The potential for using risk models in future lung cancer screening trials

Computed tomography screening for early diagnosis of lung cancer is one of the more potentially useful strategies, aside from smoking cessation programmes, for reducing mortality and improving the current poor survival from this disease. The long-term success of lung cancer screening will be dependent upon identifying populations at sufficient risk in order to maximise the benefit-to-harm ratio of the intervention. Risk prediction models could potentially play a major role in the selection of high-risk individuals who would benefit most from screening intervention programmes for the early detection of lung cancer. Improvements of developed lung cancer risk prediction models (through incorporation of objective clinical factors and genetic and molecular biomarkers for precise and accurate estimation of risks), demonstration of their clinical usefulness in decision making, and their use in future screening programmes are the focus of current research

Phenotypic Variability of Morphological and Nutritional Parameters of Pepper (Capsicum Spp) Accessions in the Derived Savanna Agro-Ecology of Nigeria

Variability studies on newly collected accessions and identification of superior genotypes enhances their suitability for breeding programmes. This study was aimed to estimate variation and assess the mean performance of pepper accessions collected across Nigeria. The study evaluated eighteen pepper genotypes and the experiment was laid out in a randomized complete block design with three replicates. Analysis of variance showed significant (P < 0.01) differences among accessions for all measured, except for number of fruits per plant. Correlation coefficients ranged from -0.27 to 0.84 and the strongest relationship was observed between stem colour and fruit length (r = 0.84, P < 0.001). Strong significant (P < 0.001) correlations between several traits were observed and fruit yield was either positively or negatively associated with other traits. Results from principal component analysis showed that the first six principal components accounted for 86 % of the total variability among the accessions. Cluster analysis differentiated the accessions and formed three distinct groups which were not in accordance with their source of collection. Accession NHPP-0144 combined high fruit yield with other desirable agronomic traits. Other promising accessions were NHPP-0137, NHPP 0319, NHPP-0332 and NHPP-0334 which possess favourable genes for yield potential and quality traits, a basis for future selection in pepper breeding programmes

Topical Ear Drop Self-medication Practice among the Ear, Nose, and Throat Patients in Ido Ekiti, Nigeria: A Cross - sectional Study

Background: Self‑medication is a common habit in our country; Nigeria, especially among patients with otorhinolaryngological disorders. Medication when taken wrongly may bring dire consequences to the individual, such as masking developing diseases and may cause many other undesirable effects. The aim of this study was to determine the prevalence and to analyze topical ear drop self‑medication practices among respondents attending the Ear, Nose, and Throat Clinic of Federal Teaching Hospital Ido Ekiti, Nigeria. Design and Methodology: A 6‑month hospital based cross‑sectional study was conducted among patients who were seen in the Ear, Nose, and Throat facility of Federal Teaching Hospital, Ido Ekiti from July to December 2016 to determine topical ear drop self‑medication practices. A pretested semi‑structured questionnaire was used to obtained information from respondents. Results: A total of 162 respondents out of 493 patients seen during the study had otological problems. Of which 107 (66%) respondents had engaged in self‑medication with topical ear drops. Their ages ranged between 2 and 83 years with a mean age of 36.6 ± 19.1 years. There were 75 males and 87 females. The major reason for self‑medication was that their ailments were minor in about 40.2% and the most common indication for self‑medication was ear blockage with hearing impairment (33.6%). Pharmacy/chemist shops (42%) were major sources of information for those that self‑medicated. Chloramphenicol and gentamycin were the major drugs that were used by the respondents. Conclusion: Majority of the respondents in this study practiced self‑medication using different topical ear drops. Major source of information on the topical ear drops used was from pharmacy/chemist shops. There is a need for adequate public health education to create awareness among people on the danger of self‑medication and to enact or enforce the law to reduce access to over the counter drugs. Healthcare should be made available and avoidable at primary health‑care level

Topical Ear Drop Self-medication Practice among the Ear, Nose, and Throat Patients in Ido Ekiti, Nigeria: A Cross - sectional Study

