To treat or not to treat? A meta-analysis of the use of cholinesterase inhibitors in mild cognitive impairment for delaying progression to Alzheimer`s disease

Individual randomized clinical trials (RCTs) with cholinesterase inhibitors (ChEIs) aiming to delay the progression from mild cognitive impairment (MCI) to Alzheimer`s disease (AD) have not found significant benefit of their use for this purpose. The objective of this study is to meta-analyze the RCTs conducted with ChEIs in order to assess whether pooled analysis could show the benefit of these drugs in delaying the progression from MCI to AD. We searched for references of published and unpublished studies on electronic databases (Medline, Embase, Web of Science, and Clinical Trial Database Registry, particularly the Clinicaltrials.gov-http://www.clinicaltrials.gov). We retrieved 173 references, which yielded three references for data extraction. A total of 3.574 subjects from four RCTs were included in the meta-analysis. Among 1,784 subjects allocated in the ChEI-treatment group, 275 (15.4%) progressed to AD/dementia, as opposed to 366 (20.4%) out of 1,790 subjects in the placebo group. The relative risk (RR) for progression to AD/dementia in the ChEI-treated group was 0.75 [CI(95%) 0.66-0.87], z = -3.89, P < 0.001. The patients on the ChEI group had a significantly higher all-cause dropout risk than the patients on the placebo group (RR = 1.36 CI(95%) [1.24-1.49]; z = 6.59, P < 0.001). The RR for serious adverse events (SAE) in the ChEI-treated group showed no significantly statistical difference from the placebo group (RR = 0.95 [CI(95%) 0.83-1.09], z = -0.72, P = 0.47). The subjects in the ChEI-treated group had a marginally, non-significant, higher risk of death due to any cause than those in the placebo-treated group (RR = 1.04, CI(95%) 0.63-1.70, z = 0.16, P = 0.86). The long-term use of ChEIs in subjects with MCI may attenuate the risk of progression to AD/dementia. This finding may have a significant impact on public health and pharmaco-economic policies.

Role of promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene as a risk factor for cerebral venous thrombosis

Background and Purpose-Plasma glutathione peroxidase (GPx-3) is a major antioxidant enzyme in plasma and the extracellular space that scavenges reactive oxygen species produced during normal metabolism or after oxidative insult. A deficiency of this enzyme increases extracellular oxidant stress, promotes platelet activation, and may promote oxidative posttranslational modification of fibrinogen. We recently identified a haplotype (H-2) in the GPx-3 gene promoter that increases the risk of arterial ischemic stroke among children and young adults. Methods-The aim of this study is to identify possible relationships between promoter haplotypes in the GPx-3 gene and cerebral venous thrombosis (CVT). We studied the GPx-3 gene promoter from 23 patients with CVT and 123 young controls (18 to 45 years) by single-stranded conformational polymorphism and sequencing analysis. Results-Over half of CVT patients (52.1%) were heterozygous (H1H2) or homozygous (H2H2) carriers of the H-2 haplotype compared with 12.2% of controls, yielding a more than 10-fold independent increase in the risk of CVT (OR=10.7; 95% CI, 2.70 to 42.36; P<0.0001). Among women, the interaction of the H2 haplotype with hormonal risk factors increased the OR of CVT to almost 70 (P<0.0001). Conclusions-These findings show that a novel GPx-3 promoter haplotype is a strong, independent risk factor for CVT. As we have previously shown that this haplotype is associated with a reduction in transcriptional activity, which compromises antioxidant activity and antithrombotic benefits of the enzyme, these results suggest that a deficiency of GPx-3 leads to a cerebral venous thrombophilic state.

Prevalence of Insulin Resistance and Related Risk Factors for Cardiovascular Disease in Patients With Essential Hypertension

BACKGROUND There is evidence that the subgroup of patients with essential hypertension who are also insulin resistant is at increased risk of cardiovascular disease (CVD). We are unaware of the frequency of insulin resistance in patients with essential hypertension as well as the CVD risk in this subgroup of patients. This analysis was aimed at providing the prevalence of insulin resistance and associated CVD risk factors in treated and untreated patients with essential hypertension. METHODS The study population consisted of 126 patients with hypertension: 56 untreated and 70 in a stable treatment program. Body mass index (BMI), blood pressure, plasma glucose and insulin responses to an oral glucose challenge, lipid and lipoprotein concentrations, and steady-state plasma glucose (SSPG) concentration during the insulin suppression test were measured. Insulin resistance was defined operationally as a SSPG concentration >180 mg/dl. RESULTS Demographic characteristics and metabolic CVD risk factors were comparable in both groups, with 30-50% of both treated and untreated patients having abnormalities of all risk factors measured. Approximately 50% of patients met the criteria for insulin resistance in both groups, and the prevalence of abnormal CVD risk factors in this group was increased two to threefold as compared to the other half of the subjects. CONCLUSIONS Approximately 50% of patients with essential hypertension, both treated and untreated, appear to be insulin resistant, and CVD risk factors are greatly accentuated in this subset of patients.

