Epigenomic landscape of the human dorsal root ganglion: sex differences and transcriptional regulation of nociceptive genes.

Gene expression is influenced by chromatin architecture via controlled access of regulatory factors to DNA. To better understand gene regulation in the human dorsal root ganglion (hDRG) we used bulk and spatial transposase-accessible chromatin technology followed by sequencing (ATAC-seq). Using bulk ATAC-seq, we detected that in females diverse differentially accessible chromatin regions (DARs) mapped to the X chromosome and in males to autosomal genes. EGR1/3 and SP1/4 transcription factor binding motifs were abundant within DARs in females, and JUN, FOS and other AP-1 factors in males. To dissect the open chromatin profile in hDRG neurons, we used spatial ATAC-seq. The neuron cluster showed higher chromatin accessibility in GABAergic, glutamatergic, and interferon-related genes in females, and in Ca2+- signaling-related genes in males. Sex differences in transcription factor binding sites in neuron-proximal barcodes were consistent with the trends observed in bulk ATAC-seq data. We validated that EGR1 expression is biased to female hDRG compared to male. Strikingly, XIST, the long-noncoding RNA responsible for X inactivation, hybridization signal was found to be highly dispersed in the female neuronal but not non-neuronal nuclei suggesting weak X inactivation in female hDRG neurons. Our findings point to baseline epigenomic sex differences in the hDRG that likely underlie divergent transcriptional responses that determine mechanistic sex differences in pain.

Chemotherapy for pain: reversing inflammatory and neuropathic pain with the anticancer agent mithramycin A.

ABSTRACT: The persistence of inflammatory and neuropathic pain is poorly understood. We investigated a novel therapeutic paradigm by targeting gene networks that sustain or reverse persistent pain states. Our prior observations found that Sp1-like transcription factors drive the expression of TRPV1, a pain receptor, that is blocked in vitro by mithramycin A (MTM), an inhibitor of Sp1-like factors. Here, we investigate the ability of MTM to reverse in vivo models of inflammatory and chemotherapy-induced peripheral neuropathy (CIPN) pain and explore MTM's underlying mechanisms. Mithramycin reversed inflammatory heat hyperalgesia induced by complete Freund adjuvant and cisplatin-induced heat and mechanical hypersensitivity. In addition, MTM reversed both short-term and long-term (1 month) oxaliplatin-induced mechanical and cold hypersensitivity, without the rescue of intraepidermal nerve fiber loss. Mithramycin reversed oxaliplatin-induced cold hypersensitivity and oxaliplatin-induced TRPM8 overexpression in dorsal root ganglion (DRG). Evidence across multiple transcriptomic profiling approaches suggest that MTM reverses inflammatory and neuropathic pain through broad transcriptional and alternative splicing regulatory actions. Mithramycin-dependent changes in gene expression following oxaliplatin treatment were largely opposite to and rarely overlapped with changes in gene expression induced by oxaliplatin alone. Notably, RNAseq analysis revealed MTM rescue of oxaliplatin-induced dysregulation of mitochondrial electron transport chain genes that correlated with in vivo reversal of excess reactive oxygen species in DRG neurons. This finding suggests that the mechanism(s) driving persistent pain states such as CIPN are not fixed but are sustained by ongoing modifiable transcription-dependent processes.

Peripheral Neuroinflammation and Pain: How Acute Pain Becomes Chronic.

The number of individuals suffering from severe chronic pain and its social and financial impact is staggering. Without significant advances in our understanding of how acute pain becomes chronic, effective treatments will remain out of reach. This mini review will briefly summarize how critical signaling pathways initiated during the early phases of peripheral nervous system inflammation/ neuroinflammation establish long-term modifications of sensory neuronal function. Together with the recruitment of non-neuronal cellular elements, nociceptive transduction is transformed into a pathophysiologic state sustaining chronic peripheral sensitization and pain. Inflammatory mediators, such as nerve growth factor (NGF), can lower activation thresholds of sensory neurons through posttranslational modification of the pain-transducing ion channels transient-receptor potential TRPV1 and TRPA1. Performing a dual role, NGF also drives increased expression of TRPV1 in sensory neurons through the recruitment of transcription factor Sp4. More broadly, Sp4 appears to modulate a nociceptive transcriptome including TRPA1 and other genes encoding components of pain transduction. Together, these findings suggest a model where acute pain evoked by peripheral injury-induced inflammation becomes persistent through repeated cycles of TRP channel modification, Sp4-dependent overexpression of TRP channels and ongoing production of inflammatory mediators.

