Management of seizures following a stroke: what are the options?

Post-stroke seizures are a frequent cause of remote symptomatic epilepsy in adults, especially in older age. About 10% of stroke patients will suffer a seizure, depending on risk factors, such as the type, location and severity of the stroke. Previous stroke accounts for 30-40% of all cases of epilepsy in the elderly. Compared with that in younger patients, the appearance of seizures in old age is less specific and may take time before a diagnosis can be proven. The optimal timing and type of antiepileptic drug (AED) treatment for patients with post-stroke seizures is still a controversial issue. Many population- and hospital-based studies have been performed, ending with generalized recommendations, but still the decision to initiate AED treatment after a first or second seizure should be individualized. Prospective studies in the literature showed that immediate treatment after a first unprovoked seizure does not improve the long-term remission rate. However, because of the physical and psychological influences of recurrent seizures, prophylactic treatment should be considered after a first unprovoked event in an elderly person at high risk of recurrence, taking into consideration the individuality of the patient and a discussion with the patient and his/her family about the risks and benefits of both options. The latest studies regarding post-stroke seizure treatment showed that 'new-generation' drugs, such as lamotrigine, gabapentin and levetiracetam, in low doses would be reasonable because of their high rate of long-term seizure-free periods, improved safety profile, and fewer interactions with other drugs, especially anticoagulant ones, compared with first-generation AEDs. On the other hand, first-generation drugs, such as phenytoin, carbamazepine and phenobarbital, have the potential to have a harmful impact on recovery, bone health, cognition and blood sodium levels and may interact with other treatments used by the elderly population. The drug chosen for use in the elderly population should possess a wide spectrum of activity and have few side effects. An assessment should be done to identify possible drug-drug interactions, the drug should be started at a low dose and titrated slowly to the lowest maintenance dose possible, and enhanced quality of life should be a focus of treatment. So, in the end, further research is needed to determine, more appropriately, the type of AED therapy, timing and duration of treatment.     

Periodontal Disease and Atherosclerotic Cardiovascular Disease: Confounding Effects or Epiphenomenon?

Recent evidence suggests that periodontal disease may predispose to atherosclerotic cardiovascular disease. Data support mechanisms of host-derived local and systemic proinflammatory responses similar to atherosclerosis, consisting of monocytic-derived cytokines and other inflammatory mediators, which are induced by periodontal pathogens and its endotoxin, lipopolysaccharide. These mechanisms may contribute to the start of vascular endothelial dysfunction and further sequelae leading to atherosclerosis. Experimental evidence and biologic plausibility appear to support this proposal. However, clinical evidence from a MEDLINE search from January 1966-December 1999 proposed a weak or no correlation primarily due to confounding factors. The aim of care is to reduce vulnerable pathogens from the infected periodontium by standard treatment; however, new approaches appear promising. Increased awareness of a potential link among infective agents, immunoinflammatory processes, and atherosclerosis may clarify clinical implications.     

Vitamins and cognition: what is the evidence?

Vitamin supplements are consumed for their purported health benefits by a large segment of the populations of developed countries. Several indirect strands of evidence suggest that increasing levels of vitamins may improve brain function. These include evidence that individual vitamins are intrinsically involved in the cellular and physiological processes underpinning brain function; that small proportions of the population exhibit biochemical deficiencies in each individual vitamin, suggesting that a much larger proportion have less than optimal overall micronutrient status; and that epidemiological research suggests a relationship between individual vitamins (or the potentially neurotoxic amino acid homocysteine, which is related to B vitamin status), and cognitive function and mood. The related question as to whether direct supplementation with vitamins can therefore improve psychological functioning in cognitively intact individuals has been addressed in a number of studies. The evidence reviewed here suggests that, whereas studies involving supplementation with single vitamins, or restricted ranges of vitamins, have demonstrated equivocal results, evidence from studies involving the administration of broader ranges of vitamins, or multivitamins, suggest potential efficacy in terms of cognitive and psychological functioning. In contrast to the literature investigating restricted ranges of vitamins, most of the evidence regarding multivitamins was collected from healthy, non-elderly samples, suggesting that more research in this population is warranted.     

Nanoparticulate Systems for Nasal Delivery of Drugs: A Real Improvement over Simple Systems?

This review discusses the possible benefits of using nanoparticles for nasal delivery of drugs and vaccines. It considers the various factors affecting particle transport across the nasal tissue. The evidence for the improved transport of drugs, such as peptides and proteins, across the nasal epithelium when formulated in a nanoparticulate system, as compared to an optimal solution formulation, is not convincing. For instance it has been shown that a chitosan solution and especially a chitosan powder formulation was superior in enhancing the nasal absorption of insulin as compared to chitosan nanoparticles. On the other hand, the use of nanoparticles for vaccine delivery seems beneficial in that good immune responses are achieved. This could be due to the fact that small particles can be transported preferentially by the lymphoid tissue of the nasal cavity (NALT). However, apparently no studies have been published comparing directly other adjuvant nasal systems with nanoparticulate systems.     

