Benzodiazepines are safe and effective when administered by paramedics for out-of-hospital status epilepticus in adults. Lorazepam is likely to be a better therapy than diazepam.
This prognostic index, incorporating age, sex, self-reported comorbid conditions, and functional measures, accurately stratifies community-dwelling older adults into groups at varying risk of mortality.
New vertebral fractures, even those not recognized clinically, are associated with substantial increases in back pain and functional limitation due to back pain in older white women. Prevention of new vertebral fractures should reduce the burden of back pain and functional limitation in women with vertebral osteoporosis.
We studied the effect of prenatal maternal cigarette smoking on the pulmonary function (PF) of 80 healthy infants tested shortly after birth (mean, 4.2 +/- 1.9 wk). Mothers' prenatal smoking was measured by: (1) questionnaire reports at each prenatal visit of the number of cigarettes smoked per day, and (2) urine cotinine concentrations (corrected for creatinine) obtained at each visit. Infant PF was assessed by partial expiratory flow-volume curves and helium-dilution measurement of FRC. Forced expiratory flow rates were significantly lower in infants born to smoking mothers, both when unadjusted and after controlling for infant size, age, sex, and passive exposure to environmental tobacco smoke (ETS) between birth and the time of PF testing. Flow at functional residual capacity (VFRC) in infants born to smoking mothers was lower than that found in infants whose mothers did not smoke during pregnancy (74.3 +/- 15.9 versus 150.4 +/- 8.9 ml/s; p = 0.0007). Differences remained significant when flow was corrected for lung size (VFRC/FRC: 0.87 +/- 0.26 versus 1.77 +/- 0.12 s-1; p = 0.013). No differences in pulmonary function were evident among infants exposed and unexposed to ETS in the home after stratifying by prenatal exposure status. We conclude that maternal smoking during pregnancy is associated with significant reductions in forced expiratory flow rates in young infants. The results suggest that maternal smoking during pregnancy may impair in utero airway development and/or alter lung elastic properties. We speculate that these effects of maternal prenatal smoking on early levels of forced expiratory flow may be an important factor predisposing infants to the occurrence of wheezing illness later in childhood.
Summary
Background
The frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed to develop and validate a practical, reliable assay that improves risk stratification compared with conventional staging.
Methods
A 14-gene expression assay that uses quantitative PCR, runs on formalin-fixed paraffin-embedded tissue samples, and differentiates patients with heterogeneous statistical prognoses was developed in a cohort of 361 patients with non-squamous NSCLC resected at the University of California, San Francisco. The assay was then independently validated by the Kaiser Permanente Division of Research in a masked cohort of 433 patients with stage I non-squamous NSCLC resected at Kaiser Permanente Northern California hospitals, and on a cohort of 1006 patients with stage I–III non-squamous NSCLC resected in several leading Chinese cancer centres that are part of the China Clinical Trials Consortium (CCTC).
Findings
Kaplan-Meier analysis of the Kaiser validation cohort showed 5 year overall survival of 71·4% (95% CI 60·5–80·0) in low-risk, 58·3% (48·9–66·6) in intermediate-risk, and 49·2% (42·2–55·8) in high-risk patients (ptrend=0·0003). Similar analysis of the CCTC cohort indicated 5 year overall survivals of 74·1% (66·0–80·6) in low-risk, 57·4% (48·3–65·5) in intermediate-risk, and 44·6% (40·2–48·9) in high-risk patients (ptrend<0·0001). Multivariate analysis in both cohorts indicated that no standard clinical risk factors could account for, or provide, the prognostic information derived from tumour gene expression. The assay improved prognostic accuracy beyond National Comprehensive Cancer Network criteria for stage I high-risk tumours (p<0·0001), and differentiated low-risk, intermediate-risk, and high-risk patients within all disease stages.
Interpretation
Our practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection.
Funding
UCSF Thoracic Oncology Laboratory and Pinpoint Genomics.
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