Comparison of single daily dose of methimazole and propylthiouracil in the treatment of Graves' hyperthyroidism

OBJECTIVE: The present study was to compare the efficacy of a single daily dose of methimazole (MMI) and propylthiouracil (PTU) in the treatment of Graves' hyperthyroidism. BACKGROUND: Antithyroid drugs, MMI and PTU, are widely used in the treatment of hyperthyroidism. Previous studies in the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a more favourable result with MMI. However, the efficacy of a single daily dose of PTU was inconsistent. In this study, we examined the therapeutic efficacy of single daily doses of MMI and PTU on the change of thyroid hormones and thyrotropin receptor antibodies (TRAb) levels. METHODS: Thirty patients with newly diagnosed Graves' hyperthyroidism were randomly divided into two groups, each receiving a single dose of either 15 mg MMI or 150 mg PTU daily for 12 weeks. The therapeutic efficacy was determined by serum total triiodothyronine (TT3), total thyroxine (TT4), thyrotropin (TSH), free thyroxine (FT4), and TRAb levels at baseline and at the end of 4, 8 and 12 weeks during the study period. RESULTS: There was no significant difference in baseline thyroid function parameters. Serum TT3, TT4 and FT4 levels in the MMI-treated group were significantly lower than those of the PTU-treated group after 4 weeks and through the end of the study. MMI also has superior effect on reducing serum TRAb levels than PTU after 8 weeks and at the end of the study. CONCLUSION: During the 12-week treatment of Graves' hyperthyroidism, a single daily dose of 15 mg MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg PTU. In the doses used in this study, MMI is preferable to PTU when a once-daily regimen of antithyroid drug is considered for the treatment of Graves' hyperthyroidism.     

Delayed post-myocardial infarction invasive measures, helpful or harmful? A subgroup analysis

BACKGROUND: In patients who have experienced acute myocardial infarction (MI), primary percutaneous coronary intervention (PCI) has been shown to be of benefit in terms of clinical outcomes. However, the value of performing routine PCI in patients with early MI (ie, an MI occurring > 12 h to < or = 7 days before patient presentation) or recent MI (ie, an MI occurring > or = 8 days to < 30 days before patient presentation) has not been established. The purposes of this prospective observational study were to evaluate the impact of PCI on outcomes, and to delineate the predictors of lack of response to reperfusion and the prognostic determinants in patients with this clinical condition. METHODS AND RESULTS: A total of 377 consecutive unselected patients who had experienced early or recent MI underwent PCI. Successful reperfusion (ie, Thrombolysis in Myocardial Infarction flow grade 3 of the infarct-related artery [IRA]) was achieved in 90.2% of patients. By multiple stepwise logistic regression analysis, high-burden thrombus formation (odds ratio [OR], 15.53; 95% confidence interval [CI], 6.09 to 39.60; p < 0.0001) in the IRA, early PCI (ie, < or = 3 days) [OR, 4.10; 95% CI, 1.79 to 7.36; p = 0.0008], advanced congestive heart failure (CHF) [OR, 4.10; 95% CI, 1.70 to 9.91; p = 0.002], and diabetes (OR, 3.03; 95% CI, 1.03 to 7.06; p = 0.010) were independent predictors for lack of response to reperfusion. The 30-day mortality rate was 6.8%. The only variables that were independently related to the 30-day mortality rate were advanced CHF (OR, 29.85; 95% CI, 7.84 to 113.7; p < 0.0001), lack of response to reperfusion (OR, 7.57; 95% CI, 2.29 to 25.07; p = 0.0009), early PCI (OR, 4.81; 95% CI, 1.60 to 14.41; p = 0.005), and multivessel disease (OR, 9.22; 95% CI, 1.63 to 52.04; p = 0.0119). The surviving 351 patients were discharged from the hospital and followed-up for a mean (+/- SD) 38.9 +/- 14.2 months. Coronary angiographic follow-up was performed in 285 patients (81.2%). Restenosis of the IRA was found in 101 patients (35.4%). Reinterventions of the IRA were required in 69 patients (24.2%). Follow-up measurements of left ventricular ejection fraction (LVEF) showed significantly more improvement than the initial LVEF (59.3 +/- 13.8% vs 50.4 +/- 13%; p < 0.0001). The total cumulative mortality rate after hospital discharge was 6.5% for the entire group. Only advanced CHF (OR, 3.46; 95% CI, 1.26 to 9.52; p = 0.016) and old age (ie, > or = 70 years of age) [OR, 4.41; 95% CI, 1.59 to 12.24; p = 0.004] were independent predictors of long-term mortality. CONCLUSION: The performance of PCI on > or = day 4 in patients after they had experienced an MI was safe and had a high rate of success. The clinical benefits of a relative low mortality rate associated with successful PCI for patients with early and recent MI was maintained during the long-term follow-up. However, patients with advanced CHF along with old age continued to have a poor prognosis.     

Comparison of clinical outcome between patients continuing and discontinuing lamivudine therapy after biochemical breakthrough of YMDD mutants

BACKGROUND/AIMS: The aim of this study was to compare the clinical outcome between patients continuing and discontinuing lamivudine therapy after the biochemical breakthrough of hepatitis B virus tyrosine-methionine-aspartate-aspartate (YMDD) mutant. METHODS: YMDD mutants were detected in 51 chronic hepatitis B patients who experienced a flare-up of alanine aminotransferase (ALT) during lamivudine treatment. Twenty-seven of them discontinued lamivudine therapy (group A), and 24 continued therapy (group B) after biochemical breakthrough. The follow-up period was 12 months in both the groups. RESULTS: There was no significant difference between groups A and B in the incidence and severity of ALT peaks and hepatic decompensation within the first 3 months after biochemical breakthrough. After the fourth month of biochemical breakthrough, however, group A experienced acute exacerbation more frequently [20/26 (77%) vs. 7/23 (30%); P=0.002] and higher ALT peaks than group B. The same result was found when the patients were divided into na?ve and retreated or cirrhotic and non-cirrhotic groups. Hepatic decompensation at the onset of biochemical breakthrough was associated with higher mortality (OR=70, 95% CI=6.06-807.75). CONCLUSIONS: Patients who discontinued lamivudine therapy increased the frequency of flare-ups and higher ALT peaks than those who continued therapy after 4 months post-breakthrough.     

Tuberculous peritonitis in different dialysis patients in Southern Taiwan

Eleven cases of tuberculous peritonitis (TBP) in hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients at the Kaohsiung Veterans General Hospital in Kaohsiung, Taiwan between 1991 and 2000 were studied retrospectively (six cases in the HD group and five cases in the CAPD group) The diagnosis of TBP was established by either positive ascite tuberculosis (TB) culture or biopsy-proven chronic granulomatous inflammation. Fever and abdominal pain were the most common symptoms, while leukocytosis and unexplained hypercalcemia were the most common laboratory findings. Ascite analysis showed a lymphocyte predominance in all HD patients, but in only 40% of the CAPD patients. The mean duration of a diagnosis by ascite TB cultures was six weeks, while a diagnosis confirmed by laparascopic biopsy took one week. All four fatal cases were diagnosed by TB cultures. Laparoscopic biopsy provided a rapid diagnosis and resulted in low morbidity and mortality in our patients. Based on our review of all possible abstracts found in a Medline search from 1966 to 2002 using the keywords tuberculosis, peritonitis, uremia, and dialysis, this may be the first study of TBP in different dialysis patients.     

Acquirement and disappearance of HBsAg and anti‐HCV in an aged population: a follow‐up study in an endemic township

Background: HBsAg and anti‐hepatitis C virus (anti‐HCV) are stable markers and widely used. The seroconversion and seroclearance of HBsAg and anti‐HCV are important for disease control and prognosis of diseases. Aims: To investigate acquirement and disappearance of HBsAg and anti‐HCV in an endemic area. Methods: Seven years after a community screening, 1002 of 2909 residents of Tzukuan Township were recruited. HBsAg, anti‐HCV and alanine transaminase (ALT) were checked in all who participated and hepatitis B virus (HBV) DNA, anti‐HBs, anti‐HBc, HCV RNA, anti‐HDV and upper abdominal ultrasonography were studied in different groups. Results: There were 461 male and 541 female residents with a mean age of 66.7±8.6 years. No new HBsAg carrier was noted and the HBsAg clearance rate was 1.58% per year. One of the 17 cases with HBsAg clearance had positive HBV DNA, three had ALT elevation, two had cirrhosis and seven had anti‐HBs seroconversion. Quantitative of HBsAg and HBV DNA were concordant and 78.1% subjects had low levels of titration. Anti‐HBc alone contributed to 32.1% and was prominent in old age and the anti‐HCV‐positive group. The anti‐HCV seroconversion rate was only 0.74% per year and household transmission was the only risk factor. Only 37.5% of cases with anti‐HCV seroconversion had HCV viraemia and the anti‐HCV seroreversion rate was 0.63% per year. The anti‐HDV seroconversion rate was 0.72% per year and no subject showed anti‐HDV clearance. Conclusions: Much higher rates of HBsAg seroclearance, anti‐HCV seroreversion and anti‐HBc alone were noted in this endemic area and no subject showed anti‐HDV clearance.     

Characteristics of adefovir resistance in patients with or without lamivudine‐resistant hepatitis B virus treated with adefovir: a 4‐year experience

Background/Aim: We investigated the 4‐year incidence and predictors of adefovir resistance in chronic hepatitis B patients with or without lamivudine (LAM)‐resistance treated with adefovir dipivoxil with or without short‐term LAM overlapping. Methods: One hundred and two LAM‐resistant patients and 79 without LAM resistance (36 naïve and 43 prior LAM exposure) treated with adefovir for >12 months were prospectively examined. Results: Cumulative incidences of adefovir resistance at month 12, 24, 36 and 48 were 3.9, 21.1, 31.8 and 43% respectively in LAM‐resistant patients. Cirrhosis was a significant risk factor for adefovir resistance. A similar rate of adefovir resistance was observed for LAM‐resistant patients and those with prior LAM exposure without resistance. Regarding LAM‐resistant patients, compared with those having hepatitis B virus (HBV) DNA levels <300 copies/ml, patients having HBV DNA levels >10⁴ copies/ml at week 24 of therapy had a hazard ratio (HR) of 9.8 for adefovir resistance development, while those without LAM resistance having the same HBV DNA levels at week 48 had a similar HR (9.5). Multidrug‐resistant (LAM+adefovir) variants were detected by direct sequencing in three of 35 LAM‐resistant patients treated with a switch to adefovir. Two of them had resistant mutations to both drugs on the same viral genome as determined by molecular cloning and sequencing. Conclusion: The incidence of adefovir resistance was high in LAM‐resistant patients treated with sequential adefovir. High HBV DNA levels at week 24 and 48 of therapy were the strongest predictors for adefovir resistance development in patients with and without LAM resistance respectively.     

Outcome predictors of cirrhotic patients with spontaneous bacterial empyema

Background: Spontaneous bacterial empyema (SBE) is a complication of cirrhotic patients in which a pre‐existing pleural effusion becomes infected. This retrospective study was designed to investigate the bacteriology and outcome predictors of SBE in cirrhotic patients. Methods: Medical records of cirrhotic patients treated in a tertiary care university hospital from December 2004 to December 2008 were retrospectively reviewed. Results: Of 3390 cirrhotic patients seen during the study period, 81 cases of SBE were diagnosed. The incidence of SBE was 2.4% (81/3390) in cirrhotic patients and 16% (81/508) in patients with cirrhosis with hydrothorax. There were 46 monomicrobial infections found in 46 SBE patients. Aerobic Gram‐negative organisms were the predominant pathogens (n=29, 63%), and Escherichia coli (n=9, 20%) was the most frequently isolated sole pathogen. The mortality rate of SBE was 38% (31/81). Univariate analysis showed that Child–Pugh score, model for end‐stage liver disease (MELD)–Na score, concomitant bacteraemia, concomitant spontaneous bacterial peritonitis, initial intensive care unit (ICU) admission and initial antibiotic treatment failure were predictors of poor outcomes. Multivariate regression analysis demonstrated that the independent factors related to a poor outcome were initial ICU admission [odds ratio (OR): 4.318; 95% confidence interval 1CI) 1.09–17.03; P=0.037], MELD–Na score (OR: 1.267; 95% CI 1.08–1.49; P=0.004) and initial antibiotic treatment failure (OR: 13.10; 95% CI 2.60–66.03). Conclusion: Spontaneous bacterial empyema in cirrhotic patients is a high mortality complication. The independent factors related to poor outcome are high MELD–Na score, initial ICU admission and initial antibiotic treatment failure. High MELD–Na score may be a useful mortality predictor of SBE in cirrhotic patients.     

Prevalence and risk factor correlates of elevated C-reactive protein in an adult Australian population

