[The PRISMA 2020 statement: an updated guideline for reporting systematic reviewsDeclaración PRISMA 2020: una guía actualizada para la publicación de revisiones sistemáticas]. / A declaração PRISMA 2020: diretriz atualizada para relatar revisões sistemáticas.

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.

La declaración PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), publicada en 2009, se diseñó para ayudar a los autores de revisiones sistemáticas a documentar de manera transparente el porqué de la revisión, qué hicieron los autores y qué encontraron. Durante la última década, ha habido muchos avances en la metodología y terminología de las revisiones sistemáticas, lo que ha requerido una actualización de esta guía. La declaración PRISMA 2020 sustituye a la declaración de 2009 e incluye una nueva guía de presentación de las publicaciones que refleja los avances en los métodos para identificar, seleccionar, evaluar y sintetizar estudios. La estructura y la presentación de los ítems ha sido modificada para facilitar su implementación. En este artículo, presentamos la lista de verificación PRISMA 2020 con 27 ítems, y una lista de verificación ampliada que detalla las recomendaciones en la publicación de cada ítem, la lista de verificación del resumen estructurado PRISMA 2020 y el diagrama de flujo revisado para revisiones sistemáticas.

The PRISMA 2020 statement: An updated guideline for reporting systematic reviews.

Matthew Page and co-authors describe PRISMA 2020, an updated reporting guideline for systematic reviews and meta-analyses.

Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization: The STROBE-MR Statement.

Importance: Mendelian randomization (MR) studies use genetic variation associated with modifiable exposures to assess their possible causal relationship with outcomes and aim to reduce potential bias from confounding and reverse causation. Objective: To develop the STROBE-MR Statement as a stand-alone extension to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guideline for the reporting of MR studies. Design, Setting, and Participants: The development of the STROBE-MR Statement followed the Enhancing the Quality and Transparency of Health Research (EQUATOR) framework guidance and used the STROBE Statement as a starting point to draft a checklist tailored to MR studies. The project was initiated in 2018 by reviewing the literature on the reporting of instrumental variable and MR studies. A group of 17 experts, including MR methodologists, MR study design users, developers of previous reporting guidelines, and journal editors, participated in a workshop in May 2019 to define the scope of the Statement and draft the checklist. The draft checklist was published as a preprint in July 2019 and discussed on the preprint platform, in social media, and at the 4th Mendelian Randomization Conference. The checklist was then revised based on comments, further refined through 2020, and finalized in July 2021. Findings: The STROBE-MR checklist is organized into 6 sections (Title and Abstract, Introduction, Methods, Results, Discussion, and Other Information) and includes 20 main items and 30 subitems. It covers both 1-sample and 2-sample MR studies that assess 1 or multiple exposures and outcomes, and addresses MR studies that follow a genome-wide association study and are reported in the same article. The checklist asks authors to justify why MR is a helpful method to address the study question and state prespecified causal hypotheses. The measurement, quality, and selection of genetic variants must be described and attempts to assess validity of MR-specific assumptions should be well reported. An item on data sharing includes reporting when the data and statistical code required to replicate the analyses can be accessed. Conclusions and Relevance: STROBE-MR provides guidelines for reporting MR studies. Improved reporting of these studies could facilitate their evaluation by editors, peer reviewers, researchers, clinicians, and other readers, and enhance the interpretation of their results.

Ten Eleven Things Not to Say to Healthcare Professionals During the Coronavirus Disease 2019 Pandemic.

