PCOM Library / Archive for "Hot Topics in Research"

Category: Hot Topics in Research

Hot Topics: Flu Vaccine Antibodies Inhibit Two Viral Proteins

Jackie Werner Hot Topics in Research, Infectious Disease

Neuraminidase inhibition contributes to influenza A virus neutralization by anti-hemagglutinin stem antibodies

Kosik I, Angeletti D, Gibbs JS, et al. Neuraminidase inhibition contributes to influenza A virus neutralization by anti-hemagglutinin stem antibodies. J Exp Med. 2019. dx.doi.org/10.1084/jem.20181624.

Broadly neutralizing antibodies (Abs) that bind the influenza virus hemagglutinin (HA) stem may enable universal influenza vaccination. Here, we show that anti-stem Abs sterically inhibit viral neuraminidase (NA) activity against large substrates, with activity inversely proportional to the length of the fibrous NA stalk that supports the enzymatic domain. By modulating NA stalk length in recombinant IAVs, we show that anti-stem Abs inhibit virus release from infected cells by blocking NA, accounting for their in vitro neutralization activity. NA inhibition contributes to anti-stem Ab protection in influenza-infected mice, likely due at least in part to NA-mediated inhibition of FcγR-dependent activation of innate immune cells by Ab bound to virions. Food and Drug Administration–approved NA inhibitors enhance anti-stem–based Fc-dependent immune cell activation, raising the possibility of therapeutic synergy between NA inhibitors and anti-stem mAb treatment in humans.

Hot Topics: Bias Minimizes Girls’ Pain

Jackie Werner Ethics, Hot Topics in Research, Pediatrics

Gender bias in pediatric pain assessment

Earp BD, Monrad JT, LaFrance M, Bargh JA, Cohen LL, Richeson JA. Gender bias in pediatric pain assessment. 2019. https://dx.doi.org/10.1093/jpepsy/jsy104.

Objective
Accurate assessment of pain is central to diagnosis and treatment in healthcare, especially in pediatrics. However, few studies have examined potential biases in adult observer ratings of children’s pain. Cohen, Cobb, & Martin (2014. Gender biases in adult ratings of pediatric pain. Children’s Health Care, 43, 87–95) reported that adult participants rated a child undergoing a medical procedure as feeling more pain when the child was described as a boy as compared to a girl, suggesting a possible gender bias. To confirm, clarify, and extend this finding, we conducted a replication experiment and follow-up study examining the role of explicit gender stereotypes in shaping such asymmetric judgments.

Methods
In an independent, pre-registered, direct replication and extension study with open data and materials (https://osf.io/t73c4/), we showed participants the same video from Cohen et al. (2014), with the child described as a boy or a girl depending on condition. We then asked adults to rate how much pain the child experienced and displayed, how typical the child was in these respects, and how much they agreed with explicit gender stereotypes concerning pain response in boys versus girls.

Results
Similar to Cohen et al. (2014), but with a larger and more demographically diverse sample, we found that the “boy” was rated as experiencing more pain than the “girl” despite identical clinical circumstances and identical pain behavior across conditions. Controlling for explicit gender stereotypes eliminated the effect.

Conclusions
Explicit gender stereotypes—for example, that boys are more stoic or girls are more emotive—may bias adult assessment of children’s pain.

Hot Topics: New Therapy Enhances Peanut Allergy Tolerance

Jackie Werner Hot Topics in Research, Internal Medicine

AR101 Oral Immunotherapy for Peanut Allergy

PALISADE Group of Clinical Investigators, Vickery BP, Vereda A, et al. AR101 oral immunotherapy for peanut allergy. N Engl J Med. 2018;379(21):1991-2001. http://dx.doi.org/10.1056/NEJMoa1812856

BACKGROUND
Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions.

METHODS
In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms.

RESULTS
Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; P<0.001). During the exit food challenge, the maximum severity of symptoms was moderate in 25% of the participants in the active-drug group and 59% of those in the placebo group and severe in 5% and 11%, respectively. Adverse events during the intervention period affected more than 95% of the participants 4 to 17 years of age. A total of 34.7% of the participants in the active-drug group had mild events, as compared with 50.0% of those in the placebo group; 59.7% and 44.4% of the participants, respectively, had events that were graded as moderate, and 4.3% and 0.8%, respectively, had events that were graded as severe. Efficacy was not shown in the participants 18 years of age or older.

CONCLUSIONS
In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo.