Measurement of the inflammatory biomarker C-reactive protein (CRP) is advocated for coronary heart disease risk assessment. The distribution and correlates of CRP in the general population should be known before it is used in clinical practice. CRP was measured in 1,761 men and 2,248 women aged 25 to 84 years who attended the 1994/1995 Busselton Health Survey. Prevalences of increased CRP >3 mg/L for age groups 25 to 39, 40 to 59, and 60 to 84 years were 15.7%, 20.6%, and 38.7%, respectively, in men and 21.2%, 22.1%, and 33.7%, respectively, in women not on hormone therapy. Logistic regression analysis identified independent predictors of increased CRP in men as obesity (odds ratio [OR] 3.5, 95% confidence interval [CI] 2.4 to 5.0), smoking (OR 3.1, 95% CI 2.1 to 4.5), hypertension (OR 1.6, 95% CI 1.1 to 2.3), and low high-density lipoprotein cholesterol (OR 1.4, 95% CI 1.0 to 1.8). In women, predictors were obesity (OR 7.8, 95% CI 5.8 to 10.6), hypertension (OR 1.4, 95% CI 1.0 to 1.9), high triglycerides (OR 1.6, 95% CI 1.1 to 2.4), vigorous exercise (OR 0.7, 95% CI 0.5 to 0.9), oral contraceptive use (OR 4.6, 95% CI 3.3 to 6.5), and hormone replacement therapy (OR 2.8, 95% CI 1.9 to 4.0). Overall, risks of increased CRP attributable to the presence of an abnormal or borderline coronary heart disease risk factor were 59% for men and 64% for women. In conclusion, despite gender-related differences in cardiovascular risk, increased CRP occurred commonly in men and women. Because increased CRP was largely attributable to conventional coronary heart disease risk factors, measurement of CRP may have limited utility for risk screening and primary prevention.     

Outcome of off-pump coronary artery bypass in renal dialysis patients

BACKGROUND: Renal dialysis patients are a subgroup at major operative risk when undergoing coronary artery bypass grafting (CABG). Even though CABG without cardiopulmonary bypass (CPB) has decreased the surgical risk and provided good short-term results, the long-term survival seems uncertain. We report here on the long-term outcome of CABG without CPB in renal dialysis patients. METHODS: From 1998 to 2002, 44 renal dialysis patients underwent elective CABG without CPB, including 17 minimally invasive direct coronary artery bypass (MIDCAB) and 27 off-pump CABG (OPCAB) procedures. There were 5 one-vessel, 12 two-vessel and 27 multi-vessel coronary artery disease patients, who mainly had left internal thoracic artery (LITA) to left anterior descending coronary artery (LAD) grafting with an additional saphenous vein graft to non-LAD coronaries. RESULTS: All 44 patients were followed up for 44.4 +/- 31.2 months. Three (6.8 %) surgical deaths within 30 days occurred and 25 late mortalities happened over a period of 2 - 79 months. The 5-year cumulative rate of total survival is 38.2 % and the freedom from cardiac death is 70.9 %. Using hazard analysis, old age (> 60 years) and incomplete coronary revascularization was found to significantly affect the total survival. CONCLUSIONS: CABG without CPB provided an acceptable surgical mortality and morbidity. The high incidence of non-cardiac death associated with dialysis complications had an adverse impact on the overall outcome. The LITA bypass operation method combined with intensive care for dialysis complications would hopefully fulfill the goal to improve the short- and long-term results in this subgroup.     

High body mass index is not associated with coronary artery disease in angina patients with chronic kidney disease: a coronary angiography study

BACKGROUND: High body mass index (BMI) is an established risk factor for coronary artery disease (CAD) in the general population. This relationship is less clear in CAD patients with different stages of chronic kidney disease (CKD) because many complications of CKD can cause malnutrition and low BMI. We studied the association of BMI and angiography-confirmed CAD in CKD patients. METHODS: Thousand one hundred thirty-three patients admitted for coronary angiography was stratified by CKD classification. Demographic, clinical, hemodynamic, and angiographic findings were assessed. CKD patients (n = 980) were divided into angiographic CAD and non-CAD groups to compare traditional CAD risk factors. Patients with angiography-confirmed CAD (n = 496) were further analyzed for the association between BMI and CAD risk at different stages of CKD patients. RESULTS: Mean BMI was 27.4 +/- 4.1, 27.7 +/- 4.0, 25.9 +/- 3.5, 24.2 +/- 3.8, 23.2 +/- 3.0 and 23.8 +/- 4.2 kg/m for normal renal function, stage I, II, III, IV, and V CKD patients, respectively. Male, old age, presence of CKD, diabetes, hypertension, smoking, and higher cholesterol had significant association with angiographic CAD in the CKD sub-cohort. Obesity was not related to CAD in the CKD sub-cohort. Using WHO category for obesity, mild CKD patients were more likely to be overweight (62.8%) and obese (72%); meanwhile, most moderate and severe CKD patients were not obese (P < 0.05). Only 17.6% and 18.8% of moderate and severe CKD patients were obese (P < 0.05), by Taiwan classification. CONCLUSION: High BMI was not associated with angiographic CAD in CKD patients with angina.