Exploring Definitions and Predictors of Severe Asthma Clinical Remission Post-Biologic in Adults.

RATIONALE: There is no consensus on criteria to include in an asthma remission definition in real-life. Factors associated with achieving remission post-biologic-initiation remain poorly understood. OBJECTIVES: To quantify the proportion of adults with severe asthma achieving multi-domain-defined remission post-biologic-initiation and identify pre-biologic characteristics associated with achieving remission which may be used to predict it. METHODS: This was a longitudinal cohort study using data from 23 countries from the International Severe Asthma Registry. Four asthma outcome domains were assessed in the 1-year pre- and post-biologic-initiation. A priori-defined remission cut-offs were: 0 exacerbations/year, no long-term oral corticosteroid (LTOCS), partly/well-controlled asthma, and percent predicted forced expiratory volume in one second ≥80%. Remission was defined using 2 (exacerbations + LTOCS), 3 (+control or +lung function) and 4 of these domains. The association between pre-biologic characteristics and post-biologic remission was assessed by multivariable analysis. MEASUREMENTS AND MAIN RESULTS: 50.2%, 33.5%, 25.8% and 20.3% of patients met criteria for 2, 3 (+control), 3 (+lung function) and 4-domain-remission, respectively. The odds of achieving 4-domain remission decreased by 15% for every additional 10-years asthma duration (odds ratio: 0.85; 95% CI: 0.73, 1.00). The odds of remission increased in those with fewer exacerbations/year, lower LTOCS daily dose, better control and better lung function pre-biologic-initiation. CONCLUSIONS: One in 5 patients achieved 4-domain remission within 1-year of biologic-initiation. Patients with less severe impairment and shorter asthma duration at initiation had a greater chance of achieving remission post-biologic, indicating that biologic treatment should not be delayed if remission is the goal. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Exploring definitions and predictors of response to biologics for severe asthma.

BACKGROUND: Biologic effectiveness is often assessed as 'response', a term which eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging. OBJECTIVE: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response. METHODS: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in 4 asthma outcome domains were assessed in the 1-year period pre- and post-biologic-initiation in patients with predefined level of pre-biologic impairment. Responder cut-offs were: ≥50% reduction in exacerbation rate, ≥50% reduction in long-term oral corticosteroid [LTOCS] daily dose, ≥1 category improvement in asthma control, and ≥100mL improvement in FEV1. Responders were defined using single- and multiple-domains. The association between pre-biologic characteristics and post-biologic-initiation response were examined by multivariable analysis. RESULTS: 2,210 patients were included. Responder rate ranged from 80.7% (n=566/701) for exacerbation-response to 10.6% (n=9/85) for 4-domain-response. Many responders still exhibited significant impairment post-biologic-initiation: 46.7% (n=206/441) of asthma control-responders with uncontrolled asthma pre-biologic still had incompletely-controlled disease post-biologic-initiation. Predictors of response were outcome-dependent. Lung function-responders were more likely to have higher pre-biologic FeNO (OR:1.20 for every 25ppb increase), and shorter asthma duration (OR:0.81, for every 10-year increase in duration). Higher BEC and presence of T2-related comorbidities were positively associated with higher odds of meeting LTOCS-, control- and lung function-responder criteria. CONCLUSION: Our findings underscore the multi-modal nature of 'response', show that many responders experience residual symptoms post-biologic-initiation, and that predictors of response vary according to outcome assessed

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

RATIONALE: Previous studies investigating comorbidity impact on biologic effectiveness have been relatively small, of short duration, and have not compared biologic classes. OBJECTIVES: To determine the association between T2-related comorbidities and biologic effectiveness in adults with severe asthma (SA). METHODS: This cohort study used International Severe Asthma Registry data (n=21 countries, 2017-2022) to quantify pre- to post-biologic change for four outcomes (annual asthma exacerbation rate, % predicted FEV1 (ppFEV1), asthma control, and long-term oral corticosteroid daily dose [LTOCS]) in patients with/without allergic rhinitis (AR), chronic rhinosinusitis +/- nasal polyps (CRS+/-NP), NP, or eczema/atopic dermatitis (AD). MAIN RESULTS: Of 1765 patients, 1257, 421, and 87 initiated anti-IL-5/5R, anti-IgE, and anti-IL-4/13 therapies, respectively. In general, pre- to post-biologic improvements were noted in all four asthma outcomes assessed, irrespective of comorbidity status. However, patients with comorbid CRS+/-NP experienced 23% (95% CI 10-35%, p<0.001) fewer exacerbations/year and had 59% (95% CI: 26-102%, p<0.001) higher odds of better post-biologic control than those without CRS+/-NP. Similar estimates were noted for those with comorbid NP (22% less exacerbations and 56% higher odds of better post-biologic control). Patients with SA and CRS+/-NP had an additional ppFEV1 improvement of 3.2% (95% CI: 1.0-5.3; p=0.004), a trend that was also noted in those with comorbid NP. The presence of AR or AD were not associated with pre- to post-biologic effect for any outcome assessed. CONCLUSIONS: These findings highlight the importance of systematic comorbidity evaluation. The presence of CRS+/-NP or NP may be considered a predictor of biologic effectiveness in patients with 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 GINA as 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. Thirty comorbidities were identified and categorized a priori as either (1) potentially T2-related, (2) potentially oral corticosteroid (OCS)-related or (3) mimicking/aggravating asthma. The association between comorbidities and asthma-related outcomes was investigated using multivariable models adjusted for country, age at enrollment, and sex. RESULTS: Of 11,821 patients, 69%, 67%, and 55% had ≥1 potentially T2-related, potentially OCS-related, or mimicking/aggravating comorbidities, respectively; 57% had ≥3 comorbidities, and 33% had comorbidities in all three categories. Patients with allergic rhinitis (AR), nasal polyposis (NP), and chronic rhinosinusitis (CRS) experienced 1.12- (p=0.003), 1.16- (p<0.001) and 1.29-times (p<0.001) more exacerbations/year, respectively, than those without. Patients with NP and CRS were 40% and 46% more likely (p<0.001), respectively, to have received long-term (LT) OCS. All assessed potential OCS-related comorbidities (except obesity) were associated with greater likelihood of LTOCS use (ORs: 1.23-2.77) and, except for dyslipidemia, with greater likelihood of uncontrolled asthma (ORs: 1.29-1.68). All mimicking/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 COPD) with increased likelihood of LTOCS use (ORs: 1.37-1.57). Greater number of comorbidities was associated with worse outcome. CONCLUSION: In a global study, comorbidity or multimorbidity is reported in most adults with severe asthma and is associated with poorer asthma-related outcomes