On March 11, 2020, the infection caused by the coronavirus disease 2019 (COVID-19) virus was declared a pandemic. Throughout this pandemic, healthcare professionals (HCPs) have experienced difficulties stemming from poor communications, resource scarcity, lack of transparency, disbelief, and threats to the safety of their loved ones, their patients, and themselves. As part of these hardships, negative statements have been heard repeatedly. This paper describes 11 scenarios of unhelpful and dysfunctional messages heard by the authors and their colleagues during the COVID-19 pandemic, reported to us by a combination of peers, administrative leadership, and the public. We explain why not to use such messaging, and we suggest more helpful and compassionate expressions based upon recommendations published by scientific organizations and well-established psychological principles. The first 10 scenarios discussed include (1) lack of understanding regarding the extent of the pandemic; (2) shaming over not seeing patients in person; (3) lack of clear and consistent communication from leadership on pandemic-related practice changes; (4) opinions that personal protective equipment (PPE) use by HCPs causes fear or is unnecessary; (5) forcing in-person care without appropriate PPE; (6) the risk of exposure to asymptomatic individuals as it relates to opening clinics; (7) media gag orders; (8) pay and benefit reductions; (9) spreading of misinformation about the COVID-19 pandemic; and (10) workload expectations. The 11th scenario addresses HCPs' psychological and physical reactions to this challenging and prolonged stressful situation. We close by discussing the need for support and compassion at this difficult and unpredictable time and by offering suggestions to foster resilience and feelings of self-efficacy among HCPs.

Safety Problems With a Transdermal Patch for Migraine: Lessons From the Development, Approval, and Marketing Process.

OBJECTIVE: We sought to analyze publicly available information about patient harm associated with an iontophoretic sumatriptan patch, to identify what went wrong and to suggest ways in which similar problems might be prevented in the future. BACKGROUND: The Zecuity® sumatriptan iontophoretic transdermal system was marketed for acute treatment of migraine. The patch was withdrawn less than 10 months after its introduction because of multiple reports of scarring and burning. As of 2018, the FDA Adverse Event Reporting System public dashboard lists a total of 2889 reports of safety problems with the patch, 904 of which were classified as serious. METHODS: For this narrative review, we examined US Food and Drug Administration documents related to the new drug application for this product and its approval. We searched Clinicaltrials.gov, PubMed, Google, Facebook, Twitter, and Instagram public posts for relevant information relating to the patch, its approval, marketing, and complications. RESULTS: The FDA knew about problems with burns and scarring prior to approval of the product, and turned down the initial new drug application for this reason and because of other quality problems with the patch. The reapplication was approved despite continued concerns of several FDA reviewers about safety. The approval required the manufacturer to comply with enhanced postmarketing safety reporting. However, product information and labeling did not mention the possibility of burns or scarring. Approval was based on 1 clinical trial and 2 open label studies in which reporting of adverse events was suboptimal. The clinical trials had been prospectively registered but outcomes had been changed around the time the trial concluded. Aggressive marketing efforts and social media activity may have contributed to inaccurate perceptions of safety and efficacy, but social media also provided a written and photographic record of burns and other harm suffered by patients who used the patch. CONCLUSIONS: Our review identified several problems with the development, testing, approval, and marketing of the Zecuity patch. To improve the process of developing headache treatments, it is important to consider the lessons that can be drawn from an examination of this high-profile failure of the drug development and regulatory system.

Amitriptyline Dose and Treatment Outcomes in Specialty Headache Practice: A Retrospective Cohort Study.

OBJECTIVE: To characterize treatment patterns and real world outcomes in headache patients treated with amitriptyline in an academic headache center. DESIGN AND METHODS: A retrospective chart review identified 178 patients in our center who were given a new prescription for amitriptyline in treatment of headache, and who were seen in follow-up within one year. Charts were reviewed to identify dosing patterns (initial and maximum dose) and persistence, patient-reported headache benefit, and reported side effects. Variables assessed in relation to medication use were comorbid psychiatric disease, headache characteristics, and prior use of a preventive medication. RESULTS: We followed patients for an average of 6.5 months. Initial and maximum prescribed amitriptyline doses were characterized as: "very low" (≤10 mg daily), "low" (11-25 mg daily), and "traditional" (≥25 mg daily). The initial dose of amitriptyline ranged from 2.5 to 50 mg daily, though most patients were started on a dose of 10 mg daily (112/178, 63%). Approximately 3/4 of the patients were found to have improvement (134/178) and 85% (129/151) were still taking amitriptyline at the last follow-up appointment. Maximum dosing ranged from 2.5 to 100 mg daily with most patients taking 10-25 mg (86/146, 58%). The most commonly reported adverse effect was daytime fatigue (17/151, 11%). There did not appear to be any effect from gender, ethnicity, race, diagnosis of sleep apnea, chronicity of migraine, presence of aura on our outcome measures. CONCLUSION: Our study supports the common clinical practice of using low doses of amitriptyline to treat chronic headache disorders and suggests that it was effective and well tolerated at doses lower than those used in many clinical trials. Use of low dosage amitriptyline may also improve medication persistence, an important clinical consideration in the management of this common and chronic condition. A subgroup of patients may experience a dramatic benefit from amitriptyline and this could warrant further investigation.

