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The branched-chain amino acid, leucine, acts as a nutrient signal to stimulate protein synthesis in skeletal muscle of young pigs. However, the chemical structure responsible for this effect has not been identified. We have shown that the other branched-chain amino acids, isoleucine and valine, are not able to stimulate protein synthesis when raised in plasma to levels within the postprandial range. In this study, we evaluated the effect of leucine, alpha-ketoisocaproic acid (KIC), and norleucine infusion (0 or 400 micromol kg(-1) h(-1) for 60 min) on protein synthesis and activation of translation initiation factors in piglets. Infusion of leucine, KIC, and norleucine raised plasma levels of each compound compared with controls. KIC also increased (P < 0.01) and norleucine reduced (P < 0.02) plasma levels of leucine compared with controls. Administration of leucine and KIC resulted in greater (P < 0.006) phosphorylation of eukaryotic initiation factor (eIF) 4E binding protein-1 (4E-BP1) and eIF4G, lower (P < 0.04) abundance of the inactive 4E-BP1.eIF4E complex, and greater (P < 0.05) active eIF4G.eIF4E complex formation in skeletal muscle compared with controls. Protein synthesis in skeletal muscle was greater (P < 0.02) in leucine- and KIC-infused pigs than in those in the control group. Norleucine infusion did not affect muscle protein synthesis or translation initiation factor activation. In liver, neither protein synthesis nor activation of translation initiation factors was affected by treatment. These results suggest that the ability of leucine to act as a nutrient signal to stimulate skeletal muscle protein synthesis is specific for leucine and/or its metabolite, KIC. [ABSTRACT FROM AUTHOR]

Objective: To assess the radiation dose received by the radiologist when performing wire localisation for axillary radio-isotope sentinel node imaging-guided biopsy in patients with impalpable breast cancers treated with breast-preserving excision. When wire placement follows radio-isotope sentinel node imaging (RSNI) the radiologist is exposed to a radiation risk that has never been previously assessed.Methods: Radiation doses to radiologists performing ultrasound-guided localisation following nuclear medicine sentinel node imaging were measured for procedures on the day of surgery (20 MBq) and also on the day before surgery (40 MBq). These measurements were compared with theoretically calculated doses.Results: Twelve patients showed comparable results between measurements and estimated doses. The mean measured dose was 1.8 muSv (estimated 1.8 muSv) for same-day and 4.8 muSv (estimated 3.4 muSv) for next-day surgery cases. At worst, radiologists who perform 36 wire localisations per year immediately following RSNI receive a radiation dose of 0.17 mSv.Conclusions: This study highlights the need to inform radiologists of the relative risk when performing pre-surgical localisation after RSNI. This risk should be justified locally in accordance with the total dose received by the localising radiologist. Particular consideration should be given to pregnant staff and the possibility of performing wire localisations before radio-isotope injection. [ABSTRACT FROM AUTHOR]

