaded with Gadoteridol (GDL) as a tracer that allows us to follow infusions in real-time on magnetic resonance imaging (MRI). MRI allows precise tracking and measurement of liposomes loaded with markers and therapeutics. This review provides an overview of real-time delivery of liposomes to the central nervous system (CNS), and discusses the technical aspects of delivery, liposomes as colloidal systems of delivery, real-time distribution of liposomes in CNS, and quantification of liposome distribution. Our data suggests that real-time monitoring of liposomal drug infusion is likely to improve outcomes of clinical trials where convection-enhanced delivery (CED) is being used to target drugs to specific brain structures through limitation of systemic toxicity and reduction of side effects. This review is a summary of work done by our group over the past four years.     

Botulinum Toxin Type A for the Treatment of Neuropathic Pain in Neuro-Rehabilitation

Pain is a natural protective mechanism and has a warning function signaling imminent or actual tissue damage. Neuropathic pain (NP) results from a dysfunction and derangement in the transmission and signal processing along the nervous system and it is a recognized disease in itself. The prevalence of NP is estimated to be between 6.9% and 10% in the general population. This condition can complicate the recovery from stroke, multiple sclerosis, spinal cord lesions, and several neuropathies promoting persistent disability and poor quality of life. Subjects suffering from NP describe it as burning, itching, lancing, and numbness, but hyperalgesia and allodynia represent the most bothersome symptoms. The management of NP is a clinical challenge and several non-pharmacological and pharmacological interventions have been proposed with variable benefits. Botulinum toxin (BTX) as an adjunct to other interventions can be a useful therapeutic tool for the treatment of disabled people. Although BTX-A is predominantly used to reduce spasticity in a neuro-rehabilitation setting, it has been used in several painful conditions including disorders characterized by NP. The underlying pharmacological mechanisms that operate in reducing pain are still unclear and include blocking nociceptor transduction, the reduction of neurogenic inflammation by inhibiting neural substances and neurotransmitters, and the prevention of peripheral and central sensitization. Some neurological disorders requiring rehabilitative intervention can show neuropathic pain resistant to common analgesic treatment. This paper addresses the effect of BTX-A in treating NP that complicates frequent disorders of the central and peripheral nervous system such as spinal cord injury, post-stroke shoulder pain, and painful diabetic neuropathy, which are commonly managed in a rehabilitation setting. Furthermore, BTX-A has an effect in relief pain that may characterize less common neurological disorders including post-traumatic neuralgia, phantom limb, and complex regional pain syndrome with focal dystonia. The use of BTX-A could represent a novel therapeutic strategy in caring for neuropathic pain whenever common pharmacological tools have been ineffective. However, large and well-designed clinical trials are needed to recommend BTX-A use in the relief of neuropathic pain.     

我院354例药品不良反应报告分析

目的：分析我院药品不良反应（ADR）发生的特点与一般规律,促进临床合理用药。方法：对我院354份ADR报告,按患者的性剐、年龄、引起ADR的药品种类、给药途径、涉及器官或系统以及临床表现等进行统计分析。结果：354倒ADR中,主要与静脉给药方式、患者年龄较大、抗感染药使用以及中药注射荆的质量有关。静脉滴注较其它给药途径更易发生ADR,ADR最常见表现为皮肤及其附件损害。结论：应加强ADR监测意识,完善相关报告分析制度,促进临床合理用药。     

Providing comprehensive smoking cessation care to surgical patients: The case for computers

