INTRODUCTIONInstitutional febrile neutropenia (FN) management protocols were changed following the finding of a high prevalence of ceftazidime-resistant Gram-negative bacteraemia (CR-GNB) among haematology patients with FN. Piperacillin/tazobactam replaced ceftazidime as the initial empirical antibiotic of choice, whereas carbapenems were prescribed empirically for patients with recent extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae colonisation/infection. An audit was conducted to determine the impact of these changes.

METHODSData from all FN episodes between October 2008 and December 2010 were collected prospectively, with mid-November 2009 demarking the transition between pre-intervention and intervention periods. Outcomes measured included 30-day mortality post-development of FN and the presence of CR-GNB.

RESULTSThere were 427 FN episodes (200 in the pre-intervention period) from 225 patients. The prevalence of CRGNB was 10.3%, while the 30-day mortality was 4.7%, with no difference between pre-intervention and intervention periods. Independent risk factors for 30-day mortality included the presence of active haematological disease, vancomycin prescription and older age. Independent factors associated with initial CR-GNB were profound neutropenia, the presence of severe sepsis and active haematological disease. Recent ESBL-producing Enterobacteriaceae colonisation/infection was not predictive of subsequent CR-GNB (positive predictive value 17.3%), whereas a model based on independent risk factors had better negative predictive value (95.4%) but similarly poor positive predictive value (21.4%), despite higher sensitivity.

CONCLUSIONA change in the FN protocol did not result in improved outcomes. Nonetheless, the audit highlighted that empirical carbapenem prescription may be unnecessary in FN episodes without evidence of severe sepsis or septic shock, regardless of previous microbiology results.

Academic Medical Centers ; Adult ; Bacteremia ; complications ; drug therapy ; Carbapenems ; therapeutic use ; Ceftazidime ; pharmacology ; Drug Resistance, Multiple ; Febrile Neutropenia ; complications ; drug therapy ; Female ; Gram-Negative Bacteria ; Humans ; Male ; Middle Aged ; Penicillanic Acid ; administration & dosage ; analogs & derivatives ; Piperacillin ; administration & dosage ; Prevalence ; Prospective Studies ; Risk Factors ; Sepsis ; Singapore ; Treatment Outcome ; Universities

INTRODUCTIONHealth-related quality of life (HRQoL) is an important patient-centred outcome in chronic obstructive pulmonary disease (COPD). The aim of the current study is to compare the discriminative capacity of the modified Medical Research Council (mMRC) dyspnoea scale and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric classification of COPD on HRQoL, as well as determine other factors that are simple and determinative of HRQoL.

METHODSIn this cross-sectional observational study, a total of 328 patients with COPD were enrolled from the pulmonology outpatient clinic. HRQoL was measured using the St George's Respiratory Questionnaire (SGRQ) and the World Health Organization Quality of Life-BREF (WHOQOL-BREF). HRQoL scores were compared between the four GOLD stages and the five grades of the mMRC scale. Significant differences were determined using analysis of variance with Scheffe post-hoc test. Multiple linear regression was applied to explore the major determinants of HRQoL and exclude confounding factors.

RESULTSSignificant differences were found in many more domains of the two questionnaires between mMRC grades than between GOLD stages. In the multiple linear regression model, the mMRC scale was the only factor that remained determinative of all the domains of SGRQ and WHOQOL-BREF. Patients with chronic productive cough, sleep disorders and frequent exacerbations had poorer HRQoL, as reflected by higher scores in SGRQ or lower scores in WHOQOL-BREF.

CONCLUSIONThe mMRC dyspnoea scale is a concise and practical tool to assess the HRQoL of patients with COPD in daily clinical practice.

Adult ; Aged ; Aged, 80 and over ; Cough ; Cross-Sectional Studies ; Dyspnea ; diagnosis ; psychology ; Female ; Humans ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; diagnosis ; psychology ; Quality of Life ; Regression Analysis ; Spirometry ; Surveys and Questionnaires

OBJECTIVETo review our experience of the treatment of bilateral primary spontaneous pneumothorax (PSP) by video-assisted thoracoscopic surgery (VATS).

MATERIALS AND METHODSRetrospective chart review was followed by an on-clinic or telephone interview. Patients were cared for by one thoracic surgeon in four medical centers or community hospitals in Northern and Central Taiwan. Thirteen patients with bilateral PSP underwent bilateral VATS simultaneously or sequentially from July 1994 to December 2005.

