Background Pulmonary function tests predict respiratory complications and mortality after lung resection through thoracotomy. We sought to determine the impact of pulmonary function tests upon ...complications after thoracoscopic lobectomy. Methods A model for morbidity, including published preoperative risk factors and surgical approach, was developed by multivariable logistic regression. All patients who underwent lobectomy for primary lung cancer between December 1999 and October 2007 with preoperative forced expiratory volume in 1 second (FEV1 ) or diffusion capacity to carbon monoxide (D lco ) 60% or less predicted were reviewed. Preoperative, histopathologic, perioperative, and outcome variables were assessed using standard descriptive statistics. Pulmonary complications were defined as atelectasis requiring bronchoscopy, pneumonia, reintubation, and tracheostomy. Results During the study period, 340 patients (median age 67) with D lco or FEV1 60% or less (mean % predicted FEV1 , 55 ± 1; mean % predicted D lco , 61 ± 1) underwent lobectomy (173 thoracoscopy, 167 thoracotomy). Operative mortality was 5% (17 patients) and overall morbidity was 48% (164 patients). At least one pulmonary complication occurred in 57 patients (17%). Significant predictors of pulmonary complications by multivariable analysis for all patients included D lco (odds ratio 1.03, p = 0.003), FEV1 (odds ratio 1.04, p = 0.003), and thoracotomy as surgical approach (odds ratio 3.46, p = 0.0007). When patients were analyzed according to operative approach, D lco and FEV1 remained significant predictors of pulmonary morbidity for patients undergoing thoracotomy but not thoracoscopy. Conclusions In patients with impaired pulmonary function, preoperative pulmonary function tests are predictors of pulmonary complications when lobectomy for lung cancer is performed through thoracotomy but not through thoracoscopy.
Men with metastatic hormone-refractory prostate cancer have a life expectancy of only about a year. More than 1000 such men were randomly assigned to receive the standard chemotherapy — mitoxantrone ...plus prednisone — or docetaxel (given every three weeks or every week) plus prednisone. Men who received docetaxel every 3 weeks survived for a median of almost 19 months, as compared with a median of 16.5 months among men in the standard-therapy group. Docetaxel was also associated with better pain control and quality of life.
The results offer a new choice of treatment that has advantages over standard chemotherapy.
Prostate cancer is the most common cancer among men, with approximately 220,000 cases and 29,000 deaths annually in the United States.
1
About 10 to 20 percent of men with prostate cancer present with metastatic disease, and in many others, metastases develop despite treatment with surgery or radiotherapy.
Treatment of metastatic prostate cancer is palliative. In about 80 percent of men, primary androgen ablation leads to symptomatic improvement and a reduction in serum levels of prostate-specific antigen (PSA), but in all patients the disease eventually becomes refractory to hormone treatment. The options then include symptomatic care with narcotic analgesics, radiotherapy to . . .
Globally documented widespread drought‐induced forest mortality has important ramifications for plant community structure, ecosystem function, and the ecosystem services provided by forests. Yet the ...characteristics of drought seasonality, severity, and duration that trigger mortality events have received little attention despite evidence of changing precipitation regimes, shifting snow melt timing, and increasing temperature stress. This study draws upon stand level ecohydrology and statewide climate and spatial analysis to examine the drought characteristics implicated in the recent widespread mortality of trembling aspen (Populus tremuloides Michx.). We used isotopic observations of aspen xylem sap to determine water source use during natural and experimental drought in a region that experienced high tree mortality. We then drew upon multiple sources of climate data to characterize the drought that triggered aspen mortality. Finally, regression analysis was used to examine the drought characteristics most associated with the spatial patterns of aspen mortality across Colorado. Isotopic analysis indicated that aspens generally utilize shallow soil moisture with little plasticity during drought stress. Climate analysis showed that the mortality‐inciting drought was unprecedented in the observational record, especially in 2002 growing season temperature and evaporative deficit, resulting in record low shallow soil moisture reserves. High 2002 summer temperature and low shallow soil moisture were most associated with the spatial patterns of aspen mortality. These results suggest that the 2002 drought subjected Colorado aspens to the most extreme growing season water stress of the past century by creating high atmospheric moisture demand and depleting the shallow soil moisture upon which aspens rely. Our findings highlight the important role of drought characteristics in mediating widespread aspen forest mortality, link this aspen die‐off to regional climate change trends, and provide insight into future climate vulnerability of these forests.
