Current Role at Stanford
Senior Research Scientist Anesthesia Informatics and Media Lab
Associate Director Stanford Anesthesia Summer Institute
Co-Director Learnly Anesthesia/Stanford AIM Lab COVID-19 Evidence Service
Senior Research Advisor Stanford Medicine X
Co-Instructor Partnering with Patients EdX Online Series
Addressing Personal Protective Equipment (PPE) Decontamination: Methylene Blue and Light Inactivates SARS-CoV-2 on N95 Respirators and Medical Masks with Maintenance of Integrity and Fit.
Infection control and hospital epidemiology
OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE) underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate SARS-CoV-2-exposed masks and respirators. We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.DESIGN: The two arms of the study included: 1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment, and 2) PPE treatment with MBL for 5 cycles of decontamination (5CD) to determine maintenance of PPE performance.METHODS: MBL treatment was used to inactivate coronaviruses on three N95 filtering facepiece respirator (FFR) and two medical mask (MM) models. We inoculated FFR and MM materials with three coronaviruses, including SARS-CoV-2, and treated with 10 M MB and exposed to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5CD using multiple US and international test methods and compared to the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.RESULTS: Overall, MBL robustly and consistently inactivated all three coronaviruses with 99.8 - to >99.9% virus inactivation across all FFRs and MMs tested. FFR and MM integrity was maintained after 5 cycles of MBL treatment, whereas one FFR model failed after 5 cycles of VHP+O3.CONCLUSIONS: MBL treatment decontaminated respirators and masks by inactivating three tested coronaviruses without compromising integrity through 5CD. MBL decontamination is effective, low-cost and does not require specialized equipment, making it applicable in all-resource settings.
View details for DOI 10.1017/ice.2021.230
View details for PubMedID 34016200
An evidence review of face masks against COVID-19.
Proceedings of the National Academy of Sciences of the United States of America
2021; 118 (4)
The science around the use of masks by the public to impede COVID-19 transmission is advancing rapidly. In this narrative review, we develop an analytical framework to examine mask usage, synthesizing the relevant literature to inform multiple areas: population impact, transmission characteristics, source control, wearer protection, sociological considerations, and implementation considerations. A primary route of transmission of COVID-19 is via respiratory particles, and it is known to be transmissible from presymptomatic, paucisymptomatic, and asymptomatic individuals. Reducing disease spread requires two things: limiting contacts of infected individuals via physical distancing and other measures and reducing the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces transmissibility per contact by reducing transmission of infected respiratory particles in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. Given the current shortages of medical masks, we recommend the adoption of public cloth mask wearing, as an effective form of source control, in conjunction with existing hygiene, distancing, and contact tracing strategies. Because many respiratory particles become smaller due to evaporation, we recommend increasing focus on a previously overlooked aspect of mask usage: mask wearing by infectious people ("source control") with benefits at the population level, rather than only mask wearing by susceptible people, such as health care workers, with focus on individual outcomes. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation.
View details for DOI 10.1073/pnas.2014564118
View details for PubMedID 33431650
- Measuring the success of blinding in placebo-controlled trials: should we be so quick to dismiss it? Journal of clinical epidemiology 2021
- Survey of an online pulmonary wellness & rehabilitation program in people with chronic respiratory disease EUROPEAN RESPIRATORY SOC JOURNALS LTD. 2020
Household Materials Selection for Homemade Cloth Face Coverings and Their Filtration Efficiency Enhancement with Triboelectric Charging.
The COVID-19 pandemic is currently causing a severe disruption and shortage in the global supply chain of necessary personal protective equipment (e.g., N95 respirators). The U.S. CDC has recommended use of household cloth by the general public to make cloth face coverings as a method of source control. We evaluated the filtration properties of natural and synthetic materials using a modified procedure for N95 respirator approval. Common fabrics of cotton, polyester, nylon, and silk had filtration efficiency of 5-25%, polypropylene spunbond had filtration efficiency 6-10%, and paper-based products had filtration efficiency of 10-20%. An advantage of polypropylene spunbond is that it can be simply triboelectrically charged to enhance the filtration efficiency (from 6 to >10%) without any increase in pressure (stable overnight and in humid environments). Using the filtration quality factor, fabric microstructure, and charging ability, we are able to provide an assessment of suggested fabric materials for homemade facial coverings.
View details for DOI 10.1021/acs.nanolett.0c02211
View details for PubMedID 32484683
Managing ICU surge during the COVID-19 crisis: rapid guidelines.
Intensive care medicine
Given the rapidly changing nature of COVID-19, clinicians and policy makers require urgent review and summary of the literature, and synthesis of evidence-based guidelines to inform practice. The WHO advocates for rapid reviews in these circumstances. The purpose of this rapid guideline is to provide recommendations on the organizational management of intensive care units caring for patients with COVID-19 including: planning a crisis surge response; crisis surge response strategies; triage, supporting families, and staff.
View details for DOI 10.1007/s00134-020-06092-5
View details for PubMedID 32514598
TIDieR-Placebo: A guide and checklist for reporting placebo and sham controls.