RESULTSTwelve males and one female, with age ranging from 15 to 36 years (mean 23.1 years), were treated with VATS for bilateral PSP, under the indications of bilateral pneumothoracis simultaneously (n=4) or sequentially (n=9). The interval between the first and second contra-lateral VATS procedure for non-simultaneous PSP patients ranged from 7 d to 6 years. Eleven of 13 patients (84.6%) had prominent pulmonary bullae/blebs, and underwent bullae resection with mechanical or chemical pleurodesis. The mean operative time was (45.6+/-18.3) min (range 25 approximately 96 min) and (120.6+/-28.7) min (range 84 approximately 166 min) respectively for the non-simultaneous (second VATS for the recurrence of contralateral side after first VATS) and simultaneous (bilateral VATS in one operation) procedures. There was no postoperative mortality. However, prolonged air leakage (>7 d) occurred in one patient (7.7%) who recovered after conservative treatment. The mean duration of chest tube drainage was 3.1 d and the median follow up period was 3.4 years.

CONCLUSIONSVATS is a safe and effective procedure in the treatment of bilateral PSP. Bilateral VATS is only recommended for patients with simultaneously bilateral PSP, because the incidence of recurrence, even with visible bullae, was not so high in my group and in some previous literature. Bilateral VATS in a supine position should only be used in selective cases, because of possible pleural adhesion or hidden bullae on the posterior side.

Adolescent ; Adult ; Blister ; diagnosis ; pathology ; Female ; Humans ; Lung ; pathology ; Male ; Pleura ; Pleurodesis ; Pneumothorax ; diagnosis ; surgery ; Retrospective Studies ; Thoracic Surgery, Video-Assisted ; methods ; Tomography, X-Ray Computed ; methods ; Treatment Outcome

PURPOSE: Epidermal growth factor receptor (EGFR) T790M mutation serves as an important predictor of osimertinib efficacy. However, little is known about how it works among patients with various timings of T790M emergence and treatment. MATERIALS AND METHODS: Advanced EGFR-mutant lung adenocarcinoma patients with positive T790M mutation in tumor were retrospectively enrolled and observed to determine the outcomes of osimertinib treatment. We evaluated the association between patients’ characteristics and the efficacy of osimertinib treatment, particularly with respect to the timing of T790M emergence and osimertinib prescription. RESULTS: A total of 91 patients were enrolled, including 14 (15.4%) with primary and 77 (84.6%) with acquired T790M mutation. The objective response rate and disease controlratewere 60.9% and 85.1%, respectively. The median progression-free survival (PFS) and overall survival were 11.5 months (95% confidence interval [CI], 9.0 to 14.0) and 30.4 months (95% CI, 11.3 to 49.5), respectively. There was no significant difference in response rate and PFS between primary and acquired T790M populations. In the acquired T790M subgroup, patientswho received osimertinib after T790M had been confirmed by rebiopsy had a longer PFS than those with intercalated treatments between rebiopsy and osimertinib prescription (14.0 months [95% CI, 9.0 to 18.9] vs. 7.2 months [95% CI, 3.7 to 10.8]; adjusted hazard ratio, 0.48 [95% CI, 0.24 to 0.98; p=0.043]). Rebiopsy timing did not influence the outcome. CONCLUSION: Osimertinib prescription with intercalated treatment following rebiopsy but not the timing of T790M emergence influenced the treatment outcome. We suggest that it is better to start osimertinib treatment once T790M mutation has been confirmed by biopsy.
Adenocarcinoma ; Biopsy ; Disease-Free Survival* ; Humans ; Lung ; Prescriptions ; Receptor, Epidermal Growth Factor ; Retrospective Studies ; Treatment Outcome

PURPOSE: The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)–mutant lung adenocarcinoma patients with acquired resistance after firstline EGFR–tyrosine kinase inhibitor (TKI) treatment. MATERIALS AND METHODS: We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFR mutation status. RESULTS: A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression-free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). CONCLUSION: PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746-A750 mutation are associated with the frequency of T790M mutation.
Adenocarcinoma* ; Disease-Free Survival ; Epidermal Growth Factor* ; Exons ; Humans ; Lung Neoplasms ; Lung* ; Mutation Rate ; Odds Ratio ; Phosphotransferases ; Point Mutation ; Prevalence ; Receptor, Epidermal Growth Factor* ; Sequence Deletion

Purpose: The aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients. Materials and Methods: From August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis. Results: A total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481). Conclusion Our research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients.