Cost‐utility analysis of proton pump inhibitors and other gastro‐protective agents for prevention of gastrointestinal complications in elderly patients taking nonselective nonsteroidal anti‐inflammatory agents

Aliment Pharmacol Ther 31 , 1354–1364

Summary

Background  The use of proton pump inhibitors (PPIs) among elderly patients using nonselective nonsteroidal anti‐inflammatory drugs (nsNSAIDs) has increased; the price of PPIs is higher than that of majority of alternative treatment strategies. Aim  To evaluate the cost‐effectiveness of nsNSAIDS + PPIs relative to alternative gastroprotective regimens in the prevention of GI complications among elderly patients (aged ≥65 years). Methods  An incremental cost‐utility analysis, comparing PPIs with alternative gastroprotective regimens was conducted using a decision analytical model. Clinical outcomes, costs and utilities were derived from recently published studies. Probabilistic and deterministic sensitivity analyses were performed to test the robustness of the results to variation in model inputs and assumptions. Results  The incremental cost‐utility ratio (ICUR) of PPIs, relative to nsNSAID alone, was $206 315 per QALY gained or were more costly and less effective. Other co‐prescribed treatment options had higher costs per QALY gained. In patients with a history of a complicated or uncomplicated ulcer, PPIs had ICURs of $24 277 and $40 876, respectively. Conclusions  Use of PPIs in all elderly patients taking nsNSAIDs is unlikely to represent an efficient use of finite healthcare resources. Co‐prescribing PPIs, however, to elderly patients taking nsNSAIDs who have a history of complicated or uncomplicated ulcers appears to be economically attractive.     

A comparison of the acid-inhibitory effects of esomeprazole and pantoprazole in relation to pharmacokinetics and CYP2C19 polymorphism

Background  Esomeprazole and pantoprazole are metabolized in the liver and the polymorphic CYP2C19 enzyme is involved in that process. This genetic polymorphism determines fast (70% of Caucasians), intermediate (25–30% of Caucasians) and slow (2–5% of Caucasians) metabolism of PPIs.
Aim  To compare the acid-inhibitory effects of esomeprazole 40 mg and pantoprazole 40 mg at 4, 24 and 120 h after oral administration in relation to CYP2C19 genotype and pharmacokinetics.
Methods  CYP2C19*2, *3, *4, *5 and *17 genotypes were determined in healthy Helicobacter pylori- negative Caucasian subjects. 7 wt/wt, 7 wt/*2, 2 wt/*17, 2 *2/*17 and 1 *2/*2 were included in a randomized investigator-blinded cross-over study with esomeprazole 40 mg and pantoprazole 40 mg. Intragastric 24-h pH-monitoring was performed on days 0, 1 and 5 of oral dosing.
Results  A total of 19 subjects (mean age 24 years, 7 male) completed the study. At day 1 and 5, acid-inhibition with esomeprazole was significantly greater and faster than with pantoprazole. Differences in acid-inhibition and pharmacokinetics between wt/wt and wt/*2 genotype were significant for pantoprazole at day 1 and 5.
Conclusions  Esomeprazole provides acid-inhibition faster than and superior to pantoprazole after single and repeated administration. The acid-inhibitory effect and the kinetics of pantoprazole are influenced by CYP2C19 genotype.     

Tilt Training: A Treatment for Malignant and Recurrent Neurocardiogenic Syncope

The treatment of neurocardiogenic syncope is insufficient in many cases. We hypothesized that the repeated exposure of the cardiovascular system to orthostatic stress could have a therapeutic effect on the regulation of cardiovascular reflex mechanisms. We have started a program of tilt training for heavily symptomatic patients. After hospital admission, patients were tilted daily (60-degree inclination), until syncope, or until a maximum of 45–90 minutes. The patients were instructed to continue a program of daily tilt training at home: two 30-minute sessions of upright standing against a vertical wall. No medication was prescribed. A total of 260 tilt table sessions were performed in 42 patients. The first tilt test was positive after 21 ± 13 minutes. The syncope was cardioinhibitory in 14 cases, vasodepressor in 19, mixed in 9. At the time of hospital discharge, 41 patients could support 45 minutes of head-up tilting. After a mean follow-up time of 15.1 (SD 7.8) months, 36 patients remained completely free of syncope. Syncope still occurred in one patient and presyncope in four patients. One patient died from an extensive myocardial infarction. The abnormal autonomic reflex activity of neurocardiogenic syncope can be remedied by a program of continued tilt training without the administration of drugs. This new treatment has proven to be effective for the vasodepressor and the cardioinhibitory type of syncope.     

韩氏仪应用于腹腔镜手术的临床报告

根据电针刺激可促使中枢释放阿片肽产生内源性镇痛的原理,用韩氏仪辅助硬膜外阻滞行腹腔镜妇科手术、可解除人工气腹时恶心、呕吐等副作用,又不影响自主呼吸,血气分析,ＰＨ值,ＰＣＯ２均无明显异常。循环稳定,血压、心率、心电与气腹前无明显差别。本法具有安全,简单、病人恢复快,费用少等优点,值得推广使用。     

Shift of Exit Site During Ablation of Ventricular Tachycardia Originating from the Vicinity of Left Ventricular Summit

A 44‐year‐old man with structurally normal heart underwent catheter ablation of left ventricular summit tachycardia. The initial mapping revealed the origin of tachycardia at the junction of great cardiac vein and anterior interventricular vein. During ablation the exit site shifted to the nearby regions, which was recognized by subtle changes of 12‐lead ECG. Mapping and ablating at different exit sites rendered the tachycardia noninducible.     