Body composition assessment of undernourished older subjects by dual-energy x-ray absorptiometry and bioelectric impedance analysis

The prevention and treatment of diseases related to changes in body composition require accurate methods for the measurement of body composition. However, few studies have dealt specifically with the assessment of body composition of undernourished older subjects by different methodologies. To assess the body composition of undernourished older subjects by two different methods, dual energy x-ray absorptiometry (DXA) and bioelectric impedance (BIA), and to compare results with those of an eutrophic group. The study model was cross-sectional; the study was performed at the University Hospital of the School of Medicine of Ribeiro Preto, University of So Paulo, Brazil. Forty-one male volunteers aged 62 to 91 years. The groups were selected on the basis of anamnesis, physical examination and nutritional assessment according to the Mini Nutritional Assessment (MNA) score. Body composition was assessed by DXA and BIA. Body weight, arm and calf circumference, body mass index (BMI), fat free mass (FFM) and fat mass (FM) were significantly lower in the undernourished group as compared to the eutrophic group. There were no significant differences between FFM and FM mean values determined by DXA and BIA in both groups, but the agreement between methods in the undernourished group was less strong. Our results suggest caution when BIA is to be applied in studies including undernourished older subjects. This study does not support BIA as an accurate method for the individual assessment of body composition.

HbA(1c) as a risk factor for heart failure in persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) study

Heart failure (HF) incidence in diabetes in both the presence and absence of CHD is rising. Prospective population-based studies can help describe the relationship between HbA(1c), a measure of glycaemia control, and HF risk. We studied the incidence of HF hospitalisation or death among 1,827 participants in the Atherosclerosis Risk in Communities (ARIC) study with diabetes and no evidence of HF at baseline. Cox proportional hazard models included age, sex, race, education, health insurance status, alcohol consumption, BMI and WHR, and major CHD risk factors (BP level and medications, LDL- and HDL-cholesterol levels, and smoking). In this population of persons with diabetes, crude HF incidence rates per 1,000 person-years were lower in the absence of CHD (incidence rate 15.5 for CHD-negative vs 56.4 for CHD-positive, p < 0.001). The adjusted HR of HF for each 1% higher HbA(1c) was 1.17 (95% CI 1.11-1.25) for the non-CHD group and 1.20 (95% CI 1.04-1.40) for the CHD group. When the analysis was limited to HF cases which occurred in the absence of prevalent or incident CHD (during follow-up) the adjusted HR remained 1.20 (95% CI 1.11-1.29). These data suggest HbA(1c) is an independent risk factor for incident HF in persons with diabetes with and without CHD. Long-term clinical trials of tight glycaemic control should quantify the impact of different treatment regimens on HF risk reduction.

LONGITUDINAL REFERENCE VALUES FOR DUCTUS VENOSUS DOPPLER IN LOW-RISK PREGNANCIES

The aim of this study was to establish normal ranges of blood flow velocities and indices in the fetal ductus venosus (DV) during the second half of normal pregnancy. A Doppler study of 60 healthy pregnant women without fetal pathologies was performed during the second half of pregnancy. The peak systolic velocity (PSV), peak diastolic velocity (PDV), maximum velocity during atrial contraction (VAC), peak systolic velocity/maximum velocity during atrial contraction (S/A ratio), pulsatility index for the vein (PIV), preload index (PLI) and velocity index for the vein (VIV) were calculated from the DV at 4-week intervals. A significant increase in PSV, PDV and VAC was observed from the 20-23(6/7) to the 28-31(6/7) weeks, with stabilization of values until the end of the pregnancy. On the other hand, the study showed a significant decrease for the S/A ratio, PIV, PLI and VIV from the 20-23(6/7) to the 28-31(6/7) weeks and remaining stable from then until term. (E-mail:dralemar@uol.com.br) (C) 2010 World Federation for Ultrasound in Medicine & Biology.

