Pacemaker implantation and quality of life in the Mode Selection Trial (MOST)

BACKGROUND: Dual-chamber pacemakers restore AV synchrony compared with ventricular pacemakers, but the effects on health-related quality of life (QOL) are uncertain. OBJECTIVES: The purpose of this study was to assess the effect of pacemaker implantation, clinical factors, and pacing mode on QOL. METHODS: The Mode Selection Trial (MOST) randomized 2,010 patients with sinus node dysfunction to rate-modulated right ventricular (VVIR) or dual-chamber (DDDR) pacing. A longitudinal analysis of serial QOL measures (Short Form-36 [SF-36], Specific Activity Scale, and time trade-off utility) was performed. In patients who crossed over from VVIR to DDDR because of severe pacemaker syndrome, the last known QOL prior to crossover was carried forward. RESULTS: Pacemaker implantation resulted in substantial improvement in almost all QOL measures. Subjects 75 years or older experienced significantly less improvement in functional status and physical component summary scores than did younger subjects. In longitudinal analyses of the effect of pacing mode on QOL, significant improvement in three SF-36 subscales was observed with DDDR pacing compared with VVIR pacing: role physical [62.8 points (95% confidence interval [CI] 60.2, 65.5) vs 56.4 (95% CI 53.7, 59.1)], role emotional [85.0 (95% CI 82.9, 87.0) vs 81.9 (95% CI 79.9, 84.0)], and vitality [51.8 (95% CI 50.3, 53.3) vs 49.3 (95% CI 47.8, 50.7)], but not in other SF-36 subscales, the Specific Activity Scale, or utilities. The gains in QOL were larger than the declines associated with 1 year of aging but smaller than those associated with heart failure. CONCLUSION: Pacemaker implantation improved health-related QOL. The mode selected was associated with much smaller, but significant, improvements in several domains, particularly role physical function.     

High incidence of pacemaker syndrome in patients with sinus node dysfunction treated with ventricular-based pacing in the Mode Selection Trial (MOST)

OBJECTIVES: We evaluated the incidence, predictors, and treatment of pacemaker syndrome in patients with sinus node dysfunction treated with ventricular-based (VVIR) pacing in the Mode Selection Trial (MOST). BACKGROUND: Pacemaker syndrome, or intolerance to VVIR pacing, consists of cardiovascular signs and symptoms induced by VVIR pacing. METHODS: The definition of pacemaker syndrome required that a patient with single-chamber VVIR pacing develop either congestive signs and symptoms associated with retrograde conduction during VVIR pacing or a >or=20 mm Hg reduction of systolic blood pressure during VVIR pacing, associated with reproducible symptoms of weakness, lightheadedness, or syncope. RESULTS: Of 996 patients randomized to VVIR pacing, 182 (18.3%) met criteria for pacemaker syndrome in follow-up. Pacemaker syndrome occurred early in most patients (13.8% at 6 months, 16.0% at 1 year, increasing to 19.7% at 4 years). Baseline univariate predictors of pacemaker syndrome included a lower sinus rate and higher programmed pacemaker rate. Previous heart failure, ejection fraction, and drop in systolic blood pressure with VVIR pacing at implantation did not predict the development of pacemaker syndrome. Post-implantation predictors of pacemaker syndrome were a higher percentage of paced beats, higher programmed low rate, and slower underlying spontaneous sinus rate. Quality of life decreased at the time of diagnosis of pacemaker syndrome and improved with reprogramming to atrial-based pacing. CONCLUSIONS: Severe pacemaker syndrome developed in nearly 20% of VVIR-paced patients and improved with reprogramming to the dual-chamber pacing mode. Because prediction of pacemaker syndrome is difficult, the only way to prevent pacemaker syndrome is to implant atrial-based pacemakers in all patients.     

