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The COVID-19 pandemic has created increased need for telehealth appointments. To assess differences in appointment adherence for telehealth compared to in-person HIV medical care visits, we conducted a cross-sectional study of patients receiving HIV care in a safety-net hospital-based outpatient infectious disease clinic in a large urban area (Chicago, IL). The sample (N = 347) was predominantly Black (n = 251) and male (62.5%, n = 217); with a mean age of 44.2 years. Appointment attendance was higher for telehealth (78.9%) compared to in-person (61.9%) appointments. Compared to patients without drug use, those with drug use had 19.4 percentage point lower in-person appointment attendance. Compared to those with stable housing, those in unstable housing arrangements had 15.0 percentage point lower in-person appointment attendance. Telehealth as a modality will likely have some staying power as it offers patients newfound flexibility, but barriers to telehealth need to be assessed and addressed.

BACKGROUND: The ultrasound-guided retroclavicular block (RCB) is a recently described alternative approach to brachial plexus blockade at the level of the cords. Although more distal blockade of the brachial plexus is thought to be associated with a lower incidence of phrenic nerve block, the impact of RCB on ipsilateral diaphragmatic function has not been formally investigated. OBJECTIVE: To compare the effects of supraclavicular and retroclavicular brachial plexus block on diaphragmatic function. SETTING: A single tertiary hospital, study period from December 2017 to May 2019. DESIGN: Double-blinded, randomised study. PATIENTS: A total of 40 patients undergoing upper extremity surgery below the axilla. Exclusion criteria included significant pulmonary disease, BMI more than 40 and contraindication to peripheral nerve block. INTERVENTIONS: Patients were randomised to supraclavicular or retroclavicular brachial plexus block with ropivacaine 0.5%. OUTCOME MEASURES: Phrenic block was assessed by measuring changes in diaphragmatic excursion using M-mode ultrasound, and maximum inspiratory volume on incentive spirometry from baseline, at 15 and 30 min postblock, and postoperatively. Comparative assessment of block characteristics included timing and distribution of sensory and motor block onset in the upper extremity, and scanning and block performance times. RESULTS: The incidence of phrenic block in the supraclavicular group was higher by ultrasound imaging (70 vs. 15%) and also by pulmonary function testing (55 vs. 5%), with both diaphragmatic excursion and maximum inspiratory volume decreasing to a greater extent after supraclavicular block (SCB) compared with RCB at 15, 30 min and postoperative time points (repeated measures analysis of variance, P < 0.001). There was no difference in timing and extent of distal arm block, but suprascapular and axillary nerves were more consistently blocked after SCB than after RCB. CONCLUSION: The current study confirms the hypothesis that a RCB is significantly less likely to affect ipsilateral diaphragmatic function than a SCB. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02631122

Objective. Music has been shown to modulate pain, although the impact of music on specific aspects of nociceptive processing is less well understood. Using quantitative sensory testing (QST), we assessed the impact of a novel music app on specific aspects of nociceptive processing. Design. Within-subjects paired comparison of pain processing in control vs music condition. Setting. Human psychophysical laboratory. Subjects. Sixty healthy adult volunteers. Methods. Subjects were assessed for baseline anxiety, depression, and catastrophizing using validated questionnaires. QSTs measured included 1) pain threshold and tolerance to deep muscle pressure, 2) pain with mechanical pinprick, 3) temporal summation of pain (TSP) with a repeated pain stimulus, and 4) conditioned pain modulation (CPM) with a second painful stimulus. QSTs were performed in the absence and presence of music delivered through a music app. Results. We found an increase in pressure pain thresholds in both the forearm (P = 0.007) and trapezius (P = 0.002) with music, as well as a decrease in the amount of pinprick pain (P