Development of the Illinois Surgical Quality Improvement Collaborative (ISQIC): Implementing 21 Components to Catalyze Statewide Improvement in Surgical Care.

INTRODUCTION: In 2014, 56 Illinois hospitals came together to form a unique learning collaborative, the Illinois Surgical Quality Improvement Collaborative (ISQIC). Our objectives are to provide an overview of the first three years of ISQIC focused on (1) how the collaborative was formed and funded, (2) the 21 strategies implemented to support quality improvement (QI), (3) collaborative sustainment, and (4) how the collaborative acts as a platform for innovative QI research. METHODS: ISQIC includes 21 components to facilitate QI that target the hospital, the surgical QI team, and the peri-operative microsystem. The components were developed from available evidence, a detailed needs assessment of the hospitals, reviewing experiences from prior surgical and non-surgical QI Collaboratives, and interviews with QI experts. The components comprise 5 domains: guided implementation (e.g., mentors, coaches, statewide QI projects), education (e.g., process improvement (PI) curriculum), hospital- and surgeon-level comparative performance reports (e.g., process, outcomes, costs), networking (e.g., forums to share QI experiences and best practices), and funding (e.g., for the overall program, pilot grants, and bonus payments for improvement). RESULTS: Through implementation of the 21 novel ISQIC components, hospitals were equipped to use their data to successfully implement QI initiatives and improve care. Formal (QI/PI) training, mentoring, and coaching were undertaken by the hospitals as they worked to implement solutions. Hospitals received funding for the program and were able to work together on statewide quality initiatives. Lessons learned at one hospital were shared with all participating hospitals through conferences, webinars, and toolkits to facilitate learning from each other with a common goal of making care better and safer for the surgical patient in Illinois. Over the first three years, surgical outcomes improved in Illinois. DISCUSSION: The first three years of ISQIC improved care for surgical patients across Illinois and allowed hospitals to see the value of participating in a surgical QI learning collaborative without having to make the initial financial investment themselves. Given the strong support and buy-in from the hospitals, ISQIC has continued beyond the initial three years and continues to support QI across Illinois hospitals.

N-Oleoyl dopamine induces IL-10 via central nervous system TRPV1 and improves endotoxemia and sepsis outcomes.

BACKGROUND: The transient receptor potential vanilloid 1 (TRPV1) participates in thermosensation and inflammatory pain, but its immunomodulatory mechanisms remain enigmatic. N-Oleoyl dopamine (OLDA), an endovanilloid and endocannabinoid, is a TRPV1 agonist that is produced in the central nervous system and the peripheral nervous system. We studied the anti-inflammatory effects and TRPV1-dependent mechanisms of OLDA in models of inflammation and sepsis. METHODS: Mice were challenged intratracheally or intravenously with LPS, or intratracheally with S. aureus to induce pneumonia and sepsis, and then were treated intravenously with OLDA. Endpoints included plasma cytokines, leukocyte activation marker expression, mouse sepsis scores, lung histopathology, and bacterial counts. The role of TRPV1 in the effects of OLDA was determined using Trpv1-/- mice, and mice with TRPV1 knockdown pan-neuronally, in peripheral nervous system neurons, or in myeloid cells. Circulating monocytes/macrophages were depleted using clodronate to determine their role in the anti-inflammatory effects of OLDA in endotoxemic mice. Levels of exogenous OLDA, and of endovanilloids and endocannabinoids, at baseline and in endotoxemic mice, were determined by LC-MS/MS. RESULTS: OLDA administration caused an early anti-inflammatory response in endotoxemic and septic mice with high serum levels of IL-10 and decreased levels of pro-inflammatory cytokines. OLDA also reduced lung injury and improved mouse sepsis scores. Blood and lung bacterial counts were comparable between OLDA- and carrier-treated mice with S. aureus pneumonia. OLDA's effects were reversed in mice with pan-neuronal TRPV1 knockdown, but not with TRPV1 knockdown in peripheral nervous system neurons or myeloid cells. Depletion of monocytes/macrophages reversed the IL-10 upregulation by OLDA in endotoxemic mice. Brain and blood levels of endovanilloids and endocannabinoids were increased in endotoxemic mice. CONCLUSIONS: OLDA has strong anti-inflammatory actions in mice with endotoxemia or S. aureus pneumonia. Prior studies focused on the role of peripheral nervous system TRPV1 in modulating inflammation and pneumonia. Our results suggest that TRPV1-expressing central nervous system neurons also regulate inflammatory responses to endotoxemia and infection. Our study reveals a neuro-immune reflex that during acute inflammation is engaged proximally by OLDA acting on neuronal TRPV1, and through a multicellular network that requires circulating monocytes/macrophages, leads to the systemic production of IL-10.

