Worldwide risk factors for heart failure: A systematic review and pooled analysis

Background

Heart failure risk factors are diverse and likely to vary among world regions. Systematic review and pooled analysis were used to describe contributions of major underlying risk factors for heart failure in six world regions.

Methods

Electronic databases were systematically searched, and 37 clinic-based studies representing 40 countries published in 1980–2008 and reporting underlying risk factors for heart failure were included. Risk factors were classified as ischemic heart disease (IHD), hypertension, rheumatic/other valvular heart disease, cardiopulmonary disease, cardiomyopathy, and “other”. Crude and age- and sex-adjusted risk factor prevalences were estimated for each region using a regression analysis, under specifications of overlapping as well as additive contributions.

Results

Many heart failure cases were assigned multiple underlying risk factors, leading to a considerable overlap. Crude IHD prevalence among heart failure patients was > 50% in Europe and North America, approximately 30–40% in East Asia and Latin America and the Caribbean, and < 10% in Sub-Saharan Africa. Age and sex adjustment attenuated regional differences in IHD-as-risk factor but IHD remained rare in Sub-Saharan Africa. Hypertension prevalence was high in heart failure patients of all regions but the highest in Eastern and Central Europe and Sub-Saharan Africa (age- and sex-adjusted, 35.0% and 32.6%, respectively). Cardiomyopathy was most common in Latin America, the Caribbean and Sub-Saharan Africa (age- and sex-adjusted, 19.8% and 25.7%).

Conclusions

Heart failure risk factors vary substantially among world regions. More detailed regional heart failure epidemiology studies are needed in order to quantify the global burden of heart failure and identify regional prevention and treatment strategies.     

Overexpression of FoxM1 offers a promising therapeutic target in diffuse large B-cell lymphoma

Background

FoxM1 has been shown to play a critical role in the pathogenesis of various epithelial malignancies. However, its role in lymphoid malignancies has not been fully clarified. We, therefore, investigated the role of FoxM1 expression in a large cohort of diffuse large B-cell lymphoma samples and panel of cell lines.

Design and Methods

FoxM1 expression was investigated in a large series of diffuse large B-cell lymphoma tissues in a tissue microarray format by immunohistochemistry. Apoptosis was measured by flow cytometry and protein expression was detected by immunoblotting using diffuse large B-cell lymphoma cell lines following treatment with either pharmacological inhibitor of FoxM1 or small interference RNA knockdown strategy. Invasion/migration and soft agar colony assays were also performed following treatment with FoxM1 inhibitor.

Results

FoxM1 expression was detected in 84.6% of diffuse large B-cell lymphoma tumors and found to be significantly associated with proliferative tumor marker Ki67 (P<0.0001), matrix metalloproteinases-2 (P=0.0008), matrix metalloproteinases-9 (P=0.0002), S-phase kinase associated protein-2 (P<0.0001) and inversely associated with p27 expression (P=0.0215). Expression of small interference RNA targeted against FoxM1 or treatment of diffuse large B-cell lymphoma cells with thiostrepton caused its downregulation accompanied by decreased expression of matrix metalloproteinases-2 and matrix metalloproteinases-9. Inhibition of FoxM1 in diffuse large B-cell lymphoma cells also decreased invasive and migratory capability, and induced caspase dependent apoptosis via activation of the mitochondrial apoptotic pathway. Finally, combined thiostrepton and bortezomib at sub-toxic doses led to efficient apoptosis in diffuse large B-cell lymphoma cells.

Conclusions

Altogether, these results suggest that FoxM1 is over-expressed in the majority of diffuse large B-cell lymphoma samples. These data also indicate that targeting FoxM1 signaling can serve as a potential therapeutic modality in the management of diffuse large B-cell lymphoma.     

