Trends and outcomes of hospitalizations for peptic ulcer disease in the United States, 1993 to 2006.

OBJECTIVES: Despite progress in diagnosis and treatment, peptic ulcer disease (PUD) remains a common reason for hospitalization and operation. The purpose of this study was to quantify the time trends of hospitalizations and operations for PUD in the United States (US) since 1993. DATA AND METHODS: The Healthcare Cost and Utilization Project Nationwide Inpatient Sample is a 20% stratified sample of all hospitalizations in the United States. It was used to study hospitalizations with PUD as the principal diagnosis during 1993 to 2006, including details on ulcer site, complications, procedures, and mortality. Statistical methods included the chi test and multivariate logistic regression. RESULTS: The national estimate of hospitalizations for PUD decreased significantly from 222,601 in 1993 to 156,108 in 2006 (-29.9%), with a larger reduction in duodenal ulcers (95,552 in 1993 vs. 60,029 in 2006, -37.2%) than gastric ulcers (106,987 in 1993 vs. 86,064 in 2006, -19.6%). The inpatient mortality rate of PUD decreased from 3.8% to 2.7% during 1993 to 2006 (P < 0.001). Hemorrhage remained the most common complication (71.6% in 1993; 73.3% in 2006) but perforation had the highest mortality (15.1% in 1993; 10.6% in 2006). In comparison to 1993, patients hospitalized for PUD in 2006 more frequently had endoscopic treatment to control bleeding (12.9% vs. 22.2%, P < 0.001), similar use of surgical oversewing of ulcer (7.6% vs. 7.4%), less use of gastrectomy (4.4% vs. 2.1%, P < 0.001), and less use of vagotomy (5.7% vs. 1.7%, P < 0.001). In multivariate logistic regressions, the determinants of mortality were similar in 1993 and 2006. CONCLUSIONS: Hospitalizations for PUD decreased in the United States from 1993 to 2006, suggesting a decrease in the prevalence and/or severity of ulcer complications over this recent time period. Despite increased patient age and comorbidities, there has been a significant decrease in PUD mortality, a significant increase in the use of therapeutic endoscopy for bleeding ulcer, and a significant decrease in the use of definitive surgery (vagotomy or resection) for ulcer complications.

Symptoms of gastroparesis: use of the gastroparesis cardinal symptom index in symptomatic patients referred for gastric emptying scintigraphy.

BACKGROUND/AIM: The Gastroparesis Cardinal Symptom Index (GCSI) was developed to assess symptoms of gastroparesis. The aim of this study was to correlate symptoms using the GCSI with delayed gastric emptying (DGE) in symptomatic patients referred for gastric emptying scintigraphy (GES). METHODS: A total of 226 consecutive symptomatic patients referred for GES completed the 9-question GCSI. GES was performed using a (99)Tc-labeled egg meal. Gastroparesis was defined as DGE at 2 h and/or 4 h. RESULTS: Using linear regression, nausea (p = 0.09), not able to finish a normal-size meal (p = 0.005), postprandial fullness subscore (p = 0.01), and total GCSI score (p = 0.06) were predictors of the gastric retention values at 2 h, but not at 4 h. Patients with gastroparesis had significant higher symptom scores for nausea (p = 0.035) and vomiting (p = 0.040) compared to patients with normal gastric emptying. The positive predictive value varied between 51 and 61% for total GCSI scores between 20 and 35, respectively. CONCLUSION: The individual symptoms of nausea, vomiting, and early satiety were associated with DGE at 2 h but not at 4 h. In contrast, the total or average GCSI score did not reliably predict the diagnosis of gastroparesis in symptomatic patients referred for GES.

Trends of Heller myotomy hospitalizations for achalasia in the United States, 1993-2005: effect of surgery volume on perioperative outcomes.

OBJECTIVES: Achalasia is a rare chronic disorder of esophageal motor function. Single-center reports suggest that there has been greater use of laparoscopic Heller myotomy for achalasia in the United States since its introduction in 1992. We aimed to study the trends of Heller myotomy and the relationship between surgery volume and perioperative outcomes. DATA AND METHODS: The Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS) is a 20% stratified sample of all hospitalizations in the United States. It was used to study the macro-trends of Heller myotomy hospitalizations during 1993-2005. We also used the NIS 2003-2005 micro-data to study the perioperative outcomes of Heller myotomy hospitalizations, using other achalasia and laparoscopic cholecystectomy hospitalizations as control groups. The generalized linear model with repeated observations from the same unit was used to adjust for multiple hospitalizations from the same hospital. RESULTS: The national estimate of Heller myotomy hospitalizations increased from 728 to 2,255 during 1993-2005, while its mean length of stay decreased from 9.9 to 4.3 days. Of the 1,117 Heller myotomy hospitalizations in the NIS 2003-2005, 10 (0.9%) had the diagnosis of esophageal perforation at discharge. Length of stay was negatively correlated with a hospital's number of Heller myotomy per year (correlation coefficient -0.171, P < 0.001). In multivariate log-linear regressions with a control group, a hospital's number of Heller myotomy per year was negatively associated with length of stay (coefficient -0.215 to -0.119, both P < 0.001) and total charges (coefficient -0.252 to -0.073, both P < 0.10). These findings were robust in alternative statistical models, specifications, and subgroup analyses. CONCLUSIONS: On a national level, the introduction of laparoscopic Heller myotomy for achalasia was associated with greater use of surgery and shorter length of stay. A larger volume of Heller myotomy in a hospital was associated with better perioperative outcomes in terms of shorter length of stay and lower total charges.

Outpatient hypertension treatment, treatment intensification, and control in Western Europe and the United States.

BACKGROUND: Hypertension guidelines in the United States tend to have more aggressive treatment recommendations than those in European countries. METHODS: To explore international differences in hypertension treatment, treatment intensification, and hypertension control in western Europe and the United States, we conducted cross-sectional analyses of the nationally representative CardioMonitor 2004 survey, which included 21 053 hypertensive patients visiting 291 cardiologists and 1284 primary care physicians in 5 western European countries and the United States. The main outcome measures were latest systolic and diastolic blood pressure (BP) levels, hypertension control (latest BP level, <140/90 mm Hg), and medication increase (dose escalation or an addition to or switch of drug therapy) for inadequately controlled hypertension. RESULTS: At least 92% of patients in each country received antihypertensive drug treatment. The initial pretreatment BP levels were lowest and the use of combination drug therapy (>or=2 antihypertensive drug classes) was highest in the United States. Multivariate analyses controlling for age, sex, current smoking, and physician specialty indicated that, compared with US patients, European patients had higher latest systolic BP levels (by 5.3-10.2 mm Hg across countries examined) and diastolic BP levels (by 1.9-5.3 mm Hg), a smaller likelihood of hypertension control (odds ratios, 0.27-0.50), and a smaller likelihood of medication increase for inadequately controlled hypertension (odds ratios, 0.29-0.65) (all P<.001). In addition, controlling for initial pretreatment BP level attenuated the differences in latest systolic and diastolic BP levels and the likelihood of hypertension control. CONCLUSION: Lower treatment thresholds and more intensive treatment contribute to better hypertension control in the United States compared with the western European countries studied.

Lack of effect of guideline changes on hypertension control for patients with diabetes in the U.S., 1995-2005.

OBJECTIVE: To study the effect of new Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) guidelines on hypertension control for patients with diabetes in the U.S. using patients without diabetes as the control group for the time trend. RESEARCH DESIGN AND METHODS: The JNC VI and VII guidelines, published in 1997 and 2003, set more aggressive goal blood pressure for patients with diabetes. Data from the National Disease and Therapeutic Index, a nationally representative survey of outpatient visits in the U.S., was used to compare the difference in hypertension control (blood pressure <140/90 mmHg) between diabetic and nondiabetic visits during 1995-2005. RESULTS: Hypertension control improved for both diabetic and nondiabetic visits in the study period. Compared with nondiabetic visits, there was no change in hypertension control for diabetic visits before 2001 and an approximately 4% increase afterward (P < 0.001). CONCLUSIONS: The publication of new JNC guidelines did not result in substantially better hypertension control for patients with diabetes in the U.S.

Spillover effects of restrictive drug formularies in the statin class: a descriptive study of the Medicaid preferred drug list in Texas.

This study examines whether the implementation of Texas' Medicaid preferred drug list (PDL) influenced, or had a spillover effect, on the prescribing of statin products for non-Medicaid patients. Simvastatin and pravastatin were on the PDL, but atorvastatin was not. Physicians in Texas were categorized into four groups with increasing Medicaid exposure. Compared with physicians with very low, low, or medium Medicaid exposure, the non-Medicaid marketshare of atorvastatin dropped approximately two percentage points and the non-Medicaid marketshare of simvastatin and pravastatin increased by approximately one percentage point among physicians with high Medicaid exposure after six months. Therefore, the restrictive Medicaid PDL in Texas spilled over to non-Medicaid patients.

