Nemolizumab with concomitant topical therapy in adolescents and adults with moderate-to-severe atopic dermatitis (ARCADIA 1 and ARCADIA 2): results from two replicate, double-blind, randomised controlled phase 3 trials.

BACKGROUND: Nemolizumab, an interleukin (IL)-31 receptor subunit α antagonist, inhibits the IL-31 pathway of itch and skin inflammation in atopic dermatitis. Two international phase 3 studies were done to assess the efficacy and safety of nemolizumab in atopic dermatitis. In this Article we report results for the 16-week initial treatment period of both trials. METHODS: ARCADIA 1 and ARCADIA 2 were identical 48-week randomised, double-blind, placebo-controlled phase 3 trials in adult and adolescent participants (aged ≥12 years) with moderate-to-severe atopic dermatitis, associated pruritus, and inadequate response to topical steroids. Participants were enrolled from 281 clinics, hospitals, and academic centres in 22 countries across both trials, and were randomly assigned (2:1) to receive nemolizumab 30 mg subcutaneously (baseline loading dose 60 mg) or matching placebo once every 4 weeks with background topical corticosteroids (TCS) with or without topical calcineurin inhibitors (TCI; ie, TCS-TCI background treatment). Randomisation was done via interactive response technology and stratified by baseline disease and pruritus severity. Study staff and participants were masked throughout the study, with outcome assessors masked until database lock. Coprimary endpoints at week 16 post-baseline were Investigator's Global Assessment (IGA) success (score of 0 [clear skin] or 1 [almost clear skin] with a ≥2-point improvement from baseline) and at least 75% improvement in Eczema Area and Severity Index score from baseline (EASI-75 response). Outcome rates were compared between groups with the Cochran-Mantel-Haenszel test adjusting for randomisation strata. The key secondary endpoints were the proportion of participants with Peak Pruritus Numerical Rating Scale (PP-NRS) score improvement of at least 4 points at weeks 1, 2, 4, and 16; PP-NRS score below 2 at weeks 4 and 16; Sleep Disturbance Numerical Rating Scale score improvement of at least 4 points at week 16; EASI-75 response plus PP-NRS score improvement of at least 4 points at week 16; and IGA success plus PP-NRS score improvement of at least 4 points at week 16. Efficacy analyses were done on an intention-to-treat basis; safety analyses included all participants who received one dose of nemolizumab or placebo. Both studies are completed (ClinicalTrials.gov: ARCADIA 1, NCT03985943 and ARCADIA 2, NCT03989349). FINDINGS: Between Aug 9, 2019, and Nov 2, 2022, 1728 participants were enrolled across both trials: 1142 were allocated to nemolizumab plus TCS-TCI (620 in ARCADIA 1 and 522 in ARCADIA 2) and 586 to placebo plus TCS-TCI (321 in ARCADIA 1 and 265 in ARCADIA 2). ARCADIA 1 included 500 (53%) male participants and 441 (47%) female participants, and ARCADIA 2 included 381 (48%) male participants and 406 (52%) female participants. Mean age ranged from 33·3 (SD 15·6) years to 35·2 (17·0) years across the treatment groups. Both trials met the coprimary endpoints; at week 16, a greater proportion of participants receiving nemolizumab plus TCS-TCI versus placebo plus TCS-TCI had IGA success (ARCADIA 1: 221 [36%] of 620 vs 79 [25%] of 321, adjusted percentage difference 11·5% [97·5% CI 4·7-18·3], p=0·0003; ARCADIA 2: 197 [38%] of 522 vs 69 [26%] of 265, adjusted difference 12·2% [4·6-19·8], p=0·0006) and an EASI-75 response (ARCADIA 1: 270 [44%] vs 93 [29%], adjusted difference 14·9% [7·8-22·0], p<0·0001; ARCADIA 2: 220 [42%] vs 80 [30%], adjusted difference 12·5% [4·6-20·3], p=0·0006). Significant benefits were observed with nemolizumab for all key secondary endpoints including improvement in itch, as early as week 1, and sleep improvement by week 16. The safety profile was similar between nemolizumab plus TCS-TCI and placebo plus TCS-TCI. In the safety sets, 306 (50%) of 616 participants (ARCADIA 1) and 215 (41%) of 519 participants (ARCADIA 2) who received nemolizumab plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in six [1%] and 13 [3%], respectively); and 146 (45%) of 321 (ARCADIA 1) and 117 (44%) of 263 (ARCADIA 2) who received placebo plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in four [1%] and three [1%], respectively). Ten serious treatment-emergent adverse events possibly related to nemolizumab were reported in five (1%) participants in ARCADIA 2. No deaths occurred. INTERPRETATION: Nemolizumab plus TCS-TCI was efficacious and showed statistically and clinically significant improvements in inflammation and itch in adults and adolescents with moderate-to-severe atopic dermatitis. Nemolizumab might offer a valuable extension of current therapies if approved. FUNDING: Galderma.

Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks.

BACKGROUND: Remibrutinib (LOU064), an oral, highly selective Bruton tyrosine kinase inhibitor, offers fast disease control in patients with chronic spontaneous urticaria (CSU) who remain symptomatic despite treatment with second-generation H1 antihistamines. It is currently in phase 3 development for CSU. OBJECTIVE: We sought to evaluate long-term safety and efficacy of remibrutinib in patients with CSU inadequately controlled with H1 antihistamines. METHODS: In this phase 2b extension study, patients who completed the core study and had a weekly Urticaria Activity Score (UAS7) ≥16 at the beginning of the extension study received remibrutinib 100 mg twice daily for 52 weeks. The primary objective was to assess long-term safety and tolerability. Key efficacy end points included change from baseline in UAS7 and proportion of patients with complete response to treatment (UAS7 = 0) and well-controlled disease (UAS7 ≤6) at week 4 and over 52 weeks. RESULTS: Overall, 84.3% (194/230) of patients entered the treatment period and received ≥1 doses of remibrutinib. The overall safety profile of remibrutinib was comparable between the extension and core studies. Most treatment-emergent adverse events were mild to moderate and considered unrelated to remibrutinib by investigators. The 3 most common treatment-emergent adverse events by system organ class were infections (30.9%), skin and subcutaneous tissue (26.8%), and gastrointestinal disorders (16.5%). At week 4 and 52, mean ± SD change from baseline in UAS7 was -17.6 ± 13.40 and -21.8 ± 10.70; UAS7 = 0 (as observed) was achieved in 28.2% and 55.8% and UAS7 ≤6 (as observed) was achieved in 52.7% and 68.0% of patients, respectively. CONCLUSIONS: Remibrutinib demonstrated a consistent favorable safety profile with fast and sustained efficacy for up to 52 weeks in patients with CSU.

Remibrutinib, a novel BTK inhibitor, demonstrates promising efficacy and safety in chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is inadequately controlled in many patients and greatly affects quality of life. Remibrutinib, a highly selective, oral, novel covalent Bruton tyrosine kinase inhibitor, might be effective in CSU. OBJECTIVE: This first-in-patient trial aimed to evaluate the efficacy and safety of remibrutinib in CSU treatment and characterize the dose-response. METHODS: This randomized, double-blind, placebo-controlled, phase 2b dose-finding trial evaluated remibrutinib (12 weeks) in patients inadequately controlled with second-generation H1-antihistamines, with at least moderately active CSU, with or without prior anti-IgE treatment (NCT03926611). Patients received remibrutinib 10 mg once daily, 35 mg once daily, 100 mg once daily, 10 mg twice daily, 25 mg twice daily, 100 mg twice daily, or placebo (1:1:1:1:1:1:1 ratio). The main end points were weekly Urticaria Activity Score change from baseline at week 4 and safety. RESULTS: Overall, 311 patients were randomized. Reduced symptom score was observed for all remibrutinib doses from week 1 until week 12, with weekly Urticaria Activity Score change from baseline at week 4: -19.1 (10 mg once daily), -19.1 (35 mg once daily), -14.7 (100 mg once daily), -16.0 (10 mg twice daily), -20.0 (25 mg twice daily), -18.1 (100 mg twice daily), and -5.4 for placebo (nominal P < .0001 for all doses vs placebo). Most adverse events were mild or moderate, with no dose-dependent pattern. CONCLUSION: Remibrutinib was highly effective in the treatment of CSU over the entire dose range, with a rapid onset of action and a favorable safety profile.

