Sleep disturbance, stroke, and heart disease events: evidence from the Caerphilly cohort

PubMed Central

Elwood, Peter; Hack, Melissa; Pickering, Janet; Hughes, Janie; Gallacher, John

2006-01-01

Objective To test the hypothesis that sleep disorders are relevant to the risk of ischaemic stroke and ischaemic heart disease events in older men. Design A cohort study. Setting The Caerphilly cohort, a representative population sample of older men in South Wales, UK. Participants 1986 men aged 55–69 years completed a questionnaire on sleep patterns with help from their partners. This asked about symptoms of disturbed sleep: insomnia, snoring, restless legs, obstructive sleep apnoea, and about daytime sleepiness. During the following 10 years 107 men experienced an ischaemic stroke and 213 had an ischaemic heart disease event. Main results Up to one third of the men reported at least one symptom suggestive of sleep disturbance, and one third reported daytime sleepiness. Compared with men who reported no such symptoms, the adjusted relative odds of an ischaemic stroke were significantly increased in men with any sleep disturbance, the strongest association being with sleep apnoea (relative odds 1.97; 1.26 to 3.09). The association with daytime sleepiness was not significant for stroke. Relations with ischaemic heart disease events were all raised in men with symptoms of sleep disturbance, but none was significant, other than daytime sleepiness (relative odds: 1.41; 1.04 to 1.92). There were no significant relations with blood pressure. Conclusion The risk of an ischaemic stroke is increased in men whose sleep is frequently disturbed, and daytime sleepiness is associated with a significant increase in ischaemic heart disease events. PMID:16361457

[Field epidemiological study on news reports that related to public health emergencies].

PubMed

Zhang, Shun-xiang; Li, Xue-mei; Luo, Nian-ci; Mei, Shu-jiang; Jiang, Li-juan

2013-12-01

All news reports (NR) that were related to public health emergency (PHE) were collected from the Southern Metropolis Daily (SMD) to explore the characteristics of epidemiology in the fields. Based on the theory of communication that including both case and text analysis, qualitative analysis on all the NR regarding PHE published in SMD from the years of 2008 to 2012, was carried out and input to database using the EpiData. Numbers of articles as indicators were compared to show the yearly change of different types of events. Various features of the NR including coverage, source of information, location of the incident, style and size of news, with or without editorials etc. were statistically analyzed by SPSS version 18.0. Among all the 998 reports related to PHE, higher proportion was found in the events of Infectious diseases (35.3%) and food safety (34.1%)respectively. Events on vaccines and drugs used for disease prevention and control (8.9%), environmental pollution caused incidents (8.0%)appeared to be less frequent. Events related to occupational disease, poisoning, bioterrorism and biochemical events were rare. Looking at the monthly distribution of reports, we noticed that the peaks occurred in 2008 and in 2009, which were caused by the Melamine-contamination events and the 2009 H1N1 pandemic. Between 2010 and 2012, figures of monthly reports were smooth, including some critical events from the interests of the media. Most events took place in Guangdong province (34.3%) and other provinces (50.9%), with some were from Hong Kong, Macao and Taiwan regions (9.5%). However, international events (5.2%)were less seen. Extensive coverage accounted for 17.6% of all of reports, and 11.5% allotted the editorials or other forms of in-depth reports. Most of the source of reports on infectious diseases and food safety were from the official release, however. The main sources of occupational diseases and poisoning, vaccines and drug incidents, environmental pollution related incidents were reported by active journalists through interview. Reports on hand, foot and mouth disease, influenza, milk safety, AIDS and lead pollution showed continued concern in the past five years by SMD. NR on public health emergencies by SM had encompassed all 10 categories-related events formulated by the Ministry of Health. Sustained and in-depth coverage were more commonly seen. Field-epidemiologists should learn interdisciplinary sciences on the theory and methodology of communication. They also need to interact with media people during the whole processes of public health emergency preparedness and responses.

Serum urate and the risk of major coronary heart disease events.

PubMed Central

Wannamethee, S. G.; Shaper, A. G.; Whincup, P. H.

1997-01-01

OBJECTIVE: To examine the relation between serum urate and the risk of major coronary heart disease events. DESIGN: A prospective study of a male cohort. SETTING: One general practice in each of 24 British towns. SUBJECTS: 7688 men aged 40-59 years at screening. MAIN OUTCOME MEASURES: Fatal and non-fatal coronary heart disease events. RESULTS: There were 1085 major coronary heart disease events during the average follow up period of 16.8 years. Serum urate was significantly associated with a wide range of cardiovascular risk factors including body mass index, alcohol intake, antihypertensive treatment, pre-existing coronary heart disease, serum triglycerides, cholesterol, and diastolic blood pressure. There was a significant positive association between serum urate and risk of coronary heart disease after adjustment for lifestyle factors and disease indicators. This relation was attenuated to non-significance upon additional adjustment for diastolic blood pressure and serum total cholesterol: cholesterol appeared to be the critical factor in attenuating this relation. When the association between serum urate and risk of coronary heart disease was examined by presence and grade of pre-existing coronary heart disease, a positive association was seen only in men with previous definite myocardial infarction, even after full adjustment (P = 0.07). CONCLUSIONS: The relation between serum urate and the risk of coronary heart disease depends heavily upon the presence of pre-existing myocardial infarction and widespread underlying atherosclerosis as well as the clustering of risk factors. Thus serum urate is not a truly independent risk factor for coronary heart disease. Raised serum urate appears to be an integral part of the cluster of risk factors associated with the insulin resistance syndrome that include obesity, raised serum triglycerides, and serum cholesterol. PMID:9326988

Adjusting for Confounding in Early Postlaunch Settings: Going Beyond Logistic Regression Models.

PubMed

Schmidt, Amand F; Klungel, Olaf H; Groenwold, Rolf H H

2016-01-01

Postlaunch data on medical treatments can be analyzed to explore adverse events or relative effectiveness in real-life settings. These analyses are often complicated by the number of potential confounders and the possibility of model misspecification. We conducted a simulation study to compare the performance of logistic regression, propensity score, disease risk score, and stabilized inverse probability weighting methods to adjust for confounding. Model misspecification was induced in the independent derivation dataset. We evaluated performance using relative bias confidence interval coverage of the true effect, among other metrics. At low events per coefficient (1.0 and 0.5), the logistic regression estimates had a large relative bias (greater than -100%). Bias of the disease risk score estimates was at most 13.48% and 18.83%. For the propensity score model, this was 8.74% and >100%, respectively. At events per coefficient of 1.0 and 0.5, inverse probability weighting frequently failed or reduced to a crude regression, resulting in biases of -8.49% and 24.55%. Coverage of logistic regression estimates became less than the nominal level at events per coefficient ≤5. For the disease risk score, inverse probability weighting, and propensity score, coverage became less than nominal at events per coefficient ≤2.5, ≤1.0, and ≤1.0, respectively. Bias of misspecified disease risk score models was 16.55%. In settings with low events/exposed subjects per coefficient, disease risk score methods can be useful alternatives to logistic regression models, especially when propensity score models cannot be used. Despite better performance of disease risk score methods than logistic regression and propensity score models in small events per coefficient settings, bias, and coverage still deviated from nominal.

Predictors and Outcomes of Health–Related Quality of Life in Adults with CKD

PubMed Central

Lash, James P.; Xie, Dawei; Pan, Qiang; DeLuca, Jennifer; Kanthety, Radhika; Kusek, John W.; Lora, Claudia M.; Nessel, Lisa; Ricardo, Ana C.; Wright Nunes, Julie; Fischer, Michael J.

2016-01-01

Background and objectives Low health–related quality of life is associated with increased mortality in patients with ESRD. However, little is known about demographic and clinical factors associated with health–related quality of life or its effect on outcomes in adults with CKD. Design, settings, participants, & measurements Data from 3837 adult participants with mild to severe CKD enrolled in the prospective observational Chronic Renal Insufficiency Cohort and Hispanic Chronic Renal Insufficiency Cohort Studies were analyzed. Health–related quality of life was assessed at baseline with the Kidney Disease Quality of Life-36 and its five subscales: mental component summary, physical component summary, burden of kidney disease (burden), effects of kidney disease (effects), and symptoms and problems of kidney disease (symptoms). Low health–related quality of life was defined as baseline score >1 SD below the mean. Using Cox proportional hazards analysis, the relationships between low health–related quality of life and the following outcomes were examined: (1) CKD progression (50% eGFR loss or incident ESRD), (2) incident cardiovascular events, and (3) all-cause death. Results Younger age, women, low education, diabetes, vascular disease, congestive heart failure, obesity, and lower eGFR were associated with low baseline health–related quality of life (P<0.05). During a median follow-up of 6.2 years, there were 1055 CKD progression events, 841 cardiovascular events, and 694 deaths. Significantly higher crude rates of CKD progression, incident cardiovascular events, and all-cause death were observed among participants with low health–related quality of life in all subscales (P<0.05). In fully adjusted models, low physical component summary, effects, and symptoms subscales were independently associated with a higher risk of incident cardiovascular events and death, whereas low mental component summary was independently associated with a higher risk of death (P<0.05). Low health–related quality of life was not associated with CKD progression. Conclusions Low health–related quality of life across several subscales was independently associated with a higher risk of incident cardiovascular events and death but not associated with CKD progression. PMID:27246012

Current trends in lifestyle-related disease management by general practitioners: a report from the "Heart Care Network" groups.

PubMed

2009-01-01

In Japan, it is believed that guidelines for lifestyle-related disease are used in routine clinical practice, however, there are few reports on the actual rate of healthcare conducted in accordance with these guidelines by general practitioners and on their usefulness in preventing cardiovascular events. Therefore, the Heart Care Network (HCN) groups were organized mainly by general practitioners treating lifestyle diseases in 62 areas of Japan. The HCN has collected data on lifestyle diseases in high-risk patients in routine practices and investigated management conditions, guideline target achievement rates and medication. Additionally, the incidence of cardiovascular events was assessed. We analyzed 14,064 cases. The lipid profile, blood pressure, glycemic control were significantly improved over the 3 years. The incidence of cardiovascular events were significantly reduced by the achievement of target LDL cholesterol, systolic blood pressure and hemoglobin A1c and even after adjustment for age, gender, history of myocardial infarction, the reduction of these lifestyle-related parameters remains significant. These results revealed the current trends in the healthcare activities of general practitioners, the management conditions for lifestyle diseases in CHD high-risk patients and their effects on reducing cardiovascular events.

Cardiovascular disease in live related renal transplantation.

PubMed

Kaul, A; Sharm, R K; Gupta, A; Sinha, N; Singh, U

2011-11-01

Cardiovascular disease has become the leading cause of morbidity and mortality in renal transplant recipients, although its pathogenesis and treatment are poorly understood. Modifiable cardiovascular risk factors and graft dysfunction both play an important role in development of post transplant cardiovascular events. Prevalence of cardiovascular disease was studied in stable kidney transplant patients on cyclosporine based triple immunosuppression in relation to the various risk factors and post transplant cardiovascular events. Analysis of 562 post transplant patients with stable graft function for 6 months, the patients were evaluated for cardiovascular events in post transplant period. Pre and post transplant risk factors were analyzed using the COX proportional hazard model. 174 patients had undergone pre transplant coronary angiography, 15 of these patients underwent coronary revascularization (angioplasty in 12, CABG in 3). The prevalence of CAD was 7.2% in transplant recipients. Of 42 patients with CAD 31 (73.8%) had cardiovascular event in post transplant period. Age > or = 40 yrs, male sex, graft dysfunction, diabetes as primary renal disease, pre transplant cardiovascular event, chronic rejection showed significant correlation in univariate analysis and there was significant between age > or = 40 years (OR = 2.16 with 95% CI, 0.977-4.78) S creatinine > or = 1.4 mg % (OR = 2.40 with 95% CI, 1.20 - 4.82), diabetes as primary disease (OR with 95% CI 3.67, 3.2-14.82), PTDM (OR 3.67, 95% CI 1.45-9.40), pre-transplant cardiovascular disease (OR 4.14, 95% CI .38-13.15) with post transplant cardiovascular event on multivariate analysis. There was poor patient and graft survival among those who suffered post transplant cardiovascular event. The incidence of cardiovascular disease continues to be high after renal transplantation and modifiable risk factors should be identified to prevent occurrence of events in post transplant period.

Sexual intercourse and risk of ischaemic stroke and coronary heart disease: the Caerphilly study

PubMed Central

Ebrahim, S; May, M; Ben, S; McCarron, P; Frankel, S; Yarnell, J; Davey, S

2002-01-01

Objective: To examine the relation between frequency of sexual intercourse and risk of ischaemic stroke and coronary heart disease. Design: Cohort study with 20 year follow up. Setting: The town of Caerphilly, South Wales and five adjacent villages. Subjects: 914 men aged 45–59 years at time of recruitment in 1979 to 1983. Main outcome measures: Ischaemic stroke and coronary heart disease, all first events and fatal events. Results: Of the 914 men studied, 197 (21.5%) reported sexual intercourse less often than once a month, 231 (25.3%) reported sexual intercourse twice or more a week, and the remaining 486 (53.2%) men fell into the intermediate category. Frequency of sexual intercourse was not associated with all first ischaemic stroke events: age adjusted odds ratios (95% CI) for intermediate and low frequency of sexual intercourse of 0.61 (0.32 to 1.16) and 0.71 (0.34 to 1.49) respectively compared with the reference category of high frequency. A graded relation with fatal coronary heart disease events was observed in events recorded up to 10 years. The age adjusted relative risk (95% CI) of fatal coronary heart disease contrasting low frequency of sexual intercourse (that is, less than monthly) with the highest group (at least twice a week) was 2.80 (1.13 to 6.96, test for trend, p=0.04) which was not attenuated by adjustment for a wide range of potential confounders. Longer follow up to 20 years showed attenuation of this risk with odds of 1.69 (95% CI 0.90 to 3.20), contrasting low frequency of sexual intercourse with the highest group. Conclusions: The differential relation between frequency of sexual intercourse, stroke and coronary heart disease suggests that confounding is an unlikely explanation for the observed association with fatal coronary heart disease events. Middle aged men should be heartened to know that frequent sexual intercourse is not likely to result in a substantial increase in risk of strokes, and that some protection from fatal coronary events may be an added bonus. PMID:11812807

C-reactive protein predicts further ischemic events in first-ever transient ischemic attack or stroke patients with intracranial large-artery occlusive disease.

PubMed

Arenillas, Juan F; Alvarez-Sabín, José; Molina, Carlos A; Chacón, Pilar; Montaner, Joan; Rovira, Alex; Ibarra, Bernardo; Quintana, Manuel

2003-10-01

The role of inflammation in intracranial large-artery occlusive disease is unclear. We sought to investigate the relationship between high-sensitivity C-reactive protein (CRP) levels and the risk of further ischemic events in first-ever transient ischemic attack (TIA) or stroke patients with intracranial large-artery occlusive disease. Of a total of 127 consecutive first-ever TIA or ischemic stroke patients with intracranial stenoses detected by transcranial Doppler ultrasonography, 71 fulfilled all inclusion criteria, which included angiographic confirmation. Serum high-sensitivity CRP level was determined a minimum of 3 months after the qualifying event. Patients were followed up during 1 year after blood sampling. Thirteen patients (18.3%) with intracranial large-artery occlusive disease experienced an end point event: 9 cerebral ischemic events, 7 of which were attributable to intracranial large-artery occlusive disease, and 4 myocardial infarctions. Patients in the highest quintile of high-sensitivity CRP level had a significantly higher adjusted odds ratio for new events compared with those in the first quintile (odds ratio, 8.66; 95% CI, 1.39 to 53.84; P=0.01). A high-sensitivity CRP level above the receiver operating characteristic curve cutoff value of 1.41 mg/dL emerged as an independent predictor of new end point events (hazard ratio, 7.14; 95% CI, 1.77 to 28.73; P=0.005) and of further intracranial large-artery occlusive disease-related ischemic events (hazard ratio, 30.67; 95% CI, 3.6 to 255.5; P=0.0015), after adjustment for age, sex, and risk factors. Kaplan-Meier curves showed that a significantly lower proportion of patients with a high-sensitivity CRP >1.41 mg/dL remained free of a new ischemic event (P<0.0001). High-sensitivity CRP serum level predicts further intracranial large-artery occlusive disease-related and any major ischemic events in patients with first-ever TIA or stroke with intracranial large-artery occlusive disease. These findings are consistent with the hypothesis that inflammation may be involved in the progression and complication of intracranial large-artery occlusive disease.

Matters of the heart: cardiovascular disease in U.S. women.

PubMed

Bybee, Kevin A; Stevens, Tracy L

2013-01-01

Cardiovascular disease is the leading cause of death in United States women and accounts for approximately 500,000 deaths annually. Over half of cardiovascular disease-related deaths in women result from coronary artery disease including acute coronary syndromes. This paper reviews gender specific issues in women as they relate to current cardiovascular disease epidemiology, trends in cardiovascular disease epidemiology, coronary artery disease detection, risk factor modification, and prevention of cardiovascular disease-related events.

Using thresholds based on risk of cardiovascular disease to target treatment for hypertension: modelling events averted and number treated

PubMed Central

Baker, Simon; Priest, Patricia; Jackson, Rod

2000-01-01

Objective To estimate the impact of using thresholds based on absolute risk of cardiovascular disease to target drug treatment to lower blood pressure in the community. Design Modelling of three thresholds of treatment for hypertension based on the absolute risk of cardiovascular disease. 5 year risk of disease was estimated for each participant using an equation to predict risk. Net predicted impact of the thresholds on the number of people treated and the number of disease events averted over 5 years was calculated assuming a relative treatment benefit of one quarter. Setting Auckland, New Zealand. Participants 2158 men and women aged 35-79 years randomly sampled from the general electoral rolls. Main outcome measures Predicted 5 year risk of cardiovascular disease event, estimated number of people for whom treatment would be recommended, and disease events averted over 5 years at different treatment thresholds. Results 46 374 (12%) Auckland residents aged 35-79 receive drug treatment to lower their blood pressure, averting an estimated 1689 disease events over 5 years. Restricting treatment to individuals with blood pressure ⩾170/100 mm Hg and those with blood pressure between 150/90-169/99 mm Hg who have a predicted 5 year risk of disease ⩾10% would increase the net number for whom treatment would be recommended by 19 401. This 42% relative increase is predicted to avert 1139/1689 (68%) additional disease events overall over 5 years compared with current treatment. If the threshold for 5 year risk of disease is set at 15% the number recommended for treatment increases by <10% but about 620/1689 (37%) additional events can be averted. A 20% threshold decreases the net number of patients recommended for treatment by about 10% but averts 204/1689 (12%) more disease events than current treatment. Conclusions Implementing treatment guidelines that use treatment thresholds based on absolute risk could significantly improve the efficiency of drug treatment to lower blood pressure in primary care. PMID:10710577

A role of high impact weather events in waterborne disease outbreaks in Canada, 1975 - 2001.

PubMed

Thomas, Kate M; Charron, Dominique F; Waltner-Toews, David; Schuster, Corinne; Maarouf, Abdel R; Holt, John D

2006-06-01

Recent outbreaks of Escherichia coli O157:H7, Campylobacter, and Cryptosporidium have heightened awareness of risks associated with contaminated water supply. The objectives of this research were to describe the incidence and distribution of waterborne disease outbreaks in Canada in relation to preceding weather conditions and to test the association between high impact weather events and waterborne disease outbreaks. We examined extreme rainfall and spring snowmelt in association with 92 Canadian waterborne disease outbreaks between 1975 and 2001, using case-crossover methodology. Explanatory variables including accumulated rainfall, air temperature, and peak stream flow were used to determine the relationship between high impact weather events and the occurrence of waterborne disease outbreaks. Total maximum degree-days above 0 degrees C and accumulated rainfall percentile were associated with outbreak risk. For each degree-day above 0 degrees C the relative odds of an outbreak increased by a factor of 1.007 (95% confidence interval [CI] = 1.002 - 1.012). Accumulated rainfall percentile was dichotomized at the 93rd percentile. For rainfall events greater than the 93rd percentile the relative odds of an outbreak increased by a factor of 2.283 (95% [CI] = 1.216 - 4.285). These results suggest that warmer temperatures and extreme rainfall are contributing factors to waterborne disease outbreaks in Canada. This could have implications for water management and public health initiatives.

Immediate effects of lumacaftor/ivacaftor administration on lung function in patients with severe cystic fibrosis lung disease.

PubMed

Popowicz, Natalia; Wood, Jamie; Tai, Anna; Morey, Sue; Mulrennan, Siobhain

2017-05-01

Safety-data for lumacaftor/ivacaftor (LUM/IVA) combination therapy in patients with severe lung disease (percent predicted forced expiratory volume in 1s [ppFEV 1 ] <40) remain limited. We report immediate post-dose respiratory-related adverse events in 12 patients with severe cystic fibrosis (CF) lung disease (median [IQR] ppFEV 1 : 34 [31-36]) prescribed LUM/IVA. All patients experienced a decline in ppFEV 1 from baseline at 2-hours (median [IQR] relative change: -19 [-21 to -11]%, p<0.001) that persisted at 24-hours but recovered in most patients at 1-month. No pre- and post-differences in bronchodilator response were observed. Ten (83.3%) patients reported non-severe respiratory-related adverse events within 24-hours of LUM/IVA initiation. At 1-month, eight (67%) patients had persistent symptoms and six (50%) were treated for a pulmonary exacerbation. Our results highlight that LUM/IVA respiratory-related adverse events are common in patients with a ppFEV 1 <40. We recommend close assessment of adverse events. Further studies are required to evaluate the efficacy of LUM/IVA in patients with severe lung disease. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Methodology for computing the burden of disease of adverse events following immunization.

PubMed

McDonald, Scott A; Nijsten, Danielle; Bollaerts, Kaatje; Bauwens, Jorgen; Praet, Nicolas; van der Sande, Marianne; Bauchau, Vincent; de Smedt, Tom; Sturkenboom, Miriam; Hahné, Susan

2018-03-24

Composite disease burden measures such as disability-adjusted life-years (DALY) have been widely used to quantify the population-level health impact of disease or injury, but application has been limited for the estimation of the burden of adverse events following immunization. Our objective was to assess the feasibility of adapting the DALY approach for estimating adverse event burden. We developed a practical methodological framework, explicitly describing all steps involved: acquisition of relative or absolute risks and background event incidence rates, selection of disability weights and durations, and computation of the years lived with disability (YLD) measure, with appropriate estimation of uncertainty. We present a worked example, in which YLD is computed for 3 recognized adverse reactions following 3 childhood vaccination types, based on background incidence rates and relative/absolute risks retrieved from the literature. YLD provided extra insight into the health impact of an adverse event over presentation of incidence rates only, as severity and duration are additionally incorporated. As well as providing guidance for the deployment of DALY methodology in the context of adverse events associated with vaccination, we also identified where data limitations potentially occur. Burden of disease methodology can be applied to estimate the health burden of adverse events following vaccination in a systematic way. As with all burden of disease studies, interpretation of the estimates must consider the quality and accuracy of the data sources contributing to the DALY computation. © 2018 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

Identifying Adverse Events Using International Classification of Diseases, Tenth Revision Y Codes in Korea: A Cross-sectional Study.

PubMed

Ock, Minsu; Kim, Hwa Jung; Jeon, Bomin; Kim, Ye-Jee; Ryu, Hyun Mi; Lee, Moo-Song

2018-01-01

The use of administrative data is an affordable alternative to conducting a difficult large-scale medical-record review to estimate the scale of adverse events. We identified adverse events from 2002 to 2013 on the national level in Korea, using International Classification of Diseases, tenth revision (ICD-10) Y codes. We used data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC). We relied on medical treatment databases to extract information on ICD-10 Y codes from each participant in the NHIS-NSC. We classified adverse events in the ICD-10 Y codes into 6 types: those related to drugs, transfusions, and fluids; those related to vaccines and immunoglobulin; those related to surgery and procedures; those related to infections; those related to devices; and others. Over 12 years, a total of 20 817 adverse events were identified using ICD-10 Y codes, and the estimated total adverse event rate was 0.20%. Between 2002 and 2013, the total number of such events increased by 131.3%, from 1366 in 2002 to 3159 in 2013. The total rate increased by 103.9%, from 0.17% in 2002 to 0.35% in 2013. Events related to drugs, transfusions, and fluids were the most common (19 446, 93.4%), followed by those related to surgery and procedures (1209, 5.8%) and those related to vaccines and immunoglobulin (72, 0.3%). Based on a comparison with the results of other studies, the total adverse event rate in this study was significantly underestimated. Improving coding practices for ICD-10 Y codes is necessary to precisely monitor the scale of adverse events in Korea.

Inflammatory bowel disease and cancer response due to anti-CTLA-4: is it in the flora?

PubMed

Carbonnel, Franck; Soularue, Emilie; Coutzac, Clélia; Chaput, Nathalie; Mateus, Christine; Lepage, Patricia; Robert, Caroline

2017-04-01

Checkpoint inhibitors blocking CTLA-4 (ipilimumab) and PD-1 (nivolumab, pembrolizumab) have transfigured our cancer treatment paradigm. However, these drugs can induce immune-related adverse events that share clinical and pathological characteristics with immune-mediated diseases. One of the most severe immune-related adverse event observed with anti-CTLA-4 is an enterocolitis that mirrors naturally occurring inflammatory bowel disease. This paper reviews the clinical, immunological, and microbiota data associated with the immune-related enterocolitis induced by the cancer immunotherapy blocking CTLA-4, ipilimumab. A parallel analysis of the mechanisms underlying inflammatory bowel diseases on the one hand, and anti-CTLA-4-induced colitis on the other hand, stresses the crucial role of the gut microbiota and of resident T reg in the genesis of both iatrogenic and spontaneous inflammatory bowel diseases.

Mobile technologies for disease surveillance in humans and animals.

PubMed

Mwabukusi, Mpoki; Karimuribo, Esron D; Rweyemamu, Mark M; Beda, Eric

2014-04-23

A paper-based disease reporting system has been associated with a number of challenges. These include difficulties to submit hard copies of the disease surveillance forms because of poor road infrastructure, weather conditions or challenging terrain, particularly in the developing countries. The system demands re-entry of the data at data processing and analysis points, thus making it prone to introduction of errors during this process. All these challenges contribute to delayed acquisition, processing and response to disease events occurring in remote hard to reach areas. Our study piloted the use of mobile phones in order to transmit near to real-time data from remote districts in Tanzania (Ngorongoro and Ngara), Burundi (Muyinga) and Zambia (Kazungula and Sesheke). Two technologies namely, digital and short messaging services were used to capture and transmit disease event data in the animal and human health sectors in the study areas based on a server-client model. Smart phones running the Android operating system (minimum required version: Android 1.6), and which supported open source application, Epicollect, as well as the Open Data Kit application, were used in the study. These phones allowed collection of geo-tagged data, with the opportunity of including static and moving images related to disease events. The project supported routine disease surveillance systems in the ministries responsible for animal and human health in Burundi, Tanzania and Zambia, as well as data collection for researchers at the Sokoine University of Agriculture, Tanzania. During the project implementation period between 2011 and 2013, a total number of 1651 diseases event-related forms were submitted, which allowed reporters to include GPS coordinates and photographs related to the events captured. It was concluded that the new technology-based surveillance system is useful in providing near to real-time data, with potential for enhancing timely response in rural remote areas of Africa. We recommended adoption of the proven technologies to improve disease surveillance, particularly in the developing countries.

Utility analysis and calibration of QOL assessment in disease management.

PubMed

Liu, Mo

2018-05-02

In clinical trials, the assessment of health-related quality of life (QOL) (or patient-reported outcome [PRO] measure) has become very popular especially for clinical studies conducted for evaluating clinical benefits of patients with chronic, severe, and/or life threatening diseases. Health-related QOL information and PRO measures are useful for disease management for achieving best clinical practice. In this article, we will focus on health-related QOL assessment. The concept, design, and analysis of health-related QOL in clinical trials are reviewed. Validation of the use of health-related QOL instrument in terms of some key performance characteristics such as accuracy, reliability, sensitivity, and responsibility for assuring quality, integrity, and validity of collected QOL data are discussed. The concept of utility analysis and calibration (e.g., with respect to life events) for achieving the optimization of disease management are proposed. The change of the QOL could be translated into different life events for effective disease management. These translations could evaluate the treatment effect by more directly displaying the change of the QOL.

Risk factors for heart failure in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl.

PubMed

Chin, Melanie P; Wrolstad, Danielle; Bakris, George L; Chertow, Glenn M; de Zeeuw, Dick; Goldsberry, Angie; Linde, Peter G; McCullough, Peter A; McMurray, John J; Wittes, Janet; Meyer, Colin J

2014-12-01

A phase 3 randomized clinical trial was designed to test whether bardoxolone methyl, a nuclear factor erythroid-2-related factor 2 (Nrf2) activator, slows progression to end-stage renal disease in patients with stage 4 chronic kidney disease and type 2 diabetes mellitus. The trial was terminated because of an increase in heart failure in the bardoxolone methyl group; many of the events were clinically associated with fluid retention. We randomized 2,185 patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD) (estimated glomerular filtration rate 15 to <30 mL min(-1) 1.73 m(-2)) to once-daily bardoxolone methyl (20 mg) or placebo. We used classification and regression tree analysis to identify baseline factors predictive of heart failure or fluid overload events. Elevated baseline B-type natriuretic peptide and previous hospitalization for heart failure were identified as predictors of heart failure events; bardoxolone methyl increased the risk of heart failure by 60% in patients with these risk factors. For patients without these baseline characteristics, the risk for heart failure events among bardoxolone methyl- and placebo-treated patients was similar (2%). The same risk factors were also identified as predictors of fluid overload and appeared to be related to other serious adverse events. Bardoxolone methyl contributed to events related to heart failure and/or fluid overload in a subpopulation of susceptible patients with an increased risk for heart failure at baseline. Careful selection of participants and vigilant monitoring of the study drug will be required in any future trials of bardoxolone methyl to mitigate the risk of heart failure and other serious adverse events. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Event-related potentials show taste and risk effects on food evaluation.

PubMed

Ma, Qingguo; Wang, Cuicui; Wu, Yifan; Wang, Xiaoyi

2014-07-09

Tastes and claims about unhealthy food are important factors that affect consumption. This study investigated the correlation of the event-related potential (ERP) of the evaluation of processing of food information with the task of positive judgment. Given the information on possible diseases that arise with food consumption, sweet-tasting food elicited more conflict than salty food, and this conflict was reflected by a negative ERP component at 250-500 ms (N400). Moreover, the late positive wave at 500-800 ms that was evoked by presentation of food with the names of chronic diseases that could arise from the consumption of such food was larger than that evoked when acute diseases were presented. Sweet-tasting food caused a more intense conflict with disease-related risk than salty food, and chronic diseases aroused a stronger emotional fear than acute diseases. These findings provide new insights into the N400 component and the neurocognitive processes of evaluating food combined with taste and risk information.

Spatial event cluster detection using an approximate normal distribution.

PubMed

Torabi, Mahmoud; Rosychuk, Rhonda J

2008-12-12

In geographic surveillance of disease, areas with large numbers of disease cases are to be identified so that investigations of the causes of high disease rates can be pursued. Areas with high rates are called disease clusters and statistical cluster detection tests are used to identify geographic areas with higher disease rates than expected by chance alone. Typically cluster detection tests are applied to incident or prevalent cases of disease, but surveillance of disease-related events, where an individual may have multiple events, may also be of interest. Previously, a compound Poisson approach that detects clusters of events by testing individual areas that may be combined with their neighbours has been proposed. However, the relevant probabilities from the compound Poisson distribution are obtained from a recursion relation that can be cumbersome if the number of events are large or analyses by strata are performed. We propose a simpler approach that uses an approximate normal distribution. This method is very easy to implement and is applicable to situations where the population sizes are large and the population distribution by important strata may differ by area. We demonstrate the approach on pediatric self-inflicted injury presentations to emergency departments and compare the results for probabilities based on the recursion and the normal approach. We also implement a Monte Carlo simulation to study the performance of the proposed approach. In a self-inflicted injury data example, the normal approach identifies twelve out of thirteen of the same clusters as the compound Poisson approach, noting that the compound Poisson method detects twelve significant clusters in total. Through simulation studies, the normal approach well approximates the compound Poisson approach for a variety of different population sizes and case and event thresholds. A drawback of the compound Poisson approach is that the relevant probabilities must be determined through a recursion relation and such calculations can be computationally intensive if the cluster size is relatively large or if analyses are conducted with strata variables. On the other hand, the normal approach is very flexible, easily implemented, and hence, more appealing for users. Moreover, the concepts may be more easily conveyed to non-statisticians interested in understanding the methodology associated with cluster detection test results.

Screening for coronary artery disease in patients with type 2 diabetes: a meta-analysis and trial sequential analysis

PubMed Central

Leitão, Cristiane B; Gross, Jorge L

2017-01-01

Objective To evaluate the efficacy of coronary artery disease screening in asymptomatic patients with type 2 diabetes and assess the statistical reliability of the findings. Methods Electronic databases (MEDLINE, EMBASE, Cochrane Library and clinicaltrials.org) were reviewed up to July 2016. Randomised controlled trials evaluating coronary artery disease screening in asymptomatic patients with type 2 diabetes and reporting cardiovascular events and/or mortality were included. Data were summarised with Mantel-Haenszel relative risk. Trial sequential analysis (TSA) was used to evaluate the optimal sample size to detect a 40% reduction in outcomes. Main outcomes were all-cause mortality and cardiac events (non-fatal myocardial infarction and cardiovascular death); secondary outcomes were non-fatal myocardial infarction, myocardial revascularisations and heart failure. Results One hundred thirty-five references were identified and 5 studies fulfilled the inclusion criteria and totalised 3315 patients, 117 all-cause deaths and 100 cardiac events. Screening for coronary artery disease was not associated with decrease in risk for all-cause deaths (RR 0.95(95% CI 0.66 to 1.35)) or cardiac events (RR 0.72(95% CI 0.49 to 1.06)). TSA shows that futility boundaries were reached for all-cause mortality and a relative risk reduction of 40% between treatments could be discarded. However, there is not enough information for firm conclusions for cardiac events. For secondary outcomes no benefit or harm was identified; optimal sample sizes were not reached. Conclusion Current available data do not support screening for coronary artery disease in patients with type 2 diabetes for preventing fatal events. Further studies are needed to assess the effects on cardiac events. PROSPERO CRD42015026627. PMID:28490559

The influence of baseline risk on the relation between HbA1c and risk for new cardiovascular events and mortality in patients with type 2 diabetes and symptomatic cardiovascular disease.

PubMed

Bots, Sophie H; van der Graaf, Yolanda; Nathoe, Hendrik M W; de Borst, Gert Jan; Kappelle, Jaap L; Visseren, Frank L J; Westerink, Jan

2016-07-19

Strict glycaemic control in patients with type 2 diabetes has proven to have microvascular benefits while the effects on CVD and mortality are less clear, especially in high risk patients. Whether strict glycaemic control would reduce the risk of future CVD or mortality in patients with type 2 diabetes and pre-existing CVD, is unknown. This study aims to evaluate whether the relation between baseline HbA1c and new cardiovascular events or mortality in patients with type 2 diabetes and pre-existing cardiovascular disease (CVD) is modified by baseline vascular risk. A cohort of 1096 patients with type 2 diabetes and CVD from the Second Manifestations of ARTerial Disease (SMART) study was followed. The relation between HbA1c at baseline and future vascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality was evaluated with Cox proportional hazard analyses in a population that was stratified for baseline risk for vascular events as calculated with the SMART risk score. The mean follow-up duration was 6.9 years for all-cause mortality and 6.4 years for vascular events, in which period 243 and 223 cases were reported, respectively. A 1 % increase in HbA1c was associated with a higher risk for all-cause mortality (HR 1.18, 95 % CI 1.06-1.31). This association was also found in the highest SMART risk quartile (HR 1.33, 95 % CI 1.11-1.60). There was no relation between HbA1c and the occurrence of cardiovascular events during follow-up (HR 1.03, 95 % CI 0.91-1.16). The interaction term between HbA1c and SMART risk score was not significantly related to any of the outcomes. In patients with type 2 diabetes and CVD, HbA1c is related to the risk of all-cause mortality, but not to the risk of cardiovascular events. The relation between HbA1c and all-cause mortality in patients with type 2 diabetes and vascular disease is not dependent on baseline vascular risk.

Evaluation of the risk of endocarditis and other cardiovascular events on the basis of the severity of periodontal disease in dogs.

PubMed

Glickman, Lawrence T; Glickman, Nita W; Moore, George E; Goldstein, Gary S; Lewis, Hugh B

2009-02-15

To test the hypothesis that increased severity of periodontal disease in dogs is associated with an increased risk of cardiovascular-related events, such as endocarditis and cardiomyopathy, as well as markers of inflammation. Historical cohort observational study. 59,296 dogs with a history of periodontal disease (periodontal cohort), of which 23,043 had stage 1 disease, 20,732 had stage 2 disease, and 15,521 had stage 3 disease; and an age-matched comparison group of 59,296 dogs with no history of periodontal disease (nonperiodontal cohort). Cox proportional hazard regression models were used to estimate the risk of cardiovascular-related diagnoses and examination findings in dogs as a function of the stage of periodontal disease (1, 2, or 3 or no periodontal disease) over time while controlling for the effect of potential confounding factors. Significant associations were detected between the severity of periodontal disease and the subsequent risk of cardiovascular-related conditions, such as endocarditis and cardiomyopathy, but not between the severity of periodontal disease and the risk of a variety of other common noncardiovascular-related conditions. The findings of this observational study, similar to epidemiologic studies in humans, suggested that periodontal disease was associated with cardiovascular-related conditions, such as endocarditis and cardiomyopathy. Chronic inflammation is probably an important mechanism connecting bacterial flora in the oral cavity of dogs with systemic disease. Canine health may be improved if veterinarians and pet owners place a higher priority on routine dental care.

Bat Predation by Cercopithecus Monkeys: Implications for Zoonotic Disease Transmission.

PubMed

Tapanes, Elizabeth; Detwiler, Kate M; Cords, Marina

2016-06-01

The relationship between bats and primates, which may contribute to zoonotic disease transmission, is poorly documented. We provide the first behavioral accounts of predation on bats by Cercopithecus monkeys, both of which are known to harbor zoonotic disease. We witnessed 13 bat predation events over 6.5 years in two forests in Kenya and Tanzania. Monkeys sometimes had prolonged contact with the bat carcass, consuming it entirely. All predation events occurred in forest-edge or plantation habitat. Predator-prey relations between bats and primates are little considered by disease ecologists, but may contribute to transmission of zoonotic disease, including Ebolavirus.

Relating phylogenetic trees to transmission trees of infectious disease outbreaks.

PubMed

Ypma, Rolf J F; van Ballegooijen, W Marijn; Wallinga, Jacco

2013-11-01

Transmission events are the fundamental building blocks of the dynamics of any infectious disease. Much about the epidemiology of a disease can be learned when these individual transmission events are known or can be estimated. Such estimations are difficult and generally feasible only when detailed epidemiological data are available. The genealogy estimated from genetic sequences of sampled pathogens is another rich source of information on transmission history. Optimal inference of transmission events calls for the combination of genetic data and epidemiological data into one joint analysis. A key difficulty is that the transmission tree, which describes the transmission events between infected hosts, differs from the phylogenetic tree, which describes the ancestral relationships between pathogens sampled from these hosts. The trees differ both in timing of the internal nodes and in topology. These differences become more pronounced when a higher fraction of infected hosts is sampled. We show how the phylogenetic tree of sampled pathogens is related to the transmission tree of an outbreak of an infectious disease, by the within-host dynamics of pathogens. We provide a statistical framework to infer key epidemiological and mutational parameters by simultaneously estimating the phylogenetic tree and the transmission tree. We test the approach using simulations and illustrate its use on an outbreak of foot-and-mouth disease. The approach unifies existing methods in the emerging field of phylodynamics with transmission tree reconstruction methods that are used in infectious disease epidemiology.

The effect of folic acid based homocysteine lowering on cardiovascular events in people with kidney disease: systematic review and meta-analysis.

PubMed

Jardine, Meg J; Kang, Amy; Zoungas, Sophia; Navaneethan, Sankar D; Ninomiya, Toshiharu; Nigwekar, Sagar U; Gallagher, Martin P; Cass, Alan; Strippoli, Giovanni; Perkovic, Vlado

2012-06-13

To systematically review the effect of folic acid based homocysteine lowering on cardiovascular outcomes in people with kidney disease. Systematic review and meta-analysis. Medline, Embase, the Cochrane Library, and ClinicalTrials.gov to June 2011. Randomised trials in people with non-dialysis dependent chronic kidney disease or end stage kidney disease or with a functioning kidney transplant reporting at least 100 patient years of follow-up and assessing the effect of folic acid based homocysteine lowering therapy. No language restrictions were applied. Two reviewers independently extracted data on study setting, design, and outcomes using a standardised form. The primary endpoint was cardiovascular events (myocardial infarction, stroke, and cardiovascular mortality, or as defined by study author). Secondary endpoints included the individual composite components, all cause mortality, access thrombosis, requirement for renal replacement therapy, and reported adverse events, including haematological and neurological events. The effect of folic acid based homocysteine lowering on outcomes was assessed with meta-analysis using random effects models. 11 trials were identified that reported on 4389 people with chronic kidney disease, 2452 with end stage kidney disease, and 4110 with functioning kidney transplants (10,951 participants in total). Folic acid based homocysteine therapy did not prevent cardiovascular events (relative risk 0.97, 95% confidence interval 0.92 to 1.03, P = 0.326) or any of the secondary outcomes. There was no evidence of heterogeneity in subgroup analyses, including those of kidney disease category, background fortification, rates of pre-existing disease, or baseline homocysteine level. The definitions of chronic kidney disease varied widely between the studies. Non-cardiovascular events could not be analysed as few studies reported these outcomes. Folic acid based homocysteine lowering does not reduce cardiovascular events in people with kidney disease. Folic acid based regimens should not be used for the prevention of cardiovascular events in people with kidney disease.

A spatial scan statistic for compound Poisson data.

PubMed

Rosychuk, Rhonda J; Chang, Hsing-Ming

2013-12-20

The topic of spatial cluster detection gained attention in statistics during the late 1980s and early 1990s. Effort has been devoted to the development of methods for detecting spatial clustering of cases and events in the biological sciences, astronomy and epidemiology. More recently, research has examined detecting clusters of correlated count data associated with health conditions of individuals. Such a method allows researchers to examine spatial relationships of disease-related events rather than just incident or prevalent cases. We introduce a spatial scan test that identifies clusters of events in a study region. Because an individual case may have multiple (repeated) events, we base the test on a compound Poisson model. We illustrate our method for cluster detection on emergency department visits, where individuals may make multiple disease-related visits. Copyright © 2013 John Wiley & Sons, Ltd.

Low-Density Lipoprotein Cholesterol, Non-High-Density Lipoprotein Cholesterol, Triglycerides, and Apolipoprotein B and Cardiovascular Risk in Patients With Manifest Arterial Disease.

PubMed

van den Berg, M Johanneke; van der Graaf, Yolanda; de Borst, Gert Jan; Kappelle, L Jaap; Nathoe, Hendrik M; Visseren, Frank L J

2016-09-15

Low-density lipoprotein cholesterol (LDL-C) only partly represents the atherogenic lipid burden, and a growing body of evidence suggests that non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and apolipoprotein B (apoB) are more accurate in estimating lipid-related cardiovascular disease risk. Our objective was to compare the relation among LDL-C, non-HDL-C, triglycerides, and apoB and the occurrence of future vascular events and mortality in patients with manifest arterial disease. This is a prospective cohort study of 7,216 patients with clinically manifest arterial disease in the Secondary Manifestations of Arterial Disease Study. Cox proportional hazard models were used to quantify the risk of major cardiovascular events (MACE; i.e., stroke, myocardial infarction, and vascular mortality) and all-cause mortality. Interaction was tested for type of vascular disease at inclusion. MACE occurred in 1,185 subjects during a median follow-up of 6.5 years (interquartile range 3.4 to 9.9 years). Adjusted hazard ratios (HRs) of MACE per 1 SD higher were for LDL-C (HR 1.15, 95% confidence interval [CI] 1.09 to 1.22), for non-HDL-C (HR 1.17, 95% CI 1.11 to 1.23), for log(triglycerides) (HR 1.12, 95% CI 1.06 to 1.19), and for apoB HR (1.12, 95% CI 0.99 to 1.28). The relation among LDL-C, non-HDL-C, and cardiovascular events was comparable in patients with cerebrovascular disease, coronary artery disease, or polyvascular disease and absent in those with aneurysm of abdominal aorta or peripheral artery disease. In conclusion, in patients with a history of cerebrovascular, coronary artery, or polyvascular disease, but not aneurysm of abdominal aorta or peripheral artery disease, higher levels of LDL-C and non-HDL-C are related to increased risk of future MACE and of comparable magnitude. Copyright © 2016 Elsevier Inc. All rights reserved.

[Late adverse events after concurrent chemoradiation therapy in long-term survivors with non-small cell lung cancer].

PubMed

Hasegawa, Takaaki; Sawa, Toshiyuki; Futamura, Yohei; Horiba, Akane; Ishiguro, Takashi; Yoshida, Tsutomu; Iida, Takayoshi; Marui, Tsutomu

2013-11-01

Long-term survival in patients with non-small cell lung cancer( NSCLC) can be achieved more frequently with combined modality therapy. However, an increased risk of late treatment-related toxicities has been reported for this treatment strategy. We retrospectively evaluated NSCLC patients treated with chemoradiation therapy from January 1988 to January 2007. Patients who had survived for more than 5 years after treatment were included in an analysis of late adverse events (excluding radiation pneumonitis and pulmonary fibrosis). A total of 188 NSCLC patients treated with chemoradiation therapy were evaluated, with 25 patients having survived for more than 5 years. Of these patients, 4 had stage I disease, 4 had stage IIB disease, 1 had stage IIIA disease, 14 had stage IIIB disease, 1 had stage IV disease, and 1 had disease of unknown stage. The following grade 3 late adverse events were noted: skin ulceration( n=1), skin induration( n=1), brachial plexopathy( n=1), malignant neoplasm( n=1). Adequate management of late adverse events due to chemoradiation therapy is needed for long-term NSCLC survivors.

Effect of pravastatin on cardiovascular events and mortality in 1516 women with coronary heart disease: results from the Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) study.

PubMed

Hague, Wendy; Forder, Peta; Simes, John; Hunt, David; Tonkin, Andrew

2003-04-01

The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study showed that cholesterol-lowering therapy prevented further events in patients with coronary heart disease and average cholesterol levels. The aim of this subgroup analysis was to assess the effects of pravastatin in women. A total of 1516 women (756 assigned to take pravastatin) in a cohort of 9014 patients with previous myocardial infarction or unstable angina and a baseline plasma cholesterol level of 4.0 to 7.0 mmol/L (155-271 mg/dL) were assigned to receive pravastatin (40 mg/d) or placebo. Major cardiovascular disease events in 6 years were measured. Women were at a lesser risk than men for death from any cause (10.3% vs 14.8%, P <.01), death from coronary heart disease (6.6% vs 8.6%, P =.04), and coronary revascularization (13.6% vs 16.2%, P =.05) and at a similar risk of myocardial infarction (9.2% vs 10.5%, P =.26), stroke (3.6% vs 4.7%, P =.11), and hospitalization for unstable angina (25.1% vs 24.5%, P = 0.90). Pravastatin significantly reduced the risk of all prespecified cardiovascular events in all LIPID patients. Relative treatment effects in women did not differ significantly from those in men (P >.05) for any events except hospitalization for unstable angina. There were too few events to demonstrate separately significant effects in women; the estimated relative risk reduction with pravastatin was 11% (95% CI -18%-33%) for coronary heart disease death or nonfatal myocardial infarction, 18% (95% CI -25%-46%) for coronary heart disease death, 16% (95% CI -19%-41%) for myocardial infarction, and 17% (95% CI -2%-33%) for coronary heart disease death, myocardial infarction, or coronary revascularization. The study had the largest secondary-prevention female cohort studied thus far, but was not adequately powered to show separate effects in women. Nevertheless, the results were consistent with the main results of this and other trials in showing reduced risks with cholesterol-lowering treatment.

Safety of endoscopic removal of self-expandable stents after treatment of benign esophageal diseases.

PubMed

van Halsema, Emo E; Wong Kee Song, Louis M; Baron, Todd H; Siersema, Peter D; Vleggaar, Frank P; Ginsberg, Gregory G; Shah, Pari M; Fleischer, David E; Ratuapli, Shiva K; Fockens, Paul; Dijkgraaf, Marcel G W; Rando, Giacomo; Repici, Alessandro; van Hooft, Jeanin E

2013-01-01

Temporary placement of self-expandable stents has been increasingly used for the management of benign esophageal diseases. To evaluate the safety of endoscopic removal of esophageal self-expandable stents placed for the treatment of benign esophageal diseases. Multicenter retrospective study. Six tertiary care centers in the United States and Europe. A total of 214 patients with benign esophageal diseases undergoing endoscopic stent removal. Endoscopic stent removal. Endoscopic techniques for stent removal, time to stent removal, and adverse events related to stent removal. A total of 214 patients underwent a total of 329 stent extractions. Stents were mainly placed for refractory strictures (49.2%) and fistulae (49.8%). Of the removed stents, 52% were fully covered self-expandable metal stents (FCSEMSs), 28.6% were partially covered self-expandable metal stents (PCSEMSs), and 19.5% were self-expandable plastic stents. A total of 35 (10.6%) procedure-related adverse events were reported, including 7 (2.1%) major adverse events. Multivariate analysis revealed that use of PCSEMSs (P < .001) was a risk factor for adverse events during stent removal. Favorable factors for successful stent removal were FCSEMSs (P ≤ .012) and stent migration (P = .010). No significant associations were found for stent indwelling time (P = .145) and stent embedding (P = .194). Retrospective analysis, only tertiary care centers. With an acceptable major adverse event rate of 2.1%, esophageal stent removal in the setting of benign disease was found to be a safe and feasible procedure. FCSEMSs were more successfully removed than self-expandable plastic stents and PCSEMSs. Adverse events caused by stent removal were not time dependent. Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Epidemiological Evaluation of Notifications of Environmental Events in the State of São Paulo, Brazil

PubMed Central

Nery, Telma de Cassia dos Santos; Christensen, Rogerio Araujo; Pereira, Farida; Leite, Andre Pereira

2014-01-01

Increasing urbanization across the globe, combined with an increased use of chemicals in various regions, contributes to several environmental events that influence environmental health. Measures that identify environmental factors and events should be introduced to facilitate epidemiological investigations by health services. The Brazilian Ministry of Health published a new list of notifiable diseases on 25 January 2011 and introduced environmental events as a new category of notifiable occurrences. The Center for Epidemiologic Surveillance in State of Sao Paulo, Brazil, created an online notification system that highlights “environmental events”, such as exposure to chemical contaminants, drinking water with contaminants outside of the recommended range, contaminated air, and natural or anthropogenic disasters. This paper analyzed 300 notifications received between May 2011 and May 2012. It reports the number of notifications with event classifications and analyzes the events relating to accidents with chemical substances. This paper describes the characteristics of the accidents that involved chemical substances, methods used, types of substances, exposed population, and measures adopted. The online notification of environmental events increases the analysis of the main events associated with diseases related to environmental chemicals; thus, it facilitates the adoption of public policies to prevent environmental health problems. PMID:25050657

[Exercise for prevention of osteoporosis and other lifestyle-related diseases].

PubMed

Suzuki, Takao

2011-05-01

The prevalence of lifestyle-related diseases including hypertension, dyslipidemia (hyperlipidemia) and diabetes increases with aging, and all these conditions are risk factors of arteriosclerotic diseases such as cerebrovascular event (stroke) and myocardial infarction. The term "metabolic domino" has been used to describe the collective concept of the development and progression of these lifestyle-related diseases, the sequence of events, and the progression process of complications. Like the first tile of a domino toppling game, undesirable lifestyle such as overeating and underexercising first triggers obesity, and is followed in succession by onset of an insulin resistance state (underlied by a genetic background indigenous to Japanese) , hypertension, hyperlipidemia, and further postprandial hyperglycemia (the pre-diabetic state) , the so-called metabolic syndrome, at around the same time. On the other hand, apart from the other lifestyle-related diseases, the prevalence of osteoporosis also increases rapidly accompanying aging. Osteoporosis is known to be strongly related to disorders due to the metabolic domino such as arteriosclerosis and vascular calcification, and a new disease category called "osteo-vascular interaction" has attracted attention recently. Regarding "osteo-vascular interaction" , a close relation between bone density loss or osteoporotic changes and vascular lesion-associated lifestyle-related diseases such as hypertension, dyslipidemia and diabetes has been reported. Therefore, as a common preventive factor for bone mass loss or osteoporosis and lifestyle-related diseases including hypertension, dyslipidemia and diabetes (osteo-vascular interaction) , exercise has been recognized anew as an important non-pharmaceutical therapy that should take top priority. This article overviews the evidence of exercise therapy for the prevention of osteoporosis and other lifestyle-related diseases, from the viewpoint of health promotion, especially of the skeletal system (motor system) .

International Classification of Impairments, Disabilities, and Handicaps: A Manual of Classification Relating to the Consequences of Disease.

ERIC Educational Resources Information Center

World Health Organization, Geneva (Switzerland).

The manual contains three classifications (impairments, disabilities, and handicaps), each relating to a different plane of experience consequent upon disease. Section 1 attempts to clarify the nature of health related experiences by addressing reponse to acute and chronic illness; the unifying framework for classification (principle events in the…

Neuro-Cardio Mechanisms in Huntington's Disease and Other Neurodegenerative Disorders.

PubMed

Critchley, Bethan J; Isalan, Mark; Mielcarek, Michal

2018-01-01

Although Huntington's disease is generally considered to be a neurological disorder, there is mounting evidence that heart malfunction plays an important role in disease progression. This is perhaps not unexpected since both cardiovascular and nervous systems are strongly connected - both developmentally and subsequently in health and disease. This connection occurs through a system of central and peripheral neurons that control cardiovascular performance, while in return the cardiovascular system works as a sensor for the nervous system to react to physiological events. Hence, given their permanent interconnectivity, any pathological events occurring in one system might affect the second. In addition, some pathological signals from Huntington's disease might occur simultaneously in both the cardiovascular and nervous systems, since mutant huntingtin protein is expressed in both. Here we aim to review the source of HD-related cardiomyopathy in the light of recently published studies, and to identify similarities between HD-related cardiomyopathy and other neuro-cardio disorders.

Aspirin for primary prevention of cardiovascular and all-cause mortality events in diabetes: updated meta-analysis of randomized controlled trials.

PubMed

Kunutsor, S K; Seidu, S; Khunti, K

2017-03-01

To evaluate the benefits and harms of aspirin for the primary prevention of cardiovascular disease and all-cause mortality events in people with diabetes by conducting a systematic review and meta-analysis. Randomized controlled trials of aspirin compared with placebo (or no treatment) in people with diabetes with no history of cardiovascular disease were identified from MEDLINE, EMBASE, Web of Science, the Cochrane Library and a manual search of bibliographies to November 2015. Study-specific relative risks with 95% CIs were aggregated using random effects models. A total of 10 randomized trials were included in the review. There was a significant reduction in risk of major adverse cardiovascular events: relative risk of 0.90 (95% CI 0.81-0.99) in groups taking aspirin compared with placebo or no treatment. Limited subgroup analyses suggested that the effect of aspirin on major adverse cardiovascular events differed by baseline cardiovascular disease risk, medication compliance and sex (P for interaction for all > 0.05).There was no significant reduction in the risk of myocardial infarction, coronary heart disease, stroke, cardiovascular mortality or all-cause mortality. Aspirin significantly reduced the risk of myocardial infarction for a treatment duration of ≤ 5 years. There were differences in the effect of aspirin by dosage and treatment duration on overall stroke outcomes (P for interaction for all < 0.05). There was an increase in risk of major or gastrointestinal bleeding events, but estimates were imprecise and not significant. The emerging data do not clearly support guidelines that encourage the use of aspirin for the primary prevention of cardiovascular disease in adults with diabetes who are at increased cardiovascular disease risk. © 2016 Diabetes UK.

Enzyme therapy in Fabry disease: severe adverse events associated with anti-agalsidase cross-reactive IgG antibodies.

PubMed

Tesmoingt, Chloe; Lidove, Olivier; Reberga, Axele; Thetis, Marguerite; Ackaert, Chloe; Nicaise, Pascale; Arnaud, Philippe; Papo, Thomas

2009-11-01

To report a severe adverse event related to enzyme replacement therapy with agalsidase in an hemizygous male patient treated for Fabry disease. Retrospective analysis of clinical, radiological and biochemical data in a patient who suffered adverse events related to both agalsidase alfa and agalsidase beta treatments. A hemizygous male patient was first treated for Fabry disease with agalsidase alfa. After more than 1 year of therapy, infusion-related symptoms necessitated systemic steroids and antihistaminic therapy. Decline in kidney function prompted a switch for agalsidase beta. Anaphylactoid shock occurred after the second infusion. No serum IgE antibodies were disclosed. Skin-test reactivity to agalsidase beta was negative. Following a published rechallenge infusion protocol, agalsidase beta was reintroduced, leading to a second anaphylactoid shock episode. Enzyme replacement therapy was stopped and the patient was treated with symptomatic therapy only. This case was referred to the pharmacovigilance department. The negativity of immunological tests (specific anti-agalsidase IgE antibodies and skin tests) does not rule out the risk of repeated anaphylactoid shock following agalsidase infusion.

Enzyme therapy in Fabry disease: severe adverse events associated with anti-agalsidase cross-reactive IgG antibodies

PubMed Central

Tesmoingt, Chloe; Lidove, Olivier; Reberga, Axele; Thetis, Marguerite; Ackaert, Chloe; Nicaise, Pascale; Arnaud, Philippe; Papo, Thomas

2009-01-01

AIMS To report a severe adverse event related to enzyme replacement therapy with agalsidase in an hemizygous male patient treated for Fabry disease. METHODS Retrospective analysis of clinical, radiological and biochemical data in a patient who suffered adverse events related to both agalsidase alfa and agalsidase beta treatments. RESULTS A hemizygous male patient was first treated for Fabry disease with agalsidase alfa. After more than 1 year of therapy, infusion-related symptoms necessitated systemic steroids and antihistaminic therapy. Decline in kidney function prompted a switch for agalsidase beta. Anaphylactoid shock occurred after the second infusion. No serum IgE antibodies were disclosed. Skin-test reactivity to agalsidase beta was negative. Following a published rechallenge infusion protocol, agalsidase beta was reintroduced, leading to a second anaphylactoid shock episode. Enzyme replacement therapy was stopped and the patient was treated with symptomatic therapy only. This case was referred to the pharmacovigilance department. CONCLUSION The negativity of immunological tests (specific anti-agalsidase IgE antibodies and skin tests) does not rule out the risk of repeated anaphylactoid shock following agalsidase infusion. PMID:19917001

How to measure the outcomes of chronic disease management.

PubMed

Lewis, Al

2009-02-01

The fastest-growing methodology for disease management outcomes measurement is valid, transparent, easy to apply, and freely available in the public domain and this article. It measures the actual goal of disease management, which is to reduce the rate of adverse events associated with the disease(s) being managed. Changes in this rate can be translated into a return on investment using some explicit assumptions about comorbidities and episode costs. Outcomes measured in this way show that in the health plan community as a whole, disease management in the broadest sense is working, as measured by the relative stability in the rate of adverse medical events closely associated with common chronic disease during this decade of increasing prevalence of most of the common chronic conditions.

Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials.

PubMed

Mega, J L; Stitziel, N O; Smith, J G; Chasman, D I; Caulfield, M; Devlin, J J; Nordio, F; Hyde, C; Cannon, C P; Sacks, F; Poulter, N; Sever, P; Ridker, P M; Braunwald, E; Melander, O; Kathiresan, S; Sabatine, M S

2015-06-06

Genetic variants have been associated with the risk of coronary heart disease. In this study, we tested whether or not a composite of these variants could ascertain the risk of both incident and recurrent coronary heart disease events and identify those individuals who derive greater clinical benefit from statin therapy. A community-based cohort study (the Malmo Diet and Cancer Study) and four randomised controlled trials of both primary prevention (JUPITER and ASCOT) and secondary prevention (CARE and PROVE IT-TIMI 22) with statin therapy, comprising a total of 48,421 individuals and 3477 events, were included in these analyses. We studied the association of a genetic risk score based on 27 genetic variants with incident or recurrent coronary heart disease, adjusting for traditional clinical risk factors. We then investigated the relative and absolute risk reductions in coronary heart disease events with statin therapy stratified by genetic risk. We combined data from the different studies using a meta-analysis. When individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient in risk for incident or recurrent coronary heart disease was shown. Compared with the low genetic risk category, the multivariable-adjusted hazard ratio for coronary heart disease for the intermediate genetic risk category was 1·34 (95% CI 1·22-1·47, p<0·0001) and that for the high genetic risk category was 1·72 (1·55-1·92, p<0·0001). In terms of the benefit of statin therapy in the four randomised trials, we noted a significant gradient (p=0·0277) of increasing relative risk reductions across the low (13%), intermediate (29%), and high (48%) genetic risk categories. Similarly, we noted greater absolute risk reductions in those individuals in higher genetic risk categories (p=0·0101), resulting in a roughly threefold decrease in the number needed to treat to prevent one coronary heart disease event in the primary prevention trials. Specifically, in the primary prevention trials, the number needed to treat to prevent one such event in 10 years was 66 in people at low genetic risk, 42 in those at intermediate genetic risk, and 25 in those at high genetic risk in JUPITER, and 57, 47, and 20, respectively, in ASCOT. A genetic risk score identified individuals at increased risk for both incident and recurrent coronary heart disease events. People with the highest burden of genetic risk derived the largest relative and absolute clinical benefit from statin therapy. National Institutes of Health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impact of Extreme Heat Events on Emergency Department Visits in North Carolina (2007-2011).

PubMed

Fuhrmann, Christopher M; Sugg, Margaret M; Konrad, Charles E; Waller, Anna

2016-02-01

Extreme heat is the leading cause of weather-related mortality in the U.S. Extreme heat also affects human health through heat stress and can exacerbate underlying medical conditions that lead to increased morbidity and mortality. In this study, data on emergency department (ED) visits for heat-related illness (HRI) and other selected diseases were analyzed during three heat events across North Carolina from 2007 to 2011. These heat events were identified based on the issuance and verification of heat products from local National Weather Service forecast offices (i.e. Heat Advisory, Heat Watch, and Excessive Heat Warning). The observed number of ED visits during these events were compared to the expected number of ED visits during several control periods to determine excess morbidity resulting from extreme heat. All recorded diagnoses were analyzed for each ED visit, thereby providing insight into the specific pathophysiological mechanisms and underlying health conditions associated with exposure to extreme heat. The most common form of HRI was heat exhaustion, while the percentage of visits with heat stroke was relatively low (<10%). The elderly (>65 years of age) were at greatest risk for HRI during the early summer heat event (8.9 visits per 100,000), while young and middle age adults (18-44 years of age) were at greatest risk during the mid-summer event (6.3 visits per 100,000). Many of these visits were likely due to work-related exposure. The most vulnerable demographic during the late summer heat event was adolescents (15-17 years of age), which may relate to the timing of organized sports. This demographic also exhibited the highest visit rate for HRI among all three heat events (10.5 visits per 100,000). Significant increases (p < 0.05) in visits with cardiovascular and cerebrovascular diseases were noted during the three heat events (3-8%). The greatest increases were found in visits with hypotension during the late summer event (23%) and sequelae during the early summer event (30%), while decreases were noted for visits with hemorrhagic stroke during the middle and late summer events (13-24%) and for visits with aneurysm during the early summer event (15%). Significant increases were also noted in visits with respiratory diseases (5-7%). The greatest increases in this category were found in visits with pneumonia and influenza (16%), bronchitis and emphysema (12%), and COPD (14%) during the early summer event. Significant increases in visits with nervous system disorders were also found during the early summer event (16%), while increases in visits with diabetes were noted during the mid-summer event (10%).

Arterial stiffness and cardiovascular events: the Framingham Heart Study.