Occurrence and perceived effectiveness of activities used to decrease chemotherapy-induced peripheral neuropathy symptoms in the feet.

PURPOSE: Investigate the reported use and perceived effectiveness of self-care activities for chemotherapy-induced peripheral neuropathy (CIPN) symptoms in the feet. METHODS: Cancer survivors with CIPN (n = 405) completed a questionnaire that assessed the use and perceived effectiveness of 25 self-care activities. Effectiveness was rated on a 0 (not at all) to 10 (completely effective) numeric rating scale. Descriptive statistics and regression analyses were conducted to identify demographic, clinical, and pain characteristics associated with the use and effectiveness of selected self-care activities. RESULTS: The five most commonly used activities were: went for a walk (73.8%); watched television (67.8%); read a book, newspaper or magazine (64.4%); listened to radio, music (60.0%); and did exercises (jogging, swimming) (58.6%). The five most effective self-care activities were: had a trigger point injection (8.3 ( ± 1.3)); took tranquilizers (4.8 ( ± 2.6)); went for ultrasonic stimulation treatment (4.3 ( ± 3.1)); used a heating pad or hot water bottle (4.3 ( ± 2.5)); and used a transcutaneous electric nerve stimulator (4.2 ( ± 2.6)). Demographic, clinical, and pain characteristics influenced use and perceived effectiveness of selected self-care activities to varying degrees. CONCLUSIONS: Two-thirds of the survivors used at least seven self-care activities to manage CIPN symptoms. The most commonly used activities did not receive the highest effectiveness ratings. Some activities that were rated as highly effective warrant more rigorous evaluation. Survivors can try a range of activities to decrease CIPN symptoms in the feet following discussion of their potential risks and benefits with their clinicians.

Implementation and Effects of a Team-Based Quality Improvement Training Program Across a Health System: The Northwestern Medicine Academy for Quality and Safety Improvement.

BACKGROUND: Professional organizations emphasize the need to train health care professionals in quality improvement (QI). Many reports of QI education programs involve small numbers of participants. Little is known about QI education programs on a larger scale and whether participants subsequently engage in QI activities. METHODS: The Northwestern Medicine Academy for Quality and Safety Improvement (NM AQSI) was developed to prepare individuals across the Northwestern health system to lead QI. The 7-month program consists of classwork and team-based project work. Participant knowledge was assessed using a multiple-choice test and adapted Quality Improvement Knowledge Application Tool (QIKAT). The study team surveyed participants 18 months after AQSI completion to assess their activity in QI. Project status was assessed at AQSI completion and at 18 months. RESULTS: Over 8 years, 80 teams consisting of 441 individuals participated, representing a range of specialties, settings, and professions. Participants had higher multiple-choice test (70.7 ± 14.0 vs. 78.1 ± 13.0; p < 0.001) and adapted QIKAT scores (56.1 ± 15.9 vs. 60.8 ± 15.8; p < 0.001) after AQSI. The majority of participants at 18 months (180/243; 74.1%) had engaged in subsequent QI efforts; many (105/243; 43.2%) had led other QI projects, and (103/243; 42.4%) provided QI mentorship to others. The majority of teams (53/80; 66.3%) improved project measure performance. CONCLUSION: NM AQSI is a team-based QI training program that shows measurable improvements in care and a high degree of participants' subsequent involvement in QI. Other health systems may use a similar approach to successfully train health care professionals to lead QI.

A Comprehensive Estimation of the Costs of 30-Day Postoperative Complications Using Actual Costs from Multiple, Diverse Hospitals.

