Modifications in Lipid Levels Are Independent of Serum TNF-α in Rheumatoid Arthritis: Results of an Observational 24-Week Cohort Study Comparing Patients Receiving Etanercept Plus Methotrexate or Methotrexate as Monotherapy

Objective. To compare the modifications in lipids between patients with rheumatoid arthritis (RA) receiving etanercept plus methotrexate (ETA + MTX) versus methotrexate (MTX) and their relationship with serum levels of tumor necrosis factor-alpha (TNF-α). Methods. In an observational cohort study, we compared changes in lipid levels in patients receiving ETA + MTX versus MTX in RA. These groups were assessed at baseline and at 4 and 24 weeks, measuring clinical outcomes, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and TNF-α. Results. Baseline values for lipid levels were similar in both groups. HDL-C levels increased significantly only in the ETA + MTX group (from 45.5 to 50.0 mg/dL at 4 weeks, a 10.2% increase, P<0.001, and to 56.0 mg/dL at 24 weeks, a 25.1% increase, P<0.001), while other lipids underwent no significant changes. ETA + MTX also exhibited a significant increase in TNF-α (44.8 pg/mL at baseline versus 281.4 pg/mL at 24 weeks, P<0.001). The MTX group had no significant changes in lipids or TNF-α. Significant differences in HDL-C between groups were observed at 24 weeks (P=0.04) and also in TNF-α  (P=0.01). Conclusion. HDL-C levels increased significantly following treatment with ETA + MTX, without a relationship with decrease of TNF-α

In the (sub)tropics Allergic Rhinitis and Its Impact on Asthma classification of allergic rhinitis is more useful than perennial-seasonal classification

Background: Two different allergic rhinitis (AR) symptom phenotype classifications exist. Treatment recommendations are based on intermittent-persistent (INT-PER) cataloging, but clinical trials still use the former seasonal AR-perennial AR (SAR-PAR) classification. This study was designed to describe how INT-PER, mild-moderate/severe and SAR-PAR of patients seen by allergists are distributed over the different climate zones in a (sub) tropical country and how these phenotypes relate to allergen sensitization patterns. Methods: Six climate zones throughout Mexico were determined, based on National Geographic Institute (Instituto Nacional de Estadistica y Geografia) data. Subsequent AR patients (2-68 years old) underwent a blinded, standardized skin-prick test and filled out a validated questionnaire phenotyping AR. Results: Five hundred twenty-nine subjects participated in this study. In the tropical zone with 87% house-dust mite sensitization, INT (80.9%; p < 0.001) and PAR (91%; p = 0.04) were more frequent than in the subtropics. In the central high-pollen areas, there was less moderate/severe AR (65.5%; p < 0.005). Frequency of comorbid asthma showed a clear north-south gradient, from 25% in the dry north to 59% in the tropics (p < 0.005). No differences exist in AR cataloging among patients with different sensitization patterns, with two minor exceptions (more PER in tree sensitized and more PAR in mold positives; p < 0.05). Conclusion: In a (sub) tropical country the SAR-PAR classification seems of limited value and bears poor relation with the INT-PER classification. INT is more frequent in the tropical zone. Because PER has been shown to relate to AR severity, clinical trials should select patients based on INT-PER combined with the severity cataloging because these make for a better treatment guide than SAR-PAR

In the (Sub)Tropics Allergic Rhinitis and Its Impact on Asthma Classification of Allergic Rhinitis is More Useful than Perennial–Seasonal Classification

Background: Two different allergic rhinitis (AR) symptom phenotype classifications exist. Treatment recommendations are based on intermittent-persistent (INT-PER) cataloging, but clinical trials still use the former seasonal AR-perennial AR (SAR-PAR) classification. This study was designed to describe how INT-PER, mild-moderate/severe and SAR-PAR of patients seen by allergists are distributed over the different climate zones in a (sub) tropical country and how these phenotypes relate to allergen sensitization patterns. Methods: Six climate zones throughout Mexico were determined, based on National Geographic Institute (Instituto Nacional de Estadistica y Geografia) data. Subsequent AR patients (2-68 years old) underwent a blinded, standardized skin-prick test and filled out a validated questionnaire phenotyping AR. Results: Five hundred twenty-nine subjects participated in this study. In the tropical zone with 87% house-dust mite sensitization, INT (80.9%; p < 0.001) and PAR (91%; p = 0.04) were more frequent than in the subtropics. In the central high-pollen areas, there was less moderate/severe AR (65.5%; p < 0.005). Frequency of comorbid asthma showed a clear north-south gradient, from 25% in the dry north to 59% in the tropics (p < 0.005). No differences exist in AR cataloging among patients with different sensitization patterns, with two minor exceptions (more PER in tree sensitized and more PAR in mold positives; p < 0.05). Conclusion: In a (sub) tropical country the SAR-PAR classification seems of limited value and bears poor relation with the INT-PER classification. INT is more frequent in the tropical zone. Because PER has been shown to relate to AR severity, clinical trials should select patients based on INT-PER combined with the severity cataloging because these make for a better treatment guide than SAR-PAR

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially