Correlates of mortality in elderly COPD patients: Focus on health-related quality of life

Background and objective:   The Saint George Respiratory Questionnaire (SGRQ) is widely used as a measure of health-related quality of life (HRQL) in patients with COPD. This study tested whether the SGRQ predicts the survival of patients with COPD.
Methods:   The study recruited 238 patients with COPD who were participants in the multicentre Salute Respiratoria nell'Anziano (Sa.R.A.) study. Patients' sociodemographic, clinical and functional characteristics were assessed and the association between the SGRQ and mortality, corrected for potential confounders, was estimated.
Results:   The mean age of study participants was 72.6 years. Over the 5-year observation period there were 88 deaths. After adjustment for potential confounders, the SGRQ score was associated with an increased risk of dying (hazard ratio (HR): 1.22 for four-point increments; 95% confidence interval (CI): 1.02–1.45). There was no association between mortality and the Symptoms subscale (corrected HR: 1.13; 95% CI: 0.96–1.32), whereas each four-point increment of the Activity (HR: 1.20; 95% CI: 1.00–1.43) and Impact (HR: 1.38; 95% CI: 1.03–1.83) subscale scores were associated with increased mortality. Higher FEV₁ relative to predicted (HR: 0.73 for each 5% increment; 95% CI: 0.58–0.91) and better performance at the 6-min walking test relative to predicted (HR: 0.93 for each 5% increment; 95% CI: 0.89–0.97) were associated with lower mortality.
Conclusions:   In elderly COPD patients, the SGRQ can improve prognostic models based on classical indicators of disease severity.     

Predictors for failed dose reduction of inhaled corticosteroids in childhood asthma

Background and objective:   Studies of Western populations have shown that increased exhaled nitric oxide (FeNO) and/or sputum eosinophils (sp-Eos) are predictive of asthma exacerbations. However, the utility of these measurements in different populations and settings is unknown. This study aimed to determine the predictors for failure of reduction of inhaled corticosteroid (ICS) doses in children with stable asthma.
Methods:   Fifty children (median age 11.8 years, interquartile range (IQR) 5.9 years) had their dose of ICS halved every 8 weeks until they reached the study end-point (exacerbation or weaned off ICS). Spirometry, FeNO and induced sputum cells were measured at baseline and at each stage of ICS reduction.
Results:   Eleven subjects suffered an asthma exacerbation and the remainder was successfully weaned off ICS. Subjects with an exacerbation were older (15.4 years (IQR 5.4) vs 11.4 years (IQR 3.9), P  = 0.019) and more likely to be boys ( P  = 0.035). FeNO (median 156 p.p.b. (IQR 131) vs 76.1 p.p.b. (IQR 79.5), P  = 0.013) and sp-Eos (17.3% (IQR 33.8%) vs 7.1% (IQR 9.9%), P  = 0.019) were significantly greater in those who had an exacerbation. The areas under the receiver operating characteristic curves for FeNO (0.78, 95% CI: 0.59–0.97, P  = 0.013) and sp-Eos (0.76, 95% CI: 0.56–0.96, P  = 0.016) were similar ( P  = 0.88) and both were significantly greater than that for FEV₁% predicted (0.12, 95% CI: 0.08–0.56, P  = 0.0013).
Conclusions:   Older boys with raised FeNO and sp-Eos are at higher risk of failure of reduction in their ICS dose. Monitoring airway inflammation in children with asthma using FeNO or sp-Eos is clinically useful in guiding ICS dose reduction in a non-Western outpatient setting.     

Determinants of survival in AIDS patients on antiretroviral therapy in a rural centre in the Far-North Province, Cameroon

Objective  To analyse the outcomes of antiretroviral therapy (ART) in routine conditions in a rural hospital in the Far-North province of Cameroon.
Method  Retrospective cohort study of 1187 patients >15 years who started ART between July 2001 and December 2006. The survival time was estimated by Kaplan–Meier analysis and Cox proportional hazard models were fitted to explain survival.
Results  Upon enrolment, 90.4% patients were in WHO stage III or IV and 56.1% had a BMI <18.5. Median CD4 count was 105 cells/mm³ (IQR 40–173). At the end of the study period, 338/1187 had died and 59/1187 were lost to follow-up. The survival probability was 77% at 1 year [95% CI: 75–80] and 47% at 5 years [95% CI: 40–55]. The median survival time was 58 months. CD4 count, haemoglobin, BMI, sex and clinical stage at enrolment were independent predictors of mortality.
Conclusion  This study confirms the clinical benefit of ART programs in a remote and resource-constrained setting operating in routine conditions. The challenge ahead is to secure earlier access to ART and to maintain its longer-term benefit.     

Combination therapy with transarterial chemoembolization and interferon-α compared with transarterial chemoembolization alone for hepatitis B virus related unresectable hepatocellular carcinoma

Background and Aims:  The present study was carried out to test the hypothesis that interferon-α (IFN-α) treatment would reduce or postpone the recurrence rate and improve the overall survival rate in patients after transarterial chemoembolization (TACE) treatment of hepatitis B virus (HBV) related unresectable hepatocellular carcinoma (HCC).
Methods:  216 patients with unresectable HBV-related HCC were randomized into a TACE group and a TACE-IFN group, each group had 108 patients. In the TACE-IFN group, patients received IFN-α1b at a dose of 3 million units (mu) three times a week by intramuscular injection one week after/before TACE treatment, for 48 weeks.
Results:  The median disease-free survival in the TACE-IFN treatment group was 23.6 months (95% CI: 21.4–25.8) and 20.3 months (95% CI: 15.8–24.8) in the TACE group ( P  = 0.027). The disease free rate at 24 months in the TACE group was lower than in the TACE-IFN group (39.8% vs 59.3%, P  = 0.004). The median overall survival was 29 months (95% CI: 27.5–32.1) in the TACE-IFN group and 26 months (95% CI: 20.1–31.9) in the TACE group ( P  = 0.003). The 2-year overall survival in the TACE-IFN group was higher than in the TACE group (72.2% vs 52.8%, P  = 0.003).
Conclusions:  IFN-α treatment reduced recurrence and improved the survival of patients after TACE treatment of HBV-related HCC, with acceptable toxicities.     

Relationship Between Higher Estradiol Levels and 9-Year Mortality in Older Women: The Invecchiare in Chianti Study

OBJECTIVES: To investigate the relationship between total estradiol (E2) levels and 9-year mortality in older postmenopausal women not taking hormone replacement therapy (HRT).
DESIGN: Population-based study of persons living in the Chianti geographic area (Tuscany, Italy).
SETTING: Community.
PARTICIPANTS: A representative sample of 509 women aged 65 and older with measures of total E2.
MEASUREMENTS: Serum total E2 was measured at the University of Parma using ultrasensitive radioimmunoassay (RIA).
RESULTS: Women who died (n=135) during 9 years of follow up were older; had higher total E2 levels; and were more likely to have evidence of stroke, hypertension, diabetes mellitus, and congestive heart failure at baseline than survivors. Higher E2 levels were associated with a greater likelihood of death (hazard ratio (HR)=1.03, 95% confidence interval (CI)=1.01–1.06), and the relationship was independent of age, waist:hip ratio, C-reactive protein, education, cognitive function, physical activity, caloric intake, smoking, and chronic disease (HR=1.08 pg/mL, 95% CI=1.03–1.13, P =.003). The excessive risk of death associated with higher total E2 was not attenuated after adjustment for total testosterone (HR=1.12, 95% CI=1.02–1.18, P <.001) and after further adjustment for insulin resistance evaluated using the homeostasis model assessment (HR=1.07, 95% CI=1.03–1.17, P <.001).
Total E2 was highly predictive of death after more than 5 years (HR=1.42: CI 1.01–1.91, P =.04) and not predictive of death for less than 5 years ( P =.78).
CONCLUSION: Higher total E2 concentration predicts mortality in older women not taking HRT.     