PubMed

Mitchell, Gary F; Hwang, Shih-Jen; Vasan, Ramachandran S; Larson, Martin G; Pencina, Michael J; Hamburg, Naomi M; Vita, Joseph A; Levy, Daniel; Benjamin, Emelia J

2010-02-02

Various measures of arterial stiffness and wave reflection have been proposed as cardiovascular risk markers. Prior studies have not assessed relations of a comprehensive panel of stiffness measures to prognosis in the community. We used proportional hazards models to analyze first-onset major cardiovascular disease events (myocardial infarction, unstable angina, heart failure, or stroke) in relation to arterial stiffness (pulse wave velocity [PWV]), wave reflection (augmentation index, carotid-brachial pressure amplification), and central pulse pressure in 2232 participants (mean age, 63 years; 58% women) in the Framingham Heart Study. During median follow-up of 7.8 (range, 0.2 to 8.9) years, 151 of 2232 participants (6.8%) experienced an event. In multivariable models adjusted for age, sex, systolic blood pressure, use of antihypertensive therapy, total and high-density lipoprotein cholesterol concentrations, smoking, and presence of diabetes mellitus, higher aortic PWV was associated with a 48% increase in cardiovascular disease risk (95% confidence interval, 1.16 to 1.91 per SD; P=0.002). After PWV was added to a standard risk factor model, integrated discrimination improvement was 0.7% (95% confidence interval, 0.05% to 1.3%; P<0.05). In contrast, augmentation index, central pulse pressure, and pulse pressure amplification were not related to cardiovascular disease outcomes in multivariable models. Higher aortic stiffness assessed by PWV is associated with increased risk for a first cardiovascular event. Aortic PWV improves risk prediction when added to standard risk factors and may represent a valuable biomarker of cardiovascular disease risk in the community.

Weather and environmental hazards at mass gatherings.

PubMed

Soomaroo, Lee; Murray, Virginia

2012-07-31

Introduction Reviews of mass gathering events have traditionally concentrated on crowd variables that affect the level and type of medical care needed. Weather and environmental hazards at mass gathering events have not been fully researched. This review examines these events and aims to provide future suggestions for event organisers, medical resource planners, and emergency services, including local hospital emergency departments. Methods A review was conducted using computerised data bases: MEDLINE, The Cochrane Library, HMIC and EMBASE, with Google used to widen the search beyond peer-reviewed publications, to identify grey literature. All peer-review literature articles found containing information pertaining to lessons identified from mass gathering disasters due to weather or environmental hazards leading to participant death, injury or illness were analysed and reviewed. Disasters occurring due to crowd variables were not included. These articles were read, analysed, abstracted and summarised. Results 20 articles from literature search were found detailing mass gathering disasters relating directly to weather or environmental hazards from 1988 - 2011, with only 17 cases found within peer-review literature. Two events grey literature from 2011 are due to undergo further inquiry while one article reviews an event originally occurring in 1922. Analysis of cases were categorised in to heat and cold-related events, lightning and storms and disease outbreak. Conclusions Mass gathering events have an enormous potential to place a severe strain on the local health care system, Prior health resource and environmental planning for heat & cold-related illness, lightning & storms, and disease outbreak can advance emergency preparedness and response to potential disasters. Soomaroo L, Murray V. Weather and Environmental Hazards at Mass Gatherings. PLoS Currents Disasters. 2012 Jul 31 KEYWORDS: Mass Gatherings, Disasters, Sporting Events, Festivals, Concerts, Storm, Lightning, Cyclone, Hot-weather illness, Cold-weather illness, Disease, Public Health, Syndromic Surveillance Abbreviations: ALS - Advance Life support; BLS - Basic Life support; ED - Emergency Department; EMS - Emergency Medical Services; PPR - Patient Presentation Rate.

Weather and Environmental Hazards at Mass Gatherings

PubMed Central

Soomaroo, Lee; Murray, Virginia

2012-01-01

Introduction Reviews of mass gathering events have traditionally concentrated on crowd variables that affect the level and type of medical care needed. Weather and environmental hazards at mass gathering events have not been fully researched. This review examines these events and aims to provide future suggestions for event organisers, medical resource planners, and emergency services, including local hospital emergency departments. Methods A review was conducted using computerised data bases: MEDLINE, The Cochrane Library, HMIC and EMBASE, with Google used to widen the search beyond peer-reviewed publications, to identify grey literature. All peer-review literature articles found containing information pertaining to lessons identified from mass gathering disasters due to weather or environmental hazards leading to participant death, injury or illness were analysed and reviewed. Disasters occurring due to crowd variables were not included. These articles were read, analysed, abstracted and summarised. Results 20 articles from literature search were found detailing mass gathering disasters relating directly to weather or environmental hazards from 1988 – 2011, with only 17 cases found within peer-review literature. Two events grey literature from 2011 are due to undergo further inquiry while one article reviews an event originally occurring in 1922. Analysis of cases were categorised in to heat and cold-related events, lightning and storms and disease outbreak. Conclusions Mass gathering events have an enormous potential to place a severe strain on the local health care system, Prior health resource and environmental planning for heat & cold-related illness, lightning & storms, and disease outbreak can advance emergency preparedness and response to potential disasters. Citation: Soomaroo L, Murray V. Weather and Environmental Hazards at Mass Gatherings. PLoS Currents Disasters. 2012 Jul 31 Keywords: Mass Gatherings, Disasters, Sporting Events, Festivals, Concerts, Storm, Lightning, Cyclone, Hot-weather illness, Cold-weather illness, Disease, Public Health, Syndromic Surveillance Abbreviations: ALS – Advance Life support; BLS – Basic Life support; ED – Emergency Department; EMS – Emergency Medical Services; PPR – Patient Presentation Rate PMID:22953242

Multi-state modelling of repeated hospitalisation and death in patients with heart failure: The use of large administrative databases in clinical epidemiology.

PubMed

Ieva, Francesca; Jackson, Christopher H; Sharples, Linda D

2017-06-01

In chronic diseases like heart failure (HF), the disease course and associated clinical event histories for the patient population vary widely. To improve understanding of the prognosis of patients and enable health care providers to assess and manage resources, we wish to jointly model disease progression, mortality and their relation with patient characteristics. We show how episodes of hospitalisation for disease-related events, obtained from administrative data, can be used as a surrogate for disease status. We propose flexible multi-state models for serial hospital admissions and death in HF patients, that are able to accommodate important features of disease progression, such as multiple ordered events and competing risks. Fully parametric and semi-parametric semi-Markov models are implemented using freely available software in R. The models were applied to a dataset from the administrative data bank of the Lombardia region in Northern Italy, which included 15,298 patients who had a first hospitalisation ending in 2006 and 4 years of follow-up thereafter. This provided estimates of the associations of age and gender with rates of hospital admission and length of stay in hospital, and estimates of the expected total time spent in hospital over five years. For example, older patients and men were readmitted more frequently, though the total time in hospital was roughly constant with age. We also discuss the relative merits of parametric and semi-parametric multi-state models, and model assessment and comparison.

[Study on the timeliness of detection and reporting on public health emergency events in China].

PubMed

Li, Ke-Li; Feng, Zi-Jian; Ni, Da-Xin

2009-03-01

To analyze the timeliness of detection and reporting on public health emergency events, and to explore the effective strategies for improving the relative capacity on those issues. We conducted a retrospective survey on 3275 emergency events reported through Public Health Emergency Events Surveillance System from 2005 to the first half of 2006. Developed by county Centers for Disease Control and Prevention, a uniformed self-administrated questionnaire was used to collect data, which would include information on the detection, reporting of the events. For communicable diseases events, the median of time interval between the occurrence of first case and the detection of event was 6 days (P25 = 2, P75 = 13). For food poisoning events and clusters of disease with unknown origin, the medians were 3 hours (P25, P75 = 16) and 1 days (P25 = 0, P75 = 5). 71.54% of the events were reported by the discoverers within 2 hours after the detection. In general, the ranges of time intervals between the occurrence, detection or reporting of the events were different, according to the categories of events. The timeliness of detection and reporting of events could have been improved dramatically if the definition of events, according to their characteristics, had been more reasonable and accessible, as well as the improvement of training program for healthcare staff and teachers.

Work-related posttraumatic stress disorder (PTSD) and other emotional diseases as consequence of traumatic events in public transportation: a systematic review.

PubMed

Clarner, Annika; Graessel, Elmar; Scholz, Johanna; Niedermeier, Alexander; Uter, Wolfgang; Drexler, Hans

2015-07-01

Drivers in public transportation are at risk of experiencing potential traumatic events such as accidents involving persons, collisions, or suicides. In this context, the question arises to what extent psychological traumatization and posttraumatic diseases occur. The aim of this systematic review was to describe the frequency and nature of work-related posttraumatic disorders, to analyze risk and prognostic factors after potentially traumatic events (accidents resulting in damage to property and/or in injury or death), and address sick leave after such events in the realm of public transportation, based on the available literature. Systematic review based on four databases (PubMed, PSYNDEX/MEDLINE, ScienceDirect, PILOTS) between 1980 and June 2013. We identified seven studies (four longitudinal, three cross-sectional) that examine employees after person under train (PUT) events. PTSD prevalences varied broadly between 0.7 and 17 %. The same applies to dysthymia/neurotic depression (1-26 %). However, similarly low prevalences of major depression (1.3-2.8 %) and panic disorder (0.5-1.3 %) have been observed. Risk factors of PTSD comprised individual, work-related, event-related, and prognostic aspects. Following the traumatic event, a total of 69-81 % of the drivers were absent, and if sick leave occurs, this was on average 3-19 days. It became evident that drivers in public transportation run a high risk of sick leave. It was also striking that despite the immense impact of PUT and high number of suicides, only an infinitesimal number of studies exists. Due to various differences (period of follow-up, instrument of measurement and study period), it turned out that the comparability of the results of the studies is limited. For various reasons, further research is urgently needed, as from an occupational health point of view the issue of posttraumatic diseases and implications for fitness for service should be addressed.

Cardiovascular risk in pulmonary alveolar proteinosis.

PubMed

Manali, Effrosyni D; Papadaki, Georgia; Konstantonis, Dimitrios; Tsangaris, Iraklis; Papaioannou, Andriana I; Kolilekas, Likurgos; Schams, Andrea; Kagouridis, Konstantinos; Karakatsani, Anna; Orfanos, Stylianos; Griese, Matthias; Papiris, Spyros A

2016-02-01

We hypothesized that cardiovascular events and/or indices of cardiac dysfunction may be increased in pulmonary alveolar proteinosis (PAP). Systemic and pulmonary arterial hypertension, arrhythmias, pulmonary embolism, stroke and ischemic heart attack were reported. Patients underwent serum anti-GM-CSF antibodies, disease severity score (DSS), Doppler transthoracic echocardiograph, glucose, thyroid hormones, lipids, troponin and pro-Brain natriuretic peptide (BNP) examination. Thirteen patients (8 female) were studied, median age of 47. Pro-BNP inversely related to DLCO% and TLC%; troponin directly related to DSS, age, P(A-a)O2, left atrium-, left ventricle-end-diastole diameter and BMI. On multiple regression analysis DSS was the only parameter significantly and strongly related with troponin (R(2) = 0.776, p = 0.007). No cardiovascular event was reported during follow-up. In PAP cardiovascular risk indices relate to lung disease severity. Therefore, PAP patients could be at increased risk for cardiovascular events. Quantitation of its magnitude and potential links to lungs' physiologic derangement will be addressed in future studies.

Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial.

PubMed

Gulley, James L; Rajan, Arun; Spigel, David R; Iannotti, Nicholas; Chandler, Jason; Wong, Deborah J L; Leach, Joseph; Edenfield, W Jeff; Wang, Ding; Grote, Hans Juergen; Heydebreck, Anja von; Chin, Kevin; Cuillerot, Jean-Marie; Kelly, Karen

2017-05-01

Avelumab, a human Ig-G1 monoclonal antibody targeting PD-L1 and approved in the USA for the treatment of metastatic Merkel cell carcinoma, has shown antitumour activity and an acceptable safety profile in patients with advanced solid tumours in a dose-escalation phase 1a trial. In this dose-expansion cohort of that trial, we assess avelumab treatment in a cohort of patients with advanced, platinum-treated non-small-cell lung cancer (NSCLC). In this dose-expansion cohort of a multicentre, open-label, phase 1 study, patients with progressive or platinum-resistant metastatic or recurrent NSCLC were enrolled at 58 cancer treatment centres and academic hospitals in the USA. Eligible patients had confirmed stage IIIB or IV NSCLC with squamous or non-squamous histology, measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), tumour biopsy or archival sample for biomarker assessment, and Eastern Cooperative Oncology Group performance status 0 or 1, among other criteria. Patient selection was not based on PD-L1 expression or expression of other biomarkers, including EGFR or KRAS mutation or ALK translocation status. Patients received infusional avelumab monotherapy 10 mg/kg every 2 weeks until disease progression or toxicity. The primary objective was to assess safety and tolerability. This trial is registered with ClinicalTrials.gov, number NCT01772004; enrolment in this cohort is closed and the trial is ongoing. Between Sept 10, 2013, and June 24, 2014, 184 patients were enrolled and initiated treatment with avelumab. Median follow-up duration was 8·8 months (IQR 7·2-11·9). The most common treatment-related adverse events of any grade were fatigue (46 [25%] of 184 patients), infusion-related reaction (38 [21%]), and nausea (23 [13%]). Grade 3 or worse treatment-related adverse events occurred in 23 (13%) of 184 patients; the most common (occurring in more than two patients) were infusion-related reaction (four [2%] patients) and increased lipase level (three [2%]). 16 (9%) of 184 patients had a serious adverse event related to treatment with avelumab, with infusion-related reaction (in four [2%] patients) and dyspnoea (in two [1%]) occurring in more than one patient. Serious adverse events irrespective of cause occurred in 80 (44%) of 184 patients. Those occurring in more than five patients (≥3%) were dyspnoea (ten patients [5%]), pneumonia (nine [5%]), and chronic obstructive pulmonary disease (six [3%]). Immune-related treatment-related events occurred in 22 patients (12%). Of 184 patients, 22 (12% [95% CI 8-18]) achieved a confirmed objective response, including one complete response and 21 partial responses. 70 (38%) had stable disease. Overall, 92 (50%) of 184 patients achieved disease control (they had a confirmed response or stable disease as their best overall response). One patient was initially thought to have died from grade 5 radiation pneumonitis during the study; however, this adverse event was subsequently regraded to grade 3 and the death was attributed to disease progression. Avelumab showed an acceptable safety profile and antitumour activity in patients with progressive or treatment-resistant NSCLC, providing a rationale for further studies of avelumab in this disease setting. Merck KGaA and Pfizer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Incidence and Risk Factors for Perioperative Cardiovascular and Respiratory Adverse Events in Pediatric Patients With Congenital Heart Disease Undergoing Noncardiac Procedures.

PubMed

Lee, Sandra; Reddington, Elise; Koutsogiannaki, Sophia; Hernandez, Michael R; Odegard, Kirsten C; DiNardo, James A; Yuki, Koichi

2018-04-27

While mortality and adverse perioperative events after noncardiac surgery in children with a broad range of congenital cardiac lesions have been investigated using large multiinstitutional databases, to date single-center studies addressing adverse outcomes in children with congenital heart disease (CHD) undergoing noncardiac surgery have only included small numbers of patients with significant heart disease. The primary objective of this study was to determine the incidences of perioperative cardiovascular and respiratory events in a large cohort of patients from a single institution with a broad range of congenital cardiac lesions undergoing noncardiac procedures and to determine risk factors for these events. We identified 3010 CHD patients presenting for noncardiac procedures in our institution over a 5-year period. We collected demographic information, including procedure performed, cardiac diagnosis, ventricular function as assessed by echocardiogram within 6 months of the procedure, and classification of CHD into 3 groups (minor, major, or severe CHD) based on residual lesion burden and cardiovascular functional status. Characteristics related to conduct of anesthesia care were also collected. The primary outcome variables for our analysis were the incidences of intraoperative cardiovascular and respiratory events. Univariable and multivariable logistic regressions were used to determine risk factors for these 2 outcomes. The incidence of cardiovascular events was 11.5% and of respiratory events was 4.7%. Univariate analysis and multivariable analysis demonstrated that American Society of Anesthesiologists (≥3), emergency cases, major and severe CHD, single-ventricle physiology, ventricular dysfunction, orthopedic surgery, general surgery, neurosurgery, and pulmonary procedures were associated with perioperative cardiovascular events. Respiratory events were associated with American Society of Anesthesiologists (≥4) and otolaryngology, gastrointestinal, general surgery, and maxillofacial procedures. Intraoperative cardiovascular events and respiratory events in patients with CHD were relatively common. While cardiovascular events were highly associated with cardiovascular status, respiratory events were not associated with cardiovascular status.

Efficacy and safety of apatinib combined with transarterial chemoembolization for hepatocellular carcinoma with portal venous tumor thrombus: a retrospective study.

PubMed

Liu, Changfu; Xing, Wenge; Si, Tongguo; Yu, Haipeng; Guo, Zhi

2017-11-21

To investigate the efficacy and safety of combined therapy with apatinib and transarterial chemoembolization (TACE) for hepatocellular carcinoma with portal venous tumor thrombus (PVTT). We retrospectively analyzed 19 patients with hepatocellular carcinoma with PVTT who were treated with apatinib and TACE at a single center between January 2015 and January 2017. Clinical information on the patients was collected. Adverse events, overall survival, progression-free survival, objective response rate, and disease-control rate based on mRECIST criteria (American Association for the Study of Liver Diseases, 2008) were reviewed and evaluated. All patients had complete follow-up records and the median follow-up time was 13 months (1-24 months). Among the 19 patients, 63.16% achieved a partial response and 21.05% achieved stable disease. The objective response and disease-control rates for the tumor were 63.16% and 84.21%, respectively, and the objective response and disease-control rates for PVTT were 10.93% and 89.47%, respectively. The median overall survival was 11.9 months, and the 6-month and 1-year overall survival rates were 94.7% and 48.8%, respectively. The median progression-free survival rate was 8.1 months, and the 6-month and 1-year rates were 73.3% and 22.9%, respectively. The most common apatinib-related adverse events were hand-foot-skin reaction, fatigue, dyspepsia, diarrhea, and hypertension, and the most common TACE-related adverse event was fever. No procedure-related mortality or grade 4 adverse events were observed, but grade 3 adverse events were observed in two patients. This exploratory study suggested that apatinib combined with TACE treatment was safe and might improve overall and progression-free survival in patients with hepatocellular carcinoma with PVTT. Further randomized controlled trials are needed to clarify the potential role of apatinib in hepatocellular carcinoma with PVTT.

Comparison of Body Weight Trend Algorithms for Prediction of Heart Failure Related Events in Home Care Setting.

PubMed

Eggerth, Alphons; Modre-Osprian, Robert; Hayn, Dieter; Kastner, Peter; Pölzl, Gerhard; Schreier, Günter

2017-01-01

Automatic event detection is used in telemedicine based heart failure disease management programs supporting physicians and nurses in monitoring of patients' health data. Analysis of the performance of automatic event detection algorithms for prediction of HF related hospitalisations or diuretic dose increases. Rule-Of-Thumb and Moving Average Convergence Divergence (MACD) algorithm were applied to body weight data from 106 heart failure patients of the HerzMobil-Tirol disease management program. The evaluation criteria were based on Youden index and ROC curves. Analysis of data from 1460 monitoring weeks with 54 events showed a maximum Youden index of 0.19 for MACD and RoT with a specificity > 0.90. Comparison of the two algorithms for real-world monitoring data showed similar results regarding total and limited AUC. An improvement of the sensitivity might be possible by including additional health data (e.g. vital signs and self-reported well-being) because body weight variations obviously are not the only cause of HF related hospitalisations or diuretic dose increases.

Cumulative clinical trial data on atorvastatin for reducing cardiovascular events: the clinical impact of atorvastatin.

PubMed

Bybee, Kevin A; Lee, John H; O'Keefe, James H

2008-04-01

Since the 1990s a multitude of statin trials have definitively demonstrated the ability of statin therapy to reduce the risk of adverse coronary heart disease (CHD) events. Among these, the Atorvastatin Landmarks program - a group of 32 major atorvastatin trials - has assessed the efficacy and safety of atorvastatin across its full dose range and has helped illustrate its effectiveness in treatment of cardiovascular disease and its related disorders and also in non-cardiovascular outcomes. This paper will review the major atorvastatin clinical trials and report the important findings and their clinical significance. Clinical trials with atorvastatin have established significant reductions in cardiovascular events in patients with and without CHD. Studies show that high-dose atorvastatin will reduce LDL to approximately 70 mg/dL in many patients and improve cardiac outcomes. Current evidence suggests that high-dose atorvastatin can halt and, in some cases, reverse atherosclerotic progression. A study of diabetic patients showed atorvastatin decreased the occurrence of acute CHD events, coronary revascularizations, and stroke. Atorvastatin has been found to be effective for reducing nonfatal myocardial infarctions and fatal CHD in hypertensive patients with three or more additional risk factors. High-dose atorvastatin was found to be effective in reducing risk of recurrent stroke in patients with prior cerebrovascular events, has been shown to benefit patients suffering a recent acute coronary syndrome, and to slow cognitive decline in preliminary studies of patients with Alzheimer's disease. Atorvastatin has been associated with reduced progression of mild chronic kidney disease; however, in a randomized trial of patients with end stage renal disease on hemodialysis, atorvastatin showed no statistically significant benefit. Limitations of this review include lack of generalizability of the atorvastatin trial data to other statins, lack of head to head outcome trials involving the newer more potent statins, and the relatively short study durations (none exceeded 5 years) when atherosclerosis is typically a decades-long disease. A compelling body of evidence documents that atorvastatin reduces major cardiovascular events in both secondary and primary prevention of CHD and in a broad range of patients and disease conditions. Furthermore, throughout its dose range, atorvastatin is safe and well tolerated.

The shackles of misfortune: social adversity assessment and representation in a chronic-disease epidemiological setting.

PubMed

Surtees, Paul G; Wainwright, Nicholas W J

2007-01-01

Research evidence is accumulating to support an association between social adversity and the development of predisease processes and physical disease outcomes. While methodological advances have been achieved in the assessment of social adversity, significant barriers remain to their adoption in chronic disease epidemiological settings consequent upon the need to limit participant burden and restrictions imposed by cohort size and cost. A large-scale population-based cohort study, as part of the European Prospective Investigation into Cancer, Norfolk, UK, provided an opportunity to include a comprehensive postal assessment of social adversity. A total of 20,921 participants reported details of 16,031 adverse circumstances during childhood, 119,056 life events and 106,170 person-years of difficulties experienced during adulthood. Impact and adaptation indices were constructed from responses to questions regarding specific life events experienced. There was no evidence that younger participants reported more difficulties in childhood than those who were older, and no evidence of clustering of loss events involving the death of first degree relatives according to their recency. However, there was evidence of recall bias for events not involving loss with increased event rates observed in the few years immediately prior to questionnaire completion. Women reported similar events as more upsetting, and that they took longer to get over their effects, than men. Difficulties experienced in childhood, life events and difficulties in adulthood, event impact and adaptation were all associated with worse physical functional health. Reported slow adaptation to the effects of life events was associated with the largest decrement in physical functional health. These findings strengthen the rationale for including a collection of comprehensive social adversity data within chronic disease epidemiological settings and offer promise for aiding understanding of individual differences in physical disease aetiology.

The Modification of Diet in Renal Disease 4-calculated glomerular filtration rate is a better prognostic factor of cardiovascular events than classical cardiovascular risk factors in patients with peripheral arterial disease.

PubMed

Romero, Jose-María; Bover, Jordi; Fite, Joan; Bellmunt, Sergi; Dilmé, Jaime-Félix; Camacho, Mercedes; Vila, Luis; Escudero, Jose-Román

2012-11-01

Risk prediction is important in medical management, especially to optimize patient management before surgical intervention. No quantitative risk scores or predictors are available for patients with peripheral arterial disease (PAD). Surgical risk and prognosis are usually based on anesthetic scores or clinical evaluation. We suggest that renal function is a better predictor of risk than other cardiovascular parameters. This study used the four-variable Modification of Diet in Renal Disease (MDRD-4)-calculated glomerular filtration rate (GFR) to compare classical cardiovascular risk factors with prognosis and cardiovascular events of hospitalized PAD patients. The study evaluated 204 patients who were admitted for vascular intervention and diagnosed with grade IIb, III, or IV PAD or with carotid or renal stenosis. Those with carotid or renal stenosis were excluded, leaving 188 patients who were randomized from 2004 to 2005 and monitored until 2010. We performed a life-table analysis with a 6-year follow-up period and one final checkpoint. The following risk factors were evaluated: age, sex, ischemic heart disease, ictus (as a manifestation of cerebrovascular disease related to systemic arterial disease), diabetes, arterial hypertension, dyslipidemia, smoking, chronic obstructive pulmonary disease, type of vascular intervention, and urea and creatinine plasma levels. The GFR was calculated using the MDRD-4 equation. Death, major cardiovascular events, and reintervention for arterial disease were recorded during the follow-up. Patients (73% men) were a mean age of 71.38 ± 11.43 (standard deviation) years. PAD grade IIb was diagnosed in 41 (20%) and grade III-IV in 147 (72%). Forty-two minor amputations (20.6%), 21 major amputations (10.3%), and 102 revascularizations (50%) were performed. A major cardiovascular event occurred in 60 patients (29.4%), and 71 (34.8%) died. Multivariate logistic regression analysis showed that the MDRD-4 GFR, age, and male sex were independent variables related to death and that the MDRD-4 GFR and chronic obstructive pulmonary disease were related to major cardiovascular events. A statistically significant relationship was also found between serum creatinine levels and reintervention rates. The MDRD-4 GFR was a better predictor of risk of death or infarction than classical cardiovascular risk factors in patients with PAD. This suggests that its routine use in the initial evaluation in patients with PAD is beneficial. Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Pre-event smallpox vaccination for healthcare workers revisited--the need for a carefully screened multidisciplinary cadre.

PubMed

Malone, John D

2007-03-01

As healthcare institutions are a focus of smallpox transmission early in an epidemic, several mathematical models support pre-event smallpox vaccination of healthcare workers (HCWs). The deciding factor for HCW voluntary vaccination is the risk of disease exposure versus the risk of vaccine adverse events. In a United States military population, with careful screening to exclude atopic dermatitis/eczema and immunosuppression, over 1 million vaccinia (smallpox) vaccinations were delivered with one fatality attributed to vaccination. Among 37901 United States civilian volunteer HCWs vaccinated, 100 serious adverse events were reported including 10 ischemic cardiac episodes and six myocardial infarctions - two were fatal. This older population had a higher rate of adverse events due to age-related coronary artery disease. T-cell mediated inflammatory processes induced by live vaccinia vaccination may have a role in the observed acute coronary artery events. With exclusion of individuals at risk for coronary artery disease, atopic dermatitis/eczema, and immunosuppression, HCWs can be smallpox vaccinated with minimal risk. A carefully screened multidisciplinary cadre (physician, nurse, infection control practitioner, technician), pre-event vaccinated for smallpox, will supply the necessary leadership to alleviate fear and uncertainty while limiting spread and initial mortality of smallpox.

Mining heart disease risk factors in clinical text with named entity recognition and distributional semantic models.

PubMed

Urbain, Jay

2015-12-01

We present the design, and analyze the performance of a multi-stage natural language processing system employing named entity recognition, Bayesian statistics, and rule logic to identify and characterize heart disease risk factor events in diabetic patients over time. The system was originally developed for the 2014 i2b2 Challenges in Natural Language in Clinical Data. The system's strengths included a high level of accuracy for identifying named entities associated with heart disease risk factor events. The system's primary weakness was due to inaccuracies when characterizing the attributes of some events. For example, determining the relative time of an event with respect to the record date, whether an event is attributable to the patient's history or the patient's family history, and differentiating between current and prior smoking status. We believe these inaccuracies were due in large part to the lack of an effective approach for integrating context into our event detection model. To address these inaccuracies, we explore the addition of a distributional semantic model for characterizing contextual evidence of heart disease risk factor events. Using this semantic model, we raise our initial 2014 i2b2 Challenges in Natural Language of Clinical data F1 score of 0.838 to 0.890 and increased precision by 10.3% without use of any lexicons that might bias our results. Copyright © 2015 Elsevier Inc. All rights reserved.

Multivariate Bayesian modeling of known and unknown causes of events--an application to biosurveillance.

PubMed

Shen, Yanna; Cooper, Gregory F

2012-09-01

This paper investigates Bayesian modeling of known and unknown causes of events in the context of disease-outbreak detection. We introduce a multivariate Bayesian approach that models multiple evidential features of every person in the population. This approach models and detects (1) known diseases (e.g., influenza and anthrax) by using informative prior probabilities and (2) unknown diseases (e.g., a new, highly contagious respiratory virus that has never been seen before) by using relatively non-informative prior probabilities. We report the results of simulation experiments which support that this modeling method can improve the detection of new disease outbreaks in a population. A contribution of this paper is that it introduces a multivariate Bayesian approach for jointly modeling both known and unknown causes of events. Such modeling has general applicability in domains where the space of known causes is incomplete. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Does Distress Tolerance Moderate the Impact of Major Life Events on Psychosocial Variables and Behaviors Important in the Management of HIV?

ERIC Educational Resources Information Center

O'Cleirigh, Conall; Ironson, Gail; Smits, Jasper A. J.

2007-01-01

Living with HIV involves management of multiple stressful disease-related and other life events. Distress tolerance may provide a functional, individual-based context for qualifying the established relationships between major life events and psychosocial variables important in the management of HIV. The present study provided a preliminary test of…

Alcohol and ischaemic heart disease in middle aged British men.

PubMed Central

Shaper, A G; Phillips, A N; Pocock, S J; Walker, M

1987-01-01

The relation between alcohol intake and ischaemic heart disease was examined in a large scale prospective study of middle aged men drawn from general practices in 24 British towns. After an average follow up of 6.2 years 335 of the 7729 men had experienced a myocardial infarction (fatal or non-fatal) or sudden cardiac death. No significant relation was found between reported alcohol intake and the incidence of such events. Though the group of light daily drinkers had the lowest incidence of ischaemic heart disease events, it also contained the lowest proportion of current smokers, had the lowest mean blood pressure, had the lowest mean body mass index, and contained the lowest proportion of manual workers. These characteristics are more likely to account for the apparent protective effect of alcohol against ischaemic heart disease than a direct effect of alcohol. Compared with the effects of established risk factors alcohol seems to be quite unimportant in the development of ischaemic heart disease. PMID:3105714

Atmospheric pressure fluctuations in the far infrasound range and emergency transport events coded as circulatory system diseases.

PubMed

Didyk, L A; Gorgo, Yu P; Dirckx, J J J; Bogdanov, V B; Buytaert, J A N; Lysenko, V A; Didyk, N P; Vershygora, A V; Erygina, V T

2008-09-01

This study examines whether a relation exists between rapid atmospheric pressure fluctuations, attributed to the far infrasound frequency range (APF), and a number of emergency transport events coded as circulatory system diseases (EEC). Over an entire year, the average integral amplitudes of APF in the range of periods from 3 s to 120 s over each hour (HA) were measured. Daily dynamics of HA averaged over the year revealed a wave shape with smooth increase from night to day followed by decrease from day to night. The total daily number of EEC within the city of Kiev, Ukraine, was related to the daily mean of HA (DHA) and to the ratio of HA averaged over the day time to HA averaged over the night time (Rdn), and was checked for confounding effects of classical meteorological variables through non-parametric regression algorithms. The number of EEC were significantly higher on days with high DHA (3.72-11.07 Pa, n = 87) compared to the low DHA (0.7-3.62 Pa, n = 260, p = 0.01), as well at days with low Rdn (0.21-1.64, n = 229) compared to the high Rdn (1.65-7.2, n = 118, p = 0.03). A difference between DHA and Rdn effects on the emergency events related to different categories of circulatory diseases points to a higher sensitivity of rheumatic and cerebro-vascular diseases to DHA, and ischaemic and hypertensive diseases to Rdn. Results suggest that APF could be considered as a meteorotropic factor capable of influencing circulatory system diseases.

Atmospheric pressure fluctuations in the far infrasound range and emergency transport events coded as circulatory system diseases

NASA Astrophysics Data System (ADS)

Didyk, L. A.; Gorgo, Yu. P.; Dirckx, J. J. J.; Bogdanov, V. B.; Buytaert, J. A. N.; Lysenko, V. A.; Didyk, N. P.; Vershygora, A. V.; Erygina, V. T.

2008-09-01

This study examines whether a relation exists between rapid atmospheric pressure fluctuations, attributed to the far infrasound frequency range (APF), and a number of emergency transport events coded as circulatory system diseases (EEC). Over an entire year, the average integral amplitudes of APF in the range of periods from 3 s to 120 s over each hour (HA) were measured. Daily dynamics of HA averaged over the year revealed a wave shape with smooth increase from night to day followed by decrease from day to night. The total daily number of EEC within the city of Kiev, Ukraine, was related to the daily mean of HA (DHA) and to the ratio of HA averaged over the day time to HA averaged over the night time (Rdn), and was checked for confounding effects of classical meteorological variables through non-parametric regression algorithms. The number of EEC were significantly higher on days with high DHA (3.72 11.07 Pa, n = 87) compared to the low DHA (0.7 3.62 Pa, n = 260, p = 0.01), as well at days with low Rdn (0.21 1.64, n = 229) compared to the high Rdn (1.65 7.2, n = 118, p = 0.03). A difference between DHA and Rdn effects on the emergency events related to different categories of circulatory diseases points to a higher sensitivity of rheumatic and cerebro-vascular diseases to DHA, and ischaemic and hypertensive diseases to Rdn. Results suggest that APF could be considered as a meteorotropic factor capable of influencing circulatory system diseases.

Economic burden of cardiovascular events and fractures among patients with end-stage renal disease.

PubMed

Doan, Quan V; Gleeson, Michelle; Kim, John; Borker, Rohit; Griffiths, Robert; Dubois, Robert W

2007-07-01

To quantify direct medical costs of fractures and cardiovascular diseases among end-stage renal disease (ESRD) patients. Medicare claims data from year 2001 of the United States Renal Data System were used to quantify direct medical costs of acute episodic events (acute myocardial infarction (MI), stroke, heart valve repair, heart valve replacement, fractures) and chronic conditions (arrhythmia, peripheral vascular disease (PVD), heart valve disease (HVD), congestive heart failure (CHF), coronary heart disease, and non-acute stroke). Costs of hospitalized episodes of arrhythmia, PVD, CHF, and angina were also quantified. For acute events, costs were quantified using an episode-of-care approach. For chronic conditions, annualized costs were reported. Only costs specific to the events or conditions of interest were included and reported, in 2006 US dollars. Drug and dialysis-related costs were excluded. Diagnosis and procedure codes were used to identify these events and conditions. Among acute events analyzed as clinical episodes, PVD ($358 million) was associated with the greatest economic burden, followed by CHF, arrhythmia, angina, acute MI, heart valve replacement, hip fracture, acute stroke, heart valve repair, vertebral fracture, and pelvic fracture ($8.6 million). The cost per episode ranged from approximately $12,000 to 104,000. Among chronic conditions, CHF ($681 million) contributed the greatest economic burden; HVD ($100 million) contributed the least. The costs per patient-year ranged from $23,000 to 45,000 among chronic conditions. The costing methodology utilized could contribute to an underestimate of the economic impact of each condition; therefore these results are considered conservative. The economic burden of these selected conditions was substantial to health services payers who finance ESRD patient care. Episodic costs were high for most acute events.

Coronary heart disease risk in patients with stroke or transient ischemic attack and no known coronary heart disease: findings from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.

PubMed

Amarenco, Pierre; Goldstein, Larry B; Sillesen, Henrik; Benavente, Oscar; Zweifler, Richard M; Callahan, Alfred; Hennerici, Michael G; Zivin, Justin A; Welch, K Michael A

2010-03-01

Noncoronary forms of atherosclerosis (including transient ischemic attacks or stroke of carotid origin or >50% stenosis of the carotid artery) are associated with a 10-year vascular risk of >20% and are considered as a coronary heart disease (CHD) -risk equivalent from the standpoint of lipid management. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial included patients with stroke or transient ischemic attack and no known CHD regardless of the presence of carotid atherosclerosis. We evaluated the risk of developing clinically recognized CHD in SPARCL patients. A total of 4731 patients (mean age, 63 years) was randomized to 80 mg/day atorvastatin placebo. The rates of major coronary event, any CHD event, and any revascularization procedure were evaluated. After 4.9 years of follow-up, the risks of a major coronary event and of any CHD end point in the placebo group were 5.1% and 8.6%, respectively. The rate of outcome of stroke decreased over time, whereas the major coronary event rate was stable. Relative to those having a large vessel-related stroke at baseline, those having a transient ischemic attack, hemorrhagic stroke, small vessel stroke, or a stroke of unknown cause had similar absolute rates for a first major coronary event and for any CHD event; transient ischemic attack, small vessel, and unknown cause groups had lower absolute revascularization procedure rates. Major coronary event, any CHD event, and any revascularization procedure rates were similarly reduced in all baseline stroke subtypes in the atorvastatin arm compared with placebo with no heterogeneity between groups. CHD risk can be substantially reduced by atorvastatin therapy in patients with recent stroke or transient ischemic attack regardless of stroke subtype.

Comparison of hospitalizations, emergency department visits, and costs in a historical cohort of Texas Medicaid patients with chronic obstructive pulmonary disease, by initial medication regimen.

PubMed

Rascati, Karen L; Akazawa, Manabu; Johnsrud, Michael; Stanford, Richard H; Blanchette, Christopher M

2007-06-01

Limited information is available on the relative outcomes and treatment costs of various pharmacotherapies for chronic obstructive pulmonary disease (COPD) in a Medicaid population. This study compared the effects of initial medication regimens for COPD on COPD-related and all-cause events (hospitalizations and/or emergency department [ED] visits) and COPD-related and all-cause costs. The study population was a historical cohort of Texas Medicaid beneficiaries aged 40 to 64 years with COPD-related medical costs (International Classification of Diseases, Ninth Revision, Clinical Modification codes 491.xx, 492.xx, 496.xx), 24 months of continuous Medicaid enrollment (12 months before and after the index prescription), and at least 1 prescription claim (index) for a combination product containing fluticasone propionate + salmeterol, an inhaled corticosteroid, salmeterol, or ipratropium between April 1, 2001, and March 31, 2003. The analyses of events employed Cox proportional hazards regression, controlling for baseline factors and preindex events. The analyses of costs used a 2-part model with logistic regression and generalized linear model to adjust for baseline characteristics and preindex utilization and costs. The study population included 6793 patients (1211 combination therapy, 968 inhaled corticosteroid, 401 salmeterol, and 4213 ipratropium). Only combination therapy was associated with a significantly lower risk for any COPD-related event (hazard ratio [HR] = 0.733; 95% CI, 0.650-0.826) and any all-cause event (HR = 0.906; 95% CI, 0.844-0.972) compared with ipratropium. COPD-related prescription costs were higher in all cohorts compared with the ipratropium cohort, but COPD-related medical costs were lower, offsetting the increase in prescription costs. For all-cause costs, prescription costs were higher in the combination-therapy cohort (+$415; P < 0.05) and the salmeterol cohort (+$247; P < 0.05) compared with the ipratropium cohort, but significant reductions in all-cause medical costs in the combination-therapy cohort (-$1735; P < 0.05) and salmeterol cohort (-$1547; P < 0.05) more than offset the increase in prescription costs. In this historical population of Texas Medicaid beneficiaries, the combination-therapy cohort was 27% less likely to have a COPD-related event than the ipratropium cohort, 10% less likely to have any all-cause event, had similar COPD-related costs, and had reduced all-cause costs. Thus, compared with the ipratropium cohort, the combination-therapy cohort had an improvement in outcomes (based on the decreased time to a hospitalization or ED visit), with similar or decreased direct medical costs. Future research is needed in other patient groups.

[Current movements of four serious adverse events induced by medicinal drugs based on spontaneous reports in Japan].

PubMed

Sudo, Chie; Azuma, Yu-ichiro; Maekawa, Keiko; Kaniwa, Nahoko; Sai, Kimie; Saito, Yoshiro

2011-01-01

Spontaneous reports on suspected serious adverse events caused by medicines from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated by the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety features. Although causal relationship between the medicine and the adverse event is not evaluated, and one incidence may be redundantly reported, this information would be useful to roughly grasp the current movements of drug-related serious adverse events, We searched open-source data of the spontaneous reports publicized by Pharmaceutical and Medical Devices Agency for 4 serious adverse events (interstitial lung disease, rhabdomyolysis, anaphylaxis, and Stevens-Johnson syndrome/toxic epidermal necrolysis) from 2004 to 2010 fiscal year (for 2010, from April 1 st to January 31th). Major drug-classes suspected to the adverse events were antineoplastics for interstitial lung disease, hyperlipidemia agents and psychotropics for rhabdomyolysis, antibiotics/chemotherapeutics, antineoplastics and intracorporeal diagnostic agents for anaphylaxis (anaphylactic shock, anaphylactic reactions, anaphylactoid shock and anaphylactoid reactions), and antibiotics/chemotherapeutics, antipyretics and analgesics, anti-inflammatory agents/common cold drugs, and antiepileptics for Stevens-Johnson syndrome/toxic epidermal necrolysis. These results would help understanding of current situations of the 4 drug-related serious adverse events in Japan.

Quantifying the effect of media limitations on outbreak data in a global online web-crawling epidemic intelligence system, 2008–2011

PubMed Central

Scales, David; Zelenev, Alexei; Brownstein, John S.

2013-01-01

Background This is the first study quantitatively evaluating the effect that media-related limitations have on data from an automated epidemic intelligence system. Methods We modeled time series of HealthMap's two main data feeds, Google News and Moreover, to test for evidence of two potential limitations: first, human resources constraints, and second, high-profile outbreaks “crowding out” coverage of other infectious diseases. Results Google News events declined by 58.3%, 65.9%, and 14.7% on Saturday, Sunday and Monday, respectively, relative to other weekdays. Events were reduced by 27.4% during Christmas/New Years weeks and 33.6% lower during American Thanksgiving week than during an average week for Google News. Moreover data yielded similar results with the addition of Memorial Day (US) being associated with a 36.2% reduction in events. Other holiday effects were not statistically significant. We found evidence for a crowd out phenomenon for influenza/H1N1, where a 50% increase in influenza events corresponded with a 4% decline in other disease events for Google News only. Other prominent diseases in this database – avian influenza (H5N1), cholera, or foodborne illness – were not associated with a crowd out phenomenon. Conclusions These results provide quantitative evidence for the limited impact of editorial biases on HealthMap's web-crawling epidemic intelligence. PMID:24206612

Risk factors for clinical coronary heart disease in systemic lupus erythematosus: the lupus and atherosclerosis evaluation of risk (LASER) study.

PubMed

Haque, Sahena; Gordon, Caroline; Isenberg, David; Rahman, Anisur; Lanyon, Peter; Bell, Aubrey; Emery, Paul; McHugh, Neil; Teh, Lee Suan; Scott, David G I; Akil, Mohamed; Naz, Sophia; Andrews, Jacqueline; Griffiths, Bridget; Harris, Helen; Youssef, Hazem; McLaren, John; Toescu, Veronica; Devakumar, Vinodh; Teir, Jamal; Bruce, Ian N

2010-02-01

Accelerated atherosclerosis and premature coronary heart disease (CHD) are recognized complications of systemic lupus erythematosus (SLE), but the exact etiology remains unclear and is likely to be multifactorial. We hypothesized that SLE patients with CHD have increased exposure to traditional risk factors as well as differing disease phenotype and therapy-related factors compared to SLE patients free of CHD. Our aim was to examine risk factors for development of clinical CHD in SLE in the clinical setting. In a UK-wide multicenter retrospective case-control study we recruited 53 SLE patients with verified clinical CHD (myocardial infarction or angina pectoris) and 96 SLE patients without clinical CHD. Controls were recruited from the same center as the case and matched by disease duration. Charts were reviewed up to time of event for cases, or the same "dummy-date" in controls. SLE patients with clinical CHD were older at the time of event [mean (SD) 53 (10) vs 42 (10) yrs; p < 0.001], more likely to be male [11 (20%) vs 3 (7%); p < 0.001], and had more exposure to all classic CHD risk factors compared to SLE patients without clinical CHD. They were also more likely to have been treated with corticosteroids (OR 2.46; 95% CI 1.03, 5.88) and azathioprine (OR 2.33; 95% CI 1.16, 4.67) and to have evidence of damage on the pre-event SLICC damage index (SDI) (OR 2.20; 95% CI 1.09, 4.44). There was no difference between groups with regard to clinical organ involvement or autoantibody profile. Our study highlights the need for clinical vigilance to identify modifiable risk factors in the clinical setting and in particular with male patients. The pattern of organ involvement did not differ in SLE patients with CHD events. However, the higher pre-event SDI, azathioprine exposure, and pattern of damage items (disease-related rather than therapy-related) in cases suggests that a persistent active lupus phenotype contributes to CHD risk. In this regard, corticosteroids and azathioprine may not control disease well enough to prevent CHD. Clinical trials are needed to determine whether classic risk factor modification will have a role in primary prevention of CHD in SLE patients and whether new therapies that control disease activity can better reduce CHD risk.

Factors Influencing Performance of Internet-Based Biosurveillance Systems Used in Epidemic Intelligence for Early Detection of Infectious Diseases Outbreaks

PubMed Central

Barboza, Philippe; Vaillant, Laetitia; Le Strat, Yann; Hartley, David M.; Nelson, Noele P.; Mawudeku, Abla; Madoff, Lawrence C.; Linge, Jens P.; Collier, Nigel; Brownstein, John S.; Astagneau, Pascal

2014-01-01

Background Internet-based biosurveillance systems have been developed to detect health threats using information available on the Internet, but system performance has not been assessed relative to end-user needs and perspectives. Method and Findings Infectious disease events from the French Institute for Public Health Surveillance (InVS) weekly international epidemiological bulletin published in 2010 were used to construct the gold-standard official dataset. Data from six biosurveillance systems were used to detect raw signals (infectious disease events from informal Internet sources): Argus, BioCaster, GPHIN, HealthMap, MedISys and ProMED-mail. Crude detection rates (C-DR), crude sensitivity rates (C-Se) and intrinsic sensitivity rates (I-Se) were calculated from multivariable regressions to evaluate the systems’ performance (events detected compared to the gold-standard) 472 raw signals (Internet disease reports) related to the 86 events included in the gold-standard data set were retrieved from the six systems. 84 events were detected before their publication in the gold-standard. The type of sources utilised by the systems varied significantly (p<0001). I-Se varied significantly from 43% to 71% (p = 0001) whereas other indicators were similar (C-DR: p = 020; C-Se, p = 013). I-Se was significantly associated with individual systems, types of system, languages, regions of occurrence, and types of infectious disease. Conversely, no statistical difference of C-DR was observed after adjustment for other variables. Conclusion Although differences could result from a biosurveillance system's conceptual design, findings suggest that the combined expertise amongst systems enhances early detection performance for detection of infectious diseases. While all systems showed similar early detection performance, systems including human moderation were found to have a 53% higher I-Se (p = 00001) after adjustment for other variables. Overall, the use of moderation, sources, languages, regions of occurrence, and types of cases were found to influence system performance. PMID:24599062

Factors influencing performance of internet-based biosurveillance systems used in epidemic intelligence for early detection of infectious diseases outbreaks.

PubMed

Barboza, Philippe; Vaillant, Laetitia; Le Strat, Yann; Hartley, David M; Nelson, Noele P; Mawudeku, Abla; Madoff, Lawrence C; Linge, Jens P; Collier, Nigel; Brownstein, John S; Astagneau, Pascal

2014-01-01

Internet-based biosurveillance systems have been developed to detect health threats using information available on the Internet, but system performance has not been assessed relative to end-user needs and perspectives. Infectious disease events from the French Institute for Public Health Surveillance (InVS) weekly international epidemiological bulletin published in 2010 were used to construct the gold-standard official dataset. Data from six biosurveillance systems were used to detect raw signals (infectious disease events from informal Internet sources): Argus, BioCaster, GPHIN, HealthMap, MedISys and ProMED-mail. Crude detection rates (C-DR), crude sensitivity rates (C-Se) and intrinsic sensitivity rates (I-Se) were calculated from multivariable regressions to evaluate the systems' performance (events detected compared to the gold-standard) 472 raw signals (Internet disease reports) related to the 86 events included in the gold-standard data set were retrieved from the six systems. 84 events were detected before their publication in the gold-standard. The type of sources utilised by the systems varied significantly (p<0001). I-Se varied significantly from 43% to 71% (p=0001) whereas other indicators were similar (C-DR: p=020; C-Se, p=013). I-Se was significantly associated with individual systems, types of system, languages, regions of occurrence, and types of infectious disease. Conversely, no statistical difference of C-DR was observed after adjustment for other variables. Although differences could result from a biosurveillance system's conceptual design, findings suggest that the combined expertise amongst systems enhances early detection performance for detection of infectious diseases. While all systems showed similar early detection performance, systems including human moderation were found to have a 53% higher I-Se (p=00001) after adjustment for other variables. Overall, the use of moderation, sources, languages, regions of occurrence, and types of cases were found to influence system performance.

Sex-based Prognostic Implications of Nonobstructive Coronary Artery Disease: Results from the International Multicenter CONFIRM Study

PubMed Central

Taylor, Carolyn M.; Gransar, Heidi; Shaw, Leslee J.; Ahmadi, Amir; Thompson, Angus; Humphries, Karin; Berman, Daniel S.; Hausleiter, Jörg; Achenbach, Stephan; Al-Mallah, Mouaz; Budoff, Matthew J.; Cademartiri, Fillippo; Callister, Tracy Q.; Chang, Hyuk-Jae; Chow, Benjamin J. W.; Cury, Ricardo C.; Delago, Augustin J.; Dunning, Allison L.; Feuchtner, Gudrun M.; Hadamitzky, Martin; Kaufmann, Philipp A.; Lin, Fay Y.; Chinnaiyan, Kavitha M.; Maffei, Erica; Raff, Gilbert L.; Villines, Todd C.; Gomez, Millie J.; Min, James K.

2014-01-01

Purpose To determine the clinical outcomes of women and men with nonobstructive coronary artery disease (CADcoronary artery disease) with coronary computed tomographic (CT) angiography data in patients who were similar in terms of CADcoronary artery disease risk factors, angina typicality, and CADcoronary artery disease extent and distribution. Materials and Methods Institutional review board approval was obtained for all participating sites, with either informed consent or waiver of informed consent. In a prospective international multicenter cohort study of 27 125 patients undergoing coronary CT angiography at 12 centers, 18 158 patients with no CADcoronary artery disease or nonobstructive (<50% stenosis) CADcoronary artery disease were examined. Men and women were propensity matched for age, CADcoronary artery disease risk factors, angina typicality, and CADcoronary artery disease extent and distribution, which resulted in a final cohort of 11 462 subjects. Nonobstructive CADcoronary artery disease presence and extent were related to incident major adverse cardiovascular events (MACEmajor adverse cardiovascular events), which were inclusive of death and myocardial infarction and were estimated by using multivariable Cox proportional hazards models. Results At a mean follow-up ± standard deviation of 2.3 years ± 1.1, MACEmajor adverse cardiovascular events occurred in 164 patients (0.6% annual event rate). After matching, women and men experienced identical annualized rates of myocardial infarction (0.2% vs 0.2%, P = .72), death (0.5% vs 0.5%, P = .98), and MACEmajor adverse cardiovascular events (0.6% vs 0.6%, P = .94). In multivariable analysis, nonobstructive CADcoronary artery disease was associated with similarly increased MACEmajor adverse cardiovascular events for both women (hazard ratio: 1.96 [95% confidence interval {CIconfidence interval}: 1.17, 3.28], P = .01) and men (hazard ratio: 1.77 [95% CIconfidence interval: 1.07, 2.93], P = .03). Conclusion When matched for age, CADcoronary artery disease risk factors, angina typicality, and nonobstructive CADcoronary artery disease extent, women and men experience comparable rates of incident mortality and myocardial infarction. © RSNA, 2014 Online supplemental material is available for this article. PMID:25028784

Sex-based prognostic implications of nonobstructive coronary artery disease: results from the international multicenter CONFIRM study.

PubMed

Leipsic, Jonathon; Taylor, Carolyn M; Gransar, Heidi; Shaw, Leslee J; Ahmadi, Amir; Thompson, Angus; Humphries, Karin; Berman, Daniel S; Hausleiter, Jörg; Achenbach, Stephan; Al-Mallah, Mouaz; Budoff, Matthew J; Cademartiri, Fillippo; Callister, Tracy Q; Chang, Hyuk-Jae; Chow, Benjamin J W; Cury, Ricardo C; Delago, Augustin J; Dunning, Allison L; Feuchtner, Gudrun M; Hadamitzky, Martin; Kaufmann, Philipp A; Lin, Fay Y; Chinnaiyan, Kavitha M; Maffei, Erica; Raff, Gilbert L; Villines, Todd C; Gomez, Millie J; Min, James K

2014-11-01

To determine the clinical outcomes of women and men with nonobstructive coronary artery disease ( CAD coronary artery disease ) with coronary computed tomographic (CT) angiography data in patients who were similar in terms of CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution. Institutional review board approval was obtained for all participating sites, with either informed consent or waiver of informed consent. In a prospective international multicenter cohort study of 27 125 patients undergoing coronary CT angiography at 12 centers, 18 158 patients with no CAD coronary artery disease or nonobstructive (<50% stenosis) CAD coronary artery disease were examined. Men and women were propensity matched for age, CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution, which resulted in a final cohort of 11 462 subjects. Nonobstructive CAD coronary artery disease presence and extent were related to incident major adverse cardiovascular events ( MACE major adverse cardiovascular events ), which were inclusive of death and myocardial infarction and were estimated by using multivariable Cox proportional hazards models. At a mean follow-up ± standard deviation of 2.3 years ± 1.1, MACE major adverse cardiovascular events occurred in 164 patients (0.6% annual event rate). After matching, women and men experienced identical annualized rates of myocardial infarction (0.2% vs 0.2%, P = .72), death (0.5% vs 0.5%, P = .98), and MACE major adverse cardiovascular events (0.6% vs 0.6%, P = .94). In multivariable analysis, nonobstructive CAD coronary artery disease was associated with similarly increased MACE major adverse cardiovascular events for both women (hazard ratio: 1.96 [95% confidence interval { CI confidence interval }: 1.17, 3.28], P = .01) and men (hazard ratio: 1.77 [95% CI confidence interval : 1.07, 2.93], P = .03). When matched for age, CAD coronary artery disease risk factors, angina typicality, and nonobstructive CAD coronary artery disease extent, women and men experience comparable rates of incident mortality and myocardial infarction.

Can discrete event simulation be of use in modelling major depression?

PubMed Central

Le Lay, Agathe; Despiegel, Nicolas; François, Clément; Duru, Gérard

2006-01-01

Background Depression is among the major contributors to worldwide disease burden and adequate modelling requires a framework designed to depict real world disease progression as well as its economic implications as closely as possible. Objectives In light of the specific characteristics associated with depression (multiple episodes at varying intervals, impact of disease history on course of illness, sociodemographic factors), our aim was to clarify to what extent "Discrete Event Simulation" (DES) models provide methodological benefits in depicting disease evolution. Methods We conducted a comprehensive review of published Markov models in depression and identified potential limits to their methodology. A model based on DES principles was developed to investigate the benefits and drawbacks of this simulation method compared with Markov modelling techniques. Results The major drawback to Markov models is that they may not be suitable to tracking patients' disease history properly, unless the analyst defines multiple health states, which may lead to intractable situations. They are also too rigid to take into consideration multiple patient-specific sociodemographic characteristics in a single model. To do so would also require defining multiple health states which would render the analysis entirely too complex. We show that DES resolve these weaknesses and that its flexibility allow patients with differing attributes to move from one event to another in sequential order while simultaneously taking into account important risk factors such as age, gender, disease history and patients attitude towards treatment, together with any disease-related events (adverse events, suicide attempt etc.). Conclusion DES modelling appears to be an accurate, flexible and comprehensive means of depicting disease progression compared with conventional simulation methodologies. Its use in analysing recurrent and chronic diseases appears particularly useful compared with Markov processes. PMID:17147790

Can discrete event simulation be of use in modelling major depression?

PubMed

Le Lay, Agathe; Despiegel, Nicolas; François, Clément; Duru, Gérard

2006-12-05

Depression is among the major contributors to worldwide disease burden and adequate modelling requires a framework designed to depict real world disease progression as well as its economic implications as closely as possible. In light of the specific characteristics associated with depression (multiple episodes at varying intervals, impact of disease history on course of illness, sociodemographic factors), our aim was to clarify to what extent "Discrete Event Simulation" (DES) models provide methodological benefits in depicting disease evolution. We conducted a comprehensive review of published Markov models in depression and identified potential limits to their methodology. A model based on DES principles was developed to investigate the benefits and drawbacks of this simulation method compared with Markov modelling techniques. The major drawback to Markov models is that they may not be suitable to tracking patients' disease history properly, unless the analyst defines multiple health states, which may lead to intractable situations. They are also too rigid to take into consideration multiple patient-specific sociodemographic characteristics in a single model. To do so would also require defining multiple health states which would render the analysis entirely too complex. We show that DES resolve these weaknesses and that its flexibility allow patients with differing attributes to move from one event to another in sequential order while simultaneously taking into account important risk factors such as age, gender, disease history and patients attitude towards treatment, together with any disease-related events (adverse events, suicide attempt etc.). DES modelling appears to be an accurate, flexible and comprehensive means of depicting disease progression compared with conventional simulation methodologies. Its use in analysing recurrent and chronic diseases appears particularly useful compared with Markov processes.

Extreme water-related weather events and waterborne disease.

PubMed

Cann, K F; Thomas, D Rh; Salmon, R L; Wyn-Jones, A P; Kay, D

2013-04-01

Global climate change is expected to affect the frequency, intensity and duration of extreme water-related weather events such as excessive precipitation, floods, and drought. We conducted a systematic review to examine waterborne outbreaks following such events and explored their distribution between the different types of extreme water-related weather events. Four medical and meteorological databases (Medline, Embase, GeoRef, PubMed) and a global electronic reporting system (ProMED) were searched, from 1910 to 2010. Eighty-seven waterborne outbreaks involving extreme water-related weather events were identified and included, alongside 235 ProMED reports. Heavy rainfall and flooding were the most common events preceding outbreaks associated with extreme weather and were reported in 55·2% and 52·9% of accounts, respectively. The most common pathogens reported in these outbreaks were Vibrio spp. (21·6%) and Leptospira spp. (12·7%). Outbreaks following extreme water-related weather events were often the result of contamination of the drinking-water supply (53·7%). Differences in reporting of outbreaks were seen between the scientific literature and ProMED. Extreme water-related weather events represent a risk to public health in both developed and developing countries, but impact will be disproportionate and likely to compound existing health disparities.

The natural history of prevalent ischaemic heart disease in middle-aged men.

PubMed

Lampe, F C; Whincup, P H; Wannamethee, S G; Shaper, A G; Walker, M; Ebrahim, S

2000-07-01

To describe the long-term outcome of different forms of symptomatic and asymptomatic ischaemic heart disease in middle-aged men. 7735 men aged 40-59, randomly selected from 24 general practices in Britain were classified into one of seven ischaemic heart disease groups according to a questionnaire and electrocardiogram (ECG): I=diagnosed myocardial infarction; II=unrecognized myocardial infarction; III= diagnosed angina; IV=angina symptoms; V=possible myocardial infarction symptoms; VI=ECG ischaemia or possible myocardial infarction; VII=no evidence of ischaemic heart disease. The association of disease group with a range of fatal and non-fatal outcomes during 15 years of follow-up was assessed. At baseline 25% of men had evidence of ischaemic heart disease (groups I-VI). Risks of major ischaemic heart disease events, total and cardiovascular mortality, stroke, and major cardiovascular events tended to increase strongly from group VII to I. Diagnosed myocardial infarction was associated with a much poorer prognosis than all other groups (including unrecognized infarction) for all cardiovascular outcomes other than stroke. The relative risk associated with ischaemic heart disease at baseline declined dramatically over time. However, men with myocardial infarction who survived event-free for 10 years continued to experience a high excess risk in the subsequent 5 years, in contrast to event-free survivors of angina and other ischaemic heart disease. Adjusted to an average age of 50, the percentage of men surviving for 15 years free of a new major cardiovascular event was 44 for diagnosed myocardial infarction, 52 for unrecognized myocardial infarction, 66 for diagnosed angina, 68 for angina symptoms, 73 for possible myocardial infarction symptoms, 73 for ECG ischaemia, and 79 for no ischaemic heart disease. Comparison of outcome between prevalent and incident myocardial infarction illustrated the improved prognosis of men surviving the initial years after their event. Differing manifestations of prevalent ischaemic heart disease are associated with widely differing outcome, and the majority of middle-aged men in the community who have evidence of ischaemic heart disease short of myocardial infarction survive for 15 years without heart attack or stroke. The excess risk associated with myocardial infarction appears more persistent than that associated with angina and other ischaemic heart disease, remaining high even after 10 years of event-free survival.

Association between consumption of soy and risk of cardiovascular disease: A meta-analysis of observational studies.

PubMed

Yan, Zhaoli; Zhang, Xinyue; Li, Chunlin; Jiao, Shouchun; Dong, Wenyao

2017-05-01

Background The relationships between dietary intake of soy foods and risk of cardiovascular disease are uncertain. The aims of this study were to evaluate and summarize the evidence on the association between consumption of soy and risk of cardiovascular disease (including stroke and coronary heart disease). Methods We systematically searched the MEDLINE and EMBASE databases from their inception up to 22 February 2016. We included only observational studies, and used random-effects models to calculate summary relative risks (SRRs) and 95% confidence intervals (CIs). Results A total of 10 prospective cohort and seven case-control studies met the inclusion criteria. There were a total of 17,269 cardiovascular disease events, including 6265 stroke events, 10,806 coronary heart disease events, and 198 other cardiovascular disease events. A significant negative association was shown between soy intake and risk of cardiovascular disease (SRR = 0.84 95% CI: 0.75-0.94; p heterogeneity <0.001, I 2  = 71.4%). Subgroup meta-analyses indicated that a statistically significant protective effect was primarily observed in case-control studies and in Asian populations. There was a borderline significant association between intake of tofu and the risk of cardiovascular disease (SRR = 0.80, 95% CI: 0.64-1.00). A significant negative association was shown for the association between soy intake and risk of stroke (SRR = 0.82, 95% CI: 0.68-0.99) and coronary heart disease (SRR = 0.83, 95% CI: 0.72-0.95). There were no associations between soy isoflavones consumption and risk of cardiovascular disease, stroke, and coronary heart disease. Conclusion Overall evidence indicated that consumption of soy was negatively associated with the risk of cardiovascular disease, stroke, and coronary heart disease risk.

Unprecedented Disease-Related Coral Mortality in Southeastern Florida

NASA Astrophysics Data System (ADS)

Precht, William F.; Gintert, Brooke E.; Robbart, Martha L.; Fura, Ryan; van Woesik, Robert

2016-08-01

Anomalously high water temperatures, associated with climate change, are increasing the global prevalence of coral bleaching, coral diseases, and coral-mortality events. Coral bleaching and disease outbreaks are often inter-related phenomena, since many coral diseases are a consequence of opportunistic pathogens that further compromise thermally stressed colonies. Yet, most coral diseases have low prevalence (<5%), and are not considered contagious. By contrast, we document the impact of an extremely high-prevalence outbreak (61%) of white-plague disease at 14 sites off southeastern Florida. White-plague disease was observed near Virginia Key, Florida, in September 2014, and after 12 months had spread 100 km north and 30 km south. The disease outbreak directly followed a high temperature coral-bleaching event and affected at least 13 coral species. Eusmilia fastigiata, Meandrina meandrites, and Dichocoenia stokesi were the most heavily impacted coral species, and were reduced to <3% of their initial population densities. A number of other coral species, including Colpophyllia natans, Pseudodiploria strigosa, Diploria labyrinthiformis, and Orbicella annularis were reduced to <25% of their initial densities. The high prevalence of disease, the number of susceptible species, and the high mortality of corals affected suggests this disease outbreak is arguably one of the most lethal ever recorded on a contemporary coral reef.

Unprecedented Disease-Related Coral Mortality in Southeastern Florida.

PubMed

Precht, William F; Gintert, Brooke E; Robbart, Martha L; Fura, Ryan; van Woesik, Robert

2016-08-10

Anomalously high water temperatures, associated with climate change, are increasing the global prevalence of coral bleaching, coral diseases, and coral-mortality events. Coral bleaching and disease outbreaks are often inter-related phenomena, since many coral diseases are a consequence of opportunistic pathogens that further compromise thermally stressed colonies. Yet, most coral diseases have low prevalence (<5%), and are not considered contagious. By contrast, we document the impact of an extremely high-prevalence outbreak (61%) of white-plague disease at 14 sites off southeastern Florida. White-plague disease was observed near Virginia Key, Florida, in September 2014, and after 12 months had spread 100 km north and 30 km south. The disease outbreak directly followed a high temperature coral-bleaching event and affected at least 13 coral species. Eusmilia fastigiata, Meandrina meandrites, and Dichocoenia stokesi were the most heavily impacted coral species, and were reduced to <3% of their initial population densities. A number of other coral species, including Colpophyllia natans, Pseudodiploria strigosa, Diploria labyrinthiformis, and Orbicella annularis were reduced to <25% of their initial densities. The high prevalence of disease, the number of susceptible species, and the high mortality of corals affected suggests this disease outbreak is arguably one of the most lethal ever recorded on a contemporary coral reef.