Price competition in the Chinese pharmaceutical market.

We study price competition between high-quality global products and low-quality local products in a developing country, i.e., China, Nearly all previous studies on pharmaceutical price competition focused on developed countries with bioequivalent generics. In China, local generic products are not bioequivalent and are deemed of lower quality, while global products in the same class are considered similar in quality and better substitutes. We hypothesize that local generic competition drives down local product price but not global product price. In addition, we hypothesize that therapeutic competition among similar global products lowers global product price. Our empirical results support both hypotheses. Number of local generic competitors has a significantly negative effect on local product price but no effect on global product price, while number of global therapeutic competitors has a significantly negative effect on global product price. Policy changes that encourage bioequivalent local products and accelerate global product approvals will enhance price competition in China.

The prevalence of diagnosed cutaneous manifestations during ambulatory diabetes visits in the United States, 1998-2002.

BACKGROUND: The prevalence of diabetes has been rapidly increasing. Previous reports indicated that diabetics are prone to certain cutaneous diseases. OBJECTIVE: To determine the frequencies of diagnosed skin conditions during ambulatory diabetes visits in the USA. METHODS: We evaluated two national ambulatory medical care surveys between 1998 and 2002 and compared the diagnoses of 7 categories of skin conditions in diabetics (n = 9,626) to patients with hypertension (n = 15,997) or gastroesophageal reflux disease (GERD; n = 2,362) using chi2 tests and multivariate logistic regressions. RESULTS: Diabetics were prone to chronic skin ulcers (odds ratio = 62.5, 95% confidence interval = 3.95-989 compared to GERD; 9.97, 6.34-15.7 compared to hypertension), bacterial skin infections (5.95, 2.86-12.4 compared to GERD; 5.15, 3.74-7.08 compared to hypertension) and fungal skin infections (2.66, 1.15-6.16 compared to GERD; 1.99, 1.32-3.01 compared to hypertension) but not to other skin conditions. These findings remained true during primary care physician visits. CONCLUSION: Chronic skin ulcers, bacterial and fungal skin infections are more frequently diagnosed in diabetics. We could not verify that other skin conditions are associated with diabetes, in part due to potential underdiagnosis and underreporting.

The quantity and quality of worldwide new drug introductions, 1982-2003.

We examined trends in the introduction of new chemical entities (NCEs) worldwide from 1982 through 2003. Although annual introductions of NCEs decreased over time, introductions of high-quality NCEs (that is, global and first-in-class NCEs) increased moderately. Both biotech and orphan products enjoyed tremendous growth, especially for cancer treatment. Country-level analyses for 1993-2003 indicate that U.S. firms overtook their European counterparts in innovative performance or the introduction of first-in-class, biotech, and orphan products. The United States also became the leading market for first launch.

Screening and treatment of hypercholesterolemia for prevention of coronary heart disease.

Undertreatment of hypercholesterolemia for secondary prevention of coronary heart disease has been widely documented. Less is known about screening and treatment for primary prevention. To evaluate recent trends, the rates of low-density lipoprotein (LDL) cholesterol screening and treatment for primary and secondary prevention of coronary heart disease in 1999 and 2003 were quantified from the National Disease and Therapeutic Index and compared. Data were used to examine LDL level reporting, rates at which target levels were attained, and drug therapy among National Cholesterol and Education Panel (NCEP) risk groups. The rate of LDL level reporting increased with greater NCEP risk, ranging from 6% to 7% for visits without risk factors to 31% to 42% for secondary prevention. Rates of meeting LDL targets decreased with greater NCEP risk, ranging from 87% to 88% for visits without risk factors to 29% to 43% for secondary prevention. Drug therapy recommendation also decreasedwith greater NCEP risk. Despite improvements, underscreening and undertreatment of hypercholesterolemia persists in outpatient visits.

The Chinese pharmaceutical market at the crossroads: pro-competition solutions to improve access, quality and affordability.

The Chinese pharmaceutical market is large in absolute size (the second largest in Asia), but it faces similar problems to those that plague other developing countries, such as a lack of adequate patent protection, low pharmaceutical spending per capita, but high pharmaceutical expenditure as a proportion of total medical spending, and a lack of health insurance coverage. In this article, the pros and cons of two pro-competition policy proposals for China are explored. The first proposal is to follow the E5 guideline of the International Conference on Harmonisation and waive unnecessary local clinical trials for global new drugs that have been approved by the US Food and Drug Administration or the European Medicines Agency (except for drugs for which there is a real possibility of there being ethnic differences in patient responses). The second proposal is to tighten the standards for generic drugs and approve only bioequivalent ones. While the first proposal encourages price competition between similar compounds in the same therapeutic class, the second proposal enhances generic competition for off-patent drugs. Working together, these two proposals would improve access to and the quality and affordability of pharmaceuticals in China.