Introduction and Aims. The provision of smoking cessation care to surgical patients before admission can reduce post‐operative complications and encourage long‐term smoking cessation. Our aim was to show how a comprehensive computer‐based smoking cessation intervention, developed to enhance smoking cessation care to surgical patients, addresses barriers to care provision. Design and Methods. Consultations with preoperative clinic staff and reviews of the scientific literature were conducted and identified the following barriers to the provision of effective smoking cessation care: a lack of organisational support, perceived patient objection, a lack of systems to identify smokers, a lack of staff time and skill, perceived inability to change care practices, a perceived lack of efficacy of cessation care and the cost of providing care. Based on positive findings of a pilot trial, a comprehensive computer‐based smoking cessation intervention was implemented in a preoperative clinic. Data from previous evaluations of the intervention were used to assess the extent to which the intervention addressed clinician barriers to care. Results. The computer‐based intervention was found to provide a means to accurately and systematically identify smokers; it required little clinical staff time or skill; it was considered an acceptable form of care by staff and patients; it was effective in encouraging patient cessation and it was inexpensive to deliver relative to other surgical costs. Furthermore, the computer‐based intervention continues to operate in the preoperative clinic in the absence of ongoing research support. Discussion and Conclusions. The implementation of such a model of care should be considered by clinical services interested in reducing the smoking related morbidity and mortality of patients.[Wolfenden L, Wiggers J, Campbell E, Knight J, Kerridge R & Spigelman A. Providing comprehensive smoking cessation care to surgical patients: The case for computers. Drug Alcohol Rev 2009;28:60–65]     

Comparison of computer assisted scan diagnoses and clinical diagnoses of major mental disorders in Butajira, rural Ethiopia

One of the major difficulties in mental health research is finding suitable research instruments. In the last few decades questionnaires that are supposed to work in different languages and cultures have been developed by WHO to solve this problem. One of such instruments is SCAN, an instrument which uses computer algorithm to make a diagnosis. It is meant to be used for semi-structured interview by qualified psychiatrists or clinical psychologists. This and a few other research instruments have been translated and used in clinical and community settings for psychiatric research in Ethiopia over the last few years. In this study computer assisted SCAN Diagnoses and clinical diagnoses made by trainee psychiatrists in Butajira, a rural setting in Ethiopia, were compared Seven hundred twenty nine persons were diagnosed to have schizophrenia and bipolar disorder using both methods. The agreement between the clinical and SCAN derived diagnosis was shown to be 100% for schizophrenia (Kappa = 1.0). However, the agreement between the two methods of diagnosis was shown to be lower when it comes to subtypes of schizophrenia. The agreement for the diagnoses of bipolar disorder was 95.3%, kappa = 0.9, P < 0.0001 and for depression it was 93.0%, kappa = 0.8, p < 0.0001. Taking into account the limited number of psychiatrists and clinical psychologists in the third world countries like Ethiopia we have shown that using trainees in psychiatry for SCAN interview is a feasible and reliable method to identify major categories of mental disorders in community studies.     

Diagnostic data in clinical toxicology--should we use a Bayesian approach?

A number of toxidromes (toxicology syndromes) have been described for various poisonings and are promoted as a means of reaching a diagnosis in patients presenting with unknown poisonings. Many are based entirely on deductive reasoning from the known pharmacological effects of these drugs rather than on documented clinical experience. In this paper, we used our database, where we have recorded clinical signs on presentation in unselected poisonings to explore how clinical signs actually alter the odds of ingestion of different poisons. Many signs substantially altered the list of drugs likely to have been ingested. We found that the most important factor determining whether an unconscious patient had ingested a particular drug was how frequently that drug was taken generally (i.e., the a priori probability), rather than the presence of any particular physical sign. It also follows that our (or anyone else's) intuitive or deductive approach to diagnosis, derived from experience, will not necessarily be very useful at another place where predominantly different drugs are involved in poisoning. Our data were used to derive odds ratios as a measure of the strength of association of physical signs or investigations with ingested poisons. These can be used to develop simple diagnostic algorithms orflow charts to identify the most likely drugs ingested, or using more complicated programming, could also be used to calculate the precise probability of different drug-ingestion using Bayes' Theorem. The usefulness (i.e., external validity) of clinical research from other centers can also be determined.     

