Publications

There is significant heterogeneity in survival time among patients with idiopathic pulmonary fibrosis. Studies of baseline clinical and physiologic variables as predictors of survival time have reported inconsistent results. We evaluated the predictive value of changes in clinical and physiologic variables over time for survival time in 81 patients with biopsy-proven idiopathic pulmonary fibrosis. Six-month changes in dyspnea score, total lung capacity, thoracic gas volume, FVC, FEV1, diffusing capacity of carbon monoxide, partial pressure of arterial oxygen, oxygen saturation, and alveolar-arterial oxygen gradient were predictive of survival time even after adjustment for baseline values. Analyses were repeated on 51 patients with 12-month change data. Twelve-month changes in dyspnea score, total lung capacity, FVC, partial pressure of arterial oxygen, oxygen saturation, and alveolar-arterial oxygen gradient were predictive of survival time after adjustment for baseline values. Evaluation of changes in clinical and physiological variables over 6 and 12 months may provide clinicians with more accurate prognostic information than baseline values alone.

BACKGROUND

Guidelines recommend Helicobacter pylori (HP) testing and treatment for patients with a history of peptic ulcer disease (PUD), assuming that PUD has been documented and that successful HP eradication would eliminate the need for further therapy and medical utilization.

METHODS

An open-label, randomized controlled trial in a managed care setting evaluated the clinical outcome and costs of an HP test-and-treat (T & T) strategy in 650 patients receiving long-term acid suppression therapy for physician-diagnosed PUD. Patients were randomized to T & T for HP (n = 321) or to usual care (n = 329). Outcome measures included presence and severity of PUD symptoms, use of acid-reducing medication, and acid-peptic-related health care costs during 12-month follow-up.

RESULTS

Only 17% of study participants had PUD confirmed by radiography or endoscopy; only 38% of the T & T group tested positive for HP. At 12 months, patients in the T & T group were less likely to report ulcerlike dyspepsia or use of acid-reducing medication; however, 75% of the T & T group used acid-reducing medication during the second half of the 12-month follow-up. In the 12 months after randomization, the T & T group had higher total acid-peptic-related costs than the usual care group.

CONCLUSIONS

Most patients receiving long-term acid suppression therapy for physician-diagnosed PUD in community practice settings are likely to have HP-negative, uninvestigated dyspepsia. Routine testing and treating for HP will not reduce acid-peptic-related costs and have only a modest (though statistically significant) effect in reducing clinical symptoms and use of acid-reducing medications.

Although only a partial mu-opiate agonist, buprenorphine can be abused and diverted from medical therapy to the illicit drug market. A combination of buprenorphine and naloxone for sublingual administration may discourage diversion and abuse by precipitating opiate withdrawal when taken parenterally. Because opiate-abusing populations are not homogeneous and have varying levels of opiate dependence, the efficacy of buprenorphine and naloxone in precipitating opiate withdrawal or in attenuating the pleasurable effects of buprenorphine may vary. This chapter describes the effects of sublingual and parenteral buprenorphine and naloxone combinations in several populations of opiate-dependent people. We conclude that buprenorphine and naloxone combinations should not diminish the efficacy of sublingual buprenorphine, but should have lower abuse liability than buprenorphine alone.

Endothelin-1 (ET-1) is a potent vasoconstrictor that increases vascular tone in the resistance vessels of subjects with hypertension. It is unclear whether endogenous ET-1 affects resistance-vessel function equally in patients with other cardiovascular risk factors. Vasoconstriction to ET-1 is mediated principally via the endothelin-A (ETA) receptor on vascular smooth muscle cells. Accordingly, we used an ETA-specific antagonist, BQ-123, to test the hypothesis that endogenous ET-1 increases vascular resistance selectively in subjects with hypertension compared with other risk factors. BQ-123 was infused at 100 nmol/min for 80 minutes into the brachial artery of 10 subjects with hypertension (mean+/-SEM arterial pressure, 106+/-5 mm Hg), 12 subjects with hypercholesterolemia (mean+/-SEM total cholesterol, 7.1+/-0.2 mmol/L), 10 active smokers (mean+/-SEM, 42+/-11 pack-years), and 11 healthy, age-matched individuals. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. BQ-123 dilated resistance arterioles in hypertensive subjects, with FBF's increasing by 46+/-7% from baseline (P<0.001). BQ-123 increased FBF to a lesser extent in hypercholesterolemic (24+/-5%, P<0.001) and healthy (20+/-8%, P=0.007) individuals but did not affect FBF significantly in smokers (10+/-8%, P=0.185). The vasodilator response in hypertensive subjects, but not in hypercholesterolemic patients or smokers, was significantly greater than that in healthy individuals (P=0.012). Endogenous ET-1, acting via the ETA receptor, increases resistance-vessel tone in subjects with hypertension more than in subjects with hypercholesterolemia or in smokers. These results indicate that ET-1 contributes more to the pathophysiology of hypertension than of other risk factors in subjects without overt atherosclerosis.