Describing Perspectives of Telehealth and the Impact on Equity in Access to Health Care from Community and Provider Perspectives: A Multimethod Analysis.

Introduction: The rapid adoption of telehealth as a result of the COVID-19 pandemic provided the opportunity to examine perceptions of health care access and use of telehealth for delivery of effective and equitable care in low-income and historically marginalized communities. Methods: Focusing on communities with high social vulnerability, a multimethod analysis of combined perspectives, collected February through August 2022 from 112 health care providers, obtained from surveys and interviews, and 23 community members via 3 focus groups on access to care and telehealth. Qualitative data were analyzed using the Health Equity and Implementation Framework to identify barriers, facilitators, and recommendations for the implementation of telehealth using a health equity lens. Results: Participants perceived that telehealth helped maintain access to health care during the pandemic by addressing barriers including provider shortages, transportation concerns, and scheduling conflicts. Additional benefits suggested were improved care quality and coordination attributed to convenient avenues for care delivery and communication among providers and patients. However, many barriers to telehealth were reported and considered to limit equitable access to care. These included restrictive or changing policies regarding allowable services provided via telehealth, and availability of technology and broadband services to enable telehealth visits. Recommendations provided insight into care delivery innovation opportunities and potential policy changes to address equitable access to care. Conclusion: Integration of telehealth into models of care delivery could improve access to health care services and promote communication among providers and patients to improve care quality. Our findings have implications that are critical for future policy reforms and telehealth research.

What Explains Inequalities in Telehealth Utilization Among North Carolina Medicaid Beneficiaries?

Background: Increased availability of telehealth can improve access to health care. However, there is evidence of persistent disparities in telehealth usage, as well as among people from minoritized racial and ethnic groups and rural residents. The objective of our work was to explore the degree to which disparities in telehealth use for behavioral health (BH) and musculoskeletal (MSK) related services during the COVID-19 pandemic are explained by observed beneficiary- and area-level characteristics. Methods: Using North Carolina Medicaid claims data of Medicaid beneficiaries with BH or MSK conditions, we apply nonlinear regression-based decomposition analysis-based models developed by Kitagawa, Oaxaca, and Blinder to determine which observed variables are associated with racial, ethnic, and rural inequalities in telehealth usage. Results: In the BH cohort, we found statistically significant differences in telehealth usage by race in the adult population, and by race, Hispanic ethnicity, and rurality in the pediatric population. In the MSK cohort, we found significant inequities by Hispanic ethnicity and rurality among adults, and by race and rurality among children. Inequalities in telehealth use between groups were small, ranging from 0.7 percentage points between urban and rural adults with MSK conditions to 3.8 percentage points between white adults and people of color among those with BH conditions. Overall, we found that racial and ethnic inequalities in telehealth use are not well explained by the observed variables in our data. Rural disparities in telehealth use are better explained by observed variables, particularly area-level broadband internet use. Conclusions: For inequalities between rural and urban residents, our analysis provides observational evidence that infrastructure such as broadband internet access is an important driver of differences in telehealth use. For racial and ethnic inequalities, the pathways may be more complex and difficult to measure, particularly when relying on administrative data sources in place of more detailed data on individual-level socioeconomic factors.

Evaluating Telehealth Uptake Among North Carolina Medicaid Beneficiaries With Musculoskeletal Conditions: Insights From the COVID-19 Pandemic.

BACKGROUND: The shift from in-person to virtual visits, known as telehealth (TH), during the COVID-19 pandemic was a significant change for North Carolina (NC) Medicaid beneficiaries seeking treatment for musculoskeletal (MSK) conditions, as remote care for these conditions was previously unavailable. We used this policy change to investigate factors associated with TH uptake and whether TH availability mitigated disparities in access to care or affected emergency department (ED) visits among these beneficiaries. RESEARCH DESIGN: Using 2019-2021 NC Medicaid claims, we identified beneficiaries receiving treatment for MSK conditions before COVID-19 (March 2019-February 2020) and analyzed uptake of newly available TH during COVID-19 (April 2020-March 2021). We used descriptive analysis and Poisson generalized estimating equations to quantify TH uptake, factors associated with TH uptake, and the association with ED visits during COVID-19. RESULTS: Black and Hispanic beneficiaries were less likely to use TH compared with White and non-Hispanic counterparts (10%, P <0.001 and 20%, P =0.03, respectively). Adults eligible for Tailored Plans, specialized NC Medicaid plans for those with significant behavioral health needs or intellectual/developmental disabilities, were less likely to use TH [adjusted risk ratio (ARR):0.83, 95% CI (0.78, 0.87)]; youth eligible for Tailored Plans were more likely to use TH [ARR:1.28, 95% CI (1.16, 1.42)]. Lower county-level internet access was associated with lower TH use [ARR: 0.85, 95% CI (0.82, 0.99)]. No statistical difference in ED utilization was observed between TH users and non-users. CONCLUSIONS: TH has the potential to deliver convenient care to beneficiaries with MSK conditions who can access it. Further research and policy changes should explore and address underlying factors driving disparities and improve equitable access to care for this population.