Cardiovascular and renal effects of nociceptin/orphanin FQ: a new mediator to target?

Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the N/OFQ peptide receptor. N/OFQ acts directly on blood vessels as a relaxant, and is unlikely to cross the blood-brain barrier due to its size. In anesthetized rats and conscious animals, intravenous N/OFQ produces transient hypotension and bradycardia that may involve interactions with the sympathetic and parasympathetic nervous systems. Injected intracerebro-ventricularly or directly into brain tissue, N/OFQ also affects the cardiovascular system. For example, N/OFQ causes water diuresis (aquaresis), which may represent the most immediate potential of targeting N/OFQ in the cardiovascular/ renal systems. Aquaretics are useful in the treatment of edema/hyponatremia which ultimately occurs in end-stage heart failure, liver cirrhosis and the syndrome of inappropriate secretion of antidiuretic hormone.     

Drug-Related Visits to the Emergency Department: How Big Is the Problem?

OBJECTIVES: To review the literature concerning drug-related problems that result in emergency department visits, estimate the frequency of these problems and the rates of hospital admissions, and identify patient risk factors and drugs that are associated with the greatest risk. METHODS: A systematic search of MEDLINE (January 1966-December 2001), EMBASE (January 1980-December 2001), and PubMed (January 1966-December 2001) databases for full reports published in English was performed. The Ottawa Valley Regional Drug Information Service database of nonindexed pharmacy journals also was searched. RESULTS: Data from eight retrospective and four prospective trials retrieved indicated that as many as 28% of all emergency department visits were drug related. Of these, 70% were preventable, and as many as 24% resulted in hospital admission. Drug classes often implicated in drug-related visits to an emergency department were nonsteroidal antiinflammatory drugs, anticonvulsants, antidiabetic drugs, antibiotics, respiratory drugs, hormones, central nervous system drugs, and cardiovascular drugs. Common drug-related problems resulting in emergency department visits were adverse drug reactions, noncompliance, and inappropriate prescribing. CONCLUSION: Drug-related problems are a significant cause of emergency department visits and subsequent resource use. Primary caregivers, such as family physicians and pharmacists, should collaborate more closely to provide and reinforce care plans and monitor patients to prevent drug-related visits to the emergency department and subsequent morbidity and mortality.     

Psychoneurendocrinology: a science of the past or a new pathway for the future?

Psychoneuroendocrinology is a branch of neuroscience that developed in the beginning of the last century, which investigates the possibility of a cause-effect link between endocrinopathies and mental disorders - with these studies ending in negative results. Psychoneuroendocrinology was then used as a methodological approach for the investigation of neurotransmitter function, on the basis of the observation that neurotransmitters regulate neurohormone and peripheral hormone secretions. Data were obtained for hypothalamic noradrenergic, serotoninergic, dopaminergic, gabaergic and acetylcholinergic functions, which could not be automatically extended to higher brain centers whose impairments might be etiopathogenetically involved in the development of mental disorders. Future studies should focus on new methodological approaches to brain biochemistry, on investigation of genetic, molecular biology, brain imaging, psychoneuroimmunoendocrinology, neuropeptide and neurosteroid secretion in relation to brain endocrine function in mental diseases.     

Satisfaction Survey for a Medication Management Program: Satisfaction Guaranteed?

Background:

Providing clinical pharmacy services to patients in their homes after discharge from hospital has been reported to reduce health care costs and improve outcomes. The Medication Management Program of the Fraser Health Authority involves pharmacists making home visits to provide clinical pharmacy services to elderly patients who have recently been discharged from hospital and others considered to be at high risk for adverse drug events. Although clinical and economic outcomes of this program have been evaluated, humanistic outcomes such as satisfaction have not been assessed. Moreover, very little evaluation of patient satisfaction with home pharmacy services has been reported in the literature.

Objective:

To evaluate patient satisfaction with the Medication Management Program.

Methods:

A telephone survey instrument, consisting of 7 Likert-scale items and 2 open-ended questions, was developed and administered to patients who received a home pharmacist visit between September 1 and November 23, 2011. In addition to the survey responses, demographic and clinical data for both respondents and nonrespondents were collected.

Results:

Of the 175 patients invited to participate in the survey, 103 (58.9%) agreed to participate. The majority of respondents agreed or strongly agreed with all of the survey items, indicating satisfaction with the program. For example, 97 (94%) agreed or strongly agreed that they would recommend the pharmacist home visit program continue to be available, and all 103 (100%) agreed or strongly agreed that they were satisfied with the pharmacist home visit. Respondents provided some suggestions for program improvement.

Conclusions:

The survey findings demonstrate that patients were satisfied with the home clinical pharmacy services offered through the Fraser Health Medication Management Program.     

Management of simple insect bites: where's the evidence?

