Taking ACTION to reduce pain: ACTION study rationale, design and protocol of a randomized trial of a proactive telephone-based coaching intervention for chronic musculoskeletal pain among African Americans

Abstract Background Rates of chronic pain are rising sharply in the United States and worldwide. Presently, there is evidence of racial disparities in pain treatment and treatment outcomes in the United States but few interventions designed to address these disparities. There is growing consensus that chronic musculoskeletal pain is best addressed by a biopsychosocial approach that acknowledges the role of psychological and environmental factors, some of which differ by race. Methods/Design The primary aim of this randomized controlled trial is to test the effectiveness of a non-pharmacological, self-regulatory intervention, administered proactively by telephone, at improving pain outcomes and increasing walking among African American patients with hip, back and knee pain. Participants assigned to the intervention will receive a telephone counselor delivered pedometer-mediated walking intervention that incorporates action planning and motivational interviewing. The intervention will consist of 6 telephone counseling sessions over an 8–10 week period. Participants randomly assigned to Usual Care will receive an informational brochure and a pedometer. The primary outcome is chronic pain-related physical functioning, assessed at 6 months, by the revised Roland and Morris Disability Questionnaire, a measure recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). We will also examine whether the intervention improves other IMMPACT-recommended domains (pain intensity, emotional functioning, and ratings of overall improvement). Secondary objectives include examining whether the intervention reduces health care service utilization and use of opioid analgesics and whether key contributors to racial/ethnic disparities targeted by the intervention mediate improvement in chronic pain outcomes Measures will be assessed by mail and phone surveys at baseline, three months, and six months. Data analysis of primary aims will follow intent-to-treat methodology. Discussion We will tailor our intervention to address key contributors to racial pain disparities and examine the effects of the intervention on important pain treatment outcomes for African Americans with chronic musculoskeletal pain. Trial registration ClinicalTrials.gov: NCT01983228. Registered 6 November 2013

Taking ACTION to reduce pain: ACTION study rationale, design and protocol of a randomized trial of a proactive telephone-based coaching intervention for chronic musculoskeletal pain among African Americans

Abstract Background Rates of chronic pain are rising sharply in the United States and worldwide. Presently, there is evidence of racial disparities in pain treatment and treatment outcomes in the United States but few interventions designed to address these disparities. There is growing consensus that chronic musculoskeletal pain is best addressed by a biopsychosocial approach that acknowledges the role of psychological and environmental factors, some of which differ by race. Methods/Design The primary aim of this randomized controlled trial is to test the effectiveness of a non-pharmacological, self-regulatory intervention, administered proactively by telephone, at improving pain outcomes and increasing walking among African American patients with hip, back and knee pain. Participants assigned to the intervention will receive a telephone counselor delivered pedometer-mediated walking intervention that incorporates action planning and motivational interviewing. The intervention will consist of 6 telephone counseling sessions over an 8–10 week period. Participants randomly assigned to Usual Care will receive an informational brochure and a pedometer. The primary outcome is chronic pain-related physical functioning, assessed at 6 months, by the revised Roland and Morris Disability Questionnaire, a measure recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). We will also examine whether the intervention improves other IMMPACT-recommended domains (pain intensity, emotional functioning, and ratings of overall improvement). Secondary objectives include examining whether the intervention reduces health care service utilization and use of opioid analgesics and whether key contributors to racial/ethnic disparities targeted by the intervention mediate improvement in chronic pain outcomes Measures will be assessed by mail and phone surveys at baseline, three months, and six months. Data analysis of primary aims will follow intent-to-treat methodology. Discussion We will tailor our intervention to address key contributors to racial pain disparities and examine the effects of the intervention on important pain treatment outcomes for African Americans with chronic musculoskeletal pain. Trial registration ClinicalTrials.gov: NCT01983228. Registered 6 November 2013

Extracellular NAD + Is an Agonist of the Human P2Y 11 Purinergic Receptor in Human Granulocytes

Micromolar concentrations of extracellular beta-NAD+ (NAD(e)+) activate human granulocytes (superoxide and NO generation and chemotaxis) by triggering: (i) overproduction of cAMP, (ii) activation of protein kinase A, (iii) stimulation of ADP-ribosyl cyclase and overproduction of cyclic ADP-ribose (cADPR), a universal Ca2+ mobilizer, and (iv) influx of extracellular Ca2+. Here we demonstrate that exposure of granulocytes to millimolar rather than to micromolar NAD(e)+ generates both inositol 1,4,5-trisphosphate (IP3) and cAMP, with a two-step elevation of intracellular calcium levels ([Ca2+]i): a rapid, IP3-mediated Ca2+ release, followed by a sustained influx of extracellular Ca2+ mediated by cADPR. Suramin, an inhibitor of P2Y receptors, abrogated NAD(e)+-induced intracellular increases of IP3, cAMP, cADPR, and [Ca2+]i, suggesting a role for a P2Y receptor coupled to both phospholipase C and adenylyl cyclase. The P2Y(11) receptor is the only known member of the P2Y receptor subfamily coupled to both phospholipase C and adenylyl cyclase. Therefore, we performed experiments on hP2Y(11)-transfected 1321N1 astrocytoma cells: micromolar NAD(e)+ promoted a two-step elevation of the [Ca2+]i due to the enhanced intracellular production of IP3, cAMP, and cADPR in 1321N1-hP2Y(11) but not in untransfected 1321N1 cells. In human granulocytes NF157, a selective and potent inhibitor of P2Y(11), and the down-regulation of P2Y(11) expression by short interference RNA prevented NAD(e)+-induced intracellular increases of [Ca2+]i and chemotaxis. These results demonstrate that beta-NAD(e)+ is an agonist of the P2Y(11) purinoceptor and that P2Y(11) is the endogenous receptor in granulocytes mediating the sustained [Ca2+]i increase responsible for their functional activation