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Widespread drought-induced mortality of woody plants has recently occurred worldwide, is likely to be exacerbated by future climate change and holds large ecological consequences. Yet despite decades ...of research on plant-water relations, the pathways through which drought causes plant mortality are poorly understood. Recent work on the physiology of tree mortality has begun to reveal how physiological dysfunction induced by water stress leads to plant death; however, we are still far from being able to predict tree mortality using easily observed or modeled meteorological variables. In this review, we contend that, in order to fully understand when and where plants will exceed mortality thresholds when drought occurs, we must understand the entire path by which precipitation deficit is translated into physiological dysfunction and lasting physiological damage. In temperate ecosystems with seasonal climate patterns, precipitation characteristics such as seasonality, timing, form (snow versus rain) and intensity interact with edaphic characteristics to determine when and how much water is actually available to plants as soil moisture. Plant and community characteristics then mediate how quickly water is used and seasonally varying plant physiology determines whether the resulting soil moisture deficit is physiologically damaging. Recent research suggests that drought seasonality and timing matter for how an ecosystem experiences drought. But, mortality studies that bridge the gaps between climatology, hydrology, plant ecology and plant physiology are rare. Drawing upon a broad hydrological and ecological perspective, we highlight key and underappreciated processes that may mediate drought-induced tree mortality and propose steps to better include these components in current research.
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Background
Prostate‐specific membrane antigen (PSMA) is a well‐characterized target that is overexpressed selectively on prostate cancer cells. PSMA antibody‐drug conjugate (ADC) is a fully human ...IgG1 monoclonal antibody conjugated to the microtubule disrupting agent monomethyl auristatin E (MMAE), which is designed to specifically bind PSMA‐positive cells, internalize, and then release its cytotoxic payload into the cells. PSMA ADC has demonstrated potent and selective antitumor activity in preclinical models of advanced prostate cancer. A Phase 1 study was conducted to assess the safety, pharmacokinetics, and preliminary antitumor effects of PSMA ADC in subjects with treatment‐refractory prostate cancer.
Methods
In this first‐in‐man dose‐escalation study, PSMA ADC was administered by intravenous infusion every three weeks to subjects with progressive metastatic castration‐resistant prostate cancer (mCRPC) who were previously treated with docetaxel chemotherapy. The primary endpoint was to establish a maximum tolerated dose (MTD). The study also examined the pharmacokinetics of the study drug, total antibody, and free MMAE. Antitumor effects were assessed by measuring changes in serum prostate‐specific antigen (PSA), circulating tumor cells (CTCs), and radiologic imaging.
Results
Fifty‐two subjects were administered doses ranging from 0.4 to 2.8 mg/kg. Subjects had a median of two prior chemotherapy regimens and prior treatment with abiraterone and/or enzalutamide. Neutropenia and peripheral neuropathy were identified as important first‐cycle and late dose‐limiting toxicities, respectively. The dose of 2.5 mg/kg was determined to be the MTD. Pharmacokinetics were approximately dose‐proportional with minimal drug accumulation. Reductions in PSA and CTCs in subjects treated with doses of ≥1.8 mg/kg were durable and often concurrent.
Conclusions
In an extensively pretreated mCRPC population, PSMA ADC demonstrated acceptable toxicity. Antitumor activity was observed over dose ranges up to and including 2.5 mg/kg. The observed anti‐tumor activity supported further evaluation of this novel agent for the treatment of advanced metastatic prostate cancer.
