The progressive cost of complications in type 2 diabetes mellitus.

BACKGROUND: A substantial proportion of the costs of diabetes treatment arises from treating long-term complications, particularly cardiovascular and renal disease. However, little is known about the progressive cost of these complications. Firmer knowledge would improve diabetes modeling and might increase the financial and organizational support for the prevention of diabetic complications. METHODS: We analyzed 9 years of clinical data on 11 768 members of a large group-model health maintenance organization who had probable type 2 diabetes mellitus. We ascertained the presence of cardiovascular and renal complications, staged the members progression, and estimated their incremental costs by stage. RESULTS: We found no significant differences between men and women in the prevalence or staging of complications. Per-person costs increased over baseline ($2033) by more than 50% ($1087) after initiation of cardiovascular drug therapy and/or use of a cardiologist, and by 360% ($7352) after a major cardiovascular event. Abnormal renal function increased diabetes treatment costs by 65% ($1337); advanced renal disease, by 195% ($3979); and end-stage renal disease, by 771% ($15 675). Both cardiovascular and renal diseases were more common among older subjects, but age did not affect the additional costs of these complications. Women had substantially higher medical care costs after controlling for age and presence of complications. Incremental cost estimates based solely on "labeled" events significantly underestimate true incremental cost. CONCLUSIONS: In an aggregate population, the greatest cost savings would be achieved by preventing major cardiovascular events. For individuals, the greatest savings would be achieved by preventing progression to stage 3 renal disease.

Type 2 diabetes: incremental medical care costs during the first 8 years after diagnosis.

OBJECTIVE: To describe and analyze the time course of medical care costs caused by type 2 diabetes, from the time of diagnosis through the first 8 postdiagnostic years. RESEARCH DESIGN AND METHODS: From electronic health maintenance organization (HMO) records, we ascertained the ongoing medical care costs for all members with type 2 diabetes who were newly diagnosed between 1988 and 1995. To isolate incremental costs (costs caused by the diagnosis of diabetes), we subtracted the costs of individually matched HMO members without diabetes from costs of members with diabetes. RESULTS: The economic burden of diabetes is immediately apparent from the time of diagnosis. In year 1, total medical costs were 2.1 times higher for patients with diabetes compared with those without diabetes. Diabetes-associated incremental costs (type 2 diabetic costs minus matched costs for people without diabetes) averaged $2,257 per type 2 diabetic patient per year during the first 8 postdiagnostic years. Annual incremental costs varied relatively little over the period but were higher during years 1, 7, and 8 because of higher-cost hospitalizations for causes other than diabetes or its complications. CONCLUSIONS: For the first 8 years after diabetes diagnosis, patients with type 2 diabetes incurred substantially higher costs than matched nondiabetic patients, but those high costs remained largely flat. Once the growth in costs due to general aging is controlled for, it appears that diabetic complications do not increase incremental costs as early as is commonly believed. Additional research is needed to better understand how diabetes and its diagnosis affect medical care costs over longer periods of time.

Effects of the dipyridamole test on left ventricular function in coronary artery disease.

The dipyridamole stress test is used with thallium-201 to detect areas of inhomogeneity of blood flow that point to coronary artery disease (CAD). It is unclear whether dipyridamole produces inhomogeneous perfusion only or whether it actually decreases net flow in the obstructed vessels and produces true ischemia. It is also unclear what effect dipyridamole has on global and segmental left ventricular function. Therefore, ejection fraction, segmental wall motion and ventricular volume equivalents were measured before and after dipyridamole in 113 patients and 32 normal subjects. Ejection fraction responded in an abnormal fashion in 98 patients (87%), decreasing from 49 +/- 11% to 43 +/- 13% (p less than 0.0001), whereas it increased in 29 normal subjects (90%) from 57 +/- 6% to 64 +/- 10% (p less than 0.0001). Wall motion worsened distinctly in 75 patients (66%), and pressure/volume ratio deteriorated in 72%. The effect of dipyridamole lasted between 10 and 25 minutes, but was promptly reversed by aminophylline. These findings indicate that dipyridamole generally induces true ischemia in CAD. Furthermore, the degree of dysfunction is related to the angiographically assessed severity of CAD. The shortness of breath (seen in 10% of patients) may be partially explained by the findings, and it seems advisable to give aminophylline to every patient in order to promptly correct left ventricular dysfunction.

Continuous intravenous epoprostenol therapy for pulmonary hypertension in Gaucher's disease.