Clinical Relevance of a Raised Plasma N-Terminal Pro-Brain Natriuretic Peptide Level in a Population-Based Cohort of Nonagenarians

OBJECTIVES: To investigate whether plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) remains a specific marker of cardiac illness in very old age and can be used to identify very elderly people at high risk for death independent of the presence of known cardiac diagnoses.
DESIGN: Prospective, observational, population-based follow-up study within the Leiden 85-Plus Study of a 2-year birth cohort (1912–1914).
SETTING: General population, municipality of Leiden, the Netherlands.
PARTICIPANTS: Two hundred seventy-four participants were followed up from age 90 onward (median follow-up 42.3 months, interquartile range 20.2–50.2 months).
MEASUREMENTS: Plasma NT-proBNP level, indicators of general health and functioning, and specific cardiac diagnoses at age 90 and mortality from age 90 onward.
RESULTS: Plasma levels of NT-proBNP were not correlated with indicators of poor health or poor functioning, but the level of NT-proBNP increased significantly with increasing numbers of cardiac diagnoses ( P <.001). High NT-proBNP was associated with overall mortality in participants with (hazard ratio (HR)=2.8, 95% confidence interval (CI)=1.5–5.2) and without (HR=3.5, 95% CI=1.6–7.5) specific cardiac diagnoses. This was also found for cardiovascular mortality risks (with specific cardiac diagnoses HR=4.1, 95% CI=1.5–11 vs without HR=5.6, 95% CI=1.0–30) and noncardiovascular mortality risks (with specific cardiac diagnoses HR=1.9, 95% CI=0.84–4.5 vs without HR=3.4, 95% CI=1.3–8.6).
CONCLUSION: Plasma NT-proBNP is a disease-specific marker of cardiac illness in nonagenarians and can possibly be used as a predictor of mortality in elderly people with and without specific cardiac diagnoses.     

The Prognostic Significance of Bundle Branch Block in High-Risk Chronic Stable Vascular Disease Patients: A Report from the HOPE Trial

Objective: The prognostic significance of left and right bundle branch block (LBBB and RRBB) in patients with chronic stable cardiovascular (CV) disease is not well characterized and was evaluated in the Heart Outcomes Prevention Evaluation (HOPE) study cohort.
Design: Observational analysis of data prospectively collected in the HOPE trial.
Setting and Patients: HOPE was a multicenter, international trial, which evaluated ramipril and vitamin E in 9,541 patients aged ≥55 years with CV disease or diabetes with ≥1 CV risk factor(s) but without heart failure (HF) or known left ventricular systolic dysfunction. Follow-up extended for a median of 4.5 years. Electrocardiograms were obtained at baseline in all study participants and were read centrally.
Main Outcome Measures: Major CV events (defined as CV death, myocardial infarction, or stroke), heart failure, CV death, all-cause death, and sudden death.
Results: Baseline LBBB was present in 246 (2.6%) patients and was associated with increased risk for major CV events (HR = 1.54; 95% CI, 1.18–2.02), CV death (HR 2.29; 95% CI, 1.63–3.20), heart failure (HR 2.99; 95% CI, 2.31–3.87), sudden death (HR 3.17; 95% CI, 2.13–4.73), and all-cause death (HR = 2.10; 95% CI, 1.59–2.77). In multivariate models, LBBB remained an independent predictor of heart failure, sudden death, CV death, and all-cause death (P ≤ 0.002 for all). Baseline RBBB was present in 428 (4.5%) of patients and was not associated with increased CV risk.
Conclusions: In patients with stable chronic CV disease, LBBB but not RBBB is an independent predictor of heart failure, sudden death, CV death, and all-cause death.     

Cigarette smoking and the risk of supraventricular and ventricular tachyarrhythmias in high-risk cardiac patients with implantable cardioverter defibrillators

