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An introduction is presented in which author discusses articles on topics including focuses on the gap between a profession that has patient care as its vocation and one that called upon to adjudicate on that same professional performance.

An editorial is presented on sufferings and deaths due to COVID-19. Topics include cancer research company BioNTech dedicated to the search for a vaccine against Sars-Cov-2 with new ways of getting the vaccines for activating the immune system with mRNA; and science appeared as less successful in statistics, epidemiology, and particularly prediction.

The authors reflect on fake news in science and the possible adverse effects of deliberately changing, deleting, or suppressing factual material evidence. Topics include the importance of the use of the right tools to analyze findings from research and how value judgements are affected by the experience, knowledge and biases of researchers.

The world changes continuously and pharmacovigilance as a new discipline also must change. There are new fields opening with novel challenges whilst we are still perfecting ways to manage and improve the basic challenges such as inadequate data for decision making and under-reporting. Traditional medicines, vaccines, poisoning and medication error are all aspects of the safety of medicines that we have monitored for decades, though without perhaps paying enough attention to their special aspects. There are many new stakeholders taking serious interest in pharmacovigilance outside the regulatory sphere and they often focus on improving individual patient care, rather than the more traditional concentration on broad public health. The same stakeholders are also drawing attention to other iatrogenic outcomes that should be recognised, evaluated and their outcomes compared and contrasted with medication, such as harm from medical devices. The vigilance methods used for medication are very much applicable to all these new fields, though more and different expertise will be needed to evaluate outcomes. [ABSTRACT FROM AUTHOR]

Causality in pharmacovigilance is a difficult and time consuming exercise. This paper presents the challenges in determining causation by drug therapy. The first is that causation is complex and needs to be viewed from the context of the patient treated, rather than the drug product. Multiple causal vectors should be considered if we are to tackle the many issues involved in, for example, medication error and the many other factors that lead to bad outcomes from therapy, including failure to recognise known risk factors. The aim of pharmacovigilance is not only a bureaucratic exercise in public health norms, but is mainly concerned with small minorities of statistical outliers-and even individuals-whose experiences from harms may together form messages about causation that will prevent further at-risk patients from exposure, or at least assist with earlier recognition of drug-related harm and better management of such harm. This requires more time, more data, more analysis and more patient and clinical involvement in reporting useful clinical detail. The paradigm shift back towards gathering more case data relating to possible causation can be selective and would not be just retrogressive, nor necessarily too costly. Greater transparency of hypotheses and availability of anonymised case data will enrol more expertise into evaluations and hypothesis testing, and the provision of more complete and useful information should reduce clinical burdens from bad patient outcomes as well as their overall costs to society. [ABSTRACT FROM AUTHOR]

Background: High-dose short-term methylprednisolone is the recommended treatment in the management of multiple sclerosis relapses, although it has been suggested that lower doses may be equally effective. Also, glucocorticoids are associated with multiple and often dose-dependent adverse effects. This quantitative benefit-risk assessment compares high- and low-dose methylprednisolone (at least 2000 mg and less than 1000 mg, respectively, during at most 31 days) and a no treatment alternative, with the aim of determining which regimen, if any, is preferable in multiple sclerosis relapses.Methods: An overall framework of probabilistic decision analysis was applied, combining data from different sources. Effectiveness as well as risk of non-serious adverse effects were estimated from published clinical trials. However, as these trials recorded very few serious adverse effects, risk intervals for the latter were derived from individual case reports together with a range of plausible distributions. Probabilistic modelling driven by logically implied or clinically well motivated qualitative relations was used to derive utility distributions.Results: Low-dose methylprednisolone was not a supported option in this assessment; there was, however, only limited data available for this treatment alternative. High-dose methylprednisolone and the no treatment alternative interchanged as most preferred, contingent on the risk distributions applied for serious adverse effects, the assumed level of risk aversiveness in the patient population, and the relapse severity.Conclusions: The data presently available do not support a change of current treatment recommendations. There are strong incentives for further clinical research to reduce the uncertainty surrounding the effectiveness and the risks associated with methylprednisolone in multiple sclerosis relapses; this would enable better informed and more precise treatment recommendations in the future. [ABSTRACT FROM AUTHOR]