Metoprolol for the Prevention of Acute Exacerbations of COPD.

BACKGROUND: Observational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease (COPD), but these findings have not been confirmed in randomized trials. METHODS: In this prospective, randomized trial, we assigned patients between the ages of 40 and 85 years who had COPD to receive either a beta-blocker (extended-release metoprolol) or placebo. All the patients had a clinical history of COPD, along with moderate airflow limitation and an increased risk of exacerbations, as evidenced by a history of exacerbations during the previous year or the prescribed use of supplemental oxygen. We excluded patients who were already taking a beta-blocker or who had an established indication for the use of such drugs. The primary end point was the time until the first exacerbation of COPD during the treatment period, which ranged from 336 to 350 days, depending on the adjusted dose of metoprolol. RESULTS: A total of 532 patients underwent randomization. The mean (±SD) age of the patients was 65.0±7.8 years; the mean forced expiratory volume in 1 second (FEV1) was 41.1±16.3% of the predicted value. The trial was stopped early because of futility with respect to the primary end point and safety concerns. There was no significant between-group difference in the median time until the first exacerbation, which was 202 days in the metoprolol group and 222 days in the placebo group (hazard ratio for metoprolol vs. placebo, 1.05; 95% confidence interval [CI], 0.84 to 1.32; P = 0.66). Metoprolol was associated with a higher risk of exacerbation leading to hospitalization (hazard ratio, 1.91; 95% CI, 1.29 to 2.83). The frequency of side effects that were possibly related to metoprolol was similar in the two groups, as was the overall rate of nonrespiratory serious adverse events. During the treatment period, there were 11 deaths in the metoprolol group and 5 in the placebo group. CONCLUSIONS: Among patients with moderate or severe COPD who did not have an established indication for beta-blocker use, the time until the first COPD exacerbation was similar in the metoprolol group and the placebo group. Hospitalization for exacerbation was more common among the patients treated with metoprolol. (Funded by the Department of Defense; BLOCK COPD ClinicalTrials.gov number, NCT02587351.).

Ability of Exhaled Nitric Oxide to Discriminate for Airflow Obstruction Among Frequent Exacerbators of Clinically Diagnosed Asthma.

OBJECTIVE: Fraction of exhaled nitric oxide (FENO) has been proposed as a non-invasive biomarker for allergic inflammation seen in asthma. Many asthmatics in clinical practice have never had spirometry and recent data report misdiagnoses in patients with physician diagnosed (PD) asthma. The aim of this study was to assess the ability of FENO to discriminate between those with and without airflow obstruction (AO) among patients with PD-asthma. METHODS: Frequent exacerbators of PD-asthma (with 2 or more asthma exacerbations leading to emergency room visit or hospitalization within last 12 months) were enrolled. All patients underwent diagnostic evaluations including spirometry, FENO testing and serum immunoglobulin (IgE) and eosinophils. Serial spirometry and methacholine challenge testing (MCT) were performed as indicated. AO was defined by a decreased FEV1/FVC ratio (< 70% and/or < LLN), or a positive MCT. RESULTS: Of the 222 patients with PD-asthma, AO was found in 136 (vs. 86 without AO). 81.6% of patients with AO and 66.2% without AO completed FENO testing. There was no significant difference in the mean FENO levels among patients with or without AO (40.8 vs. 30.4 ppb, P = 0.10). Likewise, there was no difference in the serum IgE levels and serum eosinophils. CONCLUSIONS: Our analyses suggest that FENO levels do not help discriminate between those with and without AO in patients with PD-asthma. Patients who experience symptoms of asthma may have elevated FENO levels above the suggested cut points of 20-25 ppb. Objective confirmation of AO should be considered in all patients with PD-asthma, irrespective of FENO levels.

Misdiagnosis Among Frequent Exacerbators of Clinically Diagnosed Asthma and COPD in Absence of Confirmation of Airflow Obstruction.

PURPOSE: Clinical diagnosis of severe asthma and chronic obstructive lung disease (COPD) remains a challenge and often flawed with lack of objective confirmation of airflow obstruction (AO). Misdiagnosis of asthma and COPD has been reported in stable disease, data are non-existent in frequent exacerbators. We investigated misdiagnosis and its predictors in frequent exacerbators. METHODS: The cohort comprised of frequent severe exacerbators (requiring ≥2 emergency room (ER) visits or hospitalizations) of physician diagnosed (PD)-asthma and PD-COPD. All patients underwent a rigorous diagnostic algorithm over a follow-up period of 10 ± 6 months. Two board-certified pulmonologists ascertained final diagnosis. Patients with persistent absence of AO were identified to have misdiagnosis. Multivariate logistic regression analyses were used to identify predictors of misdiagnoses. RESULTS: Among 333 frequent exacerbators analyzed (171 patients with PD-asthma, 162 with PD-COPD, mean annual exacerbations 3.4 ± 2.8), 24 % of patients had a baseline post-bronchodilator spirometry. Misdiagnosis was found in 26 % (87 of 333) of patients. Another 12 % (41 of 333) of patients had obstructive lung diseases other than asthma and COPD. Independent risk factors for misdiagnosis were spirometry underutilization (PD-asthma: OR = 2.8, 95 % CI 1.16-6.78, p = 0.02 and PD-COPD: OR = 10.7, 95 % CI 2.05-56.27, p = 0.005) and pack years of smoking (PD-COPD: OR = 1.05, 95 % CI 1.01-1.11, p = 0.03). CONCLUSIONS: Objective confirmation of AO is essential in preventing misdiagnosis in frequent severe exacerbators of clinically diagnosed asthma and COPD, a third of whom have neither. Spirometry utilization is strongly associated with a reduced risk of misdiagnosis. Smoking is associated with increased risk of misdiagnosis in severe COPD, but not asthma.

Long-term safety and efficacy of cipaglucosidase alfa plus miglustat in individuals living with Pompe disease: an open-label phase I/II study (ATB200-02).

Cipaglucosidase alfa plus miglustat (cipa + mig) is a novel, two-component therapy for Pompe disease. We report data from the Phase I/II ATB200-02 study for up to 48 months of treatment. Four adult cohorts, including one non-ambulatory ERT-experienced (n = 6) and three ambulatory cohorts, (two enzyme replacement therapy [ERT]-experienced cohorts [2-6 years (n = 11) and ≥ 7 years (n = 6)]), one ERT-naïve cohort (n = 6), received 20 mg/kg intravenous-infused cipa plus 260 mg oral mig biweekly. Change from baseline (CFBL) for multiple efficacy endpoints at 12, 24, 36, and 48 months, pharmacodynamics, pharmacokinetics, safety, and immunogenicity data were assessed. Six-minute walking distance (% predicted) improved at 12, 24, 36, and 48 months: pooled ambulatory ERT-experienced cohorts, mean(± standard deviation [SD]) CFBL: 6.1(± 7.84), n = 16; 5.4(± 10.56), n = 13; 3.4(± 14.66), n = 12; 5.9(± 17.36), n = 9, respectively; ERT-naïve cohort: 10.7(± 3.93), n = 6; 11.0(± 5.06), n = 6; 9.0(± 7.98), n = 5; 11.7(± 7.69), n = 4, respectively. Percent predicted forced vital capacity was generally stable in ERT-experienced cohorts, mean(± SD) CFBL - 1.2(± 5.95), n = 16; 1.0(± 7.96), n = 13; - 0.3(± 6.68), n = 10; 1.0(± 6.42), n = 6, respectively, and improved in the ERT-naïve cohort: 3.2(± 8.42), n = 6; 4.7(± 5.09), n = 6; 6.2(± 3.35), n = 5; 8.3(± 4.50), n = 4, respectively. Over 48 months, CK and Hex4 biomarkers improved in ambulatory cohorts. Overall, cipa + mig was well tolerated with a safety profile like alglucosidase alfa. ATB200-02 results show the potential benefits of cipa + mig as a long-term treatment option for Pompe disease. Trial registration number: NCT02675465 January 26, 2016.

Lung volume abnormalities and its correlation to spirometric and demographic variables in adult asthma.

BACKGROUND: Presence of airflow obstruction in asthma has been based on a fixed FEV1(forced expiratory volume at 1 second)/FVC (forced vital capacity) ratio abnormality. The accuracy of FEV1/FVC ratio in diagnosing airflow obstruction remains controversial. Lung volume abnormalities have been observed in severe asthma. We utilized simultaneously measured spirometry and lung volume to determine the utility of residual volume (RV)/total lung capacity (TLC) ratio in diagnosing airflow obstruction and to identify predictors of abnormal RV in asthmatic subjects. METHODS: Data from physician-diagnosed asthmatics referred for lung function tests were collected retrospectively. Patient demographics and lung function data were analyzed using general linear modeling. RESULTS: Of the 321 subjects, 221 were female (69%). The ethnicity was Caucasian in 157 (49%), Hispanic in 131 (41%), and African-American in 33 (10%). The percentage of subjects with FEV(1)/FVC ratio <70%, FEV(1)-predicted <80%, and FEF25-75% <65% were 25%, 25%, and 38%, respectively. Fifty-two and fifty-seven percent of the patients had abnormal residual volume and abnormal RV/TLC ratio, respectively. A significant bronchodilator response was observed in 32% of the patients. A positive correlation was observed between RV to age (r = 0.4) and height (r = 0.3). A negative correlation was observed between RV to FEF25-75% (r = 0.5) and body weight (r = 0.07). There was no significant correlation between FEV1 reversibility and residual volume (r = 0.1). RV correlated significantly better with FEF25-75% (r(2) = 0.25) than FEV(1) (r(2) = 0.16). CONCLUSION: A significant proportion of asthmatic patients have elevated residual volume and abnormal RV/TLC ratio in the presence of normal FEV1/FVC ratio and absence of significant bronchodilator response. The clinical significance of these findings in asthma needs further prospective study.

A game theory data science-based mechanism for licensed pharmaceutical products concerning their deterioration: a case of a micro, small, and medium enterprise in Iran.

One of the main characteristics of health systems and pharmaceutical supply chains is their significant costs in the public sector, which has forced governments and companies active in this field to find ways to reduce costs. In this paper, the deterioration of imported pharmaceutical items is investigated as one of the challenges of the supply chain of pharmaceutical firms. Specifically, the micro, small medium enterprise (MSME), and a collaborative strategy to reduce its costs is presented. The technical solution of the cooperative strategy is the formation of a partnership alliance between the foreign patent holder of brand drugs and a domestic manufacturer through an exclusive license contract in the local country. This leads to a significant reduction of costs in the distribution network of the pharmaceutical supply chain. On the other hand, supply chain management techniques in the cooperative strategy provide the necessary motivation for its practical implementation by splitting fair profits between producers and other members, namely local government, distributors, and pharmacies. For these purposes, a cooperative game theory-based contract is utilized to set the parameters of the license agreement, and then a profit-sharing mechanism is introduced that splits the benefits of cooperation among the supply chain members based on their afforded costs. The most important contribution of the current research is to propose an integrated framework that combines the logistics network models, valuation methods, and profit split mechanisms that embody more facts from real-world problems than separate models in this regard in previous studies. Moreover, results of the proposed strategy in the supply chain of a drug for thalassemia patients in Iran indicate the effectiveness of the proposed strategy in reducing costs and deterioration. Further, it is shown that the higher the ordering costs of the imported drugs, the lower the market share of the patent holder, and the lower the financing expenses of the cooperative alliance, the more efficient is the proposed strategy.

Sustainability performance evaluation of the E-waste closed-loop supply chain with the SCOR model.

From a sustainability perspective, the performance of a company's supply chain will be satisfactory when it has reached in all aspects a desirable eco-environmentally friendly level. Assessing the sustainability performance in the closed-loop e-waste supply chain becomes vital because its activities are primarily targeted towards sustainability goals related to the process of production, supply, recycling, and disposal of electrical components. This study evaluates the performance of e-waste supply chain sustainability and identifies its performance indicators as a framework for evaluating supply chain performance using the Best-Worst Method (BWM), which is a multi-criteria decision-making (MCDM) approach. For this, the supply chain operations reference (SCOR) model is considered the basic performance evaluation reference. Moreover, through reviewing the literature, the complementary indicators of this model, especially in terms of sustainability, are added to the performance evaluation indices using the Nominal Group Technique (NGT). After specifying and forming a performance evaluation hierarchy, the BWM method is used to determine the criteria score. The results of implementing the framework on some well-known supply chains in New Zealand indicate that the attributes of "Costs," "Quality," and "GreenScor" are crucial for achieving high performance, while in this developed country, there is less concern about social issues.