2020; 17 (9): e1003294
Placebo or sham controls are the standard against which the benefits and harms of many active interventions are measured. Whilst the components and the method of their delivery have been shown to affect study outcomes, placebo and sham controls are rarely reported and often not matched to those of the active comparator. This can influence how beneficial or harmful the active intervention appears to be. Without adequate descriptions of placebo or sham controls, it is difficult to interpret results about the benefits and harms of active interventions within placebo-controlled trials. To overcome this problem, we developed a checklist and guide for reporting placebo or sham interventions.We developed an initial list of items for the checklist by surveying experts in placebo research (n = 14). Because of the diverse contexts in which placebo or sham treatments are used in clinical research, we consulted experts in trials of drugs, surgery, physiotherapy, acupuncture, and psychological interventions. We then used a multistage online Delphi process with 53 participants to determine which items were deemed to be essential. We next convened a group of experts and stakeholders (n = 16). Our main output was a modification of the existing Template for Intervention Description and Replication (TIDieR) checklist; this allows the key features of both active interventions and placebo or sham controls to be concisely summarised by researchers. The main differences between TIDieR-Placebo and the original TIDieR are the explicit requirement to describe the setting (i.e., features of the physical environment that go beyond geographic location), the need to report whether blinding was successful (when this was measured), and the need to present the description of placebo components alongside those of the active comparator.We encourage TIDieR-Placebo to be used alongside TIDieR to assist the reporting of placebo or sham components and the trials in which they are used.
View details for DOI 10.1371/journal.pmed.1003294
View details for PubMedID 32956344
Critical patient insights from the same-day feedback programme at Stanford Health Care.
BMJ open quality
2020; 9 (3)
Healthcare organisations now integrate patient feedback into value-based compensation formulas. This research considered Stanford Healthcare's same-day feedback, a programme designed to evaluate the patient experience. Specifically, how did patients with cancer interviewed in the programme assess their physicians? Furthermore, how did assessments differ across emotional, physical, practical and informational needs when interviewed by volunteer patient and family partners (PAFPs) versus hospital staff?Integral to this research was Communication Accommodation Theory (CAT), which suggests individuals adjust interactions based on conversational roles, needs and understanding. Previous influential research was conducted by Frosch et al (2012) and Di Bartolo et al (2017), who revealed barriers to patient-physician communication, and Baker et al (2011) who associated CAT with these interactions. However, we still did not know if patients alter physician assessments between interviewers.This mixed methods study worked with 190 oncology unit patient interviews from 2009 to 2017. Open-ended interview responses underwent thematic analysis. When compared with hospital staff, PAFPs collected more practical and informational needs from patients. PAFPs also collected more verbose responses that resembled detailed narratives of the patients' hospital experiences. This study contributed insightful patient perspectives of physician care in a novel hospital programme.
View details for DOI 10.1136/bmjoq-2019-000773
View details for PubMedID 32816863
Consistency of Recommendations for Evaluation and Management of Hypertension.
JAMA network open
2019; 2 (11): e1915975
Importance: Hypertension is very common, but guideline recommendations for hypertension have been controversial, are of increasing interest, and have profound implications.Objective: To systematically assess the consistency of recommendations regarding hypertension management across clinical practice guidelines (CPGs).Design, Setting, and Participants: This cross-sectional study of hypertension management recommendations included CPGs that had been published as of April 2018. Two point-of-care resources that provided graded recommendations were included for secondary analyses. Discrete and unambiguous specifications of the population, intervention, and comparison states were used to define a series of reference recommendations. Three raters reached consensus on coding the direction and strength of each recommendation made by each CPG. Three independent raters reached consensus on the importance of each reference recommendation.Main Outcomes and Measures: The main outcomes were rates of consistency for direction and strength among CPGs. Sensitivity analyses testing the robustness were conducted by excluding recommendation statements that were described as insufficient evidence, excluding single recommendation sources, and stratifying by importance of recommendations.Results: The analysis included 8 CPGs with a total of 71 reference recommendations, 68 of which had clear recommendations from 2 or more CPGs. Across CPGs, 22 recommendations (32%) were consistent in direction and strength, 18 recommendations (27%) were consistent in direction but inconsistent in strength, and 28 recommendations (41%) were inconsistent in direction. The rate of consistency was lower in secondary analyses. When insufficient evidence ratings were excluded, there was still substantial inconsistency, and a leave-one-out sensitivity analysis suggested the inconsistency could not be attributed to any single recommendation source. Inconsistency in direction was more common for recommendations deemed to be of lower importance (11 of 20 recommendations [55%]), but 17 of 48 high-importance recommendations (35%) had inconsistency in direction.Conclusions and Relevance: Hypertension is a common chronic condition with widespread expectations surrounding guideline-based care, yet CPGs have a high rate of inconsistency. Further investigations should determine the reasons for inconsistency, the implications for recommendation development, and the role of synthesis across recommendations for optimal guidance of clinical care.
View details for DOI 10.1001/jamanetworkopen.2019.15975
View details for PubMedID 31755945
Inadequate description of placebo and sham controls in a systematic review of recent trials
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
Poorly described placebo/sham controls make it difficult to appraise active intervention benefits and harms. The 12-item Template for Intervention Description and Replication (TIDieR) checklist was developed to improve the reporting of active interventions. The extent to which TIDieR has been used to improve description of placebo or sham control is not known.We systematically identified and examined all placebo/sham-controlled randomised trials published in 2018 in the top six general medical journals. We reported how many of the TIDieR checklist items were used to describe the placebo/sham control(s). We supplemented this with a sample of 100 placebo/sham-controlled trials from any journal and searched Google Scholar to identify placebo/sham-controlled trials citing TIDieR.We identified 94 placebo/sham-controlled trials published in the top journals in 2018. None reported using TIDieR, and none reported placebo or sham components completely. On average eight TIDieR items were addressed, with placebo/sham control name (100%) and when and how much was administered (97.9%) most commonly reported. Some items (rationale, 8.5%, whether there were modifications, 25.5%) were less often reported. In our sample of less well-cited journals, reporting was poorer (average of six items) and followed a similar pattern. Since TIDieR's first publication, six placebo-controlled trials have cited it according to Google Scholar. Two of these used the checklist to describe placebo controls; neither one completely desribed the placebo intervention.Placebo and sham controls are poorly described within randomised trials, and TIDieR is rarely used to guide these descriptions. We recommend developing guidelines to promote better descriptions of placebo/sham control components within clinical trials.