Risk of thromboembolic complications in adult congenital heart disease: A literature review.

PubMed

Karsenty, Clement; Zhao, Alexandre; Marijon, Eloi; Ladouceur, Magalie

2018-05-30

Adult congenital heart disease (ACHD) is a constantly expanding population with challenging issues. Initial medical and surgical treatments are seldom curative, and the majority of patients still experience late sequelae and complications, especially thromboembolic events. These common and potentially life-threating adverse events are probably dramatically underdiagnosed. Better identification and understanding of thromboembolic risk factors are essential to prevent long-term related morbidities. In addition to specific situations associated with a high risk of thromboembolic events (Fontan circulation, cyanotic congenital heart disease), atrial arrhythmia has been recognized as an important risk factor for thromboembolic events in ACHD. Unlike in patients without ACHD, thromboembolic risk stratification scores, such as the CHA 2 DS 2 -VASc score, may not be applicable in ACHD. Overall, after a review of the scientific data published so far, it is clear that the complexity of the underlying congenital heart disease represents a major risk factor for thromboembolic events. As a consequence, prophylactic anticoagulation is indicated in patients with complex congenital heart disease and atrial arrhythmia, regardless of the other risk factors, as opposed to simple heart defects. The landscape of ACHD is an ongoing evolving process, and specific thromboembolic risk scores are needed, especially in the setting of simple heart defects; these should be coupled with specific trials or long-term follow-up of multicentre cohorts. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Life events and stress reactivity as predictors of cancer, coronary heart disease and anxiety disorders.

PubMed

Chorot, P; Sandín, B

1994-01-01

The topic relative to the differential psychobiological mechanisms between cancer and coronary illness has been showing for the last years. In this sense, some theoretical models which have been formulated by relevant authors have suggested the possibility of differentiating cancer and cardiovascular disease, both the onset and the progression, from coping strategies, personality variables and affective states, as well as the different categories of psychosocial stress. Likewise, the implication of psychological distress, such as anxiety, anger and depression for the occurrence of somatic disease has been reported frequently. This research was designed to analyze the psychosocial patterns which could explain the incidence of heart disease, cancer and anxiety based disorders. Measures of life events and stress reactivity were obtained from a total of 109 patients diagnosed as having breast cancer (37), infarct (37), and anxiety (35), and from 72 normal control subjects. Our data tend to show that the cancer group was strongly predicted by lost and illness events, while the coronary group was more associated with work events. The anxiety disorders group lacked a life events dimension, but shared the same category of the infarct group. We also found a strong relationship between depressive reactions and cancer in contrast to the anxiety-anger variable that was more relevant in the infarct patients. The interaction between internal and external stress factors in the etiology of disease is also discussed.

Digital disease detection: A systematic review of event-based internet biosurveillance systems.

PubMed

O'Shea, Jesse

2017-05-01

Internet access and usage has changed how people seek and report health information. Meanwhile,infectious diseases continue to threaten humanity. The analysis of Big Data, or vast digital data, presents an opportunity to improve disease surveillance and epidemic intelligence. Epidemic intelligence contains two components: indicator based and event-based. A relatively new surveillance type has emerged called event-based Internet biosurveillance systems. These systems use information on events impacting health from Internet sources, such as social media or news aggregates. These systems circumvent the limitations of traditional reporting systems by being inexpensive, transparent, and flexible. Yet, innovations and the functionality of these systems can change rapidly. To update the current state of knowledge on event-based Internet biosurveillance systems by identifying all systems, including current functionality, with hopes to aid decision makers with whether to incorporate new methods into comprehensive programmes of surveillance. A systematic review was performed through PubMed, Scopus, and Google Scholar databases, while also including grey literature and other publication types. 50 event-based Internet systems were identified, including an extraction of 15 attributes for each system, described in 99 articles. Each system uses different innovative technology and data sources to gather data, process, and disseminate data to detect infectious disease outbreaks. The review emphasises the importance of using both formal and informal sources for timely and accurate infectious disease outbreak surveillance, cataloguing all event-based Internet biosurveillance systems. By doing so, future researchers will be able to use this review as a library for referencing systems, with hopes of learning, building, and expanding Internet-based surveillance systems. Event-based Internet biosurveillance should act as an extension of traditional systems, to be utilised as an additional, supplemental data source to have a more comprehensive estimate of disease burden. Copyright © 2017 Elsevier B.V. All rights reserved.

The frequency of anesthesia-related cardiac arrests in patients with congenital heart disease undergoing cardiac surgery.

PubMed

Odegard, Kirsten C; DiNardo, James A; Kussman, Barry D; Shukla, Avinash; Harrington, James; Casta, Al; McGowan, Francis X; Hickey, Paul R; Bacha, Emile A; Thiagarajan, Ravi R; Laussen, Peter C

2007-08-01

The frequency of anesthesia-related cardiac arrests during pediatric anesthesia has been reported between 1.4 and 4.6 per 10,000 anesthetics. ASA physical status >III and younger age are risk factors. Patients with congenital cardiac disease may also be at increased risk. Therefore, in this study, we evaluated the frequency of cardiac arrest in patients with congenital heart disease undergoing cardiac surgery at a large pediatric tertiary referral center. Using an established data registry, all cardiac arrests from January 2000 through December 2005 occurring in the cardiac operating rooms were reviewed. A cardiac arrest was defined as any event requiring external or internal chest compressions, with or without direct cardioversion. Events determined to be anesthesia-related were classified as likely related or possibly related. There were 41 cardiac arrests in 40 patients (median age, 2.9 mo; range, 2 days to 23 yr) during 5213 anesthetics over the time period, for an overall frequency of 0.79%; 78% were open procedures requiring cardiopulmonary bypass and 22% closed procedures not requiring cardiopulmonary bypass. Eleven cardiac arrests (26.8%) were classified as either likely (n = 6) or possibly related (n = 5) to anesthesia, (21.1 per 10,000 anesthetics) but with no mortality; 30 were categorized as procedure-related. The incidence of anesthesia-related and procedure-related cardiac arrests was highest in neonates (P < 0.001). There was no association with year of event or experience of the anesthesiologist. The frequency of anesthesia-related cardiac arrest in patients undergoing cardiac surgery is increased, but is not associated with an increase in mortality. Neonates and infants are at higher risk. Careful preparation and anticipation is important to ensure timely and effective resuscitation.

Inflammation-Related Morbidity and Mortality Among HIV-Positive Adults: How Extensive Is It?

PubMed

Hart, Brian B; Nordell, Anna D; Okulicz, Jason F; Palfreeman, Adrian; Horban, Andrzej; Kedem, Eynat; Neuhaus, Jacqueline; Jacobs, David R; Duprez, Daniel A; Neaton, James D

2018-01-01

To determine the rate of grade 4, potentially life-threatening events not attributable to AIDS, cardiovascular disease (CVD), or non-AIDS cancer among participants on antiretroviral therapy and to describe associations of these events with interleukin-6 (IL-6) and D-dimer. Cohort study. HIV-infected participants on antiretroviral therapy (N = 3568) with an HIV-RNA level ≤ 500 copies/mL were followed for grade 4, AIDS, CVD, non-AIDS cancer, and all-cause mortality events. Grade 4 events were further classified masked to biomarker levels as reflecting chronic inflammation-related disease (ChrIRD) or not (non-ChrIRD). Associations of baseline IL-6 and D-dimer with events were studied using Cox models. Over a median follow-up of 4.3 years, 339 participants developed a grade 4 event (22.9 per 1000 person-years); 165 participants developed a ChrIRD grade 4 event (10.7 per 1000 person-years). Grade 4 events were more common than AIDS (54 participants), CVD (132), and non-AIDS cancer (80) events, any of which developed in 252 participants (17.1 per 1000 person-years). Grade 4 and AIDS events were associated with similar risks of death. Higher IL-6 [hazard ratio (HR) = 1.19 per doubling of biomarker; P = 0.003] and D-dimer (HR = 1.23; P < 0.001) levels were associated with an increased risk of grade 4 events. IL-6 associations were stronger for ChrIRD (HR = 1.38; P < 0.001) than non-ChrIRD grade 4 events (HR = 1.11; P = 0.21). Morbidity and mortality associated with activation of inflammatory and coagulation pathways include conditions other than AIDS, CVD, and non-AIDS cancer events. Effective inflammation-dampening interventions could greatly affect the health of people with HIV.

[ELSA-Brasil strategies for outcome identification, investigation and ascertainment].

PubMed

Barreto, Sandhi Maria; Ladeira, Roberto Marini; Bastos, Maria do Socorro Castelo Branco de Oliveira; Diniz, Maria de Fátima Haueisen Sander; Jesus, Elcimara Amorim de; Kelles, Silvana Márcia Bruschi; Luft, Vivian Cristine; Melo, Enirtes Caetano Prates; Oliveira, Elizabete Regina Araújo de

2013-06-01

The article describes the strategies adopted by the Brazilian Longitudinal Study for Adult Health (ELSA-Brasil) for participation and retention of subjects. This is key to ensure internal validity of longitudinal studies, and to identify, investigate, and ascertain outcomes of interest. The follow-up strategies include annual telephone contacts with new assessments and interviews every three to four years this approach aims to identify transient outcomes (reversible or not), permanent outcomes as well as complications related to the progression of major diseases--cardiovascular diseases and diabetes--to be studied. Telephone interviews are designed to monitor subjects' health status and to identify potential health-related events such as hospital admissions, medical visits or pre-selected medical procedures. Subjects are also encouraged to report to the ELSA-Brasil team any new health-related events. When a potential event is identified, a thorough investigation is carried out to collect relevant information about that event from medical records. All data are blinded and reviewed and analyzed by a medical expert committee. Incident outcome ascertainment follows well-established international criteria to ensure data comparability and avoid misclassification. In addition to these strategies, the occurrence of health-related events is also investigated through linkage of secondary databases, such as national mortality and hospital admission databases. Accurate identification of outcomes will allow to estimating their incidence in the study cohort and to investigate the effect of the exposures studied in the ELSA-Brasil at baseline and at its subsequent waves.

Postintensive care unit psychological burden in patients with chronic obstructive pulmonary disease and informal caregivers: A multicenter study.

PubMed

de Miranda, Sandra; Pochard, Frédéric; Chaize, Marine; Megarbane, Bruno; Cuvelier, Antoine; Bele, Nicolas; Gonzalez-Bermejo, Jesus; Aboab, Jérome; Lautrette, Alexandre; Lemiale, Virginie; Roche, Nicolas; Thirion, Marina; Chevret, Sylvie; Schlemmer, Benoit; Similowski, Thomas; Azoulay, Elie

2011-01-01

To determine the prevalence and risk factors of symptoms of anxiety, depression, and posttraumatic stress disorder-related symptoms in patients with chronic obstructive pulmonary disease and their relatives after an intensive care unit stay. Prospective multicenter study. Nineteen French intensive care units. One hundred twenty-six patients with chronic obstructive pulmonary disease who survived an intensive care unit stay and 102 relatives. None. Patients and relatives were interviewed at intensive care unit discharge and 90 days later to assess symptoms of anxiety and depression using Hospital Anxiety and Depression Scale (HADS) and posttraumatic stress disorder-related symptoms using the Impact of Event Scale (IES). At intensive care unit discharge, 90% of patients recollected traumatic psychological events in the intensive care unit. At day 90, we were able to conduct telephone interviews with 53 patients and 47 relatives. Hospital Anxiety and Depression Scale scores indicated symptoms of anxiety and depression in 52% and 45.5% of patients at intensive care unit discharge and in 28.3% and 18.9% on day 90, respectively. Corresponding prevalence in relatives were 72.2% and 25.7% at intensive care unit discharge and 40.4% and 14.9% on day 90, respectively. The Impact of Event Scale indicated posttraumatic stress disorder-related symptoms in 20.7% of patients and 29.8% of relatives on day 90. Peritraumatic dissociation assessed using the Peritraumatic Dissociative Experiences Questionnaire was independently associated with posttraumatic stress disorder-related symptoms in the patients and relatives. Previous intensive care unit experience and recollection of bothersome noise in the intensive care unit predicted posttraumatic stress disorder-related symptoms in the patients. Psychiatric symptoms were found to be common in a group of 126 patients with chronic obstructive pulmonary disease who survived an intensive care unit stay and their relatives at intensive care unit discharge and 90 days later. Peritraumatic dissociation at intensive care unit discharge was found to independently predict posttraumatic stress disorder-related symptoms in this sample of patients and relatives.

Cardiovascular Safety of Droxidopa in Patients With Symptomatic Neurogenic Orthostatic Hypotension.

PubMed

White, William B; Hauser, Robert A; Rowse, Gerald J; Ziemann, Adam; Hewitt, L Arthur

2017-04-01

The norepinephrine prodrug droxidopa improves symptoms of neurogenic orthostatic hypotension, a condition that is associated with diseases of neurogenic autonomic failure (e.g., Parkinson disease, multiple system atrophy, pure autonomic failure). These conditions are more prevalent in older patients who also have cardiovascular co-morbidities. Hence, we evaluated the cardiovascular safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension who participated in randomized controlled studies (short-term studies of 1 to 2 weeks and an intermediate 8- to 10-week study) and long-term open-label studies. Rates of cardiovascular adverse events (AEs) for patients treated with droxidopa were 4.4% in the intermediate study and 10.8% in the long-term open-label studies. Adjusting for exposure time, cardiovascular AE rates were 0.30 events/patient-year in the short-term and intermediate studies and 0.15 events/patient-year in the long-term open-label studies. The incidence of treatment discontinuation due to blood pressure-related events was approximately 2.5%. Among patients with a history of cardiac disorders at baseline, the rates of cardiovascular-related and blood pressure-related AEs were nominally higher with droxidopa compared to placebo. Most of these events were minor atrial arrhythmias; none were major adverse cardiovascular events or deaths. In conclusion, small increases in cardiovascular AEs were observed with droxidopa compared to placebo; this was most evident in patients with preexisting cardiac disorders. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

The role of quality of care in health-related quality of life in patients with IBD.

PubMed

van der Eijk, Ingrid; Vlachonikolis, Ioannis G; Munkholm, Pia; Nijman, Judy; Bernklev, Tomm; Politi, Patrizia; Odes, Selwyn; Tsianos, Epameinondas V; Stockbrügger, Reinhold W; Russel, Maurice G

2004-07-01

In the literature there are indications of associations between health-related quality of life (HRQoL) in inflammatory bowel disease and disease activity, psychological status, coping, stressful life events, and social support. The aim of this study was to examine whether a relation exists between quality of health care and HRQoL, taking possible confounding variables into account. For this purpose, one single questionnaire was compiled from existing validated questionnaires. A population-based inception cohort of 1056 patients with inflammatory bowel disease in eight countries, diagnosed 6 to 8 years prior to the study, was approached to participate. In total, 824 patients responded (78%), and 517 could be included in statistical analyses. It was shown that in inflammatory bowel disease HRQoL was indeed influenced by quality of care (particularly with regard to the parameters of "providing information," "costs," and "courtesy"), as well as by disease activity, psychological status, type of hospital, social support, stressful life events, and way of administration of the questionnaire. Patients with active disease had lower psychological status and HRQoL scores at the time of the survey than patients without active disease. However, quality of care scores did not differ between these groups. The care aspect "costs" was scored worse by CD compared with UC patients, probably caused by a potentially more expensive treatment. In conclusion, it is shown in a large exploratory study, for the first time, that in inflammatory bowel disease, quality of care has a significant role in determining health-related quality of life.

Cardiovascular Complications of Marijuana and Related Substances: A Review.

PubMed

Singh, Amitoj; Saluja, Sajeev; Kumar, Akshat; Agrawal, Sahil; Thind, Munveer; Nanda, Sudip; Shirani, Jamshid

2018-06-01

The recreational use of cannabis has sharply increased in recent years in parallel with its legalization and decriminalization in several countries. Commonly, the traditional cannabis has been replaced by potent synthetic cannabinoids and cannabimimetics in various forms. Despite overwhelming public perception of the safety of these substances, an increasing number of serious cardiovascular adverse events have been reported in temporal relation to recreational cannabis use. These have included sudden cardiac death, vascular (coronary, cerebral and peripheral) events, arrhythmias and stress cardiomyopathy among others. Many of the victims of these events are relatively young men with few if any cardiovascular risk factors. However, there are reasons to believe that older individuals and those with risk factors for or established cardiovascular disease are at even higher danger of such events following exposure to cannabis. The pathophysiological basis of these events is not fully understood and likely encompasses a complex interaction between the active ingredients (particularly the major cannabinoid, Δ 9 -tetrahydrocannabinol), and the endo-cannabinoid system, autonomic nervous system, as well as other receptor and non-receptor mediated pathways. Other complicating factors include opposing physiologic effects of other cannabinoids (predominantly cannabidiol), presence of regulatory proteins that act as metabolizing enzymes, binding molecules, or ligands, as well as functional polymorphisms of target receptors. Tolerance to the effects of cannabis may also develop on repeated exposures at least in part due to receptor downregulation or desensitization. Moreover, effects of cannabis may be enhanced or altered by concomitant use of other illicit drugs or medications used for treatment of established cardiovascular diseases. Regardless of these considerations, it is expected that the current cannabis epidemic would add significantly to the universal burden of cardiovascular diseases.

Does the clinical spectrum of incident cardiovascular disease differ between men and women?

PubMed

Lehto, Hanna-Riikka; Lehto, Seppo; Havulinna, Aki S; Salomaa, Veikko

2014-08-01

Cardiovascular diseases (CVDs) are the main cause of death and disability in the western world. Women are known to be older at the time of first CVD event, but the main types of CVD events and their relative importance and differences compared with men are not well known. Our aim was to evaluate gender differences in the clinical presentation of incident major adverse cardiovascular events (MACE). A population-based study with prospective follow-up. We used data from the population-based National FINRISK Surveys from years 1992, 1997, 2002 and 2007. People with prevalent cardiovascular disease were excluded. In total, 27,897 participants (53, 2% women) aged 25-74 years were included in the analyses. During the 292,316 person-years of follow-up, 2573 MACE were identified. MACE were more frequent in men than women (1318; 95% CI 1252-1388 in men vs. 736; 686-789 in women). Men had four times more fatal coronary heart disease (CHD) events (149; 126-174 vs. 39; 28-53) and three times more non-fatal CHD events (512; 471-555 vs. 164; 141-189) than women. Stroke incidence was higher in men than women (268; 238-301 vs. 169; 145-195). Heart failure (HF) incidence did not differ between genders. The relative proportions of MACE categories differed substantially between genders: HF was the most common type among women (50% vs. 30% in men), whereas the most common type among men was CHD (50% vs. 28% in women). Incident MACE were more common in men than women. HF was the dominant type of MACE in women, whereas CHD dominated in men. © The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Social media and internet-based data in global systems for public health surveillance: a systematic review.

PubMed

Velasco, Edward; Agheneza, Tumacha; Denecke, Kerstin; Kirchner, Göran; Eckmanns, Tim

2014-03-01

The exchange of health information on the Internet has been heralded as an opportunity to improve public health surveillance. In a field that has traditionally relied on an established system of mandatory and voluntary reporting of known infectious diseases by doctors and laboratories to governmental agencies, innovations in social media and so-called user-generated information could lead to faster recognition of cases of infectious disease. More direct access to such data could enable surveillance epidemiologists to detect potential public health threats such as rare, new diseases or early-level warnings for epidemics. But how useful are data from social media and the Internet, and what is the potential to enhance surveillance? The challenges of using these emerging surveillance systems for infectious disease epidemiology, including the specific resources needed, technical requirements, and acceptability to public health practitioners and policymakers, have wide-reaching implications for public health surveillance in the 21st century. This article divides public health surveillance into indicator-based surveillance and event-based surveillance and provides an overview of each. We did an exhaustive review of published articles indexed in the databases PubMed, Scopus, and Scirus between 1990 and 2011 covering contemporary event-based systems for infectious disease surveillance. Our literature review uncovered no event-based surveillance systems currently used in national surveillance programs. While much has been done to develop event-based surveillance, the existing systems have limitations. Accordingly, there is a need for further development of automated technologies that monitor health-related information on the Internet, especially to handle large amounts of data and to prevent information overload. The dissemination to health authorities of new information about health events is not always efficient and could be improved. No comprehensive evaluations show whether event-based surveillance systems have been integrated into actual epidemiological work during real-time health events. The acceptability of data from the Internet and social media as a regular part of public health surveillance programs varies and is related to a circular challenge: the willingness to integrate is rooted in a lack of effectiveness studies, yet such effectiveness can be proved only through a structured evaluation of integrated systems. Issues related to changing technical and social paradigms in both individual perceptions of and interactions with personal health data, as well as social media and other data from the Internet, must be further addressed before such information can be integrated into official surveillance systems. © 2014 Milbank Memorial Fund.

Social Media and Internet-Based Data in Global Systems for Public Health Surveillance: A Systematic Review

PubMed Central

VELASCO, EDWARD; AGHENEZA, TUMACHA; DENECKE, KERSTIN; KIRCHNER, GÖRAN; ECKMANNS, TIM

2014-01-01

Context: The exchange of health information on the Internet has been heralded as an opportunity to improve public health surveillance. In a field that has traditionally relied on an established system of mandatory and voluntary reporting of known infectious diseases by doctors and laboratories to governmental agencies, innovations in social media and so-called user-generated information could lead to faster recognition of cases of infectious disease. More direct access to such data could enable surveillance epidemiologists to detect potential public health threats such as rare, new diseases or early-level warnings for epidemics. But how useful are data from social media and the Internet, and what is the potential to enhance surveillance? The challenges of using these emerging surveillance systems for infectious disease epidemiology, including the specific resources needed, technical requirements, and acceptability to public health practitioners and policymakers, have wide-reaching implications for public health surveillance in the 21st century. Methods: This article divides public health surveillance into indicator-based surveillance and event-based surveillance and provides an overview of each. We did an exhaustive review of published articles indexed in the databases PubMed, Scopus, and Scirus between 1990 and 2011 covering contemporary event-based systems for infectious disease surveillance. Findings: Our literature review uncovered no event-based surveillance systems currently used in national surveillance programs. While much has been done to develop event-based surveillance, the existing systems have limitations. Accordingly, there is a need for further development of automated technologies that monitor health-related information on the Internet, especially to handle large amounts of data and to prevent information overload. The dissemination to health authorities of new information about health events is not always efficient and could be improved. No comprehensive evaluations show whether event-based surveillance systems have been integrated into actual epidemiological work during real-time health events. Conclusions: The acceptability of data from the Internet and social media as a regular part of public health surveillance programs varies and is related to a circular challenge: the willingness to integrate is rooted in a lack of effectiveness studies, yet such effectiveness can be proved only through a structured evaluation of integrated systems. Issues related to changing technical and social paradigms in both individual perceptions of and interactions with personal health data, as well as social media and other data from the Internet, must be further addressed before such information can be integrated into official surveillance systems. PMID:24597553

Bereavement as an antecedent factor in thyrotoxicosis of childhood: four case studies with survey of possible metabolic pathways.

PubMed

Morillo, E; Gardner, L I

1979-11-01

Various organic and psychosomatic factors have been postulated over the years as etiologic events antedating the onset of Graves' disease. In some patients psychological events have appeared to be important in the evocation of symptoms. Although examples of the latter have been described in adults for many years, there is little published on this phenomenon in children. The present study delineates findings in two boys and two girls with an age range of 8 to 14 years. Separating experiences appeared to be related to the onset or relapse of Graves' disease in these particular cases. In three of the patients the trigger event was represented by bereavement after death of a close relative; in the fourth case the boy's loss was enforced and traumatic separation from his mother figure. In all these children depression was the common response to loss. The observed relationship between the affective disturbance and Graves' disease is compatible with one or more hypothetical models. One such pathway, via depletion of brain monoamines associated with the state of depression, could cause an activation of the hypothalamic-pituitary-adrenal axis with resultant suppression of immune surveillance. This could permit the formation of thyroid-stimulating immunoglobulins (TSI) and hence Graves' disease in genetically susceptible (HLA B-8) persons.

Ipilimumab for Patients With Advanced Mucosal Melanoma

PubMed Central

Postow, Michael A.; Luke, Jason J.; Bluth, Mark J.; Ramaiya, Nikhil; Panageas, Katherine S.; Lawrence, Donald P.; Ibrahim, Nageatte; Flaherty, Keith T.; Sullivan, Ryan J.; Ott, Patrick A.; Callahan, Margaret K.; Harding, James J.; D'Angelo, Sandra P.; Dickson, Mark A.; Schwartz, Gary K.; Chapman, Paul B.; Gnjatic, Sacha; Wolchok, Jedd D.; Hodi, F. Stephen

2013-01-01

The outcome of patients with mucosal melanoma treated with ipilimumab is not defined. To assess the efficacy and safety of ipilimumab in this melanoma subset, we performed a multicenter, retrospective analysis of 33 patients with unresectable or metastatic mucosal melanoma treated with ipilimumab. The clinical characteristics, treatments, toxicities, radiographic assessment of disease burden by central radiology review at each site, and mutational profiles of the patients' tumors were recorded. Available peripheral blood samples were used to assess humoral immunity against a panel of cancer-testis antigens and other antigens. By the immune-related response criteria of the 30 patients who underwent radiographic assessment after ipilimumab at approximately week 12, there were 1 immune-related complete response, 1 immune-related partial response, 6 immune-related stable disease, and 22 immune-related progressive disease. By the modified World Health Organization criteria, there were 1 immune-related complete response, 1 immune-related partial response, 5 immune-related stable disease, and 23 immune-related progressive disease. Immune-related adverse events (as graded by Common Terminology Criteria for Adverse Events version 4.0) consisted of six patients with rash (four grade 1, two grade 2), three patients with diarrhea (one grade 1, two grade 3), one patient with grade 1 thyroiditis, one patient with grade 3 hepatitis, and 1 patient with grade 2 hypophysitis. The median overall survival from the time of the first dose of ipilimumab was 6.4 months (range: 1.8–26.7 months). Several patients demonstrated serologic responses to cancer-testis antigens and other antigens. Durable responses to ipilimumab were observed, but the overall response rate was low. Additional investigation is necessary to clarify the role of ipilimumab in patients with mucosal melanoma. PMID:23716015

Ipilimumab for patients with advanced mucosal melanoma.

PubMed

Postow, Michael A; Luke, Jason J; Bluth, Mark J; Ramaiya, Nikhil; Panageas, Katherine S; Lawrence, Donald P; Ibrahim, Nageatte; Flaherty, Keith T; Sullivan, Ryan J; Ott, Patrick A; Callahan, Margaret K; Harding, James J; D'Angelo, Sandra P; Dickson, Mark A; Schwartz, Gary K; Chapman, Paul B; Gnjatic, Sacha; Wolchok, Jedd D; Hodi, F Stephen; Carvajal, Richard D

2013-06-01

The outcome of patients with mucosal melanoma treated with ipilimumab is not defined. To assess the efficacy and safety of ipilimumab in this melanoma subset, we performed a multicenter, retrospective analysis of 33 patients with unresectable or metastatic mucosal melanoma treated with ipilimumab. The clinical characteristics, treatments, toxicities, radiographic assessment of disease burden by central radiology review at each site, and mutational profiles of the patients' tumors were recorded. Available peripheral blood samples were used to assess humoral immunity against a panel of cancer-testis antigens and other antigens. By the immune-related response criteria of the 30 patients who underwent radiographic assessment after ipilimumab at approximately week 12, there were 1 immune-related complete response, 1 immune-related partial response, 6 immune-related stable disease, and 22 immune-related progressive disease. By the modified World Health Organization criteria, there were 1 immune-related complete response, 1 immune-related partial response, 5 immune-related stable disease, and 23 immune-related progressive disease. Immune-related adverse events (as graded by Common Terminology Criteria for Adverse Events version 4.0) consisted of six patients with rash (four grade 1, two grade 2), three patients with diarrhea (one grade 1, two grade 3), one patient with grade 1 thyroiditis, one patient with grade 3 hepatitis, and 1 patient with grade 2 hypophysitis. The median overall survival from the time of the first dose of ipilimumab was 6.4 months (range: 1.8-26.7 months). Several patients demonstrated serologic responses to cancer-testis antigens and other antigens. Durable responses to ipilimumab were observed, but the overall response rate was low. Additional investigation is necessary to clarify the role of ipilimumab in patients with mucosal melanoma.

76 FR 4463 - Privacy Act of 1974; Report of Modified or Altered System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-25

... occupationally related mortality or morbidity is occurring. In the event of litigation where the defendant is: (a... diseases and which provides for the confidentiality of the information. In the event of litigation..., limited log-ins, virus protection, and user rights/file attribute restrictions. Password protection...

Future cardiovascular disease in China: Markov model and risk factor scenario projections from the Coronary Heart Disease Policy Model-China

PubMed Central

Moran, Andrew; Gu, Dongfeng; Zhao, Dong; Coxson, Pamela; Wang, Y. Claire; Chen, Chung-Shiuan; Liu, Jing; Cheng, Jun; Bibbins-Domingo, Kirsten; Shen, Yu-Ming; He, Jiang; Goldman, Lee

2010-01-01

Background The relative effects of individual and combined risk factor trends on future cardiovascular disease in China have not been quantified in detail. Methods and Results Future risk factor trends in China were projected based on prior trends. Cardiovascular disease (coronary heart disease and stroke) in adults ages 35 to 84 years was projected from 2010 to 2030 using the Coronary Heart Disease Policy Model–China, a Markov computer simulation model. With risk factor levels held constant, projected annual cardiovascular events increased by >50% between 2010 and 2030 based on population aging and growth alone. Projected trends in blood pressure, total cholesterol, diabetes (increases), and active smoking (decline) would increase annual cardiovascular disease events by an additional 23%, an increase of approximately 21.3 million cardiovascular events and 7.7 million cardiovascular deaths over 2010 to 2030. Aggressively reducing active smoking in Chinese men to 20% prevalence in 2020 and 10% prevalence in 2030 or reducing mean systolic blood pressure by 3.8 mm Hg in men and women would counteract adverse trends in other risk factors by preventing cardiovascular events and 2.9 to 5.7 million total deaths over 2 decades. Conclusions Aging and population growth will increase cardiovascular disease by more than a half over the coming 20 years, and projected unfavorable trends in blood pressure, total cholesterol, diabetes, and body mass index may accelerate the epidemic. National policy aimed at controlling blood pressure, smoking, and other risk factors would counteract the expected future cardiovascular disease epidemic in China. PMID:20442213

Role of the Hemostatic System on SCD Pathophysiology and Potential Therapeutics

PubMed Central

Pakbaz, Zahra; Wun, Ted

2014-01-01

Synopsis Recent studies suggest that sickle cell disease is a hypercoagulable state contributing to the vaso-occlusive events in microcirculation resulting in acute and chronic sickle cell related organ damage. In this article, we will review the existing evidence for contribution of hemostatic system perturbation to sickle cell disease pathophysiology. We will also review the data showing increased risk of thromboembolic events, particularly newer information on the incidence of VTE. Finally, the potential role of platelet inhibitors and anticoagulants in SCD will be briefly reviewed. PMID:24589271

Drug related problems with Antiparkinsonian agents: consumer Internet reports versus published data.

PubMed

Schröder, Sabrina; Zöllner, York Francis; Schaefer, Marion

2007-10-01

There is currently a lack of detailed information concerning drug related problems in the outpatient treatment of Parkinson's disease. Problems associated with drug treatment communicated anonymously in Parkinson's disease online forums were therefore retrospectively searched and documented for 1 year. Based on postings concerning 12 drugs for the treatment of Parkinson's disease, a total of 238 drug related problems were identified and categorised using the Problem Intervention Documentation (PI-Doc). Of these, 153 were adverse drug reactions. Adverse drug reactions associated with the skin were relatively common, but central effects such as cognitive or psychiatric changes, effects on the sleep/waking system and other problems like headache and dizziness accounted for the highest percentage of adverse events. A comparison with data from scientific literature revealed a number of differences. This means that an analysis of online forums detected a number of drug related problems that were otherwise largely invisible. These were mainly associated with the qualitative aspects of treatment such as medication handling, dosage and individual problems concerning adverse events. In addition, the described method of identifying and classifying drug related problems in Internet forums may also be seen as a contribution to the international discussion about consumer reports and pharmacovigilance. The information about adverse drug reactions given by Internet users can be seen as a valuable adjunct to clinical trial data and as being very timely with regard to the event itself. Online forums may be considered as a suitable source of observational information to complement data from randomised clinical trials.

Validation of aspirin response-related transcripts in patients with coronary artery disease and preliminary investigation on CMTM5 function.

PubMed

Zhang, J W; Liu, T F; Chen, X H; Liang, W Y; Feng, X R; Wang, L; Fu, Sidney W; McCaffrey, Timothy A; Liu, M L

2017-08-15

Aspirin is widely used in the prevention of cardiovascular diseases, but the antiplatelet responses vary from one patient to another. To validate aspirin response related transcripts and illustrate their roles in predicting cardiovascular events, we have quantified the relative expression of 14 transcripts previously identified as related to high on-aspirin platelet reactivity (HAPR) in 223 patients with coronary artery disease (CAD) on regular aspirin treatment. All patients were followed up regularly for cardiovascular events (CVE). The mean age of our enrolled population was 75.80±8.57years. HAPR patients showed no significant differences in terms of co-morbidities and combined drugs. Besides, the relative expression of HLA-DQA1 was significantly lower in low on-aspirin platelet reactivity (LAPR) patients, when compared with HAPR and high normal (HN) group (p=0.028). What's more, the number of arteries involved, HAPR status and the relative expression of CLU, CMTM5 and SPARC were independent risk factors for CVE during follow up (p<0.05). In addition, overexpression of CMTM5 attenuated endothelial cells (ECs) migration and proliferation, with significantly decreased phosphorylated-Akt levels, while its inhibition promoted these processes in vitro (p<0.05).Our study provides evidence that circulating transcripts might be potential biomarkers in predicting cardiovascular events. CMTM5 might exert anti-atherosclerotic effects via suppressing migration and proliferation in the vessel wall. Nevertheless, larger-scale and long-term studies are still needed. Copyright © 2017 Elsevier B.V. All rights reserved.

Introduction--databases and the assessment of complications associated with the treatment of patients with congenital cardiac disease.

PubMed

Jacobs, Jeffrey P

2008-12-01

The Multi-Societal Database Committee for Pediatric and Congenital Heart Disease was established in 2005 with the goal of providing the infrastructure, spanning geographical and subspecialty boundaries, for collaboration between health care professionals interested in the analysis of outcomes of treatments provided to patients with congenital cardiac disease, with the ultimate aim of improvement in the quality of care provided to these patients. The purpose of these collaborative efforts is to promote the highest quality comprehensive cardiac care to all patients with congenital heart disease, from the fetus to the adult, regardless of the patient's economic means, with an emphasis on excellence in teaching, research and community service. This manuscript provides the Introduction to the 2008 Supplement to Cardiology in the Young titled: "Databases and The Assessment of Complications associated with the Treatment of Patients with Congenital Cardiac Disease". This Supplement was prepared by The Multi-Societal Database Committee for Pediatric and Congenital Heart Disease. The Multi-Societal Database Committee for Pediatric and Congenital Heart Disease offers the following definition of the term "Complication": "A complication is an event or occurrence that is associated with a disease or a healthcare intervention, is a departure from the desired course of events, and may cause, or be associated with, suboptimal outcome. A complication does not necessarily represent a breech in the standard of care that constitutes medical negligence or medical malpractice. An operative or procedural complication is any complication, regardless of cause, occurring (1) within 30 days after surgery or intervention in or out of the hospital, or (2) after 30 days during the same hospitalization subsequent to the operation or intervention. Operative and procedural complications include both intraoperative/intraprocedural complications and postoperative/postprocedural complications in this time interval." The Multi-Societal Database Committee for Pediatric and Congenital Heart Disease offers the following definition of the term "Adverse Event": "An adverse event is a complication that is associated with a healthcare intervention and is associated with suboptimal outcome. Adverse events represent a subset of complications. Not all medical errors result in an adverse event; the administration of an incorrect dose of a medication is a medical error, but it does not always result in an adverse event. Similarly, not all adverse events are the result of medical error. A child may develop pneumonia after an atrial septal defect repair despite intra- and peri-operative management that is free of error. Complications of the underlying disease state, which are not related to a medical intervention, are not adverse events. For example, a patient who presents for medical care with metastatic lung cancer has already developed a complication (Metastatic spread) of the primary lung cancer without any healthcare intervention. Furthermore, complications not associated with suboptimal outcome or harm are not adverse events and are known as no harm events. The patient who receives an incorrect dose of a medication without harm has experienced a no harm event, but not an adverse event." Based on the above definitions, it is apparent that The Multi-Societal Database Committee for Pediatric and Congenital Heart Disease has taken an inclusive approach to defining the universe of complications. Complications may or may not be associated with healthcare intervention and may or may not be associated with suboptimal outcome. Meanwhile, adverse events must be associated with healthcare intervention and must be associated with suboptimal outcome.

Fundamental paradox of survival determinism: the ur-etiology disease paradigm.

PubMed

Krsmanovic, Pavle

2013-06-01

Following a common practice in medicine, biomedical researches tend to view various disease conditions as direct results of preceding, disease-causing events. Such events are commonly those that could have been previously detected and which have given the history of studies of particular diseases, been previously recognized as playing an important role in an onset and/or progression of the disease in question. Although such practice is justified from the very principles of experimental investigation and scientific observation, it comes short of finding the fundamental causes behind these disease conditions. This manuscript proposes a different view to the origin of some types of diseases as well as some other biological phenomena. Namely, the focus of the concept relates to a notion of survival determinism, proposed to have been in the very core of evolution of primordial organisms. Thereby, as various disease models are discussed in the light of the proposed mechanisms for adaptation, they could be seen as relicts of the early evolutionary history of life on Earth.

Severe Autoimmune Adverse Events Post Herpes Zoster Vaccine: A Case-Control Study of Adverse Events in a National Database.

PubMed

Lai, Yi Chun; Yew, Yik Weng

2015-07-01

Zoster vaccine is recommended to reduce the incidence of herpes zoster and its complication of postherpetic neuralgia in older adults. However, there have been reports of autoimmune side effects post vaccination. We therefore aim to investigate the possible relationship of severe autoimmune adverse events (arthritis, vasculitis, systemic lupus erythematosus, thrombocytopenia, alopecia, Guillain-Barre syndrome, optic neuritis and multiple sclerosis) post zoster vaccination with a matched case-control study of reported events in the Vaccine Adverse Event Reporting System (VAERS). Our study showed no significantly increased risks of severe autoimmune adverse events, except arthritis and alopecia, after vaccination. Compared to the unexposed, patients with zoster vaccination had 2.2 and 2.7 times the odds of developing arthritis and alopecia, respectively (P<0.001 and P=0.015, respectively). However, almost none of these events was life threatening. Zoster vaccine is, therefore, relatively safe and unlikely to exacerbate or induce autoimmune diseases. Given its benefits and safety but low coverage, dermatologists and primary care physicians should encourage zoster vaccine use in elderly patients, including selected patients with autoimmune diseases.

Cancer-associated bone disease.

PubMed

Rizzoli, R; Body, J-J; Brandi, M-L; Cannata-Andia, J; Chappard, D; El Maghraoui, A; Glüer, C C; Kendler, D; Napoli, N; Papaioannou, A; Pierroz, D D; Rahme, M; Van Poznak, C H; de Villiers, T J; El Hajj Fuleihan, G

2013-12-01

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and working groups to assist physicians in clinical decision making, providing them with evidence-based care pathways to prevent skeletal-related events and bone loss. The goal of this paper is to put forth an IOF position paper addressing bone diseases and cancer and summarizing the position papers of other organizations.

Sleep-Disordered Breathing in Neuromuscular Disease: Diagnostic and Therapeutic Challenges.

PubMed

Aboussouan, Loutfi S; Mireles-Cabodevila, Eduardo

2017-10-01

Normal sleep-related rapid eye movement sleep atonia, reduced lung volumes, reduced chemosensitivity, and impaired airway dilator activity become significant vulnerabilities in the setting of neuromuscular disease. In that context, the compounding effects of respiratory muscle weakness and disease-specific features that promote upper airway collapse or cause dilated cardiomyopathy contribute to various sleep-disordered breathing events. The reduction in lung volumes with neuromuscular disease is further compromised by sleep and the supine position, exaggerating the tendency for upper airway collapse and desaturation with sleep-disordered breathing events. The most commonly identified events are diaphragmatic/pseudo-central, due to a decrease in the rib cage contribution to the tidal volume during phasic rapid eye movement sleep. Obstructive and central sleep apneas are also common. Noninvasive ventilation can improve survival and quality of sleep but should be used with caution in the context of dilated cardiomyopathy or significant bulbar symptoms. Noninvasive ventilation can also trigger sleep-disordered breathing events, including ineffective triggering, autotriggering, central sleep apnea, and glottic closure, which compromise the potential benefits of the intervention by increasing arousals, reducing adherence, and impairing sleep architecture. Polysomnography plays an important diagnostic and therapeutic role by correctly categorizing sleep-disordered events, identifying sleep-disordered breathing triggered by noninvasive ventilation, and improving noninvasive ventilation settings. Optimal management may require dedicated hypoventilation protocols and a technical staff well versed in the identification and troubleshooting of respiratory events. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Epidemiological evidence of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease in Japan.

PubMed

Saito, Isao

2012-01-01

Although epidemiological studies in the US and Europe have confirmed that type 2 diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD) events, evidence is limited in Japan. Earlier studies in Japan showed that hypertension has a major effect on atherosclerosis in relatively lean subjects, with type 2 DM contributing more to CVD events, because of a decline in blood pressure levels in both sexes and an increase in body mass index in men. Recent cohort studies in Japan using baseline assessments carried out during the 1990s have confirmed that type 2 DM is associated with an increased risk of coronary heart disease (CHD) and all types of stroke, except hemorrhagic stroke. In addition, the metabolic syndrome, a constellation of metabolic risk factors, was shown to predict CVD events in Japanese people, independent of the presence or absence of obesity. The strong association of type 2 DM with CHD (hazard ratio: 1.5-4) and ischemic stroke (hazard ratio: 2-4) events was confirmed in Japanese adults. Individuals with impaired glucose tolerance or impaired fasting glucose were also shown to have an increased risk of a CHD event, but not a stroke.

The Fruit Fly Drosophila melanogaster as a Model for Aging Research.

PubMed

Brandt, Annely; Vilcinskas, Andreas

2013-01-01

: Average human life expectancy is increasing and so is the impact on society of aging and age-related diseases. Here we highlight recent advances in the diverse and multidisciplinary field of aging research, focusing on the fruit fly Drosophila melanogaster, an excellent model system in which to dissect the genetic and molecular basis of the aging processes. The conservation of human disease genes in D. melanogaster allows the functional analysis of orthologues implicated in human aging and age-related diseases. D. melanogaster models have been developed for a variety of age-related processes and disorders, including stem cell decline, Alzheimer's disease, and cardiovascular deterioration. Understanding the detailed molecular events involved in normal aging and age-related diseases could facilitate the development of strategies and treatments that reduce their impact, thus improving human health and increasing longevity.

Six climate change-related events in the United States accounted for about $14 billion in lost lives and health costs.

PubMed

Knowlton, Kim; Rotkin-Ellman, Miriam; Geballe, Linda; Max, Wendy; Solomon, Gina M

2011-11-01

The future health costs associated with predicted climate change-related events such as hurricanes, heat waves, and floods are projected to be enormous. This article estimates the health costs associated with six climate change-related events that struck the United States between 2000 and 2009. The six case studies came from categories of climate change-related events projected to worsen with continued global warming-ozone pollution, heat waves, hurricanes, infectious disease outbreaks, river flooding, and wildfires. We estimate that the health costs exceeded $14 billion, with 95 percent due to the value of lives lost prematurely. Actual health care costs were an estimated $740 million. This reflects more than 760,000 encounters with the health care system. Our analysis provides scientists and policy makers with a methodology to use in estimating future health costs related to climate change and highlights the growing need for public health preparedness.

Nivolumab-induced synchronous occurrence of myositis and hypothyroidism in a patient with squamous cell lung cancer.

PubMed

Badovinac, Sonja; Korsic, Marta; Zarkovic, Kamelija; Mursic, Davorka; Roglic, Mihovil; Jakopovic, Marko; Samarzija, Miroslav

2018-03-01

Alongside the proven efficacy, immunotherapy in treatment of malignant diseases can cause immune-related adverse events different from commonly known chemotherapy-related toxicities. During nivolumab treatment of metastatic squamous cell lung cancer, the patient developed a symptomatic inflammatory myositis confirmed with muscle biopsy and primary hypothyroidism. After initiation of corticosteroids and thyroid hormone replacement, the clinical and laboratory improvement occurred. To the best of our knowledge, this is the first description of a case of nivolumab-induced synchronous manifestation of immune-related myositis and hypothyroidism. Immunotherapy can trigger a wide spectrum of immune-related adverse events that could occur simultaneously. If not detected and treated, these events could become severe or even fatal and require clinicians' awareness and routine check-ups.

Comparison of QRS Duration and Associated Cardiovascular Events in American Indian Men Versus Women (The Strong Heart Study).

PubMed

Deen, Jason F; Rhoades, Dorothy A; Noonan, Carolyn; Best, Lyle G; Okin, Peter M; Devereux, Richard B; Umans, Jason G

2017-06-01

Electrocardiographic QRS duration at rest is associated with sudden cardiac death and death from coronary heart disease in the general population. However, its relation to cardiovascular events in American Indians, a population with persistently high cardiovascular disease mortality, is unknown. The relation of QRS duration to incident cardiovascular disease during 17.2 years of follow-up was assessed in 1,851 male and female Strong Heart Study participants aged 45 to 74 years without known cardiovascular disease at baseline. Cox regression with robust standard error estimates was used to determine the association between quintiles of QRS duration and incident cardiovascular disease in gender-stratified analyses, adjusted for age, systolic blood pressure, hypertension, antihypertensive medication use, body mass index, current smoking, diabetes, total cholesterol, high-density lipoprotein cholesterol, and albuminuria. In women only, QRS duration in the highest quintile (≥105 ms) conferred significantly higher risk of cardiovascular disease than QRS duration in the lowest quintile (64 to 84 ms) (hazard ratio 1.6, 95% CI 1.1 to 2.4) likely because of higher risks of coronary heart disease (hazard ratio 1.8, 95% CI 1.1 to 3.1) and myocardial infarction (hazard ratio 2.1, 95% CI 1.0 to 4.7). Furthermore, when added to the Strong Heart Study Coronary Heart Disease Risk Calculator, QRS duration significantly improved prediction of future coronary heart disease events in women (Net Reclassification Index 0.17, 95% CI 0.06 to 0.47). In conclusion, QRS duration is an independent predictor of cardiovascular disease in women in the Strong Heart Study cohort and may have value in estimating risk in populations with similar risk profiles and a high lifetime incidence of cardiovascular disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Predictive value of reactive hyperemia for cardiovascular events in patients with peripheral arterial disease undergoing vascular surgery.

PubMed

Huang, Alex L; Silver, Annemarie E; Shvenke, Elena; Schopfer, David W; Jahangir, Eiman; Titas, Megan A; Shpilman, Alex; Menzoian, James O; Watkins, Michael T; Raffetto, Joseph D; Gibbons, Gary; Woodson, Jonathan; Shaw, Palma M; Dhadly, Mandeep; Eberhardt, Robert T; Keaney, John F; Gokce, Noyan; Vita, Joseph A

2007-10-01

Reactive hyperemia is the compensatory increase in blood flow that occurs after a period of tissue ischemia, and this response is blunted in patients with cardiovascular risk factors. The predictive value of reactive hyperemia for cardiovascular events in patients with atherosclerosis and the relative importance of reactive hyperemia compared with other measures of vascular function have not been previously studied. We prospectively measured reactive hyperemia and brachial artery flow-mediated dilation by ultrasound in 267 patients with peripheral arterial disease referred for vascular surgery (age 66+/-11 years, 26% female). Median follow-up was 309 days (range 1 to 730 days). Fifty patients (19%) had an event, including cardiac death (15), myocardial infarction (18), unstable angina (8), congestive heart failure (6), and nonhemorrhagic stroke (3). Patients with an event were older and had lower hyperemic flow velocity (75+/-39 versus 95+/-50 cm/s, P=0.009). Patients with an event also had lower flow-mediated dilation (4.5+/-3.0 versus 6.9+/-4.6%, P<0.001), and when these 2 measures of vascular function were included in the same Cox proportional hazards model, lower hyperemic flow (OR 2.7, 95% CI 1.2 to 5.9, P=0.018) and lower flow-mediated dilation (OR 4.2, 95% CI: 1.8 to 9.8, P=0.001) both predicted cardiovascular events while adjusting for other risk factors. Thus, lower reactive hyperemia is associated with increased cardiovascular risk in patients with peripheral arterial disease. Furthermore, flow-mediated dilation and reactive hyperemia incrementally relate to cardiovascular risk, although impaired flow-mediated dilation was the stronger predictor in this population. These findings further support the clinical relevance of vascular function measured in the microvasculature and conduit arteries in the upper extremity.

Changes in Caribbean coral disease prevalence after the 2005 bleaching event.

PubMed

Cróquer, Aldo; Weil, Ernesto

2009-11-16

Bleaching events and disease epizootics have increased during the past decades, suggesting a positive link between these 2 causes in producing coral mortality. However, studies to test this hypothesis, integrating a broad range of hierarchical spatial scales from habitats to distant localities, have not been conducted in the Caribbean. In this study, we examined links between bleaching intensity and disease prevalence collected from 6 countries, 2 reef sites for each country, and 3 habitats within each reef site (N = 6 x 2 x 3 = 36 site-habitat combinations) during the peak of bleaching in 2005 and a year after, in 2006. Patterns of disease prevalence and bleaching were significantly correlated (Rho = 0.58, p = 0.04). Higher variability in disease prevalence after bleaching occurred among habitats at each particular reef site, with a significant increase in prevalence recorded in 4 of the 10 site-habitats where bleaching was intense and a non-significant increase in disease prevalence in 18 out of the 26 site-habitats where bleaching was low to moderate. A significant linear correlation was found (r = 0.89, p = 0.008) between bleaching and the prevalence of 2 virulent diseases (yellow band disease and white plague) affecting the Montastraea species complex. Results of this study suggest that if bleaching events become more intense and frequent, disease-related mortality of Caribbean coral reef builders could increase, with uncertain effects on coral reef resilience.

Safety of Iohexol Administration to Measure Glomerular Filtration Rate in Different Patient Populations: A 25-Year Experience.

PubMed

Gaspari, Flavio; Thakar, Surabhi; Carrara, Fabiola; Perna, Annalisa; Trillini, Matias; Aparicio, Maria Carolina; Diadei, Olimpia; Ferrari, Silvia; Cannata, Antonio; Stucchi, Nadia; Ruggenenti, Piero; Remuzzi, Giuseppe; Perico, Norberto

2018-05-17

In clinical research setting, accurate and precise measurement of glomerular filtration rate (GFR) is essential to overcome the limitations of GFR estimation with equations, which are often unreliable. In recent decades, a method for measuring GFR by plasma clearance of iohexol, a non-ionic radiocontrast agent, was developed. To evaluate the safety of the procedure, we aimed to review all immediate adverse reactions that could be related to iohexol administration in our group's 25 years worth of experience. We retrospectively reviewed all GFR investigations in 2,891 patients, between 1992 and 2016, as part of 37 clinical trials coordinated by our group. Subjects with disparate renal diseases, kidney transplant recipients, and living donors - all with different renal function categories - were included in the surveyed clinical trials. During 15,147 GFR measurements, only one treatment-related event of moderate intensity was identified. Flushing, urticaria, and itching were observed in a diabetic patient a few minutes after iohexol administration during the first GFR measurement. The event recovered without sequelae after intravenous injection of methylprednisolone sodium succinate. The patient was not hospitalized and the event was categorized as non-serious. Eight additional non-serious events observed closely following iohexol injection were considered as not related to treatment. Thus, independent of disease conditions and GFR categories, the overall rate of treatment-related events was 0.0066%. Iohexol administration for GFR measurement is a safe procedure, even in repeated investigations in the same subject, that should be adopted in clinical research and, when needed, also in clinical practice. © 2018 S. Karger AG, Basel.

Stand-structural effects on Heterobasidion abietinum-related mortality following drought events in Abies pinsapo.

PubMed

Linares, Juan Carlos; Camarero, Jesús Julio; Bowker, Matthew A; Ochoa, Victoria; Carreira, José Antonio

2010-12-01

Climate change may affect tree-pathogen interactions. This possibility has important implications for drought-prone forests, where stand dynamics and disease pathogenicity are especially sensitive to climatic stress. In addition, stand structural attributes including density-dependent tree-to-tree competition may modulate the stands' resistance to drought events and pathogen outbreaks. To assess the effects of stand structure on root-rot-related mortality after severe droughts, we focused on Heterobasidion abietinum mortality in relict Spanish stands of Abies pinsapo, a drought-sensitive fir. We compared stand attributes and tree spatial patterns in three plots with H. abietinum root-rot disease and three plots without root-rot. Point-pattern analyses were used to investigate the scale and extent of mortality patterns and to test hypotheses related to the spread of the disease. Dendrochronology was used to date the year of death and to assess the association between droughts and growth decline. We applied a structural equation modelling approach to test if tree mortality occurs more rapidly than predicted by a simple distance model when trees are subjected to high tree-to-tree competition and following drought events. Contrary to expectations of drought mortality, the effect of precipitation on the year of death was strong and negative, indicating that a period of high precipitation induced an earlier tree death. Competition intensity, related to the size and density of neighbour trees, also induced an earlier tree death. The effect of distance to the disease focus was negligible except in combination with intensive competition. Our results indicate that infected trees have decreased ability to withstand drought stress, and demonstrate that tree-to-tree competition and fungal infection act as predisposing factors of forest decline and mortality.

TERMA Framework for Biomedical Signal Analysis: An Economic-Inspired Approach.

PubMed

Elgendi, Mohamed

2016-11-02

Biomedical signals contain features that represent physiological events, and each of these events has peaks. The analysis of biomedical signals for monitoring or diagnosing diseases requires the detection of these peaks, making event detection a crucial step in biomedical signal processing. Many researchers have difficulty detecting these peaks to investigate, interpret and analyze their corresponding events. To date, there is no generic framework that captures these events in a robust, efficient and consistent manner. A new method referred to for the first time as two event-related moving averages ("TERMA") involves event-related moving averages and detects events in biomedical signals. The TERMA framework is flexible and universal and consists of six independent LEGO building bricks to achieve high accuracy detection of biomedical events. Results recommend that the window sizes for the two moving averages ( W 1 and W 2 ) have to follow the inequality ( 8 × W 1 ) ≥ W 2 ≥ ( 2 × W 1 ) . Moreover, TERMA is a simple yet efficient event detector that is suitable for wearable devices, point-of-care devices, fitness trackers and smart watches, compared to more complex machine learning solutions.

Review article: the endocannabinoid system in liver disease, a potential therapeutic target.

PubMed

Basu, P P; Aloysius, M M; Shah, N J; Brown, R S

2014-04-01

Endocannabinoids are a family of potent lipid-soluble molecules, acting on the cannabinoid (CB) receptors that mediate the effects of marijuana. The CB receptors, endocannabinoids and the enzymes involved in their synthesis and degradation are located in the brain and peripheral tissues, including the liver. To review the current understanding of the role of the endocannabinoid system in liver disease-associated pathophysiological conditions, and drugs targeting the endocannabinoid system as therapy for liver disease. Original articles and reviews were used to summarise the relevant pre-clinical and clinical research findings relating to this topic. The endocannabinoid system as a whole plays an important role in liver diseases (i.e. non-alcoholic liver disease, alcoholic liver disease, hepatic encephalopathy and autoimmune hepatitis) and related pathophysiological conditions (i.e. altered hepatic haemodynamics, cirrhotic cardiomyopathy, metabolic syndrome and ischaemia/reperfusion disease). Pharmacological targeting of the endocannabinoid system has had success as treatment for patients with liver disease, but adverse events led to withdrawal of marketing approval. However, there is optimism over novel therapeutics targeting the endocannabinoid system currently in the pre-clinical stage of development. The endocannabinoid system plays an important role in the pathophysiology of liver disease and its associated conditions. While some drugs targeting the endocannabinoid system have deleterious neurological adverse events, there is promise for a newer generation of therapies that do not cross the blood-brain barrier. © 2014 John Wiley & Sons Ltd.

Effective prevention of cardiovascular disease and diabetes-related events with atorvastatin in Japanese elderly patients with type 2 diabetes mellitus: adjusting for treatment changes using a marginal structural proportional hazards model and a rank-preserving structural failure time model.

PubMed

Shinozaki, Tomohiro; Matsuyama, Yutaka; Iimuro, Satoshi; Umegaki, Hiroyuki; Sakurai, Takashi; Araki, Atsushi; Ohashi, Yasuo; Ito, Hideki

2012-04-01

To assess the preventive effect of atorvastatin on cardiovascular disease and on diabetes-related events in elderly type 2 diabetic patients enrolled in the Japanese Elderly Diabetes Intervention Trial (J-EDIT). Data were obtained from 1173 patients aged 65-84 years who were enrolled in the J-EDIT. Patients were followed prospectively for 6 years to determine the effects of atorvastatin on serum cholesterol levels, and cardiovascular and diabetes-related events. Because the study protocol allowed atorvastatin to be prescribed according to the clinical needs of each patient, we regarded the J-EDIT data as if they came from a cohort study. We adjusted for clinical characteristics during the study as time-dependent confounders using two methods, inverse-probability-of-treatment (IPT) weighting and g-estimation method. The total follow-up period was 5310.8 person-years (5.7 years of median follow up), during which 202 patients received atorvastatin treatment. Atorvastatin was associated with moderate reductions in cholesterol levels: 24.2 mg/dL for total cholesterol, 22.9 mg/dL for low-density lipoprotein (LDL) cholesterol and 24.3 mg/dL for non-high-density lipoprotein cholesterol at the first post-treatment year. As a result, the proportion of patients who achieved targeted levels of LDL cholesterol clearly increased after atorvastatin treatment. Eight patients in 476.6 person-years among atorvastatin-treated and 113 untreated patients in 4721.4 person-years had cardiovascular events (the composite end-point of fatal/non-fatal myocardial infarction, angina pectoris, coronary intervention, and fatal/non-fatal cerebrovascular disease); hazard ratio (HR) = 0.48, 95% confidence interval (CI) = 0.19-1.16, P = 0.10, and HR = 0.32, 95% CI = 0.05-1.87, P = 0.21 from IPT weighting and g-estimation method, respectively. Furthermore, seven in 475.0 person-years among atorvastatin-treated and 149 untreated patients in 4682.4 person-years had diabetes-related events (the composite end-point of sudden death, renal failure death, death as a result of hyperglycemia or hypoglycemia, diabetic gangrene and congestive heart failure in addition to cardiovascular event); HR = 0.30, 95% CI = 0.12-0.77, P = 0.01, and HR = 0.40, 95% CI = 0.09-0.89, P = 0.03 from IPT weighting and g-estimation method, respectively. When cardiovascular events were further differentiated into coronary vascular and cerebrovascular events, atorvastatin especially decreased the cerebrovascular risk. The use of atorvastatin to lower cholesterol levels in elderly Japanese patients with type 2 diabetes mellitus appears to reduce the risk of cardiovascular and diabetes-related events. © 2012 Japan Geriatrics Society.

Incidence of clinical symptoms during long-duration orbital spaceflight.

PubMed

Crucian, Brian; Babiak-Vazquez, Adriana; Johnston, Smith; Pierson, Duane L; Ott, C Mark; Sams, Clarence

2016-01-01

The environment of spaceflight may elevate an astronaut's clinical risk for specific diseases. The purpose of this study was to derive, as accurately as currently possible, an assessment of in-flight clinical "incidence" data, based on observed clinical symptoms in astronauts on board the International Space Station (ISS). Electronic medical records were examined from 46 long-duration ISS crew members, each serving approximately a 6-month mission on board the ISS, constituting 20.57 total flight years. Incidence for immunological-related adverse health events or relevant clinical symptoms was tabulated in a non-identifiable fashion. Event categories included infectious diseases, allergies, and rashes/hypersensitivities. A subsequent re-evaluation of more notable events, either of prolonged duration or unresponsive to treatment, was performed. For the disease/symptom categories used in this evaluation, the ISS incidence rate was 3.40 events per flight year. Skin rashes were the most reported event (1.12/flight year) followed by upper respiratory symptoms (0.97/flight year) and various other (non-respiratory) infectious processes. During flight, 46% of crew members reported an event deemed "notable". Among the notable events, 40% were classified as rashes/hypersensitivities. Characterization of on-orbit rashes manifested as redness with irritation, and could present on a variety of body locations. Based on reported symptoms, astronauts experience adverse medical events of varying severity during long-duration spaceflights. The data suggests caution, from both a vehicle design and biomedical countermeasures perspective, as space agencies plan for prolonged deep space exploration missions.

Cardiovascular ischemic event rates in outpatients with symptomatic atherothrombosis or risk factors in the united states: insights from the REACH Registry.

PubMed

Eagle, Kim A; Hirsch, Alan T; Califf, Robert M; Alberts, Mark J; Steg, P Gabriel; Cannon, Christopher P; Brennan, Danielle M; Bhatt, Deepak L

2009-06-01

Atherothrombosis, defined as coronary artery, cerebrovascular, and peripheral arterial disease, is the leading cause of death in the United States. Limited data are available from outpatient populations to describe contemporary cardiovascular ischemic event rates and associated use of risk reduction treatments in patients with clinically manifest, or at risk for, atherothrombosis. The REduction of Atherothrombosis for Continued Health (REACH) Registry is an international, prospective, observational study of patients with either documented atherothrombotic syndromes or 3 or more risk factors designed to fill this knowledge gap. Baseline demographics and 1-year outcomes were evaluated for US patients enrolled in the REACH Registry. Multivariate analytic models were constructed using baseline characteristics to determine independent predictors of 1-year event rates. In the United States, 25,686 patients were enrolled into the registry. Among symptomatic patients (n = 19,069), 19% had disease in >or=1 arterial bed. As of July 2006, 1-year outcomes were available for 93.4% (n = 23,985) of patients. The composite cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke event rate was 4.3% for the overall population and highest in patients with triple bed disease (9.9%). There was a relatively high use of risk reduction medications among symptomatic patients. However, opportunity for improvement remains. Approximately 9% of symptomatic patients were not using any antithrombotic, 7% were not using any antihypertensive agents, and 17% were not taking a lipid-lowering agent, whereas >80% of patients suffered from hypertension or dyslipidemia. US patients with established atherothrombotic disease continue to experience high cardiovascular ischemic event rates; these rates increase in close association with polyvascular disease. Despite the use of risk reduction interventions, ideal secondary prevention of ischemic events has not been achieved.

The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol Rationale and study design. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH).

PubMed

2011-03-01

The aim of this study was to test the hypothesis that patients with atherosclerotic cardiovascular (CV) disease optimally treated on a statin but with residual atherogenic dyslipidemia (low high-density lipoprotein cholesterol [HDL-C] and high triglycerides) will benefit from addition of niacin with fewer CV events compared with placebo. Statin monotherapy trials have found 25%-35% CV risk reduction relative to placebo, leaving significant residual risk. Patients with atherogenic dyslipidemia have substantially increased CV risk. Participants were men and women with established CV disease and atherogenic dyslipidemia. Lipid entry criteria varied by gender and statin dose at screening. All participants received simvastatin (or simvastatin plus ezetimibe) at a dose sufficient to maintain low-density lipoprotein cholesterol (LDL-C) 40-80 mg/dL (1.03-2.07 mmol/L). Participants were randomized to extended-release niacin or matching placebo. The primary end point was time to occurrence of the first of the following: coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or symptom-driven coronary or cerebral revascularization. This event-driven trial will have 85% power to show a 25% reduction in primary event frequency after 850 patients have experienced a primary outcome event. AIM-HIGH completed enrollment in April 2010. Follow-up is expected to continue through 2012. AIM-HIGH was designed to determine whether treating residual dyslipidemia with niacin further reduces cardiovascular events in patients with CV disease on a statin at target levels of low-density lipoprotein cholesterol. Copyright © 2011 Mosby, Inc. All rights reserved.

Alcohol consumption and risk of recurrent cardiovascular events and mortality in patients with clinically manifest vascular disease and diabetes mellitus: the Second Manifestations of ARTerial (SMART) disease study.

