Stereotactic Ablative Radiotherapy (SABR) in Patients with Medically Inoperable Peripheral Early Stage Lung Cancer: Outcomes for the First UK SABR Cohort.

AIMS: To report outcomes for the first UK cohort treated for early stage peripheral lung cancer using stereotactic ablative radiotherapy (SABR). MATERIALS AND METHODS: Patients were included who received SABR between May 2009 and May 2012. Electronic medical records were reviewed for baseline characteristics, treatment details and outcomes. Patients were treated according to the UK SABR Consortium Guidelines. Univariate and multivariate Cox regression was used to determine factors that influenced overall survival and local control. RESULTS: In total, 273 patients received SABR for 288 lesions in the time period examined. The median follow-up was 19.7 months. The median overall survival for all patients was 27.3 months, with 1, 2 and 3 year overall survival of 78.0, 54.9 and 38.6%, respectively. The 1, 2 and 3 year rates of local control were 98.2, 95.7 and 95.7%, respectively. All patients completed the planned course of treatment and rates of Common Toxicity Criteria grade 3+ toxicity were low. On multivariate analysis, patients with Medical Research Council (MRC) breathlessness scores of 3-5 had worse overall survival compared with patients with scores of 1-2 (hazard ratio: 2.10; 95% confidence interval: 1.25-3.59) and the presence of histological diagnosis conferred improved overall survival (hazard ratio: 0.54; 95% confidence interval: 0.31-0.93), probably reflecting that patients who are considered well enough to undergo biopsy are generally fitter overall. No factors were identified that significantly influenced local control. CONCLUSIONS: SABR is an effective and well-tolerated treatment option for patients with early stage peripheral lung cancer who are not suitable for surgery. No patient cohort was identified in whom SABR was considered inappropriate. This series adds to the existing positive data that support SABR for this patient group.

Living on the margin: understanding the experience of living and dying with frailty in old age.

Within policy and practice there is an increasing interest in the care of frail elders. However understanding of the experience and challenges of living and dying with frailty in older age is currently undeveloped. Frailty is often used as a synonym for the increasing infirmities that accompany ageing and the slow dwindling dying trajectory of many elders. However, there is little empirical work on the experience of being frail to inform social gerontological perspectives and welfare provision. Through analysis of repeated in-depth interviews over 17 months (2006-2008) with 17 frail elders living at home in the U.K., key factors that shape elders' experience of being frail emerged. The study argues that the visible markers of functional limitations and the increasing social losses of old age bring finitude to the fore. To retain anchorage in this state of imbalance, frail elders work actively to develop and sustain connections to their physical environment, routines and social networks. This experience can be conceptualised as persistent liminality; a state of imbalance "betwixt and between" active living and clinically recognised dying. This paper highlights the precarious and often protracted dying trajectory of frail older people. Whilst it could be argued that developing into death in older age is part of a normal and successful course after a life long-lived, recognition of and support for older people deemed frail is lacking. Frail elders find themselves living in the margin between the Third and Fourth Age with little recognition of or support for the work of living and dying over time. This experience of frailty contests dominant cultural and welfare practices and policy frameworks that operate in binary modes: social or health; independent or dependent; living or dying.

Comparison of PRE-dilatation vs direct stenting in coronary treatment using the Medtronic AVE S670 Coronary Stent System (the PREDICT trial).