Background Persistent post-mastectomy pain (PPMP) varies both in its severity and impact, with psychosocial factors such as catastrophizing conferring greater risk. Preoperative regional anesthesia (RA) is an important nonopioid therapy, but with variable success at preventing PPMP in previous reports. We previously reported that RA was associated with lower acute post-mastectomy pain and opioid use, but more prominently among patients with higher baseline catastrophizing. The current longitudinal investigation at 3, 6, and 12 months postop aimed to detect differential long-term impact of RA on PPMP among patients with high vs low catastrophizing. Methods In this prospective observational study, patients (n = 123) completed preoperative psychosocial assessment and underwent mastectomy either with (n = 56) or without (n = 67) preoperative RA. Generalized estimating equation (GEE) regression analysis assessed impact of baseline catastrophizing, RA, and their interaction, on the primary outcome of pain severity index, as well as secondary outcomes including cognitive and emotional impact of pain, and persistent opioid use. Results We observed a significant interaction between the effect of catastrophizing and RA on PPMP. Specifically, RA was associated with reduced pain severity and pain impact 3, 6, and 12 months postoperatively, but only among those with high baseline catastrophizing scores. In addition, both RA and lower catastrophizing scores were associated with lower incidence of persistent opioid use. Conclusions The efficacy of therapies to prevent PPMP may be importantly influenced by pain-modulatory psychosocial characteristics. These findings underscore the importance of considering individual patient factors when applying preventive treatments, and of including their assessment in future trials.

BACKGROUND. Persistent post-mastectomy pain (PPMP) is a significant negative outcome occurring after breast surgery, and understanding which individual women are most at risk is essential to targeting of preventive efforts. The biopsychosocial model of pain suggests that factors from many domains may importantly modulate pain processing and predict the progression to pain persistence. METHODS. This prospective longitudinal observational cohort study used detailed and comprehensive psychosocial and psychophysical assessment to characterize individual pain-processing phenotypes in 259 women preoperatively. Pain severity and functional impact then were longitudinally assessed using both validated surgery-specific and general pain questionnaires to survey patients who underwent lumpectomy, mastectomy, or mastectomy with reconstruction in the first postsurgical year. An agnostic, multivariable modeling strategy identified consistent predictors of several pain outcomes at 12 months. RESULTS. The preoperative characteristics most consistently associated with PPMP outcomes were preexisting surgical area pain, less education, increased somatization, and baseline sleep disturbance, with axillary dissection emerging as the only consistent surgical variable to predict worse pain. Greater pain catastrophizing, negative affect, younger age, higher body mass index (BMI), and chemotherapy also were independently predictive of pain impact, but not severity. Sensory disturbance in the surgical area was predicted by a slightly different subset of factors, including higher preoperative temporal summation of pain. CONCLUSIONS. This comprehensive approach assessing consistent predictors of pain severity, functional impact, and sensory disturbance may inform personalized prevention of PPMP and also may allow stratification and enrichment in future preventive studies of women at higher risk of this outcome, including pharmacologic and behavioral interventions and regional anesthesia.

Placebo effects have traditionally involved concealment or deception. However, recent evidence suggests that placebo effects can also be elicited when prescribed transparently as "open-label placebos" (OLPs), and that the pairing of an unconditioned stimulus (eg, opioid analgesic) with a conditioned stimulus (eg, placebo pill) can lead to the conditioned stimulus alone reducing pain. In this randomized control trial, we investigated whether combining conditioning with an OLP (COLP) in the immediate postoperative period could reduce daily opioid use and postsurgical pain among patients recovering from spine surgery. Patients were randomized to COLP or treatment as usual, with both groups receiving unrestricted access to a typical opioid-based postoperative analgesic regimen. The generalized estimating equations method was used to assess the treatment effect of COLP on daily opioid consumption and pain during postoperative period from postoperative day (POD) 1 to POD 17. Patients in the COLP group consumed approximately 30% less daily morphine milligram equivalents compared with patients in the treatment as usual group during POD 1 to 17 (-14.5 daily morphine milligram equivalents; 95% CI: [-26.8, -2.2]). Daily worst pain scores were also lower in the COLP group (-1.0 point on the 10-point scale; 95% CI: [-2.0, -0.1]), although a significant difference was not detected in average daily pain between the groups (-0.8 point; 95% CI: [-1.7, 0.2]). These findings suggest that COLP may serve as a potential adjuvant analgesic therapy to decrease opioid consumption in the early postoperative period, without increasing pain.