PubMed

Beulens, J W J; Algra, A; Soedamah-Muthu, S S; Visseren, F L J; Grobbee, D E; van der Graaf, Y

2010-09-01

This study investigated the relation between alcohol consumption and specific vascular events and mortality in a high risk population of patients with clinical manifestations of vascular disease and diabetes. Patients with clinically manifest vascular disease or diabetes (n=5447) from the SMART study were followed for cardiovascular events and mortality. Alcohol consumption was assessed with a baseline questionnaire and analysed in relation with coronary heart disease (CHD), amputations, stroke, and all-cause and vascular death. After a follow up of 4.7 years, we documented 363 cases of CHD, 187 cases of stroke, 79 amputations and 641 cases of all-cause death, of which 382 were vascular. In multivariate-adjusted models, alcohol consumption was inversely associated with CHD (p(linear trend)=0.007) and stroke (p(linear trend)=0.051) with respective hazard ratios of 0.39 (95%CI: 0.20-0.76) and 0.67 (0.31-1.46) for consuming 10-20 drinks/week compared with abstainers. We observed significant U-shaped associations between alcohol consumption and amputations (p(quadratic trend)=0.001), all-cause death (p(quadratic trend)=0.001) and vascular death (p(quadratic trend)=0.013). Hazard ratios for consuming 10-20 drinks/week were 0.29 (0.07-1.30) for amputations, 0.40 (0.24-0.69) for all-cause death and 0.34 (0.16-0.71) for vascular death compared with abstainers. Similar associations were observed for red wine consumption only. Moderate alcohol consumption (1-2 drinks/day) is not only associated with a reduced risk of vascular and all-cause death in a high risk patients with clinical manifestations of vascular disease, but also with reduced risks of non-fatal events like CHD, stroke and possibly amputations. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Effect of micronutrient supplementation on disease progression in asymptomatic, antiretroviral-naive, HIV-infected adults in Botswana: a randomized clinical trial.

PubMed

Baum, Marianna K; Campa, Adriana; Lai, Shenghan; Sales Martinez, Sabrina; Tsalaile, Lesedi; Burns, Patricia; Farahani, Mansour; Li, Yinghui; van Widenfelt, Erik; Page, John Bryan; Bussmann, Hermann; Fawzi, Wafaie W; Moyo, Sikhulele; Makhema, Joseph; Thior, Ibou; Essex, Myron; Marlink, Richard

2013-11-27

Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive. To investigate whether long-term micronutrient supplementation is effective and safe in delaying disease progression when implemented early in adults infected with HIV subtype C who are ART-naive. Randomized clinical trial of supplementation with either daily multivitamins (B vitamins and vitamins C and E), selenium alone, or multivitamins with selenium vs placebo in a factorial design for 24 months. The study was conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/μL who were not receiving ART at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009. Daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo. Reaching a CD4 cell count less than 200/μL until May 2008; after this date, reaching a CD4 cell count of 250/μL or less, consistent with the standard of care in Botswana for initiation of ART at the time of the study. There were 878 participants enrolled and randomized into the study. All participants were ART-naive throughout the study. In intent-to-treat analysis, participants receiving the combined supplement of multivitamins plus selenium had a significantly lower risk vs placebo of reaching CD4 cell count 250/μL or less (adjusted hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01; absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17 events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events). Multivitamins plus selenium in a single supplement, vs placebo, also reduced the risk of secondary events of combined outcomes for disease progression (CD4 cell count ≤250/μL, AIDS-defining conditions, or AIDS-related death, whichever occurred earlier [adjusted HR, 0.56; 95% CI, 0.33-0.95; P = .03; AER, 6.48/100 person-years; censoring rate, 0.90; 23 events]). There was no effect of supplementation on HIV viral load. Multivitamins alone and selenium supplementation alone were not statistically different from placebo for any end point. Reported adverse events were adjudicated as unlikely to be related to the intervention, and there were no notable differences in incidence of HIV-related and health-related events among study groups. In ART-naive HIV-infected adults, 24-month supplementation with a single supplement containing multivitamins and selenium was safe and significantly reduced the risk of immune decline and morbidity. Micronutrient supplementation may be effective when started in the early stages of HIV disease.

Health-related quality of life in patients with atopic dermatitis.

PubMed

Maksimović, Nataša; Janković, Slavenka; Marinković, Jelena; Sekulović, Lidija K; Zivković, Zorica; Spirić, Vesna T

2012-01-01

Atopic dermatitis (AD) is a chronic relapsing condition that can have considerable effects on the patients' quality of life (QOL). The aim of this study was to measure the health-related QOL in patients with AD, using generic and specific instruments, to compare the scores obtained by different instruments and to verify the relationship between them. We conducted a cross-sectional study of 132 outpatients with AD. To assess the QOL, Short Form 36 (SF-36), Dermatology Life Quality Index (DLQI) and Children's Dermatology Life Quality Index (CDLQI) were administered. In order to assess the disease severity of AD, we used the Eczema Area and Severity Index (EASI) and physician assessment of disease severity. Stressful life events during the last 12 months were assessed with Paykel's Interview for Recent Life Events. Patients with AD had inferior social functioning and mental health scores compared with the general population. The correlations between the DLQI and SF-36 were found for the mental components of the QOL. Increasing disease severity was associated with greater impairment in QOL in both, children and adults. Our study found the influence of the stressful life events on the role emotional of AD patients. These results demonstrate that AD influences health-related QOL, especially in children. This study supports the decision to use both generic and skin-specific instruments to assess the impact of AD on QOL. © 2011 Japanese Dermatological Association.

Colonoscopy

MedlinePlus

... detected. 5 May detect up to 3% of advanced cancers and 23% of precancerous lesions. 6 Flexible ... events are related to sedation and increase with advanced age and other diseases. 14 Checking for any ...

Avian wildlife mortality events due to salmonellosis in the United States, 1985-2004

USGS Publications Warehouse

Hall, A.J.; Saito, E.K.

2008-01-01

Infection with Salmonella spp. has long been recognized in avian wildlife, although its significance in causing avian mortality, and its zoonotic risk, is not well understood. This study evaluates the role of Salmonella spp. in wild bird mortality events in the United States from 1985 through 2004. Analyses were performed to calculate the frequency of these events and the proportional mortality by species, year, month, state, and region. Salmonellosis was a significant contributor to mortality in many species of birds; particularly in passerines, for which 21.5% of all mortality events involved salmonellosis. The proportional mortality averaged a 12% annual increase over the 20-yr period, with seasonal peaks in January and April. Increased salmonellosis-related mortality in New England, Southeastern, and Mountain-Prairie states was identified. Based on the results of this study, salmonellosis can be considered an important zoonotic disease of wild birds. ?? Wildlife Disease Association 2008.

The Importance of First Impressions: Early Events in Mycobacterium tuberculosis Infection Influence Outcome.

PubMed

Cadena, Anthony M; Flynn, JoAnne L; Fortune, Sarah M

2016-04-05

Tuberculosis remains a major health threat in much of the world. New vaccines against Mycobacterium tuberculosis are essential for preventing infection, disease, and transmission. However, the host immune responses that need to be induced by an effective vaccine remain unclear. Increasingly, it has become clear that early events in infection are of major importance in the eventual outcome of the infection. Studying such events in humans is challenging, as they occur within the lung and thoracic lymph nodes, and any clinical signs of early infection are relatively nonspecific. Nonetheless, clinical studies and animal models of tuberculosis have provided new insights into the local events that occur in the first few weeks of tuberculosis. Development of an effective vaccine requires a clear understanding of the successful (and detrimental) early host responses against M. tuberculosis, with the goal to improve upon natural immune responses and prevent infection or disease. Copyright © 2016 Cadena et al.

Unanticipated hospital admission in pediatric patients with congenital heart disease undergoing ambulatory noncardiac surgical procedures.

PubMed

Yuki, Koichi; Koutsogiannaki, Sophia; Lee, Sandra; DiNardo, James A

2018-05-18

An increasing number of surgical and nonsurgical procedures are being performed on an ambulatory basis in children. Analysis of a large group of pediatric patients with congenital heart disease undergoing ambulatory procedures has not been undertaken. The objective of this study was to characterize the profile of children with congenital heart disease who underwent noncardiac procedures on an ambulatory basis at our institution, to determine the incidence of adverse cardiovascular and respiratory adverse events, and to determine the risk factors for unscheduled hospital admission. This is a retrospective study of children with congenital heart disease who underwent noncardiac procedures on an ambulatory basis in a single center. Using the electronic preoperative anesthesia evaluation form, we identified 3010 patients with congenital heart disease who underwent noncardiac procedures of which 1028 (34.1%) were scheduled to occur on an ambulatory basis. Demographic, echocardiographic and functional status data, cardiovascular and respiratory adverse events, and reasons for postprocedure admission were recorded. Univariable analysis was conducted. The unplanned hospital admission was 2.7% and univariable analysis demonstrated that performance of an echocardiogram within 6 mo of the procedure and procedures performed in radiology were associated with postoperative admission. Cardiovascular adverse event incidence was 3.9%. Respiratory adverse event incidence was 1.8%. Ambulatory, noncomplex procedures can be performed in pediatric patients with congenital heart disease and good functional status with a relatively low unanticipated hospital admission rate. © 2018 John Wiley & Sons Ltd.

Public health surveillance for the Toronto 2015 Pan/Parapan American Games.

PubMed

Chan, E; Hohenadel, K; Lee, B; Helferty, M; Harris, J R; Macdonald, L; Badiani, T

2017-07-06

Public health surveillance for previous Olympic and Paralympic Games have been described in the literature, but surveillance for regional, multisport events on a smaller scale have rarely been explored. To describe the public health surveillance planning, implementation, results, and lessons learned from the 2015 Pan/Parapan American Games in Toronto, Ontario, Canada. Public health surveillance planning for the Games began two years in advance and involved local, provincial and federal partners, primarily focusing on infectious disease. From June to August, 2015, enhanced public health surveillance was conducted to support situational awareness and to facilitate the detection of infectious diseases and outbreaks, environmental health hazards and impacts and other major health events. No major public health incidents occurred that were associated with or a result of hosting the Games. There were two cases of reportable infectious diseases associated with the Games, and 18 public health investigations involving Games-accredited individuals (six related to vaccine-preventable diseases and 12 related to gastrointestinal illnesses or food/water safety violations). Enhanced communication mechanisms, rather than routine and syndromic surveillance systems, were the primary sources of initial notification to surveillance partners on investigations. Working with its partners, Ontario created a robust public health surveillance system for the 2015 Pan/Parapan American Games. Lessons learned, as well as the relationships and capacity developed through this experience, will be applied towards public health surveillance planning for future events.

Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People With Parkinson Disease Psychosis.

PubMed

Ballard, Clive; Isaacson, Stuart; Mills, Roger; Williams, Hilde; Corbett, Anne; Coate, Bruce; Pahwa, Rajesh; Rascol, Olivier; Burn, David J

2015-10-01

To establish the mortality risk and adverse events associated with the use of atypical antipsychotic medications in people with Parkinson disease psychosis (PDP) in a clinically defined trial cohort. Post hoc analysis of data from a multicenter, open-label extension study of pimavanserin comparing people taking and not taking current antipsychotics. Primary and secondary care medical centers in the United States, Canada, Europe, and India. A total of 459 people with PDP enrolled in the extension study. Participants were between ages 30 and 80 years, and had an established diagnosis of idiopathic Parkinson disease and moderate to severe psychosis. Participants were categorized into 2 groups: those receiving concomitant antipsychotic medications ("concurrent APD") and those who did not take antipsychotic medications at any time during the study ("no APD"). Participants were receiving 40 mg pimavanserin daily in addition to concurrent antipsychotics and Parkinson disease medications. Safety assessments at 2 weeks; 1, 3, 6, 9, and 12 months; and every 6 months thereafter, including evaluation of adverse events (AEs), vital signs, weight, physical examinations, 12-lead electrocardiograms, clinical laboratory tests (serum chemistry, hematology, and urinalysis), and the Unified Parkinson's Disease Rating Scale Parts II and III (UPDRS-II+III, activities of daily living and motor impairment, respectively). Differences between participants taking and not taking current antipsychotics were evaluated using incidence rate ratios (IRRs) with 95% confidence intervals (CIs). There was significant increase in the mortality rate for participants taking concurrent antipsychotics compared with the group not taking antipsychotic medications (IRR 4.20, 95% CI 2.13-7.96). Participants who received a concurrent antipsychotic were also significantly more likely to experience overall a serious AE (IRR 2.95, 95% CI 2.02-4.24), any antipsychotic-related event (IRR 1.66, 95% CI 1.18-2.29), cognition-related events (IRR 2.70, 95% CI 1.19-5.58), infections (IRR 1.97, 95% CI 1.17-3.16), and edema (IRR 2.61, 95% CI 1.09-5.59). The risk of falls, stroke, sedation, orthostatic hypotension, and thromboembolic events was also increased in these individuals but this was not significant. This study highlights a significant risk of mortality, and severe AEs in patients with Parkinson disease receiving atypical antipsychotics. This is similar to or greater than the risks seen in people with Alzheimer disease, although with a less clear-cut risk of stroke and a longer delay to increased mortality. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Decision Trajectories in Dementia Care Networks: Decisions and Related Key Events.

PubMed

Groen-van de Ven, Leontine; Smits, Carolien; Oldewarris, Karen; Span, Marijke; Jukema, Jan; Eefsting, Jan; Vernooij-Dassen, Myrra

2017-10-01

This prospective multiperspective study provides insight into the decision trajectories of people with dementia by studying the decisions made and related key events. This study includes three waves of interviews, conducted between July 2010 and July 2012, with 113 purposefully selected respondents (people with beginning to advanced stages of dementia and their informal and professional caregivers) completed in 12 months (285 interviews). Our multilayered qualitative analysis consists of content analysis, timeline methods, and constant comparison. Four decision themes emerged-managing daily life, arranging support, community living, and preparing for the future. Eight key events delineate the decision trajectories of people with dementia. Decisions and key events differ between people with dementia living alone and living with a caregiver. Our study clarifies that decisions relate not only to the disease but to living with the dementia. Individual differences in decision content and sequence may effect shared decision-making and advance care planning.

Trauma, stressful life events and depression predict HIV-related fatigue

PubMed Central

Leserman, J.; Barroso, J.; Pence, B.W.; Salahuddin, N.; Harmon, J.L.

2008-01-01

Despite the fact that fatigue is a common and debilitating symptom among HIV-infected persons, we know little about the predictors of fatigue in this population. The goal of this cross-sectional study was to examine the effects of early childhood trauma, recent stressful life events and depression on intensity and impairment of fatigue in HIV, over and above demographic factors and clinical characteristics. We studied 128 HIV-infected men and women from one southern state. The median number of childhood traumatic events was two and participants tended to have at least one moderate recent stressful event. Multiple regression findings showed that patients with less income, more childhood trauma, more recent stressful events and more depressive symptoms had greater fatigue intensity and fatigue-related impairment in daily functioning. Recent stresses were a more powerful predictor of fatigue than childhood trauma. None of the disease-related measures (e.g. CD4, viral load, antiretroviral medication) predicted fatigue. Although stress and trauma have been related to fatigue in other populations, this is the first study to examine the effects of traumatic and recent stressful life events on fatigue in an HIV-infected sample. PMID:18608079

Trauma, stressful life events and depression predict HIV-related fatigue.

PubMed

Leserman, J; Barroso, J; Pence, B W; Salahuddin, N; Harmon, J L

2008-11-01

Despite the fact that fatigue is a common and debilitating symptom among HIV-infected persons, we know little about the predictors of fatigue in this population. The goal of this cross-sectional study was to examine the effects of early childhood trauma, recent stressful life events and depression on intensity and impairment of fatigue in HIV, over and above demographic factors and clinical characteristics. We studied 128 HIV-infected men and women from one southern state. The median number of childhood traumatic events was two and participants tended to have at least one moderate recent stressful event. Multiple regression findings showed that patients with less income, more childhood trauma, more recent stressful events and more depressive symptoms had greater fatigue intensity and fatigue-related impairment in daily functioning. Recent stresses were a more powerful predictor of fatigue than childhood trauma. None of the disease-related measures (e.g. CD4, viral load, antiretroviral medication) predicted fatigue. Although stress and trauma have been related to fatigue in other populations, this is the first study to examine the effects of traumatic and recent stressful life events on fatigue in an HIV-infected sample.

Surveillance for waterborne disease and outbreaks associated with recreational water use and other aquatic facility-associated health events-United States, 2005-2006

EPA Science Inventory

PROBLEM/CONDITION: Since 1971, CDC, the U.S. Environmental Protection Agency, and the Council of State and Territorial Epidemiologists have collaboratively maintained the Waterborne Disease and Outbreak Surveillance System for collecting and reporting data related to waterborne-d...

Bioterrorism and Real-World Science

ERIC Educational Resources Information Center

Johnson, Carla

2003-01-01

Recent events, such as the anthrax scares and the SARS outbreak, have forced teachers to focus on issues such as disease control and bioterrorism in their own backyards. Students are aware of the current biological issues in the news and are curious about infectious diseases and the issues relating to biological warfare. In order to address the…

Extraction of a group-pair relation: problem-solving relation from web-board documents.

PubMed

Pechsiri, Chaveevan; Piriyakul, Rapepun

2016-01-01

This paper aims to extract a group-pair relation as a Problem-Solving relation, for example a DiseaseSymptom-Treatment relation and a CarProblem-Repair relation, between two event-explanation groups, a problem-concept group as a symptom/CarProblem-concept group and a solving-concept group as a treatment-concept/repair concept group from hospital-web-board and car-repair-guru-web-board documents. The Problem-Solving relation (particularly Symptom-Treatment relation) including the graphical representation benefits non-professional persons by supporting knowledge of primarily solving problems. The research contains three problems: how to identify an EDU (an Elementary Discourse Unit, which is a simple sentence) with the event concept of either a problem or a solution; how to determine a problem-concept EDU boundary and a solving-concept EDU boundary as two event-explanation groups, and how to determine the Problem-Solving relation between these two event-explanation groups. Therefore, we apply word co-occurrence to identify a problem-concept EDU and a solving-concept EDU, and machine-learning techniques to solve a problem-concept EDU boundary and a solving-concept EDU boundary. We propose using k-mean and Naïve Bayes to determine the Problem-Solving relation between the two event-explanation groups involved with clustering features. In contrast to previous works, the proposed approach enables group-pair relation extraction with high accuracy.

Sentinel Health Events (occupational): a basis for physician recognition and public health surveillance.

PubMed Central

Rutstein, D D; Mullan, R J; Frazier, T M; Halperin, W E; Melius, J M; Sestito, J P

1983-01-01

A Sentinel Health Event (SHE) is a preventable disease, disability, or untimely death whose occurrence serves as a warning signal that the quality of preventive and/or therapeutic medical care may need to be improved. A SHE (Occupational) is a disease, disability, or untimely death which is occupationally related and whose occurrence may: 1) provide the impetus for epidemiologic or industrial hygiene studies; or 2) serve as a warning signal that materials substitution, engineering control, personal protection, or medical care may be required. The present SHE(O) list encompasses 50 disease conditions that are linked to the workplace. Only those conditions are included for which objective documentation of an associated agent, industry, and occupation exists in the scientific literature. The list will serve as a framework for developing a national system for occupational health surveillance that may be applied at the state and local level, and as a guide for practicing physicians caring for patients with occupational illnesses. We expect to update the list periodically to accommodate new occupational disease events which meet the criteria for inclusion. PMID:6881402

Edema index-guided disease management improves 6-month outcomes of patients with acute heart failure.

PubMed

Liu, Min-Hui; Wang, Chao-Hung; Huang, Yu-Yen; Tung, Tao-Hsin; Lee, Chii-Ming; Yang, Ning-I; Wang, Jong-Shyan; Kuo, Li-Tang; Cherng, Wen-Jin

2012-01-01

The efficacy of heart failure (HF) management programs is compromised by the challenge of early identification of patients at imminent risk. Segmental multifrequency bioelectrical impedance analysis can generate an "edema index" (EI) as a surrogate for the body fluid status. In this study, we tested whether integration of EI-guided management improved the 6-month outcomes of HF patients under multidisciplinary care. In total, 159 patients with acute HF were randomized into control, case management (CM), and EI-guided CM (EI) groups (n = 53 in each group). In the EI group, a management algorithm was designed based on the measured EI. The analyzed endpoints included HF-related and all cause-related events during the 6-month follow-up period. In the 6 months, there were 11 (6.9%) deaths, 19 (11.9%) HF-related rehospitalizations, and 45 (28.3%) all-cause-related rehospitalizations. Compared to the control (26.4%) and CM groups (15.1%), the EI group had a lower rate of HF-related death and rehospitalization (3.8%, P = 0.004). Multivariate analysis revealed that EI-guided management was an independent predictor of a lower HF-related event rate (hazard ratio = 0.15, 95%CI = 0.03~0.66, P = 0.012). Patients with a higher pre-discharge EI were older, had lower blood albumin and hemoglobin levels, and had a higher functional class and incidences of diabetes mellitus and chronic kidney disease. An increase in the pre-discharge EI by 0.001 increased the HF-related event rate by 6% (P = 0.002). Use of EI-guided management lowered this risk (P = 0.03). In conclusion, an EI-based HF management program demonstrated an event-lowering effect superior to traditional nurse-led multidisciplinary care in 6 months after an acute HF episode.

Stressful life events and acute kidney injury in intensive and semi-intensive care unities.

PubMed

Diniz, Denise Para; Marques, Daniella Aparecida; Blay, Sérgio Luis; Schor, Nestor

2012-03-01

Several studies point out that pathophysiological changes related to stress may influence renal function and are associated with disease onset and evolution. However, we have not found any studies about the influence of stress on renal function and acute kidney injury. To evaluate the association between stressful life events and acute kidney injury diagnosis, specifying the most stressful classes of events for these patients in the past 12 months. Case-control study. The study was carried out at Hospital São Paulo, in Universidade Federal de São Paulo and at Hospital dos Servidores do Estado de São Paulo, in Brazil. Patients with acute kidney injury and no chronic disease, admitted to the intensive or semi-intensive care units were included. Controls included patients in the same intensive care units with other acute diseases, except for the acute kidney injury, and also with no chronic disease. Out of the 579 patients initially identified, 475 answered to the Social Readjustment Rating Scale (SRRS) questionnaire and 398 were paired by age and gender (199 cases and 199 controls). The rate of stressful life events was statistically similar between cases and controls. The logistic regression analysis to detect associated effects of the independent variables to the stressful events showed that: increasing age and economic classes A and B in one of the hospitals (Hospital São Paulo - UNIFESP) increased the chance of a stressful life event (SLE). This study did not show association between the Acute Kidney Injury Group with a higher frequency of stressful life events, but that old age, higher income, and type of clinical center were associated.

Missing rings in Pinus halepensis – the missing link to relate the tree-ring record to extreme climatic events

Treesearch

Klemen Novak; Martin de Luis; Miguel A. Saz; Luis A. Longares; Roberto Serrano-Notivoli; Josep Raventos; Katarina Cufar; Jozica Gricar; Alfredo Di Filippo; Gianluca Piovesan; Cyrille B.K. Rathgeber; Andreas Papadopoulos; Kevin T. Smith

2016-01-01

Climate predictions for the Mediterranean Basin include increased temperatures, decreased precipitation, and increased frequency of extreme climatic events (ECE). These conditions are associated with decreased tree growth and increased vulnerability to pests and diseases. The anatomy of tree rings responds to these environmental conditions. Quantitatively, the width of...

Focused ultrasound subthalamotomy in patients with asymmetric Parkinson's disease: a pilot study.

PubMed

Martínez-Fernández, Raul; Rodríguez-Rojas, Rafael; Del Álamo, Marta; Hernández-Fernández, Frida; Pineda-Pardo, Jose A; Dileone, Michele; Alonso-Frech, Fernando; Foffani, Guglielmo; Obeso, Ignacio; Gasca-Salas, Carmen; de Luis-Pastor, Esther; Vela, Lydia; Obeso, José A

2018-01-01

Ablative neurosurgery has been used to treat Parkinson's disease for many decades. MRI-guided focused ultrasound allows focal lesions to be made in deep brain structures without skull incision. We investigated the safety and preliminary efficacy of unilateral subthalamotomy by focused ultrasound in Parkinson's disease. This prospective, open-label pilot study was done at CINAC (Centro Integral de Neurociencias), University Hospital HM Puerta del Sur in Madrid, Spain. Eligible participants had Parkinson's disease with markedly asymmetric parkinsonism. Patients with severe dyskinesia, history of stereotactic surgery or brain haemorrhage, a diagnosis of an unstable cardiac or psychiatric disease, or a skull density ratio of 0·3 or less were excluded. Enrolled patients underwent focused ultrasound unilateral subthalamotomy. The subthalamic nucleus was targeted by means of brain images acquired with a 3-Tesla MRI apparatus. Several sonications above the definitive ablation temperature of 55°C were delivered and adjusted according to clinical response. The primary outcomes were safety and a change in the motor status of the treated hemibody as assessed with part III of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) in both off-medication and on-medication states at 6 months. Adverse events were monitored up to 48 h after treatment and at scheduled clinic visits at 1, 3, and 6 months after treatment. The study is registered with ClinicalTrials.gov, number NCT02912871. Between April 26 and June 14, 2016, ten patients with markedly asymmetric parkinsonism that was poorly controlled pharmacologically were enrolled for focused ultrasound unilateral subthalamotomy. By 6 months follow-up, 38 incidents of adverse events had been recorded, none of which were serious or severe. Seven adverse events were present at 6 months. Three of these adverse events were directly related to subthalamotomy: off-medication dyskinesia in the treated arm (one patient, almost resolved by 6 months); on-medication dyskinesia in the treated arm (one patient, resolved after levodopa dose reduction); and subjective speech disturbance (one patient). Four of the adverse events present at 6 months were related to medical management (anxiety and fatigue [one patient each] and weight gain [two patients]). The most frequent adverse events were transient gait ataxia (related to subthalamotomy, six patients), transient pin-site head pain (related to the head frame, six patients), and transient high blood pressure (during the procedure, five patients). Transient facial asymmetry (one patient) and moderate impulsivity (two patients) were also recorded. The mean MDS-UPDRS III score in the treated hemibody improved by 53% from baseline to 6 months in the off-medication state (16·6 [SD 2·9] vs 7·5 [3·9]) and by 47% in the on-medication state (11·9 [3·1] vs 5·8 [3·5]). MRI-guided focused ultrasound unilateral subthalamotomy was well tolerated and seemed to improve motor features of Parkinson's disease in patients with noticeably asymmetric parkinsonism. Large randomised controlled trials are necessary to corroborate these preliminary findings and to assess the potential of such an approach to treat Parkinson's disease. Fundación de investigación HM Hospitales and Insightec. Copyright © 2018 Elsevier Ltd. All rights reserved.

[How safe is the recombinant human growth hormone?

PubMed

Calzada-León, Raúl

2017-01-01

In this paper, several aspects related to the safety of the use of biosynthetic human growth hormone are reviewed. For example, its classification as a biosynthetic drug, the phases that need to be performed in Mexico to verify its safety (obtaining, purification, preclinical studies, clinical trials, and finally observational clinical studies), as well as the evidence that exists in relation to the association of intracranial hypertension, muscular events, scoliosis, slipped capital femoral epiphysis, obstructive sleep apnea, pancreatitis, alterations in cortisol, thyroid hormones alterations, cardiovascular disease, metabolic risk, mortality and cancer, adverse events not related to its use, and finally dosing and safety.

Disease Prediction Models and Operational Readiness

PubMed Central

Corley, Courtney D.; Pullum, Laura L.; Hartley, David M.; Benedum, Corey; Noonan, Christine; Rabinowitz, Peter M.; Lancaster, Mary J.

2014-01-01

The objective of this manuscript is to present a systematic review of biosurveillance models that operate on select agents and can forecast the occurrence of a disease event. We define a disease event to be a biological event with focus on the One Health paradigm. These events are characterized by evidence of infection and or disease condition. We reviewed models that attempted to predict a disease event, not merely its transmission dynamics and we considered models involving pathogens of concern as determined by the US National Select Agent Registry (as of June 2011). We searched commercial and government databases and harvested Google search results for eligible models, using terms and phrases provided by public health analysts relating to biosurveillance, remote sensing, risk assessments, spatial epidemiology, and ecological niche modeling. After removal of duplications and extraneous material, a core collection of 6,524 items was established, and these publications along with their abstracts are presented in a semantic wiki at http://BioCat.pnnl.gov. As a result, we systematically reviewed 44 papers, and the results are presented in this analysis. We identified 44 models, classified as one or more of the following: event prediction (4), spatial (26), ecological niche (28), diagnostic or clinical (6), spread or response (9), and reviews (3). The model parameters (e.g., etiology, climatic, spatial, cultural) and data sources (e.g., remote sensing, non-governmental organizations, expert opinion, epidemiological) were recorded and reviewed. A component of this review is the identification of verification and validation (V&V) methods applied to each model, if any V&V method was reported. All models were classified as either having undergone Some Verification or Validation method, or No Verification or Validation. We close by outlining an initial set of operational readiness level guidelines for disease prediction models based upon established Technology Readiness Level definitions. PMID:24647562

Impact of Stressful Life Events on Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Yu, Tsung; Frei, Anja; Ter Riet, Gerben; Puhan, Milo A

There is a general notion that stressful life events may cause mental and physical health problems. We aimed to describe stressful life events reported by patients with chronic obstructive pulmonary disease (COPD) and to assess their impact on health outcomes and behaviors. Two hundred and sixty-six primary care patients who participated in the ICE COLD ERIC cohort study were asked to document any stressful life events in the past 3 years. We assessed the before-after (the event) changes for symptoms of depression and anxiety, health status, dyspnea-related quality of life, exacerbations, cigarette use, and physical activity. We used linear regression analysis to estimate the crude and adjusted magnitude of the before-after changes. About 41% (110/266) of patients reported the experience of any stressful life events and "death of relatives/important persons" was most common (31%). After accounting for age, sex, living status, lung function, and anxiety/depression status at baseline, experiencing any stressful life events was associated with a 0.9-point increase on the depression scale (95% CI 0.3 to 1.4), a 0.8-point increase on the anxiety scale (95% CI 0.3 to 1.3), and a 0.8-point decrease in the physical activity score (95% CI -1.6 to 0). Experiencing stressful life events was associated with a small to moderate increase in symptoms of depression and anxiety in COPD, but no discernable effect was found for other physical outcomes. However, confirmation of these results in other COPD cohorts and identification of patients particularly vulnerable to stressful life events are needed. © 2017 S. Karger AG, Basel.

Use of court records for supplementing occupational disease surveillance.

PubMed Central

Schwartz, E; Landrigan, P

1987-01-01

To conduct surveillance of occupationally related health events, the New Hampshire Division of Public Health Services analyzes death certificates and workers' compensation claims. In an effort to bolster these limited data sources, a previously unrecognized data-set comprised of court records was explored. Court records obtained from the Federal District Court proved to be a readily accessible and detailed source of information for identifying suspected cases of asbestos-related disease and potential sources of asbestos exposure. PMID:2959164

Cardiovascular disease prevention at the workplace: assessing the prognostic value of lifestyle risk factors and job-related conditions.

PubMed

Veronesi, Giovanni; Borchini, Rossana; Landsbergis, Paul; Iacoviello, Licia; Gianfagna, Francesco; Tayoun, Patrick; Grassi, Guido; Cesana, Giancarlo; Ferrario, Marco Mario

2018-05-25

The prognostic utility of lifestyle risk factors and job-related conditions (LS&JRC) for cardiovascular disease (CVD) risk stratification remains to be clarified. We investigated discrimination and clinical utility of LS&JRC among 2532 workers, 35-64 years old, CVD-free at the time of recruitment (1989-1996) in four prospective cohorts in Northern Italy, and followed up (median 14 years) until first major coronary event or ischemic stroke, fatal or non-fatal. From a Cox model including cigarette smoking, alcohol intake, occupational and sport physical activity and job strain, we estimated 10-year discrimination as the area under the ROC curve (AUC), and clinical utility as the Net Benefit. N = 162 events occurred during follow-up (10-year risk: 4.3%). The LS&JRC model showed the same discrimination (AUC = 0.753, 95% CI 0.700-0.780) as blood lipids, blood pressure, smoking and diabetes (AUC = 0.753), consistently across occupational classes. Among workers at low CVD risk (n = 1832, 91 CVD events), 687 were at increased LS&JRC risk; of these, 1 every 15 was a case, resulting in a positive Net Benefit (1.27; 95% CI 0.68-2.16). LS&JRC are as accurate as clinical risk factors in identifying future cardiovascular events among working males. Our results support initiatives to improve total health at work as strategies to prevent cardiovascular disease.

Stroke prevention by cilostazol in patients with atherothrombosis: meta-analysis of placebo-controlled randomized trials.

PubMed

Uchiyama, Shinichiro; Demaerschalk, Bart M; Goto, Shinya; Shinohara, Yukito; Gotoh, Fumio; Stone, William M; Money, Samuel R; Kwon, Sun Uck

2009-01-01

Cilostazol is an antiplatelet agent that inhibits phosphodiesterase III in platelets and vascular endothelium. Previous randomized controlled trials of cilostazol for prevention of cerebrovascular events have garnered mixed results. We performed a systematic review and meta-analysis of the randomized clinical trials in patients with atherothrombotic diseases to determine the effects of cilostazol on cerebrovascular, cardiac, and all vascular events, and on all major hemorrhagic events. Relevant trials were identified by searching MEDLINE, EMBASE, and the Cochrane Controlled Trial Registry for titles and abstracts. Data from 12 randomized controlled trials, involving 5674 patients, were analyzed for end points of cerebrovascular, cardiac, and major bleeding events. Searching, determination of eligibility, data extraction, and meta-analyses were conducted by multiple independent investigators. Data were available in 3782, 1187, and 705 patients with peripheral arterial disease, cerebrovascular disease, and coronary stenting, respectively. Incidence of total vascular events was significantly lower in the cilostazol group compared with the placebo group (relative risk [RR], 0.86; 95% confidence interval [CI], 0.74-0.99; P=.038). This was particularly influenced by a significant decrease of incidence of cerebrovascular events in the cilostazol group (RR, 0.58; 95% CI, 0.43-0.78; P < .001). There was no significant intergroup difference in incidence of cardiac events (RR, 0.99; 95% CI, 0.83-1.17; P=.908) and serious bleeding complications (RR, 1.00; 95% CI, 0.66-1.51; P=.996). This first meta-analysis of cilostazol in patients with atherothrombosis demonstrated a significant risk reduction for cerebrovascular events, with no associated increase of bleeding risk.

Incidence of clinical symptoms during long-duration orbital spaceflight

PubMed Central

Crucian, Brian; Babiak-Vazquez, Adriana; Johnston, Smith; Pierson, Duane L; Ott, C Mark; Sams, Clarence

2016-01-01

Background The environment of spaceflight may elevate an astronaut’s clinical risk for specific diseases. The purpose of this study was to derive, as accurately as currently possible, an assessment of in-flight clinical “incidence” data, based on observed clinical symptoms in astronauts on board the International Space Station (ISS). Methods Electronic medical records were examined from 46 long-duration ISS crew members, each serving approximately a 6-month mission on board the ISS, constituting 20.57 total flight years. Incidence for immunological-related adverse health events or relevant clinical symptoms was tabulated in a non-identifiable fashion. Event categories included infectious diseases, allergies, and rashes/hypersensitivities. A subsequent re-evaluation of more notable events, either of prolonged duration or unresponsive to treatment, was performed. Results For the disease/symptom categories used in this evaluation, the ISS incidence rate was 3.40 events per flight year. Skin rashes were the most reported event (1.12/flight year) followed by upper respiratory symptoms (0.97/flight year) and various other (non-respiratory) infectious processes. During flight, 46% of crew members reported an event deemed “notable”. Among the notable events, 40% were classified as rashes/hypersensitivities. Characterization of on-orbit rashes manifested as redness with irritation, and could present on a variety of body locations. Conclusion Based on reported symptoms, astronauts experience adverse medical events of varying severity during long-duration spaceflights. The data suggests caution, from both a vehicle design and biomedical countermeasures perspective, as space agencies plan for prolonged deep space exploration missions. PMID:27843335

Rs964184 (APOA5-A4-C3-A1) is related to elevated plasma triglyceride levels, but not to an increased risk for vascular events in patients with clinically manifest vascular disease.

PubMed

van de Woestijne, Anton P; van der Graaf, Yolanda; de Bakker, Paul I W; Asselbergs, Folkert W; Spiering, Wilko; Visseren, Frank L J

2014-01-01

Single nucleotide polymorphisms in the APOA5-A4-C3-A1 gene complex are associated with elevated plasma triglycerides and elevated vascular risk in healthy populations. In patients with clinically manifest vascular disease, hypertriglyceridemia and metabolic syndrome are frequently present, but the contribution of these single nucleotide polymorphisms to plasma triglycerides, effect modification by obesity and risk of recurrent vascular events is unknown in these patients. Prospective cohort study of 5547 patients with vascular disease. Rs964184 (APOA5-A4-C3-A1 gene complex) was genotyped, and we evaluated the relation with plasma lipid levels, presence of metabolic syndrome and the risk for new vascular events. The minor allele of rs964184 was strongly associated with log plasma triglycerides (β 0.12; 95%CI 0.10-0.15, p = 1.1*10(-19)), and was also associated with 0.03 mmol/L lower high-density lipoprotein-cholesterol (95%CI 0.01-0.04), and 0.14 mmol/L higher non-high-density lipoprotein-cholesterol (95%CI 0.09-0.20). The minor allele frequency increased from 10.9% in patients with plasma triglycerides <1 mmol/L to 24.6% in patients with plasma triglycerides between 4 and 10 mmol/L. The relation between rs964184 and plasma triglycerides was modified by body mass index in patients with one minor allele (β 0.02; (95%CI -0.04-0.09) if body mass index <24 kg/m2, β 0.17 (95%CI 0.12-0.22) if body mass index >27 kg/m2, p for interaction = 0.02). The prevalence of the metabolic syndrome increased from 52% for patients with two copies of the major allele to 62% for patients with two copies of the minor allele (p = 0.01). Rs964184 was not related with recurrent vascular events (HR 0.99; 95%CI 0.86-1.13). The single nucleotide polymorphism rs964184 (APOA5-A4-C3-A1) is associated with elevated plasma triglycerides concentrations in patients with clinically manifest vascular disease. In carriers of one minor allele, the effect on plasma triglycerides was modified by body mass index. There is no relation between rs964184 and recurrent vascular events in these patients.

VISIT-TO-VISIT VARIABILITY OF BLOOD PRESSURE AND DEATH, ESRD AND CARDIOVASCULAR EVENTS IN PATIENTS WITH CHRONIC KIDNEY DISEASE

PubMed Central

CHANG, Tara I.; TABADA, Grace H.; YANG, Jingrong; TAN, Thida X.; GO, Alan S.

2016-01-01

OBJECTIVES Visit-to-visit variability of blood pressure is an important independent risk factor for premature death and cardiovascular events, but relatively little is known about this phenomenon in patients with chronic kidney disease not yet on dialysis. METHODS We conducted a retrospective study in a community-based cohort of 114,900 adults with chronic kidney disease stages 3–4 (estimated glomerular filtration rate 15–59 mL/min per 1.73 m2). We hypothesized that visit-to-visit variability of blood pressure would be independently associated with higher risks of death, incident treated end-stage renal disease, and cardiovascular events. We defined systolic visit-to-visit variability of blood pressure using three metrics: (1) coefficient of variation (2) standard deviation of the mean systolic blood pressure, and (3) average real variability. RESULTS The highest versus the lowest quintile of the coefficient of variation was associated with higher adjusted rates of death (hazard ratio 1.22; 95% confidence interval 1.11–1.34) and hemorrhagic stroke (hazard ratio 1.91, confidence interval 1.36–2.68). Visit-to-visit variability of blood pressure was inconsistently associated with heart failure, and was not significantly associated with acute coronary syndrome and ischemic stroke. Results were similar when using the other two visit-to-visit variability of blood pressure. Visit-to-visit variability of blood pressure had inconsistent associations with end-stage renal disease, perhaps due to the relatively low incidences of this outcome. CONCLUSIONS Higher visit-to-visit variability of blood pressure is independently associated with higher rates of death and hemorrhagic stroke in patients with moderate to advanced chronic kidney disease not yet on dialysis. PMID:26599220

Characteristic features of tacrolimus-induced lung disease in rheumatoid arthritis patients.

PubMed

Sasaki, Takanori; Nakamura, Wataru; Inokuma, Shigeko; Matsubara, Erika

2016-02-01

This paper aims to study the background and clinical characteristics of tacrolimus (TAC)-induced lung disease. A case of a rheumatoid arthritis (RA) patient who developed TAC-induced interstitial lung disease (TAC-ILD) is reported. The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) website was searched for cases of TAC-ILD and its prevalence among all cases of TAC-related adverse events. As for cases of TAC-ILD, its underlying disease, preexisting lung diseases, and fatal outcome were also searched. Literature review of TAC-ILD cases was added. A 65-year-old female RA patient with preexisting bronchiectasis developed near-fatal TAC-ILD. Amelioration of RA, ground-glass opacities in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings in this patient. A search of the PMDA website revealed the following: the prevalence of TAC-ILD was 3 % of all cases of TAC-related adverse events, 56 out of 85 RA cases (66 %), and one out of 15 other cases had a preexisting lung disease; the prevalences of fatal outcome in RA and other cases were 24 and 38 %, respectively. A few cases in the literature had preexisting ILD and developed diffuse alveolar damage. In our case, preexisting bronchiectasis, arthritis remission, newly developed ground-glass opacities (GGOs) in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings. From the search of the PMDA website, about one fourth of the cases with TAC-related lung injury had a fatal outcome, and among RA patients, two thirds had preexisting lung diseases.

Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis

PubMed Central

Tonelli, Marcello; Hemmelgarn, Brenda; Reiman, Tony; Manns, Braden; Reaume, M. Neil; Lloyd, Anita; Wiebe, Natasha; Klarenbach, Scott

2009-01-01

Background Erythropoiesis-stimulating agents are used to treat anemia in patients with cancer. However, their safety and effectiveness is controversial. We did a systematic review of the clinical efficacy and harms of these agents in adults with anemia related to cancer or chemotherapy. Methods We conducted a systematic review of published and unpublished randomized controlled trials (RCTs) using accepted methods for literature searches, article selection, data extraction and quality assessment. We included RCTs involving anemic adults with cancer. We compared the use of erythropoiesis-stimulating agents with nonuse and assessed clinical outcomes (all-cause mortality, cardiovascular events and hypertension, health-related quality of life, blood transfusions and tumour response) and harms (serious adverse events) between groups. Results We identified 52 trials (n = 12 006) that met our selection criteria. The pooled all-cause mortality during treatment was significantly higher in the group receiving erythropoiesis-stimulating therapy than in the control group (relative risk [RR] 1.15, 95% confidence interval [CI] 1.03 to 1.29). Compared with no treatment, use of erythropoiesis-stimulating agents led to clinically detectable improvements in disease-specific measures of quality of life. It also reduced the use of blood transfusions (RR 0.64, 95% CI 0.56 to 0.73). However, it led to an increased risk of thrombotic events (RR 1.69, 95% CI 1.27 to 2.24) and serious adverse events (RR 1.16, 95% CI 1.08 to 1.25). Interpretation Use of erythropoiesis-stimulating agents in patients with cancer-related anemia improved some disease-specific measures of quality of life and decreased the use of blood transfusions. However, it increased the risk of death and serious adverse events. Our findings suggest that such therapy not be used routinely as an alternative to blood transfusion in patients with anemia related to cancer. PMID:19407261

TERMA Framework for Biomedical Signal Analysis: An Economic-Inspired Approach

PubMed Central

Elgendi, Mohamed

2016-01-01

Biomedical signals contain features that represent physiological events, and each of these events has peaks. The analysis of biomedical signals for monitoring or diagnosing diseases requires the detection of these peaks, making event detection a crucial step in biomedical signal processing. Many researchers have difficulty detecting these peaks to investigate, interpret and analyze their corresponding events. To date, there is no generic framework that captures these events in a robust, efficient and consistent manner. A new method referred to for the first time as two event-related moving averages (“TERMA”) involves event-related moving averages and detects events in biomedical signals. The TERMA framework is flexible and universal and consists of six independent LEGO building bricks to achieve high accuracy detection of biomedical events. Results recommend that the window sizes for the two moving averages (W1 and W2) have to follow the inequality (8×W1)≥W2≥(2×W1). Moreover, TERMA is a simple yet efficient event detector that is suitable for wearable devices, point-of-care devices, fitness trackers and smart watches, compared to more complex machine learning solutions. PMID:27827852

Identification of novel noninvasive markers for diagnosing nonalcoholic steatohepatitis and related fibrosis by data mining.

PubMed

Yoshimura, Keito; Okanoue, Takeshi; Ebise, Hayao; Iwasaki, Tsuyoshi; Mizuno, Masayuki; Shima, Toshihide; Ichihara, Junji; Yamazaki, Kazuto

2016-02-01

It is important that patients with nonalcoholic steatohepatitis (NASH) are diagnosed and treated early to prevent serious complications, such as liver cirrhosis or hepatocellular carcinoma. However, current methods for NASH diagnosis are invasive given that they rely on liver biopsy, making early diagnosis difficult. In this study, we developed novel noninvasive markers for the diagnosis of NASH and NASH-related fibrosis. A total of 132 Japanese patients with nonalcoholic fatty liver disease were included in this study. Blood samples were collected, and 261 biomolecules were quantified in serum. Using cluster and pathway analyses, we identified biomolecule modules connected to biological events that occur with disease progression to NASH. The modules were used as variables for diagnosis, leading to a NASH diagnostic marker associated with two biological events, that is, protective response to hepatic steatosis and hepatitis-causing innate immune response. Regarding the NASH-related fibrosis marker, immunological responses to hepatocyte injury were identified as a biological event. To develop diagnostic markers for NASH and NASH-related fibrosis, specific biomolecules were selected from each biomolecule module. The former marker was obtained by averaging the levels of four biomolecules, whereas the latter was obtained by averaging the levels of two biomolecules. Both markers achieved a diagnostic accuracy of almost 0.9 of the area under the receiver operating characteristic curve, and the latter exhibited equivalent performance in an independent group of 62 prospectively recruited patients. We developed highly accurate markers for the diagnosis of both NASH and NASH-related fibrosis (i.e., FM-NASH index and FM-fibro index, respectively). These markers may be used as an alternative diagnostic tool to liver biopsy. © 2015 by the American Association for the Study of Liver Diseases.

The impact of heat on mortality and morbidity in the Greater Metropolitan Sydney Region: a case crossover analysis.

PubMed

Wilson, Leigh Ann; Morgan, Geoffrey Gerard; Hanigan, Ivan Charles; Johnston, Fay H; Abu-Rayya, Hisham; Broome, Richard; Gaskin, Clive; Jalaludin, Bin

2013-11-15

This study examined the association between unusually high temperature and daily mortality (1997-2007) and hospital admissions (1997-2010) in the Sydney Greater Metropolitan Region (GMR) to assist in the development of targeted health programs designed to minimise the public health impact of extreme heat. Sydney GMR was categorized into five climate zones. Heat-events were defined as severe or extreme. Using a time-stratified case-crossover design with a conditional logistic regression model we adjusted for influenza epidemics, public holidays, and climate zone. Odds ratios (OR) and 95% confidence intervals were estimated for associations between daily mortality and hospital admissions with heat-event days compared to non-heat event days for single and three day heat-events. All-cause mortality overall had similar magnitude associations with single day and three day extreme and severe events as did all cardiovascular mortality. Respiratory mortality was associated with single day and three day severe events (95th percentile, lag0: OR = 1.14; 95%CI: 1.04 to 1.24). Diabetes mortality had similar magnitude associations with single day and three day severe events (95th percentile, lag0: OR = 1.22; 95%CI: 1.03 to 1.46) but was not associated with extreme events. Hospital admissions for heat related injuries, dehydration, and other fluid disorders were associated with single day and three day extreme and severe events. Contrary to our findings for mortality, we found inconsistent and sometimes inverse associations for extreme and severe events with cardiovascular disease and respiratory disease hospital admissions. Controlling for air pollutants did not influence the mortality associations but reduced the magnitude of the associations with hospital admissions particularly for ozone and respiratory disease. Single and three day events of unusually high temperatures in Sydney are associated with similar magnitude increases in mortality and hospital admissions. The trend towards an inverse association between cardio-vascular admissions and heat-events and the strong positive association between cardio-vascular mortality and heat-events suggests these events may lead to a rapid deterioration in persons with existing cardio-vascular disease resulting in death. To reduce the adverse effects of high temperatures over multiple days, and less extreme but more frequent temperatures over single days, targeted public health messages are critical.

The impact of heat on mortality and morbidity in the Greater Metropolitan Sydney Region: a case crossover analysis

PubMed Central

2013-01-01

Background This study examined the association between unusually high temperature and daily mortality (1997–2007) and hospital admissions (1997–2010) in the Sydney Greater Metropolitan Region (GMR) to assist in the development of targeted health programs designed to minimise the public health impact of extreme heat. Methods Sydney GMR was categorized into five climate zones. Heat-events were defined as severe or extreme. Using a time-stratified case-crossover design with a conditional logistic regression model we adjusted for influenza epidemics, public holidays, and climate zone. Odds ratios (OR) and 95% confidence intervals were estimated for associations between daily mortality and hospital admissions with heat-event days compared to non-heat event days for single and three day heat-events. Results All-cause mortality overall had similar magnitude associations with single day and three day extreme and severe events as did all cardiovascular mortality. Respiratory mortality was associated with single day and three day severe events (95thpercentile, lag0: OR = 1.14; 95%CI: 1.04 to 1.24). Diabetes mortality had similar magnitude associations with single day and three day severe events (95thpercentile, lag0: OR = 1.22; 95%CI: 1.03 to 1.46) but was not associated with extreme events. Hospital admissions for heat related injuries, dehydration, and other fluid disorders were associated with single day and three day extreme and severe events. Contrary to our findings for mortality, we found inconsistent and sometimes inverse associations for extreme and severe events with cardiovascular disease and respiratory disease hospital admissions. Controlling for air pollutants did not influence the mortality associations but reduced the magnitude of the associations with hospital admissions particularly for ozone and respiratory disease. Conclusions Single and three day events of unusually high temperatures in Sydney are associated with similar magnitude increases in mortality and hospital admissions. The trend towards an inverse association between cardio-vascular admissions and heat-events and the strong positive association between cardio-vascular mortality and heat-events suggests these events may lead to a rapid deterioration in persons with existing cardio-vascular disease resulting in death. To reduce the adverse effects of high temperatures over multiple days, and less extreme but more frequent temperatures over single days, targeted public health messages are critical. PMID:24238064

Tolerability of sibutramine during a 6-week treatment period in high-risk patients with cardiovascular disease and/or diabetes: a preliminary analysis of the Sibutramine Cardiovascular Outcomes (SCOUT) Trial.

PubMed

Maggioni, Aldo P; Caterson, Ian; Coutinho, Walmir; Finer, Nick; Gaal, Luc Van; Sharma, Arya M; Torp-Pedersen, Christian; Bacher, Peter; Shepherd, Gillian; Sun, Rui; James, Philip

2008-11-01

Uncertainties about the cardiovascular safety of sibutramine led to the SCOUT trial that is investigating sibutramine plus weight management in high-risk, overweight/obese patients. A 6-week lead-in period during which all patients received sibutramine permitted an initial assessment of tolerability. A total of 10,742 patients received sibutramine and 3.1% of these discontinued due to an adverse event; issues affecting more than 10 patients were drug intolerance, headache, insomnia, nausea, dry mouth, and constipation-, tachycardia-, and hypertension-related events. Serious adverse events, most commonly associated with the System Organ Class, Cardiac disorders, were reported by 2.7% of patients; however, the majority was not considered sibutramine-related. Adverse events relating to high blood pressure and/or pulse rate, whether reported as adverse events leading to discontinuation, or serious adverse events were reported by less than 0.2% of patients. No serious or individual events leading to discontinuation occurred in more than 25 patients. There were 15 (0.1%) deaths; 10 were attributed to a cardiovascular cause. Discontinuations for adverse events were lower than anticipated. Serious adverse events generally reflected sibutramine's known pharmacology or were related to cardiac disorders already present in this high-risk population. When compared with epidemiological data, overall mortality rate was low and sibutramine was well tolerated in this mainly off-label population. No new safety issues were detected.

Intensive lifestyle changes for reversal of coronary heart disease.

PubMed

Ornish, D; Scherwitz, L W; Billings, J H; Brown, S E; Gould, K L; Merritt, T A; Sparler, S; Armstrong, W T; Ports, T A; Kirkeeide, R L; Hogeboom, C; Brand, R J

1998-12-16

The Lifestyle Heart Trial demonstrated that intensive lifestyle changes may lead to regression of coronary atherosclerosis after 1 year. To determine the feasibility of patients to sustain intensive lifestyle changes for a total of 5 years and the effects of these lifestyle changes (without lipid-lowering drugs) on coronary heart disease. Randomized controlled trial conducted from 1986 to 1992 using a randomized invitational design. Forty-eight patients with moderate to severe coronary heart disease were randomized to an intensive lifestyle change group or to a usual-care control group, and 35 completed the 5-year follow-up quantitative coronary arteriography. Two tertiary care university medical centers. Intensive lifestyle changes (10% fat whole foods vegetarian diet, aerobic exercise, stress management training, smoking cessation, group psychosocial support) for 5 years. Adherence to intensive lifestyle changes, changes in coronary artery percent diameter stenosis, and cardiac events. Experimental group patients (20 [71%] of 28 patients completed 5-year follow-up) made and maintained comprehensive lifestyle changes for 5 years, whereas control group patients (15 [75%] of 20 patients completed 5-year follow-up) made more moderate changes. In the experimental group, the average percent diameter stenosis at baseline decreased 1.75 absolute percentage points after 1 year (a 4.5% relative improvement) and by 3.1 absolute percentage points after 5 years (a 7.9% relative improvement). In contrast, the average percent diameter stenosis in the control group increased by 2.3 percentage points after 1 year (a 5.4% relative worsening) and by 11.8 percentage points after 5 years (a 27.7% relative worsening) (P=.001 between groups. Twenty-five cardiac events occurred in 28 experimental group patients vs 45 events in 20 control group patients during the 5-year follow-up (risk ratio for any event for the control group, 2.47 [95% confidence interval, 1.48-4.20]). More regression of coronary atherosclerosis occurred after 5 years than after 1 year in the experimental group. In contrast, in the control group, coronary atherosclerosis continued to progress and more than twice as many cardiac events occurred.

Cancer-associated bone disease

PubMed Central

Body, J.-J.; Brandi, M.-L.; Cannata-Andia, J.; Chappard, D.; El Maghraoui, A.; Glüer, C.C.; Kendler, D.; Napoli, N.; Papaioannou, A.; Pierroz, D.D.; Rahme, M.; Van Poznak, C.H.; de Villiers, T.J.; El Hajj Fuleihan, G.

2016-01-01

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and working groups to assist physicians in clinical decision making, providing them with evidence-based care pathways to prevent skeletal-related events and bone loss. The goal of this paper is to put forth an IOF position paper addressing bone diseases and cancer and summarizing the position papers of other organizations. PMID:24146095

Regulation of cardiomyocyte autophagy by calcium

PubMed Central

Shaikh, Soni; Troncoso, Rodrigo; Criollo, Alfredo; Bravo-Sagua, Roberto; García, Lorena; Morselli, Eugenia; Cifuentes, Mariana; Quest, Andrew F. G.; Hill, Joseph A.

2016-01-01

Calcium signaling plays a crucial role in a multitude of events within the cardiomyocyte, including cell cycle control, growth, apoptosis, and autophagy. With respect to calcium-dependent regulation of autophagy, ion channels and exchangers, receptors, and intracellular mediators play fundamental roles. In this review, we discuss calcium-dependent regulation of cardiomyocyte autophagy, a lysosomal mechanism that is often cytoprotective, serving to defend against disease-related stress and nutrient insufficiency. We also highlight the importance of the subcellular distribution of calcium and related proteins, interorganelle communication, and other key signaling events that govern cardiomyocyte autophagy. PMID:26884385

Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the U.S. Preventive Services Task Force.

PubMed

Hayden, Michael; Pignone, Michael; Phillips, Christopher; Mulrow, Cynthia

2002-01-15

The use of aspirin to prevent cardiovascular disease events in patients without a history of cardiovascular disease is controversial. To examine the benefits and harms of aspirin chemoprevention. MEDLINE (1966 to May 2001). 1) Randomized trials at least 1 year in duration that examined aspirin chemoprevention in patients without previously known cardiovascular disease and 2) systematic reviews, recent trials, and observational studies that examined rates of hemorrhagic strokes and gastrointestinal bleeding secondary to aspirin use. One reviewer read and extracted data from each included article and constructed evidence tables. A second reviewer checked the accuracy of the data extraction. Discrepancies were resolved by consensus. Meta-analysis was performed, and the quantitative results of the review were then used to model the consequences of treating patients with different levels of baseline risk for coronary heart disease. Five trials examined the effect of aspirin on cardiovascular events in patients with no previous cardiovascular disease. For patients similar to those enrolled in the trials, aspirin reduces the risk for the combined end point of nonfatal myocardial infarction and fatal coronary heart disease (summary odds ratio, 0.72 [95% CI, 0.60 to 0.87]). Aspirin increased the risk for hemorrhagic strokes (summary odds ratio, 1.4 [CI, 0.9 to 2.0]) and major gastrointestinal bleeding (summary odds ratio, 1.7 [CI, 1.4 to 2.1]). All-cause mortality (summary odds ratio, 0.93 [CI, 0.84 to 1.02]) was not significantly affected. For 1000 patients with a 5% risk for coronary heart disease events over 5 years, aspirin would prevent 6 to 20 myocardial infarctions but would cause 0 to 2 hemorrhagic strokes and 2 to 4 major gastrointestinal bleeding events. For patients with a risk of 1% over 5 years, aspirin would prevent 1 to 4 myocardial infarctions but would cause 0 to 2 hemorrhagic strokes and 2 to 4 major gastrointestinal bleeding events. The net benefit of aspirin increases with increasing cardiovascular risk. In the decision to use aspirin chemoprevention, the patient's cardiovascular risk and relative utility for the different clinical outcomes prevented or caused by aspirin use must be considered.

Observations and simulations of the interactions between clouds, radiation, and precipitation

NASA Astrophysics Data System (ADS)

Naegele, Alexandra Claire

Increasing precipitation and warming temperatures associated with climate change have been documented across the globe, including in the Northeast US. These climate changes threaten human health in many ways. Research is necessary to understand and explain the relationship between climate change and human health. Extreme weather events such as extreme temperatures, convective storms, floods, lightning events, wintry precipitation, and low visibility, are frequently associated with adverse effects on human health. While more media attention is typically given to events that cause the most structural or economic damage (e.g., tornadoes, hurricanes, earthquakes, etc.), extreme temperatures ultimately account for the greatest loss of life in the US. Extreme weather events can be unpredictable; however, improved knowledge and technology allow meteorologists to accurately forecast many of these events, specifically extreme temperature and precipitation events. Advancing our knowledge of climate variability and trends in extreme weather can inform: public education programs to alert the community of the dangers of extreme heat or cold, emergency response plans to hazardous weather conditions, and current thresholds for emergency alerts. This study evaluates trends in extreme weather events across New Hampshire and links these extreme events to adverse health outcomes. Using data from NCEI Global Historical Climatological Network (GHCN) - Daily dataset (1981 - 2015), five daily xiii Extreme Weather Metrics (EWMs) were defined: Daily Maximum Temperature ≤32°F, Daily Maximum Temperature ≥90°F, Daily Maximum Temperature ≥95°F, Daily Precipitation ≥1", and Daily Precipitation ≥2". Relevant human health outcomes were extracted from the New Hampshire Hospital Discharge Dataset for the years 2001-2009. Health cases were defined based on the International Classification of Disease 9th Revision (ICD-9). Outcomes in this analysis include: All-Cause Injury, Vehicle Accidents, Accidental Falls, Accidents Due to Natural and Environmental (including excessive heat, excessive cold, exposure due to weather conditions, lightning, and storms and floods), Accidental Drowning, and Carbon Monoxide Poisoning. Temporal and spatial trends were assessed, and the associations between all health outcomes and EWMs, daily maximum temperature, and daily precipitation were evaluated via Spearman correlations. Once the four strongest correlations were determined, a quasi-Poisson regression model was used to evaluate the relationship between each exposureoutcome pair. These pairs were modeled to show the relation between maximum temperature and all-cause hospital visits, hospital visits related to vehicle accidents, hospital visits related to accidental falls, and hospital visits related to heat. Future work will incorporate these findings into public health planning and programming. This project is a collaboration with New Hampshire Department of Health and Human Services (NH DHHS) who have a shared interest in understanding the impact of extreme weather events on the citizens of New Hampshire. Furthermore, this work supports an ongoing effort to implement the Centers for Disease Control (CDC) Building Resilience Against Climate Effects (BRACE) Framework, which focuses on identifying climate and weather-related hazards and estimating the associated disease burden.

Beta Blockers for the Prevention of Acute Exacerbations of COPD

DTIC Science & Technology

2016-10-01

metoprolol in trials of patients with coronary artery disease , congestive heart failure and hypertension range from 12.5 to 200 mg, and doses in this...distinguish from usual, primary respiratory-related events. In add- ition to a higher frequency of ischaemic heart disease , COPD is associated with diastolic...for the diagnosis and management of patients with stable ischemic heart disease : a report of the American College of Cardiology Foundation/American

Elevated basal intestinal mucosal cytokine levels in asymptomatic first-degree relatives of patients with Crohn’s disease

PubMed Central

Indaram, Anant VK; Nandi, Santa; Weissman, Sam; Lam, Sing; Bailey, Beverly; Blumstein, Meyer; Greenberg, Ronald; Bank, Simmy

2000-01-01

AIM: To determine levels of cytokines in colonic mucosa of asymptomatic first degree relatives of Crohn’s disease patients. METHODS: Cytokines (Interleukin (IL) 1-Beta, IL-2, IL-6 and IL-8) were measured using ELISA in biopsy samples of normal looking colonic mucosa of first degree relatives of Crohn’s disease patients (n = 9) and fro m normal controls (n = 10) with no family history of Crohn’s disease. RESULTS: Asymptomatic first degree relatives of patients with Crohn’s disease had significantly higher levels of basal intestinal mucosal cytokines (IL-2, IL-6 and IL-8) than normal controls. Whether these increase d cytokine levels serve as phenotypic markers for a genetic predisposition to de veloping Crohn’s disease later on, or whether they indicate early (pre-cli nical) damage has yet to be further defined. CONCLUSION: Asymptomatic first degree relatives of Crohn’s disease patients have higher levels of cytokines in their normal-looking intestinal mucosa compared to normal controls. This supports the hypothesis that increased cytokines may be a cause or an early event in the inflammatory cascade of Crohn’s disease and are not merely a result of the inflammatory process. PMID:11819521

Optimal management of immune-related adverse events resulting from treatment with immune checkpoint inhibitors: a review and update.

PubMed

Nagai, Hiroki; Muto, Manabu

2018-06-01

Over the last two decades, molecular-targeted agents have become mainstream treatment for many types of malignancies and have improved the overall survival of patients. However, most patients eventually develop resistance to these targeted therapies. Recently, immunotherapies such as immune checkpoint inhibitors have revolutionized the treatment paradigm for many types of malignancies. Immune checkpoint inhibitors have been approved for treatment of melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck squamous cell carcinoma, Hodgkin's lymphoma, bladder cancer and gastric cancer. However, oncologists have been faced with immune-related adverse events caused by immune checkpoint inhibitors; these are generally mild but can be fatal in some cases. Because immune checkpoint inhibitors have distinct toxicity profiles from those of chemotherapy or targeted therapy, many oncologists are not familiar with the principles for optimal management of immune-related adverse events, which require early recognition and appropriate treatment without delay. To achieve this, oncologists must educate patients and health-care workers, develop checklists of appropriate tests for immune-related adverse events and collaborate closely with organ specialists. Clinical questions that remain include whether immune checkpoint inhibitors should be administered to patients with autoimmune disease and whether patients for whom immune-related adverse events lead to delays in immunotherapy should be retreated. In addition, the predicted use of combination immunotherapies in the near future means that oncologists will face a higher incidence and severity of immune-related adverse events. This review provides an overview of the optimal management of immune-related adverse events attributed to immune checkpoint inhibitors.

The Acute Risks of Exercise in Apparently Healthy Adults and Relevance for Prevention of Cardiovascular Events.