Introduction: Nicotine elevates serum catecholamine concentration and is therefore potentially arrhythmogenic. However, the effect of cigarette smoking on arrhythmic risk in coronary heart disease patients is not well established.
Methods and Results: The risk of appropriate and inappropriate defibrillator therapy by smoking status was analyzed in 717 patients who received an implantable cardioverter defibrillator (ICD) in the Multicenter Automatic Defibrillator Implantation Trial-II. Compared with patients who had quit smoking before study entry (past smokers) and patients who had never smoked (never smokers), patients who continued smoking (current smokers) were significantly younger and generally had more favorable baseline clinical characteristics. Despite this, the adjusted hazard ratio (HR) for appropriate ICD therapy for fast ventricular tachycardia (at heart rates ≥180 b.p.m) or ventricular fibrillation was highest among current smokers  (HR = 2.11 [95% CI 1.11–3.99])  and intermediate among past smokers  (HR = 1.57 [95% CI 0.95–2.58])  , as compared with never smokers (P for trend = 0.02). Current smokers also exhibited a higher risk of inappropriate ICD shocks  (HR = 2.93 [95% CI 1.30–6.63])  than past  (HR = 1.91 [95% CI 0.97–3.77])  and never smokers (P for trend = 0.008).
Conclusions: In patients with ischemic left ventricular dysfunction, continued cigarette smoking is associated with a significant increase in the risk of life-threatening ventricular tachyarrhythmias and inappropriate ICD shocks induced by rapid supraventricular arrhythmias. Our findings stress the importance of complete smoking cessation in this high-risk population.     

Predictive factors for hepatocellular carcinoma in type 1 autoimmune hepatitis

OBJECTIVE:  Hepatocellular carcinoma (HCC) is an uncommon but serious occurrence in autoimmune hepatitis. Our objective was to determine predictors for this neoplasm to improve screening strategies.
METHODS:  Two hundred twenty-seven patients underwent hepatic ultrasonography and serum alpha fetoprotein determinations at 6–12-month intervals.
RESULTS:  Nine patients developed HCC (4%), and each had cirrhosis ≥73 months prior to the malignancy (mean, 110 ± 7 months). By univariate Cox analysis, features at accession associated with a higher risk of HCC were: male gender (Hazard Ratio [HR] 7.0, 95% Confidence Interval [CI] 1.87–26.1, P = 0.004), history of blood transfusion (HR 5.6, 95% CI 1.51–21.1, P = 0.01), thrombocytopenia (HR 7.3, 95% CI 1.89–28.3, P = 0.004), ascites (HR 23.8, 95% CI 4.65–121.8, P = 0.0001), esophageal varices (HR 7.9, 95% CI 1.96–31.8, P = 0.004), and any sign of portal hypertension (HR 19.1, 95% CI 3.91–93.3, P = 0.0003). Features after accession associated with a higher risk of malignancy were: treatment for ≥3 yr (HR 7.6, 95% CI 1.25–18.2, P = 0.02), worsening laboratory tests during corticosteroid therapy (HR 7.6, 95% CI 1.81–32.1, P = 0.006), and cirrhosis for ≥10 yr (HR 8.4, 95% CI 1.69–41.9, P = 0.009).
CONCLUSIONS:  Male gender, features of portal hypertension, history of blood transfusions, immunosuppressive treatment for ≥3 yr, treatment failure, and cirrhosis of ≥10 yr duration identify patients at risk for HCC. These risk factors should focus screening in autoimmune hepatitis.     

Reduced morbidity and mortality in the first year after initiating highly active anti-retroviral therapy (HAART) among Ugandan adults

Objective  To evaluate the effect of highly active anti-retroviral therapy (HAART) and cotrimoxazole prophylaxis on morbidity after HAART eligibility.
Methods  Between 1999 and 2006, we collected morbidity data from a community-based cohort of HAART-eligible patients, comparing patients initiating HAART and those non-HAART. Patients aged 15 years or older visited the clinic every 6 months and when ill. Baseline data on patients' characteristics, WHO stage, haemoglobin and CD4+ T-cell counts, along with follow-up data on morbidity (new, recurrent and drug-related), were collected for the first year after initiating HAART or becoming HAART-eligible. We estimated the overall effect of HAART on morbidity; adjusted for the effect of cotrimoxazole prophylaxis by Mantel–Haenszel methods. A negative binomial regression model was used to assess rate ratios (RR) after adjustment for other confounders, including cotrimoxazole.
Results  A total of 219 HAART patients (median age 37 years; 73% women; 82% using cotrimoxazole prophylaxis, median haemoglobin 11.7 g/dl and median CD4+ 131 cells/μl) experienced 94 events in 127 person-years. 616 non-HAART patients (median age 33 years; 70% women; 26% using cotrimoxazole prophylaxis, median haemoglobin 11.2 g/dl and median CD4+ 130 cells/μl) experienced 862 events in 474 person-years. The overall morbidity during the first year of HAART was 80% lower than among non-HAART patients (adjusted RR = 0.20, 95% CI: 0.12–0.34). Cotrimoxazole prophylaxis also reduced morbidity (adjusted RR = 0.65, 95% CI: 0.45–0.94).
Conclusion  These results confirm the reduction in morbidity due to HAART, and the additional protection of cotrimoxazole prophylaxis.     