Learning to Apply Mindfulness to Pain (LAMP): Design for a Pragmatic Clinical Trial of Two Mindfulness-Based Interventions for Chronic Pain

Background: Mindfulness-based interventions (MBIs) are evidence-based nonpharmacological treatments for treating chronic pain. However, the predominant MBI, mindfulness-based stress reduction, has features that pose significant implementation barriers. Objectives: This study will test two approaches to delivering MBIs for improving Veterans' chronic pain and mental health comorbidities. These two approaches address key implementation barriers. Methods: We will conduct a four-site, three-arm pragmatic randomized controlled trial, Learning to Apply Mindfulness to Pain (LAMP), to test the effectiveness of two MBIs at improving pain and mental health comorbidities. Mobile+Group LAMP consists of prerecorded modules presented by a mindfulness instructor that are viewed in an online group setting and interspersed with discussions led by a facilitator. Mobile LAMP consists of the same prerecorded modules but does not include a group component. We will test whether either of these MBIs will be more effective than usual care at improving chronic pain and whether the Mobile+Group LAMP will be more effective than Mobile LAMP at improving chronic pain. Comparisons for the primary hypotheses will be conducted with continuous outcomes (Brief Pain Inventory interference score) repeated at 10 weeks, 6 months, and 12 months. The secondary hypotheses are that Mobile+Group LAMP and Mobile LAMP will be more effective than usual care at improving secondary outcomes (e.g., post-traumatic stress disorder, depression). We will also confirm the comparisons for the primary and secondary hypotheses in gender-specific strata. Implications: This trial is expected to result in two approaches for delivering MBIs that will optimize engagement, adherence, and sustainability and be able to reach large numbers of Veterans

Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

Raquel Sabino was not included as an author in the published article. It was corrected a posteriori.Erratum in - Corrigendum: Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon? [Front Microbiol. 2018] Front Microbiol. 2019 Jan 14;9:3245. doi: 10.3389/fmicb.2018.03245. eCollection 2018.Disponível em: https://www.frontiersin.org/articles/10.3389/fmicb.2018.03245/fullFree PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882871/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340063/Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods: A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results: The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions:Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.This work was supported by ECMM, ISHAM, and EFISG and in part by an unrestricted research grant through the Investigator Initiated Studies Programof Astellas, MSD, and Pfizer. This study was fundet by the Christian Doppler Laboratory for invasive fungal infections.info:eu-repo/semantics/publishedVersio

Predictors for prolonged hospital stay solely to complete intravenous antifungal treatment in patients with candidemia: Results from the ECMM candida III multinational European observational cohort study

Background To date, azoles represent the only viable option for oral treatment of invasive Candida infections, while rates of azole resistance among non-albicans Candida spp. continue to increase. The objective of this sub-analysis of the European multicenter observational cohort study Candida III was to describe demographical and clinical characteristics of the cohort requiring prolonged hospitalization solely to complete intravenous (iv) antifungal treatment (AF Tx). Methods Each participating hospital (number of eligible hospitals per country determined by population size) included the first ~ 10 blood culture proven adult candidemia cases occurring consecutively after July 1st, 2018, and treating physicians answered the question on whether hospital stay was prolonged only for completion of intravenous antifungal therapy. Descriptive analyses as well as binary logistic regression was used to assess for predictors of prolonged hospitalization solely to complete iv AF Tx. Findings Hospital stay was prolonged solely for the completion of iv AF Tx in 16% (100/621) of candidemia cases by a median of 16 days (IQR 8 – 28). In the multivariable model, initial echinocandin treatment was a positive predictor for prolonged hospitalization to complete iv AF Tx (aOR 2.87, 95% CI 1.55 – 5.32, p < 0.001), while (i) neutropenia, (ii) intensive care unit admission, (iii) catheter related candidemia, (iv) total parenteral nutrition, and (v) C. parapsilosis as causative pathogen were found to be negative predictors (aOR 0.22 – 0.45; p < 0.03). Interpretation Hospital stays were prolonged due to need of iv AF Tx in 16% of patients with candidemia. Those patients were more likely to receive echinocandins as initial treatment and were less severely ill and less likely infected with C. parapsilosis

WHO global research priorities for antimicrobial resistance in human health

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR

Family Caregiver Satisfaction with Inpatient Rehabilitation Care

Introduction: Informal family caregivers play an increasingly important role in healthcare. Despite their role in ongoing management and coordination of care, caregiver satisfaction with the healthcare services care recipients receive has been understudied. We sought to assess what influences caregiver satisfaction with inpatient care provided to their care recipient among caregivers of veterans with traumatic brain injury (TBI) and polytrauma. Methods: Data from the Family and Caregiver Experience Survey, a national survey of caregivers of veterans with TBI and polytrauma, was used to explore factors associated with caregiver satisfaction with the care his/her care recipient received while an inpatient at a US Department of Veterans Affairs (VA) Polytrauma Rehabilitation Center. Caregiver and care recipient demographic and injury factors and potential addressable factors including social support, caregiver training received, and caregiver perceptions of being valued by the VA were evaluated for their associations with caregivers’ satisfaction with their care recipients’ healthcare. Results: The majority of the 524 caregivers reported being mostly or very satisfied with their care recipient’s inpatient care (75%, n = 393). Higher satisfaction with inpatient care was significantly associated with greater caregiver social support, receipt of training from the VA, and perceptions of being valued by the VA, both on univariate analysis and after controlling for care recipient TBI severity and caregiver’s relationship to the care recipient