Treatment for low-risk gestational trophoblastic disease: Comparison of single-agent methotrexate, dactinomycin and combination regimens

Objectives. To compare the efficacy of three different standard chemotherapy regimens for low-risk gestational trophoblastic disease according to the FIGO staging system in a single-institute setting. Methods. From 1980 until 2002, we retrospectively reviewed 108 cases with low-risk persistent gestational trophoblastic disease who were treated with first-line chemotherapy. Patients were divided in three groups according to chemotherapy regimen: patients treated with methotrexate (MTX group; n=42), patients treated with dactinomycin (ACT group; n=42) and patients treated with methotrexate and dactinomycin in combination (MACT group; n=24). We compared the number of chemotherapy courses for achieving remission, the duration of treatment, the adverse side effects, the efficacy of the treatment and the need for performing a hysterectomy among the groups Results. The complete remission rates were 69%, 61.4% and 79.1% for methotrexate (MTX), dactinomycin (ACT) and the combination regimen (MACT) treated groups, respectively (p=0.7). The duration of the treatment and the number of chemotherapy courses were similar among the groups (p = 0.2 and p = 0.4, respectively). Adverse side effects rate was reported to be 62.5% in the MACT group, 28.6% in the MTX group and 19.1% in the ACT group (p=0.0003). Second-line chemotherapy was indicated for 30 patients. Hysterectomy was performed in 21 patients overall, and there was no difference among the groups (P=0.6). Conclusion. Our analysis indicates that single-agent chemotherapy regimens are as effective as combination chemotherapy for low-risk gestational trophoblastic disease. Dactinomycin is a less toxic drug and might offer the best cost-effective treatment option. Methotrexate must be considered as the regimen of choice for low resource areas because of the feasibility of its administration. (c) 2007 Elsevier Inc. All rights reserved.

Risk of Potential Drug-Drug Interactions among Brazilian Elderly A Population-Based, Cross-Sectional Study

Background: Drug-drug interactions (DDIs) are one of the main causes of adverse reactions related to medications, being responsible for up to 23% of hospital admissions. However, only a few studies have evaluated this problem in elderly Brazilians. Objectives: To determine the prevalence of potential DDIs (PDDIs) in community-dwelling elderly people in Brazil, analyse these interactions with regard to severity and clinical implications, and identify associated factors. Methods: A population-based cross-sectional study was carried out involving 2143 elderly (aged 60 years) residents of the metropolitan area of Sao Paulo, Brazil. Data were obtained from the SABE (Saude, Bem estar e Envelhecimento [Health, Well-Being, and Aging]) survey, which is a multicentre study carried out in seven countries of Latin America and the Caribbean, coordinated by the Pan-American Health Organization. PDDIs were analysed using a computerized program and categorized according to level of severity, onset, mechanism and documentation in the literature. The STATA software statistical package was used for data analysis, and logistic regression was conducted to determine whether variables were associated with PDDIs. Results: Analysis revealed that 568 (26.5%) of the elderly population included in the study were taking medications that could lead to a DDI. Almost two-thirds (64.4%) of the elderly population exposed to PDDIs were women, 50.7% were aged >= 75 years, 71.7% reported having fair or poor health and 65.8% took 2-5 medications. A total of 125 different PDDIs were identified; the treatment combination of an ACE inhibitor with a thiazide or loop diuretic (associated with hypotension) was the most frequent cause of PDDIs (n=322 patients; 56.7% of individuals with PDDIs). Analysis of the PDDIs revealed that 70.4% were of moderate severity, 64.8% were supported by good quality evidence and 56.8% were considered of delayed onset. The multivariate analysis showed that the risk of a PDDI was significantly increased among elderly individuals using six or more medications (odds ratio [OR] 3.37) and in patients with hypertension (OR 2.56), diabetes mellitus (OR 1.73) or heart problems (OR 3.36). Conclusions: Approximately one-quarter of the elderly population living in Sao Paulo could be taking two or more potentially interacting medicines. Polypharmacy predisposes elderly individuals to PDDIs. More than half of these drug combinations (57.6%, n = 72) were part of commonly employed treatment regimens and may be responsible for adverse reactions that compromise the safety of elderly individuals, especially at home. Educational initiatives are needed to avoid unnecessary risks.

