BACKGROUND: Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. A phase 3 trial compared first-line osimertinib with other EGFR-TKIs in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). The trial showed longer progression-free survival with osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or death, 0.46). Data from the final analysis of overall survival have not been reported. METHODS: In this trial, we randomly assigned 556 patients with previously untreated advanced NSCLC with an EGFR mutation (exon 19 deletion or L858R allele) in a 1:1 ratio to receive either osimertinib (80 mg once daily) or one of two other EGFR-TKIs (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily, with patients receiving these drugs combined in a single comparator group). Overall survival was a secondary end point. RESULTS: The median overall survival was 38.6 months (95% confidence interval [CI], 34.5 to 41.8) in the osimertinib group and 31.8 months (95% CI, 26.6 to 36.0) in the comparator group (hazard ratio for death, 0.80; 95.05% CI, 0.64 to 1.00; P = 0.046). At 3 years, 79 of 279 patients (28%) in the osimertinib group and 26 of 277 (9%) in the comparator group were continuing to receive a trial regimen; the median exposure was 20.7 months and 11.5 months, respectively. Adverse events of grade 3 or higher were reported in 42% of the patients in the osimertinib group and in 47% of those in the comparator group. CONCLUSIONS: Among patients with previously untreated advanced NSCLC with an EGFR mutation, those who received osimertinib had longer overall survival than those who received a comparator EGFR-TKI. The safety profile for osimertinib was similar to that of the comparator EGFR-TKIs, despite a longer duration of exposure in the osimertinib group. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125.).

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Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi. Acute respiratory distress syndrome (ARDS) is a serious complication of scrub typhus. This study retrospectively reviewed the medical records of 72 patients diagnosed with scrub typhus from January 1998 to August 2006 in Kaohsiung Chang Gung Memorial Hospital in Taiwan. Eight of 72 scrub typhus patients with ARDS were included in the study; the other patients without ARDS were used as controls. The mortality rate for the scrub typhus patients with ARDS was 25%. The eight patients seldom had underlying diseases. Initial presentations of dyspnea and cough, white blood cell count, hematocrit, total bilirubin, and delayed used of appropriate antibiotics use were significant predictors of ARDS. Multivariate analysis showed that albumin, prothrombin time, and delayed use of appropriate antibiotics were independent predictors of ARDS. Identification of these relative risk factors may help clinicians evaluate clinical cases of scrub typhus with ARDS.

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Objective: To examine the efficacy of combined inspiratory and expiratory respiratory muscle training (RMT) with respect to the swallowing function, pulmonary function, functional performance, and dysarthria in patients with stroke. Design: Prospective, randomized controlled trial. Setting: Tertiary hospital. Participants: The trial included 21 subjects (12 men, 9 women) aged 35 to 80 years presenting with 6 months history of unilateral stroke, respiratory muscle weakness (≥70% predicted maximal inspiratory pressure (MIP) and/or ≤70% maximal expiratory pressure (MEP)), dysphagia, or dysarthria. These subjects were randomly assigned to the control (n = 10, rehabilitation) and experimental (n = 11, rehabilitation with RMT) groups. Intervention: Inspiratory RMT starting from 30% to 60% of MIP and expiratory RMT starting from 15% to 75% of MEP for 5 days/week for 6 weeks. Main outcome measures: MIP, MEP, pulmonary function, peak cough flow, perception of dyspnea, Fatigue Assessment Scale, Modified Rankin Scale, Brunnstrom stage, Barthel index, Functional Oral Intake Scale (FOIS), and parameters of voice analysis. Results: Significant differences were observed between both groups in terms of MIP, forced vital capacity (FVC), and forced expiratory volume per second (FEV1) of the percentage predicted. Significant difference was found with respect to the change in fatigue, shimmer percent, amplitude perturbation quotient, and voice turbulence index (VTI) according to the acoustic analysis in the RMT group. The FEV1/FVC ratio was negatively correlated with jitter percent, relative average perturbation, pitch perturbation quotient, and VTI; the maximum mid-expiratory flow (MMEF) and MMEF% were also negatively correlated with VTI. Significant differences among participants of the same group were observed while comparing the Brunnstrom stage before and after training of the affected limbs and the Barthel scale and FOIS scores in both the groups. Conclusions: Altogether, 6-week combined inspiratory and expiratory RMT is feasible as adjuvant therapy for stroke patients to improve fatigue level, respiratory muscle strength, lung volume, respiratory flow, and dysarthria. Clinical trial registration number (Clinical Trial Identifier): NCT03491111.

Pneumonia leads to changes in body composition and weakness due to the malnourished condition. In addition, patient family caregivers always have a lack of nutritional information, and they do not know how to manage patients’ nutritional intake during hospitalization and after discharge. Most intervention studies aim to provide nutritional support for older patients. However, whether long-term nutritional intervention by dietitians and caregivers from patients’ families exert clinical effects—particularly in malnourished pneumonia—on nutritional status and readmission rate at each interventional phase, from hospitalization to postdischarge, remains unclear. To investigate the effects of an individualized nutritional intervention program (iNIP) on nutritional status and readmission rate in older adults with pneumonia during hospitalization and three and six months after discharge. Eighty-two malnourished older adults with a primary diagnosis of pneumonia participated. Patients were randomly allocated to either a nutrition intervention (NI) group or a standard care (SC) group. Participants in the NI group received an iNIP according to energy and protein intake requirements in addition to dietary advice based on face-to-face interviews with their family caregivers during hospitalization. After discharge, phone calls were adopted for prescribing iNIPs. Anthropometry (i.e., body mass index, limb circumference, and subcutaneous fat thickness), blood parameters (i.e., albumin and total lymphocyte count), hospital stay, Mini-Nutritional Assessment-Short Form (MNA-SF) score, target daily calorie intake, total calorie intake adherence rate, and three-major-nutrient intakes were assessed during hospitalization and three and six months after discharge. Both groups received regular follow-up through phone calls. Furthermore, the rate of readmission resulting from pneumonia was recorded after discharge. During hospital stay, the NI group showed significant increases in daily calorie intake, total calorie intake adherence rate, and protein intake compared with the SC group (p < 0.05); however, no significant difference was found in anthropometry, blood biochemical values, MNA-SF scores, and hospital stay. At three and six months after discharge, the NI group showed significantly higher daily calorie intake and MNA-SF scores (8.2 vs. 6.5 scores at three months; 9.3 vs. 7.6 scores at six months) than did the SC group (p < 0.05). After adjusting for sex, the readmission rate for pneumonia significantly decreased by 77% in the NI group compared with that in the SC group (p = 0.03, OR: 0.228, 95% CI: 0.06–0.87). A six-month iNIP under dietitian and patient family nutritional support for malnourished older adults with pneumonia can significantly improve their nutritional status and reduce the readmission rate.