Hot Topics: YouTube Misinforms About Prostate Cancer

Jackie Werner Hot Topics in Research, Oncology

Dissemination of Misinformative and Biased Information about Prostate Cancer on YouTube

Loeb S, Sengupta S, Butaney M, et al. Dissemination of misinformative and biased information about prostate cancer on YouTube. Eur Urolhttps://doi.org/10.1016/j.eururo.2018.10.056.

YouTube is a social media platform with more than 1 billion users and >600 000 videos about prostate cancer. Two small studies examined the quality of prostate cancer videos on YouTube, but did not use validated instruments, examine user interactions, or characterize the spread of misinformation. We performed the largest, most comprehensive examination of prostate cancer information on YouTube to date, including the first 150 videos on screening and treatment. We used the validated DISCERN quality criteria for consumer health information and the Patient Education Materials Assessment Tool, and compared results for user engagement. The videos in our sample had up to 1.3 million views (average 45 223) and the overall quality of information was moderate. More videos described benefits (75%) than harms (53%), and only 50% promoted shared decision-making as recommended in current guidelines. Only 54% of the videos defined medical terms and few provided summaries or references. There was a significant negative correlation between scientific quality and viewer engagement (views/month p = 0.004; thumbs up/views p = 0.015). The comments section underneath some videos contained advertising and peer-to-peer medical advice. A total of 115 videos (77%) contained potentially misinformative and/or biased content within the video or comments section, with a total reach of >6 million viewers.

Patient summary
Many popular YouTube videos about prostate cancer contained biased or poor-quality information. A greater number of views and thumbs up on YouTube does not mean that the information is trustworthy.

Hot Topics: Botox May Help Aftermath of Cardiac Surgery

Jackie Werner Cardiology, Hot Topics in Research, Surgery

Long-term suppression of atrial fibrillation by botulinum toxin injection into epicardial fat pads in patients undergoing cardiac surgery: Three-year follow-up of a randomized study

Romanov A, Pokushalov E, Ponomarev D, et al. Long-term suppression of atrial fibrillation by botulinum toxin injection into epicardial fat pads in patients undergoing cardiac surgery: Three-year follow-up of a randomized study. Heart Rhythm. 2018. http://dx.doi.org/10.1016/j.hrthm.2018.08.019

Background
Botulinum toxin (BTX) injections into epicardial fat pads in patients undergoing coronary artery bypass grafting (CABG) has resulted in suppression of atrial fibrillation (AF) during the early postoperative period through 1-year of follow-up in a pilot program.

Objective
The purpose of this study was to report 3-year AF patterns by the use of implantable cardiac monitors (ICMs).

Methods
Sixty patients with a history of paroxysmal AF and indications for CABG were randomized 1:1 to either BTX or placebo injections into 4 posterior epicardial fat pads. All patients received an ICM with regular follow-up for 3 years after surgery. The primary end point of the extended follow-up period was incidence of any atrial tachyarrhythmia after 30 days of procedure until 36 months on no antiarrhythmic drugs. The secondary end points included clinical events and AF burden.

Results
At the end of 36 months, the incidence of any atrial tachyarrhythmia was 23.3% in the BTX group vs 50% in the placebo group (hazard ratio 0.36; 95% confidence interval 0.14–0.88; P = .02). AF burden at 12, 24, and 36 months was significantly lower in the BTX group than in the placebo group: 0.22% vs 1.88% ( P = .003), 1.6% vs 9.5% ( P < .001), and 1.3% vs 6.9% ( P = .007), respectively. In the BTX group, 2 patients (7%) were hospitalized during follow-up compared with 10 (33%) in the placebo group ( P = .02).

Conclusion
Injection of BTX into epicardial fat pads in patients undergoing CABG resulted in a sustained and substantial reduction in atrial tachyarrhythmia incidence and burden during 3-year follow-up, accompanied by reduction in hospitalizations.

Hot Topics: Reward Behavior Provides Insights into Depression

Jackie Werner Hot Topics in Research, Mood Disorders, Neurology

Reward behaviour is regulated by the strength of hippocampus–nucleus accumbens synapses

LeGates TA, Kvarta MD, Tooley JR, et al. Reward behaviour is regulated by the strength of hippocampus–nucleus accumbens synapses. Nature. 2018. https://doi.org/10.1038/s41586-018-0740-8.

