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BACKGROUND: The prevalence of chronic disease and do-not-intubate status increases with age. Thus, we aimed to determine characteristics and outcomes associated with noninvasive ventilation (NIV) use for acute respiratory failure (ARF) in different age groups. METHODS: A database comprising prospective data collected on site on all adult patients with ARF requiring ventilatory support from 8 acute care hospitals in Massachusetts was used. RESULTS: From a total of 1,225 ventilator starts, overall NIV utilization, success, and in-hospital mortality rates were 22, 54, and 18% in younger (18-44 y); 34, 65, and 13% in middle-aged (45-64 y); 49, 68, and 17% in elderly (65-79 y); and 47, 76, and 24% in aged (>= 80 y) groups, respectively (P < .001, P = .08, and P = .11, respectively). NIV use for cardiogenic pulmonary edema and subjects with a do-not-intubate order increased significantly with advancing age (25, 57, 57, and 74% and 7, 12, 18, and 31%, respectively, in the 4 age groups [P < .001 and P = .046, respectively]). For subjects receiving NIV with a do-not-intubate order, success and in-hospital mortality rates were similar in different age groups (P = .27 and P = .98, respectively). CONCLUSIONS: NIV use and a do-not-intubate status are more frequent in subjects with ARF >= 65 y than in those < 65 y, especially for subjects with cardiogenic pulmonary edema. However, NIV success and mortality rates were similar between age groups.

Background This study determined actual utilization rates and outcomes of noninvasive positive pressure ventilation (NIV) at selected hospitals that had participated in a prior survey on NIV use. Methods This observational cohort study, based at eight acute care hospitals in Massachusetts, focused on all adult patients requiring ventilatory support for acute respiratory failure during predetermined time intervals. Results Of 548 ventilator starts, 337 (61.5%) were for invasive mechanical ventilation and 211 (38.5%) were for NIV, with an overall NIV success rate of 73.9% (ie, avoidance of intubation or death while on NIV or within 48 h of discontinuation). Causal diagnoses for respiratory failure were classified as (I) acute-on-chronic lung disease (23.5%), (II) acute de novo respiratory failure (17.9%), (III) neurologic disorders (19%), (IV) cardiogenic pulmonary edema (16.8%), (V) cardiopulmonary arrest (12.2%), and (VI) others (10.6%). NIV use and success rates for each of the causal diagnoses were, respectively, (I) 76.7% and 75.8%, (II) 37.8% and 62.2%, (III) 1.9% and 100%, (IV) 68.5% and 79.4%, (V) none, and (VI) 17.2% and 60%. Hospital mortality rate was higher in patients with invasive mechanical ventilation than in patients with NIV (30.3% vs 16.6%, P Conclusions NIV occupies an important role in the management of acute respiratory failure in acute care hospitals in selected US hospitals and is being used for a large majority of patients with acute-on-chronic respiratory failure and acute cardiogenic pulmonary edema. NIV use appears to have increased substantially in selected US hospitals over the past decade. Trial registry ClinicalTrials.gov; No.: NCT00458926; URL: www.clinicaltrials.gov

Background We hypothesized that the total face mask (TFM) would be perceived as more comfortable than a standard oronasal mask (ONM) by patients receiving noninvasive mechanical ventilation (NIV) therapy for acute respiratory failure (ARF) and would be quicker to apply by respiratory therapists. Methods Sixty patients presenting with ARF were randomized to receive NIV via either an ONM or a TFM. Mask comfort and dyspnea were assessed using visual analog scores. Other outcomes included time required to apply, vital signs and gas exchange at set time points, and early NIV discontinuation rates (ie, stoppage while still requiring ventilatory assistance). Results Mask comfort and dyspnea scores were similar for both groups through 3 h of use. The time required to apply the mask (5 min [interquartile range (IQR), 2-8] vs 3.5 min [IQR, 1.9-5]), and duration of use (15.7 h [IQR, 4.0-49.8]) vs 6.05 h [IQR, 0.9-56.7]) were not significantly different between the ONM and the TFM group, respectively. Except for heart rate, which was higher at baseline in the TFM group, no differences in vital signs or gas exchange were detected between the groups during the first 3 h ( P > .05). Early NIV discontinuation rates were similar for both the ONM group and TFM group (40% vs 57.1%); however, eight patients in the TFM group were switched to an ONM within 3 h, and none from the ONM group was switched to a TFM ( P Conclusions Among patients with ARF requiring NIV, the ONM and TFM were perceived to be equally comfortable and had similar application times. Early NIV discontinuation rates, improvements in vital signs and gas exchange, and intubation and mortality rates were also similar. Trial Registry ClinicalTrials.gov ; No.: NCT00686257 ; URL: www.clinicaltrials.gov

Few studies have examined locations of noninvasive ventilation (NIV) application for acute respiratory failure (ARF). We aimed to track actual locations of NIV delivery and related outcomes.Observational cohort study based at 8 acute care hospitals in Massachusetts on adult patients admitted for ARF requiring ventilatory support during pre-determined time intervals.Of 1225 ventilator starts, 499 were NIV; 209 (42%) in intensive care units (ICU), 185 (37%) in emergency departments (ED), 91 (18%) on general wards, and 14 (3%) in other units. Utilization (% of all ventilator starts) (1), success (2) and in-hospital mortality (3) rates for patients initiated on NIV in ICU, ED, and general and other wards were (1) 38, 36, 73, and 52%, (2) 60, 77, 68, and 93% and (3) 25, 12, 17, and 0%, respectively (p0.05 for all). Patients with acute-on-chronic lung disease (ACLD) and acute pulmonary edema (APE) were begun on NIV most often in EDs and patients with 'de novo' ARF and neurologic disorders most often in ICU's. Approximately 2/3 of patients begun on NIV outside of ICUs were transferred within 72 h to ICUs, wards or other units.Most NIV starts occurred in ICUs and EDs but utilization rate was highest (50%) on general wards where a fifth of NIV starts took place. Actual location depended on etiology of ARF as patients with ACLD and APE were started more often in EDs and "de novo" ARF in ICU. NIV failure and mortality rates were higher in ICUs related to the greater proportion of patients with "de novo" ARF.

Mammalian cells repair DNA double-strand breaks by illegitimate end-joining or by homologous recombination. We investigated the effects of restriction enzymes on illegitimate and homologous DNA integration in mammalian cells. A plasmid containing the neo(R) expression cassette, which confers G418 resistance, was used to select for illegitimate integration events in CHO wild-type and xrcc5 mutant cells. Co-transfection with the restriction enzymes BamHI, BglII, EcoRI and KpnI increased the efficiency of linearized plasmid integration up to 5-fold in CHO cells. In contrast, the restriction enzymes did not increase the integration efficiency in xrcc5 mutant cells. Effects of restriction enzymes on illegitimate and homologous integration were also studied in mouse embryonic stem (ES) cells using a plasmid containing the neo(R) gene flanked by exon 3 of HPRT: The enzymes BamHI, BglII and EcoRI increased the illegitimate integration efficiency of transforming DNA several-fold, similar to the results for CHO cells. However, all three enzymes decreased the absolute frequency of homologous integration approximately 2-fold, and the percentage of homologous integration decreased10-fold. This suggests that random DNA breaks attract illegitimate recombination (IR) events that compete with homology search.