Predictors for mortality and loss to follow-up among children receiving anti-retroviral therapy in Lilongwe, Malawi

Objectives  To determine predictors of mortality in children on anti-retroviral therapy (ART) who attended the Paediatric HIV Clinic at Kamuzu Central Hospital in Lilongwe, Malawi.
Methods  Retrospective case cohort study by chart review of children who had started ART between October 2004 and May 2006. Bivariable and multivariable analysis were performed with and without defaulters to evaluate associations according to vital status and to identify independent predictors of mortality.
Results  Forty-one of 258 children (15.9%) were deceased, 185 (71.7%) were alive, and 32 (12.4%) had defaulted: 51% were female, 7% were under 18 months, 26% were 18 months to 5 years, and 54% were >5 years of age. Most were WHO stage III or IV (56% and 37%, respectively). On multivariate analysis, factors most strongly associated with mortality and defaulting were age <18 months [hazards ratio (HR) 2.11 (95% CI 1.0–4.51)] and WHO stage IV [HR 2.00 (95% CI 1.07–3.76)].
Conclusions  To improve outcomes of HIV-positive children, they must be identified and treated early, specifically children under 18 months of age. Access to infant diagnostic procedures must be improved to allow effective initiation of ART in infants at higher risk of death.     

Expression of the HCRP1 mRNA in HCC as an independent predictor of disease-free survival after surgical resection

Aim:  Hepatocellular carcinoma (HCC)-related protein-1 ( HCRP1 ) gene was located at chromosome 8p22, a frequently deleted region in HCC. The gene product was a subunit of mammalian Endosomal Sorting Complex Required for Transport (ESCRT)-I, essential for degradation of epidermal growth factor receptors. In this study, we examined the prognostic role of HCRP1 mRNA expression in HCC.
Methods:  The expression of HCRP1 mRNA in HCC was assessed in 125 patients receiving surgical resection of HCC. Using the adjacent non-cancerous tissues as a reference, 55 and 70 patients expressing high and low levels of HCRP1 mRNA, respectively, were identified. The predictive value of HCRP1 mRNA expression in postoperative survival was evaluated.
Results:  Expression of HCRP1 mRNA was not associated with any of the baseline clinicopathological parameters. However, univariate analysis showed that it was associated with a better disease-free survival ( P  < 0.001) and overall survival ( P  = 0.032). Stepwise Cox multivariate proportional hazards regression analysis showed that the expression of HCRP1 mRNA (hazard ratio [HR], 0.396; 95% confidence interval (CI), 0.233–0.674; P  = 0.001), tumor number (HR, 1.596; 95% CI, 1.221–2.087; P  = 0.001), serum aspartate aminotransferase (HR, 1.002; 95% CI, 1.000–1.003; P  = 0.031) and the presence of microvascular invasion (HR, 1.852; 95% CI, 1.131–3.032; P  = 0.014) were included as independent predictors for disease-free survival.
Conclusion:  Expression of HCRP1 mRNA served as an independent predictor for postoperative disease-free survival in HCC patients.     

Time on antiretroviral therapy is a protective factor for liver fibrosis in HIV and hepatitis C virus (HCV) co-infected patients