Many insects bite in order to obtain a blood meal and, in the process, inject the victim with saliva that may contain a number of substances, some of which can be immunogenic. The consequences of insect bites include local reactions, immune (allergic) reactions including anaphylaxis, and secondary bacterial infections (e.g. impetigo, cellulitis). Although insect bites are perceived to be common in the UK, the exact incidence is difficult to estimate since most are likely to go unreported: only those causing the more serious reactions are seen in primary care settings. Simple insect bites are those that are not accompanied or followed by anaphylactic shock or systemic infection. Many preparations for the treatment of insect bites, including antihistamines and topical corticosteroids, are available for purchase over the counter (OTC) in the UK. However, there is a lack of evidence for the efficacy of these treatments and, in general, recommendations for treatment are based on expert opinion and clinical experience. This article reviews the evidence for the management of simple bites by insects commonly encountered in the UK, but excludes ticks, mites and lice.     

A 'league table' of contingent valuation results for pharmaceutical interventions: a hard pill to swallow?

Pharmaceutical expenditure represents a large percentage of total healthcare expenditure, and has thus received much attention within the economic evaluation literature. However, although the number of contingent valuation (CV) studies measuring willingness to pay (WTP) in healthcare has increased, little is known about the relative magnitude of values elicited across different interventions, diseases or countries, or the methodological comparability of these values. We address this gap by seeking to establish if it is feasible to use elicited WTP values in resource allocation, illustrated by attempting to compile a 'league table' of WTP values for pharmaceutical interventions. A review database was compiled for CV studies in healthcare published from January 1985 to December 2005. Of 210 studies identified, 40 considered pharmaceutical interventions. Values are presented as mean or median WTP values, adjusted where necessary to pound and $US for 2004/5. Lack of reporting in some instances of either the mean or median, together with heterogenous methods and infrequent reporting of costs, made 'league table' construction difficult. This raises questions about the use of existing studies for resource allocation decisions, despite the fact that most studies were seemingly undertaken for policy objectives. However, four interventions had more than one study, making it possible to compare the values elicited. The values elicited across studies were fairly consistent for two interventions (anti-hypertensive therapy and tumour necrosis factor [TNF]-alpha blockade for rheumatoid arthritis), whereas WTP values for insulin and post-operative emesis therapy were very divergent. No single methodological difference seemed to explain this pattern; however, the more methodological differences between studies the greater the likelihood of divergent values. A checklist, or minimum reporting set of information, is the first step towards improving the consistency of methods, and therefore values, published. In the longer term, a move towards the use of a reference case akin to that used for cost-utility studies would seem important if such studies are to be used for comparative purposes and thereby be relevant to resource allocation decision making.     

A Mechanism for Hormesis — A Problem in the Wrong Discipline

The wealth of examples of hormesis exhibiting the beta curve leave little doubt as to the generality of the phenomenon. However, its full acceptance requires a satisfactory theoretical basis to account for the diversity of instances of hormesis; without it the concept has little meaning beyond what is obvious from the defining beta curve. It has been proposed that a homeostatic hypothesis is the most plausible and is gaining support. However, there is a need to involve researchers in other disciplines than toxicology to identify physiological mechanisms to account for it, whereupon hormesis can begin to gain wider recognition and fulfill its potential in pure and applied science.

Normal science… often suppresses fundamental novelties because they are necessarily subversive of its basic commitments.

Thomas S. Kuhn 1962

Every novel idea….must, before it wins general acceptance, pass through three stages. It is, to begin with, repudiated as absurd. After that it is allowed to be reasonable. And, finally, it is belittled as obvious.

Almroth Wright (1861–1947)     

Somatostatin: a hormone for the heart?

Somatostatin (somatotropin release inhibitory factor; SRIF) peptides are widely distributed throughout the mammalian body and act through a family of genetically distinct, guanine nucleotide regulatory protein coupled (G-protein-coupled), cell surface receptors (sst(1-5)). Compelling evidence shows that SRIF and SRIF peptidyl analogs modulate vascular function, with actions upon smooth muscle and endothelium. SRIF receptors are known to exist in the carotid endothelium, a principal target for the pro-inflammatory cascade that accompanies coronary artery disease. SRIF-14 and SRIF analogs are anti-inflammatory but the molecular mechanism involved remains unclear. Since crucial steps in the endothelial inflammation response include endothelial activation by cytokines, adhesion molecule expression and cell-monocyte interactions, peptide agents that inhibit these steps might provide a novel strategy for reducing vascular inflammation. SRIF, acting through its cognate receptors, modulates a variety of intracellular effectors that are linked to inflammation including phosphotyrosine phosphatases, the extracellular regulated protein kinase 1 and 2 (ERK1/2) cascade, adenylyl cyclase and endothelial nitric oxide synthase. Directly or indirectly, SRIF also functions to inhibit endothelial cell proliferation and induce apoptosis. A detailed understanding of SRIF actions could provide a rational basis for using SRIF ligands in controlling vascular inflammation and inhibiting cytokine signaling, critical events in atherogenesis.