A higher degree of expression of DNA methyl transferase 1 in cervical cancer is associated with poor survival outcome.

BACKGROUND: Even though novel therapies based on aberrant DNA methylation could be of particular importance for the treatment of cervical cancer (CC) because the oncoproteins E6/E7 of high-risk human papillomaviruses, the causative agents for developing CC, have the capacity to bind and upregulate DNA methyltransferases (DNMTs), to our knowledge, no previous studies have evaluated the expression of this enzyme in CC in relation to survival outcomes. The purpose of the study was to evaluate the expression of DNMT1 in CC and its association with survival outcomes. METHODS: The study population consisted of 76 women treated for primary CC and followed up by the University of Alabama at Birmingham (UAB) cancer registry. The expression of DNMT1 was examined using immunohistochemistry, and the degree of expression of DNMT1 was expressed as a percentage of cells positive for DNMT1 and its intensity. Cox proportional hazards model was used to assess the relationship between the degree of expression of DNMT1 and overall survival after adjusting for relevant covariates. RESULTS: The expression of DNMT1 was significantly higher in CC cells compared to that in the normal cervical epithelium. A higher percentage of cells positive for DNMT1 and a higher intensity score for DNMT1 were significantly associated with poor survival outcome (hazard ratio [HR] =4.3, P=0.03 and HR =4.9, P=0.02, respectively). CONCLUSION: Our findings suggested that the degree of expression of DNMT1 could be considered as a target in the epigenetic treatment of CC. Replication of our results in other study populations with CC could create the opportunity of using DNMT inhibitors to treat CC.

Risk factors of peripheral arterial disease: a case control study in Sri Lanka.

BACKGROUND: Peripheral artery disease (PAD) is an important global health problem and contributes to notable proportion of morbidity and mortality. This particular manifestation of systemic atherosclerosis is largely under diagnosed and undertreated. For sustainable preventive strategies in a country, it is mandatory to identify country-specific risk factors. We intended to assess the risk factors of PAD among adults aged 40-74 years. METHODS: This case control study was conducted in 2012-2013 in Sri Lanka. Seventy-nine cases and 158 controls in the age group of 40-74 years were selected for the study in order to have case to control ratio 1:2. The criterion for selecting cases and control was based on Ankle brachial pressure index (ABPI). Cases were selected from those who had ABPI 0.85 or less (ABPI ≤0.85) in either lower limb. Controls were selected from those ABPI score between 1.18 and 1.28 in both lower limbs. Only newly identified individuals with PAD were selected as cases. Controls were selected from the same geographical location and within the 5 year age group as cases. RESULTS: The history of diabetes mellitus more than 10 years (OR 5.8, 95% CI 2.2-14.2), history of dyslipidemia for more than 10 years (OR 4.9, 95% CI 2.1-16.2), history of hypertension for more than 10 years (OR 3.8, 95% CI 1.8-12.7) and smoking (OR 2.9, 95% CI 1.2-6.9), elevated HsCRP (OR 3.7, 95% CI 1.2-12.0) and hyperhomocysteinemia (OR 3.0, 95% CI 1.1-8.1) were revealed as country specific significant risk factor of PAD. CONCLUSIONS: Diabetes mellitus, hypertension, dyslipidemia, smoking as well as elevated homocysteine and HsCRP found as risk factors of PAD. Longer the duration or higher level exposure to these risk factors has increased the risk of PAD. These findings emphasis the need for routine screening of PAD among patients with the identified risk factors.

Gaps in awareness of peripheral arterial disease in Sri Lanka: a cross sectional study.

BACKGROUND: Peripheral arterial disease (PAD) is an emerging problem in Sri Lanka, particularly with the ageing population. A considerable number of patients are detected at a late stage with severe limb ischemia or chronic non-healing leg ulceration. Public awareness about PAD is important in developing preventive strategies. METHODS: A cross sectional study was conducted to assess awareness of PAD among adults aged 40-74 years in a district in Sri Lanka. In total, 2912 adults were selected for the study using a multistage probability proportionate to size sampling technique. Data were collected by an interviewer-administered questionnaire. Participants who were aware of PAD were asked about common risk factors, possible consequences of untreated PAD, and sources of information. Multivariate logistic regression analysis was used to assess the independent predictors of PAD awareness. RESULTS: We found that 4.1 % of participants were aware of PAD (95 % confidence interval: 3.4-4.8), which was significantly lower than awareness of other cardiovascular diseases such as cerebrovascular accidents (67.3 %) and myocardial infarction (57.6 %) (p < 0.001). Being male, an urban resident, and having a higher level of education were independent predictors of high PAD awareness. CONCLUSIONS: Our findings suggest that a comprehensive PAD awareness program that covers risk factors, consequences, and preventative strategies is needed to enhance public awareness of PAD.

