An evaluation of secondary prophylaxis for rheumatic heart disease in rural Egypt.

BACKGROUND: Although essentially disappeared from the industrialized world, rheumatic heart disease (RHD) is still prevalent in developing countries, with 300,000 new cases identified each year. In Aswan, Egypt, RHD affects about 2.3% of children with over 90% of the cases being subclinical. Secondary prophylaxis has proved to be an effective method of preventing the progression of RHD. However, its efficacy is limited by low patient adherence. A systematic, generalizable tool is necessary to outline, and ultimately address these barriers. METHODS: A 43-item semi-structured questionnaire was developed based on the three domains outlined by Fishbein (capability, intention, and health care barriers). A preliminary evaluation of the barriers to RHD prophylaxis use in Aswan, Egypt was carried out as a pilot study using this tool. Participants were local school children diagnosed with RHD or flagged as high-risk (as per a set of echocardiographic criteria developed by the Aswan Heart Centre) through a previous screening program of randomly selected 3,062 school children in Aswan. RESULTS: 29 patients were interviewed (65.5% adherent to RHD prophylaxis). Compared to non-adherent patients, adherent patients had better understanding of the disease (68.4% versus 20% in the non-adherent group, p = 0.021), and were more aware of the consequences of missing prophylaxis doses (79% versus 40% of non-adherent patients, p = 0.005). Furthermore, 90% of non-adherent patients consciously choose to miss injection appointments (as compared to 31.6% of adherent patients, p = 0.005). Clinic wait time was the most frequently reported deterrent for both groups. CONCLUSION: A standardized tool that systematically outlines barriers to prophylaxis is a necessary first step to improving adherence to penicillin. Although individually developed tools exist for specific populations, a generalizable tool that takes into account the demographic and cultural differences in the populations of interest will allow for more reliable data collection methodology. Application of this tool will be used to further explore barriers to prophylaxis adherence and inform the basis for the design of future KT interventions.

Effectiveness and safety of repeat courses of hylan G-F 20 in patients with knee osteoarthritis.

OBJECTIVE: To compare the effectiveness and safety of repeat treatment with hylan G-F 20 based on data from a randomized, controlled trial [Raynauld JP, Torrance GW, Band PA, Goldsmith CH, Tugwell P, Walker V, et al. A prospective, randomized, pragmatic, health outcomes trial evaluating the incorporation of hylan G-F 20 into the treatment paradigm for patients with knee osteoarthritis (Part 1 of 2): clinical results. Osteoarthritis Cartilage 2002;10:506-17]. The hypotheses tested were whether the single-course and repeat-course subgroups would be superior to appropriate care and not different from each other. METHOD: A total of 255 patients with knee osteoarthritis were randomized to "appropriate care with hylan G-F 20" or "appropriate care without hylan G-F 20". The hylan G-F 20 group was partitioned into two subgroups: (1) patients who received a single course of hylan G-F 20; and (2) patients who received two or more courses of hylan G-F 20. RESULTS: For the primary effectiveness measure, change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score as a percent of baseline, the single-course subgroup improved by 41%, the repeat-course subgroup by 35%, and the appropriate care group by 14%. Both subgroups improved significantly more than the appropriate care group (P<0.05), and were not statistically significantly different from each other (70% power to detect a 20% difference). Secondary effectiveness measures showed similar results. In the repeat-course subgroup, no statistically significant differences were found in the number of local adverse events, the number of patients with local adverse events, or arthrocentesis rates between the first and repeat courses of treatment. CONCLUSIONS: Although the study was neither designed nor powered to examine repeat treatment, this a posteriori analysis provides support for a favorable effectiveness and safety profile of hylan G-F 20 in repeat course patients.

Evaluation of WOMAC 20, 50, 70 response criteria in patients treated with hylan G-F 20 for knee osteoarthritis.