Background: Most clinicians would probably agree that what patients think will happen can influence what does happen over the clinical course. Yet despite useful narrative reviews on expectancy of therapeutic gain and the mechanisms by which expectancy can affect health outcomes, we were unable to locate a systematic review of the predictive relation between patients' recovery expectations and their health outcomes.Methods: We searched MEDLINE for English-language articles published from 1966 to June 1998 with a title or abstract containing at least 1 of the medical subject headings (MeSH) "self-assessment," "self-concept" or "attitude to health," or the MeSH subheading "psychology," and at least 1 word from each of 3 sets: "patient" and similar words; a form of "expectation," "belief" or "prediction"; and a form of "recover," "outcome," "survival" or "improve." Relevant articles contained original research data, measured patients' recovery expectations, independently measured a subsequent health outcome and analyzed the relation between expectations and outcomes. We assessed internal validity using quality criteria for prognostic studies based on 6 categories (case definition; patient selection; extent of follow-up; objective outcome criteria; measurement and reporting of recovery expectations; and analysis).Results: A total of 1243 titles or abstracts were identified through the computer search, and 93 full-text articles were retrieved. Forty-one of these articles met the relevance criteria, along with 4 additional articles identified through other means. Agreement beyond chance on quality assessments of 18 randomly selected articles was high (kappa = 0.87, p = 0.001). Sixteen of the 45 articles provided moderate-quality evidence and included a range of clinical conditions and study designs; 15 of the 16 showed that positive expectations were associated with better health outcomes. The strength of the relation depended on the clinical conditions and the measured used.Interpretation: Consistency across the studies reviewed and the evidence they provided support the need for clinicians to clarify patients' expectations and to assist them in having appropriate expectations of recovery. The understanding of the nature, extent and clinical implications of the relation between expectations and outcomes could be enhanced by more conceptually driven and methodologically sound research, including evaluations of intervention effectiveness. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study determined whether the physical and psychosocial demands of work are associated with low back pain. METHODS: A case-control approach was used. Case subjects (n = 137) reported a new episode of low back pain to their employer, a large automobile manufacturing complex. Control subjects were randomly selected from the study base as cases accrued (n = 179) or were matched to cases by exact job (n = 65). Individual, clinical, and psychosocial variables were assessed by interview. Physical demands were assessed with direct workplace measurements of subjects at their usual jobs. The analysis used multiple logistic regression adjusted for individual characteristics. RESULTS: Self-reported risk factors included a physically demanding job, a poor workplace social environment, inconsistency between job and education level, better job satisfaction, and better coworker support. Low job control showed a borderline association. Physical-measure risk factors included peak lumbar shear force, peak load handled, and cumulative lumbar disc compression. Low body mass index and prior low back pain compensation claims were the only significant individual characteristics. CONCLUSIONS: This study identified specific physical and psychosocial demands of work as independent risk factors for low back pain. [ABSTRACT FROM AUTHOR]

Roots of the epidemic of alcohol-related problems among many Native North Americans are sought in cultural responses to European arrival, the role of alcohol in frontier society, and colonial and postcolonial policies. Evidence from the historical record is considered within the framework of current social science. Initially, Native American's responses to alcohol were heavily influenced by the example of White frontiersmen, who drank immoderately and engaged in otherwise unacceptable behavior while drunk. Whites also deliberately pressed alcohol upon the natives because it was an immensely profitable trade good; in addition, alcohol was used as a tool of 'diplomacy' in official dealings between authorities and natives. The authors argue that further research into the origins of modern indigenous people's problems with alcohol would benefit from an interdisciplinary 'determinants of health' approach in which biological influences on alcohol problems are investigated in the context of the cultural, social, and economic forces that have shaped individual and group drinking patterns. [ABSTRACT FROM AUTHOR]

The causes of reported occupational back pain are controversial. Many observers appear to believe that job insecurity increases back pain compensation claims during recessions. The purpose of this study was to formally examine the impact of macro-economic forces-the business cycle-on the incidence of lost-time back pain claim rates in order to elicit clues to both its aetiology and reporting patterns. For Ontario between 1975 and 1993, age- and sex-adjusted lost-time back pain claim rates, stratified by industry sector (construction, manufacturing and trade), were regressed on the unemployment rate of the industry sector using time series methods. As a comparison group, the association between 'acute' claim (fractures, lacerations, etc.) and the business cycle was also tested. Both back pain claim rates and acute claim rates increased during boom periods and decreased during recessionary periods. Time series analyses confirmed that these associations were statistically significant. The elasticities between claim rates and the unemployment rate were similar for back pain claims and acute claims. In addition, these associations were consistent in direction across all three industrial sectors tested. These results rebut the view that back pain claims increase during recessionary times. [ABSTRACT FROM AUTHOR]

PURPOSE: Misclassification of gestational age based on the last menstrual period (LMP) in routinely collected data creates bias in newborn birthweight and gestational age-related indicators. Common correction methods have not been evaluated. We developed a normal mixture model for use with SAS software to correct misclassification of gestational age and compare its performance with other available correction methods and estimates of gestational age. METHODS: Using the 2007 United States natality file from the National Center for Health Statistics, we compared LMP preterm and postterm birth rates and gestational age-specific birthweight percentiles against a reference subset of births, where the likelihood of misclassification in gestational age was minimized, before and after correction by a normal mixture model, two truncation methods, and the clinical/obstetric estimate of gestational age. RESULTS: The mixture model corrected preterm and postterm birth rates by 90% and 41% respectively, but previous methods performed poorly. The mixture model was also superior in correcting birthweight percentiles 50 and 90 with error reductions in the range of 68% to 85% between 28 and 36 weeks of gestation, where most misclassification occurred. CONCLUSIONS: The mixture model behaved consistently better than truncation methods, particularly between weeks 28 and 36 of gestation. [ABSTRACT FROM AUTHOR]