Assessing Barriers to Chronic Migraine Consultation, Diagnosis, and Treatment: Results From the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study.

OBJECTIVE: To assess the rates and predictors of traversing steps essential to good medical care for chronic migraine, including: (1) medical consultation, (2) accurate diagnosis, and (3) minimal pharmacologic treatment. Candidate predictors included socioeconomic, demographic, and headache-specific variables. BACKGROUND: Previous research has established that barriers to effective management for episodic migraine include the absence of health insurance, lack of appropriate medical consultation, failure to receive an accurate diagnosis, and not being offered a regimen with acute and preventive treatments. METHODS/DESIGN: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, a longitudinal web-based panel study of migraine, included a cross-sectional module focused on patterns of and barriers to medical care. Participants eligible for this analysis met the study criteria for chronic migraine, had evidence of headache-related disability, and provided data on health insurance status. The main outcomes in the current analysis included the proportion of respondents who sought consultation for headache with a designated healthcare professional, self-reported receiving a diagnosis of chronic or transformed migraine, and received minimal pharmacologic treatment for headache with a focus on prescribed acute and preventive treatments. RESULTS: In the CaMEO Study, 80,783 respondents provided study data, 16,789 (20.8% of respondents) met criteria for migraine, and 1476 (8.8% of those with migraine) met chronic migraine criteria. In total, 1254 participants (85.0% of those with chronic migraine) met inclusion criteria for this analysis. Of those, 512 respondents (40.8%) reported currently consulting with a healthcare professional for headache. Odds of consulting increased with increasing age (OR 1.02; 95% CI 1.01-1.03), body mass index (BMI) (OR 1.01; 95% CI 1.00-1.03), migraine-related disability (OR 1.02; 95% CI 1.00-1.04), and migraine severity (OR 1.16; 95% CI 1.11-1.22) and presence of health insurance (OR 4.61; 95% CI 3.05-6.96). Among those consulting a healthcare professional, 126 (24.6%) received an accurate diagnosis and 56 of those with a correct diagnosis (44.4%) received both acute and preventive pharmacologic treatments; odds of a CM diagnosis were higher for women (OR 1.93; 95% CI 1.03-3.61), those with greater migraine severity (OR 1.25; 95% CI 1.14-1.37), and those currently consulting a specialist (OR 2.38; 95% CI 1.54-3.69). No predictors of receiving appropriate treatment were identified among those currently consulting. Among our sample of people with chronic migraine, only 56 (4.5%) individuals successfully traversed the series of 3 barriers to successful chronic migraine care (ie, consulted a healthcare professional for migraine, received an accurate diagnosis, and were prescribed minimal acute and preventive pharmacologic treatments). CONCLUSION: Our findings suggest that <5% of persons with chronic migraine traversed 3 barriers to receiving care for headache (consultation, diagnosis, and treatment), representing a large unmet need for improving care in this population. Predictors of consulting a healthcare professional included age, having health insurance, greater migraine-related disability, and greater migraine symptom severity. Among those consulting, predictors of an appropriate diagnosis included consulting a specialist, female sex, and greater migraine severity. Public health efforts are needed to improve outcomes for patients with chronic migraine by a range of interventions and educational efforts aimed at improving consultation rates, diagnostic accuracy, and adherence to minimal pharmacologic treatment.

Behavioral and mind/body interventions in headache: unanswered questions and future research directions.

BACKGROUND: Many unanswered questions remain regarding behavioral and mind/body interventions in the treatment of primary headache disorders in adults. METHODS: We reviewed the literature to ascertain the most pressing unanswered research questions regarding behavioral and mind/body interventions for headache. RESULTS: We identify the most pressing unanswered research questions in this field, describe ideal and practical ways to address these questions, and outline steps needed to facilitate these research efforts. We discuss proposed mechanisms of action of behavioral and mind/body interventions and outline goals for future research in this field. CONCLUSIONS: Although challenges arise from the complex nature of the interventions under study, research that adheres to published study design and reporting standards and focuses closely on answering key questions is most likely to lead to progress in achieving these goals.

