Comparing Patient-Reported Outcomes Among Anti-TNF-Experienced Patients with Crohn's Disease Initiating Vedolizumab Versus Ustekinumab.

BACKGROUND: Primary and secondary non-response to anti-tumor necrosis factor (TNF) therapy is common in patients with Crohn's disease (CD), yet limited research has compared the effectiveness of subsequent biological therapy. OBJECTIVE: We sought to compare the effectiveness of vedolizumab and ustekinumab in anti-TNF-experienced patients with CD, focusing on patient-prioritized patient-reported outcomes (PROs). METHODS: We conducted a prospective, internet-based cohort study nested within IBD Partners. We identified anti-TNF-experienced patients initiating with CD vedolizumab or ustekinumab and analyzed PROs reported approximately 6 months later (minimum 4 months, maximum 10 months). Co-primary outcomes were Patient-Reported Outcome Measurement Information System (PROMIS) domains of Fatigue and Pain Interference. Secondary outcomes included patient-reported short Crohn's disease activity index (sCDAI), treatment persistence, and corticosteroid use. Inverse probability of treatment weighting (IPTW) was used to control for a number of potential confounders and incorporated into linear and logistic regression models for continuous and categorical outcomes, respectively. RESULTS: Overall, 141 vedolizumab and 219 ustekinumab initiators were included in our analysis. After adjustment, we found no differences between treatment groups in our primary outcomes of Pain Interference or Fatigue or the secondary outcome of sCDAI. However, vedolizumab was associated with lower treatment persistence (OR 0.4, 95% CI 0.2-0.6) and higher corticosteroid use at follow-up assessment (OR 1.7, 95% CI 1.1-2.6). DISCUSSION: Among anti-TNF experienced patients with CD, Pain Interference or Fatigue was not significantly different 4-10 months after starting ustekinumab or vedolizumab. However, reduced steroid use and increased persistence suggest superiority of ustekinumab for non-PRO outcomes.

Proton pump inhibitor therapy: preliminary results of a therapeutic interchange program.

OBJECTIVE: To analyze the experience of one Department of Veterans Affairs hospital in treating with lansoprazole all patients with acid-peptic disease requiring proton pump inhibitor therapy, including newly diagnosed patients and those who were previously stabilized on omeprazole. STUDY DESIGN: Retrospective analysis. PATIENTS AND METHODS: We evaluated the charts of 78 patients seen between March 17, 1997, and November 1998 by the Gastroenterology Section at the Togus Veterans Administration Hospital who were diagnosed with acid-peptic disease. RESULTS: Overall, side effects necessitated discontinuation of therapy in 10 (13%) of the lansoprazole-treated patients and none of the omeprazole-treated patients. Nine patients on lansoprazole suffered from persistent diarrhea and were placed on omeprazole, and one had lower back pain and was switched to cimetidine therapy. Additionally, 12 patients (15%) had their lansoprazole therapy discontinued because of lack of efficacy. Of the 78 lansoprazole-treated patients, 22 (28%) failed to respond to treatment. CONCLUSIONS: Although this study represents preliminary findings and the statistics are observational in nature, important lessons can be learned. At this particular institution, the potential 12% savings from a mandated therapeutic interchange program were quickly offset by the overall lansoprazole-associated failure rate of 28%. The reproducibility of these preliminary results from an omeprazole-to-lansoprazole therapeutic interchange program in other institutions is unknown but warrants further consideration and additional studies, including those evaluating cost efficacy.

Secondary prevention in a cardiology group practice and hospital setting after a heart-care initiative.

The American Heart Association (AHA) Consensus Panel Statement for Preventing Heart Attack and Death in Patients with Coronary Disease provides recommendations for the secondary prevention of heart disease in at-risk patients. Blackstone Cardiology Associates of Pawtucket, Rhode Island, undertook an initiative in their practice implementing secondary-prevention guidelines in patients with coronary artery disease. This retrospective study evaluates practice patterns for the management of hyperlipidemia for a cardiology group in an ambulatory and hospital setting after the institution of a physician-supervised, nurse-based disease management program. Practice patterns in patients with established coronary heart disease treated in a lipid center compared with non-lipid-center settings were evaluated. Parameters evaluated included documenting low-density lipoprotein (LDL) cholesterol, presence of lipid-lowering therapy, and achieving the National Cholesterol Education Program II (NCEP II) goal of LDL-cholesterol levels < or =100 mg/dL in patients with preexisting coronary artery disease. A total of 352 patients met inclusion criteria in the lipid-center setting and were compared with 289 non-lipid-center consecutively chosen patients. Age and gender differences were also evaluated. Inpatient medical records from a 254-bed Brown University-affiliated teaching hospital were also evaluated for lipid profile, achievement of NCEP II goal, and use of lipid-lowering medication on admission and discharge. The most recent LDL-cholesterol values of patients followed in the lipid-center and in the non-lipid-center setting of the Blackstone Cardiology Associates were compared. Blackstone Cardiology Associates consists of 4 cardiologists and 4 advanced-practice nurses. Achievement of LDL-cholesterol goal was higher in both the lipid-center and non-lipid-center settings compared with baseline. A smaller percentage of patients at goal in the lipid setting is likely due to referral bias resulting in patients with more difficult-to-manage mixed dyslipidemias and behavior-management issues ending up in the lipid center. There were no apparent sex differences at goal, and more elderly (age > or =65 years) achieved goal in the lipid clinic center. In the non-lipid-center setting, more males were at goal and had a lower mean LDL-cholesterol level.