Importance: Patients prescribed long-term opioid therapy for chronic pain often experience unrelieved pain, poor quality of life, and serious adverse events., Objective: To compare the effects of integrated pain team (IPT) vs pharmacist collaborative management (PCM) on pain and opioid dosage., Design, Setting, and Participants: This study was a pragmatic multisite 12-month randomized comparative effectiveness trial with masked outcome assessment. Patients were recruited from October 2017 to March 2021; follow-up was completed June 2022. The study sites were Veterans Affairs primary care clinics. Eligible patients had moderate to severe chronic pain despite long-term opioid therapy (≥20 mg/d for at least 3 months)., Interventions: IPT involved interdisciplinary pain care planning, visits throughout 12 months with medical and mental health clinicians, and emphasis on nondrug therapies and motivational interviewing. PCM was a collaborative care intervention involving visits throughout 12 months with a clinical pharmacist care manager who conducted structured monitoring and medication optimization. Both interventions provided individualized pain care and opioid tapering recommendations to patients., Main Outcomes and Measures: The primary outcome was pain response (≥30% decrease in Brief Pain Inventory total score) at 12 months. The main secondary outcome was 50% or greater reduction in opioid daily dosage at 12 months., Results: A total of 820 patients were randomized to IPT (n = 411) or PCM (n = 409). Participants' mean (SD) age was 62.2 (10.6) years, and 709 (86.5%) were male. A pain response was achieved in 58/350 patients in the IPT group (16.4%) vs 54/362 patients in the PCM group (14.9%) (odds ratio, 1.11 [95% CI, 0.74-1.67]; P = .61). A 50% opioid dose reduction was achieved in 102/403 patients in the IPT group (25.3%) vs 98/399 patients in the PCM group (24.6%) (odds ratio, 1.03 [95% CI, 0.75-1.42]; P = .85). Over 12 months, the mean (SD) Brief Pain Inventory total score improved from 6.7 (1.5) points to 6.1 (1.8) points (P < .001) in IPT and from 6.6 (1.6) points to 6.0 (1.9) points (P < .001) in PCM (between-group P = .82). Over 12 months, mean (SD) opioid daily dosage decreased from 80.8 (74.2) mg/d to 54.2 (65.0) mg/d in IPT (P < .001) and from 74.5 (56.9) mg/d to 52.8 (51.9) mg/d (P < .001) in PCM (between-group P = .22)., Conclusions and Relevance: Outcomes in this randomized clinical trial did not differ between groups; both had small improvements in pain and substantial reductions in opioid dosage., Trial Registration: ClinicalTrials.gov Identifier: NCT03026790.

Background: Chronic pain is common among Veterans, and rural Veterans commonly struggle obtaining chronic pain care due to large travel distances to the nearest Veterans Affairs (VA) medical center. In 2019, the VA established the Community Care Network (CCN) to provide Veterans access to care in community-based settings, including chronic pain management., Objective: To explore the experiences of rural Veterans receiving chronic pain treatment in the VA CCN, including their perceptions about perceived barriers, facilitators, and benefits to accessing comprehensive chronic pain management., Design: Qualitative study using semi-structured interviews., Participants: Ten rural Veterans receiving chronic pain management in the VA CCN took part in a qualitative interview focused on their experiences accessing and utilizing the VA CCN., Approach: A descriptive qualitative approach was used. Major themes were identified through thematic content analysis., Key Results: Veterans described challenges navigating the approval process, finding approved CCN providers for pain management, and they perceived that communication between the VA and community providers was not seamless. Once enrolled in the CCN, however, Veterans valued the freedom to choose providers specializing in pain management within their local communities, timely access to appointments, and opportunities to explore a wider range of pain treatment options and alternative therapies, in addition to traditional medical interventions, all in their local community., Conclusions: As the CCN seeks to improve collaboration between VA and community providers, recognition of Veterans' experiences could serve to drive the development of network improvements. Findings reported here suggest that Veterans preferred obtaining care in the CCN once they could navigate administrative complexity to access it. Thus, efforts to streamline VA administrative requirements for initiating CCN care would better support Veterans in meeting their needs in this context., Competing Interests: Declarations:. Conflict of Interest:: The authors declare that they do not have a conflict of interest., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Competing Interests: The authors report no conflicts of interest.