Sensory information arising from the upper neck is important in the reflex control of posture and eye position. It has also been linked to the autonomic control of the cardiovascular and respiratory systems. Whiplash associated disorders (WAD) and cervical dystonia, which involve disturbance to the neck region, can often present with abnormalities to the oromotor, respiratory and cardiovascular systems. We investigated the potential neural pathways underlying such symptoms. Simulating neck afferent activity by electrical stimulation of the second cervical nerve in a working heart brainstem preparation (WHBP) altered the pattern of central respiratory drive and increased perfusion pressure. Tracing central targets of these sensory afferents revealed projections to the intermedius nucleus of the medulla (InM). These anterogradely labelled afferents co-localised with parvalbumin and vesicular glutamate transporter 1 indicating that they are proprioceptive. Anterograde tracing from the InM identified projections to brain regions involved in respiratory, cardiovascular, postural and oro-facial behaviours-the neighbouring hypoglossal nucleus, facial and motor trigeminal nuclei, parabrachial nuclei, rostral and caudal ventrolateral medulla and nucleus ambiguus. In brain slices, electrical stimulation of afferent fibre tracts lateral to the cuneate nucleus monosynaptically excited InM neurones. Direct stimulation of the InM in the WHBP mimicked the response of second cervical nerve stimulation. These results provide evidence of pathways linking upper cervical sensory afferents with CNS areas involved in autonomic and oromotor control, via the InM. Disruption of these neuronal pathways could, therefore, explain the dysphagic and cardiorespiratory abnormalities which may accompany cervical dystonia and WAD. [ABSTRACT FROM AUTHOR]

The article discusses aim of the periodical to examine both harms and benefits of medical care outcomes in general, though with some emphasis on medicines. It mentions focus to promote the main aim of its unusual theme of describing the phenomenology of benefits and harms experienced by people in as full a way as possible and then taking that knowledge to give a picture of why medicines can be both effective and risky.

Introduction: Valproic acid is an effective first line drug for the treatment of epilepsy. Hepatotoxicity is a rare and potentially fatal adverse reaction for this medicine. Objective: Firstly to characterise valproic acid reports on children with fatal outcome and secondly to determine reporting over time of hepatotoxicity with fatal outcome. Methods: Individual case safety reports (ICSRs) for children ≤17 years with valproic acid and fatal outcome were retrieved from the WHO Global ICSR database, VigiBase, in June 2013. Reports were classified into hepatotoxic reactions or other reactions. Shrinkage observed-to-expected ratios were used to explore the relative reporting trend over time and for patient age. The frequency of polytherapy, i.e. reports with more than one antiepileptic medicine, was investigated. Results: There have been 268 ICSRs with valproic acid and fatal outcome in children, reported from 25 countries since 1977. A total of 156 fatalities were reported with hepatotoxicity, which has been continuously and disproportionally reported over time. There were 31 fatalities with pancreatitis. Other frequently reported events were coma/encephalopathy, seizures, respiratory disorders and coagulopathy. Hepatotoxicity was disproportionally and most commonly reported in children aged 6 years and under (104/156 reports) but affected children of all ages. Polytherapy was significantly more frequently reported for valproic acid with fatal outcome (58%) compared with non-fatal outcome (34%). Conclusion: Hepatotoxicity remains a considerable problem. The risk appears to be greatest in young children (6 years and below) but can occur at any age. Polytherapy is commonly reported and seems to be a risk factor for hepatotoxicity, pancreatitis and other serious adverse drug reactions with valproic acid. [ABSTRACT FROM AUTHOR]

This paper describes the personal views of the author about diagnosis and management of an adverse drug effect. It proposes that diagnosis is complicated and is also supported by carefully observed management of changes in drug therapy. Drug-related adverse effects may be due to the drug itself, though many are due to systematic errors occurring in the process from diagnosis of the primary treated condition, through prescribing and dispensing, to the way the drug is used by the patient. Bringing awareness of such systematic errors for consideration and management is part of a health care professional's responsibilities. [ABSTRACT FROM AUTHOR]