View details for DOI 10.1111/eci.13169
View details for Web of Science ID 000488572700001
View details for PubMedID 31519047
- Empathy as a state beyond feeling: a patient and clinician perspective JOURNAL OF THE ROYAL SOCIETY OF MEDICINE 2019; 112 (2): 57–60
SMOOTH: Self-Management of Open Online Trials in Health analysis found improvements were needed for reporting methods of internet-based trials
JOURNAL OF CLINICAL EPIDEMIOLOGY
2019; 105: 27–39
The growth of trials conducted over the internet has increased, but with little practical guidance for their conduct, and it is sometimes challenging for researchers to adapt the conventions used in face-to-face trials and maintain the validity of the work. The aim of the study is to systematically explore existing self-recruited online randomized trials of self-management interventions and analyze the trials to assess their strengths and weaknesses, the quality of reporting, and the involvement of lay persons as collaborators in the research process.The Online Randomized Controlled Trials of Health Information Database was used as the sampling frame to identify a subset of self-recruited online trials of self-management interventions. The authors cataloged what these online trials were assessing, appraised study quality, extracted information on how trials were run, and assessed the potential for bias. We searched out how public and patient participation was integrated into online trial design and how this was reported. We recorded patterns of use for registration, reporting, settings, informed consent, public involvement, supplementary materials, and dissemination planning.The sample included 41 online trials published from 2002 to 2015. The barriers to replicability and risk of bias in online trials included inadequate reporting of blinding in 28/41 (68%) studies; high attrition rates with incomplete or unreported data in 30/41 (73%) of trials; and 26/41 (63%) of studies were at high risk for selection bias as trial registrations were unreported. The methods for (23/41, 56%) trials contained insufficient information to replicate the trial, 19/41 did not report piloting the intervention. Only 2/41 studies were cross-platform compatible. Public involvement was most common for advisory roles (n = 9, 22%), and in the design, usability testing, and piloting of user materials (n = 9, 22%).This study catalogs the state of online trials of self-management in the early 21st century and provides insights for online trials development as early as the protocol planning stage. Reporting of trials was generally poor and, in addition to recommending that authors report their trials in accordance with CONSORT guidelines, we make recommendations for researchers writing protocols, reporting on and evaluating online trials. The research highlights considerable room for improvement in trial registration, reporting of methods, data management plans, and public and patient involvement in self-recruited online trials of self-management interventions.
View details for DOI 10.1016/j.jclinepi.2018.08.017
View details for Web of Science ID 000455971300005
View details for PubMedID 30171901
Frequency and format of clinical trial results dissemination to patients: a survey of authors of trials indexed in PubMed.
2019; 9 (10): e032701
Dissemination of research findings is central to research integrity and promoting discussion of new knowledge and its potential for translation into practice and policy. We investigated the frequency and format of dissemination to trial participants and patient groups.Survey of authors of clinical trials indexed in PubMed in 2014-2015.Questionnaire emailed to 19 321 authors; 3127 responses received (16%). Of these 3127 trials, 2690 had human participants and 1818 enrolled individual patients. Among the 1818, 498 authors (27%) reported having disseminated results to participants, 238 (13%) planned to do so, 600 (33%) did not plan to, 176 (10%) were unsure and 306 (17%) indicated 'other' or did not answer. Of the 498 authors who had disseminated, 198 (40%) shared academic reports, 252 (51%) shared lay reports, 111 (22%) shared both and 164 (33%) provided individualised study results. Of the 1818 trials, 577 authors (32%) shared/planned to share results with patients outside their trial by direct contact with charities/patient groups, 401 (22%) via patient communities, 845 (46%) via presentations at conferences with patient representation, 494 (27%) via mainstream media and 708 (39%) by online lay summaries. Relatively few of the 1818 authors reported dissemination was suggested by institutional bodies: 314 (17%) of funders reportedly suggested dissemination to trial participants, 252 (14%) to patient groups; 333 (18%) of ethical review boards reportedly suggested dissemination to trial participants, 148 (8%) to patient groups. Authors described many barriers to dissemination.Fewer than half the respondents had disseminated to participants (or planned to) and only half of those who had disseminated shared lay reports. Motivation to disseminate results to participants appears to arise within research teams rather than being incentivised by institutional bodies. Multiple factors need to be considered and various steps taken to facilitate wide dissemination of research to participants.
View details for DOI 10.1136/bmjopen-2019-032701
View details for PubMedID 31636111
Clinical significance of aberrant microRNAs expression in predicting disease relapse/refractoriness to treatment in diffuse large B-cell lymphoma: A meta-analysis.
Critical reviews in oncology/hematology
2019; 144: 102818
The clinical significance of aberrantly expressed microRNAs in predicting treatment response to chemotherapy in diffuse large B-cell lymphoma patients (DLBCL) remains uncertain. Feasibility of microRNA testing to predict treatment outcome was evaluated. Twenty-two types of aberrantly expressed microRNAs were associated with poor treatment response; pooled hazard ratio (HR) was 2.14 [95%CI:1.78-2.57, P < 0.00001]. DLBCL patients with aberrant expression of miR-155, miR-17/92 clusters, miR-21, miR-224, or miR-146b-5p had a higher risk of treatment resistance or shorter period of disease relapse/progression free survival, with HR = 2.71 (95%CI:1.66-4.42, P < 0.0001), HR = 2.70 (95%CI:1.50-4.85, P = 0.0010), HR = 2.20 (95%CI:1.31-3.69, P = 0.003), HR = 2.07 (95%CI:1.50-2.86, P < 0.00001), HR = 2.26 (95%CI:1.40-3.65, P = 0.0009), respectively. The association between aberrant expression of microRNAs and treatment response appears to be stronger in formalin-fixed-paraffin-embedded tissue (HR = 2.41, 95%CI:1.79-3.25, P < 0.00001) than in fresh-frozen samples (HR = 1.94, 95%CI: 1.22-3.08, P = 0.005) and peripheral blood samples (HR = 1.94, 95%CI:1.53-2.46, P < 0.00001). Mir-155, miR-17/92 clusters, miR-21, miR-224, and mir-146b-5p have value in predicting treatment response to chemotherapy in DLBCL.