OBJECTIVE: A secondary analysis of a previously conducted one year randomised controlled trial to evaluate the capacity of responder criteria based on the WOMAC index to detect between treatment group differences. METHODS: 255 patients with knee osteoarthritis were randomised to "appropriate care with hylan G-F 20" (AC+H) or "appropriate care without hylan G-F 20" (AC). In the original analysis, two definitions of patient response from baseline to month 12 were used: (1) at least a 20% reduction in WOMAC pain score (WOMAC 20P); (2) at least a 20% reduction in WOMAC pain score and at least a 20% reduction in either WOMAC function or stiffness score (WOMAC 20PFS). For this analysis, a responder was identified using 50% and 70% minimum clinically important response levels to investigate how increasing response affects the ability to detect treatment group differences. RESULTS: The hylan G-F 20 group had numerically more responders using all patient responder criteria. Increasing the response level from 20% to 50% detected similar differences between treatment groups (25% to 29%). Increasing the response level to 70% reduced the differences between treatment groups (11% to 12%) to a point where the differences were not significant after Bonferroni adjustment. CONCLUSIONS: These results provide evidence for incorporating response levels (WOMAC 50) in clinical trials. While differences at the highest threshold (WOMAC 70) were not statistically detectable, an appropriately powered study may be capable of detecting differences even at this very high level of improvement.

Symptom relief in gastroesophageal reflux disease: a randomized, controlled comparison of pantoprazole and nizatidine in a mixed patient population with erosive esophagitis or endoscopy-negative reflux disease.

OBJECTIVES: Gastroesophageal reflux disease (GERD) in primary care practice presents symptomatically, and resources to distinguish promptly between erosive esophagitis and endoscopy-negative reflux disease (ENRD) are limited. It is therefore important to determine the roles of proton pump inhibitors and histamine-2-receptor antagonists for first-line symptom-based therapy in patients with erosive esophagitis and ENRD. The aim of this study was to compare pantoprazole 40 mg once daily versus nizatidine 150 mg b.i.d. in a mixed GERD patient population with ENRD or erosive esophagitis (Savary-Miller grades 1-3). METHODS: A 4-wk randomized, double-blind, parallel-group, multicenter study conducted in Canada. Eligible patients had experienced GERD symptoms > or = 4 times weekly for > 6 months. Patients were randomized to pantoprazole 40 mg once daily or nizatidine 150 mg b.i.d.. Endoscopy was performed before randomization and after 4 wk of therapy. RESULTS: Of 220 patients randomized to therapy, 208 were available for a modified intent-to-treat analysis. Erosive esophagitis was present in 125 patients; 35 patients were Helicobacter pylori positive. There was complete symptom relief after 7 days of therapy in 14% of patients on nizatidine and in 40% of those on pantoprazole (p < 0.0001), and after 28 days of treatment in 36% and 63% of patients, respectively (p < 0.0001). After 28 days of treatment, adequate heartburn control was reported by 58% of the nizatidine group and in 88% of the pantoprazole (p < 0.0001); erosive esophagitis healing rates were 44% for nizatidine and 79% for pantoprazole (p < 0.001). Rescue antacid was needed by a greater number of patients using nizatidine than of those using pantoprazole (p < 0.001). H. pylori infection was associated with an increased probability of erosive esophagitis healing. CONCLUSIONS: Pantoprazole once daily was superior to nizatidine b.i.d. in producing complete heartburn relief in a mixed population of GERD patients and in achieving erosion healing. The proportions of patients with complete symptom relief were greater with pantoprazole after 7 days of therapy than with nizatidine after 28 days. The present study data suggest that pantoprazole is a highly effective first-line therapy for the management of gastroesophageal reflux disease in a primary care practice setting.

Evaluation of the role of abciximab (Reopro) as a rescue agent during percutaneous coronary interventions: in-hospital and six-month outcomes.