Prescription drug formulary design, preferred-product marketshare, and formulary noncompliance: a study of proton-pump inhibitors.

The intent of a prescription drug formulary is to shift utilization toward preferred products, but health plans must balance the benefit of these products' lower price with the cost of potential formulary noncompliance. Using proton-pump inhibitors as a model, the authors studied the influence of formulary restrictiveness and drug preference status on formulary noncompliance and marketshare. They found that although drug formulary restrictiveness increases the use of preferred products, it also leads to a high level of formulary noncompliance. The net financial effect on drug spending is ambiguous.

Spillover effects of restrictive drug formularies: a case study of PacifiCare in California.

BACKGROUND: A restrictive drug formulary may influence how physicians treat other, unaffiliated patients, a phenomenon known as the "spillover effect." In a previous study we found significant spillover effects from Maine's Medicaid formulary. OBJECTIVE: To determine whether similar spillover effects exist for private insurers with less restrictive formularies and less dominant market presence. STUDY DESIGN: We treated PacifiCare's formulary changes for proton pump inhibitors (PPIs) as a natural experiment and studied whether these changes spilled onto non-PacifiCare patients in California. Rabeprazole and pantoprazole are the newly preferred PPI products. METHODS: We analyzed the physician-level before-and-after changes in prescribing of rabeprazole and pantoprazole for PacifiCare and non-PacifiCare patients. We also estimated the effect of PacifiCare share of practice on spillover effects using linear regressions. RESULTS: The number of rabeprazole and pantoprazole prescriptions increased simultaneously for non-PacifiCare patients and the increase was positively associated with PacifiCare share of practice. For non-PacifiCare prescriptions, a 10% increase in PacifiCare share of practice led to a 3.3% share increase for rabeprazole and a 1.6% share increase for pantoprazole, respectively (both P < .001). CONCLUSIONS: PacifiCare's PPI formulary changes generated significant spillover effects onto non-PacifiCare patients in California.

The impact of price regulation on the launch delay of new drugs--evidence from twenty-five major markets in the 1990s.

We analyze the effect of price regulation on delays in launch of new drugs. Because a low price in one market may 'spill-over' to other markets, through parallel trade and external referencing, manufacturers may rationally prefer longer delay or non-launch to accepting a relatively low price. We analyze the launch in 25 major markets, including 14 EU countries, of 85 new chemical entities (NCEs) launched between 1994 and 1998. Each NCE's expected price and market size in a country are estimated using lagged average price and market size of other drugs in the same (or related) therapeutic class. We estimate a Cox proportional hazard model of launch in each country, relative to first global launch. Only 55% of the potential launches occur. The US leads with 73 launches, followed by Germany (66) and the UK (64). Only 13 NCEs are launched in Japan, 26 in Portugal and 28 in New Zealand. The results indicate that countries with lower expected prices or smaller expected market size have fewer launches and longer launch delays, controlling for per capita income and other country and firm characteristics. Controlling for expected price and volume, country effects for the likely parallel export countries are significantly negative.

Impact of Maine's Medicaid drug formulary change on non-Medicaid markets: spillover effects of a restrictive drug formulary.

BACKGROUND: Market penetration of HMOs affect physician practice styles for non-HMO patients. OBJECTIVE: To study the impact of a restrictive Medicaid drug formulary on prescribing patterns for other patients, ie, so-called spillover effects. DESIGN: A before-and-after, 3-state comparison study. EVENT: On January 1, 2001, Maine's Medicaid program implemented a restrictive drug formulary for the proton pump inhibitor class, with pantoprazole as the only preferred drug. MAIN OUTCOME MEASURE: The Medicaid and non-Medicaid market shares of pantoprazole in Maine (vs New Hampshire and Vermont and among Maine physicians with different Medicaid share of practice. RESULTS: After 3 months, the market share of pantoprazole in Maine (vs 2 control states) increased 79% among Medicaid prescriptions (vs 1%-2%), 10% among cash prescriptions (vs 3%), and 7% among other third-party payer prescriptions (vs 1%). The market shares increased more among Maine physicians with a higher Medicaid share of practice (high vs middle vs low [market]: 16% vs 8% vs 5% [cash]; 11% vs 5% vs 4% [other third-party payers]). Linear regression results indicate that practicing medicine in Maine leads to a 72% increase in pantoprazole share among Medicaid prescriptions (P < .001). In addition, for each 10% Medicaid share of practice in Maine, the share of pantoprazole increases 1.8% among cash prescriptions (P = .01) and 1.4% among other third-party payer prescriptions (P < .001). CONCLUSIONS: Maine's Medicaid drug formulary generated spillover effects in cash and other third-party payer markets, with somewhat stronger effects in the cash market.