Child age-specific information on efficacy and risk of medicines can be limited for healthcare professionals and patients. It is therefore very important to make the best use of a risk planned approach to the pharmacological treatment of children. This means pharmacovigilance in the broadest sense of gaining the best data from the use of medicines in clinical practice. We consider issues that complicate safe medication use in paediatric care, as well as current progress and provide suggestions for building knowledge within paediatric pharmacovigilance to be used to minimise patient harm. The continuous development in children constitutes a challenge to prescribing and administering age-suitable doses for individual children. Children are not only different from adults but differ vastly within their own age group. Physical growth during childhood is apparent to the eye, but less obvious is the ongoing maturation of organ function important for drug disposition and action. Systematic issues such as medication errors, off-label use and the lack of age-suitable formulations are considerable obstacles for safe medication use in paediatrics. The recognition of emerging adverse drug reactions could be more challenging in developing children. Initiatives to improve the situation have been made by the WHO and regulators in the USA and EU. Age-specific changes in physiology, pharmacology and psychology, as well as systematic issues specific for children need to be considered in the work of assessing spontaneous reports in children. Pharmacovigilance needs to broaden its aims considerably beyond merely capturing new associations between drugs and events, and encompass careful collection on patient characteristics and circumstances around the reported adverse drug reaction to provide essential information that will give clues on how to prevent harm to children. [ABSTRACT FROM AUTHOR]

An editorial is presented on the importance of this journal in dealing with a variety of issues including complications of COVID-19.

An introduction is presented in which the editor discusses articles in the issue on topics including the highest possible quality of care, and the condition of being protected from or unlikely to cause danger, risk, or injury.

The author reflects on the landscape of pharmacovigilance (PV). He mentions issues affecting efforts in improving the safety of drugs and benefit-risk balance. He also notes that the said landscape is driven by a combination of patient/health professional reports and general needs of consumers.

The author reflects on decision dilemmas in pharmacovigilance. He explores the significant role of the lack of resources in making decisions in pharmacovigilance, discussing the existence of two questions associated to drug safety and efficacy evaluation. He suggests on the importance of the readiness to share information in a general and specific matter in pharmacovigilance.

Adverse drug reactions are the fifth most frequent cause of deaths in developed countries, effectively a global epidemic. However, progress in ameliorating the problem has been slow. Pharmacovigilance currently operates without clear objectives in relation to individual decisions, with no protocol (although risk management plans are a great step forward), with obscure materials and methods used for making decisions, with very limited reasoning and discussion, and little or no follow up and audit of the results. Problems include under-reporting, poor quality reports, underuse of the latest communications technology and suboptimal individual feedback to reporters. Assessment of causality is poor, impeding decision-making. After signal detection, more active measures to assess the risk to public health are needed. Other essential factors include precision about the ways in which data are prepared and transformed into databases, the recognition of secondary effects, which may be more obvious than the primary effect, but not so easy to link causally, and cognisance of all kinds of interactions. Areas that should be developed include pharmacoepidemiology, knowledge finding (through data mining), and communication and systems technology. The general way forward seems clear: a rigorous way of documenting all the steps, from getting reports of harms into regulatory databases to assessing their effects on public health, is essential and should be publicly reviewed for weaknesses. In turn, matters would be much improved by input on benefit/harm perceptions from patient groups, influencing decisions about what should be the true targets for regulatory and pharmacovigilance activities, avoiding second guessing by regulators. [ABSTRACT FROM AUTHOR]

Causality has been a topic of debate by philosophers, scientists, lawyers and for centuries. It is essential to define as precisely as possible all steps in the logical chain of events, since each may strengthen or confound an argument. Almost always there are issues of missing and conflicting data that need to be addressed specifically. In pharmacovigilance, as in many other situations, there is not just one possible causation for an effect but several. Each must be evaluated in the given context for probability. There is also likely to be a causal chain of events to the adverse effect under consideration, and each must be considered. In an individual patient diagnosis the components of patient history, clinical findings and various laboratory test findings are combined to point to the probability of the patho-physiological diagnosis, which in turn is related to possible causes with a strength determined by the constellation of findings. The established Bradford-Hill criteria are valuable in considering all the possible causal factors. Pharmacoepidemiology allows for population incidences of causes for particular effects and therefore provides an a priori probability listing for competing possible causes, or at least of one possible cause against the background of all others in a control group. Since adverse effects of medicines are generally rare, it is not possible to exclude drug causation in an individual by reliance on epidemiological evidence alone, only to argue that the incidence is below a level determined by statistical power, of the study or studies combined. Other areas of society are concerned with the process of causal inference, and this is especially true in legal cases in which judgements are made on possible personal injury by drugs. [ABSTRACT FROM AUTHOR]