Guidelines recommend strategies to optimize opioid medication safety, including frequent reassessment of the benefits and harms of long-term opioid therapy. Prescribers, who are predominantly primary care providers (PCPs), may lack the training or resources to implement these guideline-concordant practices. Two interventions have been designed to assist PCPs and tested within the Veterans Health Administration (VHA). Telemedicine Collaborative Management (TCM) provides primarily medication management support via care manager-prescriber teams. Cooperative Pain Education and Self-Management (COPES) promotes self-management strategies for chronic pain via cognitive behavior therapy techniques. Each intervention has been shown to improve prescribing and/or patient outcomes. The added value of combining these interventions is untested. With funding and central coordination by the Integrative Management of Chronic Pain and Opioid Use Disorder for Whole Recovery (IMPOWR) Network of the National Institutes of Health Helping to End Addiction Long-term (HEAL) Initiative, we will conduct a multisite patient-level randomized hybrid II effectiveness-implementation trial within VHA to compare TCM to TCM + COPES on the primary composite outcome of pain interference and opioid safety, secondary outcomes of alcohol use, anxiety, depression, and sleep, and other consensus IMPOWR Network measures. Implementation facilitation strategies informed by interviews with healthcare providers will target site-specific needs. The impact of these strategies on TCM implementation will be assessed via established formative and summative evaluation techniques. Economic analyses will evaluate intervention cost-effectiveness., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [I.B. has served as the plaintiff’s expert witness in a case involving radiofrequency radiation. All other authors declare no competing interests.].

Background: Chronic pain is among the most common conditions presenting to primary care and guideline-based care faces several challenges. A novel pain management program, Video-Telecare Collaborative Pain Management (VCPM), was established to support primary care providers and meet new challenges to care presented by the COVID-19 pandemic., Methods: The present single-arm feasibility study aimed to evaluate the feasibility and acceptability of VCPM and its components among U.S. veterans on long-term opioid therapy for chronic pain at ≥ 50 mg morphine equivalent daily dose (MEDD). VCPM consists of evidence-based interventions, including opioid reassessment and tapering, rotation to buprenorphine and monitoring, and encouraging behavioral pain and opioid-use disorder self-management., Results: Of the 133 patients outreached for VPCM, 44 completed an initial intake (33%) and 19 attended multiple VCPM appointments (14%). Patients were generally satisfied with VCPM, virtual modalities, and provider interactions. Nearly all patients who attended multiple appointments maintained a buprenorphine switch or tapered opioids (16/19; 84%), and buprenorphine switches were generally reported as acceptable by patients. Patients completing an initial intake with VCPM had reduced morphine equivalent daily dose after three months (means = 109 mg MEDD vs 78 mg), with greater reductions among those who attended multiple appointments compared to intake only (Δ MEDD  = -58.1 vs. -8.40). Finally, 29 referrals were placed for evidence-based non-pharmacologic interventions., Conclusion: Pre-defined feasibility and acceptability targets for VCPM and its components were broadly met, and preliminary data are encouraging. Novel strategies to improve enrollment and engagement and future directions are discussed., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objectives: Scotland has the lowest life expectancy in Western Europe and significant health inequalities. A national review of public health in 2015 found that there was a lack of coherent action across organisational boundaries, inhibiting progress. This paper describes a rapid (four-month) systematic approach to prioritisation of Scotland's public health challenges, which was evidence-based, transparent and made use of significant stakeholder engagement., Study Design: Cross-sectional survey of stakeholders in deliberative meetings., Methods: An independent Expert Advisory Group (EAG) was formed to develop a typology of public health priorities, a long-list of potential priorities and ranking criteria. Deliberative stakeholder events were held at which the criteria were refined and priorities scored by participants from a wide range of stakeholder organisations., Results: The proposed typology identified three types of public health priorities: risk factors, social factors and system factors; medically defined disease entities were not used deliberately, to facilitate broad stakeholder participation. Fifteen criteria were identified to help identify priority issues, based on the scope of their burden, amenability to change, and multi-stakeholder preferences. Six public health priorities were selected by the EAG based on stakeholder scoring of a long-list against these criteria., Conclusion: Prioritisation is important in modern public health but it is challenging due to limited data availability, lack of agreed evidence on effectiveness and efficiency of interventions, and divergent stakeholder views. The Scottish experience nevertheless shows that useful public health priorities can be agreed upon by a wide range of stakeholders through a transparent, participatory and logical process., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The ongoing obesity pandemic threatens the health of hundreds of millions globally. However, to date, no country has had much success in limiting its growth, let alone reversing it. This commentary demonstrates the relevance to the obesity pandemic of the public health conceptual framework of epidemiologist Geoffrey Rose, first published as "Sick Individuals and Sick Populations" in 1985. That framework provides a useful way to analyze the pandemic's prevention and control options, based on the notions of primordial, primary, secondary and tertiary prevention-the full spectrum of "more upstream and more downstream" approaches, each with its pros and cons. Based on an analysis of key studies to date, this commentary argues strongly that only the primordial prevention approach is likely to be successful against the obesity pandemic-but its onerous requirements for society-wide behavioural and cultural change may make that public health struggle a long one., (© 2022. The Author(s).)

