Comparison of the Yield of Different Diagnostic Procedures for Cellular Differentiation and Genetic Profiling of Non–Small-Cell Lung Cancer

IntroductionAs treatments for non–small-cell lung cancer (NSCLC) become personalized, cellular and molecular differentiation of the tumor is becoming the standard of care. Our objective is to compare the yield of different diagnostic procedures for cellular differentiation of NSCLC and analysis of epidermal growth factor receptor (EGFR) mutation.MethodsWe evaluated all patients diagnosed with NSCLC from January 2004 to September 2010 at the Jewish General Hospital, Montreal. Diagnostic procedures included surgical biopsies, nonsurgical histologic biopsies (endobronchial and core needle), transbronchial needle aspirate (TBNA) and transthoracic needle aspirate (TTNA), bronchoalveolar lavage (BAL), and pleural fluid samples.ResultsWe included 702 subjects investigated for histopathologic differentiation of NSCLC. Of these, 269 were also investigated for EGFR mutation. Failure to ascertain the cellular subtype and EGFR mutation status was least likely with surgical specimens (0% and 1.8%, respectively); followed by TTNA (14% and 10%, respectively) and histologic biopsy (18% for both); and was frequent with TBNA (39% and 30%, respectively). Although BAL and pleural fluid specimens provided reasonable yield for cellular differentiation (20 % and 11%, respectively), their results were not accurate in 6% of their samples when compared with concurrent or subsequent surgical specimens (reference standard) performed in a subgroup of patients.ConclusionRadiologically guided TTNA and histologic biopsies provided high yield for both molecular and histologic analyses. The yield of unguided TBNA was relatively low. Further studies are needed to assess the adequacy of BAL and pleural fluid samples for EGFR mutation analysis and accurate characterization of cellular subtypes of NSCLC

Reduced Transmissibility of East African Indian Strains of Mycobacterium tuberculosis

BACKGROUND: Mycobacterium tuberculosis (MTB) has been classified into 4 main lineages. Some reports have associated certain lineages with particular clinical phenotypes, but there is still insufficient information regarding the clinical and epidemiologic implications of MTB lineage variation. METHODS: Using large sequence polymorphisms we classified MTB isolates from a population-based study in Montreal, Canada into the 4 major lineages, and identified the associated clinical and epidemiologic features. In addition, IS6110-RFLP and spoligotyping were used as indicators of recent TB transmission. The study population was divided into a derivation cohort, diagnosed between 2001 and 2007, and a separate validation cohort, diagnosed between 1996 and 2000. RESULTS: In the derivation cohort, when compared to the other MTB lineages, the East African-Indian (EAI) lineage was associated with lower rates of TB transmission, as measured by: positive TST among close contacts of pulmonary TB cases (adjusted odds ratio 0.6: [95% confidence interval 0.4-0.9]), and clustered TB cases (0.3: [<0.001-0.6]). Severe forms of TB were also less likely among the EAI group (0.4: [<0.001-0.8]). There were no significant differences when comparing patients with the other MTB lineages. In the validation cohort, the EAI lineage was associated with lower rates of positive TST among contacts (0.5: [0.3-0.9]) and a trend towards less clustered TB cases (0.5: [0.1-1.8]) when compared to the other lineages. Disease severity among the different groups was not significantly different in the validation cohort. CONCLUSIONS: We conclude that in Montreal, EAI strains were associated with reduced transmission compared to other MTB lineages

The impact of unsupervised and unconsented switch of inhalers in patients with controlled asthma – A targeted literature review

Inhaler combination formulations consisting of an inhaled corticosteroid (ICS) (fluticasone propionate) and a long-acting β2 agonist (salmeterol xinafoate) are indicated as maintenance treatments for patients with asthma and/or for selected patients with chronic obstructive pulmonary disease. The emergence of generic equivalents to branded inhalers is expected to offer economic edge/savings; however, some may argue that cost advantages offered by generic inhalers may be offset by worsening outcomes due to improper inhaler use, reduced adherence, and consequently worse disease control. To understand how unsupervised and unconsented switch of dry-powder inhalers and/or metered-dose inhalers affects clinical and humanistic outcomes in asthma, comprehensive searches of Embase and MEDLINE were conducted to identify research articles published in the English language since 2011. Patients with asthma of any age who underwent an unsupervised and unconsented switch from an ICS/long-acting β2 agonist to another (brand-to-generic or brand-to-brand) for non-medical reasons were the target of this research. Relevant outcomes included asthma control, medication adherence, and healthcare resource utilization. In total, 11 studies were identified for review (ten non-interventional and one post hoc); cohorts ranged from 19 to 42,553 patients. Six studies indicated that unsupervised and unconsented inhaler switch had a negative impact on asthma control; six studies indicated reduced medication adherence post-switching; and five studies reporting healthcare resource utilization showed it was unchanged or increased post-switching. Findings from this targeted review support concerns that unsupervised and unconsented inhaler switch has a largely negative impact on asthma-associated outcomes. Additional studies are warranted to further explore unsupervised and unconsented switch in asthma