summary. To assess the factors associated with liver fibrosis in human immunodeficiency virus and hepatitis C virus (HIV/HCV) co-infected patients eligible for anti-HCV therapy, we performed an observational, single-centred, cross-sectional study of 180 HIV/HCV co-infected patients who underwent liver biopsy between May 1998 and November 2001. A total of 126 patients with a known date of HCV infection were evaluated. Liver fibrosis was defined as a Knodell stage of fibrosis 1–4. The mean age was 36.7 (3.8) years, 81% were male and had a mean age of 20.5 (3.8) years at HCV infection. Mean CD4 cell count and plasma HIV-1 RNA load at the time of biopsy were 552 cell/mm³ (239) and 2.5 log₁₀ (0.9), respectively; 118 patients had been on antiretroviral therapy (ART) for a median of 45 months (Q1–Q3: 21–75) and 84 on protease inhibitor for a median of 12.0 months (Q1–Q3: 0–29.5); 55 had an AIDS event or a CD4 cell count nadir < 200 cells/mm³ prior to biopsy. Median histological activity index was 6 and 27% had a Knodell stage of fibrosis 0. On the multivariate analysis time on ART (OR for 6 months extra: 0.954, 95% CI: 0.859–0.994), CD4 cell count at the time of liver biopsy (OR for 100 cells/mL increase: 0.740, 95% CI: 0.670–0.905), age at HCV infection acquisition (OR for 5 years extra: 2.594, 95% CI: 1.326–5.133) and alcohol intake (> 50 g/day) (OR: 2.73, 95% CI: 1.108–6.731) were associated with liver fibrosis. Hence ART should be a priority in HIV/HCV co-infected patients eligible for anti-HCV treatment as it is a protective factor for liver fibrosis.     

High Levels of Serum C-Reactive Protein Are Associated with Greater Risk of All-Cause Mortality, but Not Dementia, in the Oldest-Old: Results from The 90+ Study

OBJECTIVES: To evaluate whether high levels of C-reactive protein (CRP) in serum are associated with greater risk of all-cause dementia or mortality in the oldest-old.
DESIGN: Prospective.
SETTING: Research clinic and in-home visits.
PARTICIPANTS: Population-based sample of adults (N=227; aged 93.9±2.8) from The 90+ Study, a longitudinal cohort study of people aged 90 and older.
MEASUREMENTS: CRP levels were divided into three groups according to the assay detection limit: undetectable (<0.5 mg/dL), detectable (0.5–0.7 mg/dL), and elevated (≥0.8 mg/dL). Neurological examination was used to determine dementia diagnosis ( Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition , criteria). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression, and results were stratified according to and apolipoprotein E4 (APOE4) genotype.
RESULTS: Subjects with detectable CRP levels had significantly greater risk of mortality (HR=1.7, 95% CI=1.0–2.9), but not dementia (HR=1.2, 95% CI=0.6–2.1), 0.4 to 4.5 years later than subjects with undetectable CRP. The highest relative risk for dementia and mortality was in APOE4 carriers with detectable CRP (dementia HR=4.5, 95% CI=0.9–23.3; mortality HR=5.6, 95% CI=1.0–30.7).
CONCLUSION: High levels of CRP are associated with greater risk of mortality in people aged 90 and older, particularly in APOE4 carriers. There was a trend toward greater risk of dementia in APOE4 carriers with high CRP levels, although this relationship did not reach significance. High levels of CRP in the oldest-old represent a risk factor for negative outcomes.     

Prevention of falls in nursing homes: subgroup analyses of a randomized fall prevention trial

OBJECTIVES: To evaluate the effectiveness of a multifactorial fall prevention program in prespecified subgroups of nursing home residents.
DESIGN: Secondary analysis of a cluster-randomized, controlled trial.
SETTING: Six nursing homes in Germany.
PARTICIPANTS: Seven hundred twenty-five long-stay residents; median age 86; 80% female.
INTERVENTION: Staff and resident education on fall prevention, advice on environmental adaptations, recommendation to wear hip protectors, and progressive balance and resistance training.
MEASUREMENTS: Time to first fall and the number of falls. Falls were assessed during the 12-month intervention period. Univariate regression analyses were performed, including a confirmatory test of interaction.
RESULTS: The intervention was more effective in people with cognitive impairment (hazard ratio (HR)=0.49, 95% confidence interval (CI)=0.35–0.69) than in those who were cognitively intact (HR=0.91, 95% CI=0.68–1.22), in people with a prior history of falls (HR=0.47, 95% CI=0.33–0.67) than in those with no prior fall history (HR=0.77, 95% CI=0.58–1.01), in people with urinary incontinence (HR=0.59, 95% CI=0.45–0.77) than in those with no urinary incontinence (HR=0.98, 95% CI=0.68–1.42), and in people with no mood problems (incidence rate ratio (IRR)=0.41, 95% CI=0.27–0.61) than in those with mood problems (IRR=0.74, 95% CI=0.51–1.09).
CONCLUSION: The effectiveness of a multifactorial fall prevention program differed between subgroups of nursing home residents. Cognitive impairment, a history of falls, urinary incontinence, and depressed mood were important in determining response.     