COVID19 epidemic outbreak: operating rooms scheduling, specialty teams timetabling and emergency patients' assignment using the robust optimization approach.

The health care system is characterized by limited resources, including the physical facilities as well as skilled human resources. Due to the extensive fixed cost of medical facilities and the high specialization required by the medical staff, the problem of resource scarcity in a health care supply chain is much more acute than in other industries. In the pandemic of the Coronavirus, where medical services are the most important services in communities, and protective and preventive guidelines impose new restrictions on the system, the issue of resource allocation will be more complicated and significantly affect the efficiency of health care systems. In this paper, the problem of activating the operating rooms in hospitals, assigning active operating rooms to the COVID-19 and non-COVID-19 patients, assigning specialty teams to the operating rooms and assigning the elective and emergency patients to the specialty teams, and scheduling their operations is studied by considering the new constraints of protective and preventive guidelines of the Coronavirus. To address these issues, a mixed-integer mathematical programming model is proposed. Moreover, to consider the uncertainty in the surgery duration of elective and emergency patients, the stochastic robust optimization approach is utilized. The proposed model is applied for the planning of operating rooms in the cardiovascular department of a hospital in Iran, and the results highlight the role of proper management in supplying sufficient medical resources effectively to respond to patients and scheduled surgical team to overcome the pressure on hospital resources and medical staff results from pandemic conditions.

Histopathological spectrum of duodenal polyps in a retrospective ten-year study.

INTRODUCTION AND AIMS:  Duodenal polyps are rare in patients undergoing upper gastrointestinal endoscopy. The present study is an experience of the histopathological spectrum of the duodenal polyps and its correlation with the clinical and endoscopic findings in a tertiary care centre. MATERIALS AND METHODS: The present study is a 10-year retrospective study from the year 2011 to 2020. All the relevant clinical, endoscopic and radiologic findings were retrieved from the hospital medical records. Old histopathology slides were restained, and wherever required, special stains and immunohistochemistry (IHC) were performed. All the cases were reviewed. The present study mainly included descriptive statistics with categorical and continuous variables. RESULTS: Total 81 cases of duodenal polyps were studied in the period of 10 years. The median age was 48 years. Male: female ratio was 2.2:1. The most common presenting system was abdominal pain. We experienced both solitary and multiple polyps. The majority of the duodenal polyps were non-neoplastic, with unremarkable mucosa or inflammatory type. Unlike previous studies the most common site for the hyperplastic polyp in the present study was the first part of the duodenum. Among the neoplastic polyps, adenomatous polyp was the most common type. Contrary to the previous studies, our study showed the first part of the duodenum as the most common site for the sporadic nonampullary adenomatous duodenal polyps. Of the rare entities, we encountered a single case each of lipomatous polyp and gangliocytic paraganglioma. Among the syndromes we encountered two cases of Peutz-Jeghers syndrome and one case of familial adenomatous polyp in our study population.CONCLUSION Duodenal polyps are a rare finding on endoscopic examinations, though most of them are non-neoplastic in nature, vigilant examination under the microcope is required to rule out any neoplastic pathology and identify the risk of malignancy.

Residual Volume Responsiveness Testing May Improve the Detection of Reversible Airway Obstruction in Asthma.

BACKGROUND: Residual volume responsiveness to bronchodilator administration has been observed in subjects with chronic obstructive pulmonary disease. However, the prevalence of residual volume (RV) responsiveness has not been formally studied in asthma. OBJECTIVE: To identify the prevalence and magnitude of RV responsiveness in asthma. METHODS: Physician-diagnosed adult subjects with asthma on treatment for >12 months were prospectively recruited to perform spirometry and measurement of lung volumes using body plethysmography before and after administration of 360 µg of albuterol. RESULTS: Among 120 subjects, 76% were women. The ethnic composition was 64% Caucasian, 32% Hispanic, and 13% African American. The mean age was 52 ± 15 years. The mean duration of asthma was 16 ± 15 years. The mean RV% responsiveness was -7.74 ± 14. Whereas patients with the lowest baseline forced expiratory volume in 1 second (FEV1) value showed the highest mean responsiveness (P = .001), the baseline RV value had minimal influence on RV responsiveness. Using -7.74% to define significant RV responsiveness, and ≥12% and ≥200 mL to define significant FEV1 responsiveness, more subjects showed isolated RV responsiveness (37%) compared with 6% with isolated FEV1 responsiveness and 14% with both FEV1 and RV responsiveness (P = .04). There was a minimal correlation between FEV1 responsiveness and RV responsiveness (r = 0.17, P = .06). The RV responsiveness was significantly associated with the wheeze score (P = .006) and dyspnea score (P = .029). CONCLUSION: The addition of RV responsiveness testing to spirometry based responsiveness testing can improve the identification of reversible airway obstruction in asthma. RV responsiveness may be useful in monitoring symptoms associated with air trapping in asthma.

