Mortality in individuals with Type 2 diabetes and heart disease in a unique New Zealand population.

AIMS: To determine rate and predictors of mortality in patients with Type 2 diabetes living in a population with a large proportion of Maori and Pacific peoples who were admitted to hospital with myocardial infarction (MI) or congestive cardiac failure (CCF). METHODS: The study population included 4193 individuals with Type 2 diabetes who lived in South Auckland and who participated in a primary care audit between 1994 and 1999. We studied a subgroup of 319 patients who subsequently had a hospital admission for MI or CCF between 1999 and 2001. We examined their demographics, drug treatment, vascular risk factors and mortality up to 2003. RESULTS: Following discharge, the prescription of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, aspirin and statins had all increased significantly. Vascular risk factors including total cholesterol, high-density lipoprotein (HDL) cholesterol, systolic blood pressure and glycated haemoglobin (HbA(1c)) improved significantly. Nevertheless, mortality remained high with individuals admitted because of an MI 7.2-fold more likely to die early and those with a CCF admission 5.9-fold more likely to die early than other individuals with Type 2 diabetes. Maori patients have an 80% excess mortality. CONCLUSIONS: Patients with past admission for MI and/or CCF remain at exceptionally high risk of death for at least 4 years after hospital admission, even with improvements in management of cardiovascular risk factors. Maori individuals are at particular risk.

Patient-led variable dosing with balsalazide as long-term therapy for maintenance in ulcerative colitis: a 3-year prospective observational study.

BACKGROUND: The patient-centred approach is new to the management of ulcerative colitis. To date, it has only been shown to be successful in a short-term study. AIM: To assess the feasibility, safety and efficacy of patient-led dosing using balsalazide in the long-term treatment of ulcerative colitis. METHODS: This was a 3-year, two-cohort, multi-centre study: one cohort was in stable remission (52 patients) and the other was newly in remission (76 patients) from ulcerative colitis. Two 750-mg balsalazide capsules were given twice daily for maintenance, increased by 750-mg increments to a maximum of 6 g for up to 7 days depending on symptom severity. Clinical assessments were made every 12-14 weeks; laboratory assessments were made every 6 months. RESULTS: The average median daily dose of balsalazide was 3 g (range, 1.5-6 g). In the cohort with stable remission, 23 patients (44%) had relapsed by 3 years [median time to relapse, > 1095 days (36 months)]. In the cohort newly in remission, these values were 45 patients (59%) and 656 days (22 months), respectively. In the cohort with stable remission, the time since last relapse was significantly associated with relapse during the first year of treatment (P < 0.033). CONCLUSIONS: Long-term, patient-led, maintenance treatment with balsalazide is well tolerated with a good safety profile and is effective for patients with ulcerative colitis.

A double-blind comparison of balsalazide, 6.75 g daily, and sulfasalazine, 3 g daily, in patients with newly diagnosed or relapsed active ulcerative colitis.

BACKGROUND: Sulfasalazine is well established in the treatment of active ulcerative colitis. Intolerance to sulfasalazine, however, is a common problem. Balsalazide has been designed to deliver 5-aminosalicylic acid to the colon without the poor tolerability of sulfasalazine. AIM: To compare the safety and efficacy of balsalazide, 6.75 g daily, with sulfasalazine, 3 g daily, in the treatment of active ulcerative colitis of all grades of severity. METHODS: Balsalazide and sulfasalazine were compared in a multicentre, double-blind, parallel group study over 12 weeks. Patients were stratified for disease severity and topical and/or oral steroids were co-administered where clinically necessary. RESULTS: Fifty-seven patients were randomized: 28 to receive balsalazide and 29 to receive sulfasalazine. Significantly fewer patients withdrew from the balsalazide group due to adverse events (2/28 vs. 9/29, P=0.041). These data confirm that balsalazide is better tolerated than sulfasalazine. In patients able to tolerate the treatment, similar improvements were recorded in clinical, sigmoidoscopic and histological assessments in both treatment groups. CONCLUSIONS: This study confirms the better tolerability of balsalazide compared to sulfasalazine, and supports the use of balsalazide in ulcerative colitis of all grades of severity.

Incidence of duodenal ulcer healing after 1 week of proton pump inhibitor triple therapy for eradication of Helicobacter pylori. The Lansoprazole Helicobacter Study Group.