Current stent delivery systems make primary stenting (stent placement without predilatation) possible, but few controlled trials have been performed to evaluate the success, safety, cost saving, and potential benefit of this approach in reducing late restenosis. The Comparison of PRE-Dilatation Versus Direct Stenting In Coronary Treatment using the Medtronic AVE S670 Coronary Stent System trial was a 399-patient study comparing results with the Medtronic-AVE S670 stent to objective performance criteria based on prior approved stents, with subrandomization to direct stenting versus stenting after balloon predilatation. Overall, results with the S670 stent showed excellent success and safety, with delivery success of 99%, a 14-day adverse event rate of 6.8% (including 6.5% non-Q-wave myocardial infarction), and favorable angiographic (20%) and clinical (12%) restenosis rates. Direct stenting was successful in 92% of cases, with a 99.5% secondary success rate including additional pretreatment of initially unsuccessful direct-stenting attempts, and no increase in complications. There were modest ( approximately 10%) savings in fluoroscopy time, contrast use, and a decrease in angioplasty balloon use (0.6 vs 1.3 balloons/case), but no reduction in clinical or angiographic restenosis. Patients treated later in the study, with a device that had less balloon extension beyond the edges of the stent, had slightly lower angiographic restenosis rates (19% vs 23%). In conclusion, the S670 stent showed excellent overall performance. Although direct stenting was safe and highly successful, it offered only modest cost savings, and no reduction in late restenosis compared with stenting after predilatation.

The impact of optimal stenting techniques on cardiac catheterization laboratory resource utilization and costs.

Coronary stenting has been shown to reduce angiographic restenosis and improve clinical outcomes compared with conventional balloon angioplasty, but at greater in-lab cost. Recent studies have suggested that "optimal" stent deployment can eliminate the need for intensive oral anticoagulation after stenting, with the potential to reduce vascular complications, length of stay, and hospital cost. Between January and June 1995, we performed elective 1-vessel coronary stenting in 78 patients with a single, discrete (< 15 mm) coronary stenosis (optimal single-lesion group) and in 30 patients with either a single, long stenosis or serial discrete lesions (optimal multilesion group). Compared with stent patients from the Stent Restenosis Study (STRESS) economic substudy, optimal single-lesion stenting required more stents (1.3 +/- 0.6 vs 1.1 +/- 0.4, p <0.01) and more adjunctive angioplasty balloons per patient (2.5 +/- 1.0 vs 2.0 +/- 0.9, p <0.01). As a result, catheterization laboratory costs for single-lesion stenting increased by nearly $600 between 1993 and 1995 ($4,619 +/- $1,120 [median $4,435] to $5,209 +/- $1,697 [median $4,6731, p <0.01). Compared with the STRESS angioplasty group, optimal coronary stenting increased catheterization laboratory costs by nearly $2,200 ($3,012 +/- $1,382 [median $2,548] vs $5,209 +/- $1,697 [median $4,673], p <0.01). Optimal stenting of long lesions or multiple discrete stenoses increased catheterization laboratory costs by an additional $2,000 compared with optimal single-lesion stenting ($7,201 +/- $2,428 [median $6,887] vs $5,209 +/- $1,697 [median $4,673], p <0.01). These findings demonstrate that optimal coronary stenting increases in-lab procedural resource utilization and costs compared with historical stenting techniques. Based on the downstream cost savings seen in the STRESS trial ($1,400/patient), it is unlikely that current optimal stenting techniques will result in an overall cost savings compared with balloon angioplasty.

Angiographic predictors of reocclusion after thrombolysis: results from the Thrombolysis in Myocardial Infarction (TIMI) 4 trial.

OBJECTIVES: This study attempted to determine which lesion characteristics are associated with reocclusion by 18 to 36 h. BACKGROUND: Reocclusion of the infarct-related artery after successful reperfusion is associated with significant morbidity and up to a threefold increase in mortality. METHODS: Two hundred seventy-eight patients with acute myocardial infarction were randomized to receive either anisoylated plasminogen streptokinase activator complex (APSAC) or recombinant tissue-type plasminogen activator (rt-PA) or their combination. Culprit arteries were assessed for Thrombolysis in Myocardial Infarction (TIMI) flow grade, lesion ulceration, thrombus, collateral circulation and eccentricity. Minimal lumen diameter, percent diameter stenosis and lesion irregularity (power) were calculated using quantitative angiography. RESULTS: Reocclusion was observed more frequently in arteries with TIMI 2 versus TIMI 3 flow (10.4% vs. 2.2%, p = 0.003), in ulcerated lesions (10.7% vs. 3.0%, p = 0.009) and in the presence of collateral vessels (18.2% vs. 5.6%, p = 0.03). Similar trends were observed for eccentric (7.3% vs. 2.3%, p = 0.06) and thrombotic (8.4% vs. 3.3%, p = 0.06) lesions. Reocclusion was associated with more severe mean percent stenosis (77.9% vs. 73.9%, p = 0.04). Lesion length, reference segment diameter and Fourier measures of lesion irregularity were not associated with reocclusion. CONCLUSIONS: Several simply assessed angiographic variables, such as the presence of TIMI grade 2 flow, ulceration, collateral vessels and greater percent diameter stenosis at 90 min after thrombolytic therapy, are associated with significantly higher rates of infarct-related artery reocclusion by 18 to 36 h and may aid in identifying the subset of patients who are at significantly higher risk of early reocclusion and who potentially warrant further early pharmacologic or mechanical intervention.

Hydropneumomediastinum and bilateral hydropneumothorax as delayed complications of central venous catheterization.

A case of hydropneumomediastinum and bilateral hydropneumothorax from a central venous catheter is described. The complication is related to the position of the catheter after placement through the left internal jugular vein. Proper placement of a central venous line into the superior vena cava is essential to avoid this serious complication.

Data assessing the usefulness of screening obstetrical ultrasonography for detecting fetal and placental abnormalities in uncomplicated pregnancy: effects of screening a low-risk population.

To investigate the usefulness of screening in low-risk populations, the authors evaluated the yield of ultrasonography for detecting abnormalities in 678 clinically uncomplicated pregnancies. The yield of ultrasonography in high-risk women who were referred for amniocentesis was remarkably similar to the yield in other women. All four diagnoses of twins were correct, but overall only six of 12 initial ultrasound diagnoses of fetal demise or fetal anomalies were confirmed at delivery. Of the eight major fetal anomalies present at delivery, including two cases of Down's syndrome, three had been detected by ultrasonography; none of the nine minor anomalies had been detected, usually because they were too small or might be detectable only at a later gestational age. Although ultrasonography may have a nearly perfect predictive value for certain anomalies, on average, in this study, positive ultrasonography increased the probability of an adverse outcome of pregnancy from 5.3% to 36%, while a normal ultrasound examination decreased the probability to 4.4%. These data, which emphasize the implications of screening a low-risk population, suggest that recommendations regarding routine screening obstetrical ultrasonography should await sufficiently large controlled trials demonstrating consistent clinical benefit, in terms of reassurance or of providing a baseline for future comparison or in terms of improved outcome at a reasonable cost.

Identification and preliminary validation of predictors of major bleeding in hospitalized patients starting anticoagulant therapy.

Among 617 hospitalized patients who started long-term anticoagulant therapy, major bleeding developed before discharge in 28 (5 percent) and minor bleeding in another 38 (6 percent), with daily incidence rates of 0.4 and 0.5 percent, respectively. The most common site of bleeding was gastrointestinal, and one patient died from bleeding. Four independent risk factors for major in-hospital bleeding were identified and weighted using multivariate discriminant analysis in a randomly chosen group of 411 patients: co-morbid conditions other than the indication for anticoagulant therapy (specific signs of heart, liver, or kidney dysfunction, cancer, and severe anemia); the use of heparin to begin therapy in patients age 60 years or older; the intensity of therapy (measured by the maximal prothrombin time or partial thromboplastin time); and liver dysfunction that worsened during treatment. These findings were validated in an independent testing group of 206 patients; the risk factors identified 151 patients at low (1 percent) risk of major bleeding, 33 at moderate (6 percent) risk, and 22 at high (23 percent) risk. The accuracy and clinical impact of this prediction rule should be evaluated further in other hospitals.

Correlates of cardiac and sudden death after ambulatory monitoring in a community hospital. Importance of clinical characteristics, congestive heart failure and tachyarrhythmias.