Mind-Body Exercise Performed by Physical Therapists for Reducing Pain and Disability in Low Back Pain: A Systematic Review With Meta-analysis.

OBJECTIVE: To assess the effectiveness of mind-body (MB) exercise interventions provided by physical therapists for reducing pain and disability in people with low back pain (LBP). DATA SOURCES: MEDLINE, Embase, CINAHL, and the Cochrane Library were searched for articles published in English between December 2010 and June 2020. STUDY SELECTION: Randomized controlled trials evaluating the effects of Pilates, yoga, and tai chi interventions performed by physical therapists on pain or disability outcomes in adults with musculoskeletal LBP were included. DATA EXTRACTION: Data were extracted by 2 independent reviewers. Quality of evidence and risk of bias were assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework and Cochrane risk of bias tools, respectively. DATA SYNTHESIS: 21,230 exercise trials were identified; 161 progressed to full-text review. Eight trials, 7 reporting on Pilates and 1 reporting on yoga, were included. Short-term outcomes for pain (SMD: -0.93; 95% confidence interval [CI]: -1.65 to -0.021) and disability (SMD: -0.74 95% CI: -1.36 to -0.012) indicated MB exercise was more effective than control intervention. Tests for subgroup differences between studies with exercise vs non-exercise control groups revealed a moderating effect on short-term outcomes where larger effects were observed in studies with non-exercise comparators. Long-term outcomes for pain (SMD: -0.60; 95% CI:-1.43 to 0.23) and disability (SMD: -1.05; 95% CI:-3.51 to 1.41) suggested that MB exercise is not more effective than control interventions for pain or disability. Quality of the evidence ranged from very low to low. CONCLUSIONS: Physical therapist-delivered MB exercise interventions, which overwhelmingly consisted of Pilates, were more effective than control in the short and long-term for pain and in the short-term for disability, with differences in the short-term effects lessened when compared with an active intervention. Pilates interventions delivered by physical therapists represent a viable tool for the clinical management of chronic LBP.

All non-real worlds provide exploration: Evidence from developmental psychology.

While Dubourg and Baumard argue that predisposition toward exploration draws us to fictional environments, they fail to answer their titular question: "Why Imaginary Worlds?" Research in pretend play, psychological distancing, and theatre shows that being "imaginary" (i.e., any type of unreal, rather than only fantastically unreal) makes exploration of any fictional world profoundly different than that of real-life unfamiliar environments.

Orai1 Channel Inhibition Preserves Left Ventricular Systolic Function and Normal Ca2+ Handling After Pressure Overload.

BACKGROUND: Orai1 is a critical ion channel subunit, best recognized as a mediator of store-operated Ca2+ entry (SOCE) in nonexcitable cells. SOCE has recently emerged as a key contributor of cardiac hypertrophy and heart failure but the relevance of Orai1 is still unclear. METHODS: To test the role of these Orai1 channels in the cardiac pathophysiology, a transgenic mouse was generated with cardiomyocyte-specific expression of an ion pore-disruptive Orai1R91W mutant (C-dnO1). Synthetic chemistry and channel screening strategies were used to develop 4-(2,5-dimethoxyphenyl)-N-[(pyridin-4-yl)methyl]aniline (hereafter referred to as JPIII), a small-molecule Orai1 channel inhibitor suitable for in vivo delivery. RESULTS: Adult mice subjected to transverse aortic constriction (TAC) developed cardiac hypertrophy and reduced ventricular function associated with increased Orai1 expression and Orai1-dependent SOCE (assessed by Mn2+ influx). C-dnO1 mice displayed normal cardiac electromechanical function and cellular excitation-contraction coupling despite reduced Orai1-dependent SOCE. Five weeks after TAC, C-dnO1 mice were protected from systolic dysfunction (assessed by preserved left ventricular fractional shortening and ejection fraction) even if increased cardiac mass and prohypertrophic markers induction were observed. This is correlated with a protection from TAC-induced cellular Ca2+ signaling alterations (increased SOCE, decreased [Ca2+]i transients amplitude and decay rate, lower SR Ca2+ load and depressed cellular contractility) and SERCA2a downregulation in ventricular cardiomyocytes from C-dnO1 mice, associated with blunted Pyk2 signaling. There was also less fibrosis in heart sections from C-dnO1 mice after TAC. Moreover, 3 weeks treatment with JPIII following 5 weeks of TAC confirmed the translational relevance of an Orai1 inhibition strategy during hypertrophic insult. CONCLUSIONS: The findings suggest a key role of cardiac Orai1 channels and the potential for Orai1 channel inhibitors as inotropic therapies for maintaining contractility reserve after hypertrophic stress.