This paper argues that the public health conceptual framework of epidemiologist Geoffrey Rose, first published as "Sick Individuals and Sick Populations" in 1985, provides a useful way to critically analyze prevention and control options for modern non-communicable diseases (NCD) and their forerunner, obesity, a pandemic now engulfing Lower-and-Middle-Income-Countries. That framework is based on the notions of primordial, primary, secondary and tertiary prevention-the full spectrum of "more upstream and more downstream" approaches, each with its pros and cons. These are illustrated using the pellagra epidemic in the southeastern USA from 1900 to the 1940s, which still has much to teach us about these same basic policy options for controlling the modern NCD pandemic. In particular, Rose's dictum, "Seek the causes of (population) incidence, not of (individual) cases", points up the compelling advantages of upstream prevention for controlling both epidemics.

Background: In the United States, an x-waiver credential is necessary to prescribe buprenorphine medication treatment for opioid use disorder (B-MOUD). Historically, this process has required certified training, which could be a barrier to obtaining an x-waiver and subsequently prescribing. To address this barrier, the US recently removed the training requirement for some clinicians. We sought to determine if clinicians who attended x-waiver training went on to obtain an x-waiver and prescribe B-MOUD, and to examine what facilitated or impeded B-MOUD prescribing., Methods: In September 2020, we conducted a cross-sectional, electronic survey of attendees of 15 in-person x-waiver pieces of training from June 2018 to January 2020 within the Veterans Health Administration (VHA). Of the attendees (n = 321), we surveyed current VHA clinicians who recalled taking the training. The survey assessed whether clinicians obtained the x-waiver, had prescribed B-MOUD, and barriers or facilitators that influenced B-MOUD prescribing., Results: Of 251 eligible participants, 62 (24.7%) responded to the survey, including 27 (43.5%) physicians, 16 (25.8%) advanced practice clinicians, and 12 (19.4%) pharmacists. Of the 43 clinicians who could prescribe, 29 (67.4%) had obtained their x-waiver and 16 (37.2%) had reported prescribing B-MOUD. Prominent barriers to prescribing B-MOUD included a lack of supporting clinical staff and competing demands on time. The primary facilitator to prescribing was leadership support., Conclusion and Scientific Significance: Nine months after x-waiver training, two-thirds of clinicians with prescribing credentials had obtained their x-waiver and one-third were prescribing B-MOUD. Removing the x-waiver training may not have the intended policy effect as other barriers to B-MOUD prescribing persist., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA.)

