Disease In High-risk Individuals Research Articles

Screening for pancreatic cancer in high-risk individuals using MRI: optimization of scan techniques to detect small lesions.

Pancreatic cancer has a dismal prognosis in the general population. However, early detection and treatment of disease in high-risk individuals can improve survival, as patients with localized disease and especially patients with lesions smaller than 10mm show greatly improved 5-year survival rates. To achieve early detection through MRI surveillance programs, optimization of imaging is required. Advances in MRI technologies in both hardware and software over the years have enabled reliable detection of pancreatic cancer at a small size and early stage. Standardization of dedicated imaging protocols for the pancreas are still lacking. In this review we discuss state of the art scan techniques, sequences, reduction of artifacts and imaging strategies that enable early detection of lesions. Furthermore, we present the imaging features of small pancreatic cancers from a large cohort of high-risk individuals. Refinement of MRI techniques, increased scan quality and the use of artificial intelligence may further improve early detection and the prognosis of pancreatic cancer in a screening setting.

Understanding Predictors of Crohn’s Disease: Determinants of Altered Barrier Function in Pre-Disease Phase of Crohn’s Disease

Abstract The pathogenesis of Crohn’s disease (CD) remains unknown. The current working theory is that genetic susceptibility influences host–microbe interactions, resulting in chronic inflammation. Case–control studies fail to explain the triggers or pathogenesis of the disease, notably due to confounding factors in patients with established disease. Investigating the pre-disease phase of CD improves the capacity to assess these confounding factors and enables us to identify biomarkers associated with increased risk of CD. The Crohn’s Colitis Canada-Genes, Environment, Microbial (CCC-GEM) project is a prospective cohort of healthy first-degree relatives of patients with CD, allowing us to interrogate the pre-disease phase of CD. The CCC-GEM Project has led to the identification of several demographic, serological, and microbiome composition markers associated with an increased risk of disease in pre-clinical participants. Notably, altered intestinal barrier function, as measured by the fractional urinary excretion of lactulose mannitol ratio, is associated with a significantly increased risk of CD. We review the intrinsic and external factors that are associated with altered intestinal barrier integrity, including genetic risk, subclinical inflammation, serum proteomics, intestinal microbiome composition, and environmental components, such as diet and lifestyle. Providing insights into the factors and mechanisms of altered barrier function contributes to our understanding of the pathogenic mechanisms of CD. These advances may aid in developing strategies for preventing disease in high-risk individuals. Further research and personalized strategies are needed to optimize these mitigation strategies for individuals at-risk for CD.

Identifying Risk Factors Associated with the Development of Diabetic Retinopathy in the Local Population

Objective: To identify the risk factors for developing diabetic retinopathy.
 Study Design: Cross-sectional study.
 Place and Duration of Study: Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, Pak Emirates Military Hospital (PEMH), Rawalpindi and Armed Forces Institute of Ophthalmology (AFIO), Rawalpindi Pakistan,from Jun 2021 to May 2022.
 Methodology: A total of one hundred and fifty participants aged 25-70 years were included in the study. All participants were divided into three equal groups. Group-I was of age and gender-matched healthy individuals (n=50), Group-II was of people with diabetes without retinopathy (n=50), and Group-III was of diabetic patients having retinopathy (n=50). All the data of the participants were recorded on an especially designed proforma, and 5ml of venous blood was also drawn from the subjects to measure serum lipid levels.
 Results: Male gender was more common with 33(66%), 30(60%) and 33(66%) in Group-I, Group-II, and Group-III respectively.Most of the retinopathy cases had sedentary lifestyle 33(66%), poor dietary habits 34(68%), cardiovascular disease 38(76%),diabetic foot ulcers 44(88%) and increased levels of TAGS (p-value 0.001). Nephropathy and smoking showed no significant link with dr.
 Conclusion: It can be concluded that a sedentary lifestyle, poor dietary habits, cardiovascular disease, diabetic foot and increased TAGS may be risk factors for the development of diabetic retinopathy. These findings can help in the early identification and better prognosis of the disease in high-risk individuals.