High- versus low-dose angiotensin converting enzyme inhibitor therapy in the treatment of heart failure: an economic analysis of the Assessment of Treatment with Lisinopril and Survival (ATLAS) trial.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce heart failure death and hospitalization. Prescribed doses often are lower than randomized clinical trial (RCT) targets and practice guideline recommendations. OBJECTIVE: To assess the cost-effectiveness of high- versus low-dose ACE inhibitor therapy in the ATLAS trial. STUDY DESIGN: A 19-nation RCT of high-dose (32.5-35.0 mg/day) versus low-dose (2.5-5.0 mg/day) lisinopril in 3164 patients with class II-IV heart failure and left ventricular ejection fraction < or = 30%. METHODS: Data on clinical outcomes and major cost events (hospitalizations and drug utilization) were collected prospectively. Hospital costs were estimated using Medicare and representative managed care diagnosis-related group reimbursement rates. ACE inhibitor drug costs were estimated using US average wholesale prices. Costs were discounted at 3% annually. RESULTS: Patients in the high-dose lisinopril group had fewer hospitalizations (1.98 vs 2.22, P = .014) and hospital days (18.28 vs 22.22, P = .002), especially heart failure hospitalizations (0.64 vs 0.80, P = .006) and heart failure hospital days (6.02 vs 7.45, P = .028) compared with the low-dose group. The high-dose lisinopril group also had lower heart failure hospital costs (dollars 5114 vs dollars 6361, P = .006) but higher ACE inhibitor drug costs (dollars 1368 vs dollars 855, P = .0001). Total hospital and drug costs were similar between high- and low-dose lisinopril groups (mean difference dollars -875, 95% CI dollars -2613 to dollars 884). Sensitivity analyses confirmed these findings. CONCLUSIONS: Cost savings from fewer heart failure hospitalizations offset higher ACE inhibitor costs in the high-dose group. The improved clinical outcomes were achieved without increased treatment costs.

Difference in the use of preventive services between fee-for-service plans and HMOs: is more better?

OBJECTIVE: Based on the US Preventive Services Task Force recommendations, we studied how health insurance type, ie, fee-for-service (FFS) or health maintenance organization (HMO), affects the utilization of preventive services of differing effectiveness. STUDY DESIGN: Household survey data from the 1993 and 1994 National Health Interview Surveys. METHODS: We compared the use of mammograms, Pap smears, blood pressure measurements, counseling about hormone replacement therapy (HRT), and general physical examinations in FFS plans and HMOs. We used the bivariate probit model to control for selection bias caused by the unobservable factors in the choice of health insurance type. RESULTS: Enrollees in HMOs obtained more Pap smears, blood pressure measurements, mammograms (women 40 to 49 years old), and general physical examinations than enrollees in FFS plans. No significant difference was found between FFS plans and HMOs for the use of mammograms (women aged 30 to 39 years and 50 to 64 years) or HRT counseling. The correlation ratios from bivariate probit estimations indicated no selection bias favoring HMOs; for some preventive services, selection bias favored FFS plans. CONCLUSIONS: Compared with enrollees in FFS plans, persons in HMOs used more preventive services, including less effective ones. Not controlling for selection bias underestimated the HMO effect.

Preventive care in managed care and fee-for-service plans: is it cost effective?

Lack of coverage, knowledge, and physician guidance, and low socioeconomic status are major barriers to receiving preventive care. Compared with fee-for-service insurance, managed care promotes prevention through more generous coverage, physician incentives, and patient education, and members of MCOs use more preventive services than do members of fee-for-service plans. However, cost effectiveness of prevention has not been previously examined. A study of seven preventive services suggests that managed care enrollees more frequently obtained four preventive services, including two less-effective ones. For less-effective services, it may be prudent to base disease-risk assessment on key factors other than age and sex, and screen only patients at high risk. Effective screening strategies must be identified, especially for the underserved, low-income population.