Genetic Susceptibility to Lung Cancer Based on Candidate Genes in a Sample from the Mexican Mestizo Population: A Case–Control Study

Background

Lung cancer (LC) is the leading cause of mortality caused by neoplasias worldwide. Although cigarette smoking is the primary cause, not all smokers develop LC. Polymorphic variations in genes associated with carcinogen metabolism, DNA repair, and cell-cycle dysregulation may alter an individual risk of developing LC. A polygenic cancer model was proposed, which considers genetic susceptibility to cancer is a global mechanism and suggests that it might be defined by the contributions of low-risk alleles in several candidate genes. This study focused on the analysis of 15 polymorphisms in 12 low-penetrance genes in a case–control study of a sample of Mexican Mestizo population.

Methods

A case–control study was performed with a total of 572 unrelated individuals, including 190 cases with a primary LC diagnosis and 382 healthy controls. The polymorphic status of the individuals was determined by TaqMan probe and RFLP techniques. The association between LC and genotype score (GS) was assessed by logistic regression.

Results

The results suggests a protective effect of the genotypes Arg/Lys of AhR rs2066853 (odds ratio [OR] 0.55, p = 0.03), Ile/Val of CYP1A1 rs1048943 (OR 0.49, p = 0.009), Tyr/His of EPHX1 rs1051740 (OR 0.53, p = 0.03), and A/A of CCND1 rs603965 (OR 0.44, p = 0.02). Analyses using the GS suggest that average cases have a larger number of risk alleles than controls (Student’s t test ?4.85, p = 0.001; OR 1.25, p < 0.001).

Conclusions

Our results suggest significant differences between the GS for the cases and controls, which support the hypothesis underlying the additive and polygenic models for lung cancer risk depending on the polymorphisms in low-penetrance genes.     

Comparison of UHPLC and HPLC in Benzodiazepines Analysis of Postmortem Samples: A Case–Control Study

The aim of this study was to compare system efficiency and analysis duration regarding the solvent consumption and system maintenance in high-pressure liquid chromatography (HPLC) and ultra high-pressure liquid chromatography (UHPLC).In a case–control study, standard solutions of 7 benzodiazepines (BZs) and 73 biological samples such as urine, tissue, stomach content, and bile that screened positive for BZs were analyzed by HPLC and UHPLC in laboratory of forensic toxicology during 2012 to 2013. HPLC analysis was performed using a Knauer by 100-5 C-18 column (250 mm × 4.6 mm) and Knauer photodiode array detector (PAD). UHPLC analysis was performed using Knauer PAD detector with cooling autosampler and Eurospher II 100-3 C-18 column (100 mm × 3 mm) and also 2 pumps. The mean retention time, standard deviation, flow rate, and repeatability of analytical results were compared by using 2 methods.Routine runtimes in HPLC and UHPLC took 40 and 15 minutes, respectively. Changes in mobile phase composition of the 2 methods were not required. Flow rate and solvent consumption in UHPLC decreased. Diazepam and flurazepam were detected more frequently in biological samples.In UHPLC, small particle size and short length of column cause effective separation of BZs in a very short time. Reduced flow rate, solvent consumption, and injection volume cause more efficiency and less analysis costs. Thus, in the detection of BZs, UHPLC is an accurate, sensitive, and fast method with less cost of analysis.     

Assessing Adherence in the CAPRISA 004 Tenofovir Gel HIV Prevention Trial: Results of a Nested Case–Control Study

Adherence undeniably impacts product effectiveness in microbicide trials, but the connection has proven challenging to quantify using routinely collected behavioral data. We explored this relationship using a nested case–control study in the CAPRISA 004 Tenofovir (TFV) gel HIV prevention trial. Detailed 3-month recall data on sex events, condom and gel use were collected from 72 incident cases and 205 uninfected controls. We then assessed how the relationship between self-reported adherence and HIV acquisition differed between the TFV and placebo gel groups, an interaction effect that should exist if effectiveness increases with adherence. The CAPRISA 004 trial determined that randomization to TFV gel was associated with a significant reduction in risk of HIV acquisition. In our nested case–control study, however, we did not observe a meaningful decrease in the relative odds of infection—TFV versus placebo—as self-reported adherence increased. To the contrary, exploratory sub-group analysis of the case–control data identified greater evidence for a protective effect of TFV gel among participants reporting less than 80 % adherence to the protocol-defined regimen (odds ratio (OR) 0.30; 95 % CI 0.11–0.78) than among those reporting ≥80 % adherence (Odds Ratio 0.81; 95 % CI 0.34–1.92). The small number of cases may have inhibited our ability to detect the hypothesized interaction between adherence and effectiveness. Nonetheless, our results re-emphasize the challenges faced by investigators when adherence may be miss-measured, miss-reported, or confounded with the risk of HIV.     