Background: Self‑medication is a common habit in our country; Nigeria, especially among patients with otorhinolaryngological disorders. Medication when taken wrongly may bring dire consequences to the individual, such as masking developing diseases and may cause many other undesirable effects. The aim of this study was to determine the prevalence and to analyze topical ear drop self‑medication practices among respondents attending the Ear, Nose, and Throat Clinic of Federal Teaching Hospital Ido Ekiti, Nigeria. Design and Methodology: A 6‑month hospital based cross‑sectional study was conducted among patients who were seen in the Ear, Nose, and Throat facility of Federal Teaching Hospital, Ido Ekiti from July to December 2016 to determine topical ear drop self‑medication practices. A pretested semi‑structured questionnaire was used to obtained information from respondents. Results: A total of 162 respondents out of 493 patients seen during the study had otological problems. Of which 107 (66%) respondents had engaged in self‑medication with topical ear drops. Their ages ranged between 2 and 83 years with a mean age of 36.6 ± 19.1 years. There were 75 males and 87 females. The major reason for self‑medication was that their ailments were minor in about 40.2% and the most common indication for self‑medication was ear blockage with hearing impairment (33.6%). Pharmacy/chemist shops (42%) were major sources of information for those that self‑medicated. Chloramphenicol and gentamycin were the major drugs that were used by the respondents. Conclusion: Majority of the respondents in this study practiced self‑medication using different topical ear drops. Major source of information on the topical ear drops used was from pharmacy/chemist shops. There is a need for adequate public health education to create awareness among people on the danger of self‑medication and to enact or enforce the law to reduce access to over the counter drugs. Healthcare should be made available and avoidable at primary health‑care level

DNA Methylation Biomarkers Offer Improved Diagnostic Efficiency in Lung Cancer

The exceptional high mortality of lung cancer can be instigated to a high degree by late diagnosis. Despite the plethora of studies on potential molecular biomarkers for lung cancer diagnosis, very few have reached clinical implementation. In this study we developed a panel of DNA methylation biomarkers and validated their diagnostic efficiency in bronchial washings from a large retrospective cohort. Candidate targets from previous high-throughput approaches were examined by Pyrosequencing in an independent set of 48 lung tumor/normal paired. Ten promoters were selected and quantitative methylation-specific PCR (qMSP) assays were developed and used to screen 655 bronchial washings (BWs) from the Liverpool Lung Project (LLP) subjects divided into training (194 cases and 214 Controls) and validation (139 cases and 109 controls) sets. Three statistical models were employed to select the optimal panel of markers and evaluate the performance of the discriminatory algorithms. The final logit regression model incorporated hypermethylation at p16, TERT, WT1 and RASSF1.The performance of this 4-gene methylation signature in the validation set demonstrated 82% sensitivity and 91% specificity. In comparison, cytology alone in this set provided 43% sensitivity at 100% specificity. The diagnostic efficiency of the panel did not show any biases with age, gender, smoking and the presence of a non-lung neoplasm. However, sensitivity was predictably higher in central (squamous and small cell) than peripheral (adenocarcinomas) tumors, as well as in stage 2 or greater tumors.These findings clearly demonstrate the impact of DNA methylation-based assays in the diagnosis of cytologically occult lung neoplasms. A prospective trial is currently imminent in the LLP study to provide data on the enhancement of diagnostic accuracy in a clinical setting, including by additional markers

SHOX2 DNA Methylation is a Biomarker for the diagnosis of lung cancer based on bronchial aspirates

