The evidence-based medicine paradigm: where are we 20 years later? Part 1.

The evidence-based medicine (EBM) paradigm, introduced in 1992, has had a major and positive impact on all aspects of health care. However, widespread use has also uncovered some limitations; these are discussed from the perspectives of two clinicians in this, the first of a two part narrative review. For example, there are credible reservations about the validity of hierarchical levels of evidence, a core element of the EBM paradigm. In addition, potential and actual methodological and statistical deficiencies have been identified, not only in many published randomized controlled trials but also in systematic reviews, both rated highly for evidence in EBM classifications. Ethical violations compromise reliability of some data. Clinicians need to be conscious of potential limitations in some of the cornerstones of the EBM paradigm, and to deficiencies in the literature.

The evidence-based medicine paradigm: where are we 20 years later? Part 2.

In Part 2, we discuss the challenges of keeping up with the 'literature,' evidence-based medicine (EBM) in emerging economies and the Neurosciences, and two recent approaches to classifying evidence. We conclude by summarizing information from Parts 1 and 2 which suggest the need to critically re-appraise core elements of the EBM paradigm: (1) the hierarchical ranking of evidence, (2) randomized controlled trials or systematic reviews as the gold standard for all clinical questions or situations, (3) the statistical tests that have become integral to the 'measurements' for analyzing evidence, and (4) re-incorporating a role for evidence from basic sciences and pathophysiology. An understanding of how cognitive processes influence clinical decisions is also necessary to improve evidence-based practice. Emerging economies may have to modify the design and conduct of clinical research to their settings. Like all paradigms, EBM must keep improving with input from the grassroots to remain beneficial.

Chronic daily headache in children and adolescents.

Chronic daily headache (CDH) may be primary or secondary. Secondary causes can be suspected through "red flags" in the history and examination. With a prevalence of at least 1% and several associations, primary CDH is a common, often complex, chronic pain syndrome in children and adolescents. The intricate associations between stressors, psychiatric disorders (especially anxiety and depression), and CDH can be explained by "the limbically augmented pain syndrome" proposed by Rome and Rome. Disorders of sleep and other pain syndromes also may co-occur. For these reasons, a multiaxial classification is ideal. Many with primary CDH have features of both chronic migraine and chronic tension-type headache, contributing to confusion in subtyping. Primary CDH is often transformed from a primary episodic headache type, stressors being most responsible. Genetic factors also may facilitate chronification. Management should be biopsychosocial, family-centered, and often multidisciplinary, drugs being only one component. Treatment is still based on consensus, not evidence. Girls, migraineurs, and those with psychiatric comorbidity, medication overuse, and CDH onset before the age of 13 years and lasting for 2 years or longer, are at high risk for persistence; hence, such patients should be followed up into adult life. A classification for CDH should be included in the third edition of the International Classification of Headache Disorders.

The iatrogenic opioid crisis: An example of 'institutional corruption of pharmaceuticals'?

RATIONALE: Prescribed opioids are major contributors to the international public health opioid crisis. Such widespread iatrogenic harms usually result from collective decision failures of healthcare organizations rather than solely of individual organizations or professionals. Findings from a system-wide safety analysis of the iatrogenic opioid crisis that includes roles of pertinent healthcare organizations may help avoid or mitigate similar future iatrogenic consequences. In this retrospective exploratory study, we report such an analysis. METHODS: The study population encompassed the entire age spectrum and included those in whom opioids prescribed for chronic pain (unrelated to malignancy) were associated with death or morbidity. Root cause analysis, incorporating recent suggestions for improvement, was used to identify possible contributory factors from the literature. Based on their mandated roles and potential influences to prevent or mitigate the iatrogenic crisis, relevant organizations were grouped and stratified from most to least influential. RESULTS: The analysis identified a chain of multiple interrelated causal factors within and between organizations. The most influential organizations were pharmaceutical, political, and drug regulatory; next: experts and their related societies, and publications. Less influential: accreditation, professional licensing and regulatory, academic and healthcare funding bodies. Collectively, their views and decisions influenced prescribing practices of frontline healthcare professionals and advocacy groups. Financial associations between pharmaceutical and most other organizations/groups were common. Ultimately, patients were adversely affected. There was a complex association with psychosocial variables. LIMITATIONS: The analysis suggests associations not causality. CONCLUSION: The iatrogenic crisis has multiple intricately linked roots. The major catalyst: pervasive pharma-linked financial conflicts of interest (CoIs) involving most other healthcare organizations. These extensive financial CoIs were likely triggers for a cascade of erroneous decisions and actions that adversely affected patients. The actions and decisions of pharma ranged from unethical to illegal. The iatrogenic opioid crisis may exemplify 'institutional corruption of pharmaceuticals'.

Chronic daily headache in children and adolescents: a multi-faceted syndrome.