Antioxidant vitamin supplement use and risk of dementia or Alzheimer's disease in older adults

OBJECTIVES: To examine whether use of vitamins C or E alone or in combination was associated with lower incidence of dementia or Alzheimer's disease (AD).
DESIGN: Prospective cohort study.
SETTING: Group Health Cooperative, Seattle, Washington.
PARTICIPANTS: Two thousand nine hundred sixty-nine participants aged 65 and older without cognitive impairment at baseline in the Adult Changes in Thought study.
MEASUREMENTS: Participants were followed biennially to identify incident dementia and AD diagnosed according to standard criteria. Participants were considered to be users of vitamins C or E if they self-reported use for at least 1 week during the month before baseline.
RESULTS: Over a mean follow-up±standard deviation of 5.5±2.7 years, 405 subjects developed dementia (289 developed AD). The use of vitamin E was not associated with dementia (adjusted hazard ratio (HR)=0.98, 95% confidence interval (CI)=0.77–1.25) or with AD (HR=1.04; 95% CI=0.78–1.39). No association was found between vitamin C alone (dementia: HR=0.90, 95% CI=0.71–1.13; AD: HR=0.95, 95% CI=0.72–1.25) or concurrent use of vitamin C and E (dementia: HR=0.93, 95% CI=0.72–1.20; AD: HR=1.00, 95% CI=0.73–1.35) and either outcome.
CONCLUSION: In this study, the use of supplemental vitamin E and C, alone or in combination, did not reduce risk of AD or overall dementia over 5.5 years of follow-up.     

Observational studies on the effect of dietary antioxidants on asthma: a meta-analysis

Background and objective:   It has been suggested that the rapid increase in asthma prevalence may in part be due to a decrease in the intake of dietary antioxidants, including vitamin C, vitamin E and β-carotene. Epidemiological studies investigating the association between dietary antioxidant intake and asthma have generated inconsistent results. A meta-analysis was undertaken to examine the association between dietary antioxidant intake and the risk of asthma.
Methods:   The MEDLINE database was searched for observational studies in English-language journals from 1966 to March 2007. Data were extracted using standardized forms. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random effects model. Ten studies were eligible for inclusion. Seven studies, comprising 13 653 subjects, used asthma or wheeze as their outcome; three studies explored the effect of antioxidant intake on lung function.
Results:   A higher dietary intake of antioxidants was not associated with a lower risk of having asthma. The pooled OR for having asthma were 1.06 (95% CI: 0.79–1.43) for subjects with a higher dietary vitamin C intake compared with those with a lower intake; 0.88 (95% CI: 0.61–1.25) for vitamin E; and 1.12 (95% CI: 0.77–1.62) for β-carotene. There was no significant association between dietary antioxidant intake and lung function except for a positive association between vitamin C intake and an increase in FEV₁ (29.1 mL, 95% CI: −0.4–58.6, P  = 0.05).
Conclusions:   This meta-analysis does not support the hypothesis that dietary intake of the antioxidants vitamins C and E and β-carotene influences the risk of asthma.     

Methotrexate: long-term safety and efficacy in an Australian consultant rheumatology practice