An examination of racial differences in 5-year survival of cervical cancer among African American and white American women in the southeastern US from 1985 to 2010.

Disparities in Cervical Cancer (CC) mortality outcomes between African American (AA) and White women have been studied for decades. However, conclusions about the effect of race on CC survival differ across studies. This study assessed differences in CC survival between AA and White women diagnosed between 1985 and 2010 and treated at two major hospitals in the southeastern US. The study sample included 925 AA and 1192 White women diagnosed with cervical adenocarcinoma, adenosquamous cell carcinoma, or squamous cell carcinoma. Propensity score adjustment and matching were employed to compare 5-year survival between the two racial groups. Crude comparisons suggested relevant racial differences in survival. However, the racial differences became of small magnitude after propensity-score adjustment and in matched analyses. Nonlinear models identified age at diagnosis, cancer stage, mode of treatment, and histological subtype as the most salient characteristics predicting 5-year survival of CC, yet these characteristics were also associated with race. Crude racial differences in survival might be partly explained by underlying differences in the characteristics of racial groups, such as age at diagnosis, histological subtype, cancer stage, and the mode of treatment. The study results highlight the need to improve access to early screening and treatment opportunities for AA women to improve posttreatment survival from CC.

ABPI against Colour Duplex Scan: A Screening Tool for Detection of Peripheral Arterial Disease in Low Resource Setting Approach to Validation.

Background. In Sri Lanka the ABPI has not been used as a screening tool to detect peripheral arterial disease (PAD) in epidemiological studies. This study was conducted to determine the best cutoff value of ABPI to detect PAD in Sri Lankan population. Methods. The ABPI measured by arterial Doppler to detect PAD was validated against colour duplex scan as the criterion using 165 individuals referred to vascular laboratory, National Hospital Sri Lanka. In all selected individuals ABPI was measured and lower limb colour duplex scan was performed. Narrowing of luminal diameter of lower limb arteries 50% or more was considered as haemodynamically significant and having PAD. The discriminative performance of the ABPI was assessed using Receiver Operator Characteristic (ROC) curve and calculating the area under the curve (AUC). The sensitivity and specificity of different threshold levels of ABPI and the best cutoff value of ABPI to detect PAD were determined. Results. ABPI 0.89 was determined as the best cutoff value to identify individuals with PAD. At this level of ABPI high sensitivity (87%), specificity (99.1%), positive predictive value (98.9%), and negative predictive value (88.4%) were observed. Conclusion. ABPI ≤ 0.89 could be used as the best cut off value to detect PAD.

A cross-sectional study on peripheral arterial disease in a district of Sri Lanka: prevalence and associated factors.

BACKGROUND: Peripheral arterial disease (PAD), a slowly progressive atherosclerotic disease affecting vital organs of the body, is increasingly recognized as a health burden worldwide. Epidemiological information on peripheral arterial disease is scarce in Sri Lanka. The present study intended to estimate the prevalence and associated factors of PAD among adults aged 40-74 years in Gampaha district, Sri Lanka. METHODS: A cross-sectional study was carried out to estimate the prevalence of PAD among adults aged 40-74 years in four randomly selected divisional secretariat areas in Gampaha district in 2012-2013. The sample size of 2912 adults was obtained from 104 clusters using multistage probability proportionate to size sampling. The number of individuals to be included in the 5-year age groups between 40 and 74 years was determined based on the population proportion of the respective age groups in the district. Cluster size was 28, and equal numbers of males and females were selected for each age group per cluster. PAD was defined as having an ankle-brachial pressure index ≤ 0.89. RESULTS: The age-and sex-standardized prevalence of PAD, adjusted for the sensitivity of the ankle-brachial pressure index was 3.6% (95% CI 2.9-4.3%), and no significant difference was found between males (3.7%) and females (3.6%) (p = 0.08). Eighty-eight individuals were newly identified as having PAD, and a significant trend of prevalence with increasing age was observed (p < 0.001). Histories of diabetes mellitus, hypertension, dyslipidemia, coronary artery disease, cerebrovascular accident, smoking, and erectile dysfunction among males were significantly associated with PAD (p < 0.001). Only one third of those with PAD experienced claudication symptoms. CONCLUSIONS: PAD was found to be a hidden disease in the Gampaha district population. Although there is minimal attention on PAD at present, the disease is likely to become a problematic public health concern in Sri Lanka, particularly with its aging population. Primary prevention measures to modify risk factors of PAD, including screening activities for early identification, should be a priority.