The Neurostimulation Appropriateness Consensus Committee (NACC)®: Recommendations for Spinal Cord Stimulation Long-term Outcome Optimization and Salvage Therapy.

INTRODUCTION: The International Neuromodulation Society (INS) has recognized a need to establish best practices for optimizing implantable devices and salvage when ideal outcomes are not realized. This group has established the Neurostimulation Appropriateness Consensus Committee (NACC)® to offer guidance on matters needed for both our members and the broader community of those affected by neuromodulation devices. MATERIALS AND METHODS: The executive committee of the INS nominated faculty for this NACC® publication on the basis of expertise, publications, and career work on the issue. In addition, the faculty was chosen in consideration of diversity and inclusion of different career paths and demographic categories. Once chosen, the faculty was asked to grade current evidence and along with expert opinion create consensus recommendations to address the lapses in information on this topic. RESULTS: The NACC® group established informative and authoritative recommendations on the salvage and optimization of care for those with indwelling devices. The recommendations are based on evidence and expert opinion and will be expected to evolve as new data are generated for each topic. CONCLUSIONS: NACC® guidance should be considered for any patient with less-than-optimal outcomes with a stimulation device implanted for treating chronic pain. Consideration should be given to these consensus points to salvage a potentially failed device before explant.

Real-world biologics response and super-response in the International Severe Asthma Registry cohort.

BACKGROUND: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma. METHODS: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. RESULTS: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria. CONCLUSIONS: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.

Dorsal Root Ganglion Stimulation for the Management of Inflammatory Bowel Disease: A Case Report.

This case report presents the successful use of dorsal root ganglion stimulation (DRGS) in a 30-year-old female patient with Crohn's disease. Despite extensive treatments, the patient experienced chronic abdominal pain, diarrhea, bloating, cramping, fatigue, and other debilitating symptoms. After a successful DRGS trial with leads placed on the right T6 and T10, she was implanted with a permanent system. At 18 months she continues to experience significant improvement in symptoms, including reduced abdominal pain, decreased defecation frequency, better stool consistency, less pain with eating and bowel evacuation, and enhanced quality of life.

The Effect of Simulated Obstructive Apneas on Mechanical Characteristics of Lower Airways in Individuals with Asthma.

Increased negative intrathoracic pressure that occurs during pharyngeal obstruction can increase thoracic fluid volume that may contribute to lower airway narrowing in individuals with obstructive sleep apnea (OSA) and asthma. Our previous study showed that fluid accumulation in the thorax induced by simulated OSA can increase total respiratory resistance. However, the effect of fluid shift on lower airway narrowing has not been investigated. To examine the effect of fluid accumulation in the thorax on the resistance of the lower airway. Non-asthma participants and individuals with (un)controlled asthma were recruited and underwent a single-day experiment. A catheter with six pressure sensors was inserted through the nose to continuously measure pressure at different sites of the airway, while a pneumotachograph was attached to a mouthpiece to record airflow. To simulate obstructive apneas, participants performed 25 Mueller maneuvers (MMs) while lying supine. Using the recordings of pressure sensor and airflow, total respiratory (RT), lower respiratory components (RL), and upper airway (RUA) resistances were calculated before and after MMs. Generalized estimation equation method was used to find the predictors of RL among variables including age, sex, body mass index, and the effect of MMs and asthma. Eighteen participants were included. Performing MMs significantly increased RT (2.23 ± 2.08 cmH2O/L/s, p = 0.003) and RL (1.52 ± 2.00 cmH2O/L/s, p = 0.023) in participants with asthma, while only RL was increased in non-asthma group (1.96 ± 1.73 cmH2O/L/s, p = 0.039). We found the model with age, and the effect of MMs and asthma severity generated the highest correlation (R2 = 0.69, p < 0.001). We provide evidence that fluid accumulation in the thorax caused by excessive intrathoracic pressure increases RL in both non-asthma and asthma groups. The changes in RL were related to age, having asthma and the effect of simulated OSA. This can explain the interrelationship between OSA and asthma.