Effectiveness of C1-INH therapy in angiotensin converting enzyme inhibitor induced angioedema.

INTRODUCTION: Angiotensin Converting Enzyme Inhibitors (ACEI) are a common cause of Emergency Room presentation for angioedema. Although no treatment guidelines exist, C1 esterase inhibitor concentrate (C1-INH) is used on an off label basis for management of ACEI acquired angioedema (ACEI AAE). OBJECTIVE: To evaluate the efficacy of C1-INH in management of ACEI AAE at our local centers. RESULTS: Nine patients, from 3 academic sites, were identified through Allergy Service consultation data and records from Diagnostic Services Manitoba, Canada from 2010-2020. The majority of the patients (n = 8/9) required endotracheal intubation prior to the initiation of C1-INH. Overall, approximately 56% of patients (n = 5/9) had resolution of angioedema ranging between 12 and 17 h, with a median time of 13.5 h, and no recurrence after the administration of C1-INH concentrate. One patient had transient symptom resolution in 14 h, however, recurrence of angioedema required re-intubation. The remainder of patients (n = 4/9), had resolution of angioedema between 22 and 72 h, with a median time of 33.75 h. CONCLUSION: Our findings demonstrate continued ambivalence of the efficacy and role of C1-INH concentrate in the treatment of ACEI AAE, secondary to multiple uncontrolled confounding factors. Further research into characterizing a subgroup of intubated patients in our study that responded to C1-INH concentrate needs to be completed.

Homochirality in life: two equal runners, one tripped.

Strong arguments can be found in the literature addressed to the question of the origin of homochirality in life, supporting the hypothesis that primordial life could have evolved in both homochiral forms and that early on when life was still rarely found, random events led to the survival of only one of these living mirror images. This proposal is an alternative to the generally accepted view that small enantiomeric excesses of biologically important molecules were amplified to homochirality prior to life's origin. Acceptance of the possibility of "two equal runners" leads to the importance of research investigations on routes to formation of ensembles of racemic mixtures of isotactic biologically interesting polymers, supramolecular entities and aggregates.

Comparison of antimicrobial efficacy of aqueous ozone, green tea, and normal saline as irrigants in pulpectomy procedures of primary teeth.

AIM: Sodium hypochlorite, though considered an ideal root canal irrigant, cannot be used at required concentrations in children, due to its undesirable effects. Hence, it is imperative to search for an ideal root canal irrigant to avoid these undesirable effects which we hope to achieve with this study. The antimicrobial efficacy of aqueous ozone, green tea, and normal saline as irrigants in pulpectomy procedures of the primary teeth has been compared. MATERIALS AND METHODS: Sixty patients between 4 and 8 years of age with a single-rooted deciduous tooth indicated for pulpectomy were included. The infected teeth were randomly allocated to one of the three treatment groups based on the irrigating agents used, namely normal saline, green tea extract, or ozonated water. Specimens for anaerobic culture were collected three times from the teeth: before irrigation, after initial irrigation, and on the 3rd day after final irrigation. RESULTS AND CONCLUSION: Mean colony forming unit (CFU) count after both initial and final irrigation with ozonated water was significantly lower when compared with green tea and normal saline. Further, it was observed that the mean CFU count with green tea was significantly lower than the counts obtained with normal saline on the 3rd day after final irrigation. Hence, both ozonated water and green tea could be considered a good alternative to conventional root canal irrigants in the primary teeth. Larger sample sizes with a larger variety of irrigants are recommended.