A Cross-Sectional Study in Patients with Severe COPD to Assess the Perception of Symptom Variability (COPVAR) in the Middle East and Africa

van Zyl-Smit, Richard/0000-0002-4115-5362WOS: 000503439600001PubMed: 31908444Purpose: This study was performed to assess symptom variability and its impact on morning activities in stable patients with severe COPD in the Middle East and Africa (MEA) countries. Patients and methods: Non-interventional, cross-sectional study (NCT03425760) in patients with severe COPD (GOLD 2015, C, or D categories). Symptom variability was assessed directly by interviewing the patient and using the Global Chest Symptoms Questionnaire (GCSQ). the impact on morning activities was assessed using the Capacity of Daily Living during the Morning (CDLM) and the Morning Activities and Symptoms Questionnaire (MASQ). Results: A total of 3253 patients (mean +/- SD age: 64.1 +/- 9.5 years, 90.3% males) were enrolled. Overall, 81.6% and 83.4% of patients reported weekly and daily symptom variability, respectively. the number of exacerbations in the previous year, smoking cessation, and COPD GOLD D were the most consistent factors associated with symptom variability. the GCSQ score was significantly higher (p<0.001) in GOLD D than in GOLD C patients at each time during the day. in GOLD D, the mean (+/- SD) GCSQ score was higher at night (1.6 +/- 1.2, p<0.001) and in the morning (1.5 +/- 1.0, p<0.001) than in the afternoon (1.3 +/- 0.9), suggesting daytime variability of breathlessness and chest tightness. Overall, 60.0% of GOLD D patients (versus 13.6% GOLD C, p<0.0001) had difficulty getting out of bed due to COPD. Patients with symptom variability had significantly more difficulty to get out of bed, especially patients with chest tightness variability (p<0.0001) and wheezing variability (p<0.0001). the CDLM global score was significantly lower (p<0.0001) in GOLD D than in GOLD C patients (3.5 +/- 1.1 and 4.6 +/- 3.5, respectively). Daily variability in chest tightness and wheezing was also significantly associated with CDLM scores (p<0.0001). Conclusion: in MEA countries, patients with severe stable COPD reported significant daily and weekly symptom variability which affects morning activities, particularly in GOLD D patients.AstraZeneca (United Arab Emirates)AstraZenecaThe authors would like to thank all investigators who enrolled patients in this study. To NCT (Cairo, Egypt) for clinical study management, Axonal-Biostatem (Castries, France) for data management and statistics, and Thierry Radeau Consulting (Epinay-Sous-Senart, France) for medical writing support funded by AstraZeneca (United Arab Emirates) in accordance with Good Publication Practice (GPP3) guidelines (https://www.ismpp.org/gpp3)

Short-term outcome associated with disease severity and electrolyte abnormalities among critically ill children with acute kidney injury

Abstract Background Acute kidney injury (AKI) in critically ill children is associated with increased mortality and morbidity. In this study we evaluated the effect of AKI severity on the incidence of short-term mortality and morbidity. Methods Multicenter prospective cohort study was conducted over two years period. We used the Kidney Disease Improving Global Outcomes (KDIGO) to diagnose and stage AKI. Results A total of 511 out of 1367 included children (37.4%; 95% CI: 34.8–40.0) were diagnosed with AKI. They were categorized into three KDIGO stages: stage I (mild) in 47.5% (95% CI: 43.2–52.0), stage II (moderate) in 32.8% (95% CI: 28.8–37.1) and stage III (severe) in 19.7% (95% CI: 16.4–23.5). Stage II and III AKI had higher risk of mortality and longer length of stay (LOS) in hospital. Children with stage III AKI were more likely to require mechanical ventilation, referral to pediatric nephrology and discharge with abnormal creatinine level (above 100 uml\L). Hypervolemia, hypocalcemia, anemia, and acidosis were found to be independent risk factors of mortality. Conclusion The extent of severity of AKI is directly associated with increased mortality, LOS and short-term morbidity

A Cross-Sectional Study in Patients with Severe COPD to Assess the Perception of Symptom Variability (COPVAR) in the Middle East and Africa.

This study was performed to assess symptom variability and its impact on morning activities in stable patients with severe COPD in the Middle East and Africa (MEA) countries

A Cross-Sectional Study in Patients with Severe COPD to Assess the Perception of Symptom Variability (COPVAR) in the Middle East and Africa

Purpose: This study was performed to assess symptom variability and its impact on morning activities in stable patients with severe COPD in the Middle East and Africa (MEA) countries. Patients and methods: Non-interventional, cross-sectional study (NCT03425760) in patients with severe COPD (GOLD 2015, C, or D categories). Symptom variability was assessed directly by interviewing the patient and using the Global Chest Symptoms Questionnaire (GCSQ). The impact on morning activities was assessed using the Capacity of Daily Living during the Morning (CDLM) and the Morning Activities and Symptoms Questionnaire (MASQ). Results: A total of 3253 patients (mean +/- SD age: 64.1 +/- 9.5 years, 90.3\% males) were enrolled. Overall, 81.6\% and 83.4\% of patients reported weekly and daily symptom variability, respectively. The number of exacerbations in the previous year, smoking cessation, and COPD GOLD D were the most consistent factors associated with symptom variability. The GCSQ score was significantly higher (p<0.001) in GOLD D than in GOLD C patients at each time during the day. In GOLD D, the mean (+/- SD) GCSQ score was higher at night (1.6 +/- 1.2, p<0.001) and in the morning (1.5 +/- 1.0, p<0.001) than in the afternoon (1.3 +/- 0.9), suggesting daytime variability of breathlessness and chest tightness. Overall, 60.0\% of GOLD D patients (versus 13.6\% GOLD C, p<0.0001) had difficulty getting out of bed due to COPD. Patients with symptom variability had significantly more difficulty to get out of bed, especially patients with chest tightness variability (p<0.0001) and wheezing variability (p<0.0001). The CDLM global score was significantly lower (p<0.0001) in GOLD D than in GOLD C patients (3.5 +/- 1.1 and 4.6 +/- 3.5, respectively). Daily variability in chest tightness and wheezing was also significantly associated with CDLM scores (p<0.0001). Conclusion: In MEA countries, patients with severe stable COPD reported significant daily and weekly symptom variability which affects morning activities, particularly in GOLD D patients