Chronic daily headache (CDH) is a multi-faceted, often complex pain syndrome in children and adolescents. Chronic daily headache may be primary or secondary. Chronic migraine and chronic tension-type are the most frequent subtypes. Chronic daily headache is co-morbid with adverse life events, anxiety and depressive disorders, possibly with other psychiatric disorders, other pain syndromes and sleep disorders; these conditions contribute to initiating and maintaining CDH. Hence, early management of episodic headache and treatment of associated conditions are crucial to prevention. There is evidence for the benefit of psychological therapies, principally relaxation and cognitive behavioral, and promising information on acupuncture for CDH. Data on drug treatment are based primarily on open label studies. The controversies surrounding CDH are discussed and proposals for improvement presented. The multifaceted nature of CDH makes it a good candidate for a multi-axial classification system. Such an approach should facilitate biopsychosocial management and enhance consistency in clinical research.

Susceptibility to febrile seizures: more than just a faulty thermostat!

Febrile seizures, always a hot topic, continue to fire up the interest of a wide spectrum of clinical and basic neuroscientists. Several clinical investigators, amongst them the Halifax group (spearheaded by the Camfields to whom we owe a great debt of gratitude for their contributions in this field), have provided us with a sound foundation for clinical management. We now need to explore febrile seizures in new ways to clarify factors and identify mechanisms that contribute to the intriguing age-dependent susceptibility. The complex processes involved in thermoregulation and the febrile response are important pieces of the puzzle. The contributory factors are likely different for isolated simple febrile, recurrent febrile and complex febrile seizures. A 'systems biology approach' is needed to investigate the intricate genome-proteome-metabolome interaction in determining susceptibility. Population studies that incorporate current clinical, experimental, infectious and molecular genetic knowledge in their concept and design will help to 'conquer' the final frontiers of febrile seizures. In 2006, Engel suggested that febrile seizures could 'encompass many different entities', an increasingly plausible opinion. A higher profile for febrile seizures and related syndromes in the ILAE classification scheme will further catalyze progress in the field. The resultant knowledge can only improve management.

Tension-type headache in children: the Cinderella of headache disorders!

Tension-type headache (TTH) may be as common a headache disorder as migraine in children and adolescents. TTH has a neurobiological basis with genetic and environmental factors making variable contributions to the different sub-types. The diagnostic criteria for TTH in the second edition of the "International Classification of Headache Disorders" appear to be applicable to children. Anxiety and mood disorders may be co-morbid with frequent episodic and chronic TTH. Psychosocial stressors play an important role in precipitating and maintaining TTH. Hence, a biopsychosocial approach should be adopted for care. Standardized histories and examinations together with prospective headache diaries are the foundations for good management; attention to 'red flags' will help identify secondary causes that present with headache similar to TT. There are no randomized controlled drug trials for the treatment of TTH. Relaxation and cognitive behavioral therapies are effective. TTH in children and adolescents warrants greater recognition from the clinician and scientist. Studies focusing on TTH are overdue.

Gating the holes in the Swiss cheese (part I): Expanding professor Reason's model for patient safety.

INTRODUCTION: Although patient safety has improved steadily, harm remains a substantial global challenge. Additionally, safety needs to be ensured not only in hospitals but also across the continuum of care. Better understanding of the complex cognitive factors influencing health care-related decisions and organizational cultures could lead to more rational approaches, and thereby to further improvement. HYPOTHESIS: A model integrating the concepts underlying Reason's Swiss cheese theory and the cognitive-affective biases plus cascade could advance the understanding of cognitive-affective processes that underlie decisions and organizational cultures across the continuum of care. METHODS: Thematic analysis, qualitative information from several sources being used to support argumentation. DISCUSSION: Complex covert cognitive phenomena underlie decisions influencing health care. In the integrated model, the Swiss cheese slices represent dynamic cognitive-affective (mental) gates: Reason's successive layers of defence. Like firewalls and antivirus programs, cognitive-affective gates normally allow the passage of rational decisions but block or counter unsounds ones. Gates can be breached (ie, holes created) at one or more levels of organizations, teams, and individuals, by (1) any element of cognitive-affective biases plus (conflicts of interest and cognitive biases being the best studied) and (2) other potential error-provoking factors. Conversely, flawed decisions can be blocked and consequences minimized; for example, by addressing cognitive biases plus and error-provoking factors, and being constantly mindful. Informed shared decision making is a neglected but critical layer of defence (cognitive-affective gate). The integrated model can be custom tailored to specific situations, and the underlying principles applied to all methods for improving safety. The model may also provide a framework for developing and evaluating strategies to optimize organizational cultures and decisions. LIMITATIONS: The concept is abstract, the model is virtual, and the best supportive evidence is qualitative and indirect. CONCLUSIONS: The proposed model may help enhance rational decision making across the continuum of care, thereby improving patient safety globally.

Status epilepticus in pediatric practice: neonate to adolescent.