Evaluation of Washout Periods After Dorsal Root Ganglion Stimulation Trial.

OBJECTIVE: Dorsal root ganglion stimulation (DRG-S) is a novel therapy to treat chronic pain. It has shown efficacy when delivered intermittently, suggesting a delayed washout effect exists. To measure the washout period, and to determine whether there are differences in washout times among different types of treated pain, we measured the time for pain to return at the end of the patients' one-week DRG stimulation trials. MATERIALS AND METHODS: Patients who completed a successful DRG-S trial were included. The times until 25% (t25) and 90% (t90) of baseline pain level returned were recorded. The patients were divided into neuropathic, nociceptive, and mixed pain groups for subgroup comparison. t25 and t90 were plotted in the entire cohort and subgroups using reverse Kaplan-Meier plots (failure curves) and compared using a log-rank test. RESULTS: In total, 29 consecutive patients were included. Median t25 and t90 times were 7.1 and 19.5 hours, respectively. Median (interquartile range) times were longest for the nociceptive pain group (n = 17) and shortest for the neuropathic pain group (n = 6), with the mixed-pain group (n = 6) in between (t25: 7.1 [1.7-19.4], 3.40 [1.4-8.4], and 5.7 [0.8-17.6]; t90, 22.0 [10.7-71.0], 7.6 [3.6-19.8], and 20.9 [14.2-31.2], respectively). t90 times differed significantly by pain type (p = 0.040). CONCLUSIONS: This study showed a prolonged washout period after cessation of DRG-S therapy. Washout times vary according to pain type. The observed effects are possibly due to long-term depression of pain signaling and could allow the implementation of alternative stimulation strategies with DRG-S. Further investigations evaluating DRG-S washout times are warranted.

Sacroiliac Joint Denervation-A Novel Approach to Target Sacral Lateral Branches: A Practical Approach.

INTRODUCTION: Sacroiliac joint (SIJ) pain is a relatively common cause of low back pain. Percutaneous radiofrequency (RF) techniques for SIJ are limited to ablation of the posterior SIJ innervation. Different techniques have been described for SIJ radiofrequency ablation, including conventional thermal, cooled RF, pulsed RF, bipolar RF, and specialized tip RF needle (i.e., multi-tined); however, additional costs may limit these applications. METHODS: This new technique for SIJ denervation uses anatomical landmarks and a single RF cannula. Two spinal needles are placed lateral to the posterior S1 and S2 sacral foramina; then, with caudal tilt we get a coaxial view of the sacral bone, we advance an 18-G curved 15-mm active tip RF cannula just lateral to the aligned finder needles. Ablation is performed, and then the RF cannula is retracted 2 cm and ablation is repeated for a total of four lesions. RESULTS: The two spinal needles placed lateral to the posterior sacral foramina S1 and S2 guide the final needle in the posterior aspect of the sacrum, lateral to the sacral foramina, where the lateral sacral branches are located. CONCLUSION: We introduce a cost and time efficient technique to perform radiofrequency ablation of the sacral lateral branches using a single RF needle. This technique utilizes the sacrum's reliable anatomy and angulation and maximizes the surface area of the active tip lesioning. This technique creates a strip lesion lateral to the sacral foramina and reduces time and cost efficacy compared to several of the other techniques and/or commercially available special devices designed for sacroiliac denervation.

Real-world outcomes of mepolizumab for the treatment of severe eosinophilic asthma in Canada: an observational study.