Exenatide treatment did not affect bone mineral density despite body weight reduction in patients with type 2 diabetes

Preclinical studies suggest that incretin-based therapies may be beneficial for the bone; however, clinical data are largely lacking. We assessed whether the differential effects of these therapies on body weight differed with respect to their effect on bone mineral density (BMD) and markers of calcium homeostasis in patients with type 2 diabetes (T2D). Sixty-nine metformin-treated patients with T2D were randomized to exenatide twice daily (n = 36) or insulin glargine once daily (n = 33). Total body BMD, measured by dual-energy X-ray absorptiometry, and serum markers of calcium homeostasis were assessed before and after 44-week treatment. Exenatide or insulin glargine treatment decreased body weight by 6%. Endpoint BMD was similar in both groups after 44-week therapy (LSmean ± s.e.m. between-group difference -0.002 ± 0.007 g/cm(2) ; p = 0.782). Fasting serum alkaline phosphatase, calcium and phosphate remained unaffected. Forty-four-week treatment with exenatide or insulin glargine had no adverse effects on bone density in patients with T2D, despite differential effects on body weight.     

Initial microbiologic studies did not affect outcome in adults hospitalized with community-acquired pneumonia.

Microbiologic studies (MBSs) fail to identify a specific pathogen in more than 50% of patients with community-acquired pneumonia (CAP). The 1993 American Thoracic Society guideline (ATS-GL) for the management of CAP advised selecting initial antibiotic regimens based on severity of illness and comorbidities. Our study evaluated the role of initial MBS in adult patients hospitalized with CAP and treated according to the ATS-GL. In 184 patients hospitalized at our facility for CAP in 1996, and treated according to the ATS-GL, 25 (14%) failed to respond to initial antibiotic regimens. In these nonresponders, there was no difference in mortality between those in whom antibiotics were changed empirically, and those with MBS-guided changes. We conclude that initial MBS may not be warranted in many adult patients admitted for CAP. Exceptions include patients with conditions that predispose to less common, more resistant pathogens.     

HLA-DRB1 haplotype did not affect the medium-term results of total knee arthroplasty in patients with rheumatoid arthritis

This study investigated whether the HLA-DRB1 susceptible allele (SA) genotype is predictive for total knee arthroplasty (TKA) failure in patients with rheumatoid arthritis (RA). The results of 49 TKAs (30 RA patients) with an average follow-up of 7.9 years (range 5–15 years) were analyzed using a 12-item questionnaire and the Knee Society system. HLA-DRB1 alleles were used to estimate the severity of RA and divide the patients into three categories depending upon the gene dose of SA (SA+/+, SA+/–, and SA–/–). For all three categories, the 12-item questionnaire had significantly improved postoperatively, but without significant difference. We divided the 12 items of the questionnaire into two groups: knee-relevant parameters and general parameters. Patients in all three groups improved similarly in knee-relevant parameters. In contrast, those homozygous for SA (SA+/+) benefited less in general parameters. The average radiolucency score was 1.87mm, with no difference being detected among the three groups. The HLA-DRB1 genotype did not affect the survival of the knee implants. Overall, patients without the RA-associated HLA gene benefited most from TKA as they improved not only in knee function, but also in parameters of general functional status.     

Omeprazole treatment does not affect the metabolism of caffeine

This study was performed to investigate the possible influence of repeated omeprazole dosing on the metabolism of caffeine, which has been shown to reflect the activity of one specific enzyme within the hepatic cytochrome P450 family, P450IA2. Ten healthy, nonsmoking young men participated in this placebo-controlled double-blind trial. Each subject was given omeprazole, 20 mg, every morning for 1 week and placebo every morning for 1 week in random order and separated by a 2-3 week washout period. On the sixth and seventh days of each period urine was collected twice daily, and urinary metabolites of caffeine were determined by high-performance liquid chromatography. The urinary metabolite ratio of three paraxanthine 7-demethylation products relative to a paraxanthine-hydroxylation product corresponds to caffeine clearance and, therefore, to P450IA2 activity. This calculated ratio was 4.8 (95% confidence interval, 3.9-5.6) in the placebo and 4.6 (95% confidence interval, 3.6-5.5) in the omeprazole period. These results show that the metabolism of caffeine was unaltered following omeprazole treatment, indicating that omeprazole treatment has no influence on cytochrome P450IA2 activity in the clinical situation.     

Treatment of hypothyroidism reduces low-density lipoproteins but not lipoprotein(a).