BACKGROUND: The cost of surgical care is largely measured by charges or payments, both of which are inadequate. Actual cost data from the hospital's perspective are required to accurately quantify the financial return on investment of engaging in quality improvement. The objective of this study was to define the cost of individual, 30-day postoperative complications using robust cost data from a diverse group of hospitals. METHODS: Using clinical data derived from the American College of Surgeons National Surgical Quality Improvement Program, this retrospective study assessed postoperative complications for patients who underwent surgery at one of four hospitals in 2016. Actual direct and indirect 30-day costs were obtained, and the adjusted cost per complication was determined. RESULTS: From the 6,387 patients identified, the three complications associated with the highest independent adjusted cost per event were prolonged ventilation ($48,168; 95% confidence interval [CI]: $21,861-$74,476), unplanned intubation ($26,718; 95% CI: $15,374-$38,062), and renal failure ($18,528; CI: $17,076-$19,981). The three complications associated with the lowest independent adjusted cost per event were urinary tract infection (-$372; 95% CI: -$1,336-$592), superficial surgical site infection ($2,473; 95% CI: -$256-$5,201) and venous thromboembolism ($7,909; 95% CI: -$17,903-$33,721). After colectomy, the adjusted independent cost of anastomotic leak was $10,195 (95% CI: $5,941-$14,449), while the cost of postoperative ileus was $10,205 (95% CI: $6,259-$14,149). CONCLUSION: The actual hospital costs of complications were estimated using cost data from four diverse hospitals. These data can be used by hospitals to estimate the financial benefit of reducing surgical complications.

Differential methylation and expression of genes in the hypoxia-inducible factor 1 signaling pathway are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors and with preclinical models of chemotherapy-induced neuropathic pain.

BACKGROUND: Paclitaxel is an important chemotherapeutic agent for the treatment of breast cancer. Paclitaxel-induced peripheral neuropathy (PIPN) is a major dose-limiting toxicity that can persist into survivorship. While not all survivors develop PIPN, for those who do, it has a substantial negative impact on their functional status and quality of life. No interventions are available to treat PIPN. In our previous studies, we identified that the HIF-1 signaling pathway (H1SP) was perturbed between breast cancer survivors with and without PIPN. Preclinical studies suggest that the H1SP is involved in the development of bortezomib-induced and diabetic peripheral neuropathy, and sciatic nerve injury. The purpose of this study was to identify H1SP genes that have both differential methylation and differential gene expression between breast cancer survivors with and without PIPN. METHODS: A multi-staged integrated analysis was performed. In peripheral blood, methylation was assayed using microarray and gene expression was assayed using RNA-seq. Candidate genes in the H1SP having both differentially methylation and differential expression were identified between survivors who received paclitaxel and did (n = 25) and did not (n = 25) develop PIPN. Then, candidate genes were evaluated for differential methylation and differential expression in public data sets of preclinical models of PIPN and sciatic nerve injury. RESULTS: Eight candidate genes were identified as both differential methylation and differential expression in survivors. Of the eight homologs identified, one was found to be differential expression in both PIPN and "normal" mice dorsal root ganglia; three were differential methylation in sciatic nerve injury versus sham rats in both pre-frontal cortex and T-cells; and two were differential methylation in sciatic nerve injury versus sham rats in the pre-frontal cortex. CONCLUSIONS: This study is the first to evaluate for methylation in cancer survivors with chronic PIPN. The findings provide evidence that the expression of H1SP genes associated with chronic PIPN in cancer survivors may be regulated by epigenetic mechanisms and suggests genes for validation as potential therapeutic targets.

Long-Term Trends in Postoperative Opioid Prescribing, 1994 to 2014.

