Asthma severity categorization using a claims-based algorithm or pulmonary function testing.

OBJECTIVES: This study was performed to determine whether pulmonary function test results would appreciably alter asthma severity categorization determined by an algorithm using information readily available in administrative databases. METHODS: Patients 6 to 64 years of age with asthma diagnosed from 1999-2005, who had at least one pulmonary function test, were identified from a claims database of a medical group practice located in central Massachusetts. Asthma severity for these patients was categorized using information available in an administrative database (claims-based algorithm) and by percent predicted forced expiratory volume in 1 second (FEV(1)) or peak expiratory flow (PEF) abstracted from medical charts (pulmonary function test method). Gamma rank correlation index was used to measure the association between the two severity categorization methods. Total and asthma-related healthcare costs for each severity category were compared between the two different approaches. RESULTS: There was a significant ordinal association between severity categorization with the two classification approaches (p = 0.0002). The pulmonary function test method resulted in more frequent mild categorizations and less frequent moderate and severe categorizations than the claims-based algorithm. In only 10.9% of patients did the pulmonary function test method result in a more severe asthma category than the claims-based algorithm. Patients with more severe asthma, determined by both methods, had higher total and asthma-related health care costs. Total and asthma-related health care costs were similar for each asthma severity categorization for the two classification approaches, except for asthma-related costs in the moderate severity categories. CONCLUSION: The claims-based algorithm generally categorized patients as having more severe asthma than the approach using pulmonary function test results. Pulmonary function test results would have appreciably changed asthma severity categorization in only a small percent of patients. These findings add further support to the use of administrative database analyses for the evaluation of asthma care in large populations.

The frequency of workplace exacerbation among health maintenance organisation members with asthma.

OBJECTIVES: Workplace conditions can potentially contribute to the worsening of asthma, yet it is unclear what percentage of adults with asthma experience workplace exacerbation of symptoms. The objective of this investigation was to determine the prevalence of workplace exacerbation of asthma (WEA). METHODS: Adults with asthma aged 18-44 were enrolled into the baseline survey of a longitudinal study. Members of a health maintenance organisation were considered candidates for participation if they fulfilled membership, diagnostic, and treatment criteria based on automated review of electronic billing, claims, and pharmacy records. Diagnosis and treatment were confirmed by manual review of medical records. A telephone questionnaire was administered. A work related symptom score was assigned to each participant based on responses to questions about work related asthma symptoms, medication use, and symptom triggers. Blinded to participants' answers to these questions, two researchers independently reviewed the self-reported work histories and assigned exposure ratings. A final exposure score was then calculated. Participants with sufficient evidence for work related symptoms and exposure were classified as having WEA. RESULTS: Of the 598 participants with complete data, 557 (93%) were working, and 136 (23%) fulfilled the criteria for WEA. Those with WEA were more likely to be male and to report that they had been bothered by asthma symptoms during the past seven days. CONCLUSIONS: Workplace exacerbation of asthma was common in this study population, occurring in over a fifth of these adults with asthma. Physicians should consider that work can contribute to the exacerbation of symptoms when treating adults with asthma.

Timing of oral anticoagulation therapy in the treatment of angiographically proven acute pulmonary embolism.

The optimal time to begin oral anticoagulation therapy with warfarin sodium in the treatment of acute pulmonary embolism has not been defined. To evaluate the relative cost, efficacy, and safety of early initiation of warfarin therapy, we reviewed the medical records of 38 patients with angiographically proven pulmonary embolism. Patients were divided into two groups: those who received warfarin early (less than or equal to 3 days after initial heparin sodium bolus, n = 17) and those who were treated late (greater than 3 days after initial heparin bolus, n = 21). After three months of follow-up, there was a similar incidence of mortality, recurrent pulmonary embolism, and bleeding complications in both treatment groups. Length of hospitalization was substantially less in the early group (9.6 +/- 2.0 vs 11.8 +/- 2.1 days). Early warfarin therapy in the treatment of acute pulmonary embolism appears to be both cost-effective and safe. A prospective multicenter controlled trial should be performed.

No reflow in patients undergoing primary angioplasty for acute myocardial infarction at high risk: incidence and predictive factors.