View details for DOI 10.1016/j.critrevonc.2019.102818
View details for PubMedID 31733445
- Coproduction: when users define quality. BMJ quality & safety 2019
Middle-aged man who could not afford an angioplasty.
BMJ case reports
2019; 12 (3)
Coronary artery disease managed by percutaneous coronary intervention (PCI) has been noted for profit-driven overuse medicine. Concerns mount over inappropriate use of PCI for patients in India. We describe the case of a 55-year-old Indian man who presented for a second opinion following an urgent recommendation for PCI by two cardiologists following a recent acute myocardial infarction even though the patient was symptom-free and out of the window period for primary PCI. The proposed intervention placed the patient at financial risk for insolvency. This case report highlights the challenges and consequences of inappropriate overuse of PCI. Also, we outline the current lack of shared decision-making among patients and physicians for the PCI procedure. The challenges, inherent in the assumptions that overuse of PCI is evidence-based, are discussed including recommendations for the practice of evidence based medicine for this intervention.
View details for DOI 10.1136/bcr-2018-227118
View details for PubMedID 30936331
Rusty Microglia: Trainers of Innate Immunity in Alzheimer's Disease
FRONTIERS IN NEUROLOGY
2018; 9: 1062
Alzheimer's disease, the most common form of dementia, is marked by progressive cognitive and functional impairment believed to reflect synaptic and neuronal loss. Recent preclinical data suggests that lipopolysaccharide (LPS)-activated microglia may contribute to the elimination of viable neurons and synapses by promoting a neurotoxic astrocytic phenotype, defined as A1. The innate immune cells, including microglia and astrocytes, can either facilitate or inhibit neuroinflammation in response to peripherally applied inflammatory stimuli, such as LPS. Depending on previous antigen encounters, these cells can assume activated (trained) or silenced (tolerized) phenotypes, augmenting or lowering inflammation. Iron, reactive oxygen species (ROS), and LPS, the cell wall component of gram-negative bacteria, are microglial activators, but only the latter can trigger immune tolerization. In Alzheimer's disease, tolerization may be impaired as elevated LPS levels, reported in this condition, fail to lower neuroinflammation. Iron is closely linked to immunity as it plays a key role in immune cells proliferation and maturation, but it is also indispensable to pathogens and malignancies which compete for its capture. Danger signals, including LPS, induce intracellular iron sequestration in innate immune cells to withhold it from pathogens. However, excess cytosolic iron increases the risk of inflammasomes' activation, microglial training and neuroinflammation. Moreover, it was suggested that free iron can awaken the dormant central nervous system (CNS) LPS-shedding microbes, engendering prolonged neuroinflammation that may override immune tolerization, triggering autoimmunity. In this review, we focus on iron-related innate immune pathology in Alzheimer's disease and discuss potential immunotherapeutic agents for microglial de-escalation along with possible delivery vehicles for these compounds.
View details for DOI 10.3389/fneur.2018.01062
View details for Web of Science ID 000452087700002
View details for PubMedID 30564191
View details for PubMedCentralID PMC6288235
What utility scores do mental health service users, healthcare professionals and members of the general public attribute to different health states? A co-produced mixed methods online survey
2018; 13 (10): e0205223
Utility scores are integral to health economics decision-making. Typically, utility scores have not been scored or developed with mental health service users. The aims of this study were to i) collaborate with service users to develop descriptions of five mental health states (psychosis, depression, eating disorder, medication side effects and self-harm); ii) explore feasibility and acceptability of using scenario-based health states in an e-survey; iii) evaluate which utility measures (standard gamble (SG), time trade off (TTO) and rating scale (RS)) are preferred; and iv) determine how different participant groups discriminate between the health scenarios and rank them.This was a co-produced mixed methods cross-sectional online survey. Utility scores were generated using the SG, TTO and RS methods; difficulty of the completing each method, markers of acceptability and participants' preference were also assessed.A total of 119 participants (58%) fully completed the survey. For any given health state, SG consistently generated higher utility scores compared to RS and for some health states higher also than TTO (i.e. SG produces inflated utility scores relative to RS and TTO). Results suggest that different utility measures produce different evaluations of described health states. The TTO was preferred by all participant groups over the SG. The three participant groups scored four (of five) health scenarios comparably. Psychosis scored as the worst health state to live with while medication side-effects were viewed more positively than other scenarios (depression, eating disorders, self-harm) by all participant groups. However, there was a difference in how the depression scenario was scored, with service users giving depression a lower utility score compared to other groups.Mental health state scenarios used to generate utility scores can be co-produced and are well received by a broad range of participants. Utility valuations using SG, TTO and RS were feasible for use with service users, carers, healthcare professionals and members of the general public. Future studies of utility scores in psychiatry should aim to include mental health service users as both co-investigators and respondents.