Objective: To estimate differences in average annual health care expenditures of adult women with chronic overlapping pain conditions (COPCs) by pain treatment modality as follows: (1) no long-term opioid or complementary and integrative health (CIH) use; (2) CIH only use; (3) long-term opioid only use; and (4) long-term opioid and CIH use., Data Source: Cross-sectional Medical Expenditure Panel Survey data (2012-2016)., Study Design: We estimated differences between average annual expenditures of adult women with COPCs by their use of long-term opioids and CIH modalities. Generalized linear regression with a log link function was used to estimate adjusted marginal effects in annual expenditures. The distribution family was chosen based on Modified Park Tests. We controlled for pain severity, patient demographic characteristics, physical limitations, comorbidities, mental health, insurance status, physical therapy use, and census region. We also employed propensity-score based marginal mean weighting through stratification to balance our treatment groups on observed covariates., Data Collection/extraction Methods: We identified adult women (>17 years) with one or more self-reported COPC using 3-digit International Classification of Diseases (ICD)-9/10-Clinical Modification (CM) codes (N = 9169) and categorized their use of CIH and long-term opioids., Principal Findings: Compared to women without long-term opioid or CIH use, CIH only use was significantly associated with lower inpatient expenditures (-$947 [-$1699, -$196]; p-value < 0.01), higher office-based expenditures ($1345 [$944, $1746]; p-value < 0.001), and higher patient out-of-pocket expenditures ($628 [$409, $848]; p-value < 0.001). Long-term opioid use, alone or in combination with CIH, was significantly associated with higher expenditures (p-value < 0.05) in total and across all utilization categories compared to women without any long-term opioid or CIH use., Conclusions: Our results indicate that CIH treatment approaches for chronic pain have the potential to be utilized without increasing overall costs. Future research should further examine the role of CIH modalities in achieving cost-effective pain management that reduces avoidable opioid use., (© 2021 Health Research and Educational Trust.)

Objectives: To develop a critical appraisal tool for non-computational-specialist public health professionals to assess the quality and relevance of modelling studies about Test and Trace (and Protect - TTP) programmes' impact on COVID-19 transmission., Study Design: Decision-making tool development., Methods: Using Tugwell et al.'s 1985 Health Care Effectiveness equation as a conceptual framework, combined with a purposive search of the relevant early modeling literature, we developed six critical appraisal questions for the rapid assessment of modeling studies related to the evaluation of TTP programmes' effectiveness., Results: By applying the critical appraisal tool to selected recent COVID-19 modeling studies, we demonstrate how models can be evaluated using the six questions to evaluate internal and external validity and relevance., Conclusions: These six critical appraisal questions are able to discriminate between modeling studies of higher and lower quality and relevance to evaluating TTP programmes' impact. However, these questions require independent validation in a larger and systematic sample of relevant modeling studies which have appeared in later stages of the pandemic., (Copyright © 2021 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Objective: Chronic pain is more common among veterans than among the general population. Expert guidelines recommend multimodal chronic pain care. However, there is substantial variation in the availability and utilization of treatment modalities in the Veterans Health Administration. We explored health care providers' and administrators' perspectives on the barriers to and facilitators of multimodal chronic pain care in the Veterans Health Administration to understand variation in the use of multimodal pain treatment modalities., Methods: We conducted semi-structured qualitative interviews with health care providers and administrators at a national sample of Veterans Health Administration facilities that were classified as either early or late adopters of multimodal chronic pain care according to their utilization of nine pain-related treatments. Interviews were conducted by telephone, recorded, and transcribed verbatim. Transcripts were coded and analyzed through the use of team-based inductive and deductive content analysis., Results: We interviewed 49 participants from 25 facilities from April through September of 2017. We identified three themes. First, the Veterans Health Administration's integrated health care system is both an asset and a challenge for multimodal chronic pain care. Second, participants discussed a temporal shift from managing chronic pain with opioids to multimodal treatment. Third, primary care teams face competing pressures from expert guidelines, facility leadership, and patients. Early- and late-adopting sites differed in perceived resource availability., Conclusions: Health care providers often perceive inadequate support and resources to provide multimodal chronic pain management. Efforts to improve chronic pain management should address both organizational and patient-level challenges, including primary care provider panel sizes, accessibility of training for primary care teams, leadership support for multimodal pain care, and availability of multidisciplinary pain management resources., (The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)

