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'.

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.

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.

Evidence-informed person-centred health care (part II): are 'cognitive biases plus' underlying the EBM paradigm responsible for undermining the quality of evidence?

INTRODUCTION: Recently, some leaders of the evidence-based medicine (EBM) movement drew attention to the "unintended" negative consequences associated with EBM. The term 'cognitive biases plus' was introduced in part I to encompass cognitive biases, conflicts of interests, fallacies and certain behaviours. HYPOTHESIS: 'Cognitive biases plus' in those closely involved in creating and promoting the EBM paradigm are responsible for their (1) inability to anticipate and then recognize flaws in the tenets of EBM; (2) discounting alternative views; and (3) delaying reform. METHODS: A narrative review style was used, with methods as in part I. APPRAISAL OF LITERATURE: Over the past two decades there has been mounting qualitative and quantitative methodological evidence to suggest that the faith placed in (1) the EBM hierarchy with randomized controlled trials and systematic reviews at the summit; (2) the reliability of biostatistical methods to quantitate data; and (3) the primacy of sources of pre-appraised evidence, is seriously misplaced. Consequently, the evidence that informs person-centred care is compromised. DISCUSSION: Arguments focusing on 'cognitive biases plus' are offered to support our hypothesis. To the best of our knowledge, EBM proponents have not provided an explanation. CONCLUSIONS: Reform is urgently needed to minimize continuing risks to patients. If our hypothesis is correct, then in addition to the suggestions made in part I, deficiencies in the paradigm must be corrected. Meaningful solutions are only possible if the biases of scientific inbreeding and groupthink are minimized by collaboration between EBM leaders and those who have been sounding warning bells.

Evidence-informed person-centered healthcare part I: do 'cognitive biases plus' at organizational levels influence quality of evidence?

INTRODUCTION: There is increasing concern about the unreliability of much of health care evidence, especially in its application to individuals. HYPOTHESIS: Cognitive biases, financial and non-financial conflicts of interest, and ethical violations (which, together with fallacies, we collectively refer to as 'cognitive biases plus') at the levels of individuals and organizations involved in health care undermine the evidence that informs person-centred care. METHODS: This study used qualitative review of the pertinent literature from basic, medical and social sciences, ethics, philosophy, law etc. RESULTS: Financial conflicts of interest (primarily industry related) have become systemic in several organizations that influence health care evidence. There is also plausible evidence for non-financial conflicts of interest, especially in academic organizations. Financial and non-financial conflicts of interest frequently result in self-serving bias. Self-serving bias can lead to self-deception and rationalization of actions that entrench self-serving behaviour, both potentially resulting in unethical acts. Individuals and organizations are also susceptible to other cognitive biases. Qualitative evidence suggests that 'cognitive biases plus' can erode the quality of evidence. CONCLUSIONS: 'Cognitive biases plus' are hard wired, primarily at the unconscious level, and the resulting behaviours are not easily corrected. Social behavioural researchers advocate multi-pronged measures in similar situations: (i) abolish incentives that spawn self-serving bias; (ii) enforce severe deterrents for breaches of conduct; (iii) value integrity; (iv) strengthen self-awareness; and (v) design curricula especially at the trainee level to promote awareness of consequences to society. Virtuous professionals and organizations are essential to fulfil the vision for high-quality individualized health care globally.

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.

Nontraumatic coma in children and adolescents: diagnosis and management.

The causes of nontraumatic coma (NTC) vary by country, season and period of data collection. Infective diseases are among the major worldwide causes of NTC. Nonaccidental head injury must be in the differential diagnosis. Genetic and ethnic susceptibilities to causes of coma are being recognized. A systematic history and examination are essential for diagnosis, early recognition of herniation syndromes, and management. The management of NTC is discussed, with reference to clinical approach, treatment of seizures, and increased intracranial pressure. Public health measures, education, early diagnosis, and prompt appropriate treatment are the foundations needed to reduce incidence and improve outcome.

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.

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.

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.