Short-term effectiveness of radiochemoembolization for selected hepatic metastases with a combination protocol

AIM:To introduce the combination method of radio-chemoembolization for the treatment of selected hepatic metastases. METHODS:Twenty patients with biopsy proven hepatic metastases were selected from those who underwent transarterial radiochemoembolization, a novel combination protocol, between January 2009 and July 2010. Patients had different sources of liver metastasis. The treatment included transarterial administration of three chemotherapeutic drugs (mitomycin, doxorubicin and cisplatin), followed by embolization with large (50-150 μm) radioisotope particles of chromic 32P. Multiphasiccomputer tomography or computer tomography studies, with and without contrast medium injections, were performed for all patients for a short-term period before and after the treatment sessions. The short-term effec-tiveness of this procedure was evaluated by modified response evaluation criteria in solid tumors (mRECIST), which also takes necrosis into account. The subjective percentage of necrosis was also assessed. The response evaluation methods were based on the changes in size, number, and the enhancement patterns of the lesions between the pre-and post-treatment imaging studies. RESULTS:Patients had liver metastasis from colorectal carcinomas, breast cancer, lung cancer and carcinoid tumors. The response rate based on the mRECIST criteria was 5% for complete response, 60% for partial response, 10% for stable disease, and 25% for progressive disease. Regarding the subjective necrosis percentage, 5% of patients had complete response, 50% had partial response, 25% had stable disease, and 20% had progressive disease. Based on traditional RECIST criteria, 3 patients (15%) had partial response, 13 patients (65%) had stable disease, and 4 patients (20%) had disease progression. In most patients, colorectal carcinoma was the source of metastasis (13 patients). Based on the mRECIST criteria, 8 out of these 13 patients had partial responses, while one remained stable, and 5 showed progressive disease. We also had 5 cases of breast cancer metastasis which mostly remained stable (4 cases), with only one partial response after the procedure. Six patients had bilobar involvement; three of them received two courses of radiochemoembolization. The follow up imaging study of these patients was performed after the second ses-sion. In the studied patients there was no evidence of extrahepatic occurrence, including pulmonary radioac-tive deposition, which was proven by Bremsstrahlung scintigraphy performed after the treatment sessions. For the short-term follow-ups for the 2 mo after the therapy, no treatment related death was reported. The mostly common side effect was post-embolizationsyndrome, presented as vomiting, abdominal pain, and fever. Nineteen (95%) patients experienced this syndrome in different severities. Two patient had ascites (with pleural effusion in one patient) not related to hepatic failure. Moreover, no cases of acute liver failure, hepatic infarction, hepatic abscess, biliary necrosis, tumor rupture, surgical cholecystitis, or non-targeted gut embolization were reported. Systemic toxicities such as alopecia, marrow suppression, renal toxicity, or cardiac failure did not occur in our study group. CONCLUSION:Radiochemoembolization is safe and effective for selected hepatic metastases in a short-term follow-up. Further studies are required to show the long-term effects and possible complications of this approach.     

Accuracy of routinely collected comorbidity data in patients undergoing colectomy: a retrospective study

Objectives

This paper aimed to determine the baseline accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of routinely collected comorbidity data in patients undergoing any types of colectomy.

Methods

All patients aged >18 who underwent right hemicolectomy, left hemicolectomy, sigmoid colectomy, subtotal colectomy, or total colectomy between 1 January 2015 and 1 November 2016 were identified. The following comorbidities were considered: hypertension, ischemic heart disease (IHD), diabetes, asthma, chronic obstructive pulmonary disease (COPD), cerebrovascular disease (CVD), chronic kidney disease (CKD), and hypercholesterolemia. The comorbidity data from clinical notes were compared with corresponding data in hospital episode statistics (HES) database in order to calculate accuracy, sensitivity, specificity, PPV, and NPV of HES codes for comorbidities. In order to assess the agreement between clinical notes and HES data, we also calculated Cohen’s kappa index value as a more robust measure of agreement.

Results

Overall, 267 patients comprising 2136 comorbidity codes were included. Overall, HES codes for comorbidities in patients undergoing colectomy had substandard accuracy 94% (kappa 0.542), sensitivity (39%), and NPV (89%). The HES codes were 100% specific with PPV of 100%. The results were consistent when individual comorbidities were analyzed separately.

Conclusions

Our results demonstrated that HES comorbidity codes in patients undergoing colectomy are specific with good positive predictive value; however, they have substandard accuracy, sensitivity, and negative predictive value. Better documentation of comorbidities in admission clerking proforma may help to improve the quality of source documents for coders, which in turn may improve the accuracy of coding.