Improving patient outcomes by pooling resources (the Texas Heart Care Partnership experience).

The morbidity and mortality associated with cardiovascular disease presents an enormous humanistic and economic burden in the United States. In Texas, cardiovascular disease has been the leading cause of death since 1950. Risk-factor modification has been targeted in the secondary prevention of cardiovascular disease, including lipid management, smoking cessation, improved control of blood pressure, physical activity, weight management, the use of antiplatelet agents/anticoagulants, angiotensin-converting enzyme (ACE) inhibitors in congestive heart failure, beta blockers after myocardial infarction, and estrogen replacement therapy. The Heart Care Partnership (HCP) is a multifaceted interactive program designed to improve risk-factor management in the secondary prevention of cardiovascular disease through physician education, participation, and consensus development in addition to practice improvement processes and patient education. Development and implementation of the Texas HCP was a joint effort of the Texas Medical Association, the Texas Affiliate of the American Heart Association, and Merck & Co. This program helps hospitals improve the quality of care and outcomes for patients with heart disease. Program resources include educational workshops, quality improvement processes, and patient educational materials. HCP workshops address the treatment gap, define optimal care, and help define institution-specific plans for treating heart disease. Quality-improvement processes provide hospitals with baseline data and tools to improve and measure outcomes over time. The HCP workshops are provided as a combination of lectures, interactive discussions, and small group planning sessions designed to encourage audience participation. Upon completing the HCP program, participants are able to (1) describe the evidence-based medicine supporting secondary prevention of cardiovascular disease; (2) identify and prioritize cardiovascular disease risk factors for secondary prevention; (3) identify barriers to and solutions for implementing secondary prevention; and (4) develop site-based plans for cardiovascular risk-factor modification with definite time lines for implementation ("care maps"). The HCP's initial audit of medical practices indicates that Texas appears to share the same deficiencies in the secondary prevention of cardiovascular disease as the rest of the country. However, improvements can be demonstrated in both the hospital and physician office settings through the HCP. The HCP facilitated the cooperation of the medical community in the state of Texas to work together in a synchronized, communicative manner to decrease coronary events. This partnership represents a watershed event in the history of Texas medicine. It is the first time that such a statewide team approach to address a public health issue has been initiated. In the past, medical organizations within the state have had disparate goals and multiple strategies for achieving them.

Candesartan cilexetil: an angiotensin II receptor blocker.

OBJECTIVE: To summarize and critique the medical literature on candesartan cilexetil, an angiotensin II receptor blocker (ARB). DATA SOURCES: MEDLINE searches (January 1966-January 1999) and manufacturer prescribing literature were used to identify articles on candesartan cilexetil. Bibliographies were also reviewed for germane articles. STUDY SELECTION: Study and review articles describing the chemistry, human pharmacology, pharmacodynamics, pharmacokinetics, placebo-controlled trials, comparative trials, and clinical application of candesartan cilexetil based on the published literature and premarketing clinical trials were reviewed. DATA EXTRACTION: All literature on the use of candesartan cilexetil for treating hypertension and congestive heart failure were included. DATA SYNTHESIS: ARBs are a new class of drugs with increasing use in treating hypertension. Studies are ongoing to determine the role of these agents in preventing remodeling after myocardial infarction and in patients with congestive heart failure. Candesartan cilexetil is among the newest drugs in the class that includes losartan, irbesartan, and valsartan. Candesartan cilexetil has more than 1000 times more affinity for the angiotensin II, type AT1 receptor ARBs, and the binding affinity and competitive angiotensin II receptor antagonism is stronger than that of losartan. Clinical studies in patients with hypertension have demonstrated that candesartan cilexetil, in doses of 4-16 mg, is more effective in reducing sitting diastolic blood pressure than are placebo and losartan 50 mg. Candesartan cilexetil has demonstrated reductions in blood pressure comparable to those of enalapril, with the rate of adverse events greater in the enalapril group. Dosage adjustments are not necessary in elderly patients or in patients with mild hepatic or renal dysfunction. In diabetic patients, blood glucose, hemoglobinA1c, and serum lipids are not affected. The clinical studies demonstrated that the adverse effect profile of candesartan cilexetil was similar to that of placebo and there were no dose-dependent adverse effects. CONCLUSIONS: Candesartan cilexetil provides an alternative antihypertensive therapy that is well tolerated and effective in reducing blood pressure in a wide range of patients. Due to its greater binding affinity to the angiotensin II receptor, candesartan cilexetil appears to have a longer antihypertensive effect than losartan. This may be advantageous in decreasing morbidity and mortality associated with hypertension, although further studies are required to validate this potential advantage.

