Recommendations for monitoring adherence and fidelity in pragmatic trials based on experience in the Pain Management Collaboratory.

Objective: Most pragmatic trials follow the PRagmatic Explanatory Continuum Indicator Summary (PRECIS-2) criteria. The criteria specify unobtrusive measurement of participants' protocol adherence and practitioners' intervention fidelity but suggest no special monitoring strategies to assure trial integrity. We present experience with adherence/fidelity monitoring in the Pain Management Collaboratory (PMC) and provide recommendations for their monitoring in pragmatic trials to preserve inferences of treatment comparisons.

Unmet Need: Mechanistic and Translational Studies of Sickle Cell Disease Pain as a Whole-Person Health Challenge.

Sickle cell disease (SCD) is a lifelong monogenic, autosomal-recessive blood disease that predominantly affects individuals of African descent and those who self-identify as Black or Hispanic. Common SCD pathophysiological processes include adhesion, hemolysis, hypoxia, ischemia, oxidative stress, and vaso-occlusion, which often lead to substantial comorbidities and complications. Pain is one of the most common and significant clinical complications for individuals with SCD.

Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome.

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning.

Integrated multicomponent interventions to support healthy aging of the whole person.

Healthy aging is an integrated "whole person" process that involves an individual's biology, behavior, and social/physical environment. With the recent development of antiaging drugs, careful consideration of the respective roles of pharmacologic and nonpharmacologic approaches to both health and aging is in order. Recent advances in understanding the cellular and molecular mechanisms of aging are providing new measures that can be used as clinical outcomes in studying the impact of antiaging interventions in humans.

PIEZO2 and perineal mechanosensation are essential for sexual function.

Despite the potential importance of genital mechanosensation for sexual reproduction, little is known about how perineal touch influences mating. We explored how mechanosensation affords exquisite awareness of the genitals and controls reproduction in mice and humans. Using genetic strategies and in vivo functional imaging, we demonstrated that the mechanosensitive ion channel PIEZO2 (piezo-type mechanosensitive ion channel component 2) is necessary for behavioral sensitivity to perineal touch.

A glutamatergic DRN-VTA pathway modulates neuropathic pain and comorbid anhedonia-like behavior in mice.

Chronic pain causes both physical suffering and comorbid mental symptoms such as anhedonia. However, the neural circuits and molecular mechanisms underlying these maladaptive behaviors remain elusive. Here using a mouse model, we report a pathway from vesicular glutamate transporter 3 neurons in the dorsal raphe nucleus to dopamine neurons in the ventral tegmental area (VGluT3→DA) wherein population-level activity in response to innocuous mechanical stimuli and sucrose consumption is inhibited by chronic neuropathic pain.

Complementary and integrative health therapies in whole person resilience research.

Complementary and integrative health approaches can improve health and well-being, as well as play an important role in disease prevention. The concept of whole person health builds on these concepts by empowering individuals, families, communities, and populations to improve their health in multiple interconnected domains: biological, behavioural, social, and environmental. Research on whole person health involves studies of interconnected biological systems and complex approaches to prevention and treatment.

National Institutes of Health psilocybin research speaker series: State of the science, regulatory and policy landscape, research gaps, and opportunities.

The U.S. National Institutes of Health (NIH) convened a seminal first ever psychedelic drug substance-focused speaker series, from April 22 to June 10, 2021, titled the "NIH Psilocybin Research Speaker Series.

The Effects of a Single Bout of High- or Moderate-Intensity Yoga Exercise on Circulating Inflammatory Mediators: A Pilot Feasibility Study.

Background: There is a knowledge gap in the physiological effects of short-term yoga exercise interventions.

Objective: To evaluate the feasibility of a randomized controlled trial (RCT) assessing the acute effects of a yoga exercise protocol practiced at 2 intensities (high or moderate) on temporal responses of a battery of systemic circulatory cytokines in healthy yoga-naïve adults.

Methods: This study was a three-arm, pre-post pilot-RCT employing a single bout of yoga exercise intervention.

Sound induces analgesia through corticothalamic circuits.

Sound-including music and noise-can relieve pain in humans, but the underlying neural mechanisms remain unknown. We discovered that analgesic effects of sound depended on a low (5-decibel) signal-to-noise ratio (SNR) relative to ambient noise in mice. Viral tracing, microendoscopic calcium imaging, and multitetrode recordings in freely moving mice showed that low-SNR sounds inhibited glutamatergic inputs from the auditory cortex (ACx) to the thalamic posterior (PO) and ventral posterior (VP) nuclei.

Physician Office Visits That Included Complementary Health Approaches in U.S. Adults: 2005-2015.

The Institute of Medicine has described the need for comparing models of care delivery involving complementary health approaches and conventional medical practitioners. As a step toward addressing this need, we used a nationally representative 11-year sample of office-based visits to physicians from the National Ambulatory Medical Care Survey (NAMCS), to examine a comprehensive list of factors believed to be associated with visits where complementary health approaches were recommended or provided. NAMCS is a national health care survey designed to collect data on the provision and use of ambulatory medical care services provided by office-based physicians in the United States.