BACKGROUND: Mepolizumab, the first widely available anti-interleukin 5 biologic, targets eosinophilic inflammation and has been shown in clinical trials to reduce exacerbations, oral corticosteroid dependence, and healthcare utilization in patients with severe asthma. The impact of mepolizumab in a real-world, publicly funded healthcare setting is unknown. The objective of this study was to describe the demographics and clinical characteristics of real-world patients receiving mepolizumab, and to compare asthma-related outcomes and associated asthma-related costs before and during mepolizumab use. METHODS: This retrospective, observational study in Ontario, Canada, included patients initiating mepolizumab between February 2016 and March 2019. Patients were identified using the mepolizumab patient support program and linked to the Institute for Clinical Evaluative Sciences database of publicly accessed healthcare. Patient outcomes were obtained for 12 months pre- and post-mepolizumab initiation and compared. RESULTS: A total of 275 patients were enrolled in the overall patient support program cohort (mean [standard deviation] age 57.6 [13.5] years, mean [standard deviation] of the median per-patient eosinophil count 540.4 [491.9] cells/µL). Mepolizumab was associated with reductions in asthma exacerbations (46.1%, P < 0.001) and in the number of asthma-related visits to general practitioners (40.2%, P < 0.001), specialists (27.2%, P < 0.001), and emergency departments (52.1%, P < 0.001). Associated costs were significantly lower post- versus pre-mepolizumab for asthma-related general practitioner and specialist visits, and for all-cause emergency department visits and hospital admissions. CONCLUSIONS: In a real-world population of Canadian patients with severe asthma with an eosinophilic phenotype, the use of mepolizumab within a patient support program reduced asthma exacerbations and decreased asthma-related healthcare resource utilization and associated costs.

Long-Term Safety of Dupilumab in Patients With Moderate-to-Severe Asthma: TRAVERSE Continuation Study.

BACKGROUND: Previous clinical trials have demonstrated dupilumab efficacy and safety in adults and adolescents with moderate to severe asthma for up to 3 years. OBJECTIVE: The TRAVERSE continuation study (NCT03620747), a single-arm, open-label study, assessed safety and tolerability of dupilumab 300 mg every 2 weeks up to an additional 144 weeks (∼3 years) in patients with moderate to severe asthma who previously completed TRAVERSE (NCT02134028). METHODS: Primary end points were incidence and event rates per 100 patient-years of treatment-emergent adverse events (TEAEs). Secondary end points included adverse events (AEs) of special interest, serious AEs, and AEs leading to study discontinuation. RESULTS: A total of 393 patients participated in the TRAVERSE continuation study (cumulative dupilumab exposure, 431.7 patient-years; median treatment duration, 309 days). A total of 29 patients (7.4%) received more than 958 days of treatment. A total of 214 (54.5%) patients reported at least 1 TEAE (event rate: 171.4); 37 (9.4%) experienced at least 1 treatment-related TEAE, none of which were considered severe; 2 patients reported 6 TEAEs of moderate intensity. A total of 22 (5.6%) patients reported serious AEs (event rate: 6.9). AEs of special interest were reported in 24 patients (6.1%; event rate: 6.0). Five (1.3%) deaths occurred (event rate: 1.2) following serious AEs of coronavirus disease 2019 (COVID-19)-related pneumonia (3 patients), pancreatitis (1 patient), and pulmonary embolism (1 patient). None of the TEAEs leading to death were considered treatment-related. CONCLUSIONS: Dupilumab treatment was well tolerated for up to an additional 3 years. Safety findings were consistent with the known safety profile of dupilumab. These findings further support the long-term use of dupilumab in patients with moderate to severe asthma.

Analysis of comorbidities and multimorbidity in adult patients in the International Severe Asthma Registry.

