Prevalence of supraventricular arrhythmias from the automated analysis of data stored in the DDD pacemakers of 617 patients: the AIDA study

The confirmation of the occurrence of supraventricular arrhythmias (SVAs) is possible only if a surface electrocardiogram (ECG) is recorded during an episode, or if SVAs occur during 24 h ambulatory monitoring (Holter). The automatic interpretation of memory functions in DDD pacemakers may be useful in this diagnostic task over longer periods of follow up. This hypothesis was tested in 384 men and 233 women (mean age = 70 ± 11 years) who had received Chorus 6034/6035, 6234 or 7034 pacemakers (ELA Medical, Montrouge, France) with fall-back function in case of sustained SVAs. The Automatic Interpretation for Diagnostic Assistance (AIDA) algorithm included in these pacemakers was compared with 24 h Holters recorded simultaneously (DI) and with the clinical history of symptoms consistent with SVAs up to 28 days of follow up (D28). Indications for pacing were atrioventricular block (AVB) in 269 patients, sinus node dysfunction (SND) in 248, and AVB + SND in 100. SVAs were documented before implant in 199 patients (32%). Among the 617 patients included at D1. 76 (12.4%) developed at least one SVA episode, lasting between 1 min and 24 hours, simultaneously recorded on Holter and by AIDA with a 93.8% sensitivity and 94.2% specificity. Data from 354 patients were available for analysis at D28. AIDA diagnosed SVAs in 179 patients (50.6%), 104 of whom (65%) had remained asymptomatic and 117 of whom (65%) had had no SVA documented before implant. Among the 354 patients, AIDA diagnosed SVAs in 76 (21%) asymptomatic patients who had no known SVA before implant. The prevalence of SVA in our AVB population was higher than reported in previous studies: 89 patients (56.3%) with AVB had SVAs versus 90 patients (45.9%) with other diagnoses (p=0.55). Furthermore atrial pacing was associated with fewer SVAs. These first clinical results of the AIDA study demonstrate that the memory functions of Chorus pacemakers and the AIDA software are reliable to analyze the prevalence of SVA at 1 month of follow-up. From a clinical point of view, AIDA is a valuable tool to evaluate the efficacy of antiarrhythmic therapy, particularly as it pertains to the prevention of stroke due to atrial fibrillation.     

SITE VARIABILITY IN A MULTISITE GERIATRIC DEPRESSION TRIAL

We studied differences in outcome and characteristics among 29 clinical sites of a multisite, double-blind antidepressant trial for geriatric depression. Six hundred and seventy-one outpatients aged 60 years or older (mean±SD=67.7±5.7) met DSM-III-R criteria for unipolar major depression, had baseline 17-item Hamilton Depression Rating Scale (HAMD₁₇) scores ≥16 and were randomized to fluoxetine (20 mg daily) or placebo. Effect sizes (ESs, expressed as mean differences between effects divided by the pooled standard deviation of the differences) were calculated for each site using selected outcome measures. ES ranged from 1.84 (favoring fluoxetine) to −0.91 (favoring placebo) for incidence of remitters (endpoint HAMD₁₇ total score of ≤8). A large, positive ES favoring fluoxetine for remission rates (ES≥0.65) was found at only six sites, moderate ES (0.35–0.64) at eight and small ES (0–0.34) at seven; ES favored placebo (<0) at eight of 29 sites. Private clinics showed an overall HAMD₁₇ ES for change scores more than twice that of university sites. These results suggest that individual practitioners may have vastly different clinical experiences in large, multisite trials for geriatric depression. Interrater reliability, subject selection, recruitment, inadequate or fixed dosing, few patients per site, brief study duration, heterogeneity of geriatric depression, financial incentive and characteristics of individual sites may contribute to response variability.     

Recombinant human platelet-derived growth factor-BB (becaplermin) for healing chronic lower extremity diabetic ulcers: an open-label clinical evaluation of efficacy

Topically applied recombinant human platelet-derived growth factor-BB (becaplermin) is a new pharmacologically active therapy for chronic, neuropathic, lower extremity diabetic ulcers. In previous studies, becaplermin gel was administered once daily but dressings were changed twice daily. In the present study of 134 patients with diabetes mellitus and full thickness lower extremity ulcers, dressings were changed only once per day, simplifying the treatment regimen. Efficacy criteria included the percentage of patients achieving complete healing within the 20-week treatment period, the time to achieve complete healing, the rate of ulcer recurrence during the 6-month period following healing, and treatment compliance. Complete healing of ulcers was achieved in 57. 5% of patients, with a mean time to closure of 63 days and a recurrence rate of 21% at 6 months. Of the potential factors affecting ulcer healing, only drug compliance (p < 0.001), dressing compliance (p < 0.01), the presence of infection (p < 0.01), baseline ulcer area (p < 0.05), and baseline total wound evaluation score (p < 0.05) were significantly associated with healing. Results of this study further confirm the efficacy and safety of becaplermin gel for the treatment of lower extremity diabetic ulcers.     

Phase II Study of Co-Administration of Uracil and Tegafur (UFT) in Hepatocellular Carcinoma

A Phase II study of co-administration of uracil and tegafur(UFT) was performed in 32 patients with unresectable hepatocellularcarcinoma. A dose of 400 mg/m²/day of UFT was administered orally,three times a day, for more than 4 weeks. Of 26 patients evaluablefor response, one (3.8%) showed a partial response of 9 months'duration. There were no complete responders. A dose-limitingtoxicity was gastrointestinal tract disturbance. Six patients(18.8%) had to discontinue UFT treatment because of gastrointestinaltoxicity. The clinical advantage of tegafur in the treatmentof hepatocellular carcinoma was not enhanced by co-administrationof uracil.     

Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64)

BACKGROUND: The progression of nephropathy from diagnosis of type 2 diabetes has not been well described from a single population. This study sought to describe the development and progression through the stages of microalbuminuria, macroalbuminuria, persistently elevated plasma creatinine or renal replacement therapy (RRT), and death. METHODS: Using observed and modeled data from 5097 subjects in the UK Prospective Diabetes Study, we measured the annual probability of transition from stage to stage (incidence), prevalence, cumulative incidence, ten-year survival, median duration per stage, and risk of death from all-causes or cardiovascular disease. RESULTS: From diagnosis of diabetes, progression to microalbuminuria occurred at 2.0% per year, from microalbuminuria to macroalbuminuria at 2.8% per year, and from macroalbuminuria to elevated plasma creatinine (>or=175 micromol/L) or renal replacement therapy at 2.3% per year. Ten years following diagnosis of diabetes, the prevalence of microalbuminuria was 24.9%, of macroalbuminuria was 5.3%, and of elevated plasma creatinine or RRT was 0.8%. Patients with elevated plasma creatinine or RRT had an annual death rate of 19.2% (95% confidence interval, CI, 14.0 to 24.4%). There was a trend for increasing risk of cardiovascular death with increasing nephropathy (P < 0.0001), with an annual rate of 0.7% for subjects in the stage of no nephropathy, 2.0% for those with microalbuminuria, 3.5% for those with macroalbuminuria, and 12.1% with elevated plasma creatinine or RRT. Individuals with macroalbuminuria were more likely to die in any year than to develop renal failure. CONCLUSIONS: The proportion of patients with type 2 diabetes who develop microalbuminuria is substantial with one quarter affected by 10 years from diagnosis. Relatively fewer patients develop macroalbuminuria, but in those who do, the death rate exceeds the rate of progression to worse nephropathy.     

A Survey on Occurrence of Melamine and Its Analogues in Tainted Infant Formula in China

Objective To investigate the occurrence and concentrations of melamine and its analogues in tainted infant formula and to identify the etiologic factors for the urinary stones epidemic in infants and young children in China in 2008. Methods Sanlu infant formula samples were collected from families of the affected children in Gansu province, and markets in Gansu and Hebei provinces and Beijing city. Melamine and its analogues, including cyanuric acid, ammeline, and ammelide were measured by gas chromatography/tandem mass spectrometry. Results High prevalence and concentrations of melamine were found in Sanlu infant formula samples, with low concentrations of cyanuric acid, ammeline and ammelide. Melamine were detected in 87 out of 111 Sanlu infant formula samples with a range of 118 to 4 700 mg/kg, Conclusion The results provide strong evidence for melamine as the etiological factor for the urinary stones epidemic in infants and young children in China in 2008.     

Randomized factorial trial of high-dose intravenous streptokinase, of oral aspirin and of intravenous heparin in acute myocardial infarction

619 patients with suspected acute myocardial infarction (MI)were randomized to receive either a high-dose short-term intravenousinfusion of streptokinase (1.5 MU over one hour) or placebo.Using a '2 x 2 x 2 factorial' design, patients were also randomizedto receive either oral aspirin (325 mg on alternate days for28 days) or placebo and separately randomized to receive eitherintravenous heparin (1000 1U h-1 for 48 hours) or no heparin.Streptokinase (SK) was associated with a nonsignificant (NS)increase in non-fatal reinfarc–tion (3.9% SKvs 2.9% placebo)and decrease in mortality (7.5%vs9.7% in hospital plus 6.1%vs8.7% after discharge). After SK, there were significantly fewerstrokes (0.5% vs 2.4%; 2P<0.05), but significantly more minoradverse events (e.g. hypotension and bradycardial, allergies,bruises or minor bleeds, nausea). Aspirin was associated withfewer non-fatal reinfarctions (3.2% aspirin vs 39% placebo;NS), deaths (in hospital: 61% vs 10.5%; 2P<0.05, and afterdischarge: 7.0% vs 6.9%; NS), and strokes (0.3% vs 2.0%; NS).Heparin was associated with a decrease in reinfarction (2.2%heparin vs 4.9% no heparin; NS), though not in mortality (inhospital: 8.0% vs 8.5%; NS, and after discharge: 7.0% vs 6.9%;NS), and with a trend towards more strokes (1.6% vs 0.7%; NS)and more bruising and bleeding (14% vs 12%; NS). To assess morereliability the effects of aspirin and of this SK regimen onmortality, about 400 hospitals worldwide are now collaboratingin a large (about 20 000 patients planned ) randomized trial( ISIS-2). for which the present study was a pilot.     

Epidemiological survey of foot diseases in Japan: Results of 30 000 foot checks by dermatologists

There has been no epidemiological survey of foot diseases in Japan. In this study we determined the prevalence of foot diseases, especially tinea pedis (TP) and tinea unguium (TU) in Japan. We conducted a randomized survey of outpatients who visited a dermatologist during the third week of May in 1999, 2000 and 2006. The most frequently reported condition was “fungal infection” in 8737 (40.0%) of 21 820 patients in 1999/2000, and 3848 (49.4%) of 7783 patients in 2006. The patients who visited a dermatologist for reasons other than superficial fungal infection but were diagnosed with TP or TU comprised 18.6% of the study population in 2000 and 24.1% in 2006. Of the patients with TP or TU, 63.2% used topical medication only. This survey showed that often patients are not aware of fungal infections and that their treatment is sometimes insufficient. Dermatologists should actively examine and treat patients with TP and TU.