View details for DOI 10.1371/journal.pone.0205223
View details for Web of Science ID 000448076200006
View details for PubMedID 30352071
View details for PubMedCentralID PMC6198969
- Public involvement in the production, dissemination and implementation of injury prevention research INJURY PREVENTION 2018; 24 (5): 321–22
- Better together: patient partnership in medical journals The BMJ's experience can be a springboard for others BMJ-BRITISH MEDICAL JOURNAL 2018; 362: k3798
Role of supplementary material in biomedical journal articles: surveys of authors, reviewers and readers
2018; 8 (9): e021753
Many journals permit authors to submit supplementary material for publication alongside the article. We explore the value, use and role of this material in biomedical journal articles from the perspectives of authors, peer reviewers and readers.We conducted online surveys (November-December 2016) of corresponding authors and peer reviewers at 17 BMJ Publishing Group journals in a range of specialities.Participants were asked to respond to one of three surveys: as authors, peer reviewers or readers.We received 2872/20340 (14%) responses: authors 819/6892 (12%), peer reviewers 1142/6682 (17%) and readers 911/6766 (14%). Most authors submitted (711/819, 87%) and 80% (724/911) of readers reported reading supplementary material with their last article, while 95% (1086/1142) of reviewers reported seeing these materials sometimes. Additional data tables were the most common supplementary material reported (authors: 74%; reviewers: 89%; readers: 67%). A majority in each group indicated additional tables were most useful to readers (61%-77%); 20%-36% and 3%-4% indicated they were most useful to peer reviewers and journal editors, respectively. Checklists and reporting guidelines showed the opposite: higher proportions of each group regarded these as most useful to journal editors. All three groups favoured the publication of additional tables and figures on the journal's website (80%-83%), with <4% of each group responding that these do not need to be available. Approximately one-fifth (16%-23%) responded that raw study data should be available on the journal's website, while 24%-33% said that these materials should not be made available anywhere.Authors, peer reviewers and readers agree that supplementary materials are useful. Supplementary tables and figures were favoured over reporting checklists or raw data for reading but not for study replication. Journals should consider the roles, resource costs and strategic placement of supplementary materials to ensure optimal usage and minimise waste.NCT02961036.
View details for DOI 10.1136/bmjopen-2018-021753
View details for Web of Science ID 000450417800061
View details for PubMedID 30249629
View details for PubMedCentralID PMC6157527
Ferrosenescence: The iron age of neurodegeneration?
MECHANISMS OF AGEING AND DEVELOPMENT
2018; 174: 63–75
Aging has been associated with iron retention in many cell types, including the neurons, promoting neurodegeneration by ferroptosis. Excess intracellular iron accelerates aging by damaging the DNA and blocking genomic repair systems, a process we define as ferrosenescence. Novel neuroimaging and proteomic techniques have pinpointed indicators of both iron retention and ferrosenescence, allowing for their early correction, potentially bringing prevention of neurodegenerative disorders within reach. In this review, we take a closer look at the early markers of iron dyshomeostasis in neurodegenerative disorders, focusing on preventive strategies based on nutritional and microbiome manipulations.
View details for DOI 10.1016/j.mad.2017.11.012
View details for Web of Science ID 000442067800007
View details for PubMedID 29180225
Perspectives on involvement in the peer-review process: surveys of patient and public reviewers at two journals
2018; 8 (9): e023357
In 2014/2015, The BMJ and Research Involvement and Engagement (RIE) became the first journals to routinely include patients and the public in the peer review process of journal articles. This survey explores the perspectives and early experiences of these reviewers.A cross-sectional survey.Patient and public reviewers for The BMJ and RIE who have been invited to review.The response rate was 69% (157/227) for those who had previously reviewed and 31% (67/217) for those who had not yet reviewed. Reviewers described being motivated to review by the opportunity to include the patient voice in the research process, influence the quality of the biomedical literature and ensure it meets the needs of patients. Of the 157 who had reviewed, 127 (81%) would recommend being a reviewer to other patients and carers. 144 (92%) thought more journals should adopt patient and public review. Few reviewers (16/224, 7%) reported concerns about doing open review. Annual acknowledgement on the journals' websites was welcomed as was free access to journal information. Participants were keen to have access to more online resources and training to improve their reviewing skills. Suggestions on how to improve the reviewing experience included: allowing more time to review; better and more frequent communication; a more user-friendly process; improving guidance on how to review including videos; improving the matching of papers to reviewers' experience; providing more varied sample reviews and brief feedback on the usefulness of reviews; developing a sense of community among reviewers; and publicising of the contribution that patient and public review brings.Patient and public reviewers shared practical ideas to improve the reviewing experience and these will be reviewed to enhance the guidance and support given to them.
View details for DOI 10.1136/bmjopen-2018-023357
View details for Web of Science ID 000450417800137
View details for PubMedID 30185581
View details for PubMedCentralID PMC6129098
- Atraumatic (pencil-point) versus conventional needles for lumbar puncture: a clinical practice guideline BMJ-BRITISH MEDICAL JOURNAL 2018; 361: k1920
- Epigenetic interventions for brain rejuvenation: anchoring age-related transposons NEURAL REGENERATION RESEARCH 2018; 13 (4): 635–36
Frequency of reporting on patient and public involvement (PPI) in research studies published in a general medical journal: a descriptive study
2018; 8 (3): e020452
While documented plans for patient and public involvement (PPI) in research are required in many grant applications, little is known about how frequently PPI occurs in practice. Low levels of reported PPI may mask actual activity due to limited PPI reporting requirements. This research analysed the frequency and types of reported PPI in the presence and absence of a journal requirement to include this information.A before and after comparison of PPI reported in research papers published in The BMJ before and 1 year after the introduction of a journal policy requiring authors to report if and how they involved patients and the public within their papers.Between 1 June 2013 and 31 May 2014, The BMJ published 189 research papers and 1 (0.5%) reported PPI activity. From 1 June 2015 to 31 May 2016, following the introduction of the policy, The BMJ published 152 research papers of which 16 (11%) reported PPI activity. Patients contributed to grant applications in addition to designing studies through to coauthorship and participation in study dissemination. Patient contributors were often not fully acknowledged; 6 of 17 (35%) papers acknowledged their contributions and 2 (12%) included them as coauthors.Infrequent reporting of PPI activity does not appear to be purely due to a failure of documentation. Reporting of PPI activity increased after the introduction of The BMJ's policy, but activity both before and after was low and reporting was inconsistent in quality. Journals, funders and research institutions should collaborate to move us from the current situation where PPI is an optional extra to one where PPI is fully embedded in practice throughout the research process.