Gaucher's disease is a rare disorder characterized by a deficiency of lysosomal beta-glucosidase. Pulmonary hypertension, the etiology of which is unclear, has been reported to occur in association with Gaucher's disease. We report the use of continuous intravenous epoprostenol (prostacyclin), which has been used to treat other forms of pulmonary hypertension, in a patient with pulmonary hypertension associated with Gaucher's disease. Although its mechanism of action remains unknown, epoprostenol may be an effective form of therapy for chronic pulmonary hypertension due to a variety of conditions, one of which is Gaucher's disease.

Increased intensity of the murmur of hypertrophic obstructive cardiomyopathy with carotid sinus pressure.

In a prospective study murmurs increased in intensity with carotid sinus pressure in 18 of 26 patients with hypertrophic obstructive cardiomyopathy (HOCM) (sensitivity, 69.2 percent for the 26 patients, 85.7 percent for the 21 patients in whom heart rate and blood pressure decreased with carotid sinus pressure). On the other hand, the murmur remained constant or decreased in all but one of 104 patients with valvular aortic stenosis, mitral insufficiency, hypertrophic nonobstructive cardiomyopathy, and systolic murmurs of miscellaneous origins (specificity, 99 percent; positive predictive value, 94.7 percent). Catheterization, indirect arterial pressure tracings, and echocardiographic studies indicated that carotid sinus pressure-induced bradycardia was associated with increased left ventricular outflow tract obstruction. The carotid sinus pressure-induced increase in the murmur is probably multifactorial: decreased aortic pressure and impedance; increased contractility immediately on sudden slowing of heart rate; further increase in obstruction as the mitral valve systolic anterior movement is enhanced; and delayed vasodilatation maintaining the obstruction even after return of heart rate to precarotid sinus pressure values. An increase in a systolic murmur with carotid sinus pressure is characteristic of HOCM.

Transient bradycardia induced by carotid sinus pressure increases outflow obstruction in hypertrophic obstructive cardiomyopathy but not in valvular aortic stenosis.

BACKGROUND: The murmur of hypertrophic obstructive cardiomyopathy (HOCM) increases in intensity in about 80% of those patients in whom carotid sinus pressure (CSP) slows the heart rate. This does not occur in valvular aortic stenosis (AS). STUDY OBJECTIVES, DESIGN, AND PATIENTS: It was hypothesized that left ventricular (LV) obstruction increases with CSP in HOCM and not in AS. Furthermore, it was not clear whether it was the sudden bradycardia or CSP itself that was responsible for the effect noted. Therefore, studies were performed using two different interventions: (1) Doppler echocardiography was performed before and during CSP in 36 HOCM patients and 21 AS patients; (2) two patients with DDD pacemakers and HOCM were examined before and after pacemaker rate slowing. Finally, atrial pacing was performed in three HOCM patients at catheterization, and atrial pacing was either slowed or stopped (without CSP). RESULTS: LV outflow velocity and pressure gradient increased in 28 of 30 HOCM patients (92%) in whom heart rate decreased with CSP. The peak instantaneous pressure gradient increased from 45+/-37 to 77+/-53 mm Hg (p<0.005), and the velocity contour became more typical of HOCM. The pressure gradient increased from 30 mm Hg to 64 and 81 mm Hg, respectively, in the two patients with DDD pacemakers after pacemaker rate slowing. Similar results were seen with slowing or cessation of atrial pacing at catheterization. In contrast, the pressure gradient increased in only three of 21 AS patients (14%), to 44+/-28 from 41+/-25 mm Hg, and remained unchanged in the other 18. CONCLUSION: This study shows that LV outflow velocity and pressure gradient increase markedly in most HOCM patients (92%) if CSP succeeds in slowing the heart rate, but not in patients with valvular AS. A similar effect is obtained by simply decreasing the atrial rate in patients with DDD or atrial pacemakers. This increase in outflow tract obstruction is sufficient to account for the increase in murmur intensity. Decreased afterload (secondary to greater aortic decompression with the longer diastole), increased intrinsic force of contraction with the bradycardia (the Woodworth effect), and Starling's law may play independent roles in the dynamic increase in obstruction observed during CSP in patients with HOCM. Worsening of mitral regurgitation was not clearly shown to contribute to the increase in murmur, but it cannot readily be ruled out.

Early calcification and obstruction of a mitral porcine bioprosthesis.

A patient is described in whom severe prosthetic valvular stenosis developed ten months after mitral valve replacement with an Angell-Shiley porcine heterograft. At emergency operation, calcification of the prosthesis was revealed. Early calcification and stenosis of a porcine heterograft valve is a life-threatening complication that must be recognized promptly and treated by emergency valve replacement.

Ten-year follow-up of antidiabetic drug use, nonadherence, and mortality in a defined population with type 2 diabetes mellitus.