AIM: Percutaneous coronary intervention (PCI) is a consolidated therapeutic strategy for the treatment of acute myocardial infarction (AMI), but achieving a TIMI 3 flow does not always correspond to true tissue reperfusion. The aim of the study was to evaluate the incidence and predictive factors of no reflow in patients undergoing primary angioplasty (PCI) for AMI at high risk, in the setting of a provincial cardiological emergency network. METHODS: We retrospectively analyzed the ECGs of 360 consecutive patients undergoing primary PCI, between 2001-2004, recorded before and 90 min after the procedure, and compared them with the angiographic data. RESULTS: The patients were divided into 2 groups: group A (reperfused) with a >50% reduction in ST and group B (no reflow) with a <50% reduction in ST but a TIMI 3 flow in the epicardial vessel. The 2 groups were comparable in terms of mean age, sex, diabetes and AMI site. However, there were statistically significant differences between the groups in terms of precoronary time, Killip class IV, ejection fraction, mean leukocyte count, C-reactive protein, and the periprocedural administration of abciximab. Total mortality was 6%: 14% in group B vs 3% in group A. CONCLUSIONS: Our data show that a fair percentage of patients (24%) with a TIMI 3 flow after PCI during ST-elevation MI do not show ECG signs of effective reperfusion and have a higher in-hospital mortality rate. Precoronary time and the inflammatory phlogistic substrate are important independent predictors of no reflow. Pretreatment with abciximab, particularly if it is not periprocedural, can prevent the occurrence of no reflow.

Measurement of respiratory sensation in interstitial lung disease. Evaluation of clinical dyspnea ratings and magnitude scaling.

To evaluate measurements of respiratory sensation in ILD, we compared ratings of breathlessness from three clinical scales with the perceived magnitude of added elastic loads in 20 symptomatic ILD patients. Dyspnea ratings were obtained by two independent observers for each clinical method. Perceived magnitude of four elastic loads was selected from the Borg category scale; these estimates were summarized using the psychophysical power function equation. Ten age-matched healthy subjects also scaled the magnitude of added elastic loads. Dyspnea ratings from the three clinical scales were significantly interrelated. Mean exponents for mouth pressure developed during elastic loading were similar in the patient and control groups. Dyspnea ratings and exponents for elastic loads were not significantly correlated in ILD patients. Of the physiologic parameters examined, Dsb and gas exchange during exercise correlated significantly with clinical dyspnea ratings; none correlated with the exponent for added elastic loads. These data demonstrate that clinical dyspnea ratings provide valid measures of breathlessness in patients with ILD which are independent of the perception of respiratory loads.

"Warm-up" phenomenon in adult and elderly patients with coronary artery disease: further evidence of the loss of "ischemic preconditioning" in the aging heart.

BACKGROUND: A reduction of exercise-induced ischemia in patients with coronary artery disease by means of brief period of exercise followed by resting is called the "warm-up" phenomenon. This phenomenon may represent a clinical counterpart of "ischemic preconditioning." We studied the warm-up phenomenon in both adult and elderly patients with similar angiographic evidence of coronary artery disease, using three exercise tests after excluding the "training effect." METHODS: In order to verify the presence of "training effect," three exercise tests were performed in days 1, 2, and 3 ("training" tests). The third test was used as baseline for a successive test, performed after a recovery period of 10 minutes to reestablish baseline electrocardiographic conditions. A third exercise test was performed 30 minutes later ("warm-up" tests). RESULTS: "Training" tests did not differ in all parameters in both adult and elderly patients. "Warm-up" tests showed that time to onset 1-mm ST depression was significantly higher (p < .001). whereas ST depression and time to recovery was significantly lower in the second and third test in adult but not in elderly patients (p < .001 ). Difference (in seconds) in the time at which 1-mm ST depression occurred on first warm-up exercise compared with the second was inversely correlated with age (p < .001 ). CONCLUSIONS: Previous exercise followed by resting is able to reduce the successive exercise-induced ischemia ("warm-up" phenomenon) in adult but not in elderly patients with coronary artery disease. This is independent of a greater age-related severity of coronary disease and of "training effect." These results confirm the hypothetical age-related reduction of "ischemic preconditioning" in aging heart.

Radiation-induced lung injury.

The use of radiation therapy is limited by the occurrence of the potentially fatal clinical syndromes of radiation pneumonitis and fibrosis. Radiation pneumonitis usually becomes clinically apparent from 2 to 6 months after completion of radiation therapy. It is characterized by fever, cough, dyspnea, and alveolar infiltrates on chest roentgenogram and may be difficult to differentiate from infection or recurrent malignancy. The pathogenesis is uncertain, but appears to involve both direct lung tissue toxicity and an inflammatory response. The syndrome may resolve spontaneously or may progress to respiratory failure. Corticosteroids may be effective therapy if started early in the course of the disease. The time course for the development of radiation fibrosis is later than that for radiation pneumonitis. It is usually present by 1 year following irradiation, but may not become clinically apparent until 2 years after radiation therapy. It is characterized by the insidious onset of dyspnea on exertion. It most often is mild, but can progress to chronic respiratory failure. There is no known successful treatment for this condition.