View details for DOI 10.1136/bmjopen-2017-020452
View details for Web of Science ID 000433881200215
View details for PubMedID 29572398
View details for PubMedCentralID PMC5875637
Patient and public involvement in the design of clinical trials: An overview of systematic reviews
JOURNAL OF EVALUATION IN CLINICAL PRACTICE
2018; 24 (1): 240–53
Funders encourage lay-volunteer inclusion in research. There are controversy and resistance, given concerns of role confusion, exploratory methods, and limited evidence about what value lay-volunteers bring to research. This overview explores these areas.Eleven databases were searched without date or language restrictions for systematic reviews of public and patient involvement (PPI) in clinical trials design. This systematic overview of PPI included 27 reviews from which areas of good and bad practice were identified. Strengths, weaknesses, opportunities, and threats of PPI were explored through use of meta-narrative analysis.Inclusion criteria were met by 27 reviews ranging in quality from high (n = 7), medium (n = 14) to low (n = 6) reviews. Reviews were assessed using CERQUAL NICE, CASP for qualitative research and CASP for systematic reviews. Four reviews report risk of bias. Public involvement roles were primarily in agenda setting, steering committees, ethical review, protocol development, and piloting. Research summaries, follow-up, and dissemination contained PPI, with lesser involvement in data collection, analysis, or manuscript authoring. Trialists report difficulty in finding, retaining, and reimbursing volunteers. Respectful inclusion, role recognition, mutual flexibility, advance planning, and sound methods were reported as facilitating public involvement in research. Public involvement was reported to have increased the quantity and quality of patient relevant priorities and outcomes, enrollment, funding, design, implementation, and dissemination. Challenges identified include lack of clarity within common language, roles, and research boundaries, while logistical needs include extra time, training, and funding. Researchers report struggling to report involvement and avoid tokenism.Involving patients and the public in clinical trials design can be beneficial but requires resources, preparation, training, flexibility, and time. Issues to address include reporting deficits for risk of bias, study quality, and conflicts of interests. We need to address these tensions and improve dissemination strategies to increase PPI and health literacy.
View details for DOI 10.1111/jep.12805
View details for Web of Science ID 000428647800030
View details for PubMedID 29076631
Collective Conversational Peer Review of Journal Submission: A Tool to Integrate Medical Education and Practice
ANNALS OF NEUROSCIENCES
2018; 25 (2): 112–19
In this study, we demonstrate a collective collaborative, conversational, pre-publication peer review of a randomized controlled trial.Using Critical Appraisal Skills Programme checklist, a group of research-oriented undergraduate medical and pharmacy students and their teacher collectively on an online forum, discuss and review a randomized controlled trial submitted to the Annals of Neurosciences and the explanatory commentary from each reviewer makes a basic scaffold for critical appraisal of the manuscript.This method provided the opportunity for students to engage in online interactive training and allowed them to understand tools used for critical appraisal of a study. Students were incentivized by the potential publication credit and they look forward to continuing this work and perhaps providing one small step to making medical education more interactive.Open peer review involving a group of reviewers at a time produces multidirectional reviewing concepts, thus helps to improve the quality of paper and also may reduce the time between review and publication.
View details for DOI 10.1159/000488135
View details for Web of Science ID 000438556600001
View details for PubMedID 30140123
View details for PubMedCentralID PMC6103343
- What does evidence mean? Most languages translate "evidence" into "proof" JOURNAL OF EVALUATION IN CLINICAL PRACTICE 2017; 23 (5): 971–73
- Prioritizing Shared Decision Making JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION 2017; 317 (8): 856–57
The Obesity-Impulsivity Axis: Potential Metabolic Interventions in Chronic Psychiatric Patients
FRONTIERS IN PSYCHIATRY
2017; 8: 20
Pathological impulsivity is encountered in a broad range of psychiatric conditions and is thought to be a risk factor for aggression directed against oneself or others. Recently, a strong association was found between impulsivity and obesity which may explain the high prevalence of metabolic disorders in individuals with mental illness even in the absence of exposure to psychotropic drugs. As the overlapping neurobiology of impulsivity and obesity is being unraveled, the question asked louder and louder is whether they should be treated concomitantly. The treatment of obesity and metabolic dysregulations in chronic psychiatric patients is currently underutilized and often initiated late, making correction more difficult to achieve. Addressing obesity and metabolic dysfunction in a preventive manner may not only lower morbidity and mortality but also the excessive impulsivity, decreasing the risk for aggression. In this review, we take a look beyond psychopharmacological interventions and discuss dietary and physical therapy approaches.