In writing an expert report for any court or tribunal, account must be taken of that body's needs and where necessary of its strengths and weaknesses. The essential elements are truth, clarity and conciseness. The expert should indicate the nature and source of any standards that he applies. Above all he must beware of venturing into matters that lie in any sense outside his own defined area of expertise. [ABSTRACT FROM AUTHOR]

The medical doctor is sometimes called upon to serve in the courts as expert witness. The work is challenging and has serious implications for the legal and justice system. The outcome of a case may adversely affect the lives of real people when the evidence is not presented appropriately. However, there is reluctance from doctors to participate in the court process. The health professional may not be trained in the art of being a court witness and while scientifically qualified, may not provide the due diligence in explaining the issues properly to the members of the court. Some of the issues that may affect the outcome of a legal case include late discovery of conflicts of interest, inability to communicate well and stick to scientific facts, the inefficiencies of the legal system, and testifying against a medical colleague. There is merit to recommend that all medical doctors must undergo theoretical and practical training when presented as expert witness in courts. Five cases are presented here as illustrations of doctors involved in court cases. [ABSTRACT FROM AUTHOR]

In courts case histories play a central part when a crime may have resulted from an effect of a prescribed drug; in civil cases where a person may have suffered damage from a drug; and in coroners' enquiries into the cause of unexplained deaths. The court must decide two important questions: 1. Can the suspected medication(s) cause this kind of effect? 2. Did it (or they) do so in this particular case? Many judges and coroners have not addressed these questions clearly and have not used expert witnesses consistently, on occasion disregarding scientific evidence. Courts need to appoint experts to explain and interpret the scientific evidence. Few judges are equipped to resolve contradictions between different experts. Brief accounts of five cases from four countries illustrate these points. The reluctance of legal processes to implicate drugs as a possible cause of violent behaviour leads to injustice. Courts must be required to obtain appropriate expert evidence, and be given independent data on which drugs can cause such behaviour. [ABSTRACT FROM AUTHOR]

Until recently epidemiological evidence was not regarded as helpful in determining cause and effect. It generated associations that then had to be explained in terms of bio-mechanisms and applied to individual patients. A series of legal cases surrounding possible birth defects triggered by doxylamine (Bendectin) and connective tissue disorders linked to breast implants made it clear that in some instances epidemiological evidence might have a more important role, but the pendulum swung too far so that epidemiological evidence has in recent decades been given an unwarranted primacy, partly perhaps because it suits the interests of certain stakeholders. Older and more recent epidemiological studies on doxylamine and other antihistamines are reviewed to bring out the ambiguities and pitfalls of an undue reliance on epidemiological studies. [ABSTRACT FROM AUTHOR]

A thorough analysis of a case that involves a medication that may have caused or contributed to an adverse outcome, or a comparison of two compounds in a patent dispute, requires consideration of many processes that affect the clinical effects of a medication. These include its chemical structure, its pharmacological actions (pharmacodynamics), the pharmaceutical formulation, and its absorption, distribution, metabolism, and excretion (pharmacokinetics). They also include analysis of clinical details, including the diagnosis, the quality of the prescribing decisions, the accuracy of the prescription, dispensing, and administration of medications, and how appropriately the case was managed, including monitoring. A causality assessment should be attempted for both the general case and the particular case. Knowledge of the systems that describe a medication's mechanisms of action (EIDOS) and the dose-relationships and time-courses of adverse outcomes and individual susceptibilities to them (DoTS) can inform several aspects of the analysis. Reports should be written in clear English and should not contain statements that rely on expertise that the expert does not possess. [ABSTRACT FROM AUTHOR]

Laboratory evidence of the presence and concentration of a drug in a person who has come to harm is often helpful in forensic pharmacology, and may be crucial. However, its value depends on two critical interpretations by the expert. First, the expert must make a careful analysis of the relationship between the results as measured in the sample and the drug in the patient at the time that harm occurred. That is especially difficult with post-mortem samples. Secondly, the expert must syntheses the laboratory information with the available clinical history and clinical or pathological findings. Even in the most favourable circumstances, when the sample is correctly obtained, identified, and analyzed, it can be hard to say that beyond reasonable doubt a given concentration had a given effect. [ABSTRACT FROM AUTHOR]

The article examines whether there is sufficient specialism within the existing field of forensic pharmacology to justify a discrete sub-discipline of forensic pharmacovigilance (PV). Topics include an introduction to forensic science and a description of PV and the main tasks of PV, such as identifying problems with medicinal products. Also discussed is the role and scope of PV and the challenges of the legal system, such as the legal system's unfamiliarity with PV.