BACKGROUND: A number of clinical studies have assessed the efficacy of short-term twice-daily Helicobacter pylori eradication regimens but few have investigated the proportion of patients in whom duodenal ulcer disease was healed with these regimens. AIM: To compare the safety and efficacy of four 1-week H. pylori eradication regimens in the healing of H. pylori associated duodenal ulcer disease. METHODS: Following endoscopic confirmation of duodenal ulcer disease and a positive CLO test, patients underwent a 13C-urea breath test to confirm H. pylori status. Treatment with one of four regimens: LAC, LAM, LCM or OAM, where L is lansoprazole 30 mg b.d., A is amoxycillin 1 g b.d., M is metronidazole 400 mg b.d., C is clarithromycin 250 mg b.d., and O is omeprazole 20 mg b.d., was assigned randomly to those patients who were H. pylori positive, with 62 (LAC), 64 (LAM), 61 (LCM) and 75 (OAM) patients in each treatment group. Follow-up breath tests and endoscopies were performed at least 28 days after the end of treatment. RESULTS: Duodenal ulcer disease was healed 28 days after treatment in 53/62 (85.5%) patients who were treated with LAC, 52/64 (81.3%) of patients treated with LAM, 49/61 (80.3%) of patients treated with LCM and 60/75 (80.0%) of patients treated with OAM (intention-to-treat analysis, n = 262, assumed unhealed if no follow-up endoscopy was performed). All the treatments were of similar efficacy (P = 0.85, chi-squared test) with regard to the healing of duodenal ulcer disease. CONCLUSIONS: The four 1-week treatment regimens were equally effective in healing H. pylori associated duodenal ulcer disease.

Effect of casemix funding on outcomes in patients admitted to hospital with suspected unstable angina.

OBJECTIVES: To determine the effect of the introduction of casemix funding on resource utilisation and clinical outcomes in patients admitted to hospital with suspected unstable angina. DESIGN: A prospective cohort study with a 6-month follow-up. SETTING: A suburban community hospital in Melbourne, Victoria. PATIENTS: 336 consecutive patients admitted to the coronary care unit with suspected unstable angina before (156) and after (180) the introduction of casemix funding. INTERVENTION: Introduction of casemix funding in July 1993. MAIN OUTCOME MEASURES: Indices of resource utilisation: length of stay in hospital, length of stay in the coronary care unit, and total cost of investigations (pathology and radiology). Rates of serious cardiac events during hospital stay and after discharge. Readmissions within 28 days and 6 months of discharge. RESULTS: After the introduction of casemix funding there was a 1% increase in duration of hospital stay and a 5% increase in time spent in the coronary care unit, but neither of these increases was statistically significant. However, there was a significant reduction in total cost of investigations (39% decrease; 95% confidence interval, 14%-70%; P < 0.001). The rate of serious cardiac events after discharge did not increase, and neither did readmission rates, either within 28 days or over the 6 months' follow-up. CONCLUSION: Casemix funding had no effect on short term clinical outcomes but resulted in significantly reduced investigation costs.

Balsalazide is more effective and better tolerated than mesalamine in the treatment of acute ulcerative colitis. The Abacus Investigator Group.

BACKGROUND & AIMS: Aminosalicylates are widely used in the treatment of ulcerative colitis (UC). Balsalazide is a novel mesalamine prodrug, activated by colonic bacteria. The aim of this study was to compare the efficacy and safety of balsalazide with that of a pH-dependent formulation of mesalamine in active UC. METHODS: A randomized, double-blind study was performed comparing balasalazide, 6.75 g daily, with mesalamine, 2.4 g daily, administered for 4, 8, or 12 weeks to 101 (99 evaluable) patients with symptomatic, sigmoidoscopically verified UC. RESULTS: More patients treated with balsalazide achieved symptomatic remission after 2 (64% [balsalazide] vs. 43% [mesalamine]), 4 (70% vs. 51%), 8 (78% vs. 45%), and 12 weeks (88% vs. 57%) and complete remission (none/mild symptoms, sigmoidoscopy grade 0/1, no rectal steroid use within 4 days) after 4 (38% vs. 12%), 8 (54% vs. 22%), and 12 weeks (62% vs. 37%). Patients taking balsalazide experienced more asymptomatic days (4 weeks, 24% vs. 14%) and achieved the first asymptomatic day more rapidly (median, 10 vs. 25 days). Fewer patients in the balsalazide group reported adverse events (48% vs. 71%); four serious adverse events occurred in the mesalamine group. CONCLUSIONS: Balsalazide is more effective and better tolerated than mesalamine as treatment for acute UC.

Maintenance of remission of ulcerative colitis: a comparison between balsalazide 3 g daily and mesalazine 1.2 g daily over 12 months. ABACUS Investigator group.