Characterisation of asthma management in the Fallon Community Health Plan from 1988 to 1991.

In order to characterise asthma management in a managed care setting, we identified 10,301 patients who were diagnosed with asthma between 1 January 1988 and 31 December 1991 at a group model health maintenance organisation in central Massachusetts, US. We obtained for these patients automated utilisation files containing data on medications, hospitalisations, emergency room visits, office visits, and estimated costs of these services. The medication dispensed to the greatest proportion of patients was beta 2 agonists either by inhalation (56%) or orally (21%). Theophylline was dispensed to 23% of the patients. Maintenance therapy was inhaled anti-inflammatory medication was uncommon, as inhaled corticosteroids (17%) and sodium cromoglycate (cromolyn sodium) [8%] were dispensed to fewer patients than other asthma medications. Among patients who had been hospitalised in the previous year, 36% were presently receiving inhaled corticosteroids, and among patients who used at least one beta 2 agonist metered-dose inhaler per month, 49% were presently receiving inhaled corticosteroids. Economic analyses showed that only 8% of the patients had either a hospital admission or an emergency room visit, but hospital costs among these patients accounted for 25% of the total costs of asthma care. In addition, the top 10% most expensive patients accounted for 42% of the total cost of asthma care. We conclude that a substantial proportion of patients at increased risk of a severe attack, by virtue of having a recent hospitalisation, do not receive maintenance anti-inflammatory therapy, and that hospitalisations among a relatively small proportion of asthma patients contribute significantly to the cost of asthma care.

Cardiovascular responses to rowing.

The purpose of this investigation was to evaluate the cardiovascular responses to rowing. In the first part of the study, heart rate (HR) and cardiac output (Q) were measured at rest and at three steady-state exercise levels on the variable-resistance rowing ergometer in 10 female and 11 male subjects. Q was determined non-invasively by the equilibration method of CO2 re-breathing, and stroke volume (SV) was calculated. Subjects varied in rowing ability from healthy, inexperienced rowers to competitive athletes. The linear relationships between Q and oxygen consumption for the women (r = 0.57; P less than 0.001; slope = 5.2 +/- 1.1) (mean +/- SD) and the men (r = 0.58; P less than 0.001; slope = 6.1 +/- 1.4) were similar to published values for other types of upright exercises. For both mean and women, SV increased from rest to the first level of exercise, and then reached a plateau at or before the second exercise intensity. Between the second and third levels of exercise, SV decreased significantly in the female subjects (107 +/- 18 vs 94 +/- 16 ml; P less than 0.05), but not in the male subjects (128 +/- 1 1 vs 126 +/- 15 ml; P = not statistically significant). In the second part of the study, HR, Q, and SV were compared on the cycle and rowing ergometers on successive days in eight additional subjects. At similar levels of oxygen consumption and Q, HR was significantly higher, and SV was significantly lower during rowing exercise than with cycle exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

The aging lung.

Structural changes occur in the respiratory system with advancing age. Lung elasticity decreases, stiffness of the chest wall increases, and respiratory muscle strength declines. These alterations contribute to gradual, but progressive, reductions in forced vital capacity, expiratory flow rates, diffusing capacity, gas exchange, ventilatory drive, and respiratory sensation. Cigarette smoking accelerates the age-related decline in flow rates. Understanding the effects of aging on the lung is important in order to distinguish pathologic changes from changes that are part of the normal aging process.

Managing price, gaining profit.

The fastest and most effective way for a company to realize maximum profit is to get its pricing right. The right price can boost profit faster than increasing volume will; the wrong price can shrink it just as quickly. Yet many otherwise tough-minded managers miss out on significant profits because they shy away from pricing decisions for fear that they will alienate their customers. Worse, if management isn't controlling its pricing policies, there's a good chance that the company's clients are manipulating them to their own advantage. McKinsey & Company's Michael Marn and Robert Rosiello show managers how to gain control of the pricing puzzle and capture untapped profit potential by using two basic concepts: the pocket price waterfall and the pocket price band. The pocket price waterfall reveals how price erodes between a company's invoice figure and the actual amount paid by the customer--the transaction price. It tracks the volume purchase discounts, early payment bonuses, and frequent customer incentives that squeeze a company's profits. The pocket price band plots the range of pocket prices over which any given unit volume of a single product sells. Wide price bands are commonplace: some manufacturers' transaction prices for a given product range 60%; one fastener supplier's price band ranged up to 500%. Managers who study their pocket price waterfalls and bands can identify unnecessary discounting at the transaction level, low-performance accounts, and misplaced marketing efforts. The problems, once identified, are typically easy and inexpensive to remedy.