PubMed

Goodman, Jack M; Burr, Jamie F; Banks, Laura; Thomas, Scott G

2016-04-01

Increased physical activity (PA) is associated with improved quality of life and reductions in cardiovascular (CV) morbidity and all-cause mortality in the general population in a dose-response manner. However, PA acutely increases the risk of adverse CV event or sudden cardiac death (SCD) above levels expected at rest. We review the likelihood of adverse CV events related to exercise in apparently healthy adults and strategies for prevention, and contextualize our understanding of the long-term risk reduction conferred from PA. A systematic review of the literature was performed using electronic databases; additional hand-picked relevant articles from reference lists and additional sources were included after the search. The incidence of adverse CV events in adults is extremely low during and immediately after PA of varying types and intensities and is significantly lower in those with long-standing PA experience. The risk of SCD and nonfatal events during and immediately after PA remains extremely low (well below 0.01 per 10,000 participant hours); increasing age and PA intensity are associated with greater risk. In most cases of exercise-related SCD, occult CV disease is present and SCD is typically the first clinical event. Exercise acutely increases the risk of adverse CV events, with greater risk associated with vigorous intensity. The risks of an adverse CV event during and immediately after exercise are outweighed by the health benefits of vigorous exercise performed regularly. A key challenge remains the identification of occult structural heart disease and inheritable conditions that increase the chances of lethal arrhythmias during exercise. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Effects of social support and stressful life events on health-related quality of life in coronary artery disease patients.

PubMed

Staniute, Margarita; Brozaitiene, Julija; Bunevicius, Robertas

2013-01-01

The objective of this study was to examine the effects of social support and stressful life events on health-related quality of life (HRQoL) in coronary artery disease (CAD) patients. Five hundred sixty consecutive patients with CAD attending cardiac rehabilitation program were invited to participate in the study. Data on stressful life events, perceived social support, and HRQoL were collected from the self-administered questionnaires, Social Readjustment Rating Scale, Multidimensional Scale of Perceived Social Support, and 36-Item Short Form Medical Outcome Questionnaire, respectively. In male patients, multivariate linear regression analyses revealed that physical domains of the HRQoL, specifically physical functioning, were associated with clinical aspects of the CAD, such as New York Heart Association class and angina pectoris class, and psychological domains of the HRQoL such as mental health, energy/vitality, and social functioning were associated with social characteristics such as stressful life events and perceived social support. In women, both physical and psychological domains of the HRQoL were associated only with social characteristics, especially with perceived social support. Perceived social support and stressful life events have independent significant effects on the HRQoL in CAD patients, especially in female patients. When planning cardiac rehabilitation programs, special attention should be paid to patients who experience high levels of stress and have low social support.

Modelling approaches: the case of schizophrenia.

PubMed

Heeg, Bart M S; Damen, Joep; Buskens, Erik; Caleo, Sue; de Charro, Frank; van Hout, Ben A

2008-01-01

Schizophrenia is a chronic disease characterized by periods of relative stability interrupted by acute episodes (or relapses). The course of the disease may vary considerably between patients. Patient histories show considerable inter- and even intra-individual variability. We provide a critical assessment of the advantages and disadvantages of three modelling techniques that have been used in schizophrenia: decision trees, (cohort and micro-simulation) Markov models and discrete event simulation models. These modelling techniques are compared in terms of building time, data requirements, medico-scientific experience, simulation time, clinical representation, and their ability to deal with patient heterogeneity, the timing of events, prior events, patient interaction, interaction between co-variates and variability (first-order uncertainty). We note that, depending on the research question, the optimal modelling approach should be selected based on the expected differences between the comparators, the number of co-variates, the number of patient subgroups, the interactions between co-variates, and simulation time. Finally, it is argued that in case micro-simulation is required for the cost-effectiveness analysis of schizophrenia treatments, a discrete event simulation model is best suited to accurately capture all of the relevant interdependencies in this chronic, highly heterogeneous disease with limited long-term follow-up data.

Peptidic tools applied to redirect alternative splicing events.

PubMed

Nancy, Martínez-Montiel; Nora, Rosas-Murrieta; Rebeca, Martínez-Contreras

2015-05-01

Peptides are versatile and attractive biomolecules that can be applied to modulate genetic mechanisms like alternative splicing. In this process, a single transcript yields different mature RNAs leading to the production of protein isoforms with diverse or even antagonistic functions. During splicing events, errors can be caused either by mutations present in the genome or by defects or imbalances in regulatory protein factors. In any case, defects in alternative splicing have been related to several genetic diseases including muscular dystrophy, Alzheimer's disease and cancer from almost every origin. One of the most effective approaches to redirect alternative splicing events has been to attach cell-penetrating peptides to oligonucleotides that can modulate a single splicing event and restore correct gene expression. Here, we summarize how natural existing and bioengineered peptides have been applied over the last few years to regulate alternative splicing and genetic expression. Under different genetic and cellular backgrounds, peptides have been shown to function as potent vehicles for splice correction, and their therapeutic benefits have reached clinical trials and patenting stages, emphasizing the use of regulatory peptides as an exciting therapeutic tool for the treatment of different genetic diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Inflammation markers and prediction of post-stroke vascular disease recurrence: the MITICO study.

PubMed

Castillo, J; Alvarez-Sabín, J; Martínez-Vila, E; Montaner, J; Sobrino, T; Vivancos, J

2009-02-01

Vascular disease recurrence following stroke is the main cause of morbidity and mortality. The MITICO study was designed to assess the prognostic value of markers of inflammation in relation to the risk of recurrence of vascular disease. Multi-centered prospective observational study, in patients with ischemic stroke not receiving anti-coagulation therapy and who were recruited within 1-3 months from stroke onset. Blood samples were obtained at baseline and follow- up for the determination of high-sensitive C reactive protein (CRP), IL-6, IL-10, ICAM-1, VCAM- 1, MMP-9 and cellular fibronectin. Four follow-up visits within the first year were to rule out recurrence. Of 965 patients from 65 hospitals, 780 (aged 67.5+/-11.2 years, 33.6 % female) were valid for main analysis. One-hundred and three patients (13.2 %) had a new adverse vascular event and 116 patients (14.9 %) a vascular event or vascular death (66.4 % stroke, 21.5 % coronary and 12.1 % peripheral). Levels of IL-6 > 5 pg/mL and VCAM-1 > 1350 ng/mL (ROC curve analyses) were associated with vascular disease recurrence risk (OR: 28.7; 95 % CI: 14.2-58.0 vs. OR: 4.1; 95 % CI: 2.4-7.1, respectively) following adjustment for confounding variables. Risk of adverse vascular event or death from vascular disease were associated with IL-6 (OR: 21.2; 95 % CI: 11.6-38.7) and VCAM-1 (OR: 3.8; 95 % CI: 2.3-6.4). Baseline values of IL-6 > 5 pg/mL and VCAM-1 > 1350 ng/mL increase 21-fold and 4-fold, respectively, the risk of new vascular disease event or death from vascular disease in patients with ischemic stroke not receiving anti-coagulation treatment.

Physical activity, the Framingham risk score and risk of coronary heart disease in men and women of the EPIC-Norfolk study.

PubMed

Arsenault, Benoit J; Rana, Jamal S; Lemieux, Isabelle; Després, Jean-Pierre; Wareham, Nicholas J; Kastelein, John J P; Boekholdt, S Matthijs; Khaw, Kay-Tee

2010-03-01

Test the hypothesis that considering leisure-time and work-related physical activity habits in addition to the Framingham risk score (FRS) would result into better classification of coronary heart disease (CHD) risk than FRS alone. Prospective, population-based study of 9564 men and 12165 women aged 45-79 years followed for an average of 11.4 years. A modified FRS which takes into account physical activity (evaluated using a validated lifestyle questionnaire taking into account leisure-time and work-related physical activity) was computed. During follow-up, 2191 CHD events occurred. Among 3369 men who were classified as intermediate risk (event rate of 12.4%) according to the FRS, 413 were reclassified into the low-risk category and 279 were reclassified into the high-risk category after modification of the FRS. After reclassification of these men, CHD event rate was of 5.3% and 18.6%, respectively for men classified at low and high CHD risk. Among 4766 women initially classified as intermediate risk (event rate of 8.4%), 1282 were reclassified into the low-risk category whereas 1071 women were reclassified into the high-risk category. After reclassification of these women, CHD event rate was of 6.8% and 12.2%, respectively for women classified at low and high CHD risk. Results of the present study suggest that asking simple questions about leisure-time and work-related physical activity which can be rapidly obtained by any physician at no cost could be helpful in the estimation of patients' CHD risk.

Evaluating the Quality of Research into a Single Prognostic Biomarker: A Systematic Review and Meta-analysis of 83 Studies of C-Reactive Protein in Stable Coronary Artery Disease

PubMed Central

Hemingway, Harry; Philipson, Peter; Chen, Ruoling; Fitzpatrick, Natalie K.; Damant, Jacqueline; Shipley, Martin; Abrams, Keith R.; Moreno, Santiago; McAllister, Kate S. L.; Palmer, Stephen; Kaski, Juan Carlos; Timmis, Adam D.; Hingorani, Aroon D.

2010-01-01

Background Systematic evaluations of the quality of research on a single prognostic biomarker are rare. We sought to evaluate the quality of prognostic research evidence for the association of C-reactive protein (CRP) with fatal and nonfatal events among patients with stable coronary disease. Methods and Findings We searched MEDLINE (1966 to 2009) and EMBASE (1980 to 2009) and selected prospective studies of patients with stable coronary disease, reporting a relative risk for the association of CRP with death and nonfatal cardiovascular events. We included 83 studies, reporting 61,684 patients and 6,485 outcome events. No study reported a prespecified statistical analysis protocol; only two studies reported the time elapsed (in months or years) between initial presentation of symptomatic coronary disease and inclusion in the study. Studies reported a median of seven items (of 17) from the REMARK reporting guidelines, with no evidence of change over time. The pooled relative risk for the top versus bottom third of CRP distribution was 1.97 (95% confidence interval [CI] 1.78–2.17), with substantial heterogeneity (I2 = 79.5). Only 13 studies adjusted for conventional risk factors (age, sex, smoking, obesity, diabetes, and low-density lipoprotein [LDL] cholesterol) and these had a relative risk of 1.65 (95% CI 1.39–1.96), I2 = 33.7. Studies reported ten different ways of comparing CRP values, with weaker relative risks for those based on continuous measures. Adjusting for publication bias (for which there was strong evidence, Egger's p<0.001) using a validated method reduced the relative risk to 1.19 (95% CI 1.13–1.25). Only two studies reported a measure of discrimination (c-statistic). In 20 studies the detection rate for subsequent events could be calculated and was 31% for a 10% false positive rate, and the calculated pooled c-statistic was 0.61 (0.57–0.66). Conclusion Multiple types of reporting bias, and publication bias, make the magnitude of any independent association between CRP and prognosis among patients with stable coronary disease sufficiently uncertain that no clinical practice recommendations can be made. Publication of prespecified statistical analytic protocols and prospective registration of studies, among other measures, might help improve the quality of prognostic biomarker research. Please see later in the article for the Editors' Summary PMID:20532236

Amino-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein but not cystatin C predict cardiovascular events in male patients with peripheral artery disease independently of ambulatory pulse pressure.

PubMed

Skoglund, Per H; Arpegård, Johannes; Ostergren, Jan; Svensson, Per

2014-03-01

Patients with peripheral arterial disease (PAD) are at high risk for cardiovascular (CV) events. We have previously shown that ambulatory pulse pressure (APP) predicts CV events in PAD patients. The biomarkers amino-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and cystatin C are related to a worse outcome in patients with CV disease, but their predictive values have not been studied in relation to APP. Blood samples and 24-hour measurements of ambulatory blood pressure were examined in 98 men referred for PAD evaluation during 1998-2001. Patients were followed for a median of 71 months. The outcome variable was CV events defined as either CV mortality or any hospitalization for myocardial infarction, stroke, or coronary revascularization. The predictive values of log(NT-proBNP), log(hs-CRP), and log(cystatin C) alone and together with APP were assessed by multivariable Cox regression. Area under the curve (AUC) and net reclassification improvement (NRI) were calculated compared with a model containing other significant risk factors. During follow-up, 36 patients had at least 1 CV event. APP, log(NT-proBNP), and log(hs-CRP) all predicted CV events in univariable analysis, whereas log(cystatin C) did not. In multivariable analysis log(NT-proBNP) (hazard ratio (HR) = 1.62; 95% confidence interval (CI) = 1.05-2.51) and log(hs-CRP) (HR = 1.63; 95% CI = 1.19-2.24) predicted events independently of 24-hour PP. The combination of log(NT-proBNP), log(hs-CRP), and average day PP improved risk discrimination (AUC = 0.833 vs. 0.736; P < 0.05) and NRI (37%; P < 0.01) when added to other significant risk factors. NT-proBNP and hs-CRP predict CV events independently of APP and the combination of hs-CRP, NT-proBNP, and day PP improves risk discrimination in PAD patients.

Public health surveillance for the Toronto 2015 Pan/Parapan American Games

PubMed Central

Chan, E; Hohenadel, K; Lee, B; Helferty, M; Harris, JR; Macdonald, L; Badiani, T

2017-01-01

Background Public health surveillance for previous Olympic and Paralympic Games have been described in the literature, but surveillance for regional, multisport events on a smaller scale have rarely been explored. Objective To describe the public health surveillance planning, implementation, results, and lessons learned from the 2015 Pan/Parapan American Games in Toronto, Ontario, Canada. Intervention Public health surveillance planning for the Games began two years in advance and involved local, provincial and federal partners, primarily focusing on infectious disease. From June to August, 2015, enhanced public health surveillance was conducted to support situational awareness and to facilitate the detection of infectious diseases and outbreaks, environmental health hazards and impacts and other major health events. Outcomes No major public health incidents occurred that were associated with or a result of hosting the Games. There were two cases of reportable infectious diseases associated with the Games, and 18 public health investigations involving Games-accredited individuals (six related to vaccine-preventable diseases and 12 related to gastrointestinal illnesses or food/water safety violations). Enhanced communication mechanisms, rather than routine and syndromic surveillance systems, were the primary sources of initial notification to surveillance partners on investigations. Conclusion Working with its partners, Ontario created a robust public health surveillance system for the 2015 Pan/Parapan American Games. Lessons learned, as well as the relationships and capacity developed through this experience, will be applied towards public health surveillance planning for future events. PMID:29770080

Dissecting the molecular mechanisms of gene x environment interactions: implications for diagnosis and treatment of stress-related psychiatric disorders

PubMed Central

Binder, Elisabeth B.

2017-01-01

ABSTRACT Epidemiological studies indicate a combined contribution of genetic and environmental factors, mainly exposure to adverse life events, in the risk for psychiatric disease. Understanding how adverse life events interact with genetic predisposition on the molecular level to shape risk and resilience to psychiatric disorders may yield important insight into disease mechanism. Using the example of the molecular mechanisms of interaction of functional genetic variants within the stress-regulating gene FKBP5 and early adversity, it is delineated how this interaction could contribute to transdiagnostic disease risk via a combined genetic and epigenetic disinhibition of FKBP5 transcription. This knowledge may now allow to develop biomarkers for a transdiagnostic subset of psychiatric patients and to personalize treatment. PMID:29372006

Healthcare resource utilization and costs in working-age patients with high-risk atherosclerotic cardiovascular disease: findings from a multi-employer claims database.

PubMed

Zhao, Z; Zhu, Y; Fang, Y; Ye, W; McCollam, P

2015-01-01

Patients with coronary artery disease with diabetes, a history of acute coronary syndromes, cerebrovascular atherosclerotic disease, or peripheral arterial disease are at particularly high risk for a cardiovascular (CV) event and can be defined as having high-risk atherosclerotic cardiovascular disease (ASCVD). The objective of this study is to examine healthcare resource utilization (HRU) and total healthcare costs (THC) for patients with ASCVD in a commercially insured population. A retrospective cohort study was conducted using a large, US employer-based, claims database. Patients with an ASCVD diagnosis between October 1, 2008 to September 30, 2009 who met eligibility requirements were included. All-cause and ASCVD-related HRU and THC for the first and second year of follow-up were examined for all patients and by the number of arterial beds affected. Adjusted THC were compared across groups with and without polyvascular disease. The analysis included 152,290 patients with ASCVD. Use of CV-related medications, hospitalizations, and office visits were highest among patients with three arterial beds affected. Mean all-cause THC for patients with ASCVD were ∼$19,000 per patient in Year 1 or Year 2, with medical costs as the main driver. ASCVD-related THC were also similar for Year 1 ($8699) and Year 2 ($7925) across all patients. Adjusted all-cause and ASCVD-related THC for both years were greatest for patients with three affected arterial beds compared with one or two affected beds (p < 0.001 for each comparison). This is the first study in a managed care setting to systematically estimate all-cause and ASCVD-related THC for an aggregated population of ASCVD patients at high risk for a CV event. The economic burden of ASCVD in working-age patients in the US is substantial. Significantly higher HRU and costs were found in patients with polyvascular disease compared with those with only one affected bed.

Outcomes of neuropsychiatric events in systemic lupus erythematosus based on clinical phenotypes; prospective data from the Leiden NP SLE cohort.

PubMed

Magro-Checa, C; Beaart-van de Voorde, L J J; Middelkoop, H A M; Dane, M L; van der Wee, N J; van Buchem, M A; Huizinga, T W J; Steup-Beekman, G M

2017-04-01

Objective The objective of this study was to assess whether clinical and patient's reported outcomes are associated with a different pathophysiological origin of neuropsychiatric events presenting in systemic lupus erythematosus. Methods A total of 232 neuropsychiatric events presenting in 131 systemic lupus erythematosus patients were included. Neuropsychiatric systemic lupus erythematosus diagnosis was established per event by multidisciplinary evaluation. All neuropsychiatric events were divided according to a suspected underlying pathophysiological process into one of the following: non-neuropsychiatric systemic lupus erythematosus related, inflammatory and ischaemic neuropsychiatric systemic lupus erythematosus. The clinical outcome of all neuropsychiatric events was determined by a physician-completed four-point Likert scale. Health-related quality of life was measured with the subscales of the patient-generated Short Form 36 (SF-36) health survey questionnaire. The change between scores at paired visits of all domain scores, mental component summary (SF-36 MCS) and physical component summary (SF-36 PCS) scores were retrospectively calculated and used as patient-reported outcome. The association among these outcomes and the different origin of neuropsychiatric events was obtained using multiple logistic regression analysis. Results The clinical status of 26.8% non-neuropsychiatric systemic lupus erythematosus events, 15.8% ischaemic neuropsychiatric systemic lupus erythematosus and 51.6% inflammatory neuropsychiatric systemic lupus erythematosus improved after re-assessment. Almost all SF-36 domains had a positive change at re-assessment in all groups independently of the origin of neuropsychiatric events. Neuropsychiatric systemic lupus erythematosus ( B = 0.502; p < 0.001) and especially inflammatory neuropsychiatric systemic lupus erythematosus ( B = 0.827; p < 0.001) had better clinical outcome, with change in disease activity being the only important predictor. The change in SF-36 MCS was also independently associated with neuropsychiatric systemic lupus erythematosus ( B = 5.783; p < 0.05) and inflammatory neuropsychiatric systemic lupus erythematosus ( B = 11.133; p < 0.001). Disease duration and change in disease activity were the only predictors in both cases. The change in SF-36 PCS was only negatively associated with age. Conclusion Inflammatory neuropsychiatric systemic lupus erythematosus events have better clinical outcome and meaningful improvement in SF-36 MCS than ischaemic neuropsychiatric systemic lupus erythematosus or non-neuropsychiatric systemic lupus erythematosus.

Extreme Weather Events and Impacts on Vector-borne Diseases and Agriculture

USDA-ARS?s Scientific Manuscript database

Extreme weather events during the period 2010-2012 impacted agriculture and vector-borne disease throughout the world. We evaluated specific weather events with satellite remotely sensed environmental data and evaluated crop production and diseases associated with these events. Significant droughts ...

Telemedicine to promote patient safety: Use of phone-based interactive voice response system (IVRS) to reduce adverse safety events in predialysis CKD

PubMed Central

Weiner, Shoshana; Fink, Jeffery C.

2017-01-01

Chronic kidney disease (CKD) patients have several features conferring upon them a high risk of adverse safety events, which are defined as incidents with unintended harm related to processes of care or medications. These characteristics include impaired renal function, polypharmacy, and frequent health system encounters. The consequences of such events in CKD can include new or prolonged hospitalization, accelerated renal function loss, acute kidney injury, end-stage renal disease and death. Health information technology administered via telemedicine presents opportunities for CKD patients to remotely communicate safety-related findings to providers for the purpose of improving their care. However, many CKD patients have limitations which hinder their use of telemedicine and access to the broad capabilities of health information technology. In this review we summarize previous assessments of the pre-dialysis CKD populations’ proficiency in using telemedicine modalities and describe the use of interactive voice-response system (IVRS) to gauge the safety phenotype of the CKD patient. We discuss the potential for expanded IVRS use in CKD to address the safety threats inherent to this population. PMID:28224940

Autochthonous Chikungunya Transmission and Extreme Climate Events in Southern France.

PubMed

Roiz, David; Boussès, Philippe; Simard, Frédéric; Paupy, Christophe; Fontenille, Didier

2015-06-01

Extreme precipitation events are increasing as a result of ongoing global warming, but controversy surrounds the relationship between flooding and mosquito-borne diseases. A common view among the scientific community and public health officers is that heavy rainfalls have a flushing effect on breeding sites, which negatively affects vector populations, thereby diminishing disease transmission. During 2014 in Montpellier, France, there were at least 11 autochthonous cases of chikungunya caused by the invasive tiger mosquito Aedes albopictus in the vicinity of an imported case. We show that an extreme rainfall event increased and extended the abundance of the disease vector Ae. albopictus, hence the period of autochthonous transmission of chikungunya. We report results from close monitoring of the adult and egg population of the chikungunya vector Ae. albopictus through weekly sampling over the entire mosquito breeding season, which revealed an unexpected pattern. Statistical analysis of the seasonal dynamics of female abundance in relation to climatic factors showed that these relationships changed after the heavy rainfall event. Before the inundations, accumulated temperatures are the most important variable predicting Ae. albopictus seasonal dynamics. However, after the inundations, accumulated rainfall over the 4 weeks prior to capture predicts the seasonal dynamics of this species and extension of the transmission period. Our empirical data suggests that heavy rainfall events did increase the risk of arbovirus transmission in Southern France in 2014 by favouring a rapid rise in abundance of vector mosquitoes. Further studies should now confirm these results in different ecological contexts, so that the impact of global change and extreme climatic events on mosquito population dynamics and the risk of disease transmission can be adequately understood.

Central nervous system involvement in pediatric rheumatic diseases: current concepts in treatment.

PubMed

Duzova, Ali; Bakkaloglu, Aysin

2008-01-01

Central nervous system (CNS) manifestations are not rare in pediatric rheumatic diseases. They may be a relatively common feature of the disease, as in systemic lupus erythematosus (SLE) and Behçet's disease. Direct CNS involvement of a systemic rheumatic disease, primary CNS vasculitis, indirect involvement secondary to hypertension, hypoxia and metabolic changes, and drug associated adverse events may all result in CNS involvement. We have reviewed the CNS manifestations of SLE, Behçet's disease, Henoch-Schönlein purpura, polyarteritis nodosa, juvenile idiopathic arthritis, juvenile ankylosing spondylitis, familial Mediterranean fever, scleroderma, sarcoidosis, Wegener's granulomatosis, Takayasu's arteritis, CINCA syndrome, Kawasaki disease, and primary CNS vasculitis; and adverse CNS effects of anti-rheumatic drugs in pediatric patients. The manifestations are diverse; ranging from headache, seizures, chorea, changes in personality, depression, memory and concentration problems, cognitive impairment, cerebrovascular accidents to coma, and death. The value of cerebrospinal fluid (CSF) examination (pleocytosis, high level of protein), auto-antibodies in serum and CSF, electroencephalography, neuroimaging with computerized tomography, magnetic resonance imaging, SPECT, PET, and angiography depends on the disease. Brain biopsy is gold standard for the diagnosis of CNS vasculitis, however it may be inconclusive in 25% of cases. A thorough knowledge of the rheumatic diseases and therapy-related adverse events is mandatory for the management of a patient with rheumatic disease and CNS involvement. Severe CNS involvement is associated with poor prognosis, and high mortality rate. High dose steroid and cyclophosphamide (oral or intravenous) are first choice drugs in the treatment; plasmapheresis, IVIG, thalidomide, and intratechal treatment may be valuable in treatment-resistant, and serious cases.

Molecular inflammation: underpinnings of aging and age-related diseases.

PubMed

Chung, Hae Young; Cesari, Matteo; Anton, Stephen; Marzetti, Emanuele; Giovannini, Silvia; Seo, Arnold Young; Carter, Christy; Yu, Byung Pal; Leeuwenburgh, Christiaan

2009-01-01

Recent scientific studies have advanced the notion of chronic inflammation as a major risk factor underlying aging and age-related diseases. In this review, low-grade, unresolved, molecular inflammation is described as an underlying mechanism of aging and age-related diseases, which may serve as a bridge between normal aging and age-related pathological processes. Accumulated data strongly suggest that continuous (chronic) upregulation of pro-inflammatory mediators (e.g., TNF-alpha, IL-1beta, IL-6, COX-2, iNOS) are induced during the aging process due to an age-related redox imbalance that activates many pro-inflammatory signaling pathways, including the NF-kappaB signaling pathway. These pro-inflammatory molecular events are discussed in relation to their role as basic mechanisms underlying aging and age-related diseases. Further, the anti-inflammatory actions of aging-retarding caloric restriction and exercise are reviewed. Thus, the purpose of this review is to describe the molecular roles of age-related physiological functional declines and the accompanying chronic diseases associated with aging. This new view on the role of molecular inflammation as a mechanism of aging and age-related pathogenesis can provide insights into potential interventions that may affect the aging process and reduce age-related diseases, thereby promoting healthy longevity.

Molecular Inflammation: Underpinnings of Aging and Age-related Diseases

PubMed Central

Chung, Hae Young; Cesari, Matteo; Anton, Stephen; Marzetti, Emanuele; Giovannini, Silvia; Seo, Arnold Young; Carter, Christy; Yu, Byung Pal; Leeuwenburgh, Christiaan

2013-01-01

Recent scientific studies have advanced the notion of chronic inflammation as a major risk factor underlying aging and age-related diseases. In this review, low-grade, unresolved, molecular inflammation is described as an underlying mechanism of aging and age-related diseases, which may serve as a bridge between normal aging and age-related pathological processes. Accumulated data strongly suggest that continuous (chronic) up-regulation of pro-inflammatory mediators (e.g., TNF-α, IL-1β, 6, COX-2, iNOS) are induced during the aging process due to an age-related redox imbalance that activates many pro-inflammatory signaling pathways, including the NF-κB signaling pathway. These pro-inflammatory molecular events are discussed in relation to their role as basic mechanisms underlying aging and age-related diseases. Further, the anti-inflammatory actions of aging-retarding caloric restriction and exercise are reviewed. Thus, the purpose of this review is to describe the molecular roles of age-related physiological functional declines and the accompanying chronic diseases associated with aging. This new view on the role of molecular inflammation as a mechanism of aging and age-related pathogenesis can provide insights into potential interventions that may affect the aging process and reduce age-related diseases, thereby promoting healthy longevity. PMID:18692159

Aspirin and omeprazole for secondary prevention of cardiovascular disease in patients at risk for aspirin-associated gastric ulcers.

PubMed

García-Rayado, Guillermo; Sostres, Carlos; Lanas, Angel

2017-08-01

Cardiovascular disease is the most important cause of morbidity and mortality in the world and low-dose aspirin is considered the cornerstone of the cardiovascular disease prevention. However, low-dose aspirin use is associated with gastrointestinal adverse effects in the whole gastrointestinal tract. In this setting, co-therapy with a proton pump inhibitor is the most accepted strategy to reduce aspirin related upper gastrointestinal damage. In addition, some adverse effects have been described with proton pump inhibitors long term use. Areas covered: Low-dose aspirin related beneficial and adverse effects in cardiovascular system and gastrointestinal tract are reviewed. In addition, this manuscript summarizes current data on upper gastrointestinal damage prevention and adverse events with proton pump inhibition. Finally, we discuss the benefit/risk ratio of proton pump inhibitor use in patients at risk of gastrointestinal damage taking low-dose aspirin. Expert commentary: Nowadays, with the current available evidence, the combination of low-dose aspirin with proton pump inhibitor is the most effective therapy for cardiovascular prevention in patients at high gastrointestinal risk. However, further studies are needed to discover new effective strategies with less related adverse events.

Emerging treatments for postmenopausal osteoporosis – focus on denosumab

PubMed Central

Geusens, Piet

2009-01-01

The pathway of the receptor activator of the nuclear factor κB ligand (RANKL), RANK and osteoprotegerin (OPG) plays a central role in coupling bone formation and resorption during normal bone turnover and in a wide spectrum of diseases characterized by disturbed bone remodeling, increased bone resorption and bone destruction (osteoporosis, Paget’s disease of bone, rheumatoid arthritis [RA], metastatic bone disease). Clinical trials indicate that denosumab, a RANKL-specific recombinant humanized monoclonal antibody, is effective in suppressing bone resorption, resulting in increase in bone mineral density (BMD) in post-menopausal women with low BMD, and has the potential to prevent progression of erosions in RA and of skeletal-related events in metastatic bone disease. The effects on fracture reduction in postmenopausal osteoporosis are awaited from the recently finished FREEDOM study. In clinical trials with denosumab, overall adverse events were similar to placebo or comparators, indicating a favorable safety profile in these diseases, which until now have been available up to 4 years, but data on long-term safety will be needed. PMID:19554095

Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis

PubMed Central

Baxi, Shrujal; Yang, Annie; Gennarelli, Renee L; Khan, Niloufer; Wang, Ziwei; Boyce, Lindsay

2018-01-01

Abstract Objective To evaluate rates of serious organ specific immune-related adverse events, general adverse events related to immune activation, and adverse events consistent with musculoskeletal problems for anti-programmed cell death 1 (PD-1) drugs overall and compared with control treatments. Design Systematic review and meta-analysis. Data sources Medline, Embase, Cochrane Library, Web of Science, and Scopus searched to 16 March 2017 and combined with data from ClinicalTrials.gov. Study selection Eligible studies included primary clinical trial data on patients with cancer with recurrent or metastatic disease. Data extraction Three independent investigators extracted data on adverse events from ClinicalTrials.gov and the published studies. Risk of bias was assessed using the Cochrane tool by three independent investigators. Results 13 relevant studies were included; adverse event data were available on ClinicalTrials.gov for eight. Studies compared nivolumab (n=6), pembrolizumab (5), or atezolizumab (2) with chemotherapy (11), targeted drugs (1), or both (1). Serious organ specific immune-related adverse events were rare, but compared with standard treatment, rates of hypothyroidism (odds ratio 7.56, 95% confidence interval 4.53 to 12.61), pneumonitis (5.37, 2.73 to 10.56), colitis (2.88, 1.30 to 6.37), and hypophysitis (3.38, 1.02 to 11.08) were increased with anti-PD-1 drugs. Of the general adverse events related to immune activation, only the rate of rash (2.34, 2.73 to 10.56) increased. Incidence of fatigue (32%) and diarrhea (19%) were high but similar to control. Reporting of adverse events consistent with musculoskeletal problems was inconsistent; rates varied but were over 20% in some studies for arthraligia and back pain. Conclusions Organ specific immune-related adverse events are uncommon with anti-PD-1 drugs but the risk is increased compared with control treatments. General adverse events related to immune activation are largely similar. Adverse events consistent with musculoskeletal problems are inconsistently reported but adverse events may be common. PMID:29540345

Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis.

PubMed

Baxi, Shrujal; Yang, Annie; Gennarelli, Renee L; Khan, Niloufer; Wang, Ziwei; Boyce, Lindsay; Korenstein, Deborah

2018-03-14

To evaluate rates of serious organ specific immune-related adverse events, general adverse events related to immune activation, and adverse events consistent with musculoskeletal problems for anti-programmed cell death 1 (PD-1) drugs overall and compared with control treatments. Systematic review and meta-analysis. Medline, Embase, Cochrane Library, Web of Science, and Scopus searched to 16 March 2017 and combined with data from ClinicalTrials.gov. Eligible studies included primary clinical trial data on patients with cancer with recurrent or metastatic disease. Three independent investigators extracted data on adverse events from ClinicalTrials.gov and the published studies. Risk of bias was assessed using the Cochrane tool by three independent investigators. 13 relevant studies were included; adverse event data were available on ClinicalTrials.gov for eight. Studies compared nivolumab (n=6), pembrolizumab (5), or atezolizumab (2) with chemotherapy (11), targeted drugs (1), or both (1). Serious organ specific immune-related adverse events were rare, but compared with standard treatment, rates of hypothyroidism (odds ratio 7.56, 95% confidence interval 4.53 to 12.61), pneumonitis (5.37, 2.73 to 10.56), colitis (2.88, 1.30 to 6.37), and hypophysitis (3.38, 1.02 to 11.08) were increased with anti-PD-1 drugs. Of the general adverse events related to immune activation, only the rate of rash (2.34, 2.73 to 10.56) increased. Incidence of fatigue (32%) and diarrhea (19%) were high but similar to control. Reporting of adverse events consistent with musculoskeletal problems was inconsistent; rates varied but were over 20% in some studies for arthraligia and back pain. Organ specific immune-related adverse events are uncommon with anti-PD-1 drugs but the risk is increased compared with control treatments. General adverse events related to immune activation are largely similar. Adverse events consistent with musculoskeletal problems are inconsistently reported but adverse events may be common. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The incidence and cost of cardiac surgery adverse events in Australian (Victorian) hospitals 2003-2004.

PubMed

Ehsani, Jonathon Pouya; Duckett, Stephen J; Jackson, Terri

2007-12-01

The aim of this study was to estimate the incidence of adverse events in acute surgical admissions for cardiac disease in admitted episodes in the year 2003-2004 and to estimate the cost of these complications to the Victorian health system. Cardiac surgery adverse events are among the most frequent and significant contributors to the morbidity, mortality and cost associated with hospitalisation. Patient-level costing data set for major Victorian public hospitals in 2003-2004 was analysed for adverse events using C-prefixed markers, denoting complications that arose during the course of hospital treatment for cardiac surgery diagnosis related groups (DRGs). The cost of adverse events was estimated by linear regression modelling, adjusted for age and co-morbidity. A total of 16,766 multi-day cardiac disease cases were identified, of whom 6,181 (36.85%) had at least one adverse event. Patients with adverse events stayed approximately 7 days longer and had four times the case fatality rate than those without. After adjustment for age and co-morbidity, the presence of an adverse event adds AUS$5,751. The sum of the total cost of adverse events for each DRG was AUS$42.855 million, representing 21.6% of total expenditure on cardiac surgery and adding 27.5% in broad terms to the cardiac surgery budget.

Predictive Value of Reactive Hyperemia for Cardiovascular Events in Patients With Peripheral Arterial Disease Undergoing Vascular Surgery

PubMed Central

Huang, Alex L.; Silver, Annemarie E.; Shvenke, Elena; Schopfer, David W.; Jahangir, Eiman; Titas, Megan A.; Shpilman, Alex; Menzoian, James O.; Watkins, Michael T.; Raffetto, Joseph D.; Gibbons, Gary; Woodson, Jonathan; Shaw, Palma M.; Dhadly, Mandeep; Eberhardt, Robert T.; Keaney, John F.; Gokce, Noyan; Vita, Joseph A.

2008-01-01

Objective Reactive hyperemia is the compensatory increase in blood flow that occurs after a period of tissue ischemia, and this response is blunted in patients with cardiovascular risk factors. The predictive value of reactive hyperemia for cardiovascular events in patients with atherosclerosis and the relative importance of reactive hyperemia compared with other measures of vascular function have not been previously studied. Methods and Results We prospectively measured reactive hyperemia and brachial artery flow-mediated dilation by ultrasound in 267 patients with peripheral arterial disease referred for vascular surgery (age 66±11 years, 26% female). Median follow-up was 309 days (range 1 to 730 days). Fifty patients (19%) had an event, including cardiac death (15), myocardial infarction (18), unstable angina (8), congestive heart failure (6), and nonhemorrhagic stroke (3). Patients with an event were older and had lower hyperemic flow velocity (75±39 versus 95±50 cm/s, P=0.009). Patients with an event also had lower flow-mediated dilation (4.5±3.0 versus 6.9±4.6%, P<0.001), and when these 2 measures of vascular function were included in the same Cox proportional hazards model, lower hyperemic flow (OR 2.7, 95% CI 1.2 to 5.9, P=0.018) and lower flow-mediated dilation (OR 4.2, 95% CI: 1.8 to 9.8, P=0.001) both predicted cardiovascular events while adjusting for other risk factors. Conclusions Thus, lower reactive hyperemia is associated with increased cardiovascular risk in patients with peripheral arterial disease. Furthermore, flow-mediated dilation and reactive hyperemia incrementally relate to cardiovascular risk, although impaired flow-mediated dilation was the stronger predictor in this population. These findings further support the clinical relevance of vascular function measured in the microvasculature and conduit arteries in the upper extremity. PMID:17717291

Personality, disease severity, and the risk of long-term cardiac events in patients with a decreased ejection fraction after myocardial infarction.

PubMed

Denollet, J; Brutsaert, D L

1998-01-20

Patients with myocardial infarction (MI) with a decreased left ventricular ejection fraction (LVEF) have a poor prognosis, but the role of emotional stress in prognosis is not known. We hypothesized that emotional stress in these patients (1) is unrelated to the severity of cardiac disorder, (2) predicts cardiac events, and (3) is a function of basic personality traits. Eighty-seven patients with MI (age, 41 to 69 years) with an LVEF of < or =50% underwent psychological assessment at baseline. Patients and their families were contacted after 6 to 10 years (mean, 7.9 years); cardiac events were defined as cardiac death or nonfatal MI. Emotional distress was unrelated to the severity of cardiac disorder. At follow-up, 21 patients had experienced a cardiac event (13 fatal events). These events were related to LVEF of < or =30%, poor exercise tolerance, previous MI, anxiety, anger, and depression (all P< or =.02). Patients with a distressed personality (type D; ie, the tendency to suppress negative emotions) were more likely to experience an event over time compared with non-type D patients (P=.00005). Cox proportional hazards analysis yielded LVEF of < or =30% (relative risk, 3.0; 95% confidence interval, 1.2 to 7.7; P=.02) and type D (relative risk, 4.7; 95% confidence interval, 1.9 to 11.8; P=.001) as independent predictors. Anxiety, anger, and depression did not add to the predictive power of type D; these negative emotions were highly correlated and reflected the personality domain of negative affectivity. Personality influences the clinical course of patients with a decreased LVEF. Emotional distress in these patients is unrelated to disease severity but reflects individual differences in personality. Clinical trials should take a broad view of the target of intervention; assessment of LVEF and personality may identify patients at risk.

Epigenetic Patterns in Blood Associated With Lipid Traits Predict Incident Coronary Heart Disease Events and Are Enriched for Results From Genome-Wide Association Studies.

PubMed

Hedman, Åsa K; Mendelson, Michael M; Marioni, Riccardo E; Gustafsson, Stefan; Joehanes, Roby; Irvin, Marguerite R; Zhi, Degui; Sandling, Johanna K; Yao, Chen; Liu, Chunyu; Liang, Liming; Huan, Tianxiao; McRae, Allan F; Demissie, Serkalem; Shah, Sonia; Starr, John M; Cupples, L Adrienne; Deloukas, Panos; Spector, Timothy D; Sundström, Johan; Krauss, Ronald M; Arnett, Donna K; Deary, Ian J; Lind, Lars; Levy, Daniel; Ingelsson, Erik

2017-01-01

Genome-wide association studies have identified loci influencing circulating lipid concentrations in humans; further information on novel contributing genes, pathways, and biology may be gained through studies of epigenetic modifications. To identify epigenetic changes associated with lipid concentrations, we assayed genome-wide DNA methylation at cytosine-guanine dinucleotides (CpGs) in whole blood from 2306 individuals from 2 population-based cohorts, with replication of findings in 2025 additional individuals. We identified 193 CpGs associated with lipid levels in the discovery stage ( P <1.08E-07) and replicated 33 (at Bonferroni-corrected P <0.05), including 25 novel CpGs not previously associated with lipids. Genes at lipid-associated CpGs were enriched in lipid and amino acid metabolism processes. A differentially methylated locus associated with triglycerides and high-density lipoprotein cholesterol (HDL-C; cg27243685; P =8.1E-26 and 9.3E-19) was associated with cis -expression of a reverse cholesterol transporter ( ABCG1; P =7.2E-28) and incident cardiovascular disease events (hazard ratio per SD increment, 1.38; 95% confidence interval, 1.15-1.66; P =0.0007). We found significant cis -methylation quantitative trait loci at 64% of the 193 CpGs with an enrichment of signals from genome-wide association studies of lipid levels ( P TC =0.004, P HDL-C =0.008 and P triglycerides =0.00003) and coronary heart disease ( P =0.0007). For example, genome-wide significant variants associated with low-density lipoprotein cholesterol and coronary heart disease at APOB were cis -methylation quantitative trait loci for a low-density lipoprotein cholesterol-related differentially methylated locus. We report novel associations of DNA methylation with lipid levels, describe epigenetic mechanisms related to previous genome-wide association studies discoveries, and provide evidence implicating epigenetic regulation of reverse cholesterol transport in blood in relation to occurrence of cardiovascular disease events. © 2017 The Authors.

Mitral valve surgery in emergency for severe acute regurgitation: analysis of postoperative results from a multicentre study.

PubMed

Lorusso, Roberto; Gelsomino, Sandro; De Cicco, Giuseppe; Beghi, Cesare; Russo, Claudio; De Bonis, Michele; Colli, Andrea; Sala, Andrea

2008-04-01

To evaluate postoperative outcome of emergency surgery for acute severe mitral regurgitation (ASMR) from a multicentre experience. In six centres, 279 patients (mean age 62+/-14 years, 62% female) undergoing emergency surgery for ASMR from December 1986 to March 2007 were analysed and followed up. Aetiology included acute myocardial infarction (AMI) in 126 patients (group 1, 45%), degenerative mitral valve disease in 74 (group 2, 26%), and acute endocarditis (AE) in 79 (group 3, 28%). Preoperatively, all patients were in haemodynamic instability, with 185 patients in cardiogenic shock (66%), 184 (66%) intubated, and 61 (22%) on IABP, respectively. Valve repair was performed in 76 (27%), whereas 203 (73%) underwent valve replacement. Median follow-up (98% complete) was 70.8 months (inter-quartile range 59.8-86.66 months). Overall 30-day mortality was 22.5% (63/279). Early death was significantly lower in group 2 (p<0.001 and p=0.005 vs group 1 and 3, respectively) whereas no difference was detected between group 1 and 3. At logistic regression analysis AMI, AE, shock, left ventricular dysfunction, and coronary artery disease were predictors of early death. Overall 15-year survival was 67+/-10%. Survival was lower in group 1 (39+/-11%) than in group 2 (75+/-9%) and group 3 (77+/-10%). Cox regression found AMI, and associated coronary artery disease to be predictors of late death. Overall 15-year actuarial and actual freedom from cardiac-related events were 44+/-9% and 28+/-10%, respectively, with the worst outcome in the presence of AE. Associated coronary artery disease, AE, AMI, preoperative atrial fibrillation, and chronic renal failure were independent predictors of cardiac-related events. Emergency surgery for ASMR remains a surgical challenge for high incidence of early and late cardiac-related events, particularly in patients with associated coronary artery disease and acute endocarditis. Apparently, type of mitral valve surgical approaches (repair or replacement) did not provide any influence on postoperative outcome.

Airborne spread of foot-and-mouth disease - model intercomparison

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gloster, J; Jones, A; Redington, A

2008-09-04

Foot-and-mouth disease is a highly infectious vesicular disease of cloven-hoofed animals caused by foot-and-mouth disease virus. It spreads by direct contact between animals, by animal products (milk, meat and semen), by mechanical transfer on people or fomites and by the airborne route - with the relative importance of each mechanism depending on the particular outbreak characteristics. Over the years a number of workers have developed or adapted atmospheric dispersion models to assess the risk of foot-and-mouth disease virus spread through the air. Six of these models were compared at a workshop hosted by the Institute for Animal Health/Met Office duringmore » 2008. A number of key issues emerged from the workshop and subsequent modelling work: (1) in general all of the models predicted similar directions for 'at risk' livestock with much of the remaining differences strongly related to differences in the meteorological data used; (2) determination of an accurate sequence of events is highly important, especially if the meteorological conditions vary substantially during the virus emission period; and (3) differences in assumptions made about virus release, environmental fate, and subsequent infection can substantially modify the size and location of the downwind risk area. Close relationships have now been established between participants, which in the event of an outbreak of disease could be readily activated to supply advice or modelling support.« less

Climate Change in the US: Potential Consequences for Human Health

NASA Technical Reports Server (NTRS)

Maynard, Nancy G.

2001-01-01

The U.S. National Assessment identified five major areas of consequences of climate change in the United States: temperature-related illnesses and deaths, health effects related to extreme weather events, air pollution-related health effects, water- and food-borne diseases, and insect-, tick-, and rodent-borne diseases. The U.S. National Assessment final conclusions about these potential health effects will be described. In addition, a summary of some of the new tools for studying human health aspects of climate change as well as environment-health linkages through remotely sensed data and observations will be provided.

Primary prevention of cardiovascular disease in patients with systemic lupus erythematosus: case series and literature review.

PubMed

Fasano, S; Margiotta, D P; Navarini, L; Pierro, L; Pantano, I; Riccardi, A; Afeltra, A; Valentini, G

2017-12-01

Background Systemic lupus erythematosus is associated with an increased risk of cardiovascular disease. Low-dose aspirin, hydroxychloroquine and statins have been suggested to play a prophylactic role of cardiovascular events. This study is devoted to reviewing the literature on the topic and assessing the effects of these drugs in preventing a first cardiovascular event in a two-centre Italian series. Methods A PubMed search on cardiovascular prevention in systemic lupus erythematosus was performed. Moreover, systemic lupus erythematosus patients admitted to two centres from 2000-2015, who at admission had not experienced any cardiovascular event, were investigated. Aspirin, hydroxychloroquine and statin use, and the occurrence of any cardiovascular event, were recorded at each visit. Kaplan-Meier and Cox regression analyses were performed to evaluate the role of traditional, disease-related cardiovascular risk factors and of each of the three drugs in the occurrence of new cardiovascular events. Results The literature search produced conflicting results. Two hundred and ninety-one systemic lupus erythematosus patients were included in the study and followed for a median of eight years. During follow-up, 16 cardiovascular events occurred. At multivariate analysis, taking aspirin (hazard ratio: 0.24) and hydroxychloroquine for more than five years (hazard ratio: 0.27) reduced, while antiphospholipid antibody positivity (hazard ratio: 4.32) increased, the risk of a first cardiovascular event. No effect of statins emerged. Conclusion Our study confirms an additive role of aspirin and hydroxychloroquine in the primary prophylaxis of cardiovascular events in Italian patients with systemic lupus erythematosus. The lack of any detected effect in previous reports may depend on the design of studies and their short follow-up period.

The FIFA Women's World Cup in Germany 2011--a practical example for tailoring an event-specific enhanced infectious disease surveillance system.

PubMed

Takla, Anja; Velasco, Edward; Benzler, Justus

2012-07-31

Mass gatherings require a decision from public health authorities on how to monitor infectious diseases during the event. The appropriate level of enhanced surveillance depends on parameters like the scale of the event (duration, spatial distribution, season), participants' origin, amount of public attention, and baseline disease activity in the host country. For the FIFA Men's World Cup 2006, Germany implemented enhanced surveillance. As the scale of the FIFA Women's World Cup (June 26 - July 17, 2011) was estimated to be substantially smaller in size, visitors and duration, it was not feasible to simply adopt the previously implemented measures. Our aim was therefore to develop a strategy to tailor an event-specific enhanced surveillance for this smaller-scale mass gathering. Based on the enhanced surveillance measures during the Men's Cup, we conducted a needs assessment with the district health authorities in the 9 host cities in March 2011. Specific measures with a majority consent were implemented. After the event, we surveyed the 9 district and their corresponding 7 state health authorities to evaluate the implemented measures. All 9 district health authorities participated in the pre-event needs assessment. The majority of sites consented to moving from weekly to daily (Monday-Friday) notification reporting of routine infectious diseases, receiving regular feedback on those notification reports and summaries of national/international World Cup-relevant epidemiological incidents, e.g. outbreaks in countries of participating teams. In addition, we decided to implement twice-weekly reports of "unusual events" at district and state level. This enhanced system would commence on the first day and continue to one day following the tournament. No World Cup-related infectious disease outbreaks were reported during this time period. Eight of 9 district and 6 of 8 state health authorities participated in the final evaluation. The majority perceived the implemented measures as adequate. Our approach to tailor an event-specific enhanced surveillance concept worked well. Involvement of the participating stakeholders early-on in the planning phase secured ownership of and guaranteed support for the chosen strategy. The enhanced surveillance for this event resulted as a low-level surveillance. However, we included mechanisms for rapid upscaling if the situation would require adaptations.

Major Infection Events Over 5 Years: How Is Media Coverage Influencing Online Information Needs of Health Care Professionals and the Public?

PubMed Central

Fowler, David; Wiseman, Sue; Weinberg, Julius R

2013-01-01

Background The last decade witnessed turbulent events in public health. Emerging infections, increase of antimicrobial resistance, deliberately released threats and ongoing battles with common illnesses were amplified by the spread of disease through increased international travel. The Internet has dramatically changed the availability of information about outbreaks; however, little research has been done in comparing the online behavior of public and professionals around the same events and the effect of media coverage of outbreaks on information needs. Objective To investigate professional and public online information needs around major infection outbreaks and correlate these with media coverage. Questions include (1) How do health care professionals’ online needs for public health and infection control information differ from those of the public?, (2) Does dramatic media coverage of outbreaks contribute to the information needs among the public?, and (3) How do incidents of diseases and major policy events relate to the information needs of professionals? Methods We used three longitudinal time-based datasets from mid-2006 until end of 2010: (1) a unique record of professional online behavior on UK infection portals: National electronic Library of Infection and National Resource of Infection Control (NeLI/NRIC), (2) equivalent public online information needs (Google Trends), and (3) relevant media coverage (LexisNexis). Analysis of NeLI/NRIC logs identified the highest interest around six major infectious diseases: Clostridium difficile (C difficile)/Methicillin-resistant Staphylococcus aureus (MRSA), tuberculosis, meningitis, norovirus, and influenza. After pre-processing, the datasets were analyzed and triangulated with each other. Results Public information needs were more static, following the actual disease occurrence less than those of professionals, whose needs increase with public health events (eg, MRSA/C difficile) and the release of major national policies or important documents. Media coverage of events resulted in major public interest (eg, the 2007/2008 UK outbreak of C difficile/MRSA). An exception was norovirus, showing a seasonal pattern for both public and professionals, which matched the periodic disease occurrence. Meningitis was a clear example of a disease with heightened media coverage tending to focus on individual and celebrity cases. Influenza was a major concern during the 2009 H1N1 outbreak creating massive public interest in line with the spring and autumn peaks in cases; although in autumn 2009, there was no corresponding increase in media coverage. Online resources play an increasing role in fulfilling professionals’ and public information needs. Conclusions Significant factors related to a surge of professional interest around a disease were typically key publications and major policy changes. Public interests seem more static and correlate with media influence but to a lesser extent than expected. The only exception was norovirus, exhibiting online public and professional interest correlating with seasonal occurrences of the disease. Public health agencies with responsibility for risk communication of public health events, in particular during outbreaks and emergencies, need to collaborate with media in order to ensure the coverage is high quality and evidence-based, while professionals’ information needs remain mainly fulfilled by online open access to key resources. PMID:23856364

Major infection events over 5 years: how is media coverage influencing online information needs of health care professionals and the public?

PubMed

Kostkova, Patty; Fowler, David; Wiseman, Sue; Weinberg, Julius R

2013-07-15

The last decade witnessed turbulent events in public health. Emerging infections, increase of antimicrobial resistance, deliberately released threats and ongoing battles with common illnesses were amplified by the spread of disease through increased international travel. The Internet has dramatically changed the availability of information about outbreaks; however, little research has been done in comparing the online behavior of public and professionals around the same events and the effect of media coverage of outbreaks on information needs. To investigate professional and public online information needs around major infection outbreaks and correlate these with media coverage. Questions include (1) How do health care professionals' online needs for public health and infection control information differ from those of the public?, (2) Does dramatic media coverage of outbreaks contribute to the information needs among the public?, and (3) How do incidents of diseases and major policy events relate to the information needs of professionals? We used three longitudinal time-based datasets from mid-2006 until end of 2010: (1) a unique record of professional online behavior on UK infection portals: National electronic Library of Infection and National Resource of Infection Control (NeLI/NRIC), (2) equivalent public online information needs (Google Trends), and (3) relevant media coverage (LexisNexis). Analysis of NeLI/NRIC logs identified the highest interest around six major infectious diseases: Clostridium difficile (C difficile)/Methicillin-resistant Staphylococcus aureus (MRSA), tuberculosis, meningitis, norovirus, and influenza. After pre-processing, the datasets were analyzed and triangulated with each other. Public information needs were more static, following the actual disease occurrence less than those of professionals, whose needs increase with public health events (eg, MRSA/C difficile) and the release of major national policies or important documents. Media coverage of events resulted in major public interest (eg, the 2007/2008 UK outbreak of C difficile/MRSA). An exception was norovirus, showing a seasonal pattern for both public and professionals, which matched the periodic disease occurrence. Meningitis was a clear example of a disease with heightened media coverage tending to focus on individual and celebrity cases. Influenza was a major concern during the 2009 H1N1 outbreak creating massive public interest in line with the spring and autumn peaks in cases; although in autumn 2009, there was no corresponding increase in media coverage. Online resources play an increasing role in fulfilling professionals' and public information needs. Significant factors related to a surge of professional interest around a disease were typically key publications and major policy changes. Public interests seem more static and correlate with media influence but to a lesser extent than expected. The only exception was norovirus, exhibiting online public and professional interest correlating with seasonal occurrences of the disease. Public health agencies with responsibility for risk communication of public health events, in particular during outbreaks and emergencies, need to collaborate with media in order to ensure the coverage is high quality and evidence-based, while professionals' information needs remain mainly fulfilled by online open access to key resources.

Effect of Micronutrient Supplementation on Disease Progression in Asymptomatic, Antiretroviral-Naive, HIV-Infected Adults in Botswana A Randomized Clinical Trial

PubMed Central

Baum, Marianna K.; Campa, Adriana; Lai, Shenghan; Martinez, Sabrina Sales; Tsalaile, Lesedi; Burns, Patricia; Farahani, Mansour; Li, Yinghui; van Widenfelt, Erik; Page, John Bryan; Bussmann, Hermann; Fawzi, Wafaie W.; Moyo, Sikhulele; Makhema, Joseph; Thior, Ibou; Essex, Myron; Marlink, Richard

2015-01-01

IMPORTANCE Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive. OBJECTIVE To investigate whether long-term micronutrient supplementation is effective and safe in delaying disease progression when implemented early in adults infected with HIV subtype C who are ART-naive. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of supplementation with either daily multivitamins (B vitamins and vitamins C and E), seleniumalone, or multivitamins with selenium vs placebo inafactorial design for 24 months. The study was conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/μL who were not receiving ART at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009. INTERVENTIONS Daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo. MAIN OUTCOMES AND MEASURES Reaching a CD4 cell count less than 200/μL until May 2008; after this date, reaching a CD4 cell count of 250/μL or less, consistent with the standard of care in Botswana for initiation of ART at the time of the study. RESULTS There were 878 participants enrolled and randomized into the study. All participants were ART-naive throughout the study. In intent-to-treat analysis, participants receiving the combined supplement of multivitamins plus selenium had a significantly lower risk vs placebo of reaching CD4 cell count 250/μL or less (adjusted hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01; absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17 events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events). Multivitamins plus selenium in a single supplement, vs placebo, also reduced the risk of secondary events of combined outcomes for disease progression (CD4 cell count ≤250/μL, AIDS-defining conditions, or AIDS-related death, whichever occurred earlier [adjusted HR, 0.56; 95% CI, 0.33-0.95; P = .03; AER, 6.48/100 person-years; censoring rate, 0.90; 23 events]). There was no effect of supplementation on HIV viral load. Multivitamins alone and selenium supplementation alone were not statistically different from placebo for any end point. Reported adverse events were adjudicated as unlikely to be related to the intervention, and there were no notable differences in incidence of HIV-related and health-related events among study groups. CONCLUSIONS AND RELEVANCE In ART-naive HIV-infected adults, 24-month supplementation with a single supplement containing multivitamins and selenium was safe and significantly PMID:24281460

N400 Deficits from Semantic Matching of Pictures in Probands and First-Degree Relatives from Multiplex Schizophrenia Families

ERIC Educational Resources Information Center

Guerra, Seidel; Ibanez, Agustin; Martin, Migdyrai; Bobes, Maria Antonieta; Reyes, Adnelys; Mendoza, Raul; Bravo, Tania; Dominguez, Mayelin; Sosa, Mitchell Valdes

2009-01-01

Endophenotypes is one emerging strategy in schizophrenia research that is being used to identify the functional importance of genetically transmitted, brain-based deficits present in this disease. Currently, event-related potentials (ERPs) are timely used in this search. Several ERPs, including N400, present deficits in relation to schizophrenia.…

Report on Non-fatal events cardio-cerebro-vascular to ten years in a Southern Italy cohort.

PubMed

Capuano, Vincenzo; Lamaida, Norman; Capuano, Rocco; Capuano, Eduardo; Torre, Sergio; Marchese, Federica; Capuano, Ernesto

2014-12-01

Data relating to non-fatal cardiovascular events are poor but these data are essential to organize targeted interventions on the territory and to understand their effectiveness. We calculated the rates of morbidity from cardiovascular events covering the period 1998/99-2008/09, in a cohort of 1200 persons (600 men and 600 women) aged 25 to 74 years. Data were standardized using the European standard population. The incidence of events to ten years of non-fatal myocardial infarc.ion was 2.2% in men and of 1.8% in women. PCI interventions to ten year have been 3.3% in men and 3.4% in women, the interventions of aorto-coronary bypass have been 2.4% and 0.5% for men and women respectively. While all major cardiovascular events have been more frequent in men, in women there was a higher incidence of stroke (1.6% vs 0.9%). Although by comparison with other European countries Italy is among the countries considered at low-risk of coronary heart disease, in Campania cardiovascular diseases reach higher rates than the rest of the country. Our results are in keeping with the literature data and confirm that cardiovascular diseases are a major public health problem. Local analysis are useful in providing additional information for planning prevention interventions targeted to its own territory.

Individualistic values are related to an increase in the outbreaks of infectious diseases and zoonotic diseases.

PubMed

Morand, Serge; Walther, Bruno A

2018-03-01

Collectivist versus individualistic values are important attributes of intercultural variation. Collectivist values favour in-group members over out-group members and may have evolved to protect in-group members against pathogen transmission. As predicted by the pathogen stress theory of cultural values, more collectivist countries are associated with a higher historical pathogen burden. However, if lifestyles of collectivist countries indeed function as a social defence which decreases pathogen transmission, then these countries should also have experienced fewer disease outbreaks in recent times. We tested this novel hypothesis by correlating the values of collectivism-individualism for 66 countries against their historical pathogen burden, recent number of infectious disease outbreaks and zoonotic disease outbreaks and emerging infectious disease events, and four potentially confounding variables. We confirmed the previously established negative relationship between individualism and historical pathogen burden with new data. While we did not find a correlation for emerging infectious disease events, we found significant positive correlations between individualism and the number of infectious disease outbreaks and zoonotic disease outbreaks. Therefore, one possible cost for individualistic cultures may be their higher susceptibility to disease outbreaks. We support further studies into the exact protective behaviours and mechanisms of collectivist societies which may inhibit disease outbreaks.

Factors influencing return-to-work after cerebrovascular disease: the importance of previous cardiovascular risk.

PubMed

Catalina-Romero, Carlos; Ruilope, Luis Miguel; Sánchez-Chaparro, Miguel Angel; Valdivielso, Pedro; Cabrera-Sierra, Martha; Fernández-Labandera, Carlos; Ruiz-Moraga, Montserrat; Gonzalez-Quintela, Arturo; Calvo-Bonacho, Eva

2015-09-01

The role of prior cardiovascular risk (CVR) in the multifactorial process of returning to work after a cerebrovascular event has not been adequately investigated. Therefore, the objective of the present study was to analyse the association between previous CVR level, cardiovascular risk factors (CVRFs) and return-to-work (RTW) following cerebrovascular disease. This was a prospective observational study. We analysed a cohort of 348 patients who had experienced an episode of cerebrovascular disease-related work absence. These individuals were selected from the ICARIA study (Ibermutuamur CArdiovascular RIsk Assessment). Global CVR was assessed using the SCORE system. We investigated the association between demographics, work-related variables, CVRFs and RTW following a cerebrovascular event. We found that a total of 254 individuals (73.0%; 95% CI: 68.3-77.7) returned to work after cerebrovascular disease. Also, we observed a median loss of 12 working years due to disability. Moreover, adjusting for potential confounders revealed that low CVR level and the absence of the following CVRFs was associated with a higher likelihood of RTW: low vs moderate-to-high CVR level (OR: 2.55; 95% CI: 1.42-4.57), no hypertension before stroke (OR: 1.95; 95% CI: 1.11-3.41), non-smoker status (OR: 2.26; 95% CI: 1.30-3.93) and no previous diabetes (OR: 2.46; 95% CI: 1.26-4.79). Low CVR, along with the absence of several CVRFs, can be used to predict RTW rates following cerebrovascular events. Therefore, controlling hypertension, tobacco consumption and diabetes might contribute to the effectiveness of multidisciplinary rehabilitation and/or secondary/tertiary prevention programs for cerebrovascular disease. © The European Society of Cardiology 2014.

Long-term treatment of Cushing's disease with pasireotide: 5-year results from an open-label extension study of a Phase III trial.

PubMed

Petersenn, S; Salgado, L R; Schopohl, J; Portocarrero-Ortiz, L; Arnaldi, G; Lacroix, A; Scaroni, C; Ravichandran, S; Kandra, A; Biller, B M K

2017-07-01

Treating hypercortisolism in patients with Cushing's disease after failed surgery often requires chronic medication, underlining the need for therapies with favourable long-term efficacy and safety profiles. In a randomised, double-blind study, 162 adult patients with persistent/recurrent or de novo Cushing's disease received pasireotide. Patients with mean urinary free cortisol at/below the upper limit of normal or clinical benefit at month 12 could continue receiving pasireotide during an open-ended, open-label phase, the outcomes of which are described herein. Sixteen patients received 5 years of pasireotide treatment. Among these, median (95% confidence interval) percentage change from baseline in mean urinary free cortisol was -82.6% (-89.0, -41.9) and -81.8% (-89.8, -67.4) at months 12 and 60. Eleven patients had mean urinary free cortisol ≤ upper limit of normal at month 60. Improvements in clinical signs were sustained during long-term treatment. The safety profile of pasireotide at 5 years was similar to that reported after 12 months. Fifteen of 16 patients experienced a hyperglycaemia-related adverse event; glycated haemoglobin levels were stable between months 6 and 60. Adverse events related to hyperglycaemia, bradycardia, gallbladder/biliary tract, and liver safety were most likely to first occur by month 6; adverse event severity did not tend to worsen over time. This represents the longest prospective trial of a medical therapy for Cushing's disease to date. A subset of patients treated with pasireotide maintained biochemical and clinical improvements for 5 years, with no new safety signals emerging. These data support the use of pasireotide as an effective long-term therapy for some patients with Cushing's disease.

Considering the role of semantic memory in episodic future thinking: evidence from semantic dementia.

PubMed

Irish, Muireann; Addis, Donna Rose; Hodges, John R; Piguet, Olivier

2012-07-01

Semantic dementia is a progressive neurodegenerative condition characterized by the profound and amodal loss of semantic memory in the context of relatively preserved episodic memory. In contrast, patients with Alzheimer's disease typically display impairments in episodic memory, but with semantic deficits of a much lesser magnitude than in semantic dementia. Our understanding of episodic memory retrieval in these cohorts has greatly increased over the last decade, however, we know relatively little regarding the ability of these patients to imagine and describe possible future events, and whether episodic future thinking is mediated by divergent neural substrates contingent on dementia subtype. Here, we explored episodic future thinking in patients with semantic dementia (n=11) and Alzheimer's disease (n=11), in comparison with healthy control participants (n=10). Participants completed a battery of tests designed to probe episodic and semantic thinking across past and future conditions, as well as standardized tests of episodic and semantic memory. Further, all participants underwent magnetic resonance imaging. Despite their relatively intact episodic retrieval for recent past events, the semantic dementia cohort showed significant impairments for episodic future thinking. In contrast, the group with Alzheimer's disease showed parallel deficits across past and future episodic conditions. Voxel-based morphometry analyses confirmed that atrophy in the left inferior temporal gyrus and bilateral temporal poles, regions strongly implicated in semantic memory, correlated significantly with deficits in episodic future thinking in semantic dementia. Conversely, episodic future thinking performance in Alzheimer's disease correlated with atrophy in regions associated with episodic memory, namely the posterior cingulate, parahippocampal gyrus and frontal pole. These distinct neuroanatomical substrates contingent on dementia group were further qualified by correlational analyses that confirmed the relation between semantic memory deficits and episodic future thinking in semantic dementia, in contrast with the role of episodic memory deficits and episodic future thinking in Alzheimer's disease. Our findings demonstrate that semantic knowledge is critical for the construction of novel future events, providing the necessary scaffolding into which episodic details can be integrated. Further research is necessary to elucidate the precise contribution of semantic memory to future thinking, and to explore how deficits in self-projection manifest on behavioural and social levels in different dementia subtypes.