Abciximab is effective for the prevention of complications when administered prior to percutaneous coronary intervention (PCI). The efficacy and safety of abciximab as an unplanned or rescue agent for complications of PCI is unknown. Rescue versus planned use was compared in 186 consecutive patients. Primary or rescue PCI for acute myocardial infarction (MI) and shock were excluded. Rescue abciximab use was undertaken in 101 patients (54.3%) and planned abciximab was used in 85 (45.7%). The rescue abciximab patients had a lower incidence of previous MI, preprocedural thrombus, multivessel, and vein graft intervention. In-hospital endpoints in the rescue versus planned abciximab patients were death (1.0% vs. 1. 2%, P = 1.0), Q-wave MI (2.0% vs. 2.4%, P = 1.0), any MI (14.9% vs. 9.4%, P = 0.3), target vessel revascularization (TVR; 0% vs. 1.2%, P = 1.0), and composite (15.8% vs. 10.6%, P = 0.3). At 6 months, events were death (4.0% vs. 2.3%, P = 0.69), MI (14.9% vs. 9.4%, P = 0.26), TVR (20.8% vs. 4.7%, P = 0.001), and composite (30.7% vs. 15. 3%, P = 0.01). In-hospital complications between the rescue and planned abciximab patients of major bleed (1.0% vs. 1.8%, P = NS), stroke (0% vs. 1.8%, P = NS), and thrombocytopenia (3.0% vs. 1.8%, P = NS) were similar. There was a significantly higher procedural time (99.6 min vs. 86.1 min, P = 0.02), contrast volume (278.8 ml vs. 223. 5 ml, P = 0.04), and heparin use (8984 u vs. 6003 u, P = 0.0006) in the rescue group. In this nonrandomized comparison, rescue abciximab allowed for the safe discharge from hospital in the majority of patients. However, during a 6-month follow-up, more patients treated with rescue abciximab required TVR with either repeat PCI or CABG. Further studies are warranted to evaluate the overall strategy of rescue abciximab use in PCI.

Prediction of short term mortality in systemic lupus erythematosus with time dependent measures of disease activity.

OBJECTIVE: To identify predictors of short term mortality in systemic lupus erythematosus (SLE) in terms of time dependent clinical indicators of disease activity from the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). METHODS: We studied data collected on patients followed at the University of Toronto Lupus Clinic. Clinical and laboratory indicators of disease activity are recorded at each clinic visit and a SLEDAI summary score is calculated. Survival analyses were conducted in which the prognostic value of the time dependent indicators of disease activity was examined on 6-month mortality through a multivariate Cox regression model. Relative risks, confidence intervals, and significance levels were obtained for each indicator to reflect their clinical importance and statistical significance. RESULTS: The sample consisted of 806 patients followed for a median of 6.6 years; 702 (87%) were female, 671 (83%) were Caucasian, and the mean age at first clinic visit was 36 years. Seventy-two patients died within 6 months of their last clinic visit. In a univariate regression model, a categorical variable reflecting total SLEDAI score was highly prognostic for mortality (p < 0.001) and yielded increasing relative risks of 1.28 for SLEDAI 1-5 vs 0, 2.34 for SLEDAI 6-10 vs 0, 4.74 for SLEDAI 11-19 vs 0, and 14.11 for SLEDAI > 20 vs 0. In a separate multivariate Cox model examining the individual components of SLEDAI, presence of organic brain syndrome, retinal changes, cranial nerve involvement, proteinuria, pyuria, pleurisy, fever, thrombocytopenia, and leukopenia each significantly increased the risk of death, while new rash and anti-DNA antibodies conferred protective effects. CONCLUSION: This time dependent Cox regression analysis identified the extent to which SLE disease activity, revealed by SLEDAI, is prognostic for short term mortality. Further, important individual components were identified and their prognostic value for death was estimated.

Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure.