计算机系统与药物临床试验管理规范——临床研究机构的角色和临床试验中计算机系统的职责

在临床研究中计算机系统常常用于受试者的诊断与管理,药物的调配和执行临床试验方案中规定的实验室检查。确保这些计算机系统每次都严密可控且可信地执行任务非常重要。国际法规要求这些系统均有很好的工作记录方能符合要求。临床基地的稽查和核察人员要按照药物临床试验管理规范要求审查这些系统,确保它们在研究中的可靠性以及数据的可信度。研究组长对所有方案中使用的工作系统以及从书面或计算机中收集的试验数据的质量与可靠性负责。     

Inhalation therapy: technological milestones in asthma treatment

The humble origins of the propellant driven metered dose inhaler, as a response to a child's enquiry, initiated an industry which supplies approximately a half billion inhalers globally for the treatment of asthma. These inhalers fall into three major groups: nebulizers; propellant driven metered dose inhalers and dry powder inhalers. Each requires drug formulation, metering and device technology to be successful. In recent years there have been several new developments in the field including auxiliary systems to improve drug delivery from the device to the patient and new categories of device, notably single breath aqueous systems. As device technology improves and our understanding of the disease leads to new drugs the only barrier to therapy is the patient. Patient training and compliance will continue to be important factors in the success, or failure, of inhaled therapy and the role of health care professionals will depend on who sponsors their intervention.     

Stem cell transplantation for neurometabolic and neurodegenerative diseases

Over the last decade, the potential for therapeutic use of stem cell transplantation for cell replacement or as cellular vectors for gene delivery for neurometabolic and neurodegenerative diseases has received a great deal of interest. There has been substantial progress in our understanding of stem cell biology. Potential applications of cell-mediated therapy include direct cell replacement or protection and repair of the host nervous system. Given the complexities of the cellular organization of the nervous system, especially in diseased states, it seems that using stem cells as cellular vectors to prevent or ameliorate neurological disorders rather than cell replacement and the regrowth of damaged circuitry is more likely to succeed in the near term. Recent success in the treatment of lysosomal storage diseases with genetically modified stem cells support this notion. In Alzheimer's and Parkinson's diseases, stem cell therapy is at its early stages and data generated in animal models and clinical trials using other cell types suggest that a combination of gene and stem cell therapy may be an optimal therapeutic paradigm.     

Lamotrigine-associated rash: to rechallenge or not to rechallenge?

The major burden of illness in bipolar disorder (BD) is in the depressive pole. Lamotrigine has been shown to be useful in the long-term prophylaxis of depressive episodes in BD. Current guidelines recommend discontinuing lamotrigine in patients who develop rash. Our objective in this paper is to review literature to identify possible predictors of serious vs. benign rash that might help guide clinical decision-making and recommend titration strategy for re-introduction of lamotrigine, if indicated. We performed a search of the literature between 1966 and July 2008 to investigate the phenomenon of lamotrigine-induced rash and rechallenge procedures. The search identified six reports, and we were able to identify another case series from reviewing the bibliography of all of the above papers. We reviewed all the papers of lamotrigine rash rechallenge that resulted from the literature search. These papers describe 44 cases of lamotrigine rechallenge. Currently, there are 39 reported cases in the literature of successful lamotrigine rechallenge after a rash and five cases with rash recurrence. There are some characteristics of the rash that can help identify serious cases from benign ones. In addition, very slow titration of lamotrigine is crucial to the reduction of rash recurrence rate. Several cases that develop benign rash on lamotrigine can be rechallenged without adverse consequences. We believe that lamotrigine rechallenge in bipolar depression is an under-utilized option in our clinical armamentarium, and further studies are needed to guide us in this area.     

Method for evaluating drug information systems.

A method for evaluating drug information systems is described. The method measures both qualitative and quantitative performance. For the categories, "Basic Therapeutic Information", and "Commercial and Investigational Product Information," specific data that should be present are identified; evaluated systems are searched for these data related to a standard sample of 122 drugs. Systems are also searched for the presence of any information relating to these drugs in the categories, "Applied Clinical Research Information" and "Nonclinical Laboratory Research Information". In addition, systems are searched for the presence of 215 drug-drug interactions and 244 drug-laboratory test interferences. Using relative weights that have been assigned to the content statistics, an aggregate measure of system's content is determined. The method also measures annual cost of operating a system. The application of the method to two drug information systems is discussed briefly.