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ObjectivesTo assess the relationship between changes in clinician attitude and changes in postoperative outcomes following a checklist-based surgical safety intervention.DesignPre- and post ...intervention survey.SettingEight hospitals participating in a trial of a WHO surgical safety checklist.ParticipantsClinicians actively working in the designated study operating rooms at the eight hospitals.Survey instrumentModified operating-room version Safety Attitudes Questionnaire (SAQ).Main outcome measuresChange in mean safety attitude score and correlation between change in safety attitude score and change in postoperative outcomes, plus clinician opinion of checklist efficacy and usability.ResultsClinicians in the preintervention phase (n=281) had a mean SAQ score of 3.91 (on a scale of 1 to 5, with 5 representing better safety attitude), while the postintervention group (n=257) had a mean of 4.01 (p=0.0127). The degree of improvement in mean SAQ score at each site correlated with a reduction in postoperative complication rate (r=0.7143, p=0.0381). The checklist was considered easy to use by 80.2% of respondents, while 19.8% felt that it took a long time to complete, and 78.6% felt that the programme prevented errors. Overall, 93.4% would want the checklist used if they were undergoing operation.ConclusionsImprovements in postoperative outcomes were associated with improved perception of teamwork and safety climate among respondents, suggesting that changes in these may be partially responsible for the effect of the checklist. Clinicians held the checklist in high regard and the overwhelming majority would want it used if they were undergoing surgery themselves.
Operating room (OR) crises are high-acuity events requiring rapid, coordinated management. Medical judgment and decision-making can be compromised in stressful situations, and clinicians may not ...experience a crisis for many years. A cognitive aid (e.g., checklist) for the most common types of crises in the OR may improve management during unexpected and rare events. While implementation strategies for innovations such as cognitive aids for routine use are becoming better understood, cognitive aids that are rarely used are not yet well understood. We examined organizational context and implementation process factors influencing the use of cognitive aids for OR crises.
We conducted a cross-sectional study using a Web-based survey of individuals who had downloaded OR cognitive aids from the websites of Ariadne Labs or Stanford University between January 2013 and January 2016. In this paper, we report on the experience of 368 respondents from US hospitals and ambulatory surgical centers. We analyzed the relationship of more successful implementation (measured as reported regular cognitive aid use during applicable clinical events) with organizational context and with participation in a multi-step implementation process. We used multivariable logistic regression to identify significant predictors of reported, regular OR cognitive aid use during OR crises.
In the multivariable logistic regression, small facility size was associated with a fourfold increase in the odds of a facility reporting more successful implementation (p = 0.0092). Completing more implementation steps was also significantly associated with more successful implementation; each implementation step completed was associated with just over 50% higher odds of more successful implementation (p ≤ 0.0001). More successful implementation was associated with leadership support (p < 0.0001) and dedicated time to train staff (p = 0.0189). Less successful implementation was associated with resistance among clinical providers to using cognitive aids (p < 0.0001), absence of an implementation champion (p = 0.0126), and unsatisfactory content or design of the cognitive aid (p = 0.0112).
Successful implementation of cognitive aids in ORs was associated with a supportive organizational context and following a multi-step implementation process. Building strong organizational support and following a well-planned multi-step implementation process will likely increase the use of OR cognitive aids during intraoperative crises, which may improve patient outcomes.
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To compare the efficacy and safety of docetaxel plus high-dose calcitriol (DN-101) to docetaxel plus prednisone in an open-label phase III trial.
Nine hundred fifty-three men with metastatic ...castration-resistant prostate cancer (CRPC) were randomly assigned to Androgen-Independent Prostate Cancer Study of Calcitriol Enhancing Taxotere (ASCENT; 45 μg DN-101, 36 mg/m(2) docetaxel, and 24 mg dexamethasone weekly for 3 of every 4 weeks) or control (5 mg prednisone twice daily with 75 mg/m(2) docetaxel and 24 mg dexamethasone every 3 weeks) arms. The primary end point was overall survival (OS), assessed by the Kaplan-Meier method.
At an interim analysis, more deaths were noted in the ASCENT arm, and the trial was halted. The median-follow-up for patients alive at last assessment was 11.7 months. Median OS was 17.8 months (95% CI, 16.0 to 19.5) in the ASCENT arm and 20.2 months (95% CI, 18.8 to 23.0) in the control arm (log-rank P = .002). Survival remained inferior after adjusting for baseline variables (hazard ratio, 1.33; P = .019). The two arms were similar in rates of total and serious adverse events. The most frequent adverse events were GI (reported in 75% of patients), and blood and lymphatic disorders (48%). Docetaxel toxicity leading to dose modification was more frequent in the ASCENT (31%) than in the control arm (15%).
ASCENT treatment was associated with shorter survival than the control. This difference might be due to either weekly docetaxel dosing, which, in a prior study, showed a trend toward inferior survival compared with an every-3-weeks regimen, or DN-101 therapy.