During the peri-implantation period of pregnancy in sheep, there is an initial period of loose apposition of the elongating conceptuses (embryos and associated placental membranes) to the endometrial luminal epithelium (LE) that is followed by adhesion of the conceptus trophectoderm to the endometrial LE for implantation. Integrins and maternal extracellular matrix (ECM) molecules are major contributors to stable adhesion at implantation, and the β3 integrin subunit (ITGB3) is implicated in the adhesion cascade for implantation in several species including the sheep. We blocked mRNA translation for trophectoderm-expressed ITGB3 by infusing morpholino antisense oligonucleotides into the uterine lumen of pregnant ewes on Day 9 to assess effects on conceptus elongation, and on Day 16 to assess effects on early placental development in sheep. Results indicate that sheep conceptuses elongate and implant to the uterine wall in the absence of ITGB3 expression by the conceptuses; however, loss of ITGB3 in conceptuses decreased the growth of embryos to Day 24 of gestation, and decreased expression of secreted phosphoprotein 1 (SPP1) and nitric oxide synthase 3 (NOS3). Abundant SPP1 was localized around the blood vessels in the placental allantoic membrane in normal sheep pregnancies. We hypothesize that NOS3 and SPP1 positively influence the development of the vasculature within the allantois, and that decreased expression of NOS3 and SPP1, in response to knockdown of ITGB3 in conceptuses, alters development of the vasculature in the allantois required to transport nutrients from the endometrium to support growth and development of the embryo., (© The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

New fifth generation (5G) telecommunications systems, now being rolled out globally, have become the subject of a fierce controversy. Some health protection agencies and their scientific advisory committees have concluded that there is no conclusive scientific evidence of harm. Several recent reviews by independent scientists, however, suggest that there is significant uncertainty on this question, with rapidly emerging evidence of potentially harmful biological effects from radio frequency electromagnetic field (RF-EMF) exposures, at the levels 5G roll-out will entail. This essay identifies four relevant sources of scientific uncertainty and concern: (1) lack of clarity about precisely what technology is included in 5G; (2) a rapidly accumulating body of laboratory studies documenting disruptive in vitro and in vivo effects of RF-EMFs-but one with many gaps in it; (3) an almost total lack (as yet) of high-quality epidemiological studies of adverse human health effects from 5G EMF exposure specifically, but rapidly emerging epidemiological evidence of such effects from past generations of RF-EMF exposure; (4) persistent allegations that some national telecommunications regulatory authorities do not base their RF-EMF safety policies on the latest science, related to unmanaged conflicts of interest. The author, an experienced epidemiologist, concludes that one cannot dismiss the growing health concerns about RF-EMFs, especially in an era when higher population levels of exposure are occurring widely, due to the spatially dense transmitters which 5G systems require. Based on the precautionary principle, the author echoes the calls of others for a moratorium on the further roll-out of 5G systems globally, pending more conclusive research on their safety., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The NIH-DOD-VA Pain Management Collaboratory (PMC) supports 11 pragmatic clinical trials (PCTs) on nonpharmacological approaches to management of pain and co-occurring conditions in U.S. military and veteran health organizations. The Stakeholder Engagement Work Group is supported by a separately funded Coordinating Center and was formed with the goal of developing respectful and productive partnerships that will maximize the ability to generate trustworthy, internally valid findings directly relevant to veterans and military service members with pain, front-line primary care clinicians and health care teams, and health system leaders. The Stakeholder Engagement Work Group provides a forum to promote success of the PCTs in which principal investigators and/or their designees discuss various stakeholder engagement strategies, address challenges, and share experiences. Herein, we communicate features of meaningful stakeholder engagement in the design and implementation of pain management pragmatic trials, across the PMC., Design: Our collective experiences suggest that an optimal stakeholder-engaged research project involves understanding the following: i) Who are research stakeholders in PMC trials? ii) How do investigators ensure that stakeholders represent the interests of a study's target treatment population, including individuals from underrepresented groups?, and iii) How can sustained stakeholder relationships help overcome implementation challenges over the course of a PCT?, Summary: Our experiences outline the role of stakeholders in pain research and may inform future pragmatic trial researchers regarding methods to engage stakeholders effectively., (The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. This work is written by US Government employees and is in the public domain in the US.)