BACKGROUND: Despite widespread use of aminosalicylates as maintenance treatment for ulcerative colitis (UC), patients still report troublesome symptoms, often nocturnally. AIM: To compare the efficacy and safety of balsalazide (Colazide) with mesalazine (Asacol) in maintaining UC remission. METHODS: A randomized, double-blind comparison of balsalazide 3 g daily (1.04 g 5-ASA) and mesalazine 1.2 g daily for 12 months, in 99 (95 evaluable) patients in UC remission. RESULTS: Balsalazide patients experienced more asymptomatic nights (90% vs. 77%, P=0.0011) and days (58% vs. 50%, N.S.) during the first 3 months. Balsalazide patients experienced more symptom-free nights per week (6.4+/-1.7 vs. 4.7+/-2.8; P=0.0006) and fewer nights per week with blood on their stools or on the toilet paper, mucus with their stools or with sleep disturbance resulting from symptoms or lavatory visits (each P < 0.05). Fewer balsalazide patients relapsed within 3 months (10% vs. 28%; P=0.0354). Remission at 12 months was 58%, in both groups. Similar proportions of patients reported adverse events (61% balsalazide vs. 65% mesalazine). There were five serious adverse events (two balsalazide, three mesalazine) and four withdrawals due to unacceptable adverse events (three balsalazide, one mesalazine), of which one in each group was also a serious adverse event. CONCLUSIONS: Balsalazide 3 g/day and mesalazine 1.2 g/ day effectively maintain UC remission and are equally well tolerated over 12 months. At this dose balsalazide prevents more relapses during the first 3 months of treatment and controls nocturnal symptoms more effectively.

Early prediction of risk in patients with suspected unstable angina using serum troponin T.

BACKGROUND: One-third of patients with rest angina are reported to have detectable cardiac troponin T in the serum and may be at increased risk of serious cardiac events. AIM: To investigate whether a single early estimation of serum troponin T was an independent predictor of serious cardiovascular complications in patients with suspected unstable angina. METHODS: A prospective cohort study in which patients with suspected rest angina had a serum troponin T estimation 14 hours after symptom onset and were classified using discriminator levels of serum troponin T of 0.05 and 0.1 microgram/L as well as a number of other variables. All patients were followed for six months to document any cardiac complications and a stepwise logistic regression analysis was conducted to determine independent risk factors of complications. RESULTS: One hundred and sixty-four patients were evaluated. Using a discriminator level of 0.05 microgram/L 54 patients (33%) had detectable troponin T. The admission ECG was the only independent predictor of cardiac events in hospital--odds ratio 4.0 (95% CI 1.7-9.6). Detectable troponin T did not appear to be an independent predictor of serious complications. During the six-month follow-up period, detectable troponin T using a discriminator of 0.05 microgram/L was an independent predictor of serious complications--odds ratio 3.7 (95% CI 1.8-7.6). CONCLUSIONS: In patients with suspected rest angina, detectable serum troponin T > 0.05 microgram/L is an independent predictor of serious cardiac events during the six-month follow-up period although not during hospitalisation. Using a single, early serum troponin T estimation and other variables available at the time of admission, a high risk subgroup who may benefit from early investigation and revascularisation can be identified.

Linkage analysis of candidate regions for coeliac disease genes.

A strong HLA association is seen in coeliac disease [specifically to the DQ(alpha1*0501,beta1*0201 heterodimer], but this cannot entirely account for the increased risk seen in relatives of affected cases. One or more genes at HLA-unlinked loci also predispose to coeliac disease and are probably stronger determinants of disease susceptibility than HLA. A recent study has proposed a number of candidate regions on chromosomes 6p23 (distinct from HLA), 6p12, 3q27, 5q33.3, 7q31.3, 11p11, 15q26, 19p13.3, 19q13.1, 19q13.4 and 22cen for the location of a non-HLA linked susceptibility gene. We have examined these regions in 28 coeliac disease families by linkage analysis. There was excess sharing of chromosome 6p markers, but no support for a predisposition locus telomeric to HLA. No significant evidence in favour of linkage to coeliac disease was obtained for chromosomes 3q27, 5q33.3, 7q31.3, 11p11, 19p13.3, 19q13.1, 19q13.4 or 22cen. There was, however, excess sharing close to D15S642. The maximum non-parametric linkage score was 1.99 (P = 0.03). Although the evidence for linkage of coeliac disease to chromosome 15q26 is not strong, the well established association between coeliac disease and insulin dependent diabetes mellitus, together with the mapping of an IDDM susceptibility locus (IDDM3) to chromosome 15q26, provide indirect support for this as a candidate locus conferring susceptibility to coeliac disease in some families.