View details for DOI 10.3389/fpsyt.2017.00020
View details for Web of Science ID 000393740600001
View details for PubMedID 28243210
View details for PubMedCentralID PMC5303716
Mind the gap in clinical trials: A participatory action analysis with citizen collaborators
JOURNAL OF EVALUATION IN CLINICAL PRACTICE
2017; 23 (1): 178–84
What are the strengths, gaps, expectations, and barriers to research engagement in clinical trials as communicated through social media? Clinical trials test treatments to provide reliable information for safety and effectiveness. Trials are building blocks in which what is learned in earlier research can be used to improve treatments, compare alternatives, and improve quality of life. For 20 years, the percentages of clinical trials volunteers have decreased whereas the costs of running clinical trials have multiplied. Participants enroll in trials to access latest treatments, to help others, and to advance science, but there is growing unrest. The priorities of those running the trials differ from those of the participants, and the roles for public research involvement lack clarity. Changes to bridge these gaps in the research culture are proposed through the use of participatory action research (PAR) in which stakeholders collaborate to improve research methodology, galvanize citizen participation, multiply health knowledge, problem-solve barriers to access, and explore the value of research volunteers as collaborators. PAR enabled the inclusion of citizens as full collaborators. Social media data were gathered for 120 days until saturation was reached. De-identified data were organized into a Strengths Weaknesses, Opportunities and Threats framework and coded into themes for analysis. After the analysis, the authors prioritized potential solutions for improving research engagement. Strengths and opportunities remained constant through trial phases, disease burdens, and interventions. Threats included alienation, litigation, disparity, and shaming. Poor management and barriers to inclusion were identified as weaknesses. Opportunities included improving resource management and information quality. Barriers were minimized when relationships between staff and participants were inclusive, respectful, tolerant, and open to change. Participants' communications ranged from fulfillment through trial involvement to disparities and rights violations. PAR provides a safe space without power imbalances in which researchers and citizen worked as equals rather than as researchers and objects of research.
View details for DOI 10.1111/jep.12678
View details for Web of Science ID 000395024900024
View details for PubMedID 27917564
- Medical Students Meet User Driven Health Care for Patient Centered Learning in Clinical Medicine HEALTHCARE ETHICS AND TRAINING: CONCEPTS, METHODOLOGIES, TOOLS, AND APPLICATIONS 2017: 811–20
An unfortunate injection.
BMJ case reports
Intramuscular injection has been used to administer medications for more than a hundred years. However, despite our profession's long experience with intramuscular administration, preventable complications such as injection nerve palsies are still prevalent in developing countries. Injections account for one-fifth of all traumatic nerve injuries. These injuries largely occur due to indiscriminate use of intramuscular injections for treating common illnesses, frequently by unlicensed or undertrained practitioners administering unnecessary treatment to impoverished patients. The sciatic nerve is the most commonly injured, and frequently the resulting muscle weakness and associated disability are irreversible. This case report includes a video of a patient with foot drop 6 weeks after gluteal intramuscular injection. Such injuries can be prevented by proper awareness and training, the implementation of safer injection techniques, and quality assurance methods.
View details for DOI 10.1136/bcr-2015-211127
View details for PubMedID 26931130
Evidence-based medicine meets person-centred care: a collaborative perspective on the relationship
JOURNAL OF EVALUATION IN CLINICAL PRACTICE
2015; 21 (6): 1047–51
In a recent list-serve, the way forward for evidence-based medicine was discussed. The purpose of this paper was to share the reflections and multiple perspectives discussed in this peer-to-peer encounter and to invite the reader to think with a mind for positive change in the practice of health care. Let us begin with a simple question. What if we dared to look at evidence-based medicine (EBM) and informed shared decision making like two wheels on a bike? They both need to be full of substance, well connected, lubricated and working in balance, propelled and guided by a competent driver, with good vision to get the bike where we want it to go. We need all the tools in the toolkit for the bike to stay operational and to meet the needs of the driver. By the same rationale, evidence alone is necessary but not sufficient for decision making; values are necessary and if neglected, may default to feelings based on social pressures and peer influence. Medical decisions, even shared ones, lack focus without evidence and application. Just as a bike may need a tune up from time to time to maintain optimal performance, EBM may benefit from a tune up where we challenge ourselves to move away from general assumptions and traditions and instead think clearly about the issues we face and how to ask well-formed, specific questions to get the answers to meet the needs we face in health care.
View details for DOI 10.1111/jep.12434
View details for Web of Science ID 000371414500015
View details for PubMedID 26358758
Increased water intake to reduce headache: learning from a critical appraisal
JOURNAL OF EVALUATION IN CLINICAL PRACTICE
2015; 21 (6): 1212–18
Water intake is a cost effective, non-invasive and low-risk intervention to reduce or prevent headache pain.Chronic mild dehydration may trigger headache. Increased water intake could help. A small trial shows modest benefit; however, a larger methodologically sound randomized controlled trial is needed to confirm efficacy.Spigt, M., Weerkamp, N., Troost, J., van Schayck, C. P., & Knottnerus, J. A. (2012). 'A randomized trial on the effects of regular water intake in patients with recurrent headaches.' Family practice, 29(4), 370-5. Doi: 10.1093/fampra/cmr112 CLINICAL SCENARIO: Patients from primary care registered as 'headache', 'tension headache' and/or 'migraine' for more than one year who suffer at least two episodes of moderately intense headache or more than four mildly intense episodes of headache per month with a daily fluid intake of less than 2.5 litres per day.Patient/Problem = Headache > 1 year with 2 moderately intense or 4 mildly intense episodes per month Intervention = 1.5 litres water per day + stress control and sleep hygiene Comparison/Control = stress control and sleep hygiene Outcome = Reduce or eliminate headache Methodology = Therapy RCT Table 1: Final Search Terms TRIP Data Base: hits = 517 used filter Extended Primary research 4 found 1 paper applicable 'Water intake '[MeSH Terms] AND 'Headache '[All Fields]' Best match to PICO, (2012) RCT SELECTION CRITERION AND OVERALL RESULTS: 102 headache patients in16 primary care clinics were randomized into control (n = 50) and intervention groups (n = 52) Inclusion criteria = two > episodes of moderately intense headache or five > mildly intense headaches per month and total fluid intake > 2.5 litres per day, Follow-up @ 3 months. 79% intervention and 66% of controls completed RCT. Drinking more water resulted in a statistically significant improvement of 4.5 (confidence interval: 1.3-7.8) points on Migraine-Specific Quality of Life (MSQOL). 47% in the intervention (water) group self-reported improvement (6 > on a 10-point scale) against 25% in controls. Drinking water did not reduce headache days.The transparency from the author of this critically appraised paper enables others to use this study as a teaching tool and to learn from the shortcomings in the trial. The study was underpowered and contains methodological shortcomings. Participants were partially un-blinded during the trial increasing the risk for bias. Only the subjective measures are statistically significant and attrition was significant. The intervention is low risk and of negligible cost. A methodologically sound RCT is recommended to evaluate if the intervention has beneficial effects.