SE in the pediatric age group presents challenges in diagnosis and management. There is need for renewed consensus on the temporal definition of SE, both clinical and electrographic. SE in children exhibits an age-dependent vulnerability, with genetic predisposition and etiology as determinants of susceptibility. Nonepileptic phenomena may mimic SE. Clinical and electrographic SE in neonates are relatively rare, while serial (clinical and electrographic) and repetitive seizures are more common. Neurometabolic disease, chromosomal disorders, and abnormalities of cortical development are important etiological considerations. Abrupt discontinuation of or an aberrant response to AEDs can also precipitate SE. Metabolic perturbations and toxins can further aggravate the situation. Clinical and experimental data suggest that the longer a seizure lasts, the more difficult it becomes to control, and that seizures can have immediate and long-term adverse consequences on the immature and developing brain. Hence, treatment (usually with a benzodiazepine) should be started early in the clinical course. A trial of pyridoxine, biotin, or folinic acid should be considered in the appropriate clinical setting (e.g., neonates or young infants, in particular). Phenytoin/fosphenytoin and phenobarbital remain important treatment options. Pentobarbital and midazolam are preferred choices in the management of RSE. Once metabolic causes are excluded, children with RSE should be evaluated for surgical treatment early in the clinical course. Clinical guidelines based on best available evidence have to be periodically reviewed. The clinical consequences and management of electrographic SE, especially in the neonate, have to be addressed. Guidelines for continuous (video) EEG monitoring are needed to facilitate this task. AEDs that do not have an adverse effect on the developing brain have to be developed. Our review suggests a continuing need for prospective studies into all aspects of SE in the pediatric age group.

Visual-sensitive epilepsies: classification and review.

Photosensitivity, photosensitive seizures, and photosensitive epilepsy are discussed. The International League against Epilepsy has suggested the term "visual-sensitive" replace "photosensitive". Visual-sensitive seizures may be more common than is realized. A classification for visual-sensitive epilepsies is presented. Chromosomal and DNA testing may help to refine the classification further. A standardized approach for neurophysiologic testing, such as that proposed by European experts, is recommended. These steps should promote evidenced-based management for this group of disorders.

A 'reluctant' critical review: 'Manual for evidence-based clinical practice (2015)'.

BACKGROUND: The Users' Guides to the Medical Literature Manual has been a major influence on the teaching and practice of health care globally. METHODS: The 3rd edition of the multi-authored Manual was reviewed using the principles outlined in Evidence-based Medicine (EBM) texts. One 'clinical scenario' was selected for critical appraisal, as were several chapters; objectivity was enhanced by citing references to support opinions. RESULTS (SUMMARY OF THE APPRAISAL): (1) Strengths: Clinical pearls, too numerous to list. EXAMPLES: (i) evidence is never enough to drive clinical decision making; (ii) do not rush to adopt new interventions; and (iii) question efficacy data based only on surrogate markers. (2) Weaknesses: The Manual shares shortcomings of textbooks discussed by Straus et al.: (i) references may not be current, important ones may be excluded and citations may be selective; (ii) often, opinion-based; and (iii) delays between revisions. (3) Notable omissions: Little or no discussion of: (i) important segments of the population: those <18 years of age, >65 years of age and those with multimorbidity; (ii) surgical disciplines; (iii) Greenhalgh et al.'s essay on EBM; (iv) alternate views on the hierarchy of evidence; and (vi) critical thinking. (4) Additional issues: (i) Omission of important references on dabigatran (clinical scenario: chapter 13.1); (ii) authors' advice (Chapter 13.3) to 'bypass the discussion section of published research'; and (iii) the advocacy of pre-appraised sources of evidence and network meta-analysis without warnings about limitations, are critiqued. CONCLUSION: The Manual has several clinical pearls but readers should also be aware of shortcomings.

Mixed migraine and tension-type: a common cause of recurrent headache in children.

OBJECTIVE: Determine relative frequency of recurrent headache (HA) types in children and adolescents referred to a pediatric neurologist. STUDY DESIGN: Prospective, sequential, and observational. SETTING: Private practice Pediatric Neurology Clinic in a Canadian city (Winnipeg). Patients and data collection: Information on those referred with HA between September 1998 and December 2001 was entered on data sheets. Patients were followed up for one month to four years. RESULTS: Three hundred and twenty (69%) of 463 referred with HA had recurrent HA. There were 172 males (54%) and 148 (46%) females. Their ages ranged from two years to 19 years (median: 11 years). They had had their HA disorder for one month to 14 years (median: two years) prior to assessment. Migraine was the main HA type in 124 (38%), tension-type headache (TTH) in 57 (18%) and mixed migraine and TTH in 101 (32%). Thus, 101 (45%) of 225 with migraine as one HA type also had TTH. CONCLUSIONS: Tension-type headache and migraine frequently co-exist and may represent a distinct headache type, at least in children; the association will likely influence response of affected children and adolescents to specific migraine treatments in clinical trials or practice.