Sex differences in the prevalence, symptoms, and associated features of migraine, probable migraine and other severe headache: results of the American Migraine Prevalence and Prevention (AMPP) Study.

BACKGROUND: The strikingly higher prevalence of migraine in females compared with males is one of the hallmarks of migraine. A large global body of evidence exists on the sex differences in the prevalence of migraine with female to male ratios ranging from 2:1 to 3:1 and peaking in midlife. Some data are available on sex differences in associated symptoms, headache-related disability and impairment, and healthcare resource utilization in migraine. Few data are available on corresponding sex differences in probable migraine (PM) and other severe headache (ie, nonmigraine-spectrum severe headache). Gaining a clear understanding of sex differences in a range of severe headache disorders may help differentiate the range of headache types. Herein, we compare sexes on prevalence and a range of clinical variables for migraine, PM, and other severe headache in a large sample from the US population. METHODS: This study analyzed data from the 2004 American Migraine Prevalence and Prevention Study. Total and demographic-stratified sex-specific, prevalence estimates of headache subtypes (migraine, PM, and other severe headache) are reported. Log-binomial models are used to calculate sex-specific adjusted prevalence ratios and 95% confidence intervals for each across demographic strata. A smoothed sex prevalence ratio (female to male) figure is presented for migraine and PM. RESULTS: One hundred sixty-two thousand seven hundred fifty-six individuals aged 12 and older responded to the 2004 American Migraine Prevalence and Prevention Study survey (64.9% response rate). Twenty-eight thousand two hundred sixty-one (17.4%) reported "severe headache" in the preceding year (23.5% of females and 10.6% of males), 11.8% met International Classification of Headache Disorders-2 criteria for migraine (17.3% of females and 5.7% of males), 4.6% met criteria for PM (5.3% of females and 3.9% of males), and 1.0% were categorized with other severe headache (0.9% of females and 1.0% of males). Sex differences were observed in the prevalence of migraine and PM, but not for other severe headache. Adjusted female to male prevalence ratios ranged from 1.48 to 3.25 across the lifetime for migraine and from 1.22 to 1.53 for PM. Sex differences were also observed in associated symptomology, aura, headache-related disability, healthcare resource utilization, and diagnosis for migraine and PM. Despite higher rates of migraine diagnosis by a healthcare professional, females with migraine were less likely than males to be using preventive pharmacologic treatment for headache. CONCLUSIONS: In this large, US population sample, both migraine and PM were more common among females, but a sex difference was not observed in the prevalence of other severe headache. The sex difference in migraine and PM held true across age and for most other sociodemographic variables with the exception of race for PM. Females with migraine and PM had higher rates of most migraine symptoms, aura, greater associated impairment, and higher healthcare resource utilization than males. Corresponding sex differences were not observed among individuals with other severe headache on the majority of these comparisons. Results suggest that PM is part of the migraine spectrum whereas other severe headache types are not. Results also substantiate existing literature on sex differences in primary headaches and extend results to additional headache types and related factors.

Migraine and risk of incident diabetes in women: a prospective study.

BACKGROUND: Previous cross-sectional studies evaluating the relationship between diabetes prevalence and migraine status have found conflicting results. We examined the relationship between migraine and incident type 2 diabetes (T2D) in a cohort of adult women. METHODS: Prospective cohort study conducted among participants in the Women's Health Study who provided information on migraine and did not have diabetes at baseline. Our four exposure groups were migraine with aura, migraine without aura, past history of migraine and no history of migraine. Cox proportional hazards models were used to determine the hazard ratio for incident T2D. RESULTS: Among the 38,620 women included in this study, 5062 (13.1%) women had migraine, of whom 2014 (39.8%) reported migraine with aura, and 2087 (5.4%) women had a past history of migraine. During a mean of 14.6 years of follow-up, there were 3032 cases of incident T2D. After adjustment for confounders, the hazard ratio (95% confidence interval) for developing diabetes was 1.06 (0.91-1.24) for women with migraine with aura, 1.01 (0.89-1.16) for women with migraine without aura, and 1.13 (0.98-1.30) for women with a past history of migraine compared with women with no history of migraine. CONCLUSION: Results of this prospective study in women do not support an association between migraine and incident T2D.