To analyze the prognostic importance of arrhythmias on routine 24-hour ambulatory monitoring, we prospectively followed 755 consecutive patients undergoing monitoring at a community hospital in the context of usual medical care. Of the 755 patients, 114 (15%) had ventricular tachycardia on monitoring. At a mean follow-up of 38 months, multivariate survival analysis indicated that congestive heart failure was the strongest correlate of death from all causes (relative risk (RR) = 2.6), cardiac death (RR = 3.5), and the sudden cardiac death (RR = 5.6); ventricular tachycardia was significantly correlated with death from all causes and with cardiac death, but had only a borderline association with sudden cardiac death (RR = 1.9, p = 0.08). While ventricular tachycardia on ambulatory monitoring is of prognostic importance, congestive heart failure, as determined by routine clinical examination, was a more powerful prognostic correlate of deaths from all causes, death from cardiac causes, and sudden cardiac death.

Clinical response to coronary artery reoperations.

Repeat coronary artery bypass operations were performed on 112 patients at a university hospital between 1971 and 1981. When compared with patients who did poorly after a first operation but did not have repeat surgery, patients undergoing repeat surgery tended to be younger, to have a higher smoking rate and to have fewer prior myocardial infarctions, fewer diseased vessels and fewer lesions in distal vessels. At least 1 graft was occluded in 83% of patients undergoing reoperation, and a mean of 1.7 grafts were placed at reoperation. The operative mortality rate was 4%, with a follow-up mortality rate of 6% at a mean of 3.8 years. After reoperation, patients initially showed improvement to a mean specific activity scale class of 1.6, compared with 2.4 before the first operation and 2.7 before the second operation. The principal correlate of a better long-term symptomatic response compared with that in the period before the first operation was a lower serum cholesterol level, whereas the principal correlate of a better symptomatic response compared with that in the period just before the reoperation was the left ventricular ejection fraction. As recurrent symptoms after a first coronary artery operation become more prevalent, consideration of the selection factors and prognostic correlates of reoperation will become increasingly important.

Benefits of experience. Treating coronary artery disease.

The authors examined the issue of learning by doing in terms of both the cost and outcome of treating coronary artery disease at one hospital between 1977 and 1981. Over time, the quality of outcome improved for both medical and surgical patients. During this time of cost-plus reimbursement, there was less conclusive evidence of concurrent technical efficiency gains. These findings are consistent with the hypothesis that the benefits of experience can be substantial but they do not just happen: they require proper provider motivation.

Case-control analysis of risk factors for presence of aortic stenosis in adults (age 50 years or older).

To analyze whether atherosclerotic risk factors, including systemic hypertension, an elevated serum cholesterol level, smoking and diabetes, were associated with the presence of aortic stenosis (AS) in adults, 105 adults who had AS without coronary artery disease (CAD) were compared with 110 control subjects who had other types of valvular disease, 170 control subjects who underwent catheterization and had neither valvular disease nor CAD, and 269 matched control subjects who underwent general surgery. When using each control group separately or in combination, no risk factor showed consistent evidence of a significant association with the development of AS. If the true magnitudes of these associations are of the order previously reported for the development of CAD, the power of our study for detecting statistical significance ranges from 56 to 99%. In a supplemental analysis, 45 cases with both AS and CAD did not have a higher prevalence of risk factors than cases without CAD. Although a weak association between atherosclerotic risk factors and AS cannot be excluded, any such association is unlikely to be as strong as for predicting CAD.

Comparative costs versus symptomatic and employment benefits of medical and surgical treatment of stable angina pectoris.

For patients who underwent cardiac catheterization for stable angina pectoris at the authors' hospital, initial treatment charges including the cardiac catheterization were approximately $28,000 for coronary surgery and $6,000 for medical therapy. Even after controlling for disease severity and after including medical patients who crossed over to surgery, the slightly increased 3-year follow-up costs of medical therapy offset only approximately 11% of the far higher initial costs of surgery. Surgical patients were more likely to have sustained, substantial symptomatic improvement at 3 years (68% vs. 53%, P less than 0.05) but were no more likely to have, maintain, or regain a job. Although the cost-effectiveness of coronary surgery may compare favorably with other modern therapies for other conditions, coronary surgery did not pay for itself at 3-year follow-up in our patients.