View details for DOI 10.1111/jep.12413
View details for Web of Science ID 000371414500037
View details for PubMedID 26200171
Delirium from the gliocentric perspective
FRONTIERS IN CELLULAR NEUROSCIENCE
2015; 9: 171
Delirium is an acute state marked by disturbances in cognition, attention, memory, perception, and sleep-wake cycle which is common in elderly. Others have shown an association between delirium and increased mortality, length of hospitalization, cost, and discharge to extended stay facilities. Until recently it was not known that after an episode of delirium in elderly, there is a 63% probability of developing dementia at 48 months compared to 8% in patients without delirium. Currently there are no preventive therapies for delirium, thus elucidation of cellular and molecular underpinnings of this condition may lead to the development of early interventions and thus prevent permanent cognitive damage. In this article we make the case for the role of glia in the pathophysiology of delirium and describe an astrocyte-dependent central and peripheral cholinergic anti-inflammatory shield which may be disabled by astrocytic pathology, leading to neuroinflammation and delirium. We also touch on the role of glia in information processing and neuroimaging.
View details for DOI 10.3389/fncel.2015.00171
View details for Web of Science ID 000354802700001
View details for PubMedID 26029046
View details for PubMedCentralID PMC4426724
Creating a database of internet-based clinical trials to support a public-led research programme: A descriptive analysis
2015; 1: 2055207615617854
Online trials are rapidly growing in number, offering potential benefits but also methodological, ethical and social challenges. The International Network for Knowledge on Well-being (ThinkWell™) aims to increase public and patient participation in the prioritisation, design and conduct of research through the use of technologies.We aim to provide a baseline understanding of the online trial environment, determining how many trials have used internet-based technologies; how they have been used; and how use has developed over time.We searched a range of bibliographic databases to March 2015, with no date limits, supplemented by citation searching and references provided by experts in the field. Results were screened against inclusion and exclusion criteria, and included studies mapped against a number of key dimensions, with key themes developed iteratively throughout the process.We identified 1992 internet-based trials to March 2015. The number of reported studies increased substantially over the study timeframe. The largest number of trials were conducted in the USA (49.7%), followed by The Netherlands (10.2%); Australia (8.5%); the United Kingdom (5.8%); Sweden (4.6%); Canada (4%); and Germany (2.6%). South Korea (1.5%) has the highest number of reported trials for other continents. There is a predominance of interventions addressing core public health challenges including obesity (8.6%), smoking cessation (5.9%), alcohol abuse (7.7%) and physical activity (10.2%); in mental health issues such as depression (10.9%) and anxiety (5.6%); and conditions where self-management (16.6%) or monitoring (8.1%) is a major feature of care.The results confirm an increase in the use of the internet in trials. Key themes have emerged from the analysis and further research will be undertaken in order to investigate how the data can be used to improve trial design and recruitment, and to build an open access resource to support the public-led research agenda.
View details for DOI 10.1177/2055207615617854
View details for Web of Science ID 000441806800010
View details for PubMedID 29942546
View details for PubMedCentralID PMC5999056
Proteomic and epigenomic markers of sepsis-induced delirium (SID).
Frontiers in molecular biosciences
2015; 2: 59
In elderly population sepsis is one of the leading causes of intensive care unit (ICU) admissions in the United States. Sepsis-induced delirium (SID) is the most frequent cause of delirium in ICU (Martin et al., 2010). Together delirium and SID represent under-recognized public health problems which place an increasing financial burden on the US health care system, currently estimated at 143-152 billion dollars per year (Leslie et al., 2008). The interest in SID was recently reignited as it was demonstrated that, contrary to prior beliefs, cognitive deficits induced by this condition may be irreversible and lead to dementia (Pandharipande et al., 2013; Brummel et al., 2014). Conversely, it is construed that diagnosing SID early or mitigating its full blown manifestations may preempt geriatric cognitive disorders. Biological markers specific for sepsis and SID would facilitate the development of potential therapies, monitor the disease process and at the same time enable elderly individuals to make better informed decisions regarding surgeries which may pose the risk of complications, including sepsis and delirium. This article proposes a battery of peripheral blood markers to be used for diagnostic and prognostic purposes in sepsis and SID. Though each individual marker may not be specific enough, we believe that together as a battery they may achieve the necessary accuracy to answer two important questions: who may be vulnerable to the development of sepsis, and who may develop SID and irreversible cognitive deficits following sepsis?
View details for DOI 10.3389/fmolb.2015.00059
View details for PubMedID 26579527
- Neurodegeneration Behind Bars: from molecules to jurisprudence FRONTIERS IN PSYCHIATRY 2014; 5: 115
- time for person centered research in neuroscience: users driving the change ANNALS OF NEUROSCIENCES 2014; 21 (2): 37–40