Immune system-wide Mendelian randomization and triangulation analyses support autoimmunity as a modifiable component in dementia-causing diseases

Immune system and blood–brain barrier dysfunction are implicated in the development of Alzheimer’s and other dementia-causing diseases, but their causal role remains unknown. We performed Mendelian randomization for 1,827 immune system- and blood–brain barrier-related biomarkers and identified 127 potential causal risk factors for dementia-causing diseases. Pathway analyses linked these biomarkers to amyloid-β, tau and α-synuclein pathways and to autoimmunity-related processes. A phenome-wide analysis using Mendelian randomization-based polygenic risk score in the FinnGen study (n = 339,233) for the biomarkers indicated shared genetic background for dementias and autoimmune diseases. This association was further supported by human leukocyte antigen analyses. In inverse-probability-weighted analyses that simulate randomized controlled drug trials in observational data, anti-inflammatory methotrexate treatment reduced the incidence of Alzheimer’s disease in high-risk individuals (hazard ratio compared with no treatment, 0.64, 95% confidence interval 0.49–0.88, P = 0.005). These converging results from different lines of human research suggest that autoimmunity is a modifiable component in dementia-causing diseases.

Current Therapeutics for COVID-19, What We Know about the Molecular Mechanism and Efficacy of Treatments for This Novel Virus.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has caused significant morbidity and mortality worldwide. Though previous coronaviruses have caused substantial epidemics in recent years, effective therapies remained limited at the start of the Coronavirus disease 19 (COVID-19) pandemic. The emergence and rapid spread throughout the globe of the novel SARS-CoV-2 virus necessitated a rapid development of therapeutics. Given the multitude of therapies that have emerged over the last two years and the evolution of data surrounding the efficacy of these therapies, we aim to provide an update on the major clinical trials that influenced clinical utilization of various COVID-19 therapeutics. This review focuses on currently used therapies in the United States and discusses the molecular mechanisms by which these therapies target the SARS-CoV-2 virus or the COVID-19 disease process. PubMed and EMBASE were used to find trials assessing the efficacy of various COVID-19 therapies. The keywords SARS-CoV-2, COVID-19, and the names of the various therapies included in this review were searched in different combinations to find large-scale randomized controlled trials performed since the onset of the COVID-19 pandemic. Multiple therapeutic options are currently approved for the treatment of SARS-CoV-2 and prevention of severe disease in high-risk individuals in both in the inpatient and outpatient settings. In severe disease, a combination of antiviral and immunomodulatory treatments is currently recommended for treatment. Additionally, anti-viral agents have shown promise in preventing severe disease and hospitalization for those in the outpatient setting. More recently, current therapeutic approaches are directed toward early treatment with monoclonal antibodies directed against the SARS-CoV-2 virus. Despite this, no treatment to date serves as a definitive cure and vaccines against the SARS-CoV-2 virus remain our best defense to prevent further morbidity and mortality.

Radiologically isolated syndrome: A single-center, retrospective cohort study

BackgroundRadiologically Isolated Syndrome (RIS) likely represents the earliest detectable form of multiple sclerosis (MS). There are recognized risk factors for conversion of RIS to clinically definite central nervous system (CNS) demyelinating disease. We aim to characterize a new clinical cohort with RIS and to analyze previously established risk factors for conversion to clinically definite disease. MethodsA medical records search was performed for patients who were diagnosed with RIS by their treating neurologist at our institution in Boston, USA, from January 2005 to April 2020. Demographic data, clinical outcomes, and treatment courses were analyzed. The time to first clinical event representing a demyelinating disease attack or last follow up without clinically definite disease was calculated for each person. Hazard ratios (HRs) for known risk factors for the conversion of RIS to clinically definite disease were calculated using Cox proportional hazards models. ResultsOf 89 patients, the median age at RIS diagnosis was 41.0 years (76% female, 8% with a family history of MS and 16% of any autoimmune disorder, 66% never smokers, 40% BMI >30 kg/m2, 45% with spinal cord MRI lesions). Clinically definite disease was observed in 16 patients (18%) during follow-up (median time to first event 3.4 years; median follow-up duration of full cohort 3.8 years). Median EDSS for those who developed clinically definite disease was 1.25 (range: 0–4) at most recent follow up. Of 84 patients with longitudinal brain imaging, 42 (50%) had new demyelinating lesions. Gadolinium-enhancing lesions were seen in 36 patients (43%) at either baseline (n=24) or follow-up (n=12). Most patients had at least one T1-hypointense lesion (n=70, 83%). Five patients underwent ultra-high field MRI (7 Tesla); all were positive for central vein sign, two demonstrated leptomeningeal enhancement, and one was found to have cortical lesions. Out of 30 patients with susceptibility-weighted imaging acquired during routine clinical care, 8 had at least one paramagnetic rim positive lesion. Previously reported risk factors for conversion to MS were not significant: age ≤37 years HR 1.3 (95% confidence interval (CI), 0.47–3.5), male sex 1.5 (95% CI, 0.41–5.2), and spinal cord lesions 1.3 (0.47–3.4). Nearly one-third of RIS patients (n=26) took a disease modifying therapy (DMT) for MS (median total treatment duration on any DMT=2.7 years). The sub-cohort treated with a DMT had a statistically significantly greater number of recognized risk factors for conversion to clinically definite disease compared with the untreated group (p=0.028). Most patients took a DMT for MRI changes demonstrating new demyelinating disease activity (n=16). Dimethyl fumarate (n=9) and glatiramer acetate (n=7) were the most frequently prescribed DMTs. A second-line DMT was started in 10 patients. ConclusionWe characterize a new cohort of RIS patients, demonstrating time to clinically evident demyelinating disease from RIS diagnosis of approximately 3.4 years. Our data suggest that early use of a DMT in RIS may mitigate the impact of recognized risk factors on the occurrence of clinically evident disease and reduce the likelihood of conversion to clinically definite CNS demyelinating disease in high-risk individuals.

Digital Progression Biomarkers as Novel Endpoints in Clinical Trials: A Multistakeholder Perspective.

The burden of Parkinson’s disease (PD) continues to grow at an unsustainable pace particularly given that it now represents the fastest growing brain disease. Despite seminal discoveries in genetics and pathogenesis, people living with PD oftentimes wait years to obtain an accurate diagnosis and have no way to know their own prognostic fate once they do learn they have the disease. Currently, there is no objective biomarker to measure the onset, progression, and severity of PD along the disease continuum. Without such tools, the effectiveness of any given treatment, experimental or conventional cannot be measured. Such tools are urgently needed now more than ever given the rich number of new candidate therapies in the pipeline. Over the last decade, millions of dollars have been directed to identify biomarkers to inform progression of PD typically using molecular, fluid or imaging modalities. These efforts have produced novel insights in our understanding of PD including mechanistic targets, disease subtypes and imaging biomarkers. While we have learned a lot along the way, implementation of robust disease progression biomarkers as tools for quantifying changes in disease status or severity remains elusive. Biomarkers have improved health outcomes and led to accelerated drug approvals in key areas of unmet need such as oncology. Quantitative biomarker measures such as HbA1c a standard test for the monitoring of diabetes has impacted patient care and management, both for the healthcare professionals and the patient community. Such advances accelerate opportunities for early intervention including prevention of disease in high-risk individuals. In PD, progression markers are needed at all stages of the disease in order to catalyze drug development—this allows interventions aimed to halt or slow disease progression (very early) but also facilitates symptomatic treatments at moderate stages of the disease. Recently, attention has turned to the role of digital health technologies to complement the traditional modalities as they are relatively low cost, objective and scalable. Success in this endeavor would be transformative for clinical research and therapeutic development. Consequently, significant investment has led to a number of collaborative efforts to identify and validate suitable digital biomarkers of disease progression.

Prevention strategies for type 1 diabetes: a story of promising efforts and unmet expectations.

