Pain Care at Home to Amplify Function: Protocol Article.

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.

Ultrasound Pressure-Dependent Cytokine and Immune Cell Response Lost in Aged Muscle.

OBJECTIVE: Therapeutic ultrasound remains a highly discussed topic in physical therapy due to uncertainty between treatment regimens and biological benefits. Its impact on aged populations, who are vulnerable to insufficient healing after muscle injury because of sarcopenia, is understudied. Despite the coupling between muscle inflammation and regeneration, research on the immune response after therapeutic ultrasound is limited. The objective of this study was to evaluate structure, inflammatory cytokine signaling and immune cell infiltration after therapeutic ultrasound in young and aging murine muscle. METHODS: Young (6-week-old) and Adult (52-week-old) male and female mouse non-injured gastrocnemii were treated with either low-intensity pulsed ultrasound at 2 W/cm2 (∼0.243 MPa) or high-intensity pulsed focused ultrasound at 554 W/cm2 (∼5.96 MPa). Cytokine expression was evaluated at 1, 8 and 24 hours, cell infiltration was measured via flow cytometry at 1 and 24 hours and immunofluorescence assessed muscle fiber area, fibrosis and satellite cells at 24 hours after sonication. RESULTS: Low-intensity pulsed ultrasound induced an early, transient inflammatory response where interleukin (IL)-15 and macrophages (M2 > M1) were increased 1 hour post-sonication. High-intensity pulsed focused ultrasound caused a late, extended immune response where monocyte chemoattractant protein 1 (MCP-1), neutrophils, monocytes and macrophages (M1 > M2) were increased 24 hours post-sonication. Notably, these changes manifested solely in Young gastrocnemius. The Adult gastrocnemius exhibited decreased cytokine expression (IL-1α, IL-6, IL-15, macrophage colony-stimulating factor [M-CSF]) and no alteration in immune cell recruitment post-sonication. There was no damage to muscle structure. CONCLUSION: Therapeutic ultrasound induced a pressure-dependent inflammatory response that can augment or mitigate intrinsic muscle cytokine signaling and cell recruitment in adolescent or aged muscle, respectively.

Oncogenic Oral Human Papillomavirus Clearance Patterns over 10 Years.

BACKGROUND: Effective screening for oropharyngeal cancer is lacking. Four oncogenic HPV clearance definitions were explored to understand long-term natural history for persistent oncogenic oral HPV (oncHPV), the precursor of oropharyngeal cancer. METHODS: Prospective multicenter cohort of participants living with/at-risk for HIV, with oral rinse and gargle samples collected every 6 to 12 months for up to 10 years and tested for oncHPV. HPV clearance definitions included 1 (clear1), 2 (clear2), 3 (clear3) consecutive negatives, or being negative at last two visits (clearlast). RESULTS: Median time to clearance of oncHPV exceeded 2 years for conservative definitions (clear3: 2.38, clearlast: 2.43), but not lenient (clear1: 0.68, clear2: 1.15). By clear3, most incident infections cleared at 2, 5, 8 years (55.1%, 75.6%, 79.1%), contrary to prevalent infections (37.1%, 52.5%, 59.5%, respectively). In adjusted analysis, prevalent oncHPV, older age, male sex, and living with HIV were associated with reduced clearance. Of 1,833 subjects screened, 13.8% had prevalent oncHPV and 47.5% of those infections persisted ≥5 years, representing 6.5% of persons screened. Two men with prevalent oral HPV16 developed incident oropharyngeal cancer [IR = 1.62 per 100 person-years; 95% confidence interval (CI), 0.41-6.4]. Many with oral HPV16 persisted ≥5 years (and/or developed HPV-oropharyngeal cancer) among those with 2 (72.2%), ≥2 of first 3 (65.7%), or 3 (80.0%) consecutive positive oHPV16 tests, but not after 1 (39.4%). CONCLUSIONS: In our 10-year study, most incident infections cleared quickly. However, half of prevalent oncHPV persisted ≥5 years, suggesting increased risk with persistent oncHPV at >2 visits. IMPACT: We identified groups with persistent oncHPV at increased risk of oropharyngeal cancer and contextualized risk levels for those with oral HPV16 infection.

Video-telecare collaborative pain management during COVID-19: a single-arm feasibility study.

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 (ΔMEDD = -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.

Ending the pandemic of inaccessibility in dermatology.