BACKGROUND: Investigation for the presence of asthma comorbidities is recommended by the Global Initiative for Asthma because their presence can complicate asthma management. OBJECTIVE: To understand the prevalence and pattern of comorbidities and multimorbidity in adults with severe asthma and their association with asthma-related outcomes. METHODS: This was a cross-sectional study using data from the International Severe Asthma Registry from 22 countries. A total of 30 comorbidities were identified and categorized a priori as any of the following: (1) potentially type 2-related comorbidities, (2) potentially oral corticosteroid (OCS)-related comorbidities, or (3) comorbidities mimicking or aggravating asthma. The association between comorbidities and asthma-related outcomes was investigated using multivariable models adjusted for country, age at enrollment, and sex (ie male or female). RESULTS: Of the 11,821 patients, 69%, 67%, and 55% had at least 1 potentially type 2-related, potentially OCS-related, or mimicking or aggravating comorbidities, respectively; 57% had 3 or more comorbidities, and 33% had comorbidities in all 3 categories. Patients with allergic rhinitis, nasal polyposis, and chronic rhinosinusitis experienced 1.12 (P = .003), 1.16 (P < .001), and 1.29 times (P < .001) more exacerbations per year, respectively, than those without. Patients with nasal polyposis and chronic rhinosinusitis were 40% and 46% more likely (P < .001), respectively, to have received long-term (LT) OCS. All assessed potential OCS-related comorbidities (except obesity) were associated with a greater likelihood of LTOCS use (odds ratios [ORs]: 1.23-2.77) and, except for dyslipidemia, with a greater likelihood of uncontrolled asthma (ORs: 1.29-1.68). All mimicking or aggravating comorbidities assessed were associated with more exacerbations (1.24-1.68 times more), all (except bronchiectasis) with increased likelihood of uncontrolled asthma (ORs: 1.57-1.81), and all (except chronic obstructive pulmonary disease) with increased likelihood of LTOCS use (ORs: 1.37-1.57). A greater number of comorbidities was associated with worse outcomes. CONCLUSION: In a global study, comorbidity or multimorbidity is reported in most adults with severe asthma and is associated with poorer asthma-related outcomes. CLINICAL TRIAL REGISTRATION: The International Severe Asthma Registry database has ethical approval from the Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218) and is registered with the European Union Electronic Register of Post-Authorization Studies (European Network Centres for Pharmacoepidemiology and Pharmacovigilance [ENCEPP]/DSPP/23720). The study was designed, implemented, and reported in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) Code of Conduct (EMA 2014; EUPAS44024) and with all applicable local and international laws and regulations, and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=48848). Governance was provided by ADEPT (registration number: ADEPT1121).

Lead migration rate in dorsal root ganglion stimulation using lead anchoring techniques: A follow-up study.

BACKGROUND: Lead anchoring has previously been shown to reduce the rate of dorsal root ganglion stimulation (DRG-S) lead migration. The aim of this study was to assess longer-term follow-up and consistency of lead migration prevention with lead anchoring in a new cohort of patients. METHODS: We performed a retrospective chart review from September 2017 to November 2022 of all patients who had DRG-S implants at our institute to identify the number of lead migrations that occurred over this period. The first cohort consisted of patients reported on in a previous publication (implanted from September 2017 through September 2020) subdivided into unanchored or anchored lead groups. The second cohort consisted of patients implanted during or after October 2020 who were not previously reported on for whom leads were anchored using silastic anchoring only. RESULTS: At the November 2022 data cutoff, in the initial cohort, 8 migrations had occurred in unanchored leads over an average follow-up of 49 months, equating to a migration rate of 9.1% per lead. Patients with anchored leads in the initial cohort experienced 2 migrations over an average follow-up of 38 months (0.7% migration rate per lead). There were no new lead migrations in these groups over the extended follow-up reported here. The migration rate in the new cohort was similar, with 1 migration over an average follow-up of 13 months (0.5% migration rate per lead). CONCLUSION: These results underscore the necessity of anchor placement during DRG-S lead implantation to prevent lead migration.

Burst Spinal Cord Stimulation as Compared With L2 Dorsal Root Ganglion Stimulation in Pain Relief for Nonoperated Discogenic Low Back Pain: Analysis of Two Prospective Studies.