A number of studies have investigated primary and secondary prevention strategies for type 1 diabetes (T1D), since early interventions might improve long-term outcomes through the amelioration of immune processes and the preservation of beta-cell mass. Primary prevention trials focus on genetically at-risk individuals prior to the appearance of autoimmunity, whereas secondary prevention trials aim to halt the progression of complete beta-cell destruction in subjects with established islet autoimmunity (IA). Different approaches have been tested so far, focusing on both pharmaceutical (insulin and monoclonal antibodies) and non-pharmaceutical (vitamin D, omega-3 fatty acids, probiotics, and nicotinamide) interventions, as well as on environmental factors that are believed to trigger autoimmunity in T1D (cow's milk, gluten, and bovine insulin). Albeit certain strategies have displayed efficacy in reducing IA development rates, most efforts have been unsuccessful in preventing the onset of the disease in high-risk individuals. Moreover, significant heterogeneity in study designs, included populations, and explored outcomes renders the interpretation of study results challenging. The aim of this narrative review is to present and critically evaluate primary and secondary prevention strategies for T1D, seeking to fill existing knowledge gaps and providing insight into future directions.

ORAL CANCER SCREENING IN NON-INSTITUTIONALIZED OLDER ADULTS LIVING IN RURAL COMMUNITIES OF SOUTHEAST GEORGIA

The older population in the United States is growing at an unprecedented rate. Oral diseases such as oral cancer can affect physical, psychological, and social well-being in older adults. Oral cancer screening can prevent development of the disease in high-risk individuals. The purpose of this research was to assess determinants of preventive oral health behavior including oral cancer screening in noninstitutionalized older adults living in rural/medically underserved communities of southeast Georgia. A mixed methods sequential explanatory design was used. Surveys were administered to 206 individuals aged 50 and older. Phone interviews were conducted with 22 individuals from the survey sample and 11 key informants. The majority of the participants (83.01%) said they had never been examined for oral cancer by a doctor or a dentist. Those who correctly recognized the most common sign of oral cancer were about three times more likely (OR=3.75; 95% CI: 1.04 – 13.50) to have had an exam for oral cancer (p=0.04). The survey participants who lived alone were more likely (OR = 4.39; 95% CI = 0.95 – 20.26) to have been examined for oral cancer (p = 0.05). During the interview, older adult participants rarely mentioned oral cancer with regards to an unhealthy mouth. The interview participants revealed that living alone gave them more time to pay attention to their health. For the older adults, prevention of oral diseases was grounded in the autonomy in their own behaviors, while the key informants saw more macro community and systems- level factors as the solution.

PCSK7 gene variation bridges atherogenic dyslipidemia with hepatic inflammation in NAFLD patients

Dyslipidemia and altered iron metabolism are typical features of nonalcoholic fatty liver disease (NAFLD). Proprotein convertase subtilisin/kexin type 7 (PCSK7) gene variation has been associated with circulating lipids and liver damage during iron overload. The aim of this study was to examine the impact of the PCSK7 rs236918 variant on NAFLD-related traits in 1,801 individuals from the Liver Biopsy Cohort (LBC), 500,000 from the UK Biobank Cohort (UKBBC), and 4,580 from the Dallas Heart Study (DHS). The minor PCSK7 rs236918 C allele was associated with higher triglycerides, aminotransferases, and hepatic inflammation in the LBC (P < 0.05) and with hypercholesterolemia and liver disease in the UKBBC. In the DHS, PCSK7 missense variants were associated with circulating lipids. PCSK7 was expressed in hepatocytes and its hepatic expression correlated with that of lipogenic genes (P < 0.05). The rs236918 C allele was associated with upregulation of a new "intra-PCSK7" long noncoding RNA predicted to interact with the protein, higher hepatic and circulating PCSK7 protein (P < 0.01), which correlated with triglycerides (P = 0.04). In HepG2 cells, PCSK7 deletion reduced lipogenesis, fat accumulation, inflammation, transforming growth factor β pathway activation, and fibrogenesis. In conclusion, PCSK7 gene variation is associated with dyslipidemia and more severe liver disease in high risk individuals, likely by modulating PCSK7 expression/activity.