A method for estimating occupational radiation dose to individuals, using weekly dosimetry data.

Statistical analyses of data from epidemiological studies of workers exposed to radiation have been based on recorded annual radiation doses. It is usually assumed that the annual doses are known exactly, although it is generally recognized that the data contain uncertainty due to measurement error and bias. We propose the use of a probability distribution to describe an individual's dose during a specific period and develop statistical methods for estimating this distribution. The methods take into account the "measurement error" that is produced by the dosimetry system and the bias that was introduced by policies of recording doses below a threshold as zero. The method is applied to a sample of dose histories over the period 1945 to 1955 obtained from hard-copy dosimetry records at Oak Ridge National Laboratory (ORNL). The result of this evaluation raises serious questions about the validity of the historical personnel dosimetry data that are currently being used in studies of the effects of low doses in nuclear industry workers. In particular, it appears that there was a systematic underestimation of doses for ORNL workers. This may result in biased estimates of dose-response coefficients and their standard errors.

One week triple therapy for Helicobacter pylori: a multicentre comparative study. Lansoprazole Helicobacter Study Group.

BACKGROUND: Eradication of Helicobacter pylori cures and prevents the relapse of duodenal ulceration and also results in histological resolution of chronic active gastritis. AIM: To compare four treatment regimens lasting seven days of a proton pump inhibitor and two antibiotics in the eradication of H pylori. PATIENTS: Men or women with H pylori positive duodenal ulceration or gastritis, or both. METHODS: A single blind, prospectively randomised, parallel group, comparative, multicentre study. After a positive CLO test, patients underwent histology, H pylori culture, and a 13C urea breath test to confirm H pylori status. Treatment with one of four regimens: LAC, LAM, LCM, or OAM, where L is 30 mg of lansoprazole twice daily, A is 1 g of amoxycillin twice daily, M is 400 mg of metronidazole twice daily, C is 250 mg of clarithromycin twice daily, and O is 20 mg of omeprazole twice daily, was assigned randomly. A follow up breath test was done at least 28 days after completing treatment. RESULTS: H pylori eradication (intention to treat) was 104/121 (86.0%) with LAC, 87/131 (66.4%) with LAM, 103/118 (87.3%) with LCM, and 94/126 (74.6%) with OAM. There was a significant difference (p < 0.001) in the proportion of patients in whom eradication was successful between LAC and LCM when compared with LAM, but no significant difference (p = 0.15) between LAM and OAM. Metronidazole resistance before treatment was identified as a significant prognostic factor with regard to eradication of H pylori. The regimens which contained metronidazole were significantly less effective than those without metronidazole in the presence of pretreatment resistant H pylori. There was no difference among the treatment groups with regard to the incidence and severity of adverse events reported. CONCLUSIONS: All four treatment regimens were safe and effective in eradicating H pylori in the patient population studied. LAC was the most efficacious treatment in patients with pretreatment metronidazole resistant H pylori, and was significantly better than LAM and OAM in this group of patients.

Addition of metronidazole to omeprazole/amoxycillin dual therapy increases the rate of Helicobacter pylori eradication: a double-blind, randomized trial.

AIMS: To compare the efficacy, safety and tolerability of an omeprazole/amoxycillin (OA) dual therapy Helicobacter pylori eradication regimen with an omeprazole/amoxycillin/metronidazole (OAM) triple therapy regimen. METHODS: In this double-blind trial, conducted in 19 hospitals, 119 patients with symptomatic duodenal ulcer disease were randomized to receive either 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and placebo followed by a further 14 days' treatment with omeprazole 20 mg daily (n = 59) or 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s., and metronidazole 400 mg t.d.s., followed by a further 14 days' treatment with omeprazole 20 mg daily (n = 60). H. pylori status was assessed by 13C-urea breath test at entry and at 4 weeks post-treatment. RESULTS: H. pylori infection was eradicated in 46% of the OA treated patients and in 92% of the OAM treated patients, a mean difference of 46% (P < 0.0001, 95% CI for the difference: +30 to +62). In only one patient was the duodenal ulcer not endoscopically healed after 4 weeks of treatment (OA 100%; OAM 98% healed). There were no significant differences in speed of symptom relief or improvement in symptoms between the two groups. Both regimens were well tolerated, with 96% of patients completing the course, and only one patient withdrawing due to an adverse event. The only side-effect with a significantly higher incidence in the OAM group was diarrhoea, which occurred in 36% of patients compared to 16% of patients in the OA group (P < 0.05). CONCLUSIONS: A regimen consisting of omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. for 14 days gives an appreciably higher H. pylori eradication rate than omeprazole and amoxycillin alone, with acceptable tolerability.

