PCOM Library / Archive for "Hot Topics in Research"

Category: Hot Topics in Research

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

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.

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

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.

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).

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.


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.


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.


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

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.

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.

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).

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.

Hot Topics: New Drug Found Effective for Influenza

Jackie Werner Hot Topics in Research, Infectious Disease, Pharmaceutical Sciences

Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents

Hayden FG, Sugaya N, Hirotsu N, et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med. 2018;379(10):913-923. https://doi.org/10.1056/NEJMoa1716197.


Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents.


We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After a dose-ranging (10 to 40 mg) placebo-controlled trial, we undertook a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016–2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population.


In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P<0.05). In the phase 3 trial, the intention-to-treat infected population included 1064 patients; 84.8 to 88.1% of patients in each group had influenza A(H3N2) infection. The median time to alleviation of symptoms was 53.7 hours (95% confidence interval [CI], 49.5 to 58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with placebo (P<0.001). The time to alleviation of symptoms was similar with baloxavir and oseltamivir. Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir. Adverse events were reported in 20.7% of baloxavir recipients, 24.6% of placebo recipients, and 24.8% of oseltamivir recipients. The emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced susceptibility to baloxavir occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 trial and phase 3 trial, respectively.


Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza. Evidence for the development of decreased susceptibility to baloxavir after treatment was also observed.

Hot Topics: Anesthesiology Should Look to Neuroscience and Nociception

Jackie Werner Hot Topics in Research, Neurology, Surgery

Multimodal General Anesthesia: Theory and Practice

Brown EN, Pavone KJ, Naranjo M. Multimodal general anesthesia: Theory and practice. Anesthesia & Analgesia. http://dx.doi.org/10.1213/ANE.0000000000003668

Balanced general anesthesia, the most common management strategy used in anesthesia care, entails the administration of different drugs together to create the anesthetic state. Anesthesiologists developed this approach to avoid sole reliance on ether for general anesthesia maintenance. Balanced general anesthesia uses less of each drug than if the drug were administered alone, thereby increasing the likelihood of its desired effects and reducing the likelihood of its side effects. To manage nociception intraoperatively and pain postoperatively, the current practice of balanced general anesthesia relies almost exclusively on opioids. While opioids are the most effective antinociceptive agents, they have undesirable side effects. Moreover, overreliance on opioids has contributed to the opioid epidemic in the United States. Spurred by concern of opioid overuse, balanced general anesthesia strategies are now using more agents to create the anesthetic state. Under these approaches, called “multimodal general anesthesia,” the additional drugs may include agents with specific central nervous system targets such as dexmedetomidine and ones with less specific targets, such as magnesium. It is postulated that use of more agents at smaller doses further maximizes desired effects while minimizing side effects. Although this approach appears to maximize the benefit-to-side effect ratio, no rational strategy has been provided for choosing the drug combinations. Nociception induced by surgery is the primary reason for placing a patient in a state of general anesthesia. Hence, any rational strategy should focus on nociception control intraoperatively and pain control postoperatively. In this Special Article, we review the anatomy and physiology of the nociceptive and arousal circuits, and the mechanisms through which commonly used anesthetics and anesthetic adjuncts act in these systems. We propose a rational strategy for multimodal general anesthesia predicated on choosing a combination of agents that act at different targets in the nociceptive system to control nociception intraoperatively and pain postoperatively. Because these agents also decrease arousal, the doses of hypnotics and/or inhaled ethers needed to control unconsciousness are reduced. Effective use of this strategy requires simultaneous monitoring of antinociception and level of unconsciousness. We illustrate the application of this strategy by summarizing anesthetic management for 4 representative surgeries.

Hot Topics: Health-Related Quality of Life Not Sufficiently Measured in Oncology Studies

Jackie Werner Hot Topics in Research, Oncology, Research and Scholarly Communication

Evaluating Progression-Free Survival as a Surrogate Outcome for Health-Related Quality of Life in Oncology: A Systematic Review and Quantitative Analysis

Kovic B, Jin X, Kennedy S, et al. Evaluating progression-free survival as a surrogate outcome for health-related quality of life in oncology: A systematic review and quantitative analysis. JAMA Internal Medicine. 2018. http://doi.org/10.1001/jamainternmed.2018.4710.

Importance  Progression-free survival (PFS) has become a commonly used outcome to assess the efficacy of new cancer drugs. However, it is not clear if delay in progression leads to improved quality of life with or without overall survival benefit.

Objective  To evaluate the association between PFS and health-related quality of life (HRQoL) in oncology through a systematic review and quantitative analysis of published randomized clinical trials. Eligible trials addressed oral, intravenous, intraperitoneal, or intrapleural chemotherapy or biological treatments, and reported PFS or health-related quality of life.

Data Sources  For this systematic review and quantitative analysis of randomized clinical trials of patients with cancer, we searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 2000, through May 4, 2016.

Study Selection  Paired reviewers independently screened citations, extracted data, and assessed risk of bias of included studies.

Data Extraction and Synthesis  We examined the association of difference in median PFS duration (in months) between treatment groups with difference in global, physical, and emotional HRQoL scores between groups (standardized to a range of 0-100, with higher scores representing better HRQoL) using weighted simple regressions.

Main Outcome and Measure  The association between PFS duration and HRQoL.

Results  Of 35 960 records screened, 52 articles reporting on 38 randomized clinical trials involving 13 979 patients across 12 cancer types using 6 different HRQoL instruments were included. The mean (SD) difference in median PFS between the intervention and the control arms was 1.91 (3.35) months. The mean (SD) differences in change of HRQoL adjusted to per-month values were −0.39 (3.59) for the global domain, 0.26 (5.56) for the physical domain, and 1.08 (3.49) for the emotional domain. The slope of the association between the difference in median PFS and the difference in change for global HRQoL (n = 30 trials) was 0.12 (95% CI, −0.27 to 0.52); for physical HRQoL (n = 20 trials) it was −0.20 (95% CI, −0.62 to 0.23); and for emotional HRQoL (n = 13 trials) it was 0.78 (95% CI, −0.05 to 1.60).

Conclusions and Relevance  We failed to find a significant association between PFS and HRQoL in cancer clinical trials. These findings raise questions regarding the assumption that interventions prolonging PFS also improve HRQoL in patients with cancer. Therefore, to ensure that patients are truly obtaining important benefit from cancer therapies, clinical trial investigators should measure HRQoL directly and accurately, ensuring adequate duration and follow-up.