Abstract P250: Sex-Related Differences in the Associations of Variability in Body Mass Index and Metabolic Health With Incidence of Obesity and Metabolically Unhealthy Status: The Framingham Offspring Study

Introduction: Higher variability of body mass index (BMI) is associated with both cardiometabolic and cardiovascular disease in high-risk individuals. It is unclear, however if variability of BMI impacts metabolic health or obesity risk in healthy adults and if any potential associations vary for women vs. men. Methods: We classified Framingham Offspring cohort participants (n=3,961, mean age 50.8 years, 53.8% women) according to their obesity (BMI ≥30 kg/m 2 ) and metabolic health status (&lt;2 non-obesity NCEP ATPIII conditions) and followed them prospectively 1987 to 2014. BMI and metabolic syndrome (MetS)-associated measures in the top quintile of the variance independent of the mean were classified as being variable. ‘Variable metabolic health’ (VMH) was defined as ≥2 ‘variable’ non-obesity MetS components. We estimated sex-specific incident rate ratios (IRRs) and 95% confidence intervals (95% CIs) for the associations of time-varying obesity, metabolic health status, and variability of BMI and metabolic health with the incidence of obesity and metabolically unhealthy state using Cox proportional hazards regression for interval-censored outcomes with age as the time scale. Results: On follow-up, 567 participants (313 women) developed new-onset obesity over 9,434 person-periods, and 759 individuals (437 women) developed a metabolically unhealthy state over 5,754 person-periods). After adjustment for covariates, being metabolically unhealthy was associated with a greater risk of new-onset obesity among women (153%, 95% CI 96-229%) compared with men (33%, 95% CI: 1, 79%; p sex- difference =0.005). Similarly, BMI variability was associated with a higher risk of becoming metabolically unhealthy in women (134%, 95% CI: 76, 212%) compared with men (-11%, 95% CI: -49, 53% (p sex-difference =0.0007). Among participants without obesity, BMI variability was associated with a greater risk of incident obesity in women (275%, 95% CI: 185, 393%) compared with men (33%, 95% CI: -22, 129% p sex- difference =0.005). Obesity was positively associated with greater risk of incident unhealthy metabolic state in women (157%, 95% CI: 93, 342%) compared to men (16%, 95% CI: -17, 62%; p sex-difference =0.006). Metabolic health did not alter the risk of either outcome among metabolically healthy or unhealthy individuals. Conclusions: Our longitudinal observations in a community-based sample suggest sex-related differences in the associations of variability of BMI and metabolic health on obesity and cardiometabolic risk. Additional investigations are warranted to replicate our findings and elucidate the biological basis for these sex-related differences. .

Transcatheter mitral valve replacement in mitral annulus calcification – “The art of computer simulation”

There is considerable interest in transcatheter prosthetic valve treatment for mitral valve disease in high-risk individuals. Although the presence of mitral annular calcium (MAC) may provide an anchoring zone for such devices, results to date have been modest with reported technical failure rates approaching 30% in specialist centers. This in part relates to the risk of left ventricular outflow tract obstruction and device dislodgment but also to the lack of specific imaging guidelines to plan for such procedures. We present the use of finite element analysis and computer simulation based on cardiac CT in three patients with severe MAC in whom transcatheter devices were considered. In the first two cases, the computer simulations were performed after the clinical procedure and were concordant with the clinical outcome. For the third case, computer simulation was performed prior to the clinical procedure. This indicated unsuitability for transcatheter device deployment and a subsequent medical management was adopted. Overall, our initial results suggest that computer simulation may have the potential to improve patient selection for transcatheter mitral valve replacement in the presence of significant MAC.

The J-shaped Curve for Blood Pressure and Cardiovascular Disease Risk: Historical Context and Recent Updates.