Studies performed for drug registration provide little insight into the long-term use and effectiveness of drugs in "real world" populations and settings. To obtain such insight, we used 10 years of electronic medical-record data from Kaiser Permanente Northwest Division, a large, group-model health maintenance organization in the United States, to study drug transitions, lapses in drug therapy, and mortality among 693 persons with newly diagnosed type 2 diabetes mellitus in 1988. We also studied an equivalently defined cohort of 1071 persons with new diagnoses in 1994, for whom the availability of laboratory results via electronic data permitted additional analyses. Cumulative mortality in the 1988 cohort increased steadily to 207 of 571 patients (36%) by 1997 (year 10). In 1988, 548 of 693 patients (79%) received initial monotherapy with a sulfonylurea. Insulin use rose as the use of sulfonylureas declined. Over this period, 504 of 693 patients (73%) discontinued or added drug therapy. Eight percent to 10% of both sulfonylurea users and insulin users discontinued drug use during the study period. In the 1994 cohort, two thirds of the subjects who discontinued therapy and were tested for glycosylated hemoglobin (Hb A1c) (n = 86) maintained good-to-excellent glycemic control. However, 78 discontinuers (38%) were not tested for Hb A1c, and, among this subset, 32% failed to visit a primary care clinician. The results of this study suggest that 5% to 10% of persons with type 2 diabetes mellitus avoid contact with the medical care system. Avoidance persists for at least the first 10 years after diagnosis but is more common in the first year after diagnosis. In addition, secondary failure of sulfonylureas begins within 1 year of diagnosis and continues at a steady pace. Almost 80% of patients initially treated with sulfonylureas added or switched to metformin or insulin within 10 years of diagnosis.

American translation, modification, and validation of the St. George's Respiratory Questionnaire.

BACKGROUND: The St. George's Respiratory Questionnaire (SGRQ) is a 50-item health status survey specific for chronic obstructive pulmonary disease (COPD) and other respiratory diseases that is available in British English but not American English. The SGRQ's symptom-reporting component requires a 1-year reporting period, which may be too long for reliable and accurate patient recall. OBJECTIVES: The objectives of the present study were to translate the SGRQ from British to American English, modify the reporting period of the symptom-reporting component from 1 year to 1 month, and assess the reliability, validity, and sensitivity to change of this translated modified version in a sample of patients with COPD. METHODS: Based on input from American patients with COPD and health professionals, the SGRQ was translated into American English (SGRQ-A) and then translated back to British English. For SGRQ-A reliability and validity studies, patients were asked to report symptoms experienced over 1 year (reporting period in the original SGRQ) and 1 month (modification made to SGRQ-A). We evaluated 102 patients with COPD (50% female; mean age, 68 years; mean forced expiratory volume in 1 second [FEV1], 1.01 L) at an administrative session before and after completion of a pulmonary rehabilitation program. The SGRQ-A, Chronic Respiratory Disease Questionnaire (CRQ), 36-Item Short Form Health Survey (SF-36), 6-minute walk (6MW), Medical Research Council (MRC) Dyspnea scale, and pulmonary function tests (FEV1 and % predicted FEV1) were used in the assessment battery. RESULTS: The SGRQ-A showed good agreement with the original SGRQ when translated back to British English. Internal reliability (Cronbach alpha) was > 0.70 for all SGRQ-A components except the 1-year symptom-reporting component. Test-retest intraclass correlations were 0.795 to 0.900. Construct validity was strengthened when all SGRQ-A components (except 1-year symptoms and most 1-month symptoms) correlated (P < or = 0.01) with the MRC Dyspnea scale, 6MW, all SF-36 concept scores, and 80% of CRQ domains (r = 0.30-0.72). Discriminate validity was demonstrated when all components of the SGRQ-A with the modified 1-month symptom-reporting period were shown to discriminate better between disease-severity groups (based on patient self-reports of disease severity) than did pulmonary function tests and the 6MW. Responsiveness of the SGRQ-A to change in health status was demonstrated when scores on the Symptoms-1 month and Total-1 month components detected significant improvements in patients' health status (P = 0.02 and P = 0.04, respectively). CONCLUSION: The SGRQ-A with a modified 1-month symptom-reporting period demonstrated reliability and validity in this sample of patients with COPD. Key words: chronic obstructive pulmonary disease, St. George's Respiratory Questionnaire, American translation, reliability, validity, symptom recall.

Direct medical cost of chronic obstructive pulmonary disease in the U.S.A.