Background Surgical care is a vital component of health care worldwide, yet there is no clinically meaningful measure of operative outcomes that could be applied globally. The Surgical Apgar Score, a ...simple metric derived from 3 intraoperative parameters, has been shown in U.S. academic medical centers to predict 30-day patient outcomes after operation, but has not been validated more broadly. Methods We collected the components of the Surgical Apgar Score at the time of operation for 5,909 adult patients undergoing noncardiac operative procedures under general anesthesia at 8 hospitals in diverse international settings and evaluated the relationship between patients’ scores and the incidence of inpatient postoperative morbidity and mortality, using generalized estimating equations to adjust for clustering within sites. Results During the first 30 days of postoperative hospitalization, 544 patients (9.2%) experienced ≥1 complications. Compared with patients with the median score of 7—whose complication rate was 9.1%—those with a Surgical Apgar Score <5 ( n = 302) had an adjusted complication rate of 32.9% (relative risk RR,3.6; 95% CI, 2.9–4.5), whereas those with a score of 10 ( n = 238) had a 3.0% adjusted complication rate (RR, 0.3; 95% CI, 0.1–1.1). The score’s c -statistic for prediction of any complication is 0.70; for death it is 0.77. Conclusion The Surgical Apgar Score is easily calculated, predictive, and moderately discriminative for major complications among adults undergoing inpatient noncardiac operative procedures. Such a score could provide objective indication of relative postoperative risk for inpatients and provide a potential target for quality improvement efforts, particularly in resource-limited settings.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
30.
Predicting outcome of patients with chest wall injury Pressley, Crystal M., M.D., M.P.H; Fry, William R., M.D; Philp, Allan S., M.D ...
The American journal of surgery,
12/2012, Volume:
204, Issue:
6
Journal Article
Peer reviewed
Abstract Background Rib fractures occur in 10% of injured patients, are associated with morbidity and mortality, and frequently necessitate intensive care unit (ICU) care. A scoring system that ...identifies the risk for respiratory failure early in the evaluation process may allow early intervention to improve outcomes. The aim of this study was to test the hypothesis that a scoring system based on initial clinical findings can identify patients with rib fractures at greatest risk for morbidity and mortality. Methods A simple scoring system to stratify risk was developed and applied to patients through a retrospective trauma registry review. Points were assigned as follows: age < 45 years = 1 point, age 45 to 65 years = 2 points, age > 65 years = 3 points; <3 fractures = 1 point, 3 to 5 fractures = 2 points, >5 fractures = 3 points; no pulmonary contusion = 0 points, mild pulmonary contusion = 1 point, severe pulmonary contusion = 2 points, bilateral pulmonary contusion = 3 points; and bilateral rib fracture absent = 0 points, bilateral rib fracture absent present = 2 points. A review of trauma registry patients with rib fractures (June 2008 to February 2010) at a state-designated level 1 trauma center was performed. Data reviewed included age, number of fractures, bilateral injury, presence of pulmonary contusion, classification of the contusion, length of hospital stay, mechanical ventilation, ICU admission, and length of stay. The scoring system was retrospectively applied to 649 patients to determine validity. Results A score ≤ 7 indicated lower mortality (24 of 579 4.2%) compared with patients with scores > 7 (10 of 70 14.3%) (Fisher's 2-sided P = .0018). Patients with scores ≤ 6 were less likely to be admitted to an ICU (29.7%) compared with those with scores ≥ 7 (56.7%) ( P < .0001). Patients with total scores < 7 were less likely to require intubation (20.6%) compared with those with scores ≥ 7 (40.0%) ( P < .0001). Patients with scores ≤ 4 had shorter lengths of stay (36.0% <5 days) compared with those who had scores > 4 (59.7%) ( P < .0001). Conclusions A simple scoring system predicts the likelihood that patients will require mechanical ventilation and prolonged courses of care. A score of 7 or 8 predicted increased risk for mortality, admission to the ICU, and intubation. A score > 5 predicted a longer length of stay and a longer period of ventilation. This scoring system may assist in the earlier implementation of treatment strategies such epidural anesthesia, ventilation, and operative fixation of fractures.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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