The effect of measuring serum doxycycline concentrations on clinical outcomes during treatment of chronic Q fever.

PubMed

van Roeden, S E; Bleeker-Rovers, C P; Kampschreur, L M; de Regt, M J A; Vermeulen Windsant, A; Hoepelman, A I M; Wever, P C; Oosterheert, J J

2018-04-01

First choice treatment for chronic Q fever is doxycycline plus hydroxychloroquine. Serum doxycycline concentration (SDC) >5 μg/mL has been associated with a favourable serological response, but the effect on clinical outcomes is unknown. To assess the effect of measuring SDC during treatment of chronic Q fever on clinical outcomes. We performed a retrospective cohort study, to assess the effect of measuring SDC on clinical outcomes in patients treated with doxycycline and hydroxychloroquine for chronic Q fever. Primary outcome was the first disease-related event (new complication or chronic Q fever-related mortality); secondary outcomes were all-cause mortality and PCR-positivity. Multivariable analysis was performed with a Cox proportional hazards model, with shared-frailty terms for different hospitals included. We included 201 patients (mean age 68 years, 83% male): in 167 patients (83%) SDC was measured, 34 patients (17%) were treated without SDC measurement. First SDC was >5 μg/mL in 106 patients (63%), all with 200 mg doxycycline daily. In patients with SDC measured, dosage was adjusted in 41% (n = 68), concerning an increase in 64 patients. Mean SDC was 4.1 μg/mL before dosage increase, and 5.9 μg/mL afterwards. SDC measurement was associated with a lower risk for disease-related events (HR 0.51, 95% CI 0.26-0.97, P = 0.04), but not with all-cause mortality or PCR-positivity. SDC measurement decreases the risk for disease-related events, potentially through more optimal dosing or improved compliance. We recommend measurement of SDC and striving for SDC >5 μg/mL and <10 μg/mL during treatment of chronic Q fever.

Assessing the continuum of event-based biosurveillance through an operational lens.

PubMed

Corley, Courtney D; Lancaster, Mary J; Brigantic, Robert T; Chung, James S; Walters, Ronald A; Arthur, Ray R; Bruckner-Lea, Cynthia J; Calapristi, Augustin; Dowling, Glenn; Hartley, David M; Kennedy, Shaun; Kircher, Amy; Klucking, Sara; Lee, Eva K; McKenzie, Taylor; Nelson, Noele P; Olsen, Jennifer; Pancerella, Carmen; Quitugua, Teresa N; Reed, Jeremy Todd; Thomas, Carla S

2012-03-01

This research follows the Updated Guidelines for Evaluating Public Health Surveillance Systems, Recommendations from the Guidelines Working Group, published by the Centers for Disease Control and Prevention nearly a decade ago. Since then, models have been developed and complex systems have evolved with a breadth of disparate data to detect or forecast chemical, biological, and radiological events that have a significant impact on the One Health landscape. How the attributes identified in 2001 relate to the new range of event-based biosurveillance technologies is unclear. This article frames the continuum of event-based biosurveillance systems (that fuse media reports from the internet), models (ie, computational that forecast disease occurrence), and constructs (ie, descriptive analytical reports) through an operational lens (ie, aspects and attributes associated with operational considerations in the development, testing, and validation of the event-based biosurveillance methods and models and their use in an operational environment). A workshop was held in 2010 to scientifically identify, develop, and vet a set of attributes for event-based biosurveillance. Subject matter experts were invited from 7 federal government agencies and 6 different academic institutions pursuing research in biosurveillance event detection. We describe 8 attribute families for the characterization of event-based biosurveillance: event, readiness, operational aspects, geographic coverage, population coverage, input data, output, and cost. Ultimately, the analyses provide a framework from which the broad scope, complexity, and relevant issues germane to event-based biosurveillance useful in an operational environment can be characterized.

Stressful Life Events Around the Time of Unplanned Pregnancy and Women's Health: Exploratory Findings from a National Sample.

PubMed

Hall, Kelli Stidham; Dalton, Vanessa K; Zochowski, Melissa; Johnson, Timothy R B; Harris, Lisa H

2017-06-01

Objective Little is known about how women's social context of unintended pregnancy, particularly adverse social circumstances, relates to their general health and wellbeing. We explored associations between stressful life events around the time of unintended pregnancy and physical and mental health. Methods Data are drawn from a national probability study of 1078 U.S. women aged 18-55. Our internet-based survey measured 14 different stressful life events occurring at the time of unintended pregnancy (operationalized as an additive index score), chronic disease and mental health conditions, and current health and wellbeing symptoms (standardized perceived health, depression, stress, and discrimination scales). Multivariable regression modeled relationships between stressful life events and health conditions/symptoms while controlling for sociodemographic and reproductive covariates. Results Among ever-pregnant women (N = 695), stressful life events were associated with all adverse health outcomes/symptoms in unadjusted analyses. In multivariable models, higher stressful life event scores were positively associated with chronic disease (aOR 1.21, CI 1.03-1.41) and mental health (aOR 1.42, CI 1.23-1.64) conditions, higher depression (B 0.37, CI 0.19-0.55), stress (B 0.32, CI 0.22-0.42), and discrimination (B 0.74, CI 0.45-1.04) scores, and negatively associated with ≥ very good perceived health (aOR 0.84, CI 0.73-0.97). Stressful life event effects were strongest for emotional and partner-related sub-scores. Conclusion Women with adverse social circumstances surrounding their unintended pregnancy experienced poorer health. Findings suggest that reproductive health should be considered in the broader context of women's health and wellbeing and have implications for integrated models of care that address women's family planning needs, mental and physical health, and social environments.

Saigas on the brink: Multidisciplinary analysis of the factors influencing mass mortality events

PubMed Central

Kock, Richard A.; Orynbayev, Mukhit; Robinson, Sarah; Zuther, Steffen; Singh, Navinder J.; Beauvais, Wendy; Morgan, Eric R.; Kerimbayev, Aslan; Khomenko, Sergei; Martineau, Henny M.; Rystaeva, Rashida; Omarova, Zamira; Wolfs, Sara; Hawotte, Florent; Radoux, Julien; Milner-Gulland, Eleanor J.

2018-01-01

In 2015, more than 200,000 saiga antelopes died in 3 weeks in central Kazakhstan. The proximate cause of death is confirmed as hemorrhagic septicemia caused by the bacterium Pasteurella multocida type B, based on multiple strands of evidence. Statistical modeling suggests that there was unusually high relative humidity and temperature in the days leading up to the mortality event; temperature and humidity anomalies were also observed in two previous similar events in the same region. The modeled influence of environmental covariates is consistent with known drivers of hemorrhagic septicemia. Given the saiga population’s vulnerability to mass mortality and the likely exacerbation of climate-related and environmental stressors in the future, management of risks to population viability such as poaching and viral livestock disease is urgently needed, as well as robust ongoing veterinary surveillance. A multidisciplinary approach is needed to research mass mortality events under rapid environmental change. PMID:29376120

Musculoskeletal and rheumatic diseases induced by immune checkpoint inhibitors: a review of the literature.

PubMed

Benfaremo, Devis; Manfredi, Lucia; Luchetti, Michele Maria; Gabrielli, Armando

2018-05-08

Immune checkpoint inhibitors are a new promising class of antitumor drugs that have been associated to a number of immune-related adverse events (AEs), including musculoskeletal and rheumatic disease. We searched Medline reviewing reports of musculoskeletal and rheumatic AEs induced by immune checkpoint inhibitors. Several musculoskeletal and rheumatic AEs associated with immune checkpoint inhibitors treatment are reported in literature. In particular, arthralgia and myalgia were the most common reported AEs, whereas the prevalence of arthritis, myositis and vasculitis is less characterized and mainly reported in case series and case reports. Other occasionally described AEs are sicca syndrome, polymyalgia rheumatica, systemic lupus erythematosus and sarcoidosis. Newly induced musculoskeletal and rheumatic diseases are a frequent adverse event associated with immune checkpoint inhibitors treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Regulation of cardiomyocyte autophagy by calcium.

PubMed

Shaikh, Soni; Troncoso, Rodrigo; Criollo, Alfredo; Bravo-Sagua, Roberto; García, Lorena; Morselli, Eugenia; Cifuentes, Mariana; Quest, Andrew F G; Hill, Joseph A; Lavandero, Sergio

2016-04-15

Calcium signaling plays a crucial role in a multitude of events within the cardiomyocyte, including cell cycle control, growth, apoptosis, and autophagy. With respect to calcium-dependent regulation of autophagy, ion channels and exchangers, receptors, and intracellular mediators play fundamental roles. In this review, we discuss calcium-dependent regulation of cardiomyocyte autophagy, a lysosomal mechanism that is often cytoprotective, serving to defend against disease-related stress and nutrient insufficiency. We also highlight the importance of the subcellular distribution of calcium and related proteins, interorganelle communication, and other key signaling events that govern cardiomyocyte autophagy. Copyright © 2016 the American Physiological Society.

Strengthening core public health capacity based on the implementation of the International Health Regulations (IHR) (2005): Chinese lessons

PubMed Central

Liu, Bin; Sun, Yan; Dong, Qian; Zhang, Zongjiu; Zhang, Liang

2015-01-01

As an international legal instrument, the International Health Regulations (IHR) is internationally binding in 196 countries, especially in all the member states of the World Health Organization (WHO). The IHR aims to prevent, protect against, control, and respond to the international spread of disease and aims to cut out unnecessary interruptions to traffic and trade. To meet IHR requirements, countries need to improve capacity construction by developing, strengthening, and maintaining core response capacities for public health risk and Public Health Emergency of International Concern (PHEIC). In addition, all the related core capacity requirements should be met before June 15, 2012. If not, then the deadline can be extended until 2016 upon request by countries. China has promoted the implementation of the IHR comprehensively, continuingly strengthening the core public health capacity and advancing in core public health emergency capacity building, points of entry capacity building, as well as risk prevention and control of biological events (infectious diseases, zoonotic diseases, and food safety), radiological, nuclear, and chemical events, and other catastrophic events. With significant progress in core capacity building, China has dealt with many public health emergencies successfully, ensuring that its core public health capacity has met the IHR requirements, which was reported to WHO in June 2014. This article describes the steps, measures, and related experiences in the implementation of IHR in China. PMID:26029897

Burden of vaccine preventable diseases at large events.

PubMed

Alqahtani, Amani S; Alfelali, Mohammad; Arbon, Paul; Booy, Robert; Rashid, Harunor

2015-11-27

Large events or mass gatherings (MGs) are known to amplify the risk of infectious diseases, many of which can be prevented by vaccination. In this review we have evaluated the burden of vaccine preventable diseases (VPDs) in MGs. Major databases like PubMed and Embase, Google Scholar and pertinent websites were searched by using MeSH terms and text words; this was supplemented by hand searching. Following data abstraction, the pooled estimate of the burden of VPDs was calculated when possible; otherwise a narrative synthesis was conducted. In the past, at religious MGs like Hajj and Kumbh Mela, cholera caused explosive outbreaks; but currently respiratory infections, notably influenza, are the commonest diseases not only at Hajj but also at World Youth Day and Winter Olympiad. The recent cumulative attack rate of influenza at Hajj is 8.7% (range 0.7-15.8%), and the cumulative prevalence is 3.6% (range: 0.3-38%). Small outbreaks of measles (13-42 cases per event) have been reported at sport, entertainment and religious events. A sizeable outbreak (>200 cases) was reported following a special Easter Festival in Austria. An outbreak of hepatitis A occurred following the 'Jam bands' music festival. Other VPDs including pneumococcal disease, pertussis and tuberculosis have been reported in relation to MG attendance. VPDs not only affect the participants of MGs but also their contacts; vaccine uptake is variable and vaccine implementation is likely to have beneficial effects. Research to address the knowledge gaps surrounding VPDs at MGs is needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transfer function-derived central pressure and cardiovascular disease events: the Framingham Heart Study.

PubMed

Mitchell, Gary F; Hwang, Shih-Jen; Larson, Martin G; Hamburg, Naomi M; Benjamin, Emelia J; Vasan, Ramachandran S; Levy, Daniel; Vita, Joseph A

2016-08-01

Relations between central pulse pressure (PP) or pressure amplification and major cardiovascular disease (CVD) events are controversial. Estimates of central aortic pressure derived using radial artery tonometry and a generalized transfer function may better predict CVD risk beyond the predictive value of brachial SBP. Augmentation index, central SBP, central PP, and central-to-peripheral PP amplification were evaluated using radial artery tonometry and a generalized transfer function as implemented in the SphygmoCor device (AtCor Medical, Itasca, Illinois, USA). We used proportional hazards models to examine relations between central hemodynamics and first-onset major CVD events in 2183 participants (mean age 62 years, 58% women) in the Framingham Heart Study. During median follow-up of 7.8 (limits 0.2-8.9) years, 149 participants (6.8%) had an incident event. Augmentation index (P = 0.6), central aortic systolic pressure (P = 0.20), central aortic PP (P = 0.24), and PP amplification (P = 0.15) were not related to CVD events in multivariable models that adjusted for age, sex, brachial cuff systolic pressure, use of antihypertensive therapy, total and high-density lipoprotein cholesterol concentrations, smoking, and presence of diabetes. In a model that included standard risk factors, model fit was improved (P = 0.03) when brachial systolic pressure was added after central, whereas model fit was not improved (P = 0.30) when central systolic pressure was added after brachial. After considering standard risk factors, including brachial cuff SBP, augmentation index, central PP and PP amplification derived using radial artery tonometry, and a generalized transfer function were not predictive of CVD risk.

How to minimize ischemic complication related to swollen temporalis muscle following indirect revascularization surgery in moyamoya disease: a technical report.

PubMed

Joo, Sung Pil; Kim, Tae Sun; Moon, Hyung Sik

2014-05-01

There are several reports in the literature of postoperative ischemic events due to swelling of the temporalis muscle after indirect revascularization surgery. Here, we report our surgical technique for preventing ischemic events during the acute postoperative recovery period in moyamoya patients. We used various types of titanium mesh to cover the bony defect area in 8 patients (10 operations) with moyamoya disease. The mesh was cut and manipulated according to the shape of the bony defect. Surgical results were favorable, with no newly developed ischemic event or infarction in the acute recovery period. The mesh formed an outer table of skull, so there was no compressive effect on the temporalis muscle and no cosmetic defects. The titanium mesh appears to be effective and useful for prevention of ischemic insult in the treatment of moyamoya disease. The choice of this procedure depends on both the operative findings of temporalis muscle thickness and the status of ischemic vulnerability of moyamoya brain. Georg Thieme Verlag KG Stuttgart · New York.

Evaluation of Local Media Surveillance for Improved Disease Recognition and Monitoring in Global Hotspot Regions

PubMed Central

Schwind, Jessica S.; Wolking, David J.; Brownstein, John S.; Mazet, Jonna A. K.; Smith, Woutrina A.

2014-01-01

Digital disease detection tools are technologically sophisticated, but dependent on digital information, which for many areas suffering from high disease burdens is simply not an option. In areas where news is often reported in local media with no digital counterpart, integration of local news information with digital surveillance systems, such as HealthMap (Boston Children’s Hospital), is critical. Little research has been published in regards to the specific contribution of local health-related articles to digital surveillance systems. In response, the USAID PREDICT project implemented a local media surveillance (LMS) pilot study in partner countries to monitor disease events reported in print media. This research assessed the potential of LMS to enhance digital surveillance reach in five low- and middle-income countries. Over 16 weeks, select surveillance system attributes of LMS, such as simplicity, flexibility, acceptability, timeliness, and stability were evaluated to identify strengths and weaknesses in the surveillance method. Findings revealed that LMS filled gaps in digital surveillance network coverage by contributing valuable localized information on disease events to the global HealthMap database. A total of 87 health events were reported through the LMS pilot in the 16-week monitoring period, including 71 unique reports not found by the HealthMap digital detection tool. Furthermore, HealthMap identified an additional 236 health events outside of LMS. It was also observed that belief in the importance of the project and proper source selection from the participants was crucial to the success of this method. The timely identification of disease outbreaks near points of emergence and the recognition of risk factors associated with disease occurrence continue to be important components of any comprehensive surveillance system for monitoring disease activity across populations. The LMS method, with its minimal resource commitment, could be one tool used to address the information gaps seen in global ‘hot spot’ regions. PMID:25333618

Connecting the Lines between Hypogonadism and Atherosclerosis

PubMed Central

Fahed, Akl C.; Gholmieh, Joanna M.; Azar, Sami T.

2012-01-01

Epidemiological studies show that atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality worldwide and point to gender differences with ageing males being at highest risk. Atherosclerosis is a complex process that has several risk factors and mediators. Hypogonadism is a commonly undiagnosed disease that has been associated with many of the events, and risk factors leading to atherosclerosis. The mechanistic relations between testosterone levels, atherosclerotic events, and risk factors are poorly understood in many instances, but the links are clear. In this paper, we summarize the research journey that explains the link between hypogonadism, each of the atherosclerotic events, and risk factors. We look into the different areas from which lessons could be learned, including epidemiological studies, animal and laboratory experiments, studies on androgen deprivation therapy patients, and studies on testosterone-treated patients. We finish by providing recommendations for the clinician and needs for future research. PMID:22518131

Kidney disease and obesity: epidemiology, mechanisms and treatment.

PubMed

Câmara, Niels Olsen Saraiva; Iseki, Kunitoshi; Kramer, Holly; Liu, Zhi-Hong; Sharma, Kumar

2017-03-01

The theme of World Kidney Day 2017 is 'kidney disease and obesity: healthy lifestyle for healthy kidneys'. To mark this event, Nature Reviews Nephrology invited five leading researchers to describe changes in the epidemiology of obesity-related kidney disease, advances in current understanding of the mechanisms and current approaches to the management of affected patients. The researchers also highlight new advances that could lead to the development of novel treatments and identify areas in which further basic and clinical studies are needed.

Unfairness and health: evidence from the Whitehall II Study.

PubMed

De Vogli, Roberto; Ferrie, Jane E; Chandola, Tarani; Kivimäki, Mika; Marmot, Michael G

2007-06-01

To examine the effects of unfairness on incident coronary events and health functioning. Prospective cohort study. Unfairness, sociodemographics, established coronary risk factors (high serum cholesterol, hypertension, obesity, exercise, smoking and alcohol consumption) and other psychosocial work characteristics (job strain, effort-reward imbalance and organisational justice) were measured at baseline. Associations between unfairness and incident coronary events and health functioning were determined over an average follow-up of 10.9 years. 5726 men and 2572 women from 20 civil service departments in London (the Whitehall II Study). Incident fatal coronary heart disease, non-fatal myocardial infarction and angina (528 events) and health functioning. Low employment grade is strongly associated with unfairness. Participants reporting higher levels of unfairness are more likely to experience an incident coronary event (HR 1.55, 95% CI 1.11 to 2.17), after adjustment for age, gender, employment grade, established coronary risk factors and other work-related psychosocial characteristics. Unfairness is also associated with poor physical (OR 1.46, 95% CI 1.20 to 1.77) and mental (OR 1.54, 95% CI 1.19 to 1.99) functioning at follow-up, controlling for all other factors and health functioning at baseline. Unfairness is an independent predictor of increased coronary events and impaired health functioning. Further research is needed to disentangle the effects of unfairness from other psychosocial constructs and to investigate the societal, relational and biological mechanisms that may underlie its associations with health and heart disease.

Multicenter, open-label study of recombinant human DNase in cystic fibrosis patients with moderate lung disease. DNase International Study Group.

PubMed

Harms, H K; Matouk, E; Tournier, G; von der Hardt, H; Weller, P H; Romano, L; Heijerman, H G; FitzGerald, M X; Richard, D; Strandvik, B; Kolbe, J; Kraemer, R; Michalsen, H

1998-09-01

Cystic fibrosis is characterized by the accumulation of thick viscous purulent secretions. Recombinant human deoxyribonuclease I (rhDNase) breaks down extracellular DNA, which contributes to the increased viscosity of sputum. A multinational, open-label study was conducted in 974 cystic fibrosis patients with moderate lung disease [forced vital capacity (FVC) 40-70% of predicted values] to examine the safety and efficacy of aerosolized rhDNase, 2.5 mg, once daily over a period of at least 12 weeks. Patients were assessed under conditions reflecting routine clinical practice. During rhDNase therapy, at least one respiratory tract infection (RTI) requiring intravenous antibiotics was experienced by 29.5% of patients. Forced expiratory volume in 1 second (FEV1) and FVC were significantly improved from baseline by a mean of 10.5% and 7.2%, respectively. Voice alteration and pharyngitis were the most frequent rhDNase-related adverse events, but only 2% of all patients discontinued treatment due to adverse events. The results obtained were similar to a subanalysis of data from the first 3 months of a placebo-controlled U.S. study. The patients in the present study had a similar frequency of RTIs and improvement in pulmonary function, and reported fewer rhDNase-related and cystic fibrosis-related adverse events than patients in the U.S. study. We conclude that administration of rhDNase is safe, well tolerated, and effective under conditions reflecting routine clinical practice in patients with cystic fibrosis and moderate lung disease.

Relative associations between depression and anxiety on adverse cardiovascular events: does a history of coronary artery disease matter? A prospective observational study

PubMed Central

Pelletier, Roxanne; Arsenault, André; Dupuis, Jocelyn; Laurin, Catherine; Blais, Lucie; Lavoie, Kim L

2015-01-01

Objectives To assess whether depression and anxiety increase the risk of mortality and major adverse cardiovascular events (MACE), among patients with and without coronary artery disease (CAD). Design and setting, and patients DECADE (Depression Effects on Coronary Artery Disease Events) is a prospective observational study of 2390 patients referred at the Montreal Heart Institute. Patients were followed for 8.8 years, between 1998 and 2009. Depression and anxiety were assessed using a psychiatric interview (Primary Care Evaluation of Mental Disorders, PRIME-MD). Outcomes data were obtained from Quebec provincial databases. Main outcome measures All-cause mortality and MACE. Results After adjustment for covariates, patients with depression were at increased risks of all-cause mortality (relative risk (RR)=2.84; 95% CI 1.25 to 6.49) compared with patients without depression. Anxiety was not associated with increased mortality risks (RR=0.86; 95% CI 0.31 to 2.36). When patients were stratified according to CAD status, depression increased the risk of mortality among patients with no CAD (RR=4.39; 95% CI 1.12 to 17.21), but not among patients with CAD (RR=2.32; 95% CI 0.78 to 6.88). Neither depression nor anxiety was associated with MACE among patients with or without CAD. Conclusions and relevance Depression, but not anxiety, was an independent risk factor for all-cause mortality in patients without CAD. The present study contributes to a better understanding of the relative and unique role of depression versus anxiety among patients with versus without CAD. PMID:26671946

A case of nivolumab-related cholangitis and literature review: how to look for the right tools for a correct diagnosis of this rare immune-related adverse event.

PubMed

Gelsomino, Francesco; Vitale, Giovanni; Ardizzoni, Andrea

2018-02-01

Anti-programmed cell death-1 (PD-1) monoclonal antibodies, such as nivolumab, used for the treatment of several tumors, can trigger effector T-cells against tumor- and self-antigens, leading to the occurrence of different immune-related adverse events. Among them, liver injuries are rare and usually transient. To date, only four cases of immune-related cholangitis in non-small cell lung cancer (NSCLC) patients have been described during nivolumab treatment. Here, we describe laboratory tests, imaging and liver biopsy features that confirm this diagnosis as opposed to other forms of autoimmune liver disease; nevertheless, we also provide evidence of the presence of different clinical-pathological patterns of immune-related cholangitis.

Estimated Effects of Asian Dust Storms on Spatiotemporal Distributions of Clinic Visits for Respiratory Diseases in Taipei Children (Taiwan)

PubMed Central

Chien, Lung-Chang; Yang, Chiang-Hsing

2012-01-01

Background: Increases in certain cause-specific hospital admissions have been reported during Asian dust storms (ADS), which primarily originate from north and northwest China during winter and spring. However, few studies have investigated the relationship between the ADS and clinic visits for respiratory diseases in children. Objective: We investigated the general impact to children’s health across space and time by analyzing daily clinic visits for respiratory diseases among preschool and schoolchildren registered in 12 districts of Taipei City during 1997–2007 from the National Health Insurance dataset. Methods: We applied a structural additive regression model to estimate the association between ADS episodes and children’s clinic visits for respiratory diseases, controlling for space and time variations. Results: Compared with weeks before ADS events, the rate of clinic visits during weeks after ADS events increased 2.54% (95% credible interval = 2.43, 2.66) for preschool children (≤ 6 years of age) and 5.03% (95% credible interval = 4.87, 5.20) for schoolchildren (7–14 years of age). Spatial heterogeneity in relative rates of clinic visits was also identified. Compared with the mean level of Taipei City, higher relative rates appeared in districts with or near large hospitals and medical centers. Conclusion: To our knowledge, this is the first population-based study to assess the impact of ADS on children’s respiratory health. Our analysis suggests that children’s respiratory health was affected by ADS events across all of Taipei, especially among schoolchildren. PMID:22538266

Disease management research using event graphs.

PubMed

Allore, H G; Schruben, L W

2000-08-01

Event Graphs, conditional representations of stochastic relationships between discrete events, simulate disease dynamics. In this paper, we demonstrate how Event Graphs, at an appropriate abstraction level, also extend and organize scientific knowledge about diseases. They can identify promising treatment strategies and directions for further research and provide enough detail for testing combinations of new medicines and interventions. Event Graphs can be enriched to incorporate and validate data and test new theories to reflect an expanding dynamic scientific knowledge base and establish performance criteria for the economic viability of new treatments. To illustrate, an Event Graph is developed for mastitis, a costly dairy cattle disease, for which extensive scientific literature exists. With only a modest amount of imagination, the methodology presented here can be seen to apply modeling to any disease, human, plant, or animal. The Event Graph simulation presented here is currently being used in research and in a new veterinary epidemiology course. Copyright 2000 Academic Press.

Developing a disease outbreak event corpus.

PubMed

Conway, Mike; Kawazoe, Ai; Chanlekha, Hutchatai; Collier, Nigel

2010-09-28

In recent years, there has been a growth in work on the use of information extraction technologies for tracking disease outbreaks from online news texts, yet publicly available evaluation standards (and associated resources) for this new area of research have been noticeably lacking. This study seeks to create a "gold standard" data set against which to test how accurately disease outbreak information extraction systems can identify the semantics of disease outbreak events. Additionally, we hope that the provision of an annotation scheme (and associated corpus) to the community will encourage open evaluation in this new and growing application area. We developed an annotation scheme for identifying infectious disease outbreak events in news texts. An event--in the context of our annotation scheme--consists minimally of geographical (eg, country and province) and disease name information. However, the scheme also allows for the rich encoding of other domain salient concepts (eg, international travel, species, and food contamination). The work resulted in a 200-document corpus of event-annotated disease outbreak reports that can be used to evaluate the accuracy of event detection algorithms (in this case, for the BioCaster biosurveillance online news information extraction system). In the 200 documents, 394 distinct events were identified (mean 1.97 events per document, range 0-25 events per document). We also provide a download script and graphical user interface (GUI)-based event browsing software to facilitate corpus exploration. In summary, we present an annotation scheme and corpus that can be used in the evaluation of disease outbreak event extraction algorithms. The annotation scheme and corpus were designed both with the particular evaluation requirements of the BioCaster system in mind as well as the wider need for further evaluation resources in this growing research area.

Consumption of nuts and legumes and risk of incident ischemic heart disease, stroke, and diabetes: a systematic review and meta-analysis.

PubMed

Afshin, Ashkan; Micha, Renata; Khatibzadeh, Shahab; Mozaffarian, Dariush

2014-07-01

Relations between the consumption of nuts and legumes and risk of ischemic heart disease (IHD), stroke, and diabetes have not been well established. We systematically investigated and quantified associations of nut and legume consumption with incident IHD, stroke, and diabetes. We systematically searched multiple databases to identify randomized controlled trials or observational studies that examined the relations. Studies were excluded if they reported only intermediate physiologic measures, soft cardiovascular outcomes, or crude risk estimates. Data were extracted independently and in duplicate. We assessed pooled dose-response relations by using a generalized least-squares trend estimation, and prespecified sources of heterogeneity were assessed by using metaregression. The potential for publication bias was explored by using funnel plots, Begg's and Egger's tests, and Duval and Tweedie trim-and-fill methods. Of 3851 abstracts, 25 observational studies (23 prospective and 2 retrospective studies) and 2 trial reports met inclusion criteria and comprised 501,791 unique individuals and 11,869 IHD, 8244 stroke, and 14,449 diabetes events. The consumption of nuts was inversely associated with fatal IHD (6 studies; 6749 events; RR per 4 weekly 28.4-g servings: 0.76; 95% CI: 0.69, 0.84; I(2) = 28%), nonfatal IHD (4 studies; 2101 events; RR: 0.78; 0.67, 0.92; I(2) = 0%), and diabetes (6 studies; 13,308 events; RR: 0.87; 0.81,0.94; I(2) = 22%) but not stroke (4 studies; 5544 events). Legume consumption was inversely associated with total IHD (5 studies; 6514 events; RR per 4 weekly 100-g servings: 0.86; 0.78, 0.94; I(2) = 0%) but not significantly associated with stroke (6 studies; 6690 events) or diabetes (2 studies; 2746 events). A meta-regression did not identify the effect modification by age, duration of follow-up, study location, or study quality. Mixed evidence was seen for publication bias, but analyses by using the Duval and Tweedie trim-and-fill method did not appreciably alter results. This systematic review supports inverse associations between eating nuts and incident IHD and diabetes and eating legumes and incident IHD. © 2014 American Society for Nutrition.

Consumption of nuts and legumes and risk of incident ischemic heart disease, stroke, and diabetes: a systematic review and meta-analysis1234

PubMed Central

Afshin, Ashkan; Micha, Renata; Khatibzadeh, Shahab; Mozaffarian, Dariush

2014-01-01

Background: Relations between the consumption of nuts and legumes and risk of ischemic heart disease (IHD), stroke, and diabetes have not been well established. Objective: We systematically investigated and quantified associations of nut and legume consumption with incident IHD, stroke, and diabetes. Design: We systematically searched multiple databases to identify randomized controlled trials or observational studies that examined the relations. Studies were excluded if they reported only intermediate physiologic measures, soft cardiovascular outcomes, or crude risk estimates. Data were extracted independently and in duplicate. We assessed pooled dose-response relations by using a generalized least-squares trend estimation, and prespecified sources of heterogeneity were assessed by using metaregression. The potential for publication bias was explored by using funnel plots, Begg's and Egger's tests, and Duval and Tweedie trim-and-fill methods. Results: Of 3851 abstracts, 25 observational studies (23 prospective and 2 retrospective studies) and 2 trial reports met inclusion criteria and comprised 501,791 unique individuals and 11,869 IHD, 8244 stroke, and 14,449 diabetes events. The consumption of nuts was inversely associated with fatal IHD (6 studies; 6749 events; RR per 4 weekly 28.4-g servings: 0.76; 95% CI: 0.69, 0.84; I2 = 28%), nonfatal IHD (4 studies; 2101 events; RR: 0.78; 0.67, 0.92; I2 = 0%), and diabetes (6 studies; 13,308 events; RR: 0.87; 0.81,0.94; I2 = 22%) but not stroke (4 studies; 5544 events). Legume consumption was inversely associated with total IHD (5 studies; 6514 events; RR per 4 weekly 100-g servings: 0.86; 0.78, 0.94; I2 = 0%) but not significantly associated with stroke (6 studies; 6690 events) or diabetes (2 studies; 2746 events). A meta-regression did not identify the effect modification by age, duration of follow-up, study location, or study quality. Mixed evidence was seen for publication bias, but analyses by using the Duval and Tweedie trim-and-fill method did not appreciably alter results. Conclusion: This systematic review supports inverse associations between eating nuts and incident IHD and diabetes and eating legumes and incident IHD. PMID:24898241

Risk factors for severe clinical events in male and female patients with Fabry disease treated with agalsidase beta enzyme replacement therapy: Data from the Fabry Registry.

PubMed

Hopkin, Robert J; Cabrera, Gustavo; Charrow, Joel; Lemay, Roberta; Martins, Ana Maria; Mauer, Michael; Ortiz, Alberto; Patel, Manesh R; Sims, Katherine; Waldek, Stephen; Warnock, David G; Wilcox, William R

2016-09-01

Fabry disease, an X-linked lysosomal storage disorder, causes intracellular accumulation of glycosphingolipids leading to progressive renal, cardiovascular, and cerebrovascular disease, and premature death. This longitudinal Fabry Registry study analyzed data from patients with Fabry disease to determine the incidence and type of severe clinical events following initiation of enzyme replacement therapy (ERT) with agalsidase beta, as well as risk factors associated with occurrence of these events. Severe events assessed included chronic dialysis, renal transplantation, cardiac events, stroke, and death. The analyses included 969 male and 442 female Fabry patients. The mean age at first agalsidase beta infusion was 35 and 44, and median treatment follow-up 4.3years and 3.2years, respectively. Among males, cardiac events were the most common on-ERT events, followed by renal, stroke, and non-cardiac death. Among females, cardiac events were also most common followed by stroke and renal events. Patients with on-ERT events had significantly more advanced cardiac and renal disease at baseline as compared with patients without on-ERT events. Severe events were also associated with older age at ERT initiation (males and females), a history of pre-ERT events (females; approaching statistical significance in males), and a higher urinary protein/creatinine ratio (females). Approximately 65% of patients with pre-ERT events did not experience subsequent on-ERT events. Of patients without pre-ERT events, most (84% of males, 92% of females) remained event-free. Patients with on-ERT severe events had more advanced Fabry organ involvement at baseline than those without such events and patients who initiated ERT at a younger age had less residual risk of on-ERT events. The observed patterns of residual risk may aid clinicians in multidisciplinary monitoring of male and female patients with Fabry disease receiving ERT, and in determining the need for administration of adjunctive therapies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Changes in extreme events and the potential impacts on human health.

PubMed

Bell, Jesse E; Brown, Claudia Langford; Conlon, Kathryn; Herring, Stephanie; Kunkel, Kenneth E; Lawrimore, Jay; Luber, George; Schreck, Carl; Smith, Adam; Uejio, Christopher

2018-04-01

Extreme weather and climate-related events affect human health by causing death, injury, and illness, as well as having large socioeconomic impacts. Climate change has caused changes in extreme event frequency, intensity, and geographic distribution, and will continue to be a driver for change in the future. Some of these events include heat waves, droughts, wildfires, dust storms, flooding rains, coastal flooding, storm surges, and hurricanes. The pathways connecting extreme events to health outcomes and economic losses can be diverse and complex. The difficulty in predicting these relationships comes from the local societal and environmental factors that affect disease burden. More information is needed about the impacts of climate change on public health and economies to effectively plan for and adapt to climate change. This paper describes some of the ways extreme events are changing and provides examples of the potential impacts on human health and infrastructure. It also identifies key research gaps to be addressed to improve the resilience of public health to extreme events in the future. Extreme weather and climate events affect human health by causing death, injury, and illness, as well as having large socioeconomic impacts. Climate change has caused changes in extreme event frequency, intensity, and geographic distribution, and will continue to be a driver for change in the future. Some of these events include heat waves, droughts, wildfires, flooding rains, coastal flooding, surges, and hurricanes. The pathways connecting extreme events to health outcomes and economic losses can be diverse and complex. The difficulty in predicting these relationships comes from the local societal and environmental factors that affect disease burden.

The intersection between growth factors, autophagy and ER stress: A new target to treat neurodegenerative diseases?

PubMed

Garcia-Huerta, Paula; Troncoso-Escudero, Paulina; Jerez, Carolina; Hetz, Claudio; Vidal, Rene L

2016-10-15

One of the salient features of most neurodegenerative diseases is the aggregation of specific proteins in the brain. This proteostasis imbalance is proposed as a key event triggering the neurodegenerative cascade. The unfolded protein response (UPR) and autophagy pathways are emerging as critical processes implicated in handling disease-related misfolded proteins. However, in some conditions, perturbations in the buffering capacity of the proteostasis network may be part of the etiology of the disease. Thus, pharmacological or gene therapy strategies to enhance autophagy or UPR responses are becoming an attractive target for disease intervention. Here, we discuss current evidence depicting the complex involvement of autophagy and ER stress in brain diseases. Novel pathways to modulate protein misfolding are discussed including the relation between aging and growth factor signaling. This article is part of a Special Issue entitled SI:Autophagy. Copyright © 2016 Elsevier B.V. All rights reserved.

Acute Chagas Disease: New Global Challenges for an Old Neglected Disease

PubMed Central

Andrade, Daniela V.; Gollob, Kenneth J.; Dutra, Walderez O.

2014-01-01

Chagas disease is caused by infection with the protozoan Trypanosoma cruzi, and although over 100 years have passed since the discovery of Chagas disease, it still presents an increasing problem for global public health. A plethora of information concerning the chronic phase of human Chagas disease, particularly the severe cardiac form, is available in the literature. However, information concerning events during the acute phase of the disease is scarce. In this review, we will discuss (1) the current status of acute Chagas disease cases globally, (2) the immunological findings related to the acute phase and their possible influence in disease outcome, and (3) reactivation of Chagas disease in immunocompromised individuals, a key point for transplantation and HIV infection management. PMID:25077613

Heart rate recovery after treadmill exercise testing and risk of cardiovascular disease events (The Framingham Heart Study).

PubMed

Morshedi-Meibodi, Ali; Larson, Martin G; Levy, Daniel; O'Donnell, Christopher J; Vasan, Ramachandran S

2002-10-15

A delayed heart rate (HR) recovery after graded exercise testing has been associated with increased all-cause mortality in clinic-based samples. No prior study has examined the association of HR recovery after exercise with the incidence of coronary heart disease (CHD) and cardiovascular disease (CVD) events. We evaluated 2,967 Framingham study subjects (1,400 men, mean age 43 years) who were free of CVD and underwent a treadmill exercise test (Bruce protocol) at a routine examination. We examined the relations of HR recovery indexes (decrease in HR from peak exercise) to the incidence of a first CHD or CVD event and all-cause mortality, adjusting for established CVD risk factors. During follow-up (mean 15 years), 214 subjects experienced a CHD event (156 men), 312 developed a CVD event (207 men), and 167 died (105 men). In multivariable models, continuous HR recovery indexes were not associated with the incidence of CHD or CVD events, or with all-cause mortality. However, in models evaluating quintile-based cut points, the top quintile of HR recovery (greatest decline in HR) at 1-minute after exercise was associated with a lower risk of CHD (hazards ratio vs bottom 4 quintiles 0.54, 95% confidence interval [CI], 0.32 to 0.93) and CVD (hazards ratio 0.61, 95% CI 0.41 to 0.93), but not all-cause mortality (hazards ratio 0.99, 95% CI 0.60 to 1.62). In our community-based sample, HR recovery indexes were not associated with all-cause mortality. A very rapid HR recovery immediately after exercise was associated with lower risk of CHD and CVD events. These findings should be confirmed in other settings.

Dietary intake of saturated fat is not associated with risk of coronary events or mortality in patients with established coronary artery disease.

PubMed

Puaschitz, Nathalie Genevieve; Strand, Elin; Norekvål, Tone Merete; Dierkes, Jutta; Dahl, Lisbeth; Svingen, Gard Frodahl Tveitevåg; Assmus, Jörg; Schartum-Hansen, Hall; Øyen, Jannike; Pedersen, Eva Kristine Ringdal; Drevon, Christian Andrè; Tell, Grethe Seppola; Nygård, Ottar

2015-02-01

Data from recent meta-analyses question an association between dietary intake of saturated fatty acids (SFAs) and risk of cardiovascular disease (CVD). Moreover, the prognostic effect of dietary SFA in patients with established CVD treated with modern conventional medication has not been extensively studied. We investigated the associations between self-reported dietary SFA intake and risk of subsequent coronary events and mortality in patients with coronary artery disease (CAD). This study included patients who participated in the Western Norway B-Vitamin Intervention Trial and completed a 169-item semiquantitative food-frequency questionnaire after coronary angiography. Quartiles of estimated daily intakes of SFA were related to risk of a primary composite endpoint of coronary events (unstable angina pectoris, nonfatal acute myocardial infarction, and coronary death) and separate secondary endpoints (total acute myocardial infarction, fatal coronary events, and all-cause death) with use of Cox-regression analyses. This study included 2412 patients (81% men, mean age: 61.7 y). After a median follow-up of 4.8 y, a total of 292 (12%) patients experienced at least one major coronary event during follow-up. High intake of SFAs was associated with a number of risk factors at baseline. However, there were no significant associations between SFA intake and risk of coronary events [age- and sex-adjusted HR (95% CI) was 0.85 (0.61, 1.18) for the upper vs. lower SFA quartile] or any secondary endpoint. Estimates were not appreciably changed after multivariate adjustments. There was no association between dietary intake of SFAs and incident coronary events or mortality in patients with established CAD. © 2015 American Society for Nutrition.

New Radiotracers for Imaging of Vascular Targets in Angiogenesis-related Diseases

PubMed Central

Hong, Hao; Chen, Feng; Zhang, Yin; Cai, Weibo

2014-01-01

Tremendous advances over the last several decades in positron emission tomography (PET) and single photon emission computed tomography (SPECT) allow for targeted imaging of molecular and cellular events in the living systems. Angiogenesis, a multistep process regulated by the network of different angiogenic factors, has attracted world-wide interests, due to its pivotal role in the formation and progression of different diseases including cancer, cardiovascular diseases (CVD), and inflammation. In this review article, we will summarize the recent progress in PET or SPECT imaging of a wide variety of vascular targets in three major angiogenesis-related diseases: cancer, cardiovascular diseases, and inflammation. Faster drug development and patient stratification for a specific therapy will become possible with the facilitation of PET or SPECT imaging and it will be critical for the maximum benefit of patients. PMID:25086372

The FIFA Women’s World Cup in Germany 2011 – A practical example for tailoring an event-specific enhanced infectious disease surveillance system

PubMed Central

2012-01-01

Background Mass gatherings require a decision from public health authorities on how to monitor infectious diseases during the event. The appropriate level of enhanced surveillance depends on parameters like the scale of the event (duration, spatial distribution, season), participants’ origin, amount of public attention, and baseline disease activity in the host country. For the FIFA Men’s World Cup 2006, Germany implemented enhanced surveillance. As the scale of the FIFA Women’s World Cup (June 26 – July 17, 2011) was estimated to be substantially smaller in size, visitors and duration, it was not feasible to simply adopt the previously implemented measures. Our aim was therefore to develop a strategy to tailor an event-specific enhanced surveillance for this smaller-scale mass gathering. Methods Based on the enhanced surveillance measures during the Men’s Cup, we conducted a needs assessment with the district health authorities in the 9 host cities in March 2011. Specific measures with a majority consent were implemented. After the event, we surveyed the 9 district and their corresponding 7 state health authorities to evaluate the implemented measures. Results All 9 district health authorities participated in the pre-event needs assessment. The majority of sites consented to moving from weekly to daily (Monday-Friday) notification reporting of routine infectious diseases, receiving regular feedback on those notification reports and summaries of national/international World Cup-relevant epidemiological incidents, e.g. outbreaks in countries of participating teams. In addition, we decided to implement twice-weekly reports of “unusual events” at district and state level. This enhanced system would commence on the first day and continue to one day following the tournament. No World Cup-related infectious disease outbreaks were reported during this time period. Eight of 9 district and 6 of 8 state health authorities participated in the final evaluation. The majority perceived the implemented measures as adequate. Conclusions Our approach to tailor an event-specific enhanced surveillance concept worked well. Involvement of the participating stakeholders early-on in the planning phase secured ownership of and guaranteed support for the chosen strategy. The enhanced surveillance for this event resulted as a low-level surveillance. However, we included mechanisms for rapid upscaling if the situation would require adaptations. PMID:22849632

Differential influence of distinct components of increased blood pressure on cardiovascular outcomes: from the atherosclerosis risk in communities study.

PubMed

Cheng, Susan; Gupta, Deepak K; Claggett, Brian; Sharrett, A Richey; Shah, Amil M; Skali, Hicham; Takeuchi, Madoka; Ni, Hanyu; Solomon, Scott D

2013-09-01

Elevation in blood pressure (BP) increases risk for all cardiovascular events. Nevertheless, the extent to which different indices of BP elevation may be associated to varying degrees with different cardiovascular outcomes remains unclear. We studied 13340 participants (aged 54 ± 6 years, 56% women and 27% black) of the Atherosclerosis Risk in Communities Study who were free of baseline cardiovascular disease. We used Cox proportional hazards models to compare the relative contributions of systolic BP, diastolic BP, pulse pressure, and mean arterial pressure to risk for coronary heart disease, heart failure, stroke, and all-cause mortality. For each multivariable-adjusted model, the largest area under the receiver-operating curve (AUC) and smallest -2 log-likelihood values were used to identify BP measures with the greatest contribution to risk prediction for each outcome. A total of 2095 coronary heart disease events, 1669 heart failure events, 771 stroke events, and 3016 deaths occurred during 18 ± 5 years of follow-up. In multivariable analyses adjusting for traditional cardiovascular risk factors, the BP measures with the greatest risk contributions were the following: systolic BP for coronary heart disease (AUC=0.74); pulse pressure for heart failure (AUC=0.79); systolic BP for stroke (AUC=0.74); and pulse pressure for all-cause mortality (AUC=0.74). With few exceptions, results were similar in analyses stratified by age, sex, and race. Our data indicate that distinct BP components contribute variably to risk for different cardiovascular outcomes.

Impact of testosterone replacement therapy on thromboembolism, heart disease and obstructive sleep apnoea in men.

PubMed

Cole, Alexander P; Hanske, Julian; Jiang, Wei; Kwon, Nicollette K; Lipsitz, Stuart R; Kathrins, Martin; Learn, Peter A; Sun, Maxine; Haider, Adil H; Basaria, Shehzad; Trinh, Quoc-Dien

2018-05-01

To assess the association of testosterone replacement therapy (TRT) with thromboembolism, cardiovascular disease (stroke, coronary artery disease and heart failure) and obstructive sleep apnoea (OSA). A cohort of 3 422 male US military service members, retirees and their dependents, aged 40-64 years, was identified, who were prescribed TRT between 2006 and 2010 for low testosterone levels. The men in this cohort were matched on a 1:1 basis for age and comorbidities to men without a prescription for TRT. Event-free survival and rates of thromboembolism, cardiovascular events and OSA were compared between men using TRT and the control group, with a median follow-up of 17 months. There was no difference in event-free survival with regard to thromboembolism (P = 0.239). Relative to controls, men using TRT had improved cardiovascular event-free survival (P = 0.004), mainly as a result of lower incidence of coronary artery disease (P = 0.008). The risk of OSA was higher in TRT users (2-year risk 16.5% [95% confidence interval 15.1-18.1] in the TRT group vs 12.7% [11.4-14.1] in the control group. This study adds to growing evidence that the cardiovascular risk associated with TRT may be lower than once feared. The elevated risk of OSA in men using TRT is noteworthy. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

Psychological mediators related to clinical outcome in cognitive behavioural therapy for coronary heart disease: A sub-analysis from the SUPRIM trial.

PubMed

Norlund, Fredrika; Olsson, Erik Mg; Pingel, Ronnie; Held, Claes; Svärdsudd, Kurt; Gulliksson, Mats; Burell, Gunilla

2017-06-01

Background The Secondary Prevention in Uppsala Primary Healthcare Project (SUPRIM) was a randomized controlled trial of a group-based cognitive behavioural therapy stress management programme for patients with coronary heart disease. The project was successful in reducing the risk of fatal or non-fatal first recurrent cardiovascular events. The aim of this study was to analyse the effect of cognitive behavioural therapy on self-rated stress, somatic anxiety, vital exhaustion and depression and to study the associations of these factors with the reduction in cardiovascular events. Methods A total of 362 patients were randomly assigned to intervention or usual care groups. The psychological outcomes were assessed five times during 24 months and analysed using linear mixed models. The mediating roles of the outcomes were analysed using joint modelling of the longitudinal and time to event data. Results The intervention had a positive effect on somatic anxiety ( p < 0.05), reflecting a beneficial development over time compared with the controls. Stress, vital exhaustion and depression did not differ between the groups over time. Mediator analysis suggested that somatic anxiety may have mediated the effect of treatment on cardiovascular events. Conclusions The intervention had a small positive effect on somatic anxiety, but did not affect stress, vital exhaustion or depression in patients with coronary heart disease. Somatic anxiety was associated with an increased risk of cardiovascular events and might act as a partial mediator in the treatment effect on cardiovascular events. However, the mechanisms between the intervention and the protective cardiovascular outcome remain to be identified.

Extreme weather events and infectious disease outbreaks.

PubMed

McMichael, Anthony J

2015-01-01

Human-driven climatic changes will fundamentally influence patterns of human health, including infectious disease clusters and epidemics following extreme weather events. Extreme weather events are projected to increase further with the advance of human-driven climate change. Both recent and historical experiences indicate that infectious disease outbreaks very often follow extreme weather events, as microbes, vectors and reservoir animal hosts exploit the disrupted social and environmental conditions of extreme weather events. This review article examines infectious disease risks associated with extreme weather events; it draws on recent experiences including Hurricane Katrina in 2005 and the 2010 Pakistan mega-floods, and historical examples from previous centuries of epidemics and 'pestilence' associated with extreme weather disasters and climatic changes. A fuller understanding of climatic change, the precursors and triggers of extreme weather events and health consequences is needed in order to anticipate and respond to the infectious disease risks associated with human-driven climate change. Post-event risks to human health can be constrained, nonetheless, by reducing background rates of persistent infection, preparatory action such as coordinated disease surveillance and vaccination coverage, and strengthened disaster response. In the face of changing climate and weather conditions, it is critically important to think in ecological terms about the determinants of health, disease and death in human populations.

Prognostic significance of normal quantitative planar thallium-201 stress scintigraphy in patients with chest pain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wackers, F.J.; Russo, D.J.; Russo, D.

The prognostic significance of normal quantitative planar thallium-201 stress scintigraphy was evaluated in patients with a chest pain syndrome. The prevalence of cardiac events during follow-up was related to the pretest (that is, before stress scintigraphy) likelihood of coronary artery disease determined on the basis of symptoms, age, sex and stress electrocardiography. In a consecutive series of 344 patients who had adequate thallium-201 stress scintigrams, 95 had unequivocally normal studies by quantitative analysis. The pretest likelihood of coronary artery disease in the 95 patients had a bimodal distribution. During a mean follow-up period of 22 +/- 3 months, no patientmore » died. Three patients (3%) had a cardiac event: two of these patients (pretest likelihood of coronary artery disease 54 and 94%) had a nonfatal myocardial infarction 8 and 22 months, respectively, after stress scintigraphy, and one patient (pretest likelihood 98%) underwent percutaneous transluminal coronary angioplasty 16 months after stress scintigraphy for persisting anginal complaints. Three patients were lost to follow-up; all three had a low pretest likelihood of coronary artery disease. It is concluded that patients with chest pain and normal findings on quantitative thallium-201 scintigraphy have an excellent prognosis. Cardiac events are rare (infarction rate 1% per year) and occur in patients with a moderate to high pretest likelihood of coronary artery disease.« less

Perceived job stress and incidence of coronary events: 3-year follow-up of the Belgian Job Stress Project cohort.

PubMed

De Bacquer, Dirk; Pelfrene, E; Clays, E; Mak, R; Moreau, M; de Smet, P; Kornitzer, M; De Backer, G

2005-03-01

Psychosocial characteristics have been linked to coronary heart disease. In the Belgian Job Stress Project (1994-1999), the authors examined the independent role of perceived job stress on the short-term incidence of clinical manifest coronary events in a large occupational cohort. A total of 14,337 middle-aged men completed the Job Content Questionnaire to determine the dimensions of the extended job strain model, job demands, decision latitude, and social support. Jobs were categorized into high strain, low strain, active jobs, and passive jobs. During the 3-year follow-up, 87 coronary events were registered. At baseline, 17% of workers experienced high strain. Job demands and decision latitude were not significantly related to the development of coronary heart disease after adjustment for covariates. The 38% risk excess among subjects classified in the high-strain category did not reach statistical significance. However, coronary heart disease incidence was substantially associated with the social support scale independently of other risk factors, with an adjusted hazard ratio of 2.4 (95% confidence interval: 1.4, 4.0) between extreme tertiles. No convincing evidence for an association of job demands, decision latitude, or job strain with the short-term incidence of coronary heart disease was found. However, our study underscores the importance of a supportive social work environment in the prevention of coronary heart disease.

Occurrence of early adverse events after vaccination against influenza at a Brazilian reference center.

PubMed

Lopes, Marta Heloísa; Mascheretti, Melissa; Franco, Marilia Miranda; Vasconcelos, Ricardo; Gutierrez, Eliana Battaggia

2008-02-01

Since 1999, the Ministry of Health in Brazil has conducted campaigns of vaccination against influenza targeted towards the elderly, chronically-diseased people and health care workers. The vaccine against influenza is associated with adverse events of minor importance. To investigate the early adverse events related to the vaccine against influenza. CASUISTICS AND METHODS: One hundred and ninety seven elderly individuals and health care workers vaccinated against influenza were included. An inquiry regarding adverse events related to the vaccine was applied seven days after the vaccination. Local adverse events were reported by 32.5% and systemic effects by 26.4% of the vaccinated subjects. Pain in the region of the injection, headache, myalgia, malaise, and coryza were more frequent in the workers than in the elderly (p<0.05). There was no statistically significant difference in the occurrence of fever. The belief of part of the population that credits frequent and uncomfortable adverse events to the vaccine was not confirmed. The subjective adverse events were more frequent in the health care workers, which can influence, in a negative way, the disclosure of the benefits of this vaccine due to their role as opinion makers.

Role of T cells, cytokines and antibody in dengue fever and dengue haemorrhagic fever.

PubMed

Fink, Joshua; Gu, Feng; Vasudevan, Subhash G

2006-01-01

Dengue infections are a major cause of morbidity and mortality in the tropical and sub-tropical regions of the world. There is no vaccine for dengue and also there are no anti-viral drugs to treat the infection. Some patients, typically those experiencing a secondary infection with a different dengue serotype, may progress from an acute febrile disease to the more severe forms of disease, dengue haemorrhagic fever and dengue shock syndrome. Here we discuss the significant immunopathological component to severe disease and how T cells, cytokines and cross-reactive antibody combine to contribute to the progression to dengue haemorrhagic fever. These events are thought to lead to vascular leakage, the signature event in dengue haemorrhagic fever, and are addressed in this review by incorporating the concept of heterologous T cell immunity. The need for effective measures against dengue and dengue-related illness is clear. We propose that drugs against dengue virus, or the symptoms of severe dengue disease, are a viable goal.

Hostility and platelet reactivity in individuals without a history of cardiovascular disease events.

PubMed

Shimbo, Daichi; Chaplin, William; Kuruvilla, Sujith; Wasson, Lauren Taggart; Abraham, Dennis; Burg, Matthew M

2009-09-01

To examine the association between hostility and platelet reactivity in individuals without a prior history of cardiovascular disease (CVD) events. Hostility is associated with incident CVD events, independent of traditional risk factors. Increased platelet reactivity and thrombus formation over a disrupted coronary plaque are fundamental for CVD event onset. Hypertensive patients (n = 42) without concomitant CVD event history completed the 50-item Cook-Medley Hostility Scale, and a subset score of 27 items (Barefoot Ho) was derived. We examined the relationship between Barefoot Ho scores and platelet aggregation. We also examined individual components of Barefoot Ho (aggressive responding, cynicism, and hostile affect) and their associations with platelet aggregation. Platelet reactivity, induced by adenosine diphosphate (ADP), was assessed by standard light transmission aggregometry, the current gold standard method of platelet aggregation assessment. Barefoot Ho scores were related significantly to increased rate of platelet aggregation in response to ADP. Of the three Barefoot Ho components, only aggressive responding was associated independently with increased platelet aggregation rate. The strength of these relationships did not diminish after adjusting for several standard CVD risk factors. These data demonstrate that hostility, particularly the aggressive responding subtype, is associated with platelet reactivity-a key pathophysiological pathway in the onset of CVD events.

Cinacalcet, Fibroblast Growth Factor-23, and Cardiovascular Disease in Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial.

PubMed

Moe, Sharon M; Chertow, Glenn M; Parfrey, Patrick S; Kubo, Yumi; Block, Geoffrey A; Correa-Rotter, Ricardo; Drüeke, Tilman B; Herzog, Charles A; London, Gerard M; Mahaffey, Kenneth W; Wheeler, David C; Stolina, Maria; Dehmel, Bastian; Goodman, William G; Floege, Jürgen

2015-07-07

Patients with kidney disease have disordered bone and mineral metabolism, including elevated serum concentrations of fibroblast growth factor-23 (FGF23). These elevated concentrations are associated with cardiovascular and all-cause mortality. The objective was to determine the effects of the calcimimetic cinacalcet (versus placebo) on reducing serum FGF23 and whether changes in FGF23 are associated with death and cardiovascular events. This was a secondary analysis of a randomized clinical trial comparing cinacalcet to placebo in addition to conventional therapy (phosphate binders/vitamin D) in patients receiving hemodialysis with secondary hyperparathyroidism (intact parathyroid hormone ≥300 pg/mL). The primary study end point was time to death or a first nonfatal cardiovascular event (myocardial infarction, hospitalization for angina, heart failure, or a peripheral vascular event). This analysis included 2985 patients (77% of randomized) with serum samples at baseline and 2602 patients (67%) with samples at both baseline and week 20. The results demonstrated that a significantly larger proportion of patients randomized to cinacalcet had ≥30% (68% versus 28%) reductions in FGF23. Among patients randomized to cinacalcet, a ≥30% reduction in FGF23 between baseline and week 20 was associated with a nominally significant reduction in the primary composite end point (relative hazard, 0.82; 95% confidence interval, 0.69-0.98), cardiovascular mortality (relative hazard, 0.66; 95% confidence interval, 0.50-0.87), sudden cardiac death (relative hazard, 0.57; 95% confidence interval, 0.37-0.86), and heart failure (relative hazard, 0.69; 95% confidence interval, 0.48-0.99). Treatment with cinacalcet significantly lowers serum FGF23. Treatment-induced reductions in serum FGF23 are associated with lower rates of cardiovascular death and major cardiovascular events. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00345839. © 2015 American Heart Association, Inc.

Favorable Circulatory System Outcomes as Adjuvant Traditional Chinese Medicine (TCM) Treatment for Cerebrovascular Diseases in Taiwan

PubMed Central

Chiu, Hsienhsueh Elley; Hong, Yu-Chiang; Chang, Ku-Chou; Shih, Chun-Chuan; Hung, Jen-Wen; Liu, Chia-Wei; Tan, Teng-Yeow; Huang, Chih-Cheng

2014-01-01

Abstract Background This study searches the National Health Insurance Research Database (NHIRD) used in a previous project, aiming for reconstructing possible cerebrovascular disease-related groups (DRG),and estimating the costs between cerebrovascular disease and related diseases. Methods and Materials We conducted a nationwide retrospective cohort study in stroke inpatients, we examined the overall costs in 3 municipalities in Taiwan, by evaluating the possible costs of the expecting diagnosis related group (DRG) by using the international classification of diseases version-9 (ICD-9) system, and the overall analysis of the re-admission population that received traditional Chinese medicine (TCM) treatment and those who did not. Results The trend demonstrated that the non-participant costs were consistent with the ICD-9 categories (430 to 437) because similarities existed between years 2006 to 2007. Among the TCM patients, a wide variation and additional costs were found compared to non-TCM patients during these 2 years. The average re-admission duration was significantly shorter for TCM patients, especially those initially diagnosed with ICD 434 during the first admission. In addition, TCM patients demonstrated more severe general symptoms, which incurred high conventional treatment costs, and could result in re-admission for numerous reasons. However, in Disease 7 of ICD-9 category, representing the circulatory system was most prevalent in non-TCM inpatients, which was the leading cause of re-admission. Conclusion We concluded that favorable circulatory system outcomes were in adjuvant TCM treatment inpatients, there were less re-admission for circulatory system events and a two-third reduction of re-admission within ICD-9 code 430 to 437, compared to non-TCM ones. However, there were shorter re-admission duration other than circulatory system events by means of unfavorable baseline condition. PMID:24475108

French national survey of inpatient adverse events prospectively assessed with ward staff.

PubMed

Michel, Philippe; Quenon, Jean Luc; Djihoud, Ahmed; Tricaud-Vialle, Sophie; de Sarasqueta, Anne Marie

2007-10-01

To estimate the incidence of adverse events in medical and surgical activity in public and private hospitals, and to assess the clinical situation of patients and the active errors. Prospective assessment of adverse events by external senior nursing and doctor investigators with ward staff. Random three-stage stratified cluster sampling of stays or fractions of stay in a 7-day observation period for each ward. 8754 patients observed in 292 wards in 71 hospitals, over 35,234 hospitalisation days. Number of adverse events in relation to number of days of hospitalisation. The incidence density of adverse events was 6.6 per 1000 days of hospitalisation (95% CI 5.7 to 7.5), of which 35% were preventable. Invasive procedures were the source of half the adverse events, of which 20% were preventable. Adverse events related to the psychological sphere and pain were mostly considered as preventable. Ward staff found it difficult to assess the role of care management in the occurrence of adverse events: 41% of adverse events were expected because of the disease itself, and could have occurred in the absence of the related medical management. At the national level in France, every year 120,000-190,000 adverse events during hospitalisation can be considered as preventable. Areas such as perioperative period and geriatric units should receive closer attention. As adverse events occurred more commonly in vulnerable patients, who are not specifically targeted by clinical guidance, practising evidence-based medicine is not likely to prevent all cases. Therefore clinical risk management should prioritize empowerment of local staff, provision of favourable conditions within the organisation, and staff training based on simple tools appropriate for ward-level identification and analysis of adverse events.

Search engines, news wires and digital epidemiology: Presumptions and facts.

PubMed

Kaveh-Yazdy, Fatemeh; Zareh-Bidoki, Ali-Mohammad

2018-07-01

Digital epidemiology tries to identify diseases dynamics and spread behaviors using digital traces collected via search engines logs and social media posts. However, the impacts of news on information-seeking behaviors have been remained unknown. Data employed in this research provided from two sources, (1) Parsijoo search engine query logs of 48 months, and (2) a set of documents of 28 months of Parsijoo's news service. Two classes of topics, i.e. macro-topics and micro-topics were selected to be tracked in query logs and news. Keywords of the macro-topics were automatically generated using web provided resources and exceeded 10k. Keyword set of micro-topics were limited to a numerable list including terms related to diseases and health-related activities. The tests are established in the form of three studies. Study A includes temporal analyses of 7 macro-topics in query logs. Study B considers analyzing seasonality of searching patterns of 9 micro-topics, and Study C assesses the impact of news media coverage on users' health-related information-seeking behaviors. Study A showed that the hourly distribution of various macro-topics followed the changes in social activity level. Conversely, the interestingness of macro-topics did not follow the regulation of topic distributions. Among macro-topics, "Pharmacotherapy" has highest interestingness level and wider time-window of popularity. In Study B, seasonality of a limited number of diseases and health-related activities were analyzed. Trends of infectious diseases, such as flu, mumps and chicken pox were seasonal. Due to seasonality of most of diseases covered in national vaccination plans, the trend belonging to "Immunization and Vaccination" was seasonal, as well. Cancer awareness events caused peaks in search trends of "Cancer" and "Screening" micro-topics in specific days of each year that mimic repeated patterns which may mistakenly be identified as seasonality. In study C, we assessed the co-integration and correlation between news and query trends. Our results demonstrated that micro-topics sparsely covered in news media had lowest level of impressiveness and, subsequently, the lowest impact on users' intents. Our results can reveal public reaction to social events, diseases and prevention procedures. Furthermore, we found that news trends are co-integrated with search queries and are able to reveal health-related events; however, they cannot be used interchangeably. It is recommended that the user-generated contents and news documents are analyzed mutually and interactively. Copyright © 2018 Elsevier B.V. All rights reserved.