AIMS: In addition to diabetes mellitus, less severe abnormalities of glucose and insulin metabolism may be related to functional status in patients with heart failure. We examined the relationship of hyperglycaemia (> or =6.1 mmol. l(-1)) and hyperinsulinaemia (> or =11.2 mU. l(-1)) to functional status and cardiac function in patients with heart failure. METHODS AND RESULTS: Fasting plasma glucose and insulin levels were obtained in 663 heart failure patients. The average left ventricular ejection fraction was 0.28+/-0.07, 63% were in New York Heart Association Functional Class (NYHA-FC) I/II and 37% were in NYHA-FC III/IV. Twenty seven percent had diabetes mellitus, but an additional 8% had undiagnosed diabetes mellitus (glucose > or =7 mmol. l(-1)) and 9% had glucose levels between 6.1 and 7 mmol. l(-1), so that a total of 43% (287) of patients had elevated glucose levels (> or =6.1 mmol. l(-1)). In general, more diabetic patients had NYHA-FC III/IV symptoms, shorter 6 min walk distances, but similar left ventricular ejection fractions compared to non-diabetic patients. The non-diabetic patients in NYHA-FC III/IV had higher glucose and insulin levels than patients in NYHA-FC I/II (6.3+/-0.2 vs 5.6+/-0.1 mmol. l(-1), P<0.001 and 19.6+/-2.3 vs 10. 2+/-0.6 mU. l(-1), P<0.001). Non-diabetic patients with elevated glucose levels had shorter 6 min walk distances compared to those with normal glucose levels (368.2+/-8 m vs 389.+/-4 m, P=0.02), however, left ventricular ejection fraction was similar. CONCLUSION: Glucose abnormalities are extremely common in heart failure patients (43% of patients). Diabetes mellitus and hyperglycaemia or hyperlinsulinaemia in non-diabetic patients were related to worse symptomatic status but not worsening left ventricular ejection fraction compared to patients with normal glucose and insulin levels.

Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators.

BACKGROUND: We investigated the effects of candesartan (an angiotensin II antagonist) alone, enalapril alone, and their combination on exercise tolerance, ventricular function, quality of life (QOL), neurohormone levels, and tolerability in congestive heart failure (CHF). METHODS AND RESULTS: Seven hundred sixty-eight patients in New York Heart Association functional class (NYHA-FC) II to IV with ejection fraction (EF) <0.40 and a 6-minute walk distance (6MWD) <500 m received either candesartan (4, 8, or 16 mg), candesartan (4 or 8 mg) plus 20 mg of enalapril, or 20 mg of enalapril for 43 weeks. There were no differences among groups with regard to 6MWD, NYHA-FC, or QOL. EF increased (P=NS) more with candesartan-plus-enalapril therapy (0.025+/-0.004) than with candesartan alone (0.015+/-0.004) or enalapril alone(0.015+/-0.005). End-diastolic (EDV) and end-systolic (ESV) volumes increased less with combination therapy (EDV 8+/-4 mL; ESV 1+/-4 mL; P<0.01) than with candesartan alone (EDV 27+/-4 mL; ESV 18+/-3 mL) or enalapril alone (EDV 23+/-7 mL; ESV 14+/-6 mL). Blood pressure decreased with combination therapy (6+/-1/4+/-1 mm Hg) compared with candesartan or enalapril alone (P<0.05). Aldosterone decreased (P<0.05) with combination therapy (23.2+/-5.3 pg/mL) at 17 but not 43 weeks compared with candesartan (0.7+/-7.8 pg/mL) or enalapril (-0.8+/-11. 3 pg/mL). Brain natriuretic peptide decreased with combination therapy (5.8+/-2.7 pmol/L; P<0.01) compared with candesartan (4. 4+/-3.8 pmol/L) and enalapril alone (4.0+/-5.0 pmol/L). CONCLUSIONS: Candesartan alone was as effective, safe, and tolerable as enalapril. The combination of candesartan and enalapril was more beneficial for preventing left ventricular remodeling than either candesartan or enalapril alone.