Administration of a perfluorochemical emulsion plus carbogen breathing does not alter radiation pneumonitis.

The effects of treatment with a perfluorochemical emulsion plus carbogen on radiation pneumonitis were examined in a rat model system. Rats received thoracic irradiation (15 Gy) and radiation reactions in the lungs were assessed 25 and 35 days later using bronchoalveolar lavage and histologic assessments. The irradiated lungs showed the expected evidence of acute radiation pneumonitis, including protein leaks and also alveolar infiltrates and interstitial infiltrates. Administration of a perfluoro-chemical emulsion (Fluosol; 15 ml/kg) plus carbogen breathing for 30 min before and during irradiation did not enhance the reactions seen in the irradiated lungs.

Risk and incidence of asthma attributable to occupational exposure among HMO members.

Occupational asthma may account for a significant proportion of adult-onset asthma, but incidence estimates from surveillance of physician reports and workers' compensation data (0.9 to 15/100,000) are lower than expected from community-based cross-sectional studies of asthma patients. We conducted a prospective cohort study of 79,204 health maintenance organization members between the ages of 15 and 55 at risk for asthma. Computerized files, medical records, and telephone interviews were used to identify and characterize asthma cases. Evidence for asthma attributable to occupational exposure was determined from work-related symptoms and workplace exposure. The annual incidence of clinically significant, new-onset asthma was 1.3/1,000, and increased to 3.7/1,000 when cases with reactivation of previously quiescent asthma were included. Criteria for onset of clinically significant asthma attributable to occupational exposure were met by 21% (95% CI 12-32%) of cases giving an incidence of 71/100,000 (95% CI 43-111). Physicians documented asking about work-related symptoms in 15% of charts, and recorded suggestive symptoms in three cases, but did not obtain occupational medicine consultation, diagnose occupational asthma, report to the state surveillance program, or bill workers' compensation for any of them. These data suggest that the incidence of asthma attributable to occupational exposures is significantly higher than previously reported, and accounts for a sizable proportion of adult-onset asthma.

Radiation pneumonitis. Bronchoalveolar lavage assessment and modulation by a recombinant cytokine.

A common side effect of radiotherapy is the development of fibrosis in the irradiated tissue. To study the mechanisms of this fibrogenic response, we developed a model system of whole-lung radiation in the rat and studied the evolution of injury by assessment of the cells and protein recovered by lavage. Once the pattern of injury was known, we attempted to modulate this reaction by administering the cytokine interferon-gamma (IFN-gamma). Rats received 15 Gy radiation to the whole thorax and were studied by lung lavage at intervals of 1 to 35 days after radiation. The effect of radiation was an initial (24 h) leak of protein, unaccompanied by cellular alterations, that resolved by 48 h. This was followed 2 wk later by a phase of inflammatory cell recruitment and more significant protein leak. A third phase of increase in inflammatory cells and further increase in protein flux was noted at Day 35. A significant cellular infiltrate was seen in lung sections obtained from animals treated in parallel experiments. IFN-gamma was given by osmotic pump from Day 0 to Day 35. This treatment significantly attenuated the PMN recruitment and protein leak (p < 0.002 and 0.01, respectively) at Days 25 and 35. Histologic sections demonstrated reduced alveolar cellularity and exudate at Day 25 (p < 0.05); however, significant numbers of inflammatory cells and exudate were present in irradiated and IFN-gamma-treated animals at Day 35. These data indicate that inflammatory cell recruitment may play a role in the lung injury following radiation. Furthermore, these preliminary data indicate that a cytokine blocks this reaction.

Comparison of clinical dyspnea ratings and psychophysical measurements of respiratory sensation in obstructive airway disease.