The selective impact of a cardiology data bank on physicians' therapeutic recommendations.

We asked the physicians and medical students caring for 60 patients with symptomatic coronary artery disease, immediately after reviewing cardiac catheterization data, to choose medical or surgical therapy and to estimate prognosis one and three years after either therapy. The next day, each participant was given prognostic estimates generated from a large coronary artery disease data bank and again asked to estimate prognosis and choose therapy. Participants unanimously chose medicine for 20 patients (Group I) and surgery for 21 patients (Group III). For 19 patients (Group II), participants were divided on their choice of therapy. After seeing data bank estimates, participants rarely changed recommendations for Group I or Group III, but changed ten percent (9/90, p less than 0.01) of their Group II recommendations. Changes of recommendations by far (9/12, p = 0.02) favored medicine, causing the majority recommendation to change to medicine for two Group II patients. Therapeutic recommendations were guided mostly by pathoanatomy and the chance of improving medical regimens. Computer-generated prognostic data selectively influenced choices among the Group II cases where recommendations had been divided, resulting in changes toward less costly therapy.

A comparison of effects of inhaling a combined preparation of fenoterol with ipratropium bromide (Duovent) with those of fenoterol and salbutamol.

The effects of inhaling an aerosol preparation containing fenoterol 200 micrograms and ipratropium bromide 80 micrograms were compared with those of inhaling 200 micrograms of salbutamol and a similar dose of fenoterol on 20 patients with chronic bronchitis and four patients with chronic stable asthma. The dose of each drug was contained in 2 puffs taken from a metered-dose inhaler. Changes in airways function were assessed by measuring peak expiratory flow rate. Pulse, blood pressure and presence of any tremor were monitored to detect drug-induced side effects. No significant difference was found in the onset of action and overall bronchodilator effects between the three drugs. The combined preparation was found to have a significantly greater bronchodilator action three and four hours after inhalation compared to the other two drugs. A significant effect lasting six hours was found with salbutamol and fenoterol, but the combined preparation had an effect which was significant up to seven hours. There was no significant difference in the side effects which were minimal for all three drugs.

Clinical utility and management impact of M-mode echocardiography.

To determine the clinical utility and management impact of M-mode echocardiography, 182 echocardiograms were analyzed at a university teaching hospital. The physicians who ordered the echocardiograms said that 12 percent provided crucial information that was not available from other tests and that 26 percent resulted in a change in patient management. According to two independent board-certified cardiologist-reviewers, 86 percent of echocardiograms were appropriately ordered, but only 15 echocardiograms (8 percent) were actually needed for a change to a new and appropriate management. According to the reviewers, the 77 Group I M-mode echocardiograms (those ordered to evaluate left ventricular function, left atrial size, potential cardiac sources of emboli, or the possibility of bacterial endocarditis, or those ordered in patients who, according to the ordering physician, had undergone or would undergo catheterization regardless of the results of echocardiography) were less likely than the 105 Group II M-mode echocardiograms (those ordered to evaluate possible mitral valve prolapse, hypertrophic cardiomyopathy, valvular function, or the pericardium) to be ordered appropriately, to provide helpful information, or to provide crucial results. Group I echocardiograms had reviewer-assessed appropriate management impact in only one case (1 percent) compared with a 13 percent rate of management impact for Group II M-mode echocardiograms (p less than 0.01). Although echocardiography can be accurate and valuable with yields similar to those of other noninvasive procedures, 77 (42 percent) of 182 M-mode echocardiograms in this hospital could be predicted at the time of ordering to be in a low-yield group.

Incremental value of the exercise test for diagnosing the presence or absence of coronary artery disease.