Trisomy 3 in marginal zone B-cell lymphoma: a study based on cytogenetic analysis and fluorescence in situ hybridization

Trisomy 3 represents the most frequent and consistent chromosomal abnormality characterizing the recently defined entity marginal zone B-cell lymphoma (MZBCL). By cytogenetic analysis and/or fluorescence in situ hybridization (FISH) on interphase nuclei we found an increased copy number of chromosome 3 in 22/36 (61%) successfully analysed cases, including 8/12 cases with extranodal MZBCL, 8/13 cases with nodal MZBCL, and 6/11 patients with splenic MZBCL. Sensitivity of interphase cytogenetics was somewhat higher than that of conventional cytogenetic investigation. Structural chromosomal changes involving at least one chromosome 3 were seen in 11/20 cases with an increased copy number of chromosome 3: +del(3)(p13) was demonstrated in three cases, and was the sole chromosomal abnormality in one of them; +i(3)(q10) was seen in two other patients; and rearrangements involving various breakpoints on the long arm of chromosome 3 were found in the remaining cases. FISH on metaphase spreads confirmed these structural abnormalities and additionally showed two unexpected translocations involving chromosome 3. We conclude that: (1) trisomy 3 occurs in a high proportion of extranodal, nodal and splenic MZBCL; (2) FISH on interphase nuclei is an additional and sensitive tool in detecting an increased copy number of chromosome 3 in MZBCL; (3) additional structural abnormalities involving the long arm of chromosome 3 are frequent but non-recurrent and are perhaps secondary changes; and (4) abnormalities such as +del(3)(p13) and +i(3)(q10) suggest that genes located on the long arm of chromosome 3 are of particular importance in the pathogenesis of MZBCL.     

Unconjugated serum bile acids as a marker of small intestinal bacterial overgrowth

Non-invasive methods to detect small intestinal bacterial overgrowth often lack specificity in patients who have undergone an ileal resection or have an accelerated intestinal transit. Since elevated serum unconjugated bile acid levels have been found in patients with clinical signs of bacterial overgrowth, we studied the clinical value of unconjugated serum bile acids as a marker of small intestinal bacterial overgrowth. Patients with culture-proven bacterial overgrowth had significantly elevated fasting unconjugated serum bile acid levels (median and range: 4.5; 1.4-21.5 mumol l-1) as compared to healthy subjects (0.9; 0.3-1.7 mumol l-1, P less than 0.005), to persons with an accelerated intestinal transit (1.0; 0.3-1.9 mumol l-1, P less than 0.005) and to persons who have undergone an ileal resection (2.1; 0.7-3.6 mumol l-1, P less than 0.005). The same was true 30 and 60 min after ingestion of a Lundh meal. Serum unconjugated bile acid levels above 4 mumol l-1 were found in eight of 10 patients with culture-proven small intestinal bacterial overgrowth whereas serum levels above 4 mumol l-1 were found in none of the patients from the three control groups. These results suggest that determination of unconjugated serum bile acids is of clinical value in the evaluation of patients suspected of small intestine bacterial overgrowth.     

Short-Term and Long-Term Changes of Left Ventricular Volumes During Rate-Adaptive and Single-Rate Pacing

To evaluate the adaptation of the heart to exercise during pacing, 15 patients with permanent endocardial pacemakers were studied; nine patients had atrioventricular universal (DDD) pacemakers (Symbios 7005) and six patients had activity detecting rate-responsive ventricular (VVIR) pacemakers (Activitrax 8403). Left ventricular function in each patient during rate variable pacing was compared to ventricular function during VVI single-rate pacing. End-systolic and end-diastolic volume changes during exercise were measured by radionuclide angiography and the amount of volume change was used to assess left ventricular function. Both short-term (within 4 hours) and long-term measurements (after at least 4 weeks) were made at rest and at 50% of the maximal exercise capacity in DDD or VVIR mode and were compared with VVI single-rate pacing. All patients, when changed from DDD or VVIR mode to VVI single-rate pacing showed a significant increase of the end-diastolic volume during exercise, which increased even more after long-term VVI pacing. During long-term rate variable pacing, there was no increase of the end-diastolic volume during exercise. DDD or VVIR pacing initially showed a substantial increase of the end-systolic volume during exercise combined with a decrease of left ventricular ejection fraction, suggesting a decrease of the left ventricular contractility. After 4 weeks, contractility improved both with DDD and VVIR pacing. We conclude that short-term DDD and VVIR pacing induces a temporary impairment of left ventricular function that improves after 4 weeks, whereas long-term VVI pacing is associated with left ventricular dilatation even at moderate levels of exercise.