Side-by-side comparison of published small molecule inhibitors against thapsigargin-induced store-operated Ca2+ entry in HEK293 cells.

Calcium (Ca2+) is a key second messenger in eukaryotes, with store-operated Ca2+ entry (SOCE) being the main source of Ca2+ influx into non-excitable cells. ORAI1 is a highly Ca2+-selective plasma membrane channel that encodes SOCE. It is ubiquitously expressed in mammals and has been implicated in numerous diseases, including cardiovascular disease and cancer. A number of small molecules have been identified as inhibitors of SOCE with a variety of potential therapeutic uses proposed and validated in vitro and in vivo. These encompass both nonselective Ca2+ channel inhibitors and targeted selective inhibitors of SOCE. Inhibition of SOCE can be quantified both directly and indirectly with a variety of assay setups, making an accurate comparison of the activity of different SOCE inhibitors challenging. We have used a fluorescence based Ca2+ addback assay in native HEK293 cells to generate dose-response data for many published SOCE inhibitors. We were able to directly compare potency. Most compounds were validated with only minor and expected variations in potency, but some were not. This could be due to differences in assay setup relating to the mechanism of action of the inhibitors and highlights the value of a singular approach to compare these compounds, as well as the general need for biorthogonal validation of novel bioactive compounds. The compounds observed to be the most potent against SOCE in our study were: 7-azaindole 14d (12), JPIII (17), Synta-66 (6), Pyr 3 (5), GSK5503A (8), CM4620 (14) and RO2959 (7). These represent the most promising candidates for future development of SOCE inhibitors for therapeutic use.

Interventions to Improve Long-Term Adherence to Physical Rehabilitation: A Systematic Review.

OBJECTIVE: To evaluate the impact of physical rehabilitation interventions, supplemented with one or more adherence-enhancing components, on outcomes among adults with hip or knee osteoarthritis or chronic lower back pain. DESIGN: Primary literature search from inception of each database to July 27, 2021, guided by relevant search terms and keywords to search titles and abstracts. All articles meeting eligibility criteria were included for data abstraction. DATA SOURCES: MEDLINE, CINAHL Complete, and Embase. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomized and nonrandomized trials evaluating adherence-focused intervention components conducted in addition to an index usual care or usual care-like physical rehabilitation program among adults with hip or knee osteoarthritis or chronic low back pain. Eligible studies included a comparator group of the same index physical rehabilitation intervention without the adjunctive adherence components. Included studies measured outcomes at least 3 months after the rehabilitation course. RESULTS: Of the 10 studies meeting inclusion criteria, 6 interventions were delivered concurrent to an index rehabilitation program and 4 were delivered sequentially. Of the 3 studies that reported a positive effect on long-term adherence, only 1 was a low risk of bias study. There is very limited evidence of a beneficial treatment effect of adjunct adherence interventions on long-term physical function, self-efficacy, or adverse events. CONCLUSION: We found inadequate evidence evaluating adherence-enhancing interventions for the specific promotion of long-term adherence to home rehabilitation programs. Future studies should consider testing interventions specifically built to target behavioral maintenance of home rehabilitation programs.

Association between parenthood and cardiovascular disease risk: Analysis from NHANES 2011-2016.