Opioids are routinely prescribed to manage acute postoperative pain, but changes in postoperative opioid prescribing associated with the marketing of long-acting opioids such as OxyContin have not been described in the surgical cohort. Methods: Using a large commercial claims data set, we studied postoperative opioid prescribing after selected common surgical procedures between 1994 and 2014. For each procedure and year, we calculated the mean postoperative morphine milligram equivalents (MME) filled on the index prescription and assessed the proportion of patients who filled a high-dose prescription (≥350 MME). We reported changes in postoperative opioid prescribing over time and identified predictors of filling a high-dose postoperative opioid prescription. Results: We identified 1,321,264 adult patients undergoing selected common surgical procedures between 1994 and 2014, of whom 80.3% filled a postoperative opioid prescription. One in five surgery patients filled a high-dose postoperative opioid prescription. Between 1994 and 2014, the mean MME filled increased by 145%, 84%, and 85% for lumbar laminectomy/laminotomy, total knee arthroplasty, and total hip arthroplasty, respectively. The procedures most likely to be associated with a high-dose opioid fill were all orthopaedic procedures (AOR 5.20 to 7.55, P < 0.001 for all). Patients whose postoperative opioid prescription included a long-acting formulation had the highest odds of filling a prescription that exceeded 350 MME (AOR 32.01, 95% CI, 30.23-33.90). Discussion: After the US introduction of long-acting opioids such as OxyContin, postoperative opioid prescribing in commercially insured patients increased in parallel with broader US opioid-prescribing trends, most notably among patients undergoing orthopaedic surgical procedures. The increase in the mean annual MME filled starting in the late 1990s was driven in part by the higher proportion of long-acting opioid formulations on the index postoperative opioid prescription filled by orthopaedic surgery patients.

AAAPT Diagnostic Criteria for Acute Pain Following Breast Surgery.

Acute pain after breast surgery decreases the quality of life of cancer survivors. Previous studies using a variety of definitions and methods report prevalence rates between 10% and 80%, which suggests the need for a comprehensive framework that can be used to guide assessment of acute pain and pain-related outcomes after breast surgery. A multidisciplinary task force with clinical and research expertise performed a focused review and synthesis and applied the 5 dimensional framework of the AAAPT (Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks [ACTTION], American Academy of Pain Medicine [AAPM], American Pain Society [APS] Pain Taxonomy) to acute pain after breast surgery. Application of the AAAPT taxonomy yielded the following: 1) Core Criteria: Location, timing, severity, and impact of breast surgery pain were defined; 2) Common Features: Character and expected trajectories were established in relevant surgical subgroups, and common pain assessment tools for acute breast surgery pain identified; 3) Modulating Factors: Biological, psychological, and social factors that modulate interindividual variability were delineated; 4) Impact/Functional Consequences: Domains of impact were outlined and defined; 5) Neurobiologic Mechanisms: Putative mechanisms were specified ranging from nerve injury, inflammation, peripheral and central sensitization, to affective and social processing of pain. PERSPECTIVE: The AAAPT provides a framework to define and guide improved assessment of acute pain after breast surgery, which will enhance generalizability of results across studies and facilitate meta-analyses and studies of interindividual variation, and underlying mechanism. It will allow researchers and clinicians to better compare between treatments, across institutions, and with other types of acute pain.

Perturbations in neuroinflammatory pathways are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors.

Paclitaxel is a common chemotherapy drug associated with the development of chronic paclitaxel-induced peripheral neuropathy (PIPN). PIPN is associated with neuroinflammatory mechanisms in pre-clinical studies. Here, we evaluated for differential gene expression (DGE) in peripheral blood between breast cancer survivors with and without PIPN and for neuroinflammatory (NI) related signaling pathways and whole-transcriptome profiles from other experiments. Pathway impact analysis identified 8 perturbed NI related pathways. Expression profile analysis found 15 experiments having similar whole-transcriptome profiles of DGE related to neuroinflammation and PIPN. These findings suggest that perturbations in pathways associated with neuroinflammation are found in cancer survivors with PIPN.

Hospital-Level Cardiovascular Management Practices in Kerala, India.