The article presents the author's views on the future of pharmacovigilance. It is stated that the drug safety has been considered as an epidemiological or public health exercise. The author opined that most of the adverse reactions to drugs are comparatively uncommon and they more usually result from individual patient idiosyncracy or from the way in which the drug is used.

An editorial is presented on the Transparency which is a major challenge since most of the public will wish, and there will be different needs for different people. The article discusses the varying from those who are expert to those with no relevant knowledge and varying from those with a rapid grasp of new issues and those without; and Public trust will only come if the majority feel their needs are fulfilled.

Background: The WHO Foundation Collaborating Centre for International Drug Monitoring (Uppsala Monitoring Centre [UMC]) has received many individual case safety reports (ICSRs) associating HMG-CoA reductase inhibitor drug (statin) use with the occurrence of muscle damage, including rhabdomyolysis, and also peripheral neuropathy. A new signal has now appeared of disproportionally high reporting of upper motor neurone lesions.Aim and Scope: The aim of this paper is to present the upper motor neurone lesion cases, with other evidence, as a signal of a relationship between statins and an amyotrophic lateral sclerosis (ALS)-like syndrome. The paper also presents some arguments for considering that a spectrum of severe neuromuscular damage may be associated with statin use, albeit rarely. The paper does not do more than raise the signal for further work and analysis of what must be regarded as a potentially very serious and perhaps avoidable or reversible adverse reaction, though it also suggests action to be taken if an ALS-like syndrome should occur in a patient using statins.Methods: The 43 reports accounting for the disproportional reports in Vigibase (the database of the WHO Programme for International Drug Monitoring) are summarised and analysed for the diagnosis of an ALS-like syndrome. The issues of data quality and potential reporting bias are considered.Results: 'Upper motor neurone lesion' is a rare adverse event reported in relationship to drugs in Vigibase (a database containing nearly 4 million ICSRs). Of the total of 172 ICSRs on this reported term, 43 were related to statins, of which 40 were considered further: all but one case was reported as ALS. In 34/40 reports a statin was the sole reported suspected drug. The diagnostic criteria were variable, and seven of the statin cases also had features of peripheral neuropathy. Of a total of 5534 ICSRs of peripheral neuropathy related to any drug in Vigibase, 547 were on statins. The disproportional reporting of statins and upper motor neurone lesion persisted after age stratification, and such disproportionality was not seen for statins and Parkinson's disease, Alzheimer's disease, extrapyramidal disorders, or multiple sclerosis-like syndromes.Discussion: Because the cases were sometimes atypical we propose the use of the term 'ALS-like syndrome' and speculate whether this is part of a spectrum of rare neuromuscular damage. The diagnosis of ALS is often problematic, and the insidiousness and chronicity of the disease make causality with a drug difficult to assess. The disproportionally high reporting makes this an important signal nevertheless, since ALS is serious clinically and statins are so widely used. Wide use of the statins also makes a chance finding more probable, but is unlikely to cause disproportional reporting when there are no obvious biases identified.Conclusion: We emphasise the rarity of this possible association, and also the need for further study to establish whether a causal relationship exists. We do advocate that trial discontinuation of a statin should be considered in patients with serious neuromuscular disease such as the ALS-like syndrome, given the poor prognosis and a possibility that progression of the disease may be halted or even reversed. [ABSTRACT FROM AUTHOR]

The article discusses how vaccination against COVID-19, is a current challenge with mass exposure to new agents which will be used in some disposition that may either mean the vaccines may not be as effective as found in relatively small numbers in the studies, or those with vulnerability or disease that makes individuals prone to adverse effect. It also highlights need of health professionals, scientists and politicians must play their part in evaluations and interpretation.