Management of hypercholesterolemia: practice patterns for primary care providers and cardiologists.

This retrospective study, conducted as part of a private practice quality assurance process for patients with coronary artery disease (CAD), compares practice patterns in the LIFEHELP lipid clinic and non-lipid clinic settings at the Heart Institute of St. Petersburg. Quality assurance parameters included documentation of low-density lipoprotein (LDL) cholesterol, initiation of lipid-lowering therapy, and achievement of the Second National Cholesterol Education Program (NCEP II) goal for CAD patients of LDL cholesterol < or =100 mg/dL. A total of 934 patient charts with ICD-9 codes of 410-414 for ischemic heart disease were randomly selected and reviewed by a utilization review nurse. A higher level of documentation and treatment of elevated LDL cholesterol to NCEP II goal in CAD patients was found for those followed in the lipid clinic. Among non-lipid clinic physicians, cardiologists documented and treated elevated LDL cholesterol more frequently than primary care physicians. Women and the elderly subgroups received improved care in the lipid clinic setting. Screening activities and risk-factor management by cardiologists within a lipid clinic, therefore, demonstrated an improved standard of care that came closer to achieving national guidelines in the secondary prevention of CAD.

Pharmacoeconomic considerations in peripheral arterial thrombolytic therapy.

Intraarterial thrombolytic therapy with urokinase (UK) offers documented advantages to alternatives for treating both subacute and the initial presentation of acute peripheral arterial occlusion (PAO), including reduced morbidity and mortality. Treatment with intraarterial UK does not increase overall health care costs; hospital length of stay is either similar to that with other therapies (acute PAO) or is shortened (subacute PAO). Total hospital charges associated with use of intraarterial UK are also not significantly elevated. Thus, thrombolysis with UK offers both a clinically superior and a cost-beneficial way to treat PAO.

Therapeutic alternatives for subacute peripheral arterial occlusion. Comparison by outcome, length of stay, and hospital charges.

Thrombolytic therapy using streptokinase or urokinase has been shown to be a viable alternative to surgical thrombectomy in patients with subacute peripheral arterial occlusion. Urokinase is associated with higher success and lower complication rates than streptokinase, but the cost of urokinase is at least seven times higher. To address questions of utility and effectiveness in the treatment of subacute peripheral arterial occlusions, the authors designed a retrospective study of patients treated either by surgical thrombectomy (n = 70), thrombolysis with streptokinase (n = 19), or thrombolysis with urokinase (n = 22). Outcome of therapy, length of hospital stay, and total hospital charges in the three groups were examined. Treatment successes in the three groups, defined as complete clearing of the occluded segment with patency maintained for 60 days, were 76% for thrombectomy, 32% for streptokinase, and 64% for urokinase. Total duration of hospitalization was 21.1, 21.3, and 11.5 days (P less than .05), respectively. Mean charges for thrombolytic agents were $690 for streptokinase and $6429 for urokinase. Mean total hospital charges, however, were $25,978 for streptokinase, $22,203 for urokinase, and $25,336 for thrombectomy (P = NS). The higher cost of urokinase, then, accounted for the similar total charges, despite the shortened length of stay. These results suggest that urokinase is cost-effective compared to streptokinase for subacute peripheral arterial occlusion. Compared to thrombectomy, thrombolysis with urokinase has a marginally lower patency rate at 60 days, but a significantly shorter length of hospital stay.

A comparison of regional intravenous guanethidine and reserpine in reflex sympathetic dystrophy. A controlled, randomized, double-blind crossover study.