     

Low Helicobacter pylori eradication rates with 4- and 7-day regimens in an Iranian population

BACKGROUND: In Iran, there is insufficient information on the efficacy of Helicobacter pylori eradication regimens shorter than 10 days. This study aims at assessing the efficacy of 4- and 7-day H. pylori eradication regimens in a high-incidence area of gastric cancer in Iran. METHODS: Subjects with an endoscopic diagnosis of gastritis, positive urease test, and a histological diagnosis of chronic gastritis were enrolled. Patients were randomly assigned to one of three groups: AOC7 (1000 mg amoxicillin, 20 mg omeprazole, and 500 mg clarithromycin twice daily for 7 days), FOT4 (200 mg furazolidone, 20 mg omeprazole, and 500 mg tetracycline twice daily for 4 days) and FOT7 (the same treatment as the FOT4 group but for 7 days). Sensitivity to these antibiotics was determined in all isolates recovered from culture. The efficacy of eradication was assessed 8 weeks after the end-of-treatment by the 14C-urea breath test. RESULTS: One hundred and twenty-eight patients were enrolled in the study. Culture was positive for 84 patients and none of these were resistant to amoxicillin, tetracycline or furazolidone, 1.2% were resistant to clarithromycin and 32.1% to metronidazole. Forty-five, 41 and 42 patients were randomly allocated to the AOC7, FOT4, and FOT7 groups, respectively. The intention-to-treat eradication rates were 35.5, 17.1, and 23.8% for the AOC7, FOT4, and FOT7 groups, respectively. CONCLUSION: Treatment regimens of 4 or 7 days are unacceptable for H. pylori infection in Iran, even in the presence of a favorable sensitivity profile.     

aVR sign as a risk factor for life-threatening arrhythmic events in patients with Brugada syndrome

BACKGROUND: Risk stratification in Brugada syndrome (BS) is controversial, especially in asymptomatic individuals. OBJECTIVE: The aim of this study was to evaluate the significance of lead aVR in patients with BS. METHODS: Twenty-four patients with the electrocardiogram pattern of BS (24 male, mean age 32.1 +/- 13.6 years) and 24 healthy age- and gender-matched controls were studied. RESULTS: Thirteen patients were symptomatic. The R-wave amplitude or R/q ratio in lead aVR was significantly greater in patients experiencing a recurrence compared with those who did not. The aVR sign was defined as R wave >/= 0.3 mV or R/q >/= 0.75 in lead aVR. Most of the recurrences (78%) were in patients with present aVR sign; 84% of BS patients with present aVR sign had events during follow-up. In contrast, only 27% of BS patients with absent aVR sign had events during follow-up. CONCLUSION: Our study shows significant correlation between a prominent R wave in lead aVR (aVR sign) and risk for development of arrhythmic events in BS. In the presence of BS, prominent R wave in lead aVR may reflect more right ventricular conduction delay and subsequently more electrical heterogeneity, which in turn is responsible for a higher risk of arrhythmia.     

Prevalence and correlates of snoring in adolescents

Snoring can occur alone or it may be the presenting feature of Obstructive Sleep Apnea and other common chronic conditions. In our study, we aimed to estimate the prevalence and correlates of snoring in adolescent students in Tehran, Iran. A cross-sectional study was designed and students were selected from 20 secondary and high schools, in 5 different zones in Tehran in order to have a representative sample of the adolescent population. A total of 2900 students (1200 male and 1700 female students) 11-17 year-old who were attending secondary and high schools were investigated. Information was collected via a structured face-to-face interview, based on a questionnaire. In addition to snoring, nocturnal cough, asthma-related symptoms, and daytime symptoms were also questioned. BMI was measured by two trained physicians. The prevalence of snoring was 7.9% (4.8% in girls and 12.4% in boys). The prevalence of snoring was significantly higher among males (P< 0.05). Snoring was positively associated with asthma and nocturnal cough. Overweight/obese adolescents had significantly higher rates of snoring and asthma symptoms. Prevalence of daytime symptoms increased significantly in the snoring group.These results suggest that snoring is associated with multiple factors in adolescents. We conclude that the prevalence of snoring is relatively high in children of this region. This highlights the need for awareness among physicians about the problem of sleep-disordered breathing, especially in children with asthma and obesity, and also the need for further studies to measure the prevalence of sleep breathing disorders among Iranians.