We compared the size, culturability, diversity, and dominant species similarity of the bacterial communities of Leucanthemopsis alpina (L.) Heywood rhizosphere and adjacent bare soil (interspace) along a chronosequence of soil development time (5, 50, and 70 years) in the forefield of the Dammaglacier (Switzerland). We found no evidence that the size of the bacterial community was significantly affected by either soil age or the presence of L. alpina. In contrast, the proportion of the bacterial community that could be cultured on nonselective agars, and which was taken as an indication of the proportion of r-selected populations, was significantly higher in the 50- and 70-year-old soils than in the 5-year-old soil, and was also significantly higher in the rhizosphere of L. alpina at all time points. RDA indicated significant correlations between the increased culturability of the bacterial community over time and increasing concentrations of labile N, and between the increased culturability in the rhizosphere and increased concentrations of labile C and N. HaeIII-amplified ribosomal DNA (rDNA) restriction analysis of a library of 120 clones of 16S rDNA revealed 85 distinct phylotypes. Hurlbert's probability of interspecific encounter (PIE) values derived from this library ranged from 0.95 to 1.0, indicating a very high genetic diversity. There was no significant difference in the PIE values of rhizosphere and interspace communities. Detrended correspondence analysis (DCA) of 16S ribosomal RNA (rRNA) denaturing gradient gel electrophoresis (DGGE) community profiles clearly distinguished the rhizosphere from the interspace community in the 5-year-old soils and also clearly distinguished between these communities and the rhizosphere and interspace communities of the 50- and 70-year-old soils. However, 16S rRNA DGGE revealed little difference between rhizosphere and interspace communities in the 50- and 70-year-old soils. The relative similarity of the 16S rRNA profiles strongly reflected labile carbon and nitrogen availability. Overall, our results suggest that improved C and N availability in the rhizosphere of L. alpina increases the size of r-selected bacterial species populations, but that the influence of L. alpina depends on soil age, being maximal in the youngest soils and minimal in the oldest. The reduced influence of L. alpina in the older soils may reflect a feedback between improved nutrient availability and reduced rhizodeposition. [ABSTRACT FROM AUTHOR]

The expanded use of multiple antiretroviral drugs during pregnancy has led to a reduction in the occurrence of perinatal transmission of HIV to <2%, but has led to concerns regarding both short-term toxicity and the long-term impact on the woman and her child. Enhanced toxicity of nevirapine has been noted among women with CD4+ lymphocyte counts >250 cells/μL at treatment initiation and among pregnant women on long-term didanosine and stavudine. These drugs should be avoided in such situations if alternatives are available. Efavirenz has been associated with birth defects in monkeys, and several cases of neural tube defects have been reported in humans after first trimester exposure, so treatment with this drug should be avoided during the first trimester. Protease inhibitors have been associated with an increased risk of maternal glucose intolerance, pre-eclampsia and preterm birth in some, but not all, studies. Pregnancies exposed to antiretroviral therapy should be registered with the Antiretroviral Pregnancy Registry as early in pregnancy as possible in order to provide data on the risk of birth defects after exposure.The pharmacokinetics of nucleoside and non-nucleoside reverse transcriptase inhibitors are not significantly changed in pregnancy, so standard dosing may be used. However, concentrations of several protease inhibitors are lower in pregnancy, so ritonavir-boosting or increased doses are required. Of great theoretical concern is the impact of resistance mutations that develop following single-dose nevirapine therapy on the response to later therapy among women and their infected infants. The use of dual nucleoside therapy for 3–7 days after single-dose nevirapine in the mother reduces but does not eliminate the risk of nevirapine resistance; alternative regimens for prevention of resistance are under study, as are the subsequent responses of the mother and her infant to therapy. Short courses of prophylactic zidovudine and nevirapine have been well tolerated in neonates. Concern has been raised, however, that these exposures may lead to persistent mitochondrial dysfunction or later cancers, underscoring the need for long-term surveillance of antiretroviral-exposed, HIV-uninfected infants. [ABSTRACT FROM AUTHOR]