Background & Aims Liver diseases are caused by many factors, such as genetics, nutrition, and viruses. Therefore, it is important to delineate transcriptomic changes that occur in various liver diseases. Methods We performed high-throughput sequencing of mouse livers with diverse types of injuries, including cholestasis, diet-induced steatosis, and partial hepatectomy. Comparative analysis of liver transcriptome from mice and human samples of viral infections (HBV and HCV), alcoholic hepatitis (AH), non-alcoholic steatohepatitis (NASH), and biliary atresia revealed distinct and overlapping gene profiles associated with liver diseases. We hypothesised that discrete molecular signatures could be utilised to assess therapeutic outcomes. We focused on cholestasis to test and validate the hypothesis using pharmacological approaches. Results Here, we report significant overlap in the expression of inflammatory and proliferation-related genes across liver diseases. However, cholestatic livers were unique and displayed robust induction of genes involved in drug metabolism. Consistently, we found that constitutive androstane receptor (CAR) activation is crucial for the induction of the drug metabolic gene programme in cholestasis. When challenged, cholestatic mice were protected against zoxazolamine-induced paralysis and acetaminophen-induced hepatotoxicity. These protective effects were diminished upon inhibition of CAR activity. Further, drug metabolic genes were also induced in the livers from a subset of biliary atresia patients, but not in HBV and HCV infections, AH, or NASH. We also found a higher expression of CYP2B6, a CAR target, in the livers of biliary atresia patients, underscoring the clinical importance of our findings. Conclusions Comparative transcriptome analysis of different liver disorders revealed specific induction of phase I and II metabolic genes in cholestasis. Our results demonstrate that CAR activation may lead to variations in drug metabolism and clinical outcomes in biliary atresia. Lay summary Transcriptomic analysis of diverse liver diseases revealed alterations in common and distinct pathways. Specifically, in cholestasis, we found that detoxification genes and their activity are increased. Thus, cholestatic patients may have an unintended consequence on drug metabolism and not only have a beneficial effect against liver toxicity, but also may require adjustments to their therapeutic dosage., Graphical abstract, Highlights • Cell cycle, inflammation, and glucose homeostasis are some of the common pathways altered in a variety of liver disorders. • Phase I and II metabolic genes are induced in Fxr−/−Shp−/− double knockouts (DKOs) and bile-acid-fed control mice. • Activation of xeno-sensor, constitutive androstane receptor (CAR), is observed in cholestasis. • Inhibiting CAR activity in DKO mice exacerbates zoxazolamine-induced paralysis and acetaminophen-induced hepatotoxicity. • A subset of patients with biliary atresia display increased expression of CAR target protein CYP2B6.

Hepatocellular carcinoma (HCC) is the most common liver cancer with a higher incidence in males. Here, we report that the spontaneous HCC development subsequent to the deletion of both Farnesoid X Receptor and Small Heterodimer Partner (DKO) mimics the sex-specific incidence seen clinically. In female DKO mice, we find lower levels of circulating bile acids (BA) and show that BAs can co-opt the estrogen axis to auto-regulate their homeostasis and amino acid metabolism. These regulations are lost when female mice are ovariectomized. Conversely, increasing serum BA levels is sufficient to promote tumorigenesis in female livers. To examine the translational relevance, we mined the transcriptomic signatures corresponding to that of female mice and found that it correlated well with those of low-grade tumors and associated with better outcomes for HCC patients. We demonstrate that decreasing enterohepatic recirculation of BAs using a resin dramatically reduced the liver cancer burden in male mice. These results uncover that sexual dimorphism in liver cancer incidence is linked to sex-differences in the handling of circulating BA concentrations and that lowering it might alleviate liver cancer.SignificanceWe demonstrate that serum BA concentration facilitates sex-differences in tumor burden, with reduced BA levels resulting in lower HCC risk in female mice. Increasing or decreasing circulating BA levels, promotes or alleviates HCC risk, respectively. We show that the sex-specific gene profiles identified in the DKO mice model of HCC correlate directly with patient outcomes.