Background: The aim of this study was to evaluate the rate and cause of methotrexate (MTX) termination in clinical practice, describe the types of toxicities noted, assess the incidence of achieving remission in rheumatoid arthritis (RA) patients and review the appropriateness of current clinical guidelines for monitoring MTX treatment.
Methods: A retrospective, case review of patients seen in a private rheumatology practice attached to a major Sydney Teaching Hospital was undertaken over an 18-year period. The primary outcome was time to cessation of MTX.
Results: Seven hundred and ninety patients satisfied the inclusion criteria. MTX was terminated in 272 patients (34.4%). Toxicity-related discontinuation occurred in 93 patients (11.8%) and due to non-adverse reactions in 179 patients. The median duration of therapy in these two groups was 2.0 and 2.9 years, respectively. There was no difference in the average maximum weekly dose of MTX. Of patients with RA, 47.5% were in remission at last follow up. Cox proportional hazards analyses showed that those of the female sex remained on treatment significantly longer than the male sex (hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.57–0.96; P  = 0.014); patients with RA remained on treatment significantly longer than patients with seronegative arthritis (HR 0.56, 95%CI 0.42–0.74; P  < 0.001). Being of the male sex aged more than 60 years and having a non-RA diagnosis predisposed to stopping MTX earlier.
Conclusion: MTX is a safe and effective medication. Notable remission rates are achievable in patients with RA with current conventional treatment protocols. MTX has a low toxicity profile and this study stresses the need to re-evaluate and revise the current monitoring guidelines.     

Hospitalizations for opioid poisoning: a nation-wide population-based study in Denmark, 1998–2004

Aims   To assess hospitalization rates (HR) for poisoning with heroin, methadone or strong analgesics and relate them to quantities of prescribed methadone and strong analgesics in Denmark between 1998 and 2004.
Design   Population-based ecological study.
Settings   We extracted data on all emergency department visits and hospital admissions registered in the Danish National Patient Registry with a diagnosis of poisoning with heroin ( n  = 1688), methadone ( n  = 173) or strong analgesics ( n  = 384). To ascertain sale of prescribed medications we used data from the Danish Medicines Agency.
Measurements   Age- and gender-standardized HR and defined daily doses (DDD) per 1000 people per day.
Findings   HR for heroin poisoning was 4.4 [95% confidence interval (CI): 3.8–4.9] per 100 000 person-years (p-y) in 1998 and 4.6 (CI: 4.0–5.2) per 100 000 p-y in 2004. HR for methadone poisoning increased from 0.1 (CI: 0.0–0.2) per 100 000 p-y in 1998 to 1.1 (CI: 0.8–1.4) per 100 000 p-y in 2004. HR for poisoning with strong analgesics increased from 0.6 (CI: 0.4–0.9) per 100 000 p-y in 1998 to 2.1 (CI: 1.8–2.6) per 100 000 p-y in 2004. The sale of prescribed strong analgesics (5.0 DDD per 1000 people per day in 1998 to 5.9 DDD in 2004) and methadone (3.0 DDD per 1000 people per day in 1998 to 3.4 DDD in 2004) increased slightly between 1998 and 2004.
Conclusion   Increasing sale of prescribed methadone and strong analgesics coincided with increasing HRs of poisoning with these drugs, whereas HR of heroin poisoning varied. Further longitudinal studies are important for the guidance of future policy making.     

Antiphospholipid antibodies in adults with immune thrombocytopenic purpura

To determine the clinical significance of antiphospholipid antibodies (aPL) in patients with immune thrombocytopenic purpura (ITP), anticardiolipin (aCL) (IgG and IgM) and lupus anticoagulant (LA) were sought at diagnosis in 215 ITP adults with platelets <50 × 10⁹/l. aPL (aCL and/or LA) were detected in 55 patients (26%): aCL alone in 39 (18%), aCL and LA in 15 (7%) and LA alone in one (0·5%). LA was significantly associated with high IgG-aCL levels ( P  =   0·001). Among age, sex, initial platelet count, bleeding score, acute or chronic ITP outcome, only younger age was significantly associated with LA-positivity (mean age 29 ± 14 years vs. 45 ± 20 years, P  =   0·002). After a median follow-up of 31 months, 14/215 (7%) patients developed thrombosis (four arterial, 10 venous and/or pulmonary embolism); four of them (29%) had high aCL levels and LA. Multivariate analysis significantly associated thrombosis events only with age [hazard ratio (HR)   =   1·6; 95% confidence interval (CI): 1·2–2·4], LA (HR: 9·9; 95% CI: 2·3–43·4) or high IgG-aCL level (HR: 7·5; 95% CI; 1·8–31·5). Although the thrombosis rate was low, the significant associations between thrombosis and LA or high aCL level suggest that aPL should be tested at ITP diagnosis.