To determine the incremental value of the exercise test (ETT) for diagnosing coronary artery disease (CAD), we derived a multivariate logistic regression model for the pre-ETT prediction of CAD using data from 3840 patients at Duke University. We then applied the model to 324 patients at the Brigham and Women's Hospital. Using seven clinical factors, the multivariate model had an 84% overall predictive accuracy on both the training (Duke) and the validation (Brigham) sets of patients. Three ETT factors (ST-segment change in patients not taking digitalis, absence of ST-segment change in patients taking digitalis, ETT stopped because of ECG or blood pressure changes) had incremental, significant predictive power, but overall predictive accuracy based on both clinical and ETT factors improved only to 87%. When the ETT result was important enough to move the probability of CAD across a potential therapeutic threshold, the direction of the change in probability was correct only two-thirds of the time. Thus, the ETT was of limited value in predicting the presence or absence of CAD after other easily obtainable clinical data were taken into account.

Pitfalls in the serial assessment of cardiac functional status. How a reduction in "ordinary" activity may reduce the apparent degree of cardiac compromise and give a misleading impression of improvement.

Because the New York Heart Association (NYHA) classification system categorizes patients based on subjective impression of the degree of functional compromise, a reduction in exercise might make a patient seem improved because the new lower level of ordinary activity produced fewer symptoms. To test this hypothesis, we studied three different sets of patients and compared their NYHA classes to their functional classes as determined by a new Specific Activity Scale (SAS) that is based on the metabolic equivalents of oxygen consumption required for activities the patient actually performs. Among ambulatory patients referred for exercise tests, the NYHA class was higher (i.e. indicated the patient was more limited) in 28% of patients and the SAS class was higher in 14% (p less than 0.001). Among patients interviewed at or near the time of catheterization for chest pain, the NYHA was higher in 20% and the SAS class was higher in 20% (p = NS). In both medically and surgically treated patients interviewed 1--3 yr after cardiac catheterization, the NYHA class was higher in only 4%, whereas the SAS class was higher in 28% (p less than 0.001). The SAS class was significantly more likely to be higher in patients who were not working full time and in patients who described their present activity level as sedentary or light. When the NYHA and SAS systems disagreed as to whether a patient was improved, SAS was significantly more likely to correlate with the patient's self-assessment. These findings suggest that some patients restrict their activity as their cardiac disease progresses; the resultant change in the definition of ordinary activity may reduce the apparent degree of cardiac compromise and thus give a false impression of improvement by NYHA criteria.

Dissecting the hospital stay: a method for studying patient staging in hospitals.

A methodology is proposed and tested for the staging of patients thorugh a hospital stay. Measurements in a university-affiliated hospital and a community hospital in the Boston area showed similar staging patterns with about half of the sample having abnormal signs and symptoms while under treatment. The second-largest sample group in both hospitals, consisting of 11% of the sample, occupied beds although ready for discharge. The methodology indicated those patient-time units in the hospital which might be amenable to further reduction and gave upper bounds on that compression. Contrary to prior expectations, 90% of the patients sampled followed a well-defined sequence from admission to discharge with only 10% having complications of the admitting diagnosis, new diagnosis or iatrogenic illness.

Quality, efficiency, and cost of a physician-assistant-protocol system for managment of diabetes and hypertension.

Briefly trained physicians assistants using protocols (clinical algorithms) for diabetes, hypertension, and related chronic arteriosclerotic and hypertensive heart disease abstrated information from the medical record and obtained history and physical examination data on every patient-visit to a city hospital chronic disease clinic over a 18-month period. The care rendered by the protocol system was compared with care rendered by a "traditional" system in the same clinic in which physicians delegated few clinical tasks. Increased thoroughness in collecting clinical data in the protocol system led to an increase in the recognition of new pathology. Outcome criteria reflected equivalent quality of care in both groups. Efficiency time-motion studies demonstrated a 20 per cent saving in physician time with the protocol system. Coct estimates, based on the time spent with patients by various providers and on the laboratory-test-ordering patterns, demonstrated equivalent costs of the two systems, given optimal staffing patterns. Laboratory tests were a major element of the cost of patient care,and the clinical yield per unit cost of different tests varied widely.