Celiac Disease and Lymphoma Risk: A Multicentric Case–Control Study in Spain

Celiac disease is a highly prevalent condition frequently misdiagnosed because of heterogeneity of the clinical symptoms. It is well recognized that enteropathy-associated T-cell lymphoma is an uncommon lymphoma type linked to celiac disease; it has also been suggested that other types of lymphomas may be associated with celiac disease. Our aim was to estimate the risk of all lymphoma associated with celiac disease. Serological markers and personal interviews were obtained from 298 consecutive lymphoma cases and 251 matched controls recruited in four Spanish hospitals. Celiac disease was detected in two cases (0.67%; n = 298) and in three controls (1.2%; n = 251). Treated celiac disease was observed in one patient with lymphoma and in two control subjects. In our series, there was no evidence that celiac disease was a risk factor for lymphoma (OR = 0.62, 95% CI = 0.10-3.79). Serological screening for CD is not recommended in people with lymphoma.     

Neural Autoantibody Evaluation in Functional Gastrointestinal Disorders: A Population-Based Case–Control Study

Background  

Our goal is to investigate the serum profile of neural autoantibodies in community-based patients with irritable bowel syndrome (IBS) or functional dyspepsia. The pathogenesis of functional gastrointestinal (GI) disorders, including IBS and dyspepsia, are unknown. Theories range from purely psychological to autoimmune alterations in GI tract neuromuscular function.     

Prevalence and Risk Factors of Cognitive Impairment in Parkinson Disease: A Population-Based Case–Control Study in Taiwan

The aim of this study was to evaluate the Parkinson disease (PD) prevalence of cognitive impairment in Taiwan.The case–control study consisted of 6177 cognitive impairment patients and 24,708 noncognitive impairment as controls for the period of 2006 to 2010 and both of the groups aged ≥50 years. The multivariable logistic regression analyses were used to estimate the odds ratio (OR) for cognitive impairment, and the 95% confidence intervals (CIs) among patients with PD were compared with those of non-PD patients.PD (adjusted odds ratio [aOR] is 3.07, 95% CI 2.76–3.41) is the one of the most contributed risk factors for cognitive impairment. Besides, we found a remarkable result of the diagnosed cognitive impairment of PD that was found highest in the first 6 months (aOR 11.98, 95% CI 8.51–16.86) and then decrease the incident year by year. The PD prevalence in a patient with cognitive impairment in our data present is 12.1% lower than those with truly dementia published previously and documented by western studies.We found a remarkable result of the diagnosed cognitive impairment of PD that was found highest in the first 6 months and then decrease the incident year by year.     

Blood Pressure Control in a Hypertension Telemedicine Intervention: Does Distance to Primary Care Matter?

Although telemedicine may help overcome geographic access barriers, it is unknown whether rural patients receive greater benefits. In a secondary analysis of 503 veterans participating in a hypertension telemedicine study, the authors hypothesized that patients with greater travel distances would have greater improvements in 18‐month systolic blood pressure (SBP). Patients were categorized by telemedicine exposure and travel distance to primary care, derived from zip codes. Comparisons were (1) usual care (UC), distance <30 miles (reference); (2) UC, distance ≥30 miles; (3) telemedicine, distance <30 miles; (4) telemedicine, distance ≥30 miles. Compared with patients receiving UC, distance <30 miles (intercept=127.7), no difference in 18‐month SBP was observed in patients receiving UC, distance ≥30 miles (0.13 mm Hg, 95% confidence interval [−6.6 to 6.8]); telemedicine, distance <30 miles (−1.1 mm Hg [−7.3 to 5.2]); telemedicine, distance ≥30 miles (−0.80 mm Hg [−6.6 to 5.1]). Although telemedicine may help overcome geographic access barriers, additional studies are needed to identify patients most likely to benefit.

Primary care providers manage the majority of the 65 million individuals with hypertension in the United States.¹ However, the primary care workforce is currently unable to meet the demand for clinic visits to manage patients with chronic diseases.², ³ The demand for primary care is expected to increase further with expansion of healthcare availability under the 2010 Patient Protection and Affordable Care Act (PPACA).⁴ Furthermore, our current healthcare system is designed to deliver services primarily through face‐to‐face encounters between a patient and healthcare provider. This model, however, is likely unsustainable as the demand for healthcare services continues to grow.³, ⁵ Telemedicine is the use of telecommunication technologies and the exchange of electronic medical information between different sites to improve patients'' health status.⁶ Telemedicine can support the delivery of health services over geographic distances⁷ and increase access to healthcare services for patients who live in rural areas.⁸ Telemedicine may also provide an alternative to traditional face‐to‐face clinic‐based encounters by increasing the capacity to manage chronic diseases through non–face‐to‐face visits.⁹ Hypertension telemedicine interventions have been shown to improve blood pressure (BP) control in individuals with hypertension.¹⁰, ¹¹ However, in order to optimize the effectiveness of telemedicine interventions in chronic disease management, it is critical to identify characteristics of patients most likely to benefit from this service.Although telemedicine may increase access to healthcare for patients who live in rural areas, it remains unknown whether those patients with greater travel distances to primary care have improved outcomes with telemedicine interventions compared with those with shorter travel distances. Thus, we sought to determine whether distance to primary care modified the response to a telemedicine intervention designed to improve hypertension control among veterans. We hypothesized that greater travel distance to primary care would be associated with a greater reduction in systolic BP (SBP) among veterans enrolled in a hypertension telemedicine study.     