Naming migraine and those who have it.

Medical language has implications for both public perception of and institutional responses to illness. A consensus panel of physicians, academics, advocates, and patients with diverse experiences and knowledge about migraine considered 3 questions: (1) What is migraine: an illness, disease, syndrome, condition, disorder, or susceptibility? (2) What ought we call someone with migraine? (3) What should we not call someone with migraine? Although consensus was not reached, the responses were summarized and analyzed quantitatively and qualitatively. Panelists participated in writing and editing the paper. The panelists agreed that "migraine," not "migraine headache," was generally preferable, that migraine met the dictionary definition for each candidate moniker, terms with psychiatric valence should be avoided, and "sufferer" should be avoided except in very limited circumstances. Overall, while there was no consensus, "disease" was the preferred term in the most situations, and illness the least preferred. Panelists disagreed strongly whether one ought to use the term "migraineur" at all or if "person with migraine" was preferable. Panelists drew upon a variety of principles when considering language choices, including the extent to which candidate monikers could be defended using biomedical evidence, the cultural meaning of the proposed term, and the context within which the term would be used. Panelists strove to balance the need for terms to describe the best science on migraine, with the desire to choose language that would emphasize the credibility of migraine. The wide range of symptoms of migraine and its diverse effects may require considerable elasticity of language.

Tolerance to the beneficial effects of prophylactic migraine drugs: a systematic review of causes and mechanisms.

Loss of benefit of a previously effective treatment regimen, also known as tolerance, can be an important barrier to the successful preventive treatment of migraine. We undertook a systematic review of the literature to identify the prevalence and possible mechanisms of drug tolerance in migraine prophylaxis. Results demonstrate that the frequency of tolerance to prophylactic migraine treatment is unknown, but available data support an estimate that it occurs in 1-8% of patients receiving prophylaxis. Four broad types of tolerance were identified that are likely to be relevant to migraine prophylaxis. These are pharmacokinetic, pharmacodynamic, behavioral, and cross tolerance. The mechanisms that underlie these types of tolerance determine whether their effects can be overcome or minimized. For example, certain forms of tolerance may be affected by manipulation of environmental cues associated with drug administration, by the order in which drugs are used, and by the concomitant use of other medications. Many medications used for migraine prophylaxis exert their effects through the endogenous opioid system. The implications of this finding are explored, particularly the parallels between medication overuse headache and tolerance to migraine prophylaxis. Given the many ways in which tolerance to migraine medications may develop, in some ways it is not surprising that migraine-preventive drugs stop working; it is more surprising that in many cases they do not.

Tolerance and loss of beneficial effect during migraine prophylaxis: clinical considerations.

A familiar situation in migraine treatment is the patient with an initial positive response to prophylactic drug therapy who later experiences relapse. The goals of this paper are to provide a theoretical framework to help doctors think about this problem, to evaluate factors and response patterns that may be associated with different causes of relapse, and to suggest clinical strategies that may aid in its management. Six key explanations for loss of benefit from prophylactic therapy are: (1) pharmacokinetic, pharmacodynamic, and behavioral drug tolerance; (2) non-specific or placebo effects; (3) natural variability in disease activity; (4) disease progression; (5) inaccurate recall of treatment effects; and (6) drug delivery problems. Current options for patients who experience loss of benefit from prophylactic therapy include traditional techniques such as switching, re-trying, rotating, or combining drugs. Selected behavioral and environmental treatment techniques might also be useful. We describe a practical, structured approach to evaluation and management of relapse with migraine prophylaxis.

The PRISMA 2020 statement: An updated guideline for reporting systematic reviews.

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.

The PRISMA 2020 statement: An updated guideline for reporting systematic reviews.

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.

The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. / Declaración PRISMA 2020: una guía actualizada para la publicación de revisiones sistemáticas.

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews. Full English text available from:www.revespcardiol.org/en.