Dermatology in the United States is among the global leaders in advancing scientific discovery and practicing evidence-based medicine; however, many patients face limited access to dermatologic care due to a national shortage of dermatologists, provider clustering, and the interplay of sociodemographic and socioeconomic factors. These intertwined barriers have created a landscape where race, ethnicity, insurance subtype, education, and socioeconomic status negatively impact access to dermatologic services. Leveraging the utilization of technology and community engagement provides inroads to improve access to care. We outline how teleconsultations, telementoring, specialty care extension for community health outcomes (Project ECHO), community health centers, donated specialty care models, and community health workers can be bolstered to create more equitable access to care.

Outcomes after fixation of rib fractures sustained during cardiopulmonary resuscitation: A retrospective single center analysis.

Background: Historically rib fractures have been typically treated non-operatively. Recent studies showed promising results after osteosynthesis of rib fractures in trauma patients with flail segments or multiple rib fractures. However, there is a paucity of data on rib fixation after cardiopulmonary resuscitation (CPR). This study evaluated the outcomes of patients who received rib fixation after CPR. Methods: Adult patients who received surgical fixation of rib fractures sustained during CPR between 2010 and 2020 were eligible for inclusion in this retrospective study. Outcome measures included complications, quality of life (EQ 5D 5L) and level of dyspnea. Results: Nineteen patients were included with a mean age of 66.8 years. The mean number of fractured ribs was ten, seven patients additionally had a sternum fracture. Pneumonia occurred in 15 patients (74%), of which 13 were diagnosed preoperatively and 2 post-operatively. Six patients developed a postoperative pneumothorax, none of which required revision surgery. One patient showed persistent flail chest after rib fixation and required additional fixation of a concomitant sternum fracture. One infection of the surgical site of sternal plate occurred, while no further surgery related complications were reported. Mean EQ-5D-5L was 0.908 and the average EQ VAS was 80. One patient reported persisting dyspnea. Conclusion: To date, this is the largest reported cohort of patients who received rib fixation for fractures sustained during CPR. No complications associated with rib fixation were reported whereas one infection after sternal fixation did occur. Current follow-up demonstrated a good long-term quality of life after fixation, warranting further studies on this topic. Deeper knowledge on this subject would be beneficial for a wide spectrum of physicians.

Treatment and outcome in combined scapula and rib fractures: a retrospective study.

PURPOSE: The primary aim was to describe the population characteristics of patients with combined scapula and rib fractures and outcomes associated with different treatment strategies. METHODS: All adult (≥ 18 years) patients with concurrent ipsilateral scapula and rib fractures admitted to the study hospital between 1st January 2010 and 31st June 2021 were retrospectively reviewed. RESULTS: A total of 223 patients were admitted with concurrent ipsilateral rib and scapula fractures. A total of 160 patients (72%) were treated conservatively, 63 patients (28%) operatively. Among operatively treated patients, 32 (51%) underwent rib fixation (RF) only, 24 (38%) underwent scapula fixation (SF) only, and seven patients (11%) underwent combined fixation of scapula and ribs (SRF). In general, more severely injured patients were treated with more extensive surgery. RF patients had a median hospital length of stay of 16 days, the SF patients 11 days and SRF patients 18 days. There were no significant differences in complications (pneumonia, recurrent pneumothorax and revision surgery) between groups. CONCLUSION: Injury severity resulted in different treatment modalities. As a result, different patient characteristics between treatment groups were observed, which makes direct comparison between treatment modalities impossible. All treatment modalities seem feasible; however, the additional value of both rib and scapula fixation has yet to be proven in large multicentre studies.

Mesenchymal Stromal Cell Delivery Via Cardiopulmonary Bypass Provides Neuroprotection in a Juvenile Porcine Model.

Oxidative/inflammatory stresses due to cardiopulmonary bypass (CPB) cause prolonged microglia activation and cortical dysmaturation, thereby contributing to neurodevelopmental impairments in children with congenital heart disease (CHD). This study found that delivery of mesenchymal stromal cells (MSCs) via CPB minimizes microglial activation and neuronal apoptosis, with subsequent improvement of cortical dysmaturation and behavioral alteration after neonatal cardiac surgery. Furthermore, transcriptomic analyses suggest that exosome-derived miRNAs may be the key drivers of suppressed apoptosis and STAT3-mediated microglial activation. Our findings demonstrate that MSC treatment during cardiac surgery has significant translational potential for improving cortical dysmaturation and neurological impairment in children with CHD.

Statins Utilization in Adults With HIV: The Treatment Gap and Predictors of Statin Initiation.