Background Hospital management practices are associated with cardiovascular process of care measures and patient outcomes. However, management practices related to acute cardiac care in India has not been studied. Methods and Results We measured management practices through semistructured, in-person interviews with hospital administrators, physician managers, and nurse managers in Kerala, India between October and November 2017 using the adapted World Management Survey. Trained interviewers independently scored management interview responses (range: 1-5) to capture management practices ranging from performance data tracking to setting targets. We performed univariate regression analyses to assess the relationship between hospital-level factors and management practices. Using Pearson correlation coefficients and mixed-effect logistic regression models, we explored the relationship between management practices and 30-day major adverse cardiovascular events defined as all-cause mortality, reinfarction, stroke, or major bleeding. Ninety managers from 37 hospitals participated. We found suboptimal management practices across 3 management levels (mean [SD]: 2.1 [0.5], 2.0 [0.3], and 1.9 [0.3] for hospital administrators, physician managers, and nurse managers, respectively [ P=0.08]) with lowest scores related to setting organizational targets. Hospitals with existing healthcare quality accreditation, more cardiologists, and private ownership were associated with higher management scores. In our exploratory analysis, higher physician management practice scores related to operation, performance, and target management were correlated with lower 30-day major adverse cardiovascular event. Conclusions Management practices related to acute cardiac care in participating Kerala hospitals were suboptimal but were correlated with clinical outcomes. We identified opportunities to strengthen nonclinical practices to improve patient care.

Deleterious Effects of Higher Body Mass Index on Subjective and Objective Measures of Chemotherapy-Induced Peripheral Neuropathy in Cancer Survivors.

CONTEXT: Recent, albeit, limited evidence suggests that body mass index (BMI) may be a modifiable risk factor to reduce the deleterious effects of chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors. OBJECTIVES: To evaluate for differences in demographic, clinical, pain, sensation, and balance characteristics among three BMI groups. We hypothesized that as BMI increased, survivors would report higher pain intensity scores and have significant decrements in measures of sensation and balance. METHODS: A total of 416 survivors with CIPN were evaluated using subjective and objective measures of CIPN. Survivors were divided into three BMI groups (i.e., normal weight, overweight, and obese). Differences among the BMI groups were evaluated using parametric and nonparametric statistics. RESULTS: Of the 416 survivors, 45.4% were normal weight, 32.5% were overweight, and 22.1% were obese. Compared with the normal-weight group, survivors in the other two groups had lower functional status scores, a higher comorbidity burden, higher pain intensity scores, and higher interference scores. In addition, compared with the normal-weight group, survivors in the other two BMI groups had significantly worse balance scores. CONCLUSION: Our findings support the hypothesis that as BMI increased, pain sensation and balance characteristics worsened. Our findings suggest that nutritional counseling as well as exercise and weight management programs in survivors with CIPN may improve these clinically important problems.

Transcription factor Sp4 is required for hyperalgesic state persistence.

Understanding how painful hypersensitive states develop and persist beyond the initial hours to days is critically important in the effort to devise strategies to prevent and/or reverse chronic painful states. Changes in nociceptor transcription can alter the abundance of nociceptive signaling elements, resulting in longer-term change in nociceptor phenotype. As a result, sensitized nociceptive signaling can be further amplified and nocifensive behaviors sustained for weeks to months. Building on our previous finding that transcription factor Sp4 positively regulates the expression of the pain transducing channel TRPV1 in Dorsal Root Ganglion (DRG) neurons, we sought to determine if Sp4 serves a broader role in the development and persistence of hypersensitive states in mice. We observed that more than 90% of Sp4 staining DRG neurons were small to medium sized, primarily unmyelinated (NF200 neg) and the majority co-expressed nociceptor markers TRPV1 and/or isolectin B4 (IB4). Genetically modified mice (Sp4+/-) with a 50% reduction of Sp4 showed a reduction in DRG TRPV1 mRNA and neuronal responses to the TRPV1 agonist-capsaicin. Importantly, Sp4+/- mice failed to develop persistent inflammatory thermal hyperalgesia, showing a reversal to control values after 6 hours. Despite a reversal of inflammatory thermal hyperalgesia, there was no difference in CFA-induced hindpaw swelling between CFA Sp4+/- and CFA wild type mice. Similarly, Sp4+/- mice failed to develop persistent mechanical hypersensitivity to hind-paw injection of NGF. Although Sp4+/- mice developed hypersensitivity to traumatic nerve injury, Sp4+/- mice failed to develop persistent cold or mechanical hypersensitivity to the platinum-based chemotherapeutic agent oxaliplatin, a non-traumatic model of neuropathic pain. Overall, Sp4+/- mice displayed a remarkable ability to reverse the development of multiple models of persistent inflammatory and neuropathic hypersensitivity. This suggests that Sp4 functions as a critical control point for a network of genes that conspire in the persistence of painful hypersensitive states.