To investigate the hypothesis that clinical methods and psychophysical testing provide different information about breathlessness, we compared dyspnea ratings from a modified Medical Research Council (MRC) scale, the Oxygen-Cost Diagram (OCD), and the Baseline Dyspnea Index (BDI) with the perceived magnitude of added loads in 24 patients with obstructive airway disease (OAD) who experienced dyspnea on exertion. Age of the patients was 55.8 +/- 13.7 yr (mean +/- SD), FEV1 was 1.77 +/- 0.81 L, and FEV1/FVC ratio was 52.6 +/- 10.5%. Dyspnea ratings were obtained for each clinical method by 2 independent observers; estimates of the magnitude of 5 resistive loads (10 to 85 cm H2O/L/s) were obtained using the Borg category scale (0 to 10). For comparative purposes, 12 age-matched (48.9 +/- 13.5 yr) healthy subjects were also studied. Clinical ratings of dyspnea obtained in patients for MRC (range, 0 to 4), OCD (range, 23 to 98), and BDI (range, 0.5 to 12.0) were all highly interrelated (rs = 0.79, -0.83, and -0.71; p less than 0.001 for all comparisons). Exponents of the psychophysical power function for resistive breathing loads were similar for patients with OAD (0.57 +/- 0.27) and control subjects (0.63 +/- 0.18) (p = NS). Clinical dyspnea scores were significantly correlated with both FEV1 and FVC; however, neither dyspnea ratings nor lung function were significantly related to the exponent for added breathing loads in the patient group. These comparisons indicate that in patients with symptomatic OAD, clinical methods for rating dyspnea are interrelated and are correlated with lung function, but are independent of perception of resistive breathing loads.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy and pharmacokinetics of gallopamil in patients with coronary artery disease.

We prospectively studied 10 patients with stable exertional ischaemia, selected from a larger group of patients referred for suspected coronary artery disease or to detect residual ischaemia after myocardial infarction, to evaluate pharmacokinetic changes during chronic treatment with gallopamil and its correlation with clinical efficacy in patients with coronary artery disease. Our study consisted of a 1-week run-in single-blind placebo treatment and a 4-week single-blind gallopamil treatment. At the end of the run-in period patients underwent two different exercise tests, the first 2 hours and the second 7 hours after placebo administration. During active treatment all patients underwent two different exercise tests, the first 2 hours and the second 7 hours after gallopamil (50 mg) administration on the 1st and 28th days of gallopamil therapy. On the same days in eight of the patients we evaluated gallopamil pharmacokinetic changes. Our data revealed a rapid increase of unchanged gallopamil and its metabolite (norgallopamil) in the plasma, and a peak concentration of these substances about 2 hour after oral administration on both the 1st and 28th day of observation. Moreover, our results demonstrated an increase between the first and 28th day of treatment in peak concentration of unchanged gallopamil in the plasma, and of AUC 0-infinity and AUC o-c values during chronic treatment with gallopamil. Our clinical data showed an improvement in exercise results during gallopamil therapy related to increased concentration of the drug.

Verapamil reduces dipyridamole-induced myocardial ischemia in patients with coronary artery disease.

The aim of this study was to evaluate the effects of verapamil administration on dipyridamole-induced transient wall-motion abnormalities as detected by two-dimensional echocardiographic monitoring in patients with coronary artery disease. Twenty-eight patients (16 men and 12 women; mean age, 60+/-7 years) with angiographic evidence of significant coronary artery disease, positive dipyridamole echocardiography test results at basal condition on two consecutive days, were prospectively studied. Patients were randomized to verapamil (360 mg/day) or placebo treatments, given in three divided doses daily for 7 days; at the end of this time, each patient crossed over to the alternate regimen. Dipyridamole echocardiographic testing was repeated at the end of each treatment period. Our data demonstrate that verapamil significantly reduces the dipyridamole-induced wall-motion score index, a quantitative marker of acute myocardial ischemia (1.7+/-0.4 vs. 1.3+/-0.2; p<0.001). Hemodynamic data show that the drug reduces heart rate and rate-pressure product at basal condition (heart rate from 75+/-8 to 67+/-9 beats/min; p<0.001; rate-pressure product from 99+/-13 to 86+/-13 U x 10(-2); p<0.001) and at peak dipyridamole infusion (heart rate from 96+/-8 to 89+/-6 beats/min; p<0.001; rate pressure product from 127+/-21 to 118+/-13 U x 10(-2); p<0.05) with respect to placebo treatment. We conclude that verapamil is able to reduce dipyridamole-induced ischemia, as detected by two-dimensional echocardiographic monitoring, in patients with coronary artery disease by reducing, at least partially, myocardial oxygen consumption. Moreover, its beneficial action could be related to the effects of the drug on coronary collateral circulation and on sympathetic modulation.