eNOS Genetic Polymorphisms and Cancer Risk: A Meta-Analysis and a Case–Control Study of Breast Cancer

The association between endothelial nitric oxide synthase (eNOS) polymorphisms (intron 4a/b, -786T>C and 894G>T) and cancer risk remains elusive. In addition, no studies focused on their associations with the risk of breast cancer in Chinese Han population. Thus, a meta-analysis was conducted to determine the relationship between eNOS polymorphisms and cancer risk, and then a case–control study in Chinese Han population was performed to assess their associations with breast cancer susceptibility.Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The pooled analysis indicated that eNOS intron 4a/b and -786T>C polymorphisms were significantly associated with an increased risk of overall cancer. In subgroup analyses based on cancer type, the significant association was found between eNOS intron 4a/b polymorphism and prostate cancer risk, eNOS -786T>C polymorphism and risk of prostate, bladder and breast cancers, and eNOS 894G>T polymorphism and breast cancer risk. In subgroup analyses based on ethnicity, eNOS intron 4a/b and -786T>C polymorphisms were associated with an increased risk of cancer in Caucasians. In consistent with our meta-analysis results, a case–control study in Chinese Han population showed significant associations of eNOS -786T>C and 894G>T polymorphisms with the increased risk of breast cancer. In addition, stratified analyses based on pathological type showed that eNOS 894G>T polymorphism was only associated with the risk of infiltrative ductal carcinoma. Stratified analyses by tumor stage showed that eNOS -786T>C polymorphism was only associated with the risk of tumor stage III and IV.In conclusion, our meta-analysis and case–control study suggest that eNOS -786T>C and 894G>T polymorphisms are associated with the increased risk of breast cancer.     

Primary Care Clinicians’ Recognition and Management of Depression: A Model of Depression Care in Real-World Primary Care Practice

BACKGROUND

Depression is prevalent in primary care (PC) practices and poses a considerable public health burden in the United States. Despite nearly four decades of efforts to improve depression care quality in PC practices, a gap remains between desired treatment outcomes and the reality of how depression care is delivered.

OBJECTIVE

This article presents a real-world PC practice model of depression care, elucidating the processes and their influencing conditions.

DESIGN

Grounded theory methodology was used for the data collection and analysis to develop a depression care model. Data were collected from 70 individual interviews (60 to 70 min each), three focus group interviews (n?=?24, 2 h each), two surveys per clinician, and investigators’ field notes on practice environments. Interviews were audiotaped and transcribed for analysis. Surveys and field notes complemented interview data.

PARTICIPANTS

Seventy primary care clinicians from 52 PC offices in the Midwest: 28 general internists, 28 family physicians, and 14 nurse practitioners.

KEY RESULTS

A depression care model was developed that illustrates how real-world conditions infuse complexity into each step of the depression care process. Depression care in PC settings is mediated through clinicians’ interactions with patients, practice, and the local community. A clinician’s interactional familiarity (“familiarity capital”) was a powerful facilitator for depression care. For the recognition of depression, three previously reported processes and three conditions were confirmed. For the management of depression, 13 processes and 11 conditions were identified. Empowering the patient was a parallel process to the management of depression.

CONCLUSIONS

The clinician’s ability to develop and utilize interactional relationships and resources needed to recognize and treat a person with depression is key to depression care in primary care settings. The interactional context of depression care makes empowering the patient central to depression care delivery.     