<p>Abstract</p> <p>Background</p> <p>This study aimed to show that SHOX2 DNA methylation is a tumor marker in patients with suspected lung cancer by using bronchial fluid aspirated during bronchoscopy. Such a biomarker would be clinically valuable, especially when, following the first bronchoscopy, a final diagnosis cannot be established by histology or cytology. A test with a low false positive rate can reduce the need for further invasive and costly procedures and ensure early treatment.</p> <p>Methods</p> <p>Marker discovery was carried out by differential methylation hybridization (DMH) and real-time PCR. The real-time PCR based HeavyMethyl technology was used for quantitative analysis of DNA methylation of SHOX2 using bronchial aspirates from two clinical centres in a case-control study. Fresh-frozen and Saccomanno-fixed samples were used to show the tumor marker performance in different sample types of clinical relevance.</p> <p>Results</p> <p>Valid measurements were obtained from a total of 523 patient samples (242 controls, 281 cases). DNA methylation of SHOX2 allowed to distinguish between malignant and benign lung disease, i.e. abscesses, infections, obstructive lung diseases, sarcoidosis, scleroderma, stenoses, at high specificity (68% sensitivity [95% CI 62-73%], 95% specificity [95% CI 91-97%]).</p> <p>Conclusions</p> <p>Hypermethylation of SHOX2 in bronchial aspirates appears to be a clinically useful tumor marker for identifying subjects with lung carcinoma, especially if histological and cytological findings after bronchoscopy are ambiguous.</p

Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls

Recent genome-wide association studies (GWASs) have identified common genetic variants at 5p15.33, 6p21-6p22 and 15q25.1 associated with lung cancer risk. Several other genetic regions including variants of CHEK2 (22q12), TP53BP1 (15q15) and RAD52 (12p13) have been demonstrated to influence lung cancer risk in candidate- or pathway-based analyses. To identify novel risk variants for lung cancer, we performed a meta-analysis of 16 GWASs, totaling 14 900 cases and 29 485 controls of European descent. Our data provided increased support for previously identified risk loci at 5p15 (P = 7.2 × 10−16), 6p21 (P = 2.3 × 10−14) and 15q25 (P = 2.2 × 10−63). Furthermore, we demonstrated histology-specific effects for 5p15, 6p21 and 12p13 loci but not for the 15q25 region. Subgroup analysis also identified a novel disease locus for squamous cell carcinoma at 9p21 (CDKN2A/p16INK4A/p14ARF/CDKN2B/p15INK4B/ANRIL; rs1333040, P = 3.0 × 10−7) which was replicated in a series of 5415 Han Chinese (P = 0.03; combined analysis, P = 2.3 × 10−8). This large analysis provides additional evidence for the role of inherited genetic susceptibility to lung cancer and insight into biological differences in the development of the different histological types of lung cance

Informed Conditioning on Clinical Covariates Increases Power in Case-Control Association Studies

Genetic case-control association studies often include data on clinical covariates, such as body mass index (BMI), smoking status, or age, that may modify the underlying genetic risk of case or control samples. For example, in type 2 diabetes, odds ratios for established variants estimated from low–BMI cases are larger than those estimated from high–BMI cases. An unanswered question is how to use this information to maximize statistical power in case-control studies that ascertain individuals on the basis of phenotype (case-control ascertainment) or phenotype and clinical covariates (case-control-covariate ascertainment). While current approaches improve power in studies with random ascertainment, they often lose power under case-control ascertainment and fail to capture available power increases under case-control-covariate ascertainment. We show that an informed conditioning approach, based on the liability threshold model with parameters informed by external epidemiological information, fully accounts for disease prevalence and non-random ascertainment of phenotype as well as covariates and provides a substantial increase in power while maintaining a properly controlled false-positive rate. Our method outperforms standard case-control association tests with or without covariates, tests of gene x covariate interaction, and previously proposed tests for dealing with covariates in ascertained data, with especially large improvements in the case of case-control-covariate ascertainment. We investigate empirical case-control studies of type 2 diabetes, prostate cancer, lung cancer, breast cancer, rheumatoid arthritis, age-related macular degeneration, and end-stage kidney disease over a total of 89,726 samples. In these datasets, informed conditioning outperforms logistic regression for 115 of the 157 known associated variants investigated (P-value = 1×10−9). The improvement varied across diseases with a 16% median increase in χ2 test statistics and a commensurate increase in power. This suggests that applying our method to existing and future association studies of these diseases may identify novel disease loci