The definition and treatment of hypertension have both changed dramatically over the last century, with recent trials suggesting benefit for lower blood pressure (BP) targets than ever before considered. However, tempering the enthusiasm for more intensive BP targets are long-held concerns that BP reduction below a certain threshold may pose dangers, the so-called "J-curve." In this review, we summarize the evidence for a J-curve in the treatment of hypertension. The Systolic Blood Pressure Intervention Trial (SPRINT) reported that achieving a systolic BP target of 120mmHg reduces cardiovascular disease in high-risk individuals, supporting more intensive BP reduction. However, contemporary observational studies consistently demonstrate a BP J-curve, the threshold of which is often close to the SPRINT target. Studies also suggest that the BP level of this J-curve may vary based on patient characteristics, including age and comorbidities. There is also more compelling evidence for the specific presence of a J-curve between diastolic BP and coronary events, in contrast to conflicting evidence of a J-curve with systolic BP and cardiovascular disease more generally. There is increased risk of coronary events below a diastolic BP of 60-70mmHg. In comparison, the presence of a systolic J-curve is less clear and some persons at high risk may actually benefit from systolic levels down to 120mmHg. Therefore, we suggest a personalized approach to BP management considering individual risks, benefits, and preferences when choosing therapeutic targets. Further, well-designed studies are required to support our suggestions and to define J-curve thresholds more clearly.

Effect of omega-3 fatty acid supplementation on arterial elasticity in patients with familial hypercholesterolaemia on statin therapy

Background and aimsIncreased arterial stiffness is closely linked with raised blood pressure that contributes substantially to enhanced risk of coronary heart disease in high risk individuals with familial hypercholesterolaemia (FH). Omega-3 fatty acid (ω3-FA) supplementation has been demonstrated to lower blood pressure in subjects with a high cardiovascular disease risk. Whether ω3-FA supplementation improves arterial stiffness in FH subjects, on background statin therapy, has yet to be investigated. Method and resultsWe carried out an 8-week randomized, crossover intervention trial to test the effect of 4 g/d ω3-FA supplementation (46% eicosapentaenoic acid and 38% docosahexaenoic acid) on arterial elasticity in 20 adults with FH on optimal cholesterol-lowering therapy. Large and small artery elasticity were measured by pulse contour analysis of the radial artery. ω3-FA supplementation significantly (P < 0.05 in all) increased large artery elasticity (+9%) and reduced systolic blood pressure (−6%) and diastolic blood pressure (−6%), plasma triglycerides (−20%), apoB concentration (−8%). In contrast, ω3-FAs had no significant effect on small artery elasticity. The change in large artery elasticity was not significantly associated with changes in systolic blood pressure or plasma triglyceride concentration. Conclusionsω3-FA supplementation improves large arterial elasticity and arterial blood pressure independent of statin therapy in adults with FH.Clinical Trial Registration: https://www.clinicaltrials.com/NCT01577056.

Overcoming the tyranny of distance: An analysis of outreach visits to optimise secondary prevention of cardiovascular disease in high-risk individuals living in Central Australia.

We examined the logistical challenges of conducting an outreach, secondary prevention program for adults discharged from Alice Springs Hospital following an acute presentation of cardiovascular disease. This represents a sub-study of the Central Australian Heart Protection Study (CAHPS). Clinical, logistic and demographic data were used to examine the characteristics of outreach visits in the intervention arm of the study. Fifty subjects initially allocated to the intervention arm of the trial were studied. Completion of scheduled, plus additional outreach visits according to the intervention protocol. The majority of subjects presented with an acute coronary syndrome (44/50 (88%)) and 31 (62%) were of Indigenous ethnicity. However, Indigenous subjects being younger (53.1 ± 11.1 versus 58.0 ± 11.0 years non-Indigenous) had a more complex risk factor and co-morbid profile, with significantly more diabetes (77% versus 26% P < 0.001), hypertension (81% versus 53% P = 0.04) and renal failure (52% versus 21% P = 0.03). Community of origin of Indigenous subjects was 230 ± 208 km from the hospital versus 61 ± 150 km for non-Indigenous subjects (P = 0.004). Indigenous subjects missed a significantly higher number of scheduled visits at six months (1.39 ± 2.14 versus 0.16 ± 0.50 visits; P = 0.02). However, multivariate analyses suggested that distance did not influence successful completion of visits. These early findings from CAHPS are invaluable to understanding and improving the feasibility of secondary prevention programs for Indigenous adults living with heart disease in remote communities.