BACKGROUND: We characterized trends in statin eligibility and subsequent statin initiation among people with HIV (PWH) from 2001 to 2017 and identified predictors of statin initiation between 2014 and 2017. SETTING: PWH participating in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) enrolled in 12 US cohorts collecting data on statin eligibility criteria/prescriptions from 2001 to 2017. METHODS: We determined the annual proportion eligible for statins, initiating statins, and median waiting time (from statin eligibility to initiation). Eligibility was defined using ATP III guidelines (2001-2013) and ACC/AHA guidelines (2014-2017). We assessed initiation predictors in 2014-2017 among statin-eligible PWH using Poisson regression, estimating adjusted prevalence ratios (aPRs) with 95% confidence intervals (95% CIs). RESULTS: Among 16,409 PWH, 7386 (45%) met statin eligibility criteria per guidelines (2001-2017). From 2001 to 2013, statin eligibility ranged from 22% to 25%. Initiation increased from 13% to 45%. In 2014, 51% were statin-eligible, among whom 25% initiated statins, which increased to 32% by 2017. Median waiting time to initiation among those we observed declined over time. Per 10-year increase in age, initiation increased 46% (aPR 1.46, 95% CI: 1.29 to 1.67). Per 1-year increase in calendar year from 2014 to 2017, there was a 41% increase in the likelihood of statin initiation (aPR 1.41, 95% CI: 1.25 to 1.58). CONCLUSIONS: There is a substantial statin treatment gap, amplified by the 2013 ACC/AHA guidelines. Measures are warranted to clarify reasons we observe this gap, and if necessary, increase statin use consistent with guidelines including efforts to help providers identify appropriate candidates.

Neuroinflammation associated with ultrasound-mediated permeabilization of the blood-brain barrier.

The blood-brain barrier (BBB) continues to represent one of the most significant challenges for successful drug-based treatments of neurological disease. Mechanical modulation of the BBB using focused ultrasound (FUS) and microbubbles (MBs) has shown considerable promise in enhancing the delivery of therapeutics to the brain, but questions remain regarding possible long-term effects of such forced disruption. This review examines the evidence for inflammation associated with ultrasound-induced BBB disruption and potential strategies for managing such inflammatory effects to improve both the efficacy and safety of therapeutic ultrasound in neurological applications.

Low profile dual plating for mid-shaft clavicle fractures: a meta-analysis and systematic review of observational studies.

INTRODUCTION: Low profile dual plate fixation using two mini fragment plates (< 2.7 mm thickness) is a relatively new technique and alternative to single plating for treating midshaft clavicle fractures. To date, no meta-analysis has been performed comparing these two techniques. Therefore, a systematic review and meta-analysis of observational studies and randomized clinical trials was performed comparing single plating to low profile dual plating for midshaft clavicle fractures. METHODS: PubMed/Medline/Embase/CENTRAL/CINAHL were searched for both randomized clinical trials (RCT) and observational studies comparing both treatments. Effect estimates were pooled across studies using random effects models. The primary outcome is overall complication rate and re-intervention rate. Secondary outcomes include healing, operation duration and functional scores. RESULTS: Low profile dual plating has favourable outcomes regarding overall complication rate (8.1% vs. 22.5%, OR 0.3, 95% CI 0.2-0.7, I2 = 16%, p = 0.007) and re-intervention rate (6.1% vs. 16.1%, OR 0.3, 95% CI 0.1-0.9, I2 = 25%, p = 0.02). The largest contributing factor behind these differences was the high incidence of implant related complaints in the single plating group (4.7% vs. 11.6%, OR 0.4, 95% CI 0.2-0.9, I2 = 0%, p = 0.02). The use of low profile dual plating does not have a detrimental effect on healing with union being attained in 99% compared to 97.4% in the single plating group (OR 1.8, 95% CI 0.3-10.7, I = 0%, p = 0.5). Data on operating time and functional results is limited. CONCLUSION: This meta-analysis shows that dual plating low profile plates for midshaft clavicle fractures is a safe procedure attaining the same union rates seen in patients treated with single plating. In addition, it seems to have a lower overall complication and re-intervention rate, mostly driven by the lower incidence of implant related complaints. Low profile dual plating, however, is a fairly new technique and should be further explored in respect to more differentiated endpoints to test whether these first findings are valid. LEVEL OF EVIDENCE: III.

The Ottawa 3DY Predicts Mortality in a Prospective Cohort Study.