Prevalence of trachoma in a population of the upper Rio Negro Basin and risk factors for active disease

Purpose: To determine the prevalence of trachoma in Sao Gabriel da Cachoeira (SGC), the only urban community of the upper Rio Negro Basin of the Amazon state in Brazil, near the Colombian border, and to investigate the risk factors associated with the active forms of the disease. Methods: A total of 1702 people (440 children up to 9 years and 1069 adults aged 15 years and above) were examined. The sample was selected from a probabilistic household sampling procedure based on census data and a previous study of trachoma prevalence in Sao Gabriel da Cachoeira. A two-stage probabilistic household cluster sample was drawn. Household units were randomly selected within each cluster. A variety of socioeconomic and hygiene variables were studied in order to determine the risk factors for active trachoma in a household. Results: The total prevalence of trachoma was 8.9%. Prevalence of active trachoma (TF and/or TI) in children aged 1-9 years was 11.1% and trachomatous trichiasis in adults aged 15 years and above was 0.19%. Trachomatous scarring reached a peak of 22.4% for subjects between 50 to 60 years of age. Corneal opacity occurred in subjects aged 50 years and older with a prevalence of 2.0%. No sex effect was found on the overall prevalence of trachoma in SGC. Risk factors associated with active trachoma were mainly related to poor socioeconomic indicators. Conclusions: Despite the ubiquitous presence of water, the analysis of the risk factors associated with the active forms of the disease supports the idea that a low personal standard of hygiene and not water availability per se, is the key factor associated with trachoma.

Presence of MRI-detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: the MOST study

Objective To evaluate if two different measures of synovial activation, baseline Hoffa synovitis and effusion synovitis, assessed by MRI, predict cartilage loss in the tibiofemoral joint at 30 months follow-up in subjects with neither cartilage damage nor tibiofemoral radiographic osteoarthritis of the knee. Methods Non-contrast-enhanced MRI was performed using proton density-weighted fat-suppressed sequences in the axial and sagittal planes and a short tau inversion recovery sequence in the coronal plane. Hoffa synovitis, effusion synovitis and cartilage status were assessed semiquantitatively according to the WORMS scoring system. Included were knees that had neither radiographic osteoarthritis nor MRI-detected tibiofemoral cartilage damage at the baseline visit. The presence of Hoffa synovitis was defined as any grade = 2 (range 0-3) and effusion synovitis as any grade = 2 (range 0-3). Logistic regression was performed to examine the relation of the presence of either measure to the risk of cartilage loss at 30 months adjusting for other potential confounders. Results Of 514 knees included in the analysis, the prevalence of Hoffa synovitis and effusion synovitis at the baseline visit was 8.4% and 10.3%, respectively. In the multivariable analysis, baseline effusion synovitis was associated with an increased risk of cartilage loss. No such association was observed for baseline Hoffa synovitis. Conclusions Baseline effusion synovitis, but not Hoffa synovitis, predicted cartilage loss. The findings suggest that effusion synovitis, a reflection of inflammatory activity including joint effusion and synovitic thickening, may play a role in the future development of cartilage lesions in knees without osteoarthritis.

Prognostic factors and survival analysis in a sample of oral squamous cell carcinoma patients

Objectives. The aims of this report were to describe the 5-year overall survival (OS) in a group of oral squamous cell carcinoma (OSCC) patients and to investigate the effects of age, gender, anatomic localization, tumor evolution time, smoking and alcohol intake, nodal status, tumoral recurrences, histologic classification, p53 and p63 immunoexpression, human papillomavirus DNA presence, and treatment on the prognostic outcome. Study design. Survival curves were generated using Kaplan-Meier method, and univariate and multivariate analyses were made using the log rank test and Cox regression, respectively. Results. The 5-year OS was 28.6%, and the univariate analysis showed significant results for p53 and p63 immunoexpression, age, and anatomic localization. The Cox regression demonstrated poor OS for tumors with p53 immunoexpression and for patients aged over 60 years. There were also significant differences in survival depending on the anatomic localizations. Conclusion. These results highlight the influence of p53 immunoexpression, age, and anatomic localization in OSCC evolution. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008; 106: 685-95)

Sensitivity and uncertainty analyses for burden of disease and risk factor estimates