The objective of this study was to examine the association between parenthood and cardiovascular disease (CVD) risk factors among a nationally representative sample of United States adults. A cross sectional analysis was conducted with adults aged 20-59 years from the National Health and Nutrition Examination Survey 2011-2016. Adults were classified as parents and non-parents based on the presence of children birth-17 years in the home. CVD risk factors assessed included: physical inactivity, obesity, blood pressure, HDL cholesterol, glycohemoglobin, and smoking status. Multivariable logistic regression models stratified by sex were used to examine the association between parenthood and each risk factor. 10,908 adults (5,329 [49%] male, weighted mean age 39.6 years) were included. In adjusted analyses, fathers had greater odds of obesity (OR: 1.22; 95% CI: 1.04-1.42) and lower odds of being a current smoker (OR: 0.82; 95% CI: 0.68-0.98) compared to non-fathers. Mothers had greater odds of physical inactivity (OR: 1.27; 95% CI: 1.03-1.56) and low HDL cholesterol (OR: 1.24; 95% CI: 1.06-1.45), and lower odds of being a current smoker (OR: 0.78; 95% CI: 0.63-0.96) compared to non-mothers. Parents with younger children in the household tended to have greater odds of CVD risk factors compared to non-parents. No clear patterns emerged in CVD factor risk based on the number of children in the household. Parents are at greater risk for several modifiable CVD risk factors. This illustrates the importance of including parental health promotion in settings that serve children and implementing policies that support parental health and wellbeing.

Expanding access to rehabilitation using mobile health to address musculoskeletal pain and disability.

Introduction: Musculoskeletal (MSK) disorders such as low back pain and osteoarthritis are a leading cause of disability and the leading contributor to the need for rehabilitation services globally. This need has surpassed the availability of trained clinicians; even in urban areas where services and providers are thought to be more abundant, access can be challenged by transportation options and financial costs associated with travel, care and lost time from work. However, continuing standard of fully in-person rehabilitation care for MSK-associated pain and disability may no longer be necessary. With increased ownership or access to even a basic mobile phone device, and evidence for remote management by trained clinicians, some individuals with MSK disorders may be able to continue their rehabilitation regimen predominantly from home after initial evaluation in primary care or an outpatient clinic. Methods: This manuscript describes application of a framework we used to culturally and contextually adapt an evidence-based approach for leveraging digital health technology using a mobile phone (mHealth) to expand access to rehabilitation services for MSK-associated pain and disability. We then conducted a multi-level analysis of policies related to the adapted approach for rehabilitation service delivery to identify opportunities to support sustainability. Results: Our study was conducted in Tanzania, a lower-middle income country with their first National Rehabilitation Strategic Plan released in 2021. Lessons learned can be applied even to countries with greater infrastructure or fewer barriers. The seven-step adaptation framework used can be applied in other regions to improve the likelihood of local mHealth adoption and implementation. Our practice and policy assessment for Tanzania can be applied in other regions and used collaboratively with government officials in support of building or implementing a national rehabilitation strategic plan. Conclusion: The work described, lessons learned and components of the plan are generalizable globally and can improve access to rehabilitation services using mHealth to address the significant and increasing burden of disability.

Association of Biomarkers with Individual and Multiple Body Sites of Pain: The Johnston County Osteoarthritis Project.

Introduction: Biochemical biomarkers may provide insight into musculoskeletal pain reported at individual or multiple body sites. The purpose of this study was to determine if biomarkers or pressure-pain threshold (PPT) were associated with individual or multiple sites of pain. Methods: This cross-sectional analysis included 689 community-based participants. Self-reported symptoms (ie, pain, aching, or stiffness) were ascertained about the neck, upper back/thoracic, low back, shoulders, elbows, wrist, hands, hips, knees, ankles, and feet. Measured analytes included CXCL-6, RANTES, HA, IL-6, BDNF, OPG and NPY. A standard dolorimeter measured PPT. Logistic regression was used determine the association between biomarkers and PPT with individual and summed sites of pain. Results: Increased IL-6 and HA were associated with knee pain (OR=1.30, 95% CI 1.03, 1.64) and (OR=1.32, 95% CI 1.01, 1.73) respectively; HA was also associated with elbow/wrist/hand pain (OR=1.60, 95% CI 1.22, 2.09). Those with increased NPY levels were less likely to have shoulder pain (OR=0.56, 95% CI 0.33, 0.93). Biomarkers HA (OR=1.50, 95% CI 1.07, 2.10), OPG (OR=1.74, 95% CI 1.00, 3.03), CXCL-6 (OR=1.75, 95% CI 1.02, 3.01) and decreased PPT (OR=3.97, 95% CI 2.22, 7.12) were associated with multiple compared to no sites of pain. Biomarker HA (OR=1.57, 95% CI 1.06, 2.32) and decreased PPT (OR=3.53, 95% CI 1.81, 6.88) were associated with multiple compared to a single site of pain. Conclusion: Biomarkers of inflammation (HA, OPG, IL-6 and CXCL-6), pain (NPY) and PPT may help to understand the etiology of single and multiple pain sites.