Modifiable lifestyle and social factors affect chronic kidney disease in high-risk individuals with type 2 diabetes mellitus

This observational study examined the association between modifiable lifestyle and social factors on the incidence and progression of early chronic kidney disease (CKD) among those with type 2 diabetes. All 6972 people from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) with diabetes but without macroalbuminuria were studied. CKD progression was defined as decline in GFR of more than 5% per year, progression to end-stage renal disease, microalbuminuria, or macroalbuminuria at 5.5 years. Lifestyle/social factors included tobacco and alcohol use, physical activity, stress, financial worries, the size of the social network and education. Adjustments were made for known risks such as age, diabetes duration, GFR, albuminuria, gender, body mass index, blood pressure, fasting plasma glucose, and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers use. Competing risk of death was considered. At study end, 31% developed CKD and 15% had died. The social network score (SNS) was a significant independent risk factor of CKD and death, reducing the risk by 11 and 22% when comparing the third to the first tertile of the SNS (odds ratios of CKD 0.89 and death 0.78). Education showed a significant association with CKD but stress and financial worries did not. Those with moderate alcohol consumption had a significantly decreased CKD risk compared with nonusers. Regular physical activity significantly decreased the risk of CKD. Thus, lifestyle is a determinant of kidney health in people at high cardiovascular risk with diabetes.

Genetic Association of Interferon Gamma Induced Protein-10 (IP-10), &amp;lt;i&amp;gt;CXCL-&amp;lt;/i&amp;gt;10 Gene Polymorphisms with TB Pleurisy Susceptibility in South Indian Population

CXCL-10 known as Interferon gamma-induced protein 10 (IP-10) or small-inducible cytokine 10 is a 8.7 kDa protein, which is secreted in response to IFN-γ by monocytes, endothelial cells and fi-broblasts. It has chemo-attraction for monocytes/macrophages, T cells, NK cells and dendritic cells in promotion of T cell adhesion to endothelial cells. In the present study, we investigated whether polymorphisms in CXCL-10 gene have any role in the manifestation of Tuberculous (TB) pleurisy. Two SNPs in CXCL-10 promoter region (﹣1447A > G and ﹣135G > A) were genotyped in patients with TB Pleurisy (n = 186), Pulmonary TB patients (n = 159) and healthy controls (n = 205) by PCR-RFLP. Disease associations were statistically analyzed by Fisher exact test. At the ﹣135G > A position, the frequencies of genotype GA and allele G were significantly high in TB pleurisy patients compared to healthy controls. While the frequencies of genotype AA and allele A were significantly low in TB pleurisy patients compared to healthy controls. The frequency of haplotype A-G with the combination of 1447A > G and ﹣135G > A was significantly high in TB pleurisy. Our results reveal that genotype GA and allele G at ﹣135G > A position were strongly associated with susceptibility to tuberculous pleurisy. The GA genotype may be a useful genetic marker for early detection of the disease in high risk individuals.

Getting a Grip on NCDs in China: an Evaluation of the Implementation of the Dutch-China Cardiovascular Prevention Program.

PurposeChina has experienced a rapid increase in cardiovascular diseases and related chronic conditions over the last 20 years, and there is now an urgent need for new approaches that can effectively reduce the progression of cardiovascular disease in high-risk individuals. This article reports on the evaluation of the implementation of the Dutch-China Cardiovascular Prevention Program.MethodsA screening questionnaire, based on the Dutch concept of Prevention-Consultation, was distributed among inhabitants in seven communities in Anhui Province, China. This tool categorizes individuals into being at low or high risk according to their responses to a number of self-administered questions. The “high-risk” individuals were then invited to undergo further clinical and laboratory tests, before being offered lifestyle education and counseling. The program is delivered by primary care professionals from local community health service centers (CHSCs). An evaluation of the program’s implementation was undertaken with both program participants and CHSC staff.ResultsThe screening questionnaire was completed by 9067 participants in seven demonstration communities. Thirty percent of these individuals were categorized as high risk according to their scores. About one third of these individuals returned for further clinical and laboratory tests. Almost half of those re-screened participated in lifestyle education classes. Program participants and community health staff provided mostly positive feedback about the program.ConclusionsWhile the program proved acceptable and feasible for delivery by CHSCs and by program participants, additional strategies are required to improve future uptake of both screening and subsequent lifestyle education by those at high risk.