Background: The Ottawa 3DY (O3DY) is a simple measure of cognition. Objectives: 1) To determine if the O3DY predicts mortality; and 2) To compare the discrimination of the O3DY to the Mini-Mental State Examination (MMSE) and Modified MMSE (3MS). Methods: Analyses of a population based cohort study of 1,751 participants aged 65+; conducted in 1991/2 with follow-up over five years. The O3DY, age, sex, education, comorbid conditions, the MMSE, and the 3MS were measured: 4.5% of the participants had missing data for the O3DY; 42.8% were considered as positive (one or more errors), and 52.7% were considered as negative (no errors). Logistic regression models were constructed with the outcome of death at time 2. A Receiver Operator Curve (ROC) was constructed and the Area Under the ROC (AUROC) was calculated using a c-statistic. Results: The unadjusted odds ratio (OR) and 95% confidence interval (CI) for mortality was 1.96 (1.56, 2.47); and the adjusted OR was 1.33 (1.02, 1.72). The AUROC was 0.66 for the 3MS, 0.65 for the MMSE, and 0.60 for the O3DY. Conclusions: The O3DY predicts mortality over a long time frame, although the discrimination is less than that of longer measures of cognition.

Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach.

BACKGROUND: Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment. AIMS: To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder. METHOD: This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework. RESULTS: The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data. CONCLUSIONS: Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.

The value of fibular fixation in patients with stabilized distal tibia fractures.

PURPOSE: There is currently no consensus regarding the need for fixation of concomitant fibula fractures in patients with surgically treated distal tibia fracture. Although studies have shown it to be beneficial for fractures involving the syndesmosis, it remains unclear for suprasyndesmotic fractures. This study evaluates what effect the fixation of such suprasyndesmotic fibula fractures had on patients who underwent fixation of distal tibia fractures. METHODS: This retrospective cohort study included all consecutive adult patients who received surgical treatment for an extra-articular or simple intraarticular distal tibia fracture between 2012 and 2020 and had a concomitant fibula fracture proximal to the syndesmosis. Two groups were formed depending on whether the fibula was stabilized. The need for revision surgery, the occurrence of complications, fracture healing, rotational and angular malalignment were evaluated for both groups. RESULTS: This study included 120 patients, of which 40 (33.3%) had operative treatment of the fibula fracture. Of those with stabilized fibula fractures, 28 (70%) were treated with a plate and 12 (30%) with a titanium elastic nail. The group of patients with surgically treated fibula fractures had significantly more angular malalignments (10% vs 1.2%, p = 0.042), while there was no difference regarding rotational malalignment or fracture healing. Further, infections of the fibular surgical site occurred in 15% of surgically treated patients leading to significantly more revision surgeries in this group (40% vs 20%, p = 0.03). All infections occurred when a plate was used. CONCLUSION: This study was unable to show any benefit from stabilizing concomitant, suprasyndesmotic fibula fractures in surgically treated distal tibia fractures. On the contrary, infection, revision surgery and angular malalignment were more frequent when the fibula was fixed. Therefore, such concomitant fibula fractures should not routinely be fixed and if stabilization is deemed necessary, the implant should be chosen carefully.

Are x-waiver trainings enough? Facilitators and barriers to buprenorphine prescribing after x-waiver trainings.

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.

Erratum: Focused ultrasound activates voltage-gated calcium channels through depolarizing TRPC1 sodium currents in kidney and skeletal muscle.

[This corrects the article DOI: 10.7150/thno.33876.].

Improving the protocol for whole-body CT scans in trauma patients.

PURPOSE: While whole-body computed tomography is an established diagnostic method for the work up of polytraumatized patients, the protocols used differ between trauma centers. This study aimed to compare scan duration and estimated radiation of two protocols. Secondary aim was to assess if using the revised CT protocol reduced the number of additional images of the upper extremities. METHODS: Two groups of consecutive trauma patients, which both received a whole-body CT, were analyzed. Patients, who received a three-phased CT during which their arms needed to be repositioned from their side to above the head, were assigned to group A. Those, who received a CT with their arms placed on a pillow ventral to the abdomen throughout the entire scan were assigned to group B. Estimated radiation dose, scan duration, number of upper limb injuries and number of additional images of the upper limbs within 24 h after initial CT were assessed. RESULTS: Group A consisted of 182 patients, group B of 218. The scan duration was 3 min shorter (p < 0.001) and the estimated radiation dose lower (15.0 vs 22.9 mSv, p < 0.001) in group B. There was no difference in the number of upper limb injuries detected or the number of upper limb additional images required within 24 h. CONCLUSION: Using a whole-body CT scan protocol in which the arms remain on a pillow ventral to the torso instead of one which requires a repositioning of the arms, both scan duration and estimated radiation dose can be reduced. Despite the arms being within the scanned area in the revised protocol, the number of additional imaging of the upper extremities could not be reduced.