Understanding the alterations in drug metabolism in different liver diseases is crucial for appropriate therapeutic intervention. We performed high-throughput RNA sequencing on various liver injury models, including cholestasis, diet-induced steatosis, and regeneration. Comparative liver transcriptome analysis revealed overlapping and distinct gene profiles among different liver diseases. Particularly, cholestatic livers displayed robust induction of drug metabolizing genes. This upregulation is not a generic hepatic stress response, as it was suppressed or unchanged in other models of liver diseases. Consistently, drug metabolic gene profiles were induced in a subset of biliary atresia patients, but not in individuals with hepatitis B or C viral infection, and alcoholic hepatitis. Further analysis revealed this induction was specific to genes regulated by nuclear receptor CAR (Constitutive Androstane Receptor). To test this, we challenged cholestatic mice with a paralytic agent, zoxazolamine. Compared to controls, these mice displayed significantly reduced paralysis time, reflecting increased drug metabolism, and this effect was lost upon inhibition of CAR. Thus, CAR activation can alter therapeutic efficacy of certain drugs in a subset of cholestatic individuals.

Fibromyalgia (FM) is characterized by chronic widespread pain, sleep disturbance, fatigue, and catastrophizing. This pilot study explored whether gentle, daily yoga-based exercise practice could improve pain and sleep quality, and whether certain patient phenotypes were associated with greater improvement. Fibromyalgia patients (n = 36) attended a six-week yoga program, with weekly, in-person, pain-tailored group yoga classes, and were sent daily yoga videos to practice for 30 minutes at home. Participants completed the Brief Pain Inventory (BPI), Revised Fibromyalgia Impact Questionnaire (FIQR), Promis-29 scales, Pittsburgh Sleep Quality Index (PSQI), and the Pain Catastrophizing Scale (PCS). Additionally, they completed daily electronic diaries and wore a wrist actigraph to measure sleep efficiency during 3 weeks, at baseline, 2nd, and 6th week of yoga. Pain, fatigue, and sleep quality, although improved overall, varied among participants. Multilevel modeling analysis of daily ratings in week 6 revealed no main effect for baseline anxiety and catastrophizing on pain, fatigue and sleep efficiency. However, a significant interaction between these was observed for all three outcomes (fatigue: B=.060±.022, p=0.01, sleep efficiency: B=-.40±.015, p = 0.01, pain: B=.055±.020, p=0

Music has been shown to decrease pain and modulate affect, but the mechanism by which music conveys analgesia in relatively unexplored . Using quantitative sensory testing (QST), we assessed the impact of a novel app-based music intervention on the nociceptive processing of pain. Healthy volunteers (n=60) were assessed for psychosocial traits including anxiety, depression, and catastrophizing using validated questionnaires. QST included investigation of: 1) pain sensitivity as measured by pressure pain threshold and tolerance using a handheld algometer, as well as reported pain to weighted pinprick stimuli, 2) temporal summation of pain (TSP) with a repeated pinprick stimulus, and 3) conditioned pain modulation (CPM) with pressure and cold stimuli. QST was performed in both the absence and presence of an interactive music app (Unwind), with paired t or Wilcoxon rank tests used to determine differences. Pressure pain threshold in both the forearm (p=0.007) and trapezius (p=0.002) increased with music. Initial pinprick pain severity (p