Reward drives motivated behaviours and is essential for survival, and therefore there is strong evolutionary pressure to retain contextual information about rewarding stimuli. This drive may be abnormally strong, such as in addiction, or weak, such as in depression, in which anhedonia (loss of pleasure in response to rewarding stimuli) is a prominent symptom. Hippocampal input to the shell of the nucleus accumbens (NAc) is important for driving NAc activity1,2 and activity-dependent modulation of the strength of this input may contribute to the proper regulation of goal-directed behaviours. However, there have been few robust descriptions of the mechanisms that underlie the induction or expression of long-term potentiation (LTP) at these synapses, and there is, to our knowledge, no evidence about whether such plasticity contributes to reward-related behaviour. Here we show that high-frequency activity induces LTP at hippocampus–NAc synapses in mice via canonical, but dopamine-independent, mechanisms. The induction of LTP at this synapse in vivo drives conditioned place preference, and activity at this synapse is required for conditioned place preference in response to a natural reward. Conversely, chronic stress, which induces anhedonia, decreases the strength of this synapse and impairs LTP, whereas antidepressant treatment is accompanied by a reversal of these stress-induced changes. We conclude that hippocampus–NAc synapses show activity-dependent plasticity and suggest that their strength may be critical for contextual reward behaviour.

Hot Topics: Current Patient Engagement Measures Fall Short

Jackie Werner Family Medicine, Hot Topics in Research, Uncategorized

Mishra MK, Saunders CH, Rodriguez HP, Shortell SM, Fisher E, Elwyn G. How do healthcare professionals working in accountable care organisations understand patient activation and engagement? Qualitative interviews across two time points. BMJ Open. 2018;8(10). http://dx.doi.org/10.1136/bmjopen-2018-023068

Objective If patient engagement is the new ‘blockbuster drug’ why are we not seeing spectacular effects? Studies have shown that activated patients have improved health outcomes, and patient engagement has become an integral component of value-based payment and delivery models, including accountable care organisations (ACO). Yet the extent to which clinicians and managers at ACOs understand and reliably execute patient engagement in clinical encounters remains unknown. We assessed the use and understanding of patient engagement approaches among frontline clinicians and managers at ACO-affiliated practices.

Design Qualitative study; 103 in-depth, semi-structured interviews.

Participants Sixty clinicians and eight managers were interviewed at two established ACOs.

Approach We interviewed healthcare professionals about their awareness, attitudes, understanding and experiences of implementing three key approaches to patient engagement and activation: 1) goal-setting, 2) motivational interviewing and 3) shared decision making. Of the 60 clinicians, 33 were interviewed twice leading to 93 clinician interviews. Of the 8 managers, 2 were interviewed twice leading to 10 manager interviews. We used a thematic analysis approach to the data.

Key results Interviewees recognised the term ‘patient activation and engagement’ and had favourable attitudes about the utility of the associated skills. However, in-depth probing revealed that although interviewees reported that they used these patient activation and engagement approaches, they have limited understanding of these approaches.

Conclusions Without understanding the concept of patient activation and the associated approaches of shared decision making and motivational interviewing, effective implementation in routine care seems like a distant goal. Clinical teams in the ACO model would benefit from specificity defining key terms pertaining to the principles of patient activation and engagement. Measuring the degree of understanding with reward that are better-aligned for behaviour change will minimise the notion that these techniques are already being used and help fulfil the potential of patient-centred care.

Hot Topics: Online Ratings Highlight Patient Opinions

Jackie Werner Emergency Medicine, Hot Topics in Research

Online ratings of the patient experience: Emergency departments versus urgent care centers

Agarwal AK, Mahoney K, Lanza AL, et al. Online ratings of the patient experience: Emergency departments versus urgent care centers. Annals of Emergency Medicine. 2018. http://www.sciencedirect.com/science/article/pii/S0196064418313222.

Study objective

Individuals increasingly use online rating platforms to rate and review hospitals. We seek to describe and compare publicly available online review content and ratings of emergency departments (EDs) and urgent care centers.

Methods

We analyzed Yelp reviews of EDs and urgent care centers to identify topics most correlated with 1- and 5-star ratings. Latent Dirichlet Allocation, a method of identifying groups of co-occurring words in narrative text, was used to identify and label 25 topics across 1- and 5-star reviews of urgent care centers and EDs. Differential Language Analysis was then used to measure the correlation of these topics with 1- and 5-star reviews for urgent care centers and EDs.

Results

We analyzed 100,949 Yelp reviews, 16,447 from 1,566 EDs and 84,502 from 5,601 urgent care centers. There were significantly more 5-star urgent care center reviews (n=43,487; 51%) than 5-star ED reviews (n=4,437; 27%). Themes associated with 5-star reviews among EDs and urgent care centers were similar for comfort, professionalism, facilities, pediatric care, and staff interactions. Themes associated with 1-star reviews among EDs and urgent care centers were similar for communication, telephone experience, waiting, billing, pain management, and diagnostic testing. Themes unique to 5-star ED reviews included bedside manner, care for family members, and access. Themes unique to 5-star urgent care center reviews were based on recommendation and prescription refills. Themes unique to 1-star ED reviews were service and speed of care. Themes unique to 1-star urgent care center reviews were lack of confidence and reception experience.