Reasons Office-Based Physicians in the United States Recommend Common Complementary Health Approaches to Patients: An Exploratory Study Using a National Survey.

To examine the reasons why office-based physicians do or do not recommend four selected complementary health approaches to their patients in the context of the Andersen Behavioral Model. Descriptive estimates of physician-level data from the 2012 National Ambulatory Medical Care Survey (NAMCS) Physician Induction Interview, a nationally representative survey of office-based physicians ( = 5622, weighted response rate = 59.7%).

Accounting for quality improvement during the conduct of embedded pragmatic clinical trials within healthcare systems: NIH Collaboratory case studies.

Embedded pragmatic clinical trials (ePCTs) and quality improvement (QI) activities often occur simultaneously within healthcare systems (HCSs). Embedded PCTs within HCSs are conducted to test interventions and provide evidence that may impact public health, health system operations, and quality of care. They are larger and more broadly generalizable than QI initiatives, and may generate what is considered high-quality evidence for potential use in care and clinical practice guidelines.

Longitudinal Analysis of Complementary Health Approaches in Adults Aged 25-74 Years from the Midlife in the U.S. Survey Sample.

Complementary health approaches include herbal products and mind-body practices. Several studies have identified predictors for complementary health approach use, yet there are two gaps: (1) How does use change? (2) Do factors associated with use influence this change over time? Using the Midlife in the United States (MIDUS), we examined how sociodemographic factors affected use longitudinally, and whether these associations differed between new and continued/discontinued use of herbal products, meditation, chiropractic, and massage therapy. MIDUS is a national probability sample of adults aged 25 or older that has collected more than 20 years of longitudinal data, including the use of complementary health approaches.

The Emerging Science of Interoception: Sensing, Integrating, Interpreting, and Regulating Signals within the Self.

Interoception refers to the representation of the internal states of an organism, and includes the processes by which it senses, interprets, integrates, and regulates signals from within itself. This review presents a unified research framework and attempts to offer definitions for key terms to describe the processes involved in interoception. We elaborate on these definitions through illustrative research findings, and provide brief overviews of central aspects of interoception, including the anatomy and function of neural and non-neural pathways, diseases and disorders, manipulations and interventions, and predictive modeling.

Characterization of Post-exertional Malaise in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome is characterized by persistent and disabling fatigue, exercise intolerance, cognitive difficulty, and musculoskeletal/joint pain. Post-exertional malaise is a worsening of these symptoms after a physical or mental exertion and is considered a central feature of the illness. Scant observations in the available literature provide qualitative assessments of post-exertional malaise in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Viral vectors for neuronal cell type-specific visualization and manipulations.

Characterizing neuronal cell types demands efficient strategies for specific labeling and manipulation of individual subtypes to dissect their connectivity and functions. Recombinant viral technology offers a powerful toolbox for targeted transgene expression in specific neuronal populations. In order to achieve cell type-specific targeting, exciting progress has been made to: alter viral tropisms, design rational delivery strategies, and drive selective expression patterns with engineered DNA sequences in viral genomes.

Default mode network changes in fibromyalgia patients are largely dependent on current clinical pain.

Differences in fMRI resting-state connectivity of the default mode network (DMN) seen in chronic pain patients are often interpreted as brain reorganization due to the chronic pain condition. Nevertheless, patients' pain at the time of fMRI might influence the DMN because pain, like cognitive stimuli, engages attentional mechanisms and cognitive engagement is known to alter DMN activity. Here, we aimed to dissociate the influence of chronic pain condition (trait) from the influence of current pain experience (state) on DMN connectivity in patients with fibromyalgia (FM).

What Twitter teaches us about patient-provider communication on pain.

The objective of this study was to understand how pain patients and health care providers (HCPs) are engaging on Twitter and what insights this engagement might provide. By identifying how information is spread by and between these audiences, organizations such as patient advocacy groups may be better poised to develop and share materials that facilitate online communication between HCPs and pain patients, with an end goal of improving a shared decision-making process around pain management. We analyzed the Twitter audiences most engaged on pain topics by conducting a Social Network Analysis (SNA) of a large network of connected users on Twitter.

U.S. Physician Recommendations to Their Patients About the Use of Complementary Health Approaches.

There are no nationally representative studies using a probability sample that have been published examining whether physicians recommend complementary health approaches (CHAs) to their patients, as previous research has focused only on selected medical specialties or a particular U.S. region.

The anatomy of the baroreceptor reflex.

Soohong et al. (2019) reveal a class of vagal afferents-defined by Piezo2 expression-that innervate the aorta and function to sense blood pressure fluctuations. Their study describes the morphologies and role of these neurons in vascular regulation.