Epidemiological studies report confidence or uncertainty intervals around their estimates. Estimates of the burden of diseases and risk factors are subject to a broader range of uncertainty because of the combination of multiple data sources and value choices. Sensitivity analysis can be used to examine the effects of social values that have been incorporated into the design of the disability–adjusted life year (DALY). Age weight, where a year of healthy life lived at one age is valued differently from at another age, is the most controversial value built into the DALY. The discount rate, which addresses the difference in value of current versus future health benefits, also has been criticized. The distribution of the global disease burden and rankings of various conditions are largely insensitive to alternate assumptions about the discount rate and age weighting. The major effects of discounting and age weighting are to enhance the importance of neuropsychiatric conditions and sexually transmitted infections. The Global Burden of Disease study also has been criticized for estimating mortality and disease burden for regions using incomplete and uncertain data. Including uncertain results, with uncertainty quantified to the extent possible, is preferable, however, to leaving blank cells in tables intended to provide policy makers with an overall assessment of burden of disease. No estimate is generally interpreted as no problem. Greater investment in getting the descriptive epidemiology of diseases and injuries correct in poor countries will do vastly more to reduce uncertainty in disease burden assessments than a philosophical debate about the appropriateness of social value

Prevalence and risk factors for anti-Toxoplasma gondii antibodies in goats of the Serido Oriental microregion, Rio Grande do Norte state, Northeast region of Brazil

The prevalence and risk factors for anti-Toxoplasma gondii antibodies were investigated in goats of the Serido Oriental microregion, Rio Grande do Norte state, Northeast region of Brazil. Three hundred and sixty-six blood samples from goats collected by jugular venopuncture were used. For the serologic diagnosis of Toxoplasma gondii infection, the indirect fluorescent-anti body test (IFAT) with cut-off value 1:64 was carried out. The prevalence of anti-T. gondii antibodies was 30.6% [95% CI = 25.9-35.6%] with titers ranging from 1:64 to 1: 16,384. The multivariate logistic regression analysis showed that the risk factors associated to anti-T. gondii antibodies were presence of cats in the herd, extensive/semi-intensive management systems and lack of mineral supplementation. (c) 2008 Elsevier B.V. All rights reserved.

Squamous Cell Carcinoma of the Tongue and Floor of the Mouth: Analysis of Survival Rate and Independent Prognostic Factors in the Amazon Region

Oral squamous cell carcinoma (OSCC) accounts for more than 95% of all malignant neoplasms in the oral cavity. Although several studies have shown the epidemiology of this cancer in Brazil, there do not seem to be any studies that describe the prognostic factors related to OSCC in the Amazon region. Therefore, the aim of this study was to determine the survival rate and prognostic significance of different factors in patients from this region affected by OSCC. Data from 85 patients with histologically confirmed squamous cell carcinoma of the tongue and floor of the mouth identified from the Ofir Loyola Hospital archives were collected and analyzed using univariate (log-rank test) and multivariate (Cox proportional hazard model) tests. The overall 5-year survival rate was found to be 27%. Univariate analysis showed that the 5-year survival rate was significantly higher for younger (<= 45 y) female patients, patients with T1-2 tumors and clinically clear neck nodes (N0), patients with early stage cancers (AJCC stage I-II), and patients treated with surgical procedures. However, multivariate analysis showed that the 5-year survival rate was significantly higher only in the younger patients and those who underwent surgical treatment. The age of the patient at the moment of diagnosis and treatment with surgical procedures were the only independent prognostic factors that affected the 5-year survival rate of the patients in this region.

Tooth loss prevalence and risk indicators in an isolated population of Brazil

Objective. The aim of this study was to assess the prevalence, extent, and risk indicators of tooth loss in an isolated population of Brazil. Material and methods. Two-hundred-and-forty-two subjects, ranging in age from 14 to 82 years (mean 36.2 years), were identified by census in an isolated population of Brazil. All consenting subjects received a full-mouth clinical (DFT index and information about missing teeth) and periodontal examination of 6 sites per tooth. Furthermore, they were interviewed using a structured written questionnaire in order to gather information about demographic, environmental, and biological variables. Results. Of the 200 subjects (80% response rate), 19 (9.5%) were edentulous, 90% had lost at least one tooth, and 39% had lost more than 8 teeth. The mean number of teeth lost was 9.5 (95% CI = 8.2-10.8). First mandibular molars were the most commonly missing teeth. In a multiple logistic regression analysis based on a theoretical hierarchical model of tooth loss, having more than 8 teeth lost was strongly associated with adult age (OR = 18.3-17.3, 95% CIs = 4.8-69.7 and 4.0-75.1) and female gender (OR = 5.9, 95% CI = 1.9-18.2) in the final model. Conclusions. Tooth loss was highly prevalent and extensive in this isolated population. Demographic and behavioral factors played an important role in tooth loss prevalence in this population.