New digital cholangiopancreatoscopy for diagnosis and therapy of pancreaticobiliary diseases (with videos).

PubMed

Tanaka, Reina; Itoi, Takao; Honjo, Mitsusyoshi; Tsuchiya, Takayoshi; Kurihara, Toshio; Tsuji, Shujiro; Tonozuka, Ryosuke; Kamada, Kentato; Sofuni, Atsushi; Mukai, Shuntaro

2016-04-01

Recently, a new digital cholangiopancreatoscopy (DCPS) has been developed. The aim of this study is to retrospectively evaluate the utility of new DCPS in patients with pancreaticobiliary diseases. Digital cholangiopancreatoscopy was used in 26 patients (16 men) with pancreaticobiliary diseases that could not be diagnosed and treated by standard endoscopic retrograde cholangiopancreatography (ERCP). The procedures included DCPS-guided tissue sampling and interventions. Technical success and adverse events were evaluated. Among the 26 patients, 19 patients were classified for diagnostic purposes and seven for therapeutic purposes. The detailed breakdown of the particular conditions and numbers of patients was as follows: indeterminate bile duct (BD) lesion, indeterminate pancreatic duct (PD) lesion, lithotripsy by yttrium aluminum garnet-laser or electrohydraulic lithotripsy, removal of migrated BD stent and PD stent, and guidewire passing across the biliary stricture. The overall technical success rates of visualizing the target lesions and therapeutic interventions were 100% and 85.7%, respectively. The incidence of procedure-related adverse events among the patients was 7.7% (2/26). Cholangitis developed in one of the patients and post-endoscopic sphincterotomy bleeding in one patient. All adverse events were successfully treated by conservative therapy. Digital cholangiopancreatoscopy has a high potential for providing an accurate diagnosis and facilitating therapy in patients with pancreaticobiliary diseases. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Adverse events of vaccines and the consequences of non-vaccination: a critical review

PubMed Central

Aps, Luana Raposo de Melo Moraes; Piantola, Marco Aurélio Floriano; Pereira, Sara Araujo; de Castro, Julia Tavares; Santos, Fernanda Ayane de Oliveira; Ferreira, Luís Carlos de Souza

2018-01-01

ABSTRACT OBJECTIVE: To analyze the risks related to vaccines and the impacts of non-vaccination on the world population. METHODS: This is a narrative review that has considered information present in the bibliographic databases NCBI-PubMed, Medline, Lilacs, and Scientific Electronic Library Online (SciELO), between November 2015 and November 2016. For the analysis of outbreaks caused by non-vaccination, we considered the work published between 2010 and 2016. RESULTS: We have described the main components of the vaccines offered by the Brazilian public health system and the adverse events associated with these elements. Except for local inflammatory reactions and rare events, such as exacerbation of autoimmune diseases and allergies, no causal relationship has been demonstrated between the administration of vaccines and autism, Alzheimer's disease, or narcolepsy. On the other hand, the lack of information and the dissemination of non-scientific information have contributed to the reemergence of infectious diseases in several countries in the world and they jeopardize global plans for the eradication of these diseases. CONCLUSIONS: The population should be well informed about the benefits of vaccination and health professionals should assume the role of disseminating truthful information with scientific support on the subject, as an ethical and professional commitment to society. PMID:29668817

EUS-guided methylene blue cholangiopancreatography for benign biliopancreatic diseases after failed ERCP.

PubMed

Consiglieri, Claudia F; Gornals, Joan B; Albines, Gino; De-la-Hera, Meritxell; Secanella, Lluis; Pelaez, Nuria; Busquets, Juli

2016-07-01

When ERCP fails, EUS-guided interventional techniques may be an alternative. The aim of this study was to evaluate the general outcomes and safety of EUS-guided methylene blue cholangiopancreatography in patients with failed ERCP in benign biliopancreatic diseases. Patients with benign biliopancreatic diseases and failed ERCP were included. EUS-guided cholangiopancreatography plus injection of methylene blue was performed, and then ERCP using coloring agent flow as an indicator of papilla orifice was performed. Procedures were prospectively collected in this observational, single-center study. Technical success, clinical success, and adverse events were analyzed retrospectively. Eleven patients were included (10 choledocholithiasis, 1 pancreatic stricture). The main reason for failed ERCP was an unidentifiable papilla. EUS-guided ductal access with cholangiopancreatography and papilla orifice identification was obtained in all cases. Technical success and clinical success rates of 91% were achieved, with successful biliopancreatic drainage in 10 patients. Adverse events included 1 peripancreatic abscess attributed to a precut, which was successfully treated. No adverse events were related to the first EUS-guided stage. EUS-guided cholangiopancreatography with methylene blue injection seems to be a feasible and helpful technique for treatment in patients with benign biliopancreatic diseases with previous failed ERCP because of an undetectable papilla. Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Number of recent stressful life events and incident cardiovascular disease: Moderation by lifetime depressive disorder.

PubMed

Berntson, Jessica; Patel, Jay S; Stewart, Jesse C

2017-08-01

We investigated whether number of recent stressful life events is associated with incident cardiovascular disease (CVD) and whether this relationship is stronger in adults with a history of clinical depression. Prospective data from 28,583 U.S. adults (mean age=45years) initially free of CVD who participated in Waves 1 (2001-2002) and 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were examined. Number of past-year stressful life events (Wave 1), lifetime depressive disorder (Wave 1), and incident CVD (Wave 2) were determined by structured interviews. There were 1069 cases of incident CVD. Each additional stressful life event was associated with a 15% increased odds of incident CVD [Odds Ratio (OR)=1.15, 95% Confidence Interval (CI): 1.11, 1.19]. As hypothesized, a stressful life events by lifetime depressive disorder interaction was detected (P=0.003). Stratified analyses indicated that stressful life events had a stronger association with incident CVD among adults with (OR=1.18, 95% CI: 1.10, 1.27, n=4908) versus without (OR=1.10, 95% CI: 1.07, 1.14, n=23,675) a lifetime depressive disorder. Our findings suggest that a greater number of recent stressful life events elevate the risk of new-onset CVD and that this risk is potentiated in adults with a history of clinical depression. Copyright © 2017 Elsevier Inc. All rights reserved.

Peripheral Arterial Disease study (PERART): prevalence and predictive values of asymptomatic peripheral arterial occlusive disease related to cardiovascular morbidity and mortality.

PubMed

Alzamora, María Teresa; Baena-Díez, José Miguel; Sorribes, Marta; Forés, Rosa; Toran, Pere; Vicheto, Marisa; Pera, Guillem; Reina, María Dolores; Albaladejo, Carlos; Llussà, Judith; Bundó, Magda; Sancho, Amparo; Heras, Antonio; Rubiés, Joan; Arenillas, Juan Francisco

2007-12-11

The early diagnosis of atherosclerotic disease is essential for developing preventive strategies in populations at high risk and acting when the disease is still asymptomatic. A low ankle-arm index (AAI) is a good marker of vascular events and may be diminished without presenting symptomatology (silent peripheral arterial disease). The aim of the PERART study (PERipheral ARTerial disease) is to determine the prevalence of peripheral arterial disease (both silent and symptomatic) in a general population of both sexes and determine its predictive value related to morbimortality (cohort study). This cross-over, cohort study consists of 2 phases: firstly a descriptive, transversal cross-over study to determine the prevalence of peripheral arterial disease, and secondly, a cohort study to evaluate the predictive value of AAI in relation to cardiovascular morbimortality. From September 2006 to June 2007, a total of 3,010 patients over the age of 50 years will be randomly selected from a population adscribed to 24 healthcare centres in the province of Barcelona (Spain). The diagnostic criteria of peripheral arterial disease will be considered as an AAI < 0.90, determined by portable Doppler (8 Mhz probe) measured twice by trained personnel. Cardiovascular risk will be calculated with the Framingham-Wilson tables, with Framingham calibrated by the REGICOR and SCORE groups. The subjects included will be evaluted every 6 months by telephone interview and the clnical history and death registries will be reviewed. The appearance of the following cardiovascular events will be considered as variables of response: transitory ischaemic accident, ictus, angina, myocardial infartction, symptomatic abdominal aneurysm and vascular mortality. In this study we hope to determine the prevalence of peripheral arterial disease, especially the silent forms, in the general population and establish its relationship with cardiovascular morbimortality. A low AAI may be a better marker of arterial disease than the classical cardiovascular risk factors and may, therefore, contribute to improving the predictive value of the equations of cardiovascular risk and thereby allowing optimisation of multifactorial treatment of atherosclerotic disease.

Peripheral Arterial Disease Study (PERART): Prevalence and predictive values of asymptomatic peripheral arterial occlusive disease related to cardiovascular morbidity and mortality

PubMed Central

Alzamora, María Teresa; Baena-Díez, José Miguel; Sorribes, Marta; Forés, Rosa; Toran, Pere; Vicheto, Marisa; Pera, Guillem; Reina, María Dolores; Albaladejo, Carlos; Llussà, Judith; Bundó, Magda; Sancho, Amparo; Heras, Antonio; Rubiés, Joan; Arenillas, Juan Francisco

2007-01-01

Background The early diagnosis of atherosclerotic disease is essential for developing preventive strategies in populations at high risk and acting when the disease is still asymptomatic. A low ankle-arm index (AAI) is a good marker of vascular events and may be diminished without presenting symptomatology (silent peripheral arterial disease). The aim of the PERART study (PERipheral ARTerial disease) is to determine the prevalence of peripheral arterial disease (both silent and symptomatic) in a general population of both sexes and determine its predictive value related to morbimortality (cohort study). Methods/Design This cross-over, cohort study consists of 2 phases: firstly a descriptive, transversal cross-over study to determine the prevalence of peripheral arterial disease, and secondly, a cohort study to evaluate the predictive value of AAI in relation to cardiovascular morbimortality. From September 2006 to June 2007, a total of 3,010 patients over the age of 50 years will be randomly selected from a population adscribed to 24 healthcare centres in the province of Barcelona (Spain). The diagnostic criteria of peripheral arterial disease will be considered as an AAI < 0.90, determined by portable Doppler (8 Mhz probe) measured twice by trained personnel. Cardiovascular risk will be calculated with the Framingham-Wilson tables, with Framingham calibrated by the REGICOR and SCORE groups. The subjects included will be evaluted every 6 months by telephone interview and the clnical history and death registries will be reviewed. The appearance of the following cardiovascular events will be considered as variables of response: transitory ischaemic accident, ictus, angina, myocardial infartction, symptomatic abdominal aneurysm and vascular mortality. Discussion In this study we hope to determine the prevalence of peripheral arterial disease, especially the silent forms, in the general population and establish its relationship with cardiovascular morbimortality. A low AAI may be a better marker of arterial disease than the classical cardiovascular risk factors and may, therefore, contribute to improving the predictive value of the equations of cardiovascular risk and thereby allowing optimisation of multifactorial treatment of atherosclerotic disease. PMID:18070367

Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association.

PubMed

Siscovick, David S; Barringer, Thomas A; Fretts, Amanda M; Wu, Jason H Y; Lichtenstein, Alice H; Costello, Rebecca B; Kris-Etherton, Penny M; Jacobson, Terry A; Engler, Mary B; Alger, Heather M; Appel, Lawrence J; Mozaffarian, Dariush

2017-04-11

Multiple randomized controlled trials (RCTs) have assessed the effects of supplementation with eicosapentaenoic acid plus docosahexaenoic acid (omega-3 polyunsaturated fatty acids, commonly called fish oils) on the occurrence of clinical cardiovascular diseases. Although the effects of supplementation for the primary prevention of clinical cardiovascular events in the general population have not been examined, RCTs have assessed the role of supplementation in secondary prevention among patients with diabetes mellitus and prediabetes, patients at high risk of cardiovascular disease, and those with prevalent coronary heart disease. In this scientific advisory, we take a clinical approach and focus on common indications for omega-3 polyunsaturated fatty acid supplements related to the prevention of clinical cardiovascular events. We limited the scope of our review to large RCTs of supplementation with major clinical cardiovascular disease end points; meta-analyses were considered secondarily. We discuss the features of available RCTs and provide the rationale for our recommendations. We then use existing American Heart Association criteria to assess the strength of the recommendation and the level of evidence. On the basis of our review of the cumulative evidence from RCTs designed to assess the effect of omega-3 polyunsaturated fatty acid supplementation on clinical cardiovascular events, we update prior recommendations for patients with prevalent coronary heart disease, and we offer recommendations, when data are available, for patients with other clinical indications, including patients with diabetes mellitus and prediabetes and those with high risk of cardiovascular disease, stroke, heart failure, and atrial fibrillation. © 2017 American Heart Association, Inc.

The unprecedented 2014 Legionnaires' disease outbreak in Portugal: atmospheric driving mechanisms

NASA Astrophysics Data System (ADS)

Russo, Ana; Gouveia, Célia M.; Soares, Pedro M. M.; Cardoso, Rita M.; Mendes, Manuel T.; Trigo, Ricardo M.

2018-03-01

A large outbreak of Legionnaires' disease occurred in November 2014 nearby Lisbon, Portugal. This epidemic infected 377 individuals by the Legionella pneumophila bacteria, resulting in 14 deaths. The primary source of transmission was contaminated aerosolized water which, when inhaled, lead to atypical pneumonia. The unseasonably warm temperatures during October 2014 may have played a role in the proliferation of Legionella species in cooling tower systems. The episode was further exacerbated by high relative humidity and a thermal inversion which limited the bacterial dispersion. Here, we analyze if the Legionella outbreak event occurred during a situation of extreme potential recirculation and/or stagnation characteristics. In order to achieve this goal, the Allwine and Whiteman approach was applied for a hindcast simulation covering the affected area during a near 20-year long period (1989-2007) and then for an independent period covering the 2014 event (15 October to 13 November 2014). The results regarding the average daily critical transport indices for the 1989-2007 period clearly indicate that the airshed is prone to stagnation as these events have a dominant presence through most of the study period (42%), relatively to the occurrence of recirculation (18%) and ventilation (17%) events. However, the year of 2014 represents an exceptional year when compared to the 1989-2007 period, with 53 and 33% of the days being classified as under stagnation and recirculation conditions, respectively.

The unprecedented 2014 Legionnaires' disease outbreak in Portugal: atmospheric driving mechanisms.

PubMed

Russo, Ana; Gouveia, Célia M; Soares, Pedro M M; Cardoso, Rita M; Mendes, Manuel T; Trigo, Ricardo M

2018-03-23

A large outbreak of Legionnaires' disease occurred in November 2014 nearby Lisbon, Portugal. This epidemic infected 377 individuals by the Legionella pneumophila bacteria, resulting in 14 deaths. The primary source of transmission was contaminated aerosolized water which, when inhaled, lead to atypical pneumonia. The unseasonably warm temperatures during October 2014 may have played a role in the proliferation of Legionella species in cooling tower systems. The episode was further exacerbated by high relative humidity and a thermal inversion which limited the bacterial dispersion. Here, we analyze if the Legionella outbreak event occurred during a situation of extreme potential recirculation and/or stagnation characteristics. In order to achieve this goal, the Allwine and Whiteman approach was applied for a hindcast simulation covering the affected area during a near 20-year long period (1989-2007) and then for an independent period covering the 2014 event (15 October to 13 November 2014). The results regarding the average daily critical transport indices for the 1989-2007 period clearly indicate that the airshed is prone to stagnation as these events have a dominant presence through most of the study period (42%), relatively to the occurrence of recirculation (18%) and ventilation (17%) events. However, the year of 2014 represents an exceptional year when compared to the 1989-2007 period, with 53 and 33% of the days being classified as under stagnation and recirculation conditions, respectively.

Additive prognostic value of interleukin-6 at peak phase of dobutamine stress echocardiography in patients with coronary artery disease. A 6-year follow-up study.

PubMed

Ikonomidis, Ignatios; Athanassopoulos, George; Stamatelopoulos, Kimon; Lekakis, John; Revela, Ioanna; Venetsanou, Kiriaki; Marinou, Margarita; Monaco, Claudia; Cokkinos, Dennis V; Nihoyannopoulos, Petros

2008-08-01

Interleukin-6 (IL-6) and tissue factor (TF) are elevated after myocardial ischemia during dobutamine stress echo (DSE). We examined the incremental prognostic value of IL-6 or TF measured during DSE over echocardiographic and clinical factors in patients with chronic coronary artery disease (CAD). We studied 106 patients with angiographically documented CAD. IL-6 and TF were measured at rest, peak, and during recovery. A wall motion score index was calculated. Fifty-seven (54%) patients had ischemia at DSE. During follow-up (63.7 +/- 20 months), 36 patients (33%) had an adverse event (12 cardiac deaths, 24 acute coronary events). Patients with events had a higher peak IL-6 (P = .02) but similar rest and recovery IL-6 than those without. Patients with peak IL-6 > or =3.14 pg/mL (upper tertile) had a hazard ratio of 2.7 (95% CI 1.44-5.37) (P < .01 for an adverse event). The addition of peak wall motion score index in a multivariable model including risk factors, ejection fraction, revascularization, and multivessel disease increased the model's c statistic from 0.66 to 0.70 (P = .04). The addition of peak IL-6 further increased the model's c statistic to 0.75 (P = .04). Tissue factor was not related with cardiac events. Interleuikin-6 levels measured during the peak phase of DSE incrementally contribute to risk stratification in patients with chronic CAD.

Choropleth map legend design for visualizing community health disparities.

PubMed

Cromley, Robert G; Cromley, Ellen K

2009-09-24

Disparities in health outcomes across communities are a central concern in public health and epidemiology. Health disparities research often links differences in health outcomes to other social factors like income. Choropleth maps of health outcome rates show the geographical distribution of health outcomes. This paper illustrates the use of cumulative frequency map legends for visualizing how the health events are distributed in relation to social characteristics of community populations. The approach uses two graphs in the cumulative frequency legend to highlight the difference between the raw count of the health events and the raw count of the social characteristic like low income in the geographical areas of the map. The approach is applied to mapping publicly available data on low birth weight by town in Connecticut and Lyme disease incidence by town in Connecticut in relation to income. The steps involved in creating these legends are described in detail so that health analysts can adopt this approach. The different health problems, low birth weight and Lyme disease, have different cumulative frequency signatures. Graphing poverty population on the cumulative frequency legends revealed that the poverty population is distributed differently with respect to the two different health problems mapped here. Cumulative frequency legends can be useful supplements for choropleth maps. These legends can be constructed using readily available software. They contain all of the information found in standard choropleth map legends, and they can be used with any choropleth map classification scheme. Cumulative frequency legends effectively communicate the proportion of areas, the proportion of health events, and/or the proportion of the denominator population in which the health events occurred that falls within each class interval. They illuminate the context of disease through graphing associations with other variables.

Infectious disease surveillance for the London 2012 Olympic and Paralympic Games.

PubMed

Severi, E; Heinsbroek, E; Watson, C; Catchpole, M

2012-08-02

The London 2012 Olympic and Paralympic Games will be one of the largest mass gathering events in British history. In order to minimise potential infectious disease threats related to the event, the Health Protection Agency (HPA) has set up a suite of robust and multisource surveillance systems. These include enhancements of already established systems (notification of infectious diseases, local and regional reporting,laboratory surveillance, mortality surveillance, international surveillance, and syndromic surveillance in primary care), as well as new systems created for the Games (syndromic surveillance in emergency departments and out-of-hours/unscheduled care,undiagnosed serious infectious illness surveillance).Enhanced existing and newly established surveillance systems will continue after the Games or will be ready for future reactivation should the need arise. In addition to the direct improvements to surveillance, the strengthening of relationships with national and international stakeholders will constitute a major post-Games legacy for the HPA.

Relation of Carotid Intima-Media Thickness and Plaque With Incident Cardiovascular Events in Women With Systemic Lupus Erythematosus

PubMed Central

Kao, Amy H.; Lertratanakul, Apinya; Elliott, Jennifer R.; Sattar, Abdus; Santelices, Linda; Shaw, Penny; Birru, Mehret; Avram, Zheni; Thompson, Trina; Sutton-Tyrrell, Kim; Ramsey-Goldman, Rosalind; Manzi, Susan

2013-01-01

Patients with systemic lupus erythematosus (SLE) are at increased risk for cardiovascular (CV) disease. The aim of this study was to investigate the association between subclinical CV disease as measured by carotid intima-media thickness (IMT) and plaque using B-mode carotid ultrasound and incident CV events in a combined cohort of female patients with SLE. This was a prospective, 2-center observational study of 392 adult women with SLE and no previous CV events with a mean 8 years of follow-up. Incident CV events confirmed by clinicians were defined as angina, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft, fatal cardiac arrest, transient ischemic attack, and cerebrovascular accident. Incident hard CV events excluded angina and transient ischemic attack. The mean age was 43.5 years, and most patients were Caucasian (77.3%). During follow-up, 38 patients had incident CV events, and 17 had incident hard CV events. Patients with incident hard CV events had higher mean carotid IMT (0.80 vs 0.64 mm, p <0.01) and presence of carotid plaque (76.5% vs 30.4%, p <0.01) compared with those without incident hard CV events. Baseline carotid IMT and presence of plaque were predictive of any incident hard CV event (hazard ratio 1.35, 95% confidence interval 1.12 to 1.64, and hazard ratio 4.26, 95% confidence interval 1.23 to 14.83, respectively), independent of traditional CV risk factors and medication use. In conclusion, in women with SLE without previous CV events, carotid IMT and plaque are predictive of future CV events. This suggests that carotid ultrasound may provide an additional tool for CV risk stratification in patients with SLE. PMID:23827400

Relation of carotid intima-media thickness and plaque with incident cardiovascular events in women with systemic lupus erythematosus.

PubMed

Kao, Amy H; Lertratanakul, Apinya; Elliott, Jennifer R; Sattar, Abdus; Santelices, Linda; Shaw, Penny; Birru, Mehret; Avram, Zheni; Thompson, Trina; Sutton-Tyrrell, Kim; Ramsey-Goldman, Rosalind; Manzi, Susan

2013-10-01

Patients with systemic lupus erythematosus (SLE) are at increased risk for cardiovascular (CV) disease. The aim of this study was to investigate the association between subclinical CV disease as measured by carotid intima-media thickness (IMT) and plaque using B-mode carotid ultrasound and incident CV events in a combined cohort of female patients with SLE. This was a prospective, 2-center observational study of 392 adult women with SLE and no previous CV events with a mean 8 years of follow-up. Incident CV events confirmed by clinicians were defined as angina, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft, fatal cardiac arrest, transient ischemic attack, and cerebrovascular accident. Incident hard CV events excluded angina and transient ischemic attack. The mean age was 43.5 years, and most patients were Caucasian (77.3%). During follow-up, 38 patients had incident CV events, and 17 had incident hard CV events. Patients with incident hard CV events had higher mean carotid IMT (0.80 vs 0.64 mm, p <0.01) and presence of carotid plaque (76.5% vs 30.4%, p <0.01) compared with those without incident hard CV events. Baseline carotid IMT and presence of plaque were predictive of any incident hard CV event (hazard ratio 1.35, 95% confidence interval 1.12 to 1.64, and hazard ratio 4.26, 95% confidence interval 1.23 to 14.83, respectively), independent of traditional CV risk factors and medication use. In conclusion, in women with SLE without previous CV events, carotid IMT and plaque are predictive of future CV events. This suggests that carotid ultrasound may provide an additional tool for CV risk stratification in patients with SLE. Copyright © 2013 Elsevier Inc. All rights reserved.

Grazoprevir plus elbasvir in HCV genotype-1 or -4 infected patients with stage 4/5 severe chronic kidney disease is safe and effective.

PubMed

Alric, Laurent; Ollivier-Hourmand, Isabelle; Bérard, Emilie; Hillaire, Sophie; Guillaume, Maeva; Vallet-Pichard, Anais; Bernard-Chabert, Brigitte; Loustaud-Ratti, Veronique; Bourlière, Marc; de Ledinghen, Victor; Fouchard-Hubert, Isabelle; Canva, Valerie; Minello, Anne; Nguyen-Khac, Eric; Leroy, Vincent; Saadoun, David; Trias, Dominique; Pol, Stanislas; Kamar, Nassim

2018-07-01

Patients with advanced chronic kidney disease who receive direct-acting antiviral drugs require special consideration regarding comorbid conditions. Here we assessed the efficacy and safety of grazoprevir plus elbasvir in 93 patients infected with HCV genotype 1 or 4 and with advanced chronic kidney disease in a non-randomized, multicenter, nationwide observational survey. Twenty patients with HCV genotype 1a, 51 patients with 1b, four unclassified genotype 1, 17 with genotype 4 and one with genotype 6 received grazoprevir plus elbasvir (100/50 mg) once daily. All patients had severe chronic kidney disease with 70 patients stage G5, including patients on hemodialysis (74.2%), and 23 were stage G4 chronic kidney disease. Severe liver disease (Metavir F3/F4) was found in 33 patients. A sustained virologic response 12 weeks after the end of therapy was achieved in 87 of 90 patients. Two patients had a virologic breakthrough and one had a relapse after treatment withdrawal. Most patients received many concomitant medications (mean 7.7) related to comorbid conditions. Serious adverse events occurred in six patients, including three deaths while on grazoprevir plus elbasvir, not related to this therapy. Thus, once-daily grazoprevir plus elbasvir was highly effective with a low rate of adverse events in this advanced chronic kidney disease difficult-to-treat population with an HCV genotype 1 or 4 infection. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Sexual information needs of Arab-Muslim patients with cardiac problems.

PubMed

Akhu-Zaheya, Laila M; Masadeh, Arwa B

2015-12-01

Cardiac diseases have direct and indirect effects on sexuality. Health care providers, especially nurses, have a major responsibility in addressing and discussing sexual concerns and providing sexual counseling needs for patients with cardiac diseases. Discussing sexual issues in Arabic Muslim countries is considered a taboo. Lack of information about sexual life can affect the quality of life for patients with cardiac diseases. In this study, concerns regarding counseling needs and sexual information pertaining to Jordanian patients with cardiac diseases are addressed. Non-experimental, cross-sectional, descriptive designs were employed, accompanied by a self-report questionnaire, as well as a structured interview using the Steinke Sexual Concerns and Sexual Activity questionnaires for cardiac patients. A convenient sample of Jordanian male and female patients with cardiac problems was recruited. Results revealed that only 11% of the participants with cardiac diseases reported receiving information regarding sexual life following cardiac-related events. Most patients (71%, F=81) preferred cardiologists to provide them with sexual information, and almost two-thirds of them (62%, F=75) considered nurses' gender to be a barrier, preventing them from inquiring about their sexual life. Patients with cardiac diseases had sexual concerns, but none of incredible importance. However, most patients (76%, F=94) reported changes in sexual activities following cardiac-related events. Cardiac patients had sexual concerns and sexual counseling needs that they would not discuss. Health care professionals should arrange sexual counseling plans with the patient; as every patient has individual, specific, and unique sexual counseling needs, dependent upon their lifestyle, health conditions, and their type of cardiac disease. © The European Society of Cardiology 2015.

Event-based internet biosurveillance: relation to epidemiological observation

PubMed Central

2012-01-01

Background The World Health Organization (WHO) collects and publishes surveillance data and statistics for select diseases, but traditional methods of gathering such data are time and labor intensive. Event-based biosurveillance, which utilizes a variety of Internet sources, complements traditional surveillance. In this study we assess the reliability of Internet biosurveillance and evaluate disease-specific alert criteria against epidemiological data. Methods We reviewed and compared WHO epidemiological data and Argus biosurveillance system data for pandemic (H1N1) 2009 (April 2009 – January 2010) from 8 regions and 122 countries to: identify reliable alert criteria among 15 Argus-defined categories; determine the degree of data correlation for disease progression; and assess timeliness of Internet information. Results Argus generated a total of 1,580 unique alerts; 5 alert categories generated statistically significant (p < 0.05) correlations with WHO case count data; the sum of these 5 categories was highly correlated with WHO case data (r = 0.81, p < 0.0001), with expected differences observed among the 8 regions. Argus reported first confirmed cases on the same day as WHO for 21 of the first 64 countries reporting cases, and 1 to 16 days (average 1.5 days) ahead of WHO for 42 of those countries. Conclusion Confirmed pandemic (H1N1) 2009 cases collected by Argus and WHO methods returned consistent results and confirmed the reliability and timeliness of Internet information. Disease-specific alert criteria provide situational awareness and may serve as proxy indicators to event progression and escalation in lieu of traditional surveillance data; alerts may identify early-warning indicators to another pandemic, preparing the public health community for disease events. PMID:22709988

Matrix Metalloproteinases and Neurotrauma: Evolving Roles in Injury and Reparative Processes

PubMed Central

Zhang, Haoqian; Adwanikar, Hita; Werb, Zena; Noble-Haeusslein, Linda J.

2010-01-01

Matrix metalloproteinases (MMPs) are involved in a wide range of proteolytic events in fetal development and normal tissue remodeling as well as wound healing and inflammation. In the CNS, they have been implicated in a variety of neurodegenerative diseases ranging from multiple sclerosis to Alzheimer disease and are integral to stroke-related cell damage. Although studies implicate increased activity of MMPs in pathogenesis in the CNS, there is also a growing literature to support their participation in events that support recovery processes. Here the authors provide a brief overview of MMPs and their regulation, address their complex roles following traumatic injuries to the adult and developing CNS, and consider their time- and context-dependent signatures that influence both injury and reparative processes. PMID:20400713

Receptor tyrosine kinase alterations in AML - biology and therapy.

PubMed

Stirewalt, Derek L; Meshinchi, Soheil

2010-01-01

Acute myeloid leukemia (AML) is the most common form of leukemia in adults, and despite some recent progress in understanding the biology of the disease, AML remains the leading cause of leukemia-related deaths in adults and children. AML is a complex and heterogeneous disease, often involving multiple genetic defects that promote leukemic transformation and drug resistance. The cooperativity model suggests that an initial genetic event leads to maturational arrest in a myeloid progenitor cell, and subsequent genetic events induce proliferation and block apoptosis. Together, these genetic abnormalities lead to clonal expansion and frank leukemia. The purpose of this chapter is to review the biology of receptor tyrosine kinases (RTKs) in AML, exploring how RTKs are being used as novel prognostic factors and potential therapeutic targets.

Stress is associated with unfavorable patterns of dietary intake among female chinese immigrants.

PubMed

Tseng, Marilyn; Fang, Carolyn Y

2011-06-01

Chinese immigrants experience increased risk for weight gain and chronic disease after US migration. Whether psychosocial stress affects their eating behavior is unknown. The purpose of this study is to examine psychosocial stress and dietary intake among 426 Chinese immigrant women in the Philadelphia region. Participants completed 4 days of dietary recalls and questionnaires assessing positive and negative life events in the past year and migration-related stressors. In hierarchical linear regression models, positive life events were associated with higher energy intake (β = 21.1, p =  0.04). Migration-related stress was associated with lower total gram (β  = -11.3, p < 0.0001) and overall grain (β  = -0.18, p = 0.03) intake and higher energy density (β = 0.002, p = 0.04) and percent energy from fat (β = 0.06, p = 0.05). Migration-related stress did not increase overall intake in terms of energy and total grams but selectively increased fat intake and energy density. Such dietary habits may have implications for future chronic disease risk in this immigrant population.

Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial

PubMed Central

Gulley, James L.; Rajan, Arun; Spigel, David R.; Iannotti, Nicholas; Chandler, Jason; Wong, Deborah J. L.; Leach, Joseph; Edenfield, W. Jeff; Wang, Ding; Grote, Hans Juergen; von Heydebreck, Anja; Chin, Kevin; Cuillerot, Jean-Marie; Kelly, Karen

2017-01-01

Background Avelumab, a fully human IgG1 immune checkpoint inhibitor targeting programmed death ligand 1 (PD-L1), has shown antitumour activity and an acceptable safety profile in patients with advanced solid tumours. Here, we assessed avelumab treatment in patients with advanced, platinum-treated non-small cell lung cancer (NSCLC). Methods In this dose-expansion cohort of a multicentre, open-label, phase 1 study, patients with progressive or platinum-resistant metastatic or recurrent NSCLC were enrolled at 58 sites in the United States. Eligible patients had confirmed stage IIIB or IV NSCLC with squamous or nonsquamous histology, measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), tumour biopsy or archival sample for biomarker assessment, and Eastern Cooperative Oncology Group performance status 0 or 1, among other criteria. Patient selection was not based on PD-L1 expression or other biomarkers, including EGFR or KRAS mutation or ALK translocation status. Patients received avelumab monotherapy 10 mg/kg every 2 weeks until disease progression or toxicity. The primary endpoint was safety and tolerability. Secondary endpoints included best overall response, progression-free survival, overall survival, and clinical activity associated with PD-L1 expression. Responses were evaluated using RECIST v1.1, and analyses of antitumour activity and safety were performed in all patients who received at least one dose of avelumab. This trial is registered with ClinicalTrials.gov (NCT01772004); enrolment in this cohort is closed and the trial is ongoing. Findings Between 10 September 2013 and 24 June 2014, 184 patients were enrolled and initiated treatment with avelumab. Median follow-up duration was 8·8 months (interquartile range [first and third quartiles], 7·2–11·9 months). The most common treatment-related adverse events of any grade were fatigue (n=46; 25%), infusion-related reaction (n=38; 21%), and nausea (n=23; 13%). Grade ≥3 treatment-related adverse events occurred in 23 of 184 patients (13%); the most common were infusion-related reaction (n=4; 2%), elevated lipase (n=3; 2%), constipation (n=2; 1%), and dyspnoea (n=2; 1%). 16 of 184 patients (9%) had a serious adverse event related to treatment with avelumab, with infusion-related reaction (4 [2%]) and dyspnoea (2 [1%]) occurring in more than one patient. Immune-related treatment-related events occurred in 22 patients (12%). The confirmed objective response rate, regardless of PD-L1 status, was 12% (95% CI, 8–18), including one complete response and 21 partial responses. Seventy patients had stable disease, for an overall disease-control rate of 50%. Interpretation Avelumab showed an acceptable safety profile and antitumour activity in patients with progressive or resistant NSCLC, providing a rationale for additional studies of avelumab in this disease setting. Funding Merck KGaA, Darmstadt, Germany and Pfizer, Inc, New York, USA. PMID:28373005

Single nucleotide polymorphisms in long noncoding RNA, ANRIL, are not associated with severe periodontitis but with adverse cardiovascular events among patients with cardiovascular disease.

PubMed

Schulz, S; Seitter, L; Werdan, K; Hofmann, B; Schaller, H-G; Schlitt, A; Reichert, S

2018-05-06

Biological plausibility of an association between severe periodontitis and cardiovascular disease (CVD) has been proven. Genetic characteristics play an important role in both complex inflammatory diseases. Polymorphisms (single nucleotide polymorphisms [SNPs]) in the long noncoding RNA, antisense noncoding RNA in the INK4 locus (ANRIL), were shown to play a leading role in both diseases. The primary objectives of the study were to assess, among cardiovascular (CV angiographically proven ≥50% stenosis of a main coronary artery) patients, the impact of ANRIL SNPs rs133049 and rs3217992 on the severity of periodontitis and the previous history of coronary events, as well as on the occurrence of further adverse CV events. The prevalence of severe periodontitis was analyzed in 1002 CV patients. ANRIL SNPs rs133049 and rs3217992 were genotyped. The prognostic value of both ANRIL SNPs for combined CV endpoint (stroke/transient ischemic attack [TIA], myocardial infarction, death from a CV-related event, death from stroke) was evaluated after a 3-year follow-up period. Hazard ratios (HRs) were adjusted for established CV risk factors applying Cox regression. ANRIL SNPs rs133049 and rs3217992 were not associated with severe periodontitis or history of CVD in CV patients. In the Kaplan-Meier survival curve including the log rank-test (P = .036) and Cox regression (hazard ratio = 1.684, P = .009) the AA genotype of rs3217992 was shown to be an independent predictor for adverse CV events after 3 years of follow-up. SNPs in ANRIL are not risk modulators for severe periodontitis and history of CVD in CV patients. The AA genotype of ANRIL SNPs rs3217992 possesses prognostic power for further CV events within 3 years of follow-up. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Climate Changes and Human Health: A Review of the Effect of Environmental Stressors on Cardiovascular Diseases Across Epidemiology and Biological Mechanisms.

PubMed

Giorgini, Paolo; Di Giosia, Paolo; Petrarca, Marco; Lattanzio, Francesco; Stamerra, Cosimo Andrea; Ferri, Claudio

2017-01-01

Climate change is rapidly affecting all the regions of our planet. The most relevant example is global warming, which impacts on the earth's ecosystems, threatening human health. Other effects include extreme variations in temperature and increases in air pollution. These events may negatively impact mortality and morbidity for cardiovascular diseases. In this review, we discuss the main effects of climate changes on cardiovascular diseases, reporting the epidemiological evidences and the biological mechanisms linking climate change consequences to hypertension, diabetes, ischemic heart diseases, heart failure and stroke. Up to now, findings suggest that humans acclimate under different weather conditions, even though extreme temperatures and higher levels of air pollution can influence health-related outcomes. In these cases, climate change adversely affects cardiovascular system and the high-risk subjects for cardiovascular diseases are those more exposed. Finally, we examine climate change implications on publich health and suggest adaptation strategies to monitor the high-risk population, and reduce the amount of hospital admissions associated to these events. Such interventions may minimize the costs of public health and reduce the mortality for cardiovascular diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

2010 FIFA world cup South Africa: travel health issues and new options for protection against meningococcal disease.

PubMed

Zuckerman, Jane N; Bröker, Michael; Worth, Christopher

2010-03-01

The public health implications of large crowds gathering at a range of key global events should never be underestimated. This is especially the case with the upcoming 2010 FIFA World Cup South Africa programme where thousands of local and travelling spectators, players and officials from all over the world will be present. Although meningococcal disease contracted whilst actually travelling is relatively rare, any travel health risk assessment should involve consideration of potential exposure to and transmission of this disease where crowding occurs. In South Africa, for reasons not completely understood, the incidence of meningococcal disease is higher than in most European countries. Whilst the currently available polysaccharide vaccines can help protect travellers against meningococcal disease there are some well recognised limitations of such vaccines. These can, however, be overcome with the use of newly developed conjugated quadrivalent meningococcal vaccines. A quadrivalent conjugate vaccine should be the first choice for travellers to areas in which the risk of exposure to meningococcal disease is significant. The conjugated quadrivalent meningococcal vaccine should be recommended for all those attending or playing in the 2010 FIFA World Cup South Africa as well as similar global and regional events.

76 FR 29756 - Healthcare Infection Control Practices Advisory Committee (HICPAC)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Healthcare... Director, Division of Healthcare Quality Promotion regarding (1) The practice of healthcare infection... infections), antimicrobial resistance, and related events in settings where healthcare is provided; and (3...

76 FR 63622 - Healthcare Infection Control Practices Advisory Committee, (HICPAC)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Healthcare... Director, Division of Healthcare Quality Promotion regarding (1) The practice of healthcare infection... infections), antimicrobial resistance, and related events in settings where healthcare is provided; and (3...

75 FR 50770 - Healthcare Infection Control Practices Advisory Committee (HICPAC)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Healthcare..., and related events in settings where healthcare is provided; and (3) periodic updating of guidelines and other policy statements regarding prevention of healthcare- associated infections and healthcare...

Accuracy of Cardiovascular Risk Prediction Varies by Neighborhood Socioeconomic Position: A Retrospective Cohort Study.

PubMed

Dalton, Jarrod E; Perzynski, Adam T; Zidar, David A; Rothberg, Michael B; Coulton, Claudia J; Milinovich, Alex T; Einstadter, Douglas; Karichu, James K; Dawson, Neal V

2017-10-03

Inequality in health outcomes in relation to Americans' socioeconomic position is rising. First, to evaluate the spatial relationship between neighborhood disadvantage and major atherosclerotic cardiovascular disease (ASCVD)-related events; second, to evaluate the relative extent to which neighborhood disadvantage and physiologic risk account for neighborhood-level variation in ASCVD event rates. Observational cohort analysis of geocoded longitudinal electronic health records. A single academic health center and surrounding neighborhoods in northeastern Ohio. 109 793 patients from the Cleveland Clinic Health System (CCHS) who had an outpatient lipid panel drawn between 2007 and 2010. The date of the first qualifying lipid panel served as the study baseline. Time from baseline to the first occurrence of a major ASCVD event (myocardial infarction, stroke, or cardiovascular death) within 5 years, modeled as a function of a locally derived neighborhood disadvantage index (NDI) and the predicted 5-year ASCVD event rate from the Pooled Cohort Equations Risk Model (PCERM) of the American College of Cardiology and American Heart Association. Outcome data were censored if no CCHS encounters occurred for 2 consecutive years or when state death data were no longer available (that is, from 2014 onward). The PCERM systematically underpredicted ASCVD event risk among patients from disadvantaged communities. Model discrimination was poorer among these patients (concordance index [C], 0.70 [95% CI, 0.67 to 0.74]) than those from the most affluent communities (C, 0.80 [CI, 0.78 to 0.81]). The NDI alone accounted for 32.0% of census tract-level variation in ASCVD event rates, compared with 10.0% accounted for by the PCERM. Patients from affluent communities were overrepresented. Outcomes of patients who received treatment for cardiovascular disease at Cleveland Clinic were assumed to be independent of whether the patients came from a disadvantaged or an affluent neighborhood. Neighborhood disadvantage may be a powerful regulator of ASCVD event risk. In addition to supplemental risk models and clinical screening criteria, population-based solutions are needed to ameliorate the deleterious effects of neighborhood disadvantage on health outcomes. The Clinical and Translational Science Collaborative of Cleveland and National Institutes of Health.

Strengthening core public health capacity based on the implementation of the International Health Regulations (IHR) (2005): Chinese lessons.

PubMed

Liu, Bin; Sun, Yan; Dong, Qian; Zhang, Zongjiu; Zhang, Liang

2015-04-17

As an international legal instrument, the International Health Regulations (IHR) is internationally binding in 196 countries, especially in all the member states of the World Health Organization (WHO). The IHR aims to prevent, protect against, control, and respond to the international spread of disease and aims to cut out unnecessary interruptions to traffic and trade. To meet IHR requirements, countries need to improve capacity construction by developing, strengthening, and maintaining core response capacities for public health risk and Public Health Emergency of International Concern (PHEIC). In addition, all the related core capacity requirements should be met before June 15, 2012. If not, then the deadline can be extended until 2016 upon request by countries. China has promoted the implementation of the IHR comprehensively, continuingly strengthening the core public health capacity and advancing in core public health emergency capacity building, points of entry capacity building, as well as risk prevention and control of biological events (infectious diseases, zoonotic diseases, and food safety), radiological, nuclear, and chemical events, and other catastrophic events. With significant progress in core capacity building, China has dealt with many public health emergencies successfully, ensuring that its core public health capacity has met the IHR requirements, which was reported to WHO in June 2014. This article describes the steps, measures, and related experiences in the implementation of IHR in China. © 2015 by Kerman University of Medical Sciences.

Rotigotine transdermal patch in Parkinson's disease: a systematic review and meta-analysis.

PubMed

Zhou, Chang-Qing; Li, Shan-Shan; Chen, Zhong-Mei; Li, Feng-Qun; Lei, Peng; Peng, Guo-Guang

2013-01-01

The efficacy and safety of rotigotine transdermal patch in Parkinson's disease (PD) were studied in some clinical trials. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy, tolerability, and safety of rotigotine transdermal patch versus placebo in PD. Six randomized controlled trials (1789 patients) were included in this meta-analysis. As compared with placebo, the use of rotigotine resulted in greater improvements in Unified Parkinson's Disease Rating Scale activities of daily living score (weighted mean difference [WMD] -1.69, 95% confidence interval [CI] -2.18 to -1.19), motor score (WMD -3.86, 95% CI -4.86 to -2.86), and the activities of daily living and motor subtotal score (WMD -4.52, 95% CI -5.86 to -3.17). Rotigotine was associated with a significantly higher rate of withdrawals due to adverse events (relative risk [RR] 1.82, 95% CI 1.29-2.59), and higher rates of application site reactions (RR 2.92, 95% CI 2.29-3.72), vomiting (RR 5.18, 95% CI 2.25-11.93), and dyskinesia (RR 2.52, 95% CI 1.47-4.32) compared with placebo. No differences were found in the relative risks of headache, constipation, back pain, diarrhea, or serious adverse events. Our meta-analysis showed that the use of rotigotine can reduce the symptoms of PD. However, rotigotine was also associated with a higher incidence of adverse events, especially application site reactions, compared with placebo.

Serious adverse events and compensation in registration trials: a review of data from a Japanese university hospital

PubMed Central

2014-01-01

Background Clinical trials leading to regulatory approval, or registration trials, play a central role in the development of drugs and medical devices. The contribution of support staff, such as the clinical research coordinator (CRC) and administrative officers, in registration trials is now widely recognized. Attending to serious adverse events is an important duty of the CRC and investigators alike, and managing these complications and compensation constitutes a key responsibility. We retrospectively examined the frequency of serious adverse events and compensation events reported from 2007 through 2011 at Tokushima University Hospital, an academic hospital in rural Japan. We present herein the results of our analysis. Results Over the five-year period, 284 subjects participating in 106 registration trials experienced a total of 43 serious adverse events, and eight compensation events were documented. Among the serious adverse events, 35 (81.4%) were considered not related to the investigational drug, and 17 (39.5%) resulted in withdrawal of the study drug. Patients with malignant diseases experienced serious adverse events significantly more frequently compared to those with non-malignant diseases (28.3% versus 8.2%, respectively; P < 0.01). Conclusions The CRC should be vigilant for serious adverse events in oncology clinical trials due to the generally higher frequency of these complications in subjects with malignancy. However, on an individual basis, the CRC may be seldom involved in the process for compensating serious adverse events. Therefore, the CRC’s ability to share such experiences may serve as an opportunity for educating clinical trial support staff at the study site as well as those at other sites. However, further study is warranted to determine the role of the clinical trial support staff in optimizing methods for managing adverse events requiring compensation in registration trials. PMID:24742228

The copper rush of the nineties.

PubMed

Solioz, Marc

2016-09-01

The nineties witnessed the discovery of the copper ATPases, enzymes which transport copper across the cytoplasmic membranes of bacteria and eukaryotes. In the same decade, several other key components of copper homeostasis have also been discovered, like copper chaperones and plasma membrane copper transporters. This has finally led to a molecular understanding of two inherited human diseases related to copper: Menkes disease, manifested by systemic copper deficiency, and Wilson disease, caused by defective secretion of excess copper. A historic perspective and untold stories of the events leading up to these discoveries are presented here.

Psychosocial and Neurohormonal Predictors of HIV Disease Progression (CD4 Cells and Viral Load): A 4 Year Prospective Study.

PubMed

Ironson, G; O'Cleirigh, C; Kumar, M; Kaplan, L; Balbin, E; Kelsch, C B; Fletcher, M A; Schneiderman, N

2015-08-01

Most studies of psychosocial predictors of disease progression in HIV have not considered norepinephrine (NE), a neurohormone related to emotion and stress, even though NE has been related to accelerated viral replication in vitro and impaired response to antiretroviral therapy (ART). We therefore examined NE, cortisol, depression, hopelessness, coping, and life event stress as predictors of HIV progression in a diverse sample. Participants (n = 177) completed psychological assessment, blood draws [CD4, viral load (VL)], and a 15 h urine sample (NE, cortisol) every 6 months over 4 years. Hierarchical linear modeling (HLM) was used to model slope in CD4 and VL controlling for ART at every time point, gender, age, race, SES, and initial disease status. NE (as well as depression, hopelessness, and avoidant coping) significantly predicted a greater rate of decrease in CD4 and increase in VL. Cortisol was not significantly related to CD4, but predicted VL increase. To our knowledge, this is the first study relating NE, in vivo, to accelerated disease progression over an extended time. It also extends our previous 2 year study by relating depressed mood and coping to accelerated disease progression over 4 years.

Relative associations between depression and anxiety on adverse cardiovascular events: does a history of coronary artery disease matter? A prospective observational study.

PubMed

Pelletier, Roxanne; Bacon, Simon L; Arsenault, André; Dupuis, Jocelyn; Laurin, Catherine; Blais, Lucie; Lavoie, Kim L

2015-12-15

To assess whether depression and anxiety increase the risk of mortality and major adverse cardiovascular events (MACE), among patients with and without coronary artery disease (CAD). DECADE (Depression Effects on Coronary Artery Disease Events) is a prospective observational study of 2390 patients referred at the Montreal Heart Institute. Patients were followed for 8.8 years, between 1998 and 2009. Depression and anxiety were assessed using a psychiatric interview (Primary Care Evaluation of Mental Disorders, PRIME-MD). Outcomes data were obtained from Quebec provincial databases. All-cause mortality and MACE. After adjustment for covariates, patients with depression were at increased risks of all-cause mortality (relative risk (RR)=2.84; 95% CI 1.25 to 6.49) compared with patients without depression. Anxiety was not associated with increased mortality risks (RR=0.86; 95% CI 0.31 to 2.36). When patients were stratified according to CAD status, depression increased the risk of mortality among patients with no CAD (RR=4.39; 95% CI 1.12 to 17.21), but not among patients with CAD (RR=2.32; 95% CI 0.78 to 6.88). Neither depression nor anxiety was associated with MACE among patients with or without CAD. Depression, but not anxiety, was an independent risk factor for all-cause mortality in patients without CAD. The present study contributes to a better understanding of the relative and unique role of depression versus anxiety among patients with versus without CAD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Personality trait changes among young Finns: the role of life events and transitions.

PubMed

Leikas, Sointu; Salmela-Aro, Katariina

2015-02-01

Recent research has shown that personality traits continue to develop throughout the life span, but most profound changes are typically found during young adulthood. Increasing evidence suggests that life events play a significant role in many of these changes. The present longitudinal study examined the role of work, education, social, and health-related life events in the development of the Big Five traits among young Finns. Participants were originally recruited in 2004 through elementary schools in a middle-sized Finnish city. Participants' Big Five traits and life events were measured via self-reports at ages 20 and 23 (Ns = 597 and 588, respectively). Entering work life, beginning a relationship, and studying in university predicted increases in Conscientiousness, trying drugs predicted increases in Neuroticism, and onset of a chronic disease predicted increases in Neuroticism and Conscientiousness between ages 20 and 23. The results suggest that mature life transitions relate to stronger increases in Conscientiousness in young adulthood, and that non-normative life choices and events may predict increases in Neuroticism. © 2014 Wiley Periodicals, Inc.

Association of vascular indices with novel circulating biomarkers as prognostic factors for cardiovascular complications in patients with type 2 diabetes mellitus.

PubMed

Naka, Katerina K; Papathanassiou, Katerina; Bechlioulis, Aris; Pappas, Konstantinos; Tigas, Stelios; Makriyiannis, Dimitrios; Antoniou, Sophia; Kazakos, Nikolaos; Margeli, Alexandra; Papassotiriou, Ioannis; Tsatsoulis, Agathocles; Michalis, Lampros K

2018-03-01

The pathophysiology of atherosclerosis in type 2 diabetes mellitus (T2DM) is multifactorial. The association of vascular indices with circulating biomarkers of inflammation and insulin resistance and their role in the long-term cardiovascular prognosis in T2DM patients were currently investigated. Patients with T2DM and poor glycemic control without known cardiovascular diseases (n=119) at baseline were enrolled and followed for about 9years. The end-point was the occurrence of any cardiovascular event (coronary heart disease, stroke, peripheral artery disease or cardiovascular death). Aortic pulse wave velocity (PWV), augmentation index (AIx), brachial flow-mediated dilation (FMD), hsCRP, Chitinase-3-like protein 1 (YKL-40), Neutrophil Gelatinase-Associated Lipocalin (NGAL), Fatty Acid Binding Protein (FABP-4) were assessed. Higher YKL-40 and NGAL were associated with higher PWV, while higher YKL-40 and FABP-4 were related to higher AIx (p<0.05 for all). In univariate Cox regression analysis, PWV>10m/s, YKL-40>78ng/ml and NGAL>42ng/ml were associated with cardiovascular events (p<0.05 for all). In multivariate analysis, after adjusting for classical risk factors and glycemic control, increased NGAL, YKL-40 and PWV and decreased FMD (i.e. ≤2.2%) (p<0.05 for all) were independently associated with cardiovascular events. In T2DM patients without established cardiovascular disease, novel indices of vascular inflammation (NGAL and YKL-40) were associated with subclinical atherosclerosis (arterial stiffness) but also with adverse clinical prognosis. Arterial stiffness and endothelial dysfunction were also independently related to adverse prognosis. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Sickle red cell adhesion: many issues and some answers.

PubMed

Kaul, D K

2008-01-01

Among multiple pathologies associated with sickle cell disease, sickle red cell-endothelial interaction has been implicated as a potential initiating mechanism in vaso-occlusive events that characterize this disease. Vast literature exists on various aspects of sickle red cell adhesion, but many issues remain unresolved, especially pertaining to the role of sickle red cell heterogeneity, the relative role of multiple adhesion mechanisms and targets of antiadhesive therapy. This review briefly analyzes these issues.

Legionnaire's disease complicating pregnancy: a case report with intrauterine fetal demise.

PubMed

Vimercati, A; Greco, P; Bettocchi, S; Resta, L; Selvaggi, L

2000-01-01

Legionnaire's disease complicating pregnancy is an unusual event that can seriously compromise both the mother and the fetus. We describe one case of such association, with an unfavourable intrauterine fetal outcome, secondary to acute placental insufficiency, related to infection. It is important in these high risk pregnancies complicated by acute pneumonia to take into consideration the diagnosis, as early as possible, and the appropriate treatment or the careful monitoring of fetal wellbeing.

The role of native birds and other wildlife on the emergence of zoonotic diseases

USGS Publications Warehouse

Friend, Milton; McLean, Robert G.; Burroughs, T.; Knobler, S.; Lederberg, J.

2001-01-01

Wildlife can be an important source of transmission of infectious disease to humans. One potential transmission route involves hunting and fishing, both common activities in the United States and worldwide. For example, during 1996, approximately 11 million Americans, about 40 percent of the total population 16 years of age and older, took part in some recreational activity relating to wildlife and fish. Another potential route of infection focuses on urban and suburban environments. These locations are of special concern because of their increasing role as wildlife habitat, the greater interface between humans and wildlife that takes place within those environments, the paucity of knowledge about disease in those wildlife populations, and the general lack of orderly management for wildlife within those environments. In the wild, several trends are contributing to the growing importance of zoonotic diseases. First, the spectrum of infectious diseases affecting wildlife today is greater than at any time during the previous century. Second, the occurrence of infectious diseases has changed, from sporadic, self-limiting outbreaks that generally resulted in minor losses to frequently occurring events that generally result in major losses of wildlife. Third, disease emergence has occurred on a worldwide scale in a broad spectrum of wildlife species and habitats. Given the scope of the problem, current disease surveillance efforts are inadequate. Few state wildlife agencies allocate personnel and resources to address wildlife disease, despite their statutory responsibility for managing nonmigratory wildlife. Some state agencies provide minimal support for regional programs based at universities. At the federal level, the primary surveillance effort is conducted by the National Wildlife Health Center, operated by the U.S. Geological Survey. Outside of government, some veterinary schools, agriculture diagnostic laboratories, and other programs provide additional information on animal diseases, primarily by examining carcasses of dead wildlife submitted for analysis, and individual university-based researchers carry out a variety of studies. Typically, information about the occurrence of disease in free-ranging wildlife is derived from surveys and mortality events in areas where wildlife observations by agencies and the public are frequent enough to detect their occurrence before carcasses are removed by scavengers and predatory animals. The result is that disease occurrence is grossly underreported, heavily biased toward mortality events, and biased toward species of special concern and interest, such as game and endangered species. Therefore, the available information should be viewed as the “proverbial tip of the iceberg” relative to disease activity within wildlife populations.

Alterations in late endocytic trafficking related to the pathobiology of LRRK2-linked Parkinson's disease.

PubMed

Rivero-Ríos, Pilar; Gómez-Suaga, Patricia; Fernández, Belén; Madero-Pérez, Jesús; Schwab, Andrew J; Ebert, Allison D; Hilfiker, Sabine

2015-06-01

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene comprise the most common cause of familial Parkinson's disease (PD), and variants increase the risk for sporadic PD. LRRK2 displays kinase and GTPase activity, and altered catalytic activity correlates with neurotoxicity, making LRRK2 a promising therapeutic target. Despite the importance of LRRK2 for disease pathogenesis, its normal cellular function, and the mechanism(s) by which pathogenic mutations cause neurodegeneration remain unclear. LRRK2 seems to regulate a variety of intracellular vesicular trafficking events to and from the late endosome in a manner dependent on various Rab proteins. At least some of those events are further regulated by LRRK2 in a manner dependent on two-pore channels (TPCs). TPCs are ionic channels localized to distinct endosomal structures and can cause localized calcium release from those acidic stores, with downstream effects on vesicular trafficking. Here, we review current knowledge about the link between LRRK2, TPC- and Rab-mediated vesicular trafficking to and from the late endosome, highlighting a possible cross-talk between endolysosomal calcium stores and Rab proteins underlying pathomechanism(s) in LRRK2-related PD.

Programming of endocrine mechanisms of cardiovascular control and growth.

PubMed

Green, L R

2001-01-01

Several epidemiologic studies have linked size at birth to health in adult life. One school of thought centers on the part that periconceptual or intrauterine events play in this relationship. The idea is that an event, or several events, during critical periods of development can program, or permanently alter, fetal physiology resulting in altered size at birth and subsequent adult disease, including that of the cardiovascular system. Maternal diet or body composition at the time of conception can influence placental development and subsequent transfer of nutrients and substrates to the fetus. Alterations to the maternal diet or body composition throughout gestation are then seen as challenges that are superimposed on this backdrop of periconceptual events. One task is to find an animal model that replicates the major features of the epidemiologic data: for adult cardiovascular disease this would be altered fetal size and the development of postnatal hypertension. In addition, a critical issue is to investigate the mechanisms underlying this Fetal Origins of Adult Disease hypothesis. The multiple mechanisms that constitute fetal cardiovascular responses to hypoxia in late gestation at neuronal, endocrine, and local tissue levels have been studied extensively, and there is evidence from several different experimental paradigms that these control mechanisms can be programmed by intrauterine challenges. This review synthesizes the current knowledge in this area and considers how the programming of cardiovascular control relates to fetal growth.

Characteristics of metabolic and lifestyle risk factors in young Japanese patients with coronary heart disease: a comparison with older patients.

PubMed

Azegami, Masako; Hongo, Minoru; Yanagisawa, Setsuko; Yamazaki, Akie; Sakaguchi, Kesami; Yazaki, Yoshikazu; Imamura, Hiroshi

2006-05-01

Coronary heart disease (CHD) is recognized as a lifestyle-related disease and is the second leading cause of death in Japan. However, the cardiac risk factor profile of young patients with CHD has not been clarified in suburban areas of Japan. Our study aimed to determine metabolic and lifestyle risk factors in young patients and compare them with older patients living in suburban areas of Nagano Prefecture. A multicenter study was conducted in 86 young (aged less than 40 years) and 91 older (aged 50 years and over) patients diagnosed with CHD from 1992 to 2002. There was a strong association between obesity and the occurrence of CHD events in young patients (odds ratio = 3.61, P = 0.006). Lifestyle in the young patients was characterized by a lack of physical activity and regular physical activity was found to decrease the risk of the CHD events in these patients (odds ratio = 0.31, P = 0.030). In older patients, hypertension was identified as an independent risk factor for CHD events. The results of the present study have demonstrated that obesity and a lack of regular physical exercise are independent risk factors for CHD events in younger patients. Thus, the data may be useful for the effective screening of high-risk individuals and the development of educational programs for the prevention of CHD, especially in younger Japanese.

Five-Year Safety Data for More than 55,000 Subjects following Breast Implantation: Comparison of Rare Adverse Event Rates with Silicone Implants versus National Norms and Saline Implants.

PubMed

Singh, Navin; Picha, George J; Hardas, Bhushan; Schumacher, Andrew; Murphy, Diane K

2017-10-01

The U.S. Food and Drug Administration has required postapproval studies of silicone breast implants to evaluate the incidence of rare adverse events over 10 years after implantation. The Breast Implant Follow-Up Study is a large 10-year study (>1000 U.S. sites) evaluating long-term safety following primary augmentation, revision-augmentation, primary reconstruction, or revision-reconstruction with Natrelle round silicone breast implants compared with national norms and outcomes with saline implants. Targeted adverse events in subjects followed for 5 to 8 years included connective tissue diseases, neurologic diseases, cancer, and suicide. The safety population comprised 55,279 women (primary augmentation, n = 42,873; revision-augmentation, n = 6837; primary reconstruction, n = 4828; and revision-reconstruction, n = 741). No targeted adverse events occurred at significantly greater rates in silicone implant groups versus national norms across all indications. The standardized incidence rate (observed/national norm) for all indications combined was 1.4 for cervical/vulvar cancer, 0.8 for brain cancer, 0.3 for multiple sclerosis, and 0.1 for lupus/lupus-like syndrome. Silicone implants did not significantly increase the risk for any targeted adverse events compared with saline implants. The risk of death was similar with silicone versus saline implants across all indications. The suicide rate (10.6 events per 100,000 person-years) was not significantly higher than the national norm. No implant-related deaths occurred. Results from 5 to 8 years of follow-up for a large number of subjects confirmed the safety of Natrelle round silicone implants, with no increased risk of systemic disease or suicide versus national norms or saline implants. Therapeutic, II.

[Gender differences in stressful life events and depression in Chinese adults aged 30-79 years].

PubMed

Wu, M; Li, J C; Yu, C Q; Chen, Y P; Lyu, J; Guo, Y; Bian, Z; Tan, Y L; Pei, P; Chen, J S; Chen, Z M; Li, L M

2017-11-10

Objective: To investigate gender specific differences in the association between stressful life events (SLEs) and depression in Chinese adults aged 30-79 years. Methods: In the baseline survey during 2004-2008, the China Kadoorie Biobank (CKB) recruited 512 891 men and women aged 30-79 years from 10 areas of China. Detailed information on SLEs, including demographic and socio-economic status, smoking, alcohol drinking and history of chronic disease, as well as depression symptoms and major depressive episodes (MDEs) in preceding 12 months, was collected by using standardized questionnaire. Multinomial logistic regression model was employed to estimate the relative risk ratio ( RRR ) and 95 %CI of SLEs (3 categories, 10 items) on depression and the dose-response relationship between the number of SLEs experienced and depression. The interactions between gender and SLEs on depression were examined with likelihood ratio test. Results: Among the 512 891 participants, 35 085 (6.8%) reported family-related events, 5 972 (1.2%) reported finance-related events, and 4 453 (0.9%) reported other stressful life events. Females had a higher occurrence of family-related events, while males had a higher occurrence of finance-related and other events (all P -value <0.001). After adjusted for potential confounders, SLEs were significantly associated with MDEs ( RRR =11.99, 95 %CI : 10.49-13.71 for males; RRR =14.15, 95 %CI : 12.97-15.43 for females), and with depressive symptoms ( RRR =7.43, 95 %CI : 6.94-7.95 for males; RRR =8.30, 95 %CI : 7.91-8.72 for females). And the associations were stronger in females than in males ( P for interaction=0.049). In the three categories of SLEs, family-related events showed stronger association in female ( P for interaction <0.001), while no gender specific differences were observed for the other two categories (all P -value>0.05). Furthermore, the effect of the number of SLEs experienced increased in a dose-response manner on depressive symptoms and MDEs for both genders, but no gender specific differences were found. Conclusions: The gender modifies the association between stressful life events and depression in Chinese adults, and women experienced family-related events have a greater risk of depression. The more the stressful events experienced, the more likely to have depression.

A Randomized Controlled Phase III Trial of Recombinant Human Granulocyte Colony-Stimulating Factor (Filgrastim) for Treatment of Severe Chronic Neutropenia

PubMed Central

Dale, David C.; Bonilla, Mary Ann; Davis, Mark W.; Nakanishi, Arline M.; Hammond, William P.; Kurtzberg, Joanne; Wang, Winfred; Jakubowski, Ann; Winton, Elliott; Lalezari, Parviz; Robinson, William; Glaspy, John A.; Emerson, Steve; Gabrilove, Janice; Vincent, Martha; Boxer, Laurence A.