ORAI1 Ca2+ Channel as a Therapeutic Target in Pathological Vascular Remodelling.

In the adult, vascular smooth muscle cells (VSMC) are normally physiologically quiescent, arranged circumferentially in one or more layers within blood vessel walls. Remodelling of native VSMC to a proliferative state for vascular development, adaptation or repair is driven by platelet-derived growth factor (PDGF). A key effector downstream of PDGF receptors is store-operated calcium entry (SOCE) mediated through the plasma membrane calcium ion channel, ORAI1, which is activated by the endoplasmic reticulum (ER) calcium store sensor, stromal interaction molecule-1 (STIM1). This SOCE was shown to play fundamental roles in the pathological remodelling of VSMC. Exciting transgenic lineage-tracing studies have revealed that the contribution of the phenotypically-modulated VSMC in atherosclerotic plaque formation is more significant than previously appreciated, and growing evidence supports the relevance of ORAI1 signalling in this pathologic remodelling. ORAI1 has also emerged as an attractive potential therapeutic target as it is accessible to extracellular compound inhibition. This is further supported by the progression of several ORAI1 inhibitors into clinical trials. Here we discuss the current knowledge of ORAI1-mediated signalling in pathologic vascular remodelling, particularly in the settings of atherosclerotic cardiovascular diseases (CVDs) and neointimal hyperplasia, and the recent developments in our understanding of the mechanisms by which ORAI1 coordinates VSMC phenotypic remodelling, through the activation of key transcription factor, nuclear factor of activated T-cell (NFAT). In addition, we discuss advances in therapeutic strategies aimed at the ORAI1 target.

Interventions for the Management of Acute and Chronic Low Back Pain: Revision 2021.

Low back pain (LBP) remains a musculoskeletal condition with an adverse societal impact. Globally, LBP is highly prevalent and a leading cause of disability. This is an update to the 2012 Academy of Orthopaedic Physical Therapy (AOPT), formerly the Orthopaedic Section of the American Physical Therapy Association (APTA), clinical practice guideline (CPG) for LBP. The overall objective of this update was to provide recommendations on interventions delivered by physical therapists or studied in care settings that included physical therapy providers. It also focused on synthesizing new evidence, with the purpose of making recommendations for specific nonpharmacologic treatments. J Orthop Sports Phys Ther 2021;51(11):CPG1-CPG60. doi:10.2519/jospt.2021.0304.

Tonantzitlolone is a nanomolar potency activator of transient receptor potential canonical 1/4/5 channels.

BACKGROUND AND PURPOSE: The diterpene ester tonantzitlolone (TZL) is a natural product, which displays cytotoxicity towards certain types of cancer cell such as renal cell carcinoma cells. The effect is similar to that of (-)-englerin A, and so, although it is chemically distinct, we investigated whether TZL also targets transient receptor potential canonical (TRPC) channels of the 1, 4 and 5 type (TRPC1/4/5 channels). EXPERIMENTAL APPROACH: The effects of TZL on renal cell carcinoma A498 cells natively expressing TRPC1 and TRPC4, modified HEK293 cells overexpressing TRPC4, TRPC5, TRPC4-TRPC1 or TRPC5-TRPC1 concatemer, TRPC3 or TRPM2, or CHO cells overexpressing TRPV4 were studied by determining changes in intracellular Ca2+ , or whole-cell or excised membrane patch-clamp electrophysiology. KEY RESULTS: TZL induced an elevation of intracellular Ca2+ in A498 cells, similar to that evoked by englerin A. TZL activated overexpressed channels with EC50 values of 123 nM (TRPC4), 83 nM (TRPC5), 140 nM (TRPC4-TRPC1) and 61 nM (TRPC5-TRPC1). These effects of TZL were reversible on wash-out and potently inhibited by the TRPC1/4/5 inhibitor Pico145. TZL activated TRPC5 channels when bath-applied to excised outside-out but not inside-out patches. TZL failed to activate endogenous store-operated Ca2+ entry or overexpressed TRPC3, TRPV4 or TRPM2 channels in HEK 293 cells. CONCLUSIONS AND IMPLICATIONS: TZL is a novel potent agonist for TRPC1/4/5 channels, which should be useful for testing the functionality of this type of ion channel and understanding how TRPC1/4/5 agonists achieve selective cytotoxicity against certain types of cancer cell.