INTRODUCTION: Chronic discogenic low back pain (CD-LBP) is caused by degenerated disks marked by neural and vascular ingrowth. Spinal cord stimulation (SCS) has been shown to be effective for pain relief in patients who are not responsive to conventional treatments. Previously, the pain-relieving effect of two variations of SCS has been evaluated in CD-LBP: Burst SCS and L2 dorsal root ganglion stimulation (DRGS). The aim of this study is to compare the effectivity in pain relief and pain experience of Burst SCS with that of conventional L2 DRGS in patients with CD-LBP. MATERIALS AND METHODS: Subjects were implanted with either Burst SCS (n = 14) or L2 DRGS with conventional stimulation (n = 15). Patients completed the numeric pain rating score (NRS) for back pain and Oswestry disability index (ODI) and EuroQoL 5D (EQ-5D) questionnaires at baseline, and at three, six, and 12 months after implantation. Data were compared between time points and between groups. RESULTS: Both Burst SCS and L2 DRGS significantly decreased NRS, ODI, and EQ-5D scores as compared with baseline. L2 DRGS resulted in significantly lower NRS scores at 12 months and significantly increased EQ-5D scores at six and 12 months. CONCLUSIONS: Both L2 DRGS and Burst SCS resulted in reduction of pain and disability, and increased quality of life in patients with CD-LBP. L2 DRGS provided significantly increased pain relief and improvement in quality of life when compared with Burst SCS. CLINICAL TRIAL REGISTRATION: The clinical trial registration numbers for the study are NCT03958604 and NL54405.091.15.

Association Between T2-related Comorbidities and Effectiveness of Biologics in Severe Asthma.

Rationale: Previous studies investigating the impact of comorbidities on the effectiveness of biologic agents have been relatively small and of short duration and have not compared classes of biologic agents. Objectives: To determine the association between type 2-related comorbidities and biologic agent effectiveness in adults with severe asthma (SA). Methods: This cohort study used International Severe Asthma Registry data from 21 countries (2017-2022) to quantify changes in four outcomes before and after biologic therapy-annual asthma exacerbation rate, FEV1% predicted, asthma control, and long-term oral corticosteroid daily dose-in patients with or without allergic rhinitis, chronic rhinosinusitis (CRS) with or without nasal polyps (NPs), NPs, or eczema/atopic dermatitis. Measurements and Main Results: Of 1,765 patients, 1,257, 421, and 87 initiated anti-IL-5/5 receptor, anti-IgE, and anti-IL-4/13 therapies, respectively. In general, pre- versus post-biologic therapy improvements were noted in all four asthma outcomes assessed, irrespective of comorbidity status. However, patients with comorbid CRS with or without NPs experienced 23% fewer exacerbations per year (95% CI, 10-35%; P < 0.001) and had 59% higher odds of better post-biologic therapy asthma control (95% CI, 26-102%; P < 0.001) than those without CRS with or without NPs. Similar estimates were noted for those with comorbid NPs: 22% fewer exacerbations and 56% higher odds of better post-biologic therapy control. Patients with SA and CRS with or without NPs had an additional FEV1% predicted improvement of 3.2% (95% CI, 1.0-5.3; P = 0.004), a trend that was also noted in those with comorbid NPs. The presence of allergic rhinitis or atopic dermatitis was not associated with post-biologic therapy effect for any outcome assessed. Conclusions: These findings highlight the importance of systematic comorbidity evaluation. The presence of CRS with or without NPs or NPs alone may be considered a predictor of the effectiveness of biologic agents in patients with SA.

Dorsal Root Ganglion Stimulation to Treat Chronic Shoulder Pain: A Case Report.

A 67-year-old man presented with severe 9 of 10 intractable pain of the left shoulder joint after arthroplasty and revision surgeries, with associated weakness, atrophy, and limited range of motion in all directions. Dorsal root ganglion stimulation (DRG-S) at the left C4, C5, and C6 levels was used after failed conservative and interventional measures, resulting in significant improvement in pain, function, and quality of life measures through 6 months postimplantation. Larger studies should examine if DRG-S is effective in treating chronic arthritic joint pain as well as chronic postsurgical pain of the shoulder that is not predominantly neuropathic.

Predictors of Readmission, for Patients with Chronic Obstructive Pulmonary Disease (COPD) - A Systematic Review.