Abstract 17881: Overcoming the Tyranny of Distance- an Analysis of Out-Reach Visits to Optimise Secondary Prevention of Cardiovascular Disease in High Risk Individuals Living in Central Australia

Introduction: Compared to the non-Indigenous of the population, Aboriginal Australians have a life expectancy that is 15-20 years less. Inequitable access to healthcare services (particularly in remote areas) contributes to this phenomenon. Objectives: We examined the logistical challenges of providing outreach visits, as part of an outreach, secondary prevention program in Central Australia for CVD. Methods: Prospective data from the Central Australia Heart Protection Study (n=200), a pragmatic, single-center, randomized study of a nurse-led, family-based, secondary prevention program designed to reduce major cardiac events, were analyzed. Clinical and logistic data were used to examine the characteristics of outreach visits for 50 consecutive subjects initially randomized to the study intervention. Results: Most subjects had presented with an acute coronary syndrome (44/50 [88%]) and 31 (62%) self-identified as Indigenous. Despite a similar gender profile (55% versus 58% Indigenous and non-Indigenous women), Indigenous subjects had a greater risk factor and co-morbid profile, with significantly more diabetes (77% vs. 26% p = 0.0002), hypertension (81% vs. 53% p = 0.04) and renal failure (52% vs. 21% p = 0.03). The community of origin of Indigenous subjects was 230 ± 208 km from the central hospital compared to 61 ± 150 km for the rest (p = 0.004). There was no difference in the number of subjects who missed initial baseline and ad hoc visits attended by the health care team according to ethnicity. However, perhaps reflecting their greater mobility, Indigenous subjects missed a significantly higher number of scheduled visits at 6 months (1.39 ± 2.14 vs. 0.16 ± 0.50 visits; p = 0.02). Finally, multivariate analyses (including all baseline profiling data) suggested that distance from Alice Springs did not influence completion of outreach visits. Conclusions: These data are invaluable to understanding and improving the cost dynamics and impact of secondary prevention for Indigenous adults living with heart disease remote from specialist health services.

Surveillance of chronic obstructive pulmonary disease in high-risk individuals by using regional lung cancer mass screening.

Background and objectivePatients with chronic obstructive pulmonary disease (COPD) are at risk for lung cancer; the diseases have common etiologies, including cigarette smoking. We aimed to clarify the effectiveness of COPD detection using a regional mass-screening program for lung cancer.Materials and methodsA total of 7,067 residents of Togane, Chiba, Japan received lung cancer screening between May and July, 2011. We defined four groups of possible COPD candidates: group A (n=358), positive smoking history, positive chronic respiratory symptoms; group B (n=766), positive smoking history, positive lifestyle-related disease; group C (n=75), passive smoking history, positive chronic respiratory symptoms; and group D (n=301), passive smoking history, positive lifestyle-related disease. Candidates underwent on-site pulmonary function testing (PFT).ResultsThe criteria for COPD candidates were fulfilled in 1,686 of 7,067 individuals (23.9%); 1,500 participants underwent PFT (89%), and 171 (11.4%) were diagnosed with COPD. The overall COPD detection rate was 2.4%. The frequency of COPD was significantly higher in groups A and B than in groups C and D (P=0.048); however, the distribution of COPD grades was similar among the groups (P=0.372). Multiple logistic regression analysis identified male sex, age 60 years or greater, and positive smoking history as risk factors for COPD.ConclusionCOPD screening using a community-based lung cancer-screening program may be effective for disease detection. Individuals who are 60 years of age or older with a positive smoking history should undergo PFT to detect COPD.