The increasing size of spontaneous report data sets and the increasing capability for screening such data due to increases in computational power has led to a recent increase in interest and use of data mining on such data. While data mining plays an important role in the analysis of spontaneous reports, there is general debate on how and when data mining should be best performed. While the cornerstone principles for data mining of spontaneous reports have been in place since the 1960s, several significant changes have occurred to make their use widespread. Superficially the Bayesian methods seem unnecessarily complex, particularly given the nature of the data, but in practice implementation in Bayesian framework gives clear benefits. There are difficulties evaluating the performance of the methods, but they work and save resources in managing large data sets. The use of neural networks allows more sophisticated pattern recognition to be performed. [ABSTRACT FROM AUTHOR]

Focuses on an article written about Lapdap, a combination drug for the treatment of falciparum malaria, published in the June 12, 2005 issue of "Sunday Times--Britain" newspaper. Concerns raised by the World Health Organization regarding the safety of taking Lapdap; Efforts made to delay or prevent the development of drug resistance.

Children and young people have a right to privacy and respect. However, conflict can arise, particularly in relation to family life, which cannot be side-stepped by nurses. This article gives an overview of the legal and ethical rights of children and young people. [ABSTRACT FROM AUTHOR]

Focuses on the side effects of rofecoxib. Pharmacovigilance and drug safety concerns; Signals of increased risk of cardiovascular disorders with the use of rofecoxib.

The WHO World Alliance on Patient Safety is a new, all encompassing project to improve medical care. Individual patients are the focus and all countries are encouraged to develop systems in which medical error, therapeutic accidents and failures are minimised. The potential for adverse events is present at all levels of healthcare and in all disciplines. One working group in the Alliance is charged with promoting and developing a 'reporting and learning' culture for adverse events in all areas of medical care. Central to current thinking for this group is a no-fault approach and to report near misses. The aim is not to provide certainty over the individual events, but rather to draw attention to possible improvements in systems that may prevent future problems. Adverse events relating to drug therapy have been reported for decades to national pharmacovigilance authorities, but this is aimed at finding problems with the drugs themselves as early as possible. The Alliance approach in the area of drug safety, by contrast, has a greater focus on safety in the systems of drug provision (including prescription and dispensing) and other systematic issues relating to safe drug provision, such as fraudulent drugs. Thus, current pharmacovigilance can be seen as representing a part of the reporting and learning envisaged by the Alliance. The two approaches are also complementary, but there are practical and philosophical areas of overlap in which difficulties may occur, such as anonymised reporting in a no-fault system and consequent impossibility for follow-up. In pharmacovigilance follow-up for more information is regarded as essential. Whether pharmacovigilance broadens into the area of patient safety or the latter involves completely new systems to do its work will be a matter for each country to consider. One thing is certain, working together both systems will improve patient care, but without cooperation more bureaucracy will take valuable health professional time with a lesser result. [ABSTRACT FROM AUTHOR]

The WHO World Alliance on Patient Safety is a new, all encompassing project to improve medical care. Individual patients are the focus and all countries are encouraged to develop systems in which medical error, therapeutic accidents and failures are minimised. The potential for adverse events is present at all levels of healthcare and in all disciplines. One working group in the Alliance is charged with promoting and developing a 'reporting and learning' culture for adverse events in all areas of medical care. Central to current thinking for this group is a no-fault approach and to report near misses. The aim is not to provide certainty over the individual events, but rather to draw attention to possible improvements in systems that may prevent future problems. Adverse events relating to drug therapy have been reported for decades to national pharmacovigilance authorities, but this is aimed at finding problems with the drugs themselves as early as possible. The Alliance approach in the area of drug safety, by contrast, has a greater focus on safety in the systems of drug provision (including prescription and dispensing) and other systematic issues relating to safe drug provision, such as fraudulent drugs. Thus, current pharmacovigilance can be seen as representing a part of the reporting and learning envisaged by the Alliance. The two approaches are also complementary, but there are practical and philosophical areas of overlap in which difficulties may occur, such as anonymised reporting in a no-fault system and consequent impossibility for follow-up. In pharmacovigilance follow-up for more information is regarded as essential. Whether pharmacovigilance broadens into the area of patient safety or the latter involves completely new systems to do its work will be a matter for each country to consider. One thing is certain, working together both systems will improve patient care, but without cooperation more bureaucracy will take valuable health professional time with a lesser result. [ABSTRACT FROM AUTHOR]