Introduction: Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death globally and is responsible for over 3 million deaths annually. One of the factors contributing to the significant healthcare burden for these patients is readmission. The aim of this review is to describe significant predictors and prediction scores for all-cause and COPD-related readmission among patients with COPD. Methods: A search was conducted in Ovid MEDLINE, Ovid Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials, from database inception to June 7, 2022. Studies were included if they reported on patients at least 40 years old with COPD, readmission data within 1 year, and predictors of readmission. Study quality was assessed. Significant predictors of readmission and the degree of significance, as noted by the p-value, were extracted for each study. This review was registered on PROSPERO (CRD42022337035). Results: In total, 242 articles reporting on 16,471,096 patients were included. There was a low risk of bias across the literature. Of these, 153 studies were observational, reporting on predictors; 57 studies were observational studies reporting on interventions; and 32 were randomized controlled trials of interventions. Sixty-four significant predictors for all-cause readmission and 23 for COPD-related readmission were reported across the literature. Significant predictors included 1) pre-admission patient characteristics, such as male sex, prior hospitalization, poor performance status, number and type of comorbidities, and use of long-term oxygen; 2) hospitalization details, such as length of stay, use of corticosteroids, and use of ventilatory support; 3) results of investigations, including anemia, lower FEV1, and higher eosinophil count; and 4) discharge characteristics, including use of home oxygen and discharge to long-term care or a skilled nursing facility. Conclusion: The findings from this review may enable better predictive modeling and can be used by clinicians to better inform their clinical gestalt of readmission risk.

Unraveling the link between PTBP1 and severe asthma through machine learning and association rule mining method.

Severe asthma is a chronic inflammatory airway disease with great therapeutic challenges. Understanding the genetic and molecular mechanisms of severe asthma may help identify therapeutic strategies for this complex condition. RNA expression data were analyzed using a combination of artificial intelligence methods to identify novel genes related to severe asthma. Through the ANOVA feature selection approach, 100 candidate genes were selected among 54,715 mRNAs in blood samples of patients with severe asthmatic and healthy groups. A deep learning model was used to validate the significance of the candidate genes. The accuracy, F1-score, AUC-ROC, and precision of the 100 genes were 83%, 0.86, 0.89, and 0.9, respectively. To discover hidden associations among selected genes, association rule mining was applied. The top 20 genes including the PTBP1, RAB11FIP3, APH1A, and MYD88 were recognized as the most frequent items among severe asthma association rules. The PTBP1 was found to be the most frequent gene associated with severe asthma among those 20 genes. PTBP1 was the gene most frequently associated with severe asthma among candidate genes. Identification of master genes involved in the initiation and development of asthma can offer novel targets for its diagnosis, prognosis, and targeted-signaling therapy.

Pain Education and Knowledge (PEAK) Consensus Guidelines for Neuromodulation: A Proposal for Standardization in Fellowship and Training Programs.

The need to be competent in neuromodulation is and should be a prerequisite prior to completing a fellowship in interventional pain medicine. Unfortunately, many programs lack acceptable candidates for these advanced therapies, and fellows may not receive adequate exposure to neuromodulation procedures. The American Society of Pain and Neuroscience (ASPN) desires to create a consensus of experts to set a minimum standard of competence for neurostimulation procedures, including spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), and peripheral nerve stimulation (PNS). The executive board of ASPN accepted nominations for colleagues with excellence in the subject matter of neuromodulation and physician education. This diverse group used peer-reviewed literature and, based on grading of evidence and expert opinion, developed critical consensus guides for training that all accredited fellowship programs should adopt. For each consensus point, transparency and recusal were used to eliminate bias, and an author was nominated for evidence grading oversight and bias control. Pain Education and Knowledge (PEAK) Consensus Guidelines for Neuromodulation sets a standard for neuromodulation training in pain fellowship training programs. The consensus panel has determined several recommendations to improve care in the United States for patients undergoing neuromodulation. As neuromodulation training in the United States has evolved dramatically, these therapies have become ubiquitous in pain medicine. Unfortunately, fellowship programs and the Accreditation Council for Graduate Medical Education (ACGME) pain program requirements have not progressed training to match the demands of modern advancements. PEAK sets a new standard for fellowship training and presents thirteen practice areas vital for physician competence in neuromodulation.