Age-related differences in patient-reported and objective measures of chemotherapy-induced peripheral neuropathy among cancer survivors.

PURPOSE: While older adults with cancer are more likely to develop chemotherapy-induced peripheral neuropathy (CIPN), the study aimed to determine if patient-reported and objective measures of CIPN differ by age among cancer survivors. METHODS: Cancer survivors with persistent CIPN after completion of platinum and/or taxane chemotherapy completed CIPN questionnaires (severity, interference with activities, sensory, and motor symptoms) and objective testing (light touch, vibration, pain, cold sensation). CIPN measures were compared by age group (< 65 n = 260 versus ≥ 65 n = 165) using parametric and nonparametric tests. RESULTS: Among 425 cancer survivors with CIPN, mean age was 60.9 (SD 10.5). CIPN location did not differ by age (overall 68% hands and feet, 27% only feet, 5% only hands). For patient-reported measures, older survivors reported less severe pain in the hands and feet than younger survivors. In addition, older survivors reported lower interference with general activity, routine activities, normal work, enjoyment of life, sleep, mood, relations with other people, and sexual activity. No age differences in sensory and motor symptom scores were found. In contrast, for objective measures, older survivors had worse light touch and cold sensations in their feet and worse vibration detection in their hands and feet. CONCLUSIONS: Despite having worse light touch, cold, and vibration sensations, older cancer survivors with CIPN reported less severe pain and interference with activities. This discordance highlights the importance of including both patient-reported and objective measures to assess CIPN in cancer survivors to better evaluate this clinical condition.

Immediate and long-term effects of a team-based quality improvement training programme.

BACKGROUND: Although many studies of quality improvement (QI) education programmes report improvement in learners' knowledge and confidence, the impact on learners' future engagement in QI activities is largely unknown and few studies report project measures beyond completion of the programme. METHOD: We developed the Academy for Quality and Safety Improvement (AQSI) to prepare individuals, across multiple departments and professions, to lead QI. The 7-month programme consisted of class work and team-based project work. We assessed participants' knowledge using a multiple choice test and an adapted Quality Improvement Knowledge Assessment Test (QIKAT) before and after the programme. We evaluated participants' postprogramme QI activity and project status using surveys at 6 and 18 months. RESULTS: Over 5 years, 172 individuals and 32 teams participated. Participants had higher multiple choice test (71.9±12.7 vs 79.4±13.2; p<0.001) and adapted QIKAT scores (55.7±16.3 vs 61.8±14.7; p<0.001) after the programme. The majority of participants at 6 months indicated that they had applied knowledge and skills learnt to improve quality in their clinical area (129/148; 87.2%) and to implement QI interventions (92/148; 62.2%). At 18 months, nearly half (48/101; 47.5%) had led other QI projects and many (41/101; 40.6%) had provided QI mentorship to others. Overall, 14 (43.8%) teams had positive postintervention results at AQSI completion and 20 (62.5%) had positive results at some point (ie, completion, 6 months or 18 months after AQSI). CONCLUSIONS: A team-based QI training programme resulted in a high degree of participants' involvement in QI activities beyond completion of the programme. A majority of team projects showed improvement in project measures, often occurring after completion of the programme.

Pain Management and Opioid Regulation: Continuing Public Health Challenges.

The still-growing US opioid epidemic lies at the intersection of two major public health challenges: reducing suffering from pain and containing the rising toll of harms associated with the use of opioids medications. Responding successfully to these challenges requires a substantial investment in surveillance and research on many fronts and a coordinated policy response by federal and state agencies and stakeholder organizations.A 2017 report of the National Academies of Sciences, Engineering and Medicine (NASEM) called for improved methods of measuring pain and the effects of alternative modalities of treatment as well as intensive surveillance of opioid-related harms; urged a long-term cultural transformation of how pain is perceived, assessed and treated; and outlined a comprehensive and balanced public health framework to guide Food and Drug Administration approval, monitoring, and review of opioids.We, authors of the NASEM report, use the articles published in this special section of AJPH as a platform for commenting on the public health burden of pain, the role of opioids in managing pain, global disparities in access to opioids for pain management, divergent approaches to opioid regulation, and the challenge of striking a reasonable balance between the needs of patients in pain and the prevention of opioid-related harms.