A comparison of omeprazole and ranitidine in the prevention of recurrence of benign esophageal stricture. Restore Investigator Group.

BACKGROUND/AIMS: Dilatation combined with subsequent pharmacological control of gastroesophageal reflux represents a logical but poorly documented approach to the management of benign esophageal stricture. This large trial (366 patients) aimed to assess whether omeprazole as the most effective available medication for gastroesophageal reflux disease prevents recurrent stricture formation. METHODS: Patients (n = 366) were randomized in a double-blind study to undergo either omeprazole (20 mg once daily; 180 evaluable patients) or ranitidine therapy (150 mg twice daily; 185 evaluable patients) for 1 year after dilatation to 12-18-mm diameter (36-54F gauge). Subsequently, endoscopy and dilatation were performed when clinically indicated and endoscopy on completion. Symptoms were assessed at clinic visits every 3 months and using weekly diary cards. RESULTS: Fewer patients undergoing omeprazole therapy required redilatation compared with those on ranitidine (43 of 143 [30%] vs. 66 of 143 [46%] by 12 months; P < 0.01), and patients in the omeprazole group needed fewer redilatations during the year (0.48 vs. 1.08; P < 0.01). On completion, symptom relief favored omeprazole: 76% of patients in the omeprazole group were free of dysphagia (compared with 64% in the ranitidine group; P < 0.05); 83% were able to accept a normal diet (69%; P < 0.01); and 65% were completely asymptomatic (43%; P < 0.001). CONCLUSIONS: Omeprazole, 20 mg once daily, was more effective than ranitidine, 150 mg twice daily, as prophylaxis against stricture recurrence and in providing symptom relief.

Missing dose from mortality studies of radiation effects among workers at Oak Ridge National Laboratory.

Missing dose is a problem that has not been adequately addressed in the mortality studies of radiation effects among workers at Oak Ridge National Laboratory. The missing dose is a result of recording a zero for below-detectable doses, especially for frequent (weekly) film badge readings. To make the thorough dosimetry assessment needed in the current Oak Ridge National Laboratory worker studies, it will probably be necessary to consider all data at hand including personnel dose records, daily pocket meter readings used to supplement weekly and quarterly readings from other dosimeters, and monitoring results from both building surveys and fixed stations. The fixed-station data should be extremely useful in developing a better understanding of the unusual temporal variation of the external radiation doses to Oak Ridge National Laboratory workers during the high exposure-rate periods of the 1950s and early 1960s.

Quality of Life--a personal view.

Quality of Life encompasses many aspects of individual's life experience incorporating socioeconomic factors, housing, interpersonal relationships and job satisfaction. It is strongly affected by changes in health and ageing and the ability to adapt to these changes. Quality of Life may be measured by previously validated instruments, the outcomes of which may changes our clinical direction.

Short report: comparison of two doses of balsalazide in maintaining ulcerative colitis in remission over 12 months.

In a four-centre prospective double-blind trial, 108 patients with ulcerative colitis in remission were randomized to receive balsalazide in doses of 3 g or 6 g/day for 12 months. The patients were assessed at 3-monthly intervals clinically, sigmoidoscopically and with routine haematology and biochemistry. Remission rates of 77% (3 g/day) and 68% (6 g/day) at 12 months were not significantly different. Intolerance reactions leading to withdrawal from the study occurred in only 9 patients (8%), all occurring in the first 7 weeks of the study. Balsalazide is therefore both highly effective in maintaining remission in ulcerative colitis and well tolerated in both conventional and high dosage (the latter equivalent to 5.5 g/day of sulphasalazine). In this study no distinct advantage in maintenance of remission has been found for the higher dose of balsalazide.

Source inventory limits.

A new set of values has been developed for exempting sealed sources of radioactive materials from inventory. The criteria for exemption are: (a) the annual occupational dose from external radiation at 1 m from the source is approximately 100 microSv (10 mrem) or less; and (b) the source activity is approximately equal to the annual limit on intake by inhalation or less than 4 X 10(7) Bq (1000 microCi). These criteria were selected to correspond to an annual occupational dose of approximately 50 to 500 microSv (5 to 50 mrem) and a small potential annual risk of approximately 1 X 10(-6) to 1 X 10(-5) fatal cancers or less.

Torsade de pointes associated with perhexiline maleate therapy.

Multiform ventricular tachycardia (torsade de pointes) is a recognised proarrhythmic effect of drugs which prolong the QT interval. A case is now described for the first time where torsade de pointes occurred with the administration of the anti-anginal agent perhexiline maleate.