Triple Therapy with Mometasone/Indacaterol/Glycopyrronium or Doubling the ICS/LABA Dose in GINA Step 4: IRIDIUM Analyses.

INTRODUCTION: GINA guidelines recommend increasing the dose of inhaled corticosteroids (ICS) as a step-up option for patients with inadequately controlled asthma at GINA step 4 [inadequately controlled asthma on medium-dose ICS/long-acting beta-2 agonist (LABA)]. The aim of this study was to compare the efficacy and safety of long-acting muscarinic antagonists (LAMA) add-on to medium-dose ICS/LABA in patients at GINA 2022 step 4. METHODS: This post hoc analysis of the IRIDIUM study evaluated the change from baseline in trough forced expiratory volume (FEV1 ) in patients receiving medium-dose MF/IND/GLY versus high-dose MF/IND and high-dose FLU/SAL at Week 26. Other outcomes included improvement in lung functions [peak expiratory flow (PEF), forced vital capacity (FVC), forced expiratory flow between 25% and 75% of the FVC (FEF)25-75%)], asthma control [Asthma Control Questionnaire (ACQ-7)], responder analysis (≥ 0.5 unit improvement in ACQ-7), and reduction in asthma exacerbations at Weeks 26 and 52. RESULTS: A total of 1930 patients were included in this analysis. Medium-dose MF/IND/GLY improved trough FEV1 versus high-dose MF/IND (Δ 41 mL; 95% CI - 7-90) and high-dose FLU/SAL (Δ 88 mL; 95% CI 39-137) at Week 26 which were sustained until Week 52. Exacerbation rates were 16% lower with medium-dose MF/IND/GLY versus high-dose MF/IND for all (mild, moderate, and severe) exacerbations and 21-30% lower versus high-dose FLU/SAL for all (mild, moderate, and severe), moderate or severe, and severe exacerbations over 52 weeks. Further improvements in other lung functions were observed with medium-dose MF/IND/GLY. No new safety signals were identified. CONCLUSION: Medium-dose MF/IND/GLY improved lung function and reduced asthma exacerbations compared to high-dose ICS/LABA and may be an undervalued option in patients at GINA 2022 step 4. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02571777.

Efficacy of mometasone/indacaterol/glycopyrronium in patients with inadequately controlled asthma with respect to baseline eosinophil count: Post hoc analysis of IRIDIUM study.

BACKGROUND: Baseline characteristics could potentially guide asthma treatments. We evaluated whether baseline eosinophil levels affect the efficacy of mometasone/indacaterol/glycopyrronium (MF/IND/GLY) in patients with inadequately controlled asthma. METHOD: In this post hoc analysis of IRIDIUM study, efficacy of high-dose MF/IND/GLY (160/150/50 µg, once-daily [o.d.]) versus high-dose MF/IND (320/150 µg o.d.) and high-dose fluticasone/salmeterol (FLU/SAL [500/50 µg, twice-daily [b.i.d.]); and efficacy of pooled MF/IND/GLY (160/150/50 µg and 80/150/50 µg) versus pooled MF/IND (320/150 µg and 160/150 µg) was evaluated in patient subgroups with baseline blood eosinophil count of <300 cells/µL or ≥300 cells/µL. RESULTS: Overall, 3065 patients were included. At Week 26, high-dose MF/IND/GLY showed improved trough FEV1 versus high-dose MF/IND (Δ78mL [<300 cells/µL]; Δ54mL [≥300 cells/µL]) and FLU/SAL (Δ112mL [<300 cells/µL]; Δ98mL [≥300 cells/µL]). Similarly, pooled MF/IND/GLY also showed improved trough FEV1 versus pooled MF/IND (Δ75mL [<300 cells/µL]; Δ68mL [≥300 cells/µL]). Over 52 weeks, high-dose MF/IND/GLY reduced the annualized rate of moderate or severe asthma exacerbations by 23% and 10%, severe exacerbations by 31% and 15%, and all exacerbation by 33% and 10% versus high-dose MF/IND for subgroups with <300 cells/µL and ≥300 cells/µL, respectively; and by 33% and 41%, 45% and 42%, 42% and 39% versus FLU/SAL, respectively. Similarly, pooled MF/IND/GLY reduced exacerbations by 22% and 8%, 21% and 7%, 27% and 8%, versus pooled MF/IND, for the respective subgroups. CONCLUSION: MF/IND/GLY showed improvement in lung function and reduction in asthma exacerbations over MF/IND and FLU/SAL independent of baseline eosinophil levels, indicating that eosinophil levels did not affect the efficacy of MF/IND/GLY in patients with inadequately controlled asthma. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02571777 (IRIDIUM).