Background: The Whole Health model of the U.S. Department of Veterans Affairs (VA) emphasizes holistic self-care and multimodal approaches to improve pain, functioning, and quality of life. wHOPE (Whole Health Options and Pain Education) seeks to be the first multisite pragmatic trial to establish evidence for the VA Whole Health model for chronic pain care., Design: wHOPE is a pragmatic randomized controlled trial comparing a Whole Health Team (WHT) approach to Primary Care Group Education (PC-GE); both will be compared to Usual VA Primary Care (UPC). The WHT consists of a medical provider, a complementary and integrative health (CIH) provider, and a Whole Health coach, who collaborate with VA patients to create a Personalized Health Plan emphasizing CIH approaches to chronic pain management. The active comparator, PC-GE, is adapted group cognitive behavioral therapy for chronic pain. The first aim is to test whether the WHT approach is superior to PC-GE and whether both are superior to UPC in decreasing pain interference in functioning in 750 veterans with moderate to severe chronic pain (primary outcome). Secondary outcomes include changes in pain severity, quality of life, mental health symptoms, and use of nonpharmacological and pharmacological therapies for pain. Outcomes will be collected from the VA electronic health record and patient-reported data over 12 months of follow-up. Aim 2 consists of an implementation-focused process evaluation and budget impact analysis., Summary: This trial is part of the Pain Management Collaboratory, which seeks to create national-level infrastructure to support evidence-based nonpharmacological pain management approaches for veterans and military service personnel., (Published by Oxford University Press on behalf of the American Academy of Pain Medicine. This work is written by a US Government employee and is in the public domain in the US.)

Background: There is inadequate evidence of long-term benefit from opioid medications for chronic pain and substantial evidence of potential harms. For patients, dose reduction may be beneficial when implemented voluntarily and supported by a multidisciplinary team but experts have advised against involuntary opioid reduction., Objectives: To assess the prevalence of self-reported involuntary opioid reduction and to examine whether involuntary opioid reduction is associated with changes in pain severity., Design: Prospective observational cohort study., Participants: Primary care patients treated with long-term opioid therapy in the Veterans Health Administration (N = 290)., Main Measures: The primary exposure was self-reported past year involuntary opioid reduction. The primary outcome was the three-item PEG scale, which measures past-week average pain intensity and interference with enjoyment of life and general activity., Key Results: Past year opioid reduction or discontinuation was reported by 63% (184/290). Similar numbers reported involuntary (88/290) and voluntary (96/290) opioid reduction. At baseline, there were no significant differences in pain severity between the groups (mean PEG, 7.08 vs. 6.73 vs. 7.07 for past year involuntary opioid reduction, past year voluntary opioid reduction, and no past year opioid reduction, respectively; P = 0.32). For the primary outcome of change in pain severity from baseline to 18 months, there were no significant differences between groups (mean PEG change, - 0.05 vs. - 0.44 vs. - 0.23 for past year involuntary opioid reduction, past year voluntary opioid reduction, and no past year opioid reduction, respectively; P = 0.28)., Conclusions: Self-reported past year involuntary opioid reduction was common among a national sample of veterans treated with long-term opioid therapy. Opioid dose reduction, whether involuntary or voluntary, was not associated with change in pain severity. Future studies should examine involuntary opioid reduction in different populations and trends over time and explore further patient- and provider-level factors that may impact patient experience and outcomes during opioid reduction.

Integrins and OPN are potential mediators of blastocyst attachment to the endometrium to initiate implantation. The goals were to examine the temporal/spatial pattern of expression of integrins at the endometrial-placental interface of sheep encompassing Days 9 through 80 of gestation and determine if OPN co-localizes with integrins. Results show the following: (1) αv, α4, β1, β3 and β5 integrins at the apical surface of endometrial luminal epithelium (LE) from Days 11 through 16 of pregnancy that indicate a role for these integrins during implantation; (2) large, intermittent aggregates of αv, α4, α5, β1 and β5 integrins at the endometrial-placental interface from Days 20 through 55, suggesting adaptation to a localized tissue remodeling stage of placentation; and (3) integrin adhesion complexes (IACs) containing αv, α4, α5, β1 and β5 integrins precisely distribute at the apical surfaces of apposed endometrial LE and chorion along expanses of the interplacentomal endometrial-placental interface between Days 60 and 80 of gestation, suggesting engagement of these integrins with the ECM to stabilize adhesion between endometrial LE and chorion in response to the increasing mechanical stress on this interface by the increasing size of the fetus and volumes of fetal fluids. An advancement is the clear co-localization of OPN and integrins at the endometrial-placental interface throughout gestation in sheep. The comprehensive nature of these results provide evidence that integrins potentially interact with OPN to play key roles in the mechanisms required for implantation and placentation throughout pregnancy in sheep and have implications concerning implantation and placentation in other species.