Risk Factors Involved in Patients with Bleeding Peptic Ulcers: A Case–Control Study

Our objectives were to (1) identify the risk factors involved in patients with peptic ulcer disease and determine if they predict bleeding in these patients, (2) determine the association between these risk factors, and (3) analyze the cost effectiveness of various tests for Helicobacter pylori (H. pylori). Two-hundred and thirty patients were included in our study between January 2004 and June 2005 (128 bleeding peptic ulcer disease patients constituted the cases, 102 nonbleeding ulcer patients constituted the controls). H. pylori infection was assessed by urease test and biopsy from gastric antrum. There was no statistically significant difference between these groups regarding sex, age, or location of ulcer. Nonsteroidal anti-inflammatory drug (NSAID) use was higher in the case group (P < 0.001), and the rate of H. pylori infection was lower in these patients (P < 0.05). There was no interaction between NSAID use and H. pylori infection in predicting bleeding ulcer risk (P = 0.08). Sensitivity and specificity for urease test in detecting H. pylori was 75% and 99.7%, respectively. So a positive urease test does not need confirmation with biopsy, which is cost effective.     

Correlates of Obsessive–Compulsive Disorder in a Sample of HIV-Positive,Methamphetamine-using Men Who have Sex with Men

Substance use has been identified as a risk factor for elevated levels of obsessive–compulsive disorder (OCD). This study examined methamphetamine use and sexual risk behaviors as correlates of OCD in a sample of 245 HIV-positive men having sex with men (MSM) in San Diego, CA. In a logistic regression analysis, OCD was associated with greater frequency of methamphetamine use, more depressive symptoms, seeking out risky venues and risky sexual partners when “high” on methamphetamine, and reporting fewer sex acts in the past 2 months. These data suggest the need for increased awareness and understanding of the role that OCD may play in the drug use behaviors and risky sexual practices of methamphetamine users.     

Incidence and Risks of Congenital Anomalies of Kidney and Urinary Tract in Newborns: A Population-Based Case–Control Study in Taiwan

Congenital anomalies of the kidney and urinary tract (CAKUT) are 1 of the major factors in young adults needing renal replacement therapy, but there is little extensive assessment of their incidence and risk factors. This study aimed to evaluate trends in the incidence of and risk factors for CAKUT among all births in Taiwan.This population-based case–control study design was conducted using the Taiwan national births registry, which contains detailed information about maternal health and characteristics of newborns, supplied by health professionals. Of 1,603,794 newborns registered between 2004 and 2014, 668 infants were reported to have CAKUT. Newborns without congenital anomalies were matched with CAKUT cases by birth year, month, and Apgar score in a ratio of 5:1. Odds ratio (OR) and 95% confidence interval (CI) for developing CAKUT were calculated using a conditional multivariate logistic regression model.The incidence of CAKUT was approximately 4.2 per 10,000 births. The adjusted ORs for CAKUT in newborns associated with maternal age of 20 to 29 (OR, 2.18; 95% CI, 1.11–4.28), or 30 to 39 (OR, 2.29; 95% CI, 1.17–4.51), maternal gestational diabetes (OR, 2.22, 95% CI, 1.06–4.67), maternal thalassemia/hemochromatosis (OR, 2.67; 95% CI, 1.35–5.27), polyhydramnios or oligohydramnios (OR, 9.16; 95% CI, 5.46–15.37), birth parity >1 (OR, 0.27; 95% CI, 0.15–0.50), having a gestational age <37 weeks (OR, 1.48; 95% CI, 1.23–1.78), and being a boy (OR, 1.83; 95% CI, 1.53–2.19). Infants of mother with gestational diabetes were more likely to have congenital anomalies, small gestational age (<37 weeks) and low birth weight.CAKUT are associated with several maternal health risk factors. As Taiwan has the highest prevalence and incidence rates of end-stage renal disease in the world, these findings strongly support the need to develop professional guidelines for prenatal counseling and management of women at risk of adverse birth outcomes, to prevent kidney disease progression and reduce complications.     

Association of 24 bp Duplication of Human CHIT1 Gene with Asthma in a Heterozygous Population of North India: A Case–Control Study

Purpose

CHIT1 is expressed by pulmonary macrophages, which is typically the site of entry for many environmental fungi that may increase the risk of pulmonary fungal infection and lead to hypersensitivity. The conserved expression of this gene in humans suggests its physiological importance in the mammalian lung.

Methods

The present study was conducted with a total of 964 subjects, including 483 healthy controls and 481 asthma patients. DNA samples were extracted from blood, and the genotyping was done using polymerase chain reaction method.

Results

Statistical analysis revealed that the 24 bp duplication in CHIT1 gene polymorphism shows highly significant association in heterozygous (wild/dup) genotype with OR 1.74, 95 % CI (1.29–2.36), and p = 0.000. However, the homozygous mutant genotype (dup/dup) was found to be non-significant with OR 1.06, 95 % CI (0.69–1.63), and p = 0.786. The combination of both wild/dup and dup/dup was also found to be highly significant with OR 1.57, 95 % CI (1.18–2.11), and p = 0.002.

Conclusions

This is the first study conducted in India which reports a significant association between 24 bp duplication in CHIT1 gene polymorphism and asthma in the studied North Indian population.