Chromobacterium haemolyticum infection from hot springs near Yellowstone National Park: a case report.

BACKGROUND: Chromobacterium haemolyticum is a gram-negative anaerobic sporulated rod and was only first identified in 2008. It is very rare in people with only a handful of cases having been diagnosed around the world. CASE PRESENTATION: After suffering a fall near Yellowstone National Park, a white male patient in his 50 s presented to a hospital in Eastern Idaho. With many unexplained symptoms, several changes in patient stability and recovery, over a course of 18 days in the hospital, the infecting organism could not be easily identified. Labs in the hospital, state, and eventually outside of the state were consulted for pathogen identification, which was only accomplished after the patient was discharged. CONCLUSIONS: To our knowledge, this is only the seven reported human infection with Chromobacterium haemolyticum. This bacterium is difficult to identify and may be occur in rural areas without the proper testing facilities to quickly identify the pathogen, which is essential to timely treatment.

Short-term air pollution exposure and exacerbation events in mild to moderate COPD: a case-crossover study within the CanCOLD cohort.

BACKGROUND: Infections are considered as leading causes of acute exacerbations of chronic obstructive pulmonary disease (COPD). Non-infectious risk factors such as short-term air pollution exposure may play a clinically important role. We sought to estimate the relationship between short-term air pollutant exposure and exacerbations in Canadian adults living with mild to moderate COPD. METHODS: In this case-crossover study, exacerbations ('symptom based': ≥48 hours of dyspnoea/sputum volume/purulence; 'event based': 'symptom based' plus requiring antibiotics/corticosteroids or healthcare use) were collected prospectively from 449 participants with spirometry-confirmed COPD within the Canadian Cohort Obstructive Lung Disease. Daily nitrogen dioxide (NO2), fine particulate matter (PM2.5), ground-level ozone (O3), composite of NO2 and O3 (Ox), mean temperature and relative humidity estimates were obtained from national databases. Time-stratified sampling of hazard and control periods on day '0' (day-of-event) and Lags ('-1' to '-6') were compared by fitting generalised estimating equation models. All data were dichotomised into 'warm' (May-October) and 'cool' (November-April) seasons. ORs and 95% CIs were estimated per IQR increase in pollutant concentrations. RESULTS: Increased warm season ambient concentration of NO2 was associated with symptom-based exacerbations on Lag-3 (1.14 (1.01 to 1.29), per IQR), and increased cool season ambient PM2.5 was associated with symptom-based exacerbations on Lag-1 (1.11 (1.03 to 1.20), per IQR). There was a negative association between warm season ambient O3 and symptom-based events on Lag-3 (0.73 (0.52 to 1.00), per IQR). CONCLUSIONS: Short-term ambient NO2 and PM2.5 exposure were associated with increased odds of exacerbations in Canadians with mild to moderate COPD, further heightening the awareness of non-infectious triggers of COPD exacerbations.