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL) particle in which apolipoprotein B-100 (apo B) is attached to a large plasminogen-like protein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma are inversely correlated. LDL and apo B levels are often elevated in untreated hypothyroidism and lowered by thyroxine (T4) treatment, probably due to an increase in LDL receptors. We measured plasma concentrations of LDL, apo B, and Lp(a) in 13 patients with symptomatic primary hypothyroidism before and during T4 therapy. The mean concentration of LDL decreased significantly (P = .006) from 6.05 mmol/L to 4.07 mmol/L, and the mean concentration of apo B decreased significantly (P = .005) from 1.42 g/L to 1.12 g/L. Median Lp(a) concentrations remained unchanged (P = .77); they were 17.05 mg/dL before and 16.59 mg/dL during T4 treatment. In both the untreated condition and during substitution therapy, Lp(a) levels were higher in patients than in healthy controls, probably due to a relatively high frequency of the small Lp(a) phenotypes in our patients. Since Lp(a) contains apo B, which is a ligand for the LDL receptor, it is surprising that Lp(a) is not reduced along with LDL and apo B. These findings suggest that the catabolism of LDL and Lp(a) differ in some respect, and that thyroid hormones have little, if any, effect on Lp(a).     

Lead time of carcinoembryonic antigen elevation in the postoperative follow-up of colorectal cancer did not affect the survival rate after recurrence

Background and aims

The role of carcinoembryonic antigen (CEA) in the early detection of recurrence during the postoperative follow-up of colorectal cancer remains unclear. We hypothesize that the tumor with longer lead time of CEA elevation to the definite recurrence may have a better prognosis because of its slower growth rate and closer observation.

Materials and methods

From 1995 to 2003, 4,841 consecutive patients who received curative resection of localized colorectal adenocarcinoma were enrolled from a prospective database. The patients with persisting CEA elevation after operation had been already excluded. Postoperative follow-up, including physical examination, imaging, and CEA test, were performed according to a surveillance program. A CEA ≥5 ng/mL was defined as elevated. The definition of the CEA lead time was the period between CEA elevation and detection of recurrence. All statistical analyses were performed by SPSS package for Windows (Microsoft, Redmond, WA, USA).

Results

The postoperative median follow-up time for the 4,841 patients was 68 months. A total of 999 patients (20.6%) had CEA elevation and recurrence. Among these patients, recurrence was confirmed in 727 patients (72.8%)before, at the same time, or within 3 months of CEA elevation and thus had a short lead time of CEA elevation (SLT group). In 272 patients (27.2%), recurrence was confirmed after more than 3 months of CEA elevation and thus had a longer lead time of CEA elevation (LLT group). The recurrence pattern showed similarities in these two groups. A total of 193 patients (193/999, 19.3%) received a second radical operation, and 806 patients (80.7%) were inoperable. The re-resection rate between the SLT group (146 patients, 20.1%) and the LLT group (47 patients, 17.3%) was not significantly different. The overall survival rate after recurrence showed no difference between these two groups (P?=?0.123).

Conclusion

Most cases of recurrence were detected at nearly the same time when the CEA level was elevated. Therefore, a more sensitive test is needed for early detection. The relationship between the lead time of CEA and the clinical outcome was not statistically significant. A more aggressive approach to the patient who has CEA elevation and is highly suspect of recurrence may be needed.     

Long-term treatment with cimetidine does not essentially affect the hypothalamic-pituitary-gonadal axis in man

The effect of cimetidine maintenance treatment on gonadal function has been assessed by seminal analysis plus prolactin and gonadotropin blood level concentrations. Nine patients, all with duodenal ulcer, 5 of whom had received 400 mg cimetidine at night for 18, 3 for 24 and 1 for 36 months, were studied. All patients were presumably fertile, having fathered a child born not more than 3 years before the start of cimetidine treatment. In all patients two seminal analyses were performed and blood specimens were obtained for radioimmunoassay estimation of FSH, LH and prolactin concentrations both in basal conditions and 20', 30' and 60' after the i.v. injection of Gn-RH (100 micrograms) and TRH (200 micrograms). All but one patient, in whom mild oligoasthenozoospermia was detected, had normal sperm counts and motility; moreover hormonal levels both in basal conditions and after releasing factor stimulation were found to be similar to those observed in a control group. Cimetidine maintenance treatment has no effect on sexual activity, the quality of seminal fluid or the pituitary secretion of gonadotropins or prolactin.