Conclusion

Understanding drivers for high and low online ratings and what patients value in their ED and urgent care center experiences offers insights for health systems and providers to improve acute care delivery. Patients’ perspectives may become increasingly important as they seek care in the expanding urgent care markets.

Hot Topics: Chronic Pain Lessened by Stimulating the Brain

Jackie Werner Hot Topics in Research, Neurology, Substance Use Disorders

Patients’ Experience With Opioid Tapering: A Conceptual Model With Recommendations for Clinicians

Ahn S, Prim JH, Alexander ML, McCulloch KL, Fröhlich F. Identifying and engaging neuronal oscillations by transcranial alternating current stimulation in patients with chronic low back pain: A randomized, crossover, double-blind, sham-controlled pilot study. The Journal of Pain. . https://doi.org/10.1016/j.jpain.2018.09.004

Clinical guidelines discourage prescribing opioids for chronic pain, but give minimal advice about how to discuss opioid tapering with patients. We conducted focus groups and interviews involving 21 adults with chronic back or neck pain in different stages of opioid tapering. Transcripts were qualitatively analyzed to characterize patients’ tapering experiences, build a conceptual model of these experiences, and identify strategies for promoting productive discussions of opioid tapering. Analyses revealed 3 major themes. First, owing to dynamic changes in patients’ social relationships, emotional state, and health status, patients’ pain and their perceived need for opioids fluctuate daily; this finding may conflict with recommendations to taper by a certain amount each month. Second, tapering requires substantial patient effort across multiple domains of patients’ everyday lives; patients discuss this effort superficially, if at all, with clinicians. Third, patients use a variety of strategies to manage the tapering process (eg, keeping an opioid stash, timing opioid consumption based on planned activities). Recommendations for promoting productive tapering discussions include understanding the social and emotional dynamics likely to impact patients’ tapering, addressing patient fears, focusing on patients’ best interests, providing anticipatory guidance about tapering, and developing an individualized tapering plan that can be adjusted based on patient response.

Perspective: This study used interview and focus group data to characterize patients’ experiences with opioid tapering and identify communication strategies that are likely to foster productive, patient-centered discussions of opioid tapering. Findings will inform further research on tapering and help primary care clinicians to address this important, often challenging topic.

Hot Topics: Some Seizures Start After Brain Inhibition

Jackie Werner Biomedical Sciences, Hot Topics in Research, Neurology

Low‐Voltage Fast Seizures in Humans Begin with Increased Interneuron Firing

Elahian B, Lado NE, Mankin E, et al. Low-voltage fast seizures in humans begin with increased interneuron firing. Annals of Neurology. 2018. https://doi.org/10.1002/ana.25325

Objective
Intracellular recordings from cells in entorhinal cortex tissue slices show that low‐voltage fast (LVF) onset seizures are generated by inhibitory events. Here, we determined whether increased firing of interneurons occurs at the onset of spontaneous mesial–temporal LVF seizures recorded in patients.

Methods
The seizure onset zone (SOZ) was identified using visual inspection of the intracranial electroencephalogram. We used wavelet clustering and temporal autocorrelations to characterize changes in single‐unit activity during the onset of LVF seizures recorded from microelectrodes in mesial–temporal structures. Action potentials generated by principal neurons and interneurons (ie, putative excitatory and inhibitory neurons) were distinguished using waveform morphology and K‐means clustering.

Results
From a total of 200 implanted microelectrodes in 9 patients during 13 seizures, we isolated 202 single units; 140 (69.3%) of these units were located in the SOZ, and 40 (28.57%) of them were classified as inhibitory. The waveforms of both excitatory and inhibitory units remained stable during the LVF epoch (p > > 0.05). In the mesial–temporal SOZ, inhibitory interneurons increased their firing rate during LVF seizure onset (p < 0.01). Excitatory neuron firing rates peaked 10 seconds after the inhibitory neurons (p < 0.01). During LVF spread to the contralateral mesial temporal lobe, an increase in inhibitory neuron firing rate was also observed (p < 0.01).

Interpretation
Our results suggest that seizure generation and spread during spontaneous mesial–temporal LVF onset events in humans may result from increased inhibitory neuron firing that spawns a subsequent increase in excitatory neuron firing and seizure evolution.