Both regional intravenous guanethidine and reserpine have been reported as effective in the treatment of reflex sympathetic dystrophy. Reserpine depletes storage of norepinephrine, and guanethidine interferes with transport of norepinephrine while depleting storage in the sympathetic nerve terminal. The purpose of this study was to compare drug efficacy in double-blind fashion. Twelve patients, 10 of whom had previous stellate or lumbar sympathetic blocks, were entered into this double-blind cross-over study. Each patient successively received 20 mg guanethidine in 50 ml 0.5% lidocaine, 1.25 mg reserpine in 50 ml 0.5% lidocaine, and 50 ml 0.5% lidocaine with a 1-week interval between medications. At the end of the study and before the code was broken, each patient had the option of continuing treatment with any of the three drugs: the patient merely asked for the first, second, or third drug. Pain assessment used verbal ordinal, numeric, and visual analog scales. Follow-up lasted for a minimum of 6 months. Changes in pain intensity for the first 3 days did not differ significantly among guanethidine, reserpine, and control groups. Pain relief from 2 to 14 months was achieved in two patients receiving reserpine, one receiving guanethidine, and none receiving lidocaine. None of the patients experienced permanent relief. No difference was found between reserpine and guanethidine.

Comparison of excretion of nicotinuric acid after ingestion of two controlled release nicotinic acid preparations in man.

We tested an inexpensive controlled-release nicotinic acid product (Bronson Pharmaceuticals, LaCanada, CA) and compared it with the standard, more expensive, controlled release product, Nicobid (Rorer Pharmaceuticals), by measuring the 24 hour urinary recovery of nicotinic and nicotinuric acids from ten subjects following 500 mg oral ingestion of each product. Nicotinuric acid is the major detoxification product of nicotinic acid and may serve as a simple quantitative index of hepatic biotransformation of nicotinic acid. Although both products demonstrated controlled release profiles, the rate of appearance of nicotinic and nicotinuric acid in the urine as well as the rate of in vitro drug dissolution of the Bronson product were more rapid compared with Nicobid. Moreover, the total amounts of nicotinic acid and nicotinuric acid recovered in the urine after 24 hours were greater for the Bronson product (P less than .05). Since sustained presentation of nicotinic acid to the liver may correlate with clinical antihyperlipidemic effects, our results suggest that the Bronson product may prove to be a clinically useful preparation.

Postgraduate pharmacy fellowships (1987-88).

During August and September 1987, the Brigham and Women's Hospital Pharmacy Services Department conducted its seventh annual nationwide survey of postgraduate pharmacy fellowships. There are 185 fellowships offered with 150 fellows at 53 sites.

Cardiopulmonary arrest following barium enema examination with glucagon.

This is a case report of a patient who presented to the hospital's ambulatory radiology suites for a barium enema to evaluate guaiac-positive stools. The patient, after receiving glucagon 0.5 mg iv and a small amount of rectally administered barium sulfate, experienced an "itchy tingling" feeling, vomited, became diaphoretic, and had a cardiopulmonary arrest. Despite a prompt response by the cardiac arrest team, the patient could not be resuscitated. This case demonstrates the potential for serious reactions during this procedure.

Postgraduate pharmacy fellowships (1986-87)

During September and October 1986, the Brigham and Women's Hospital Pharmacy Services Department conducted its sixth annual nationwide survey of postgraduate pharmacy fellowships. There are 170 fellowships offered with 146 fellows at 44 sites.

Postgraduate pharmacy fellowships (1985-86).

During August and September 1985, the Brigham & Women's Hospital Pharmacy Services Department conducted its fifth annual nationwide survey of postgraduate pharmacy fellowships. There are 115 fellowships offered with 89 fellows at 33 sites.

Efficacy of fenoprofen in the treatment of primary dysmenorrhea.

We compared fenoprofen calcium, 200 mg; fenoprofen calcium, 400 mg; aspirin, 650 mg; and a placebo in 85 women for the relief of primary dysmenorrhea in a double-blind, clinical trial. The usefulness of these drugs was judged from data obtained over four consecutive menstrual periods on: restriction of daily activity, pain intensity scores, need for rescue analgesics, withdrawal due to lack of efficacy, and adverse events. Both fenoprofen, 200 mg, and fenoprofen, 400 mg, offered significant (P less than .01) pain relief when compared to placebo and aspirin. Analyses of data on 1, 2 and 3 indicated that aspirin was not significantly different from placebo. The aspirin-treated group reported the greatest number of adverse reactions, but the differences between the four groups were not statistically significant. Our study lends support to the concept of a "plateau analgesic effect" of nonsteroidal antiinflammatory drugs (NSAIDs): fenoprofen, 200 mg, appears to be as effective as fenoprofen, 400 mg. When this type of drug fails to provide relief for a woman suffering from primary dysmenorrhea, switching to another NSAID may be more appropriate than increasing the dosage and the probability of dosage-related side effects.