The aim of this study was to estimate the direct medical costs of chronic obstructive pulmonary disease (COPD) in the United States using a public-payor perspective. Cost estimates were derived separately for 10 components of care using national survey databases and valued using Medicare and Medicaid reimbursement rates. COPD affects 15 million people in the U.S.A. and the total annual U.S. payment for care is $6.6 billion. Approximately one-third ($2.3 billion) is due to the cost of long-term oxygen therapy, one-quarter is attributed to hospitalizations and inpatient physician services ($1.9 billion), and one-seventh ($942 million) is due to nursing home stays. Other annual costs are outpatient physician visits ($480 million), prescription medications ($462 million), home healthcare ($309 million), emergency department visits ($148 million), outpatient diagnostic procedures ($55 million) and hospice care ($28 million). The cost of COPD is therefore considerable. The significant expenditure for long-term oxygen therapy indicates that disease severity is a major driver of costs. However, the cost of hospitalizations, nursing home stays, emergency department and physician visits are not insignificant.

Infection in surgical patients: effects on mortality, hospitalization, and postdischarge care.

In-hospital mortality, length of stay (LOS), and level of postdischarge care in infected and noninfected surgical patients were studied. An analysis was conducted of a database that included diagnostic, procedure, and drug data collected when surgical patients were discharged from the hospital. Hospitals consisted of 90 nongovernment, nonspecialty, teaching, and nonteaching acute care hospitals of more than 100 beds. Patients in the database included 288,906 patients of all ages hospitalized between July and September 1994. Patients selected of those who had undergone procedures likely to pose a moderate to high risk of infection. Of the 288,906 patients, 12,384 had undergone a moderate- to high-risk procedure; of these, 1,479 (11.9%) had had an infection during their hospitalization. Infection rates ranged from 1.9% to 25.4%, depending on the procedure. The in-hospital mortality rate in infected patients was 14.5%, versus 1.8% for noninfected patients. Similarly, LOS in infected patients (median, 14 days) was substantially greater than in noninfected patients (4 days). About 24% of infected patients required additional professional care after discharge, compared with 7% of noninfected patients. Infection occurs in a substantial portion of surgical patients and is associated with a higher death rate, longer hospitalization, and more intense postdischarge care.

Health care costs associated with escalation of drug treatment in type 2 diabetes mellitus.

The cost of different intensities of therapy in HMO patients with type 2 diabetes mellitus was studied. Health care utilization data from 1995 were obtained for 12,200 registrants from the Kaiser Permanente Northwest Diabetes Registry who had type 2 diabetes mellitus. The data were used to determine costs associated with the escalation of antidiabetic therapies in persons with type 2 diabetes mellitus. The total annual costs (in 1993 dollars) associated with no drug therapy, a sulfonylurea only, metformin, a sulfonylurea plus insulin, and insulin alone were $4400, $4187, $4838, $8856, and $7365, respectively. Per patient total costs were higher for patients who had received antidiabetic therapy in 1995 or previously than for those who had not ($5303 versus $4365) and for patients who had received insulin therapy than for those who had not ($7379 versus $4117). Macrovascular complications accounted for 62-89% of the cost associated with inpatient treatment of diabetes-related complications. The total cost of treating patients with type 2 diabetes mellitus at an HMO increased as antidiabetic therapies escalated.

Alternate delivery methods for morphine sulfate in cancer pain.

New routes of opioid administration that have become available in recent years can be managed by the primary care physician or the oncologist in an attempt to improve pain control and the quality of life. Although oral morphine sulfate is the standard treatment for cancer patients with chronic pain, these novel methods of delivering morphine have enabled some patients whose pain is refractory to traditional methods of drug administration to obtain satisfactory control of their symptoms. The authors review some of these innovative methods.

[Effect of tourniquet occlusion on peripheral blood pooling and ventricular function].

Rotating tourniquets are traditionally part of the treatment of acute pulmonary edema. However, their effectiveness has been questioned. A radioisotope technique was therefore used to evaluate directly the increments in the blood volume of the leg after venous occlusion using a pressure of 60 mmHg in 26 patients with left ventricular (LV) dysfunction following myocardial infarction. The increment in mean radionuclide count at serial 15-second intervals (reflecting the blood volume in the leg distal to the occlusion) increased significantly from the pre-occlusion value by 46 +/- 26% (p less than 0.0005). Thus satisfactory trapping of blood is achieved even in LV failure. However, mean ejection fraction decreased slightly but significantly from 0.23 +/- 0.10 to 0.21 +/- 0.10 (p less than 0.05), a decrease observed in 18 of the 26 patients. LV end-diastolic and end-systolic volume equivalents tended to decrease slightly, but not in all patients. Mean stroke volume and cardiac output equivalents were reduced by 14% (p less than 0.0005), while calculated peripheral resistance increased significantly. The present study fails to support the hypothesis that preload reduction by tourniquets improves LV function.