2014-01-01

Patients with idiopathic, cyclic, and congenital neutropenia have recurrent severe bacterial infections. One hundred twenty-three patients with recurrent infections and severe chronic neutropenia (absolute neutrophil count < 0.5 × 109/L) due to these diseases were enrolled in this multi-center phase III trial. They were randomized to either immediately beginning recombinant human granulocyte colony-stimulating factor (filgrastim) (3.45 to 11.50 μg/kg/d, subcutaneously) or entering a 4-month observation period followed by filgrastim administration. Blood neutrophil counts, bone marrow (BM) cell histology, and incidence and duration of infection-related events were monitored. Of the 123 patients enrolled, 120 received filgrastim. On therapy, 108 patients had a median absolute neutrophil count of ≥ 1.5 × 109/L. Examination of BM aspirates showed increased proportions of maturing neutrophils. Infection-related events were significantly decreased (P < .05) with approximately 50% reduction in the incidence and duration of infection-related events and almost 70% reduction in duration of antibiotic use. Asymptomatic splenic enlargement occurred frequently: adverse events frequently reported were bone pain, headache, and rash, which were generally mild and easily manageable. These data indicate that treatment of patients with severe chronic neutropenia with filgrastim results in a stimulation of BM production and maturation of neutrophils, an increase in circulating neutrophils, and a reduction in infection-related events. PMID:8490166

Microvascular Function Contributes to the Relation Between Aortic Stiffness and Cardiovascular Events: The Framingham Heart Study.

PubMed

Cooper, Leroy L; Palmisano, Joseph N; Benjamin, Emelia J; Larson, Martin G; Vasan, Ramachandran S; Mitchell, Gary F; Hamburg, Naomi M

2016-12-01

Arterial dysfunction contributes to cardiovascular disease (CVD) progression and clinical events. Inter-relations of aortic stiffness and vasodilator function with incident CVD remain incompletely studied. We used proportional hazards models to relate individual measures of vascular function to incident CVD in 4547 participants (mean age, 51±11 years; 54% women) in 2 generations of Framingham Heart Study participants. During follow-up (0.02-13.83 years), 232 participants (5%) experienced new-onset CVD events. In multivariable models adjusted for cardiovascular risk factors, both higher carotid-femoral pulse wave velocity (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.07-1.63; P=0.01) and lower hyperemic mean flow velocity (HR, 0.84; 95% CI, 0.71-0.99; P=0.04) were associated significantly with incident CVD, whereas primary pressure wave amplitude (HR, 1.12; 95% CI, 0.99-1.27; P=0.06), baseline brachial diameter (HR, 1.09; 95% CI, 0.90-1.31; P=0.39), and flow-mediated vasodilation (HR, 0.85; 95% CI, 0.69-1.04; P=0.12) were not. In mediation analyses, 8% to 13% of the relation between aortic stiffness and CVD events was mediated by hyperemic mean flow velocity. Our results suggest that associations between aortic stiffness and CVD events are mediated by pathways that include microvascular damage and remodeling. © 2016 American Heart Association, Inc.

Fatigue Is a Predictor for Cardiovascular Outcomes in Patients Undergoing Hemodialysis

PubMed Central

Fukuda, Sanae; Shoji, Tetsuo; Inaba, Masaaki; Tsujimoto, Yoshihiro; Tabata, Tsutomu; Okuno, Senji; Yamakawa, Tomoyuki; Okada, Shigeki; Okamura, Mikio; Kuratsune, Hirohiko; Fujii, Hisako; Hirayama, Yoshinobu; Watanabe, Yasuyoshi; Nishizawa, Yoshiki

2010-01-01

Background and objectives: Despite potential significance of fatigue and its underlying components in the occurrence of cardiovascular diseases, epidemiologic data showing the link are virtually limited. This study was designed to examine whether fatigue symptoms or fatigue's underlying components are a predictor for cardiovascular diseases in high-risk subjects with ESRD. Design, setting, participants, & measurements: 788 volunteer patients under hemodialysis therapy (506 male, 282 female) completed the survey between October and November 2005, with the follow-up period up to 26 months to monitor occurrence of fatal or nonfatal cardiovascular events. The questionnaire consisted of 64 questions, and promax rotation analysis of the principal component method conceptualized eight fatigue-related factors: fatigue itself, anxiety and depression, loss of attention and memory, pain, overwork, autonomic imbalance, sleep problems, and infection. Results: 14.7% of the patients showed fatigue scores higher than twice the SD of the mean for healthy volunteers. These highly fatigued patients exhibited a significantly higher risk for cardiovascular events (hazard ratio: 2.17; P < 0.01), with the relationship independent of the well-known risk factors, including age, diabetes, cardiovascular disease history, and inflammation and malnutrition markers. Moreover, comparisons of the risk in key subgroups showed that the risk of high fatigue score for cardiovascular events was more prominent in well-nourished patients, including lower age, absence of past cardiovascular diseases, higher serum albumin, and high non-HDL cholesterol. Conclusions: Fatigue can be an important predictor for cardiovascular events in patients with ESRD, with the relationship independent of the nutritional or inflammatory status. PMID:20185601

Oxidative Stress, Redox Signaling, and Autophagy: Cell Death Versus Survival

PubMed Central

Navarro-Yepes, Juliana; Burns, Michaela; Anandhan, Annadurai; Khalimonchuk, Oleh; del Razo, Luz Maria; Quintanilla-Vega, Betzabet; Pappa, Aglaia; Panayiotidis, Mihalis I.

2014-01-01

Abstract Significance: The molecular machinery regulating autophagy has started becoming elucidated, and a number of studies have undertaken the task to determine the role of autophagy in cell fate determination within the context of human disease progression. Oxidative stress and redox signaling are also largely involved in the etiology of human diseases, where both survival and cell death signaling cascades have been reported to be modulated by reactive oxygen species (ROS) and reactive nitrogen species (RNS). Recent Advances: To date, there is a good understanding of the signaling events regulating autophagy, as well as the signaling processes by which alterations in redox homeostasis are transduced to the activation/regulation of signaling cascades. However, very little is known about the molecular events linking them to the regulation of autophagy. This lack of information has hampered the understanding of the role of oxidative stress and autophagy in human disease progression. Critical Issues: In this review, we will focus on (i) the molecular mechanism by which ROS/RNS generation, redox signaling, and/or oxidative stress/damage alter autophagic flux rates; (ii) the role of autophagy as a cell death process or survival mechanism in response to oxidative stress; and (iii) alternative mechanisms by which autophagy-related signaling regulate mitochondrial function and antioxidant response. Future Directions: Our research efforts should now focus on understanding the molecular basis of events by which autophagy is fine tuned by oxidation/reduction events. This knowledge will enable us to understand the mechanisms by which oxidative stress and autophagy regulate human diseases such as cancer and neurodegenerative disorders. Antioxid. Redox Signal. 21, 66–85. PMID:24483238

Risk of cardiovascular events in people prescribed glucocorticoids with iatrogenic Cushing’s syndrome: cohort study

PubMed Central

Petersen, Irene; Nazareth, Irwin

2012-01-01

Objective To investigate whether there is an increased risk of cardiovascular events in people who exhibit iatrogenic Cushing’s syndrome during treatment with glucocorticoids. Design Cohort study. Setting 424 UK general practices contributing to The Health Improvement Network database. Participants People prescribed systemic glucocorticoids and with a diagnosis of iatrogenic Cushing’s syndrome (n=547) and two comparison groups: those prescribed glucocorticoids and with no diagnosis of iatrogenic Cushing’s syndrome (n=3231) and those not prescribed systemic glucocorticoids (n=3282). Main outcome measures Incidence of cardiovascular events within a year after diagnosis of iatrogenic Cushing’s syndrome or after a randomly selected date, and association between iatrogenic Cushing’s syndrome and risk of cardiovascular events. Results 417 cardiovascular events occurred in 341 patients. Taking into account only the first event by patient (coronary heart disease n=177, heart failure n=101, ischaemic stroke n=63), the incidence rates of cardiovascular events per 100 person years at risk were 15.1 (95% confidence interval 11.8 to 18.4) in those prescribed glucocorticoids and with a diagnosis of iatrogenic Cushing’s syndrome, 6.4 (5.5 to 7.3) in those prescribed glucocorticoids without a diagnosis of iatrogenic Cushing’s syndrome, and 4.1 (3.4 to 4.8) in those not prescribed glucocorticoids. In multivariate analyses adjusted for sex, age, intensity of glucocorticoid use, underlying disease, smoking status, and use of aspirin, diabetes drugs, antihypertensive drugs, lipid lowering drugs, or oral anticoagulant drugs, the relation between iatrogenic Cushing’s syndrome and cardiovascular events was strong (adjusted hazard ratios 2.27 (95% confidence interval 1.48 to 3.47) for coronary heart disease, 3.77 (2.41 to 5.90) for heart failure, and 2.23 (0.96 to 5.17) for ischaemic cerebrovascular events). The adjusted hazard ratio for any cardiovascular event was 4.16 (2.98 to 5.82) when the group prescribed glucocorticoids and with iatrogenic Cushing’s syndrome was compared with the group not prescribed glucocorticoids. Conclusion People who use glucocorticoids and exhibit iatrogenic Cushing’s syndrome should be aggressively targeted for early screening and management of cardiovascular risk factors. PMID:22846415

Risk of cardiovascular events in people prescribed glucocorticoids with iatrogenic Cushing's syndrome: cohort study.

PubMed

Fardet, Laurence; Petersen, Irene; Nazareth, Irwin

2012-07-30

To investigate whether there is an increased risk of cardiovascular events in people who exhibit iatrogenic Cushing's syndrome during treatment with glucocorticoids. Cohort study. 424 UK general practices contributing to The Health Improvement Network database. People prescribed systemic glucocorticoids and with a diagnosis of iatrogenic Cushing's syndrome (n = 547) and two comparison groups: those prescribed glucocorticoids and with no diagnosis of iatrogenic Cushing's syndrome (n = 3231) and those not prescribed systemic glucocorticoids (n = 3282). Incidence of cardiovascular events within a year after diagnosis of iatrogenic Cushing's syndrome or after a randomly selected date, and association between iatrogenic Cushing's syndrome and risk of cardiovascular events. 417 cardiovascular events occurred in 341 patients. Taking into account only the first event by patient (coronary heart disease n = 177, heart failure n = 101, ischaemic stroke n = 63), the incidence rates of cardiovascular events per 100 person years at risk were 15.1 (95% confidence interval 11.8 to 18.4) in those prescribed glucocorticoids and with a diagnosis of iatrogenic Cushing's syndrome, 6.4 (5.5 to 7.3) in those prescribed glucocorticoids without a diagnosis of iatrogenic Cushing's syndrome, and 4.1 (3.4 to 4.8) in those not prescribed glucocorticoids. In multivariate analyses adjusted for sex, age, intensity of glucocorticoid use, underlying disease, smoking status, and use of aspirin, diabetes drugs, antihypertensive drugs, lipid lowering drugs, or oral anticoagulant drugs, the relation between iatrogenic Cushing's syndrome and cardiovascular events was strong (adjusted hazard ratios 2.27 (95% confidence interval 1.48 to 3.47) for coronary heart disease, 3.77 (2.41 to 5.90) for heart failure, and 2.23 (0.96 to 5.17) for ischaemic cerebrovascular events). The adjusted hazard ratio for any cardiovascular event was 4.16 (2.98 to 5.82) when the group prescribed glucocorticoids and with iatrogenic Cushing's syndrome was compared with the group not prescribed glucocorticoids. People who use glucocorticoids and exhibit iatrogenic Cushing's syndrome should be aggressively targeted for early screening and management of cardiovascular risk factors.

Prevalence and nature of cardiovascular disease in methamphetamine-related death: A national study.

PubMed

Darke, Shane; Duflou, Johan; Kaye, Sharlene

2017-10-01

Methamphetamine dependence is a major public health problem. This study examined the nature, and extent, of cardiovascular disease amongst cases of methamphetamine-related death in Australia, 2009-2015. Analysis of 894 cases of methamphetamine-related death with full autopsy reports retrieved from the National Coronial Information System. The mean age was 37.9yrs (range 15-69yrs) and 78.5% were male. A quarter (26.3%) of cases had enlarged hearts and left ventricular hypertrophy was diagnosed in 18.9%. Severe coronary artery disease was present in 19.0%, the left coronary artery being the vessel most frequently stenosed (16.6%). Replacement fibrosis (evidence of earlier ischaemic events) in the heart muscle was observed in 19.8% of cases, and cardiomyopathy was diagnosed in 5.5%. Histological evidence of hypertension was observed in 32.7% of cases. With the exception of cardiomyopathy, equally common amongst both sexes, cardiovascular disease was more common amongst males, and those aged >35yrs. Clinically significant levels of cardiovascular disease were also observed amongst cases where the cause of death was not attributed to cardiovascular disease: cardiomegaly (19.3%), left ventricular hypertrophy (14.6%), severe coronary artery disease (9.4%), replacement fibrosis (14.4%), cardiomyopathy (3.3%). Cardiovascular disease was highly prevalent, despite the relatively young age of cases. With methamphetamine use increasing rapidly in major regions, cardiovascular disease and cardiovascular-related death will likely increase amongst methamphetamine users. Copyright © 2017 Elsevier B.V. All rights reserved.

Looking into the future: Using induced pluripotent stem cells to build two and three dimensional ocular tissue for cell therapy and disease modeling.

PubMed

Song, Min Jae; Bharti, Kapil

2016-05-01

Retinal degenerative diseases are the leading cause of irreversible vision loss in developed countries. In many cases the diseases originate in the homeostatic unit in the back of the eye that contains the retina, retinal pigment epithelium (RPE) and the choriocapillaris. RPE is a central and a critical component of this homeostatic unit, maintaining photoreceptor function and survival on the apical side and choriocapillaris health on the basal side. In diseases like age-related macular degeneration (AMD), it is thought that RPE dysfunctions cause disease-initiating events and as the RPE degenerates photoreceptors begin to die and patients start loosing vision. Patient-specific induced pluripotent stem (iPS) cell-derived RPE provides direct access to a patient's genetics and allow the possibility of identifying the initiating events of RPE-associated degenerative diseases. Furthermore, iPS cell-derived RPE cells are being tested as a potential cell replacement in disease stages with RPE atrophy. In this article we summarize the recent progress in the field of iPS cell-derived RPE "disease modeling" and cell therapies and also discuss the possibilities of developing a model of the entire homeostatic unit to aid in studying disease processes in the future. This article is part of a Special Issue entitled SI: PSC and the brain. Published by Elsevier B.V.

Relationship between history of coronary heart disease at dialysis initiation and onset of events associated with heart disease: a propensity-matched analysis of a prospective cohort study.

PubMed

Inaguma, Daijo; Koide, Shigehisa; Takahashi, Kazuo; Hayashi, Hiroki; Hasegawa, Midori; Yuzawa, Yukio

2017-02-28

Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease (CVD) events, and a number of reports have shown a relationship between CKD and CVD in pre-dialysis or maintenance dialysis patients. However, few studies have reported serial observations during dialysis initiation and maintenance. Therefore, we examined whether the incidence of heart disease events differed between CKD patients with and without a history of coronary heart disease (CHD) at dialysis initiation. The subjects were patients in the 17 centers participating in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis (AICOPP) from October 2011 to September 2013. We excluded nine patients whose outcomes were unknown, as determined by a survey conducted at the end of March 2015. Thus, we enrolled 1,515 subjects into the study. We classified patients into 2 groups according to the history of CHD (i.e., a CHD group and a non-CHD group). Propensity scores (PS) represented the probability of being assigned to a group with or without a history of CHD. Onset of heart disease events and associated mortality and all-cause mortality were compared in PS-matched patients by using the log-rank test for Kaplan-Meier curves. Factors contributing to heart disease events were examined using stepwise multivariate Cox proportional hazards analysis. There were 254 patients in each group after PS-matching. During observation, heart disease events occurred in 85 patients (33.5%) in the CHD group and 48 (18.9%) patients in the non-CHD group. The incidence was significantly higher in the CHD group (p < 0.0001). The CHD group was associated with higher incidence of heart disease events (vs. the non-CHD group, hazard ratio = 1.750, 95% confidence interval = 1.160-2.639). In addition, comorbidities such as diabetes mellitus, low body mass index, and low serum high-density lipoprotein cholesterol were associated with higher incidence of events. History of CHD at dialysis initiation was associated with a higher incidence of heart disease events and mortality and all-cause mortality. UMIN 000007096 . Registered 18 January 2012.

The dyspnea-anxiety-dyspnea cycle--COPD patients' stories of breathlessness: "It's scary /when you can't breathe".

PubMed

Bailey, Patricia H

2004-07-01

Dyspnea, the major symptom associated with acute exacerbation events of chronic obstructive pulmonary disease (COPD), is a subjective experience. Extensive research has been done on the pathophysiology and affective components of dyspnea; however, the precise physical mechanism of breathlessness remains elusive. One purpose of this narrative research was to explore the affective component of dyspnea/anxiety as described by patients living with COPD characterized by acute illness events. Ten patient-family units participated in interviews during an acute episode of the patient's lung disease. They described their understanding of acute dyspnea as an experience inextricably related to anxiety and emotional functioning. Their stories suggest that given the absence of clear objective measures of illness severity, patient-reported anxiety might provide an important marker during acute exacerbation events. Health care providers need to recognize anxiety as an important and potentially measurable sign of invisible dyspnea for end-stage patients with COPD in acute respiratory distress.

Extreme brain events: Higher-order statistics of brain resting activity and its relation with structural connectivity

NASA Astrophysics Data System (ADS)

Amor, T. A.; Russo, R.; Diez, I.; Bharath, P.; Zirovich, M.; Stramaglia, S.; Cortes, J. M.; de Arcangelis, L.; Chialvo, D. R.

2015-09-01

The brain exhibits a wide variety of spatiotemporal patterns of neuronal activity recorded using functional magnetic resonance imaging as the so-called blood-oxygenated-level-dependent (BOLD) signal. An active area of work includes efforts to best describe the plethora of these patterns evolving continuously in the brain. Here we explore the third-moment statistics of the brain BOLD signals in the resting state as a proxy to capture extreme BOLD events. We find that the brain signal exhibits typically nonzero skewness, with positive values for cortical regions and negative values for subcortical regions. Furthermore, the combined analysis of structural and functional connectivity demonstrates that relatively more connected regions exhibit activity with high negative skewness. Overall, these results highlight the relevance of recent results emphasizing that the spatiotemporal location of the relatively large-amplitude events in the BOLD time series contains relevant information to reproduce a number of features of the brain dynamics during resting state in health and disease.

Educational attainment has a limited impact on disease management outcomes in heart failure.

PubMed

Smith, Brad; Forkner, Emma; Krasuski, Richard A; Galbreath, Autumn Dawn; Freeman, Gregory L

2006-06-01

The objective of this study was to assess whether educational attainment moderates outcomes in the intervention group in a trial of disease management in heart failure (HF). Data were collected from a sample of 654 patients enrolled in the disease management arm of a community- based study of HF patients. The full sample was used to analyze two primary outcomes- all-cause mortality and cardiac event-free survival. Two other primary outcomes- rates of HF-related emergency department (ED) visits and inpatient admissions-and secondary outcomes (patient self-confidence in managing HF symptoms and daily dietary sodium intake in milligrams) were analyzed in a smaller sample of 602 patients who completed at least 6 months of disease management. One-way analysis of variance and chi (2) tests were used to assess differences in baseline demographic and clinical characteristics. Survival analyses were conducted with proportional hazards regression, while negative binomial regression was used to assess educational differences in ED usage and inpatient admissions. Repeated measures analysis of variance models were used to assess whether secondary outcomes differed across educational strata and/or over time. All outcome analyses were adjusted for confounders. Patients with the least education fared the poorest for all-cause mortality, but education- related differences failed to achieve statistical significance. No education-related differences were observed for cardiac event-free survival, or for the rates of inpatient admission and ED usage. For secondary outcomes, sodium intake differed significantly by education (p = 0.04), with the largest drop (-838 mg/day) observed in the least well-educated group. Confidence increased an approximately equal amount (2.1-3.0 points on a 100-point scale) across all educational strata (p = ns). Low educational attainment may not be a barrier to effective disease management.

Masitinib as an adjunct therapy for mild-to-moderate Alzheimer's disease: a randomised, placebo-controlled phase 2 trial

PubMed Central

2011-01-01

Introduction Neuroinflammation is thought to be important in Alzheimer's disease pathogenesis. Mast cells are a key component of the inflammatory network and participate in the regulation of the blood-brain barrier's permeability. Masitinib, a selective oral tyrosine kinase inhibitor, effectively inhibits the survival, migration and activity of mast cells. As the brain is rich in mast cells, the therapeutic potential of masitinib as an adjunct therapy to standard care was investigated. Methods A randomised, placebo-controlled, phase 2 study was performed in patients with mild-to-moderate Alzheimer's disease, receiving masitinib as an adjunct to cholinesterase inhibitor and/or memantine. Patients were randomly assigned to receive masitinib (n = 26) (starting dose of 3 or 6 mg/kg/day) or placebo (n = 8), administered twice daily for 24 weeks. The primary endpoint was change from baseline in the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog) to assess cognitive function and the related patient response rate. Results The rate of clinically relevant cognitive decline according to the ADAS-Cog response (increase >4 points) after 12 and 24 weeks was significantly lower with masitinib adjunctive treatment compared with placebo (6% vs. 50% for both time points; P = 0.040 and P = 0.046, respectively). Moreover, whilst the placebo treatment arm showed worsening mean ADAS-Cog, Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory, and Mini-Mental State Examination scores, the masitinib treatment arm reported improvements, with statistical significance between treatment arms at week 12 and/or week 24 (respectively, P = 0.016 and 0.030; P = 0.035 and 0.128; and P = 0.047 and 0.031). The mean treatment effect according to change in ADAS-Cog score relative to baseline at weeks 12 and 24 was 6.8 and 7.6, respectively. Adverse events occurred more frequently with masitinib treatment (65% vs. 38% of patients); however, the majority of events were of mild or moderate intensity and transitory. Severe adverse events occurred at a similar frequency in the masitinib and placebo arms (15% vs. 13% of patients, respectively). Masitinib-associated events included gastrointestinal disorders, oedema, and rash. Conclusions Masitinib administered as add-on therapy to standard care during 24 weeks was associated with slower cognitive decline in Alzheimer's disease, with an acceptable tolerance profile. Masitinib may therefore represent an innovative avenue of treatment in Alzheimer's disease. This trial provides evidence that may support a larger placebo-controlled investigation. Trial registration Clinicaltrials.gov NCT00976118 PMID:21504563

Road traffic noise, air pollution components and cardiovascular events.

PubMed

de Kluizenaar, Yvonne; van Lenthe, Frank J; Visschedijk, Antoon J H; Zandveld, Peter Y J; Miedema, Henk M E; Mackenbach, Johan P

2013-01-01

Traffic noise and air pollution have been associated with cardiovascular health effects. Until date, only a limited amount of prospective epidemiological studies is available on long-term effects of road traffic noise and combustion related air pollution. This study investigates the relationship between road traffic noise and air pollution and hospital admissions for ischemic heart disease (IHD: International Classification of Diseases (ICD9) 410-414) or cerebrovascular disease (cerebrovascular event [CVE]: ICD9 430-438). We linked baseline questionnaire data to 13 years of follow-up on hospital admissions and road traffic noise and air pollution exposure, for a large random sample (N = 18,213) of inhabitants of the Eindhoven region, Netherlands. Subjects with cardiovascular event during follow-up on average had higher road traffic noise day, evening, night level (L den) and air pollution exposure at the home. After adjustment for confounders (age, sex, body mass index, smoking, education, exercise, marital status, alcohol use, work situation, financial difficulties), increased exposure did not exert a significant increased risk of hospital admission for IHD or cerebrovascular disease. Relative risks (RRs) for a 5 (th) to 95 (th) percentile interval increase were 1.03 (0.88-1.20) for L den; 1.04 (0.90-1.21) for particulate matter (PM 10 ); 1.05 (0.91-1.20) for elemental carbon (EC); and 1.12 (096-1.32) for nitrogen dioxide (NO 2 ) in the full model. While the risk estimate seemed highest for NO 2 , for a 5 (th) to 95 (th) percentile interval increase, expressed as RRs per 1 μg/m 3 increases, hazard ratios seemed highest for EC (RR 1.04 [0.92-1.18]). In the subgroup of study participants with a history of cardiovascular disease, RR estimates seemed highest for noise exposure (1.19 [0.87-1.64] for L den); in the subgroup of elderly RR seemed highest for air pollution exposure (RR 1.24 [0.93-1.66] for NO 2 ).

Surveillance of Australian workplace Based Respiratory Events (SABRE) in New South Wales.

PubMed

Hannaford-Turner, K; Elder, D; Sim, M R; Abramson, M J; Johnson, A R; Yates, D H

2010-08-01

The Surveillance of Australian workplace Based Respiratory Events (SABRE) New South Wales (NSW) scheme is a voluntary notification scheme established to determine the incidence of occupational lung diseases in NSW Australia. Data presented in this paper summarize the last 7 years of reporting to SABRE (June 2001 to December 2008). Every 2 months, participating occupational physicians, respiratory physicians and general practitioners (accredited by the NSW WorkCover Authority) reported new cases of occupational lung disease seen in their practices. Data collected include gender, age, causal agent and the occupations and industries believed responsible. Estimated incidence was calculated for each disease. Three thousand six hundred and fifty-four cases were notified to the scheme, consisting of 3856 diagnoses. Most of the cases were males (76%). Pleural plaques [1218 (28%)] were the most frequently reported condition, followed by mesothelioma [919 (24%)]. Silicosis [90 (2%)] and occupational asthma [OA; 89 (2%)] were the most frequently reported non-asbestos-related diseases. Estimated rates for mesothelioma, diffuse pleural thickening (DPT) and OA were 83, 83 and 5 cases per million employed males per year, respectively. Trades such as carpenters and electricians associated with the building industry, electricity supply and asbestos product manufacture were the most common occupations and industries reported. Asbestos-related diseases are the most frequently reported conditions to SABRE NSW. The very low incidence of OA for NSW most likely reflects under-diagnosis as well as under-reporting. Occupational lung disease is still occurring in NSW despite current preventative strategies. The SABRE scheme currently provides the only available information in this area.

Clinical roundtable monograph. New alternatives in CLL therapy: managing adverse events.

PubMed

Chanan-Khan, Asher; Kipps, Thomas; Stilgenbauer, Stephan

2010-08-01

Chronic lymphocytic leukemia (CLL) is a B-cell leukemia mainly affecting older adults. Historically, CLL has been regarded as an incurable disease, and treatment has been confined to cytotoxic chemotherapy regimens. However, prognosis for patients treated with these agents remained poor, prompting the development of new, targeted agents. The introduction of rituximab, a CD20-targeted monoclonal antibody, revolutionized the treatment for this disease. Rituximab in combination with fludarabine improved response rates and length of progression-free survival. The success of rituximab in this setting has prompted the development of many more investigational agents for CLL, including other antibody agents. However, as with any medication, the potential benefit achieved with CLL therapies is mitigated by the safety risk for the patient. These agents have been associated with adverse events such as immunosuppression, reactivation of cytomegalovirus, and infusion-related reactions that can occur with antibody administration. Adverse events can greatly affect the patient’s quality of life and ability to tolerate therapy. Management of adverse events is a critical component of the overall treatment strategy for CLL, particularly in elderly patients. In this clinical roundtable monograph, 3 expert physicians discuss the latest clinical studies evaluating the treatment of CLL, focusing on the adverse events associated with each agent and the potential interventions that can be used to manage their occurrence.

Agalsidase-beta therapy for advanced Fabry disease: a randomized trial.

PubMed

Banikazemi, Maryam; Bultas, Jan; Waldek, Stephen; Wilcox, William R; Whitley, Chester B; McDonald, Marie; Finkel, Richard; Packman, Seymour; Bichet, Daniel G; Warnock, David G; Desnick, Robert J

2007-01-16

Fabry disease (alpha-galactosidase A deficiency) is a rare, X-linked lysosomal storage disorder that can cause early death from renal, cardiac, and cerebrovascular involvement. To see whether agalsidase beta delays the onset of a composite clinical outcome of renal, cardiovascular, and cerebrovascular events and death in patients with advanced Fabry disease. Randomized (2:1 treatment-to-placebo randomization), double-blind, placebo-controlled trial. 41 referral centers in 9 countries. 82 adults with mild to moderate kidney disease; 74 of whom were protocol-adherent. Intravenous infusion of agalsidase beta (1 mg per kg of body weight) or placebo every 2 weeks for up to 35 months (median, 18.5 months). The primary end point was the time to first clinical event (renal, cardiac, or cerebrovascular event or death). Six patients withdrew before reaching an end point: 3 to receive commercial therapy and 3 due to positive or inconclusive serum IgE or skin test results. Three patients assigned to agalsidase beta elected to transition to open-label treatment before reaching an end point. Thirteen (42%) of the 31 patients in the placebo group and 14 (27%) of the 51 patients in the agalsidase-beta group experienced clinical events. Primary intention-to-treat analysis that adjusted for an imbalance in baseline proteinuria showed that, compared with placebo, agalsidase beta delayed the time to first clinical event (hazard ratio, 0.47 [95% CI, 0.21 to 1.03]; P = 0.06). Secondary analyses of protocol-adherent patients showed similar results (hazard ratio, 0.39 [CI, 0.16 to 0.93]; P = 0.034). Ancillary subgroup analyses found larger treatment effects in patients with baseline estimated glomerular filtration rates greater than 55 mL/min per 1.73 m2 (hazard ratio, 0.19 [CI, 0.05 to 0.82]; P = 0.025) compared with 55 mL/min per 1.73 m2 or less (hazard ratio, 0.85 [CI, 0.32 to 2.3]; P = 0.75) (formal test for interaction, P = 0.09). Most treatment-related adverse events were mild or moderate infusion-associated reactions, reported by 55% of patients in the agalsidase-beta group and 23% of patients in the placebo group. The study sample was small. Only one third of the patients experienced clinical events, and some patients withdrew before experiencing any event. Agalsidase-beta therapy slowed progression to the composite clinical outcome of renal, cardiac, and cerebrovascular complications and death compared with placebo in patients with advanced Fabry disease. Therapeutic intervention before irreversible organ damage may provide greater clinical benefit.

Drug safety data mining with a tree-based scan statistic.

PubMed

Kulldorff, Martin; Dashevsky, Inna; Avery, Taliser R; Chan, Arnold K; Davis, Robert L; Graham, David; Platt, Richard; Andrade, Susan E; Boudreau, Denise; Gunter, Margaret J; Herrinton, Lisa J; Pawloski, Pamala A; Raebel, Marsha A; Roblin, Douglas; Brown, Jeffrey S

2013-05-01

In post-marketing drug safety surveillance, data mining can potentially detect rare but serious adverse events. Assessing an entire collection of drug-event pairs is traditionally performed on a predefined level of granularity. It is unknown a priori whether a drug causes a very specific or a set of related adverse events, such as mitral valve disorders, all valve disorders, or different types of heart disease. This methodological paper evaluates the tree-based scan statistic data mining method to enhance drug safety surveillance. We use a three-million-member electronic health records database from the HMO Research Network. Using the tree-based scan statistic, we assess the safety of selected antifungal and diabetes drugs, simultaneously evaluating overlapping diagnosis groups at different granularity levels, adjusting for multiple testing. Expected and observed adverse event counts were adjusted for age, sex, and health plan, producing a log likelihood ratio test statistic. Out of 732 evaluated disease groupings, 24 were statistically significant, divided among 10 non-overlapping disease categories. Five of the 10 signals are known adverse effects, four are likely due to confounding by indication, while one may warrant further investigation. The tree-based scan statistic can be successfully applied as a data mining tool in drug safety surveillance using observational data. The total number of statistical signals was modest and does not imply a causal relationship. Rather, data mining results should be used to generate candidate drug-event pairs for rigorous epidemiological studies to evaluate the individual and comparative safety profiles of drugs. Copyright © 2013 John Wiley & Sons, Ltd.

Public Health Surveillance Strategies for Mass Gatherings: Super Bowl XLIX and Related Events, Maricopa County, Arizona, 2015.

PubMed

Ayala, Aurimar; Berisha, Vjollca; Goodin, Kate; Pogreba-Brown, Kristen; Levy, Craig; McKinney, Benita; Koski, Lia; Imholte, Sara

2016-01-01

Super Bowl XLIX took place on February 1, 2015, in Glendale, Arizona. In preparation for this event and associated activities, the Maricopa County Department of Public Health (MCDPH) developed methods for enhanced surveillance, situational awareness, and early detection of public health emergencies. Surveillance strategies implemented from January 22 to February 6, 2015, included enhanced surveillance alerts; animal disease surveillance; review of NFL clinic visits; syndromic surveillance for emergency room visits, urgent care facilities, and hotels; real-time onsite syndromic surveillance; all-hazards mortality surveillance; emergency medical services surveillance, review of poison control center reports; media surveillance; and aberration detection algorithms for notifiable diseases. Surveillance results included increased influenzalike illness activity reported from urgent care centers and a few influenza cases reported in the NFL clinic. A cyanide single event exposure was investigated and determined not to be a public health threat. Real-time field syndromic surveillance documented minor injuries at all events and sporadic cases of gastrointestinal and neurological (mostly headaches) disease. Animal surveillance reports included a cat suspected of carrying plague and tularemia and an investigation of highly pathogenic avian influenza in a backyard chicken flock. Laboratory results in both instances were negative. Aberration detection and syndromic surveillance detected an increase in measles reports associated with a Disneyland exposure, and syndromic surveillance was used successfully during this investigation. Coordinated enhanced epidemiologic surveillance during Super Bowl XLIX increased the response capacity and preparedness of MCDPH to make informed decisions and take public health actions in a timely manner during these mass gathering events.

Objectives and methodology of BIOBADASER phase iii.

PubMed

Sanchez-Piedra, Carlos; Hernández Miguel, M Victoria; Manero, Javier; Roselló, Rosa; Sánchez-Costa, Jesús Tomás; Rodríguez-Lozano, Carlos; Campos, Cristina; Cuende, Eduardo; Fernández-Lopez, Jesús Carlos; Bustabad, Sagrario; Martín Domenech, Raquel; Pérez-Pampín, Eva; Del Pino-Montes, Javier; Millan-Arcineas, Ana Milena; Díaz-González, Federico; Gómez-Reino, Juan Jesús

2017-09-18

Describe the objectives, methods and results of the first year of the new version of the Spanish registry of adverse events involving biological therapies and synthetic drugs with an identifiable target in rheumatic diseases (BIOBADASER III). Multicenter prospective registry of patients with rheumatic inflammatory diseases being treated with biological drugs or synthetic drugs with an identifiable target in rheumatology departments in Spain. The main objective of BIOBADASER Phase III is the registry and analysis of adverse events; moreover, a secondary objective was added consisting of assessing the effectiveness by means of the registry of activity indexes. Patients in the registry are evaluated at least once every year and whenever they experience an adverse event or a change in treatment. The collection of data for phase iii began on 17 December 2015. During the first year, 35 centers participated. The number of patients included in this new phase in December 2016 was 2,664. The mean age was 53.7 years and the median duration of treatment was 8.1 years. In all, 40.4% of the patients were diagnosed with rheumatoid arthritis. The most frequent adverse events were infections and infestations. BIOBADASER Phase III has been launched to adapt to a changing pharmacological environment, with the introduction of biosimilars and small molecules in the treatment of rheumatic diseases. This new stage is adapted to the changes in the reporting of adverse events and now includes information related to activity scores. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease.

PubMed

Bowman, Louise; Hopewell, Jemma C; Chen, Fang; Wallendszus, Karl; Stevens, William; Collins, Rory; Wiviott, Stephen D; Cannon, Christopher P; Braunwald, Eugene; Sammons, Emily; Landray, Martin J

2017-09-28

Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .).

Estimates of Commercial Population at High Risk for Cardiovascular Events: Impact of Aggressive Cholesterol Reduction

PubMed Central

Fitch, Kathryn; Goldberg, Sara W.; Iwasaki, Kosuke; Pyenson, Bruce S.; Kuznik, Andreas; Solomon, Henry A.

2009-01-01

Objectives To model the financial and health outcomes impact of intensive statin therapy compared with usual care in a high-risk working-age population (actively employed, commercially insured health plan members and their adult dependents). The target population consists of working-age people who are considered high-risk for cardiovascular disease events because of a history of coronary heart disease. Study Design Three-year event forecast for a sample population generated from the National Health and Nutrition Examination Survey data. Methods Using Framingham risk scoring system, the probability of myocardial infarction or stroke events was calculated for a representative sample population, ages 35 to 69 years, of people at high risk for cardiovascular disease, with a history of coronary heart disease. The probability of events for each individual was used to project the number of events expected to be generated for this population. Reductions in cardiovascular and stroke events reported in clinical trials with aggressive statin therapy were applied to these cohorts. We used medical claims data to model the cohorts' event costs. All results are adjusted to reflect the demographics of a typical working-age population. Results The high-risk cohort (those with coronary heart disease) comprises 4% of the 35- to 69-year-old commercially insured population but generates 22% of the risk for coronary heart disease and stroke. Reduced event rates associated with intensive statin therapy yielded a $58 mean medical cost reduction per treated person per month; a typical payer cost for a 30-day supply of intensive statin therapy is approximately $57. Conclusions Aggressive low-density lipoprotein cholesterol–lowering therapy for working-age people at high risk for cardiovascular events and with a history of heart disease appears to have a significant potential to reduce the rate of clinical events and is cost-neutral for payers. PMID:25126293

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome.

PubMed

Machiela, Mitchell J; Zhou, Weiyin; Karlins, Eric; Sampson, Joshua N; Freedman, Neal D; Yang, Qi; Hicks, Belynda; Dagnall, Casey; Hautman, Christopher; Jacobs, Kevin B; Abnet, Christian C; Aldrich, Melinda C; Amos, Christopher; Amundadottir, Laufey T; Arslan, Alan A; Beane-Freeman, Laura E; Berndt, Sonja I; Black, Amanda; Blot, William J; Bock, Cathryn H; Bracci, Paige M; Brinton, Louise A; Bueno-de-Mesquita, H Bas; Burdett, Laurie; Buring, Julie E; Butler, Mary A; Canzian, Federico; Carreón, Tania; Chaffee, Kari G; Chang, I-Shou; Chatterjee, Nilanjan; Chen, Chu; Chen, Constance; Chen, Kexin; Chung, Charles C; Cook, Linda S; Crous Bou, Marta; Cullen, Michael; Davis, Faith G; De Vivo, Immaculata; Ding, Ti; Doherty, Jennifer; Duell, Eric J; Epstein, Caroline G; Fan, Jin-Hu; Figueroa, Jonine D; Fraumeni, Joseph F; Friedenreich, Christine M; Fuchs, Charles S; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M; Garcia-Closas, Montserrat; Gaudet, Mia M; Gaziano, J Michael; Giles, Graham G; Gillanders, Elizabeth M; Giovannucci, Edward L; Goldin, Lynn; Goldstein, Alisa M; Haiman, Christopher A; Hallmans, Goran; Hankinson, Susan E; Harris, Curtis C; Henriksson, Roger; Holly, Elizabeth A; Hong, Yun-Chul; Hoover, Robert N; Hsiung, Chao A; Hu, Nan; Hu, Wei; Hunter, David J; Hutchinson, Amy; Jenab, Mazda; Johansen, Christoffer; Khaw, Kay-Tee; Kim, Hee Nam; Kim, Yeul Hong; Kim, Young Tae; Klein, Alison P; Klein, Robert; Koh, Woon-Puay; Kolonel, Laurence N; Kooperberg, Charles; Kraft, Peter; Krogh, Vittorio; Kurtz, Robert C; LaCroix, Andrea; Lan, Qing; Landi, Maria Teresa; Marchand, Loic Le; Li, Donghui; Liang, Xiaolin; Liao, Linda M; Lin, Dongxin; Liu, Jianjun; Lissowska, Jolanta; Lu, Lingeng; Magliocco, Anthony M; Malats, Nuria; Matsuo, Keitaro; McNeill, Lorna H; McWilliams, Robert R; Melin, Beatrice S; Mirabello, Lisa; Moore, Lee; Olson, Sara H; Orlow, Irene; Park, Jae Yong; Patiño-Garcia, Ana; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M; Pooler, Loreall; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Purdue, Mark P; Qiao, You-Lin; Rajaraman, Preetha; Real, Francisco X; Riboli, Elio; Risch, Harvey A; Rodriguez-Santiago, Benjamin; Ruder, Avima M; Savage, Sharon A; Schumacher, Fredrick; Schwartz, Ann G; Schwartz, Kendra L; Seow, Adeline; Wendy Setiawan, Veronica; Severi, Gianluca; Shen, Hongbing; Sheng, Xin; Shin, Min-Ho; Shu, Xiao-Ou; Silverman, Debra T; Spitz, Margaret R; Stevens, Victoria L; Stolzenberg-Solomon, Rachael; Stram, Daniel; Tang, Ze-Zhong; Taylor, Philip R; Teras, Lauren R; Tobias, Geoffrey S; Van Den Berg, David; Visvanathan, Kala; Wacholder, Sholom; Wang, Jiu-Cun; Wang, Zhaoming; Wentzensen, Nicolas; Wheeler, William; White, Emily; Wiencke, John K; Wolpin, Brian M; Wong, Maria Pik; Wu, Chen; Wu, Tangchun; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S; Xia, Lucy; Yang, Hannah P; Yang, Pan-Chyr; Yu, Kai; Zanetti, Krista A; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Zhou, Baosen; Ziegler, Regina G; Perez-Jurado, Luis A; Caporaso, Neil E; Rothman, Nathaniel; Tucker, Margaret; Dean, Michael C; Yeager, Meredith; Chanock, Stephen J

2016-06-13

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

PubMed Central

Machiela, Mitchell J.; Zhou, Weiyin; Karlins, Eric; Sampson, Joshua N.; Freedman, Neal D.; Yang, Qi; Hicks, Belynda; Dagnall, Casey; Hautman, Christopher; Jacobs, Kevin B.; Abnet, Christian C.; Aldrich, Melinda C.; Amos, Christopher; Amundadottir, Laufey T.; Arslan, Alan A.; Beane-Freeman, Laura E.; Berndt, Sonja I.; Black, Amanda; Blot, William J.; Bock, Cathryn H.; Bracci, Paige M.; Brinton, Louise A.; Bueno-de-Mesquita, H Bas; Burdett, Laurie; Buring, Julie E.; Butler, Mary A.; Canzian, Federico; Carreón, Tania; Chaffee, Kari G.; Chang, I-Shou; Chatterjee, Nilanjan; Chen, Chu; Chen, Constance; Chen, Kexin; Chung, Charles C.; Cook, Linda S.; Crous Bou, Marta; Cullen, Michael; Davis, Faith G.; De Vivo, Immaculata; Ding, Ti; Doherty, Jennifer; Duell, Eric J.; Epstein, Caroline G.; Fan, Jin-Hu; Figueroa, Jonine D.; Fraumeni, Joseph F.; Friedenreich, Christine M.; Fuchs, Charles S.; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M.; Garcia-Closas, Montserrat; Gaudet, Mia M.; Gaziano, J. Michael; Giles, Graham G.; Gillanders, Elizabeth M.; Giovannucci, Edward L.; Goldin, Lynn; Goldstein, Alisa M.; Haiman, Christopher A.; Hallmans, Goran; Hankinson, Susan E.; Harris, Curtis C.; Henriksson, Roger; Holly, Elizabeth A.; Hong, Yun-Chul; Hoover, Robert N.; Hsiung, Chao A.; Hu, Nan; Hu, Wei; Hunter, David J.; Hutchinson, Amy; Jenab, Mazda; Johansen, Christoffer; Khaw, Kay-Tee; Kim, Hee Nam; Kim, Yeul Hong; Kim, Young Tae; Klein, Alison P.; Klein, Robert; Koh, Woon-Puay; Kolonel, Laurence N.; Kooperberg, Charles; Kraft, Peter; Krogh, Vittorio; Kurtz, Robert C.; LaCroix, Andrea; Lan, Qing; Landi, Maria Teresa; Marchand, Loic Le; Li, Donghui; Liang, Xiaolin; Liao, Linda M.; Lin, Dongxin; Liu, Jianjun; Lissowska, Jolanta; Lu, Lingeng; Magliocco, Anthony M.; Malats, Nuria; Matsuo, Keitaro; McNeill, Lorna H.; McWilliams, Robert R.; Melin, Beatrice S.; Mirabello, Lisa; Moore, Lee; Olson, Sara H.; Orlow, Irene; Park, Jae Yong; Patiño-Garcia, Ana; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M.; Pooler, Loreall; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Purdue, Mark P.; Qiao, You-Lin; Rajaraman, Preetha; Real, Francisco X.; Riboli, Elio; Risch, Harvey A.; Rodriguez-Santiago, Benjamin; Ruder, Avima M.; Savage, Sharon A.; Schumacher, Fredrick; Schwartz, Ann G.; Schwartz, Kendra L.; Seow, Adeline; Wendy Setiawan, Veronica; Severi, Gianluca; Shen, Hongbing; Sheng, Xin; Shin, Min-Ho; Shu, Xiao-Ou; Silverman, Debra T.; Spitz, Margaret R.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael; Stram, Daniel; Tang, Ze-Zhong; Taylor, Philip R.; Teras, Lauren R.; Tobias, Geoffrey S.; Van Den Berg, David; Visvanathan, Kala; Wacholder, Sholom; Wang, Jiu-Cun; Wang, Zhaoming; Wentzensen, Nicolas; Wheeler, William; White, Emily; Wiencke, John K.; Wolpin, Brian M.; Wong, Maria Pik; Wu, Chen; Wu, Tangchun; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S.; Xia, Lucy; Yang, Hannah P.; Yang, Pan-Chyr; Yu, Kai; Zanetti, Krista A.; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Zhou, Baosen; Ziegler, Regina G.; Perez-Jurado, Luis A.; Caporaso, Neil E.; Rothman, Nathaniel; Tucker, Margaret; Dean, Michael C.; Yeager, Meredith; Chanock, Stephen J.

2016-01-01

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases. PMID:27291797

Switch to agalsidase alfa after shortage of agalsidase beta in Fabry disease: a systematic review and meta-analysis of the literature.

PubMed

Pisani, Antonio; Bruzzese, Dario; Sabbatini, Massimo; Spinelli, Letizia; Imbriaco, Massimo; Riccio, Eleonora

2017-03-01

In 2009, the agalsidase beta shortage resulted in switching to agalsidase alfa treatment for many Fabry disease patients, offering the unique opportunity to compare the effects of the two drugs. Because single studies describing effects of switching on the disease course are limited and inconclusive, we performed a systematic review and meta-analysis of existing data. Relevant studies were identified in the PubMed, Cochrane, ISI Web, and SCOPUS databases from July 2009 to September 2015. The following parameters were analyzed: clinical events, changes in organ function or structure, disease-related symptoms, lyso-Gb3 plasma levels, and adverse effects. The nine studies (217 patients) included in our systematic review showed only marginal differences in most of the evaluated parameters. Seven of these studies were included in the meta-analysis (176 patients). The pooled incidence rate of major adverse events was reported for five studies (150 patients) and was equal to 0.04 events per person-year. No significant change was observed after the shift in glomerular filtration rate, whereas left ventricular mass index, left ventricular posterior wall dimension, and ejection fraction were significantly reduced over time. Our data showed that the switch to agalsidase alfa was well tolerated and associated with stable clinical conditions.Genet Med 19 3, 275-282.

Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review.

PubMed

Warren-Gash, Charlotte; Smeeth, Liam; Hayward, Andrew C

2009-10-01

Cardiac complications of influenza infection, such as myocarditis, are well recognised, but the role of influenza as a trigger of acute myocardial infarction is less clear. We did a systematic review of the evidence that influenza (including influenza-like illness and acute respiratory infection) triggers acute myocardial infarction or cardiovascular death. We examined the effectiveness of influenza vaccines at protecting against cardiac events and did a meta-analysis of data from randomised controlled trials. 42 publications describing 39 studies were identified. Many observational studies in different settings with a range of methods reported consistent associations between influenza and acute myocardial infarction. There was weaker evidence of an association with cardiovascular death. Two small randomised trials assessed the protection provided by influenza vaccine against cardiac events in people with existing cardiovascular disease. Whereas one trial found that influenza vaccination gave significant protection against cardiovascular death, the other trial was inconclusive. A pooled estimate from a random-effects model suggests a protective, though non-significant, effect (relative risk 0.51, 95% CI 0.15-1.76). We believe influenza vaccination should be encouraged wherever indicated, especially in people with existing cardiovascular disease, among whom there is often suboptimum vaccine uptake. Further evidence is needed on the effectiveness of influenza vaccines to reduce the risk of cardiac events in people without established vascular disease.

Clinical predictors of colectomy in patients with ulcerative colitis: systematic review and meta-analysis of cohort studies.

PubMed

Dias, Cláudia Camila; Rodrigues, Pedro Pereira; da Costa-Pereira, Altamiro; Magro, Fernando

2015-02-01

Colectomy is a major event that may significantly affect the outcome of ulcerative colitis (UC) in terms of both quality of life and mortality. This paper aims to identify clinical prognostic factors that may be significantly associated with this event. PubMed, ISI Web of Knowledge and Scopus were searched to identify studies investigating the association between clinical factors in adult patients with UC and studied events.The clinical factors evaluated in this meta-analysis were gender, smoking habits, disease extent,use of corticosteroids, and episodes of hospitalization. Of the 3753 initially selected papers, 20 were included. The analysis showed a significantly lower risk of colectomy for female patients (odds ratio [OR] 0.78 [95% CI 0.68, 0.90]) and for smoking patients (OR 0.55 [0.33, 0.91]), and a higher risk for patients with extensive disease (OR 3.68 [2.39,5.69]), for patients who took corticosteroids at least once (OR 2.10 [1.05, 4.22]), and for patients who were hospitalized (OR 4.13 [3.23, 5.27]). Gender, smoking habits, disease extent, need for corticosteroids, and hospitalization were all significantly associated with UC prognosis. These results may clarify the relative influences of these and other prognostic factors in the natural course of the disease and therefore help improve the management approach, thus improving the follow-up of patients.

State transition model: vorapaxar added to standard antiplatelet therapy to prevent thrombosis post myocardial infarction or peripheral artery disease.

PubMed

Du, Mark; Chase, Monica; Oguz, Mustafa; Davies, Glenn

2017-09-01

To evaluate long-term health benefits and risks of adding vorapaxar (VOR) to the standard care antiplatelet therapy (SC) of aspirin and/or clopidogrel, among a population with a recent myocardial infarction (MI) and/or peripheral artery disease (PAD). In a state-transition model, patients transition between health states (event-free, recurrent MI, stroke, death), while at risk of experiencing non-transition-related revascularization and non-fatal bleeding events. Risk equations developed from the TRA 2°P-TIMI 50 trial's patient-level data were used to predict cardiovascular (CV) outcomes over longer time horizons. Additional sources, including trials and US-based observational studies, informed the inputs for short-term CV risk, non-CV death, and health-related quality of life. Survival and quality-adjusted life-years (QALYs) were estimated over a lifetime horizon, discounted at 3% per year. Within a cohort of 7361 patients with recent MI and/or PAD, VOR + SC relative to SC alone yielded 176 fewer CV events (MIs, strokes, or CV deaths), but 27 more major bleeding events. VOR + SC was associated with increased life expectancy and health benefits (19.93 undiscounted life-years [LYs], 9.57 discounted QALYs vs. 19.61 undiscounted LYs, 9.41 discounted QALYs). The results were most sensitive to scenarios varying time of vorapaxar initiation, and the assumptions in the 90 day period post-MI. Additional analyses showed that add-on vorapaxar provides consistent incremental benefits in high-risk subgroups. This study contributes to the growing literature on secondary prevention add-on therapy, as results from these modeling analyses suggest that adding vorapaxar to SC for patients at high atherothrombotic risk can provide long-term health benefits.

Body-Weight Fluctuations and Outcomes in Coronary Disease.

PubMed

Bangalore, Sripal; Fayyad, Rana; Laskey, Rachel; DeMicco, David A; Messerli, Franz H; Waters, David D

2017-04-06

Body-weight fluctuation is a risk factor for death and coronary events in patients without cardiovascular disease. It is not known whether variability in body weight affects outcomes in patients with coronary artery disease. We determined intraindividual fluctuations in body weight from baseline weight and follow-up visits and performed a post hoc analysis of the Treating to New Targets trial, which involved assessment of the efficacy and safety of lowering low-density lipoprotein cholesterol levels with atorvastatin. The primary outcome was any coronary event (a composite of death from coronary heart disease, nonfatal myocardial infarction, resuscitated cardiac arrest, revascularization, or angina). Secondary outcomes were any cardiovascular event (a composite of any coronary event, a cerebrovascular event, peripheral vascular disease, or heart failure), death, myocardial infarction, or stroke. Among 9509 participants, after adjustment for risk factors, baseline lipid levels, mean body weight, and weight change, each increase of 1 SD in body-weight variability (measured according to average successive variability and used as a time-dependent covariate) was associated with an increase in the risk of any coronary event (2091 events; hazard ratio, 1.04; 95% confidence interval [CI], 1.01 to 1.07; P=0.01), any cardiovascular event (2727 events; hazard ratio, 1.04; 95% CI, 1.02 to 1.07; P<0.001), and death (487 events; hazard ratio,1.09; 95% CI, 1.07 to 1.12; P<0.001). Among patients in the quintile with the highest variation in body weight, the risk of a coronary event was 64% higher, the risk of a cardiovascular event 85% higher, death 124% higher, myocardial infarction 117% higher, and stroke 136% higher than it was among those in the quintile with the lowest variation in body weight in adjusted models. Among participants with coronary artery disease, fluctuation in body weight was associated with higher mortality and a higher rate of cardiovascular events independent of traditional cardiovascular risk factors. (Funded by Pfizer; ClinicalTrials.gov number, NCT00327691 .).

Personal experiences of the psoriasis and its relation to the stressful life events.

PubMed

Sarilar, Marijana; Koić, Elvira; Dervinja, Fahri

2011-09-01

Psoriasis is a disease with a profound impact on the psychological and social aspects of the patient, particularly because of its visibility. Quality of life is impaired and different mental health disorders like depression, anxiety, alcoholism, posttraumatic stress disorder (PTSD) are found among persons suffering from psoriasis. Studies have shown the influence of stressful life events on onset, exacerbation and relapse of psoriasis. Rare studies explored prevalence of psoriasis during war times and relations between psoriasis and war provoked PTSD. Psoriasis is a disease with multiple possible causes and additional caution is necessary among medical professional to recognize all contributing factors. This report describes a case of a person whose first episode of psoriasis appeared six months after engaging in combat activities. He is diagnosed with psoriasis vulgaris, psoriatic arthritis and permanent personality changes after the traumatic experiences caused by war participation. His occupational history is burdened with additional causational factors; work with heavy metals and metal dusts. Cumulative effects of different aetiological factors can contribute to psoriasis with intensive trauma induced stressors serving as a trigger. His medical history indicates cognitive difficulties typical for early dementia which makes this case even more interesting. Research results suggesting common aetiology of psoriasis, autoimmune diseases and neurodegenerative diseases, indicate a need, as in the case of our patient, for multidisciplinary approach to studying aetiology of psoriasis.

A multicenter randomized controlled evaluation of automated home monitoring and telephonic disease management in patients recently hospitalized for congestive heart failure: the SPAN-CHF II trial.

PubMed

Weintraub, Andrew; Gregory, Douglas; Patel, Ayan R; Levine, Daniel; Venesy, David; Perry, Kathleen; Delano, Christine; Konstam, Marvin A

2010-04-01

We performed a prospective, randomized investigation assessing the incremental effect of automated health monitoring (AHM) technology over and above that of a previously described nurse directed heart failure (HF) disease management program. The AHM system measured and transmitted body weight, blood pressure, and heart rate data as well as subjective patient self-assessments via a standard telephone line to a central server. A total of 188 consented and eligible patients were randomized between intervention and control groups in 1:1 ratio. Subjects randomized to the control arm received the Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) heart failure disease management program. Subjects randomized to the intervention arm received the SPAN-CHF disease management program in conjunction with the AHM system. The primary end point was prespecified as the relative event rate of HF hospitalization between intervention and control groups at 90 days. The relative event rate of HF hospitalization for the intervention group compared with controls was 0.50 (95%CI [0.25-0.99], P = .05). Short-term reductions in the heart failure hospitalization rate were associated with the use of automated home monitoring equipment. Long-term benefits in this model remain to be studied. (c) 2010 Elsevier Inc. All rights reserved.

Ostomy creation with fewer sutures using tissue adhesives (cyanoacrylates) in inflammatory bowel disease: a pilot study.

PubMed

Uchino, M; Ikeuchi, H; Bando, T; Sasaki, H; Chohno, T; Horio, Y; Takesue, Y

2018-03-01

Introduction Fistula formation around the ostomy site is a stoma-related complication often requiring surgical intervention. This complication may be caused by sutures or may develop as a complication of inflammatory bowel disease. Before conducting a clinical trial, we set out to investigate the safety of ostomy creation with fewer sutures using tissue adhesives in this pilot study. Methods Patients with inflammatory bowel disease who required surgery with ostomy creation at the Hyogo College of Medicine between January 2014 and December 2015 were enrolled. Safety was assessed by evaluating the incidence of stoma-related complications. Ostomy was restricted to loop ileostomy and was created with two sutures and tissue adhesives. Results A total of 14 patients were enrolled. Mean body mass index was 18.9 ± 2.0 kg/m 2 . There were no cases of ostomy retraction and no severe adverse events were observed. Conclusions This pilot study demonstrates that ostomy creation using tissue adhesives is safe. Although retraction and adverse events were not observed, even in patients with inflammatory bowel disease who generally exhibit delayed wound healing, the body mass index was extremely low in this series. This study does not strongly recommend ostomy creation with tissue adhesives; further studies are needed to clarify the efficacy and safety of the procedure.

Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib.

PubMed

Lipsky, Andrew H; Farooqui, Mohammed Z H; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U; Herman, Sarah E M; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M; Lozier, Jay N; Wiestner, Adrian

2015-12-01

Ibrutinib is associated with bleeding-related adverse events of grade ≤ 2 in severity, and infrequently with grade ≥ 3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤ 2 bleeding-related adverse events in 55% of 85 patients. No grade ≥ 3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤ 2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733. Copyright© Ferrata Storti Foundation.

Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib

PubMed Central

Lipsky, Andrew H.; Farooqui, Mohammed Z.H.; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M.; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U.; Herman, Sarah E. M.; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M.; Lozier, Jay N.; Wiestner, Adrian

2015-01-01

Ibrutinib is associated with bleeding-related adverse events of grade ≤2 in severity, and infrequently with grade ≥3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤2 bleeding-related adverse events in 55% of 85 patients. No grade ≥3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733 PMID:26430171

Hazardous substances releases associated with Hurricanes Katrina and Rita in industrial settings, Louisiana and Texas.

PubMed

Ruckart, Perri Zeitz; Orr, Maureen F; Lanier, Kenneth; Koehler, Allison

2008-11-15

The scientific literature concerning the public health response to the unprecedented hurricanes striking the Gulf Coast in August and September 2005 has focused mainly on assessing health-related needs and surveillance of injuries, infectious diseases, and other illnesses. However, the hurricanes also resulted in unintended hazardous substances releases in the affected states. Data from two states (Louisiana and Texas) participating in the Hazardous Substances Emergency Events Surveillance (HSEES) system were analyzed to describe the characteristics of hazardous substances releases in industrial settings associated with Hurricanes Katrina and Rita. HSEES is an active multi-state Web-based surveillance system maintained by the Agency for Toxic Substances and Disease Registry (ATSDR). In 2005, 166 hurricane-related hazardous substances events in industrial settings in Louisiana and Texas were reported. Most (72.3%) releases were due to emergency shut downs in preparation for the hurricanes and start-ups after the hurricanes. Emphasis is given to the contributing causal factors, hazardous substances released, and event scenarios. Recommendations are made to prevent or minimize acute releases of hazardous substances during future hurricanes, including installing backup power generation, securing equipment and piping to withstand high winds, establishing procedures to shutdown process operations safely, following established and up-to-date start-up procedures and checklists, and carefully performing pre-start-up safety reviews.

Contribution of Microglia-Mediated Neuroinflammation to Retinal Degenerative Diseases

PubMed Central

Madeira, Maria H.; Boia, Raquel; Santos, Paulo F.; Ambrósio, António F.; Santiago, Ana R.

2015-01-01

Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microglia-mediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy. PMID:25873768

Impact of Noncaregiving-Related Stressors on Informal Caregiver Outcomes.

PubMed

Austrom, Mary Guerriero; Lu, Yvonne Yueh-Feng; Perkins, Anthony J; Boustani, Malaz; Callahan, Christopher M; Hendrie, Hugh C

2014-08-01

Caregivers of persons with dementia are stressed. Stressors not related to care recipients' needs impact caregiver outcomes, yet are seldom reported. The purpose of this study was to report the most stressful events experienced by spouse caregivers of older adults with Alzheimer s disease during a 6-month period. 31 caregivers completed the Most Stressful Event form, Patient Health Questionnaire (PHQ-9) and the Revised Memory Behavioral Problem Checklist (R-MBPC). Fisher's exact test and two-sample t-test were used to compare Most Stressful Events between caregivers. ANOVA model tested whether the PHQ-9 and R-MBPC subscales differed by stressor. Caregivers reported no stressors 21.5% of the time, 1-2 stressors 25% of the time, and 3 stressors 53% of the time with 318 stressors reported in total. Care recipient needs (30.2%), caregiver needs (26.7%), and decision-making (16.7%) were the most frequently reported stressors. Using a mixed effects model, there were associations between the Most Stressful Events and depression (p = 0.016), mobility (p = 0.024) and caregiver issues (p = 0.009) subscales of R-MBPC. Results can be used to develop targeted intervention and support strategies for spouse caregivers experiencing non-caregiving related stressorsas well as the traditional challenges with caregiving related issues. © The Author(s) 2014.

Denosumab for the management of bone disease in patients with solid tumors.

PubMed

Body, Jean-Jacques

2012-03-01

Many patients with advanced cancer develop bone metastases, which reduces their quality of life. Bone metastases are associated with an increased risk of skeletal-related events, which can lead to increased morbidity and mortality. In patients with bone metastases, tumor cells disrupt the normal process of bone remodeling, leading to increased bone destruction. Denosumab is a fully human monoclonal antibody against receptor activator of NF-κB ligand (RANKL), a key regulatory factor in bone remodeling. By binding to RANKL, denosumab disrupts the cycle of bone destruction. In clinical studies in patients with prostate or breast cancer and bone metastases, denosumab was superior to the current standard of care, zoledronic acid, for delaying skeletal-related events, while in patients with other solid tumors or multiple myeloma, denosumab was noninferior to zoledronic acid. This article examines the pharmacokinetics, efficacy, and safety and tolerability of denosumab for the management of bone events in patients with cancer.

Lymphoma Therapy and Adverse Events: Nursing Strategies for Thinking Critically and Acting Decisively.

PubMed

Goodrich, Amy; Wagner-Johnston, Nina; Delibovi, Dana

2017-02-01

Multiple treatment options, combined with disease heterogeneity, have created nursing challenges in the management of adverse events (AEs) during antilymphoma therapy. Testing has revealed that less than half of participating nurses correctly graded peripheral neuropathy and neutropenia related to antilymphoma regimens. This article identifies nursing challenges in the management of AEs associated with therapy for lymphomas and describes how strategies in critical thinking can help meet those challenges. A comprehensive literature search in oncology nursing, nursing education, and critical thinking was conducted; participant responses to pre- and post-tests at nursing education programs were evaluated; and a roundtable meeting of authors was convened. Oncology nurses can cultivate critical thinking skills, practice thinking critically in relation to team members and patients, leverage information from the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events, and manage workflow to allow more opportunity for critical thinking.

Postcesarean thromboprophylaxis with two different regimens of bemiparin.

PubMed

Cruz, Milagros; Fernández-Alonso, Ana M; Rodríguez, Isabel; Garrigosa, Loreto; Caño, Africa; Carretero, Pilar; Vizcaíno, Amelia; Gonzalez-Ramirez, Amanda Rocío

2011-01-01

Objectives. To compare the effectiveness of postcesarean thromboprophylaxis with two different regimens of bemiparin. Material and Methods. The study included 646 women with cesarean delivery in our hospital within a 1-year period, randomly assigned to one of two groups for prophylaxis with 3500 IU bemiparin once daily for 5 days or 3500 IU bemiparin once daily for 10 days. Results. There was one case of pulmonary embolism (first day following cesarean). An additional risk factor was present in 98.52% of the women, most frequently emergency cesarean, anemia, or obesity. The only risk factors for thromboembolic disease significantly related to pulmonary thromboembolism were placental abruption and prematurity. There were no differences in thromboembolic events among the two thromboprophylaxis regimens. Conclusions. Cesarean-related thromboembolic events were reduced in our study population due to the thromboprophylactic measures taken. Thromboprophylaxis with 3500 IU bemiparin once daily for 5 days following cesarean was sufficient to avoid thromboembolic events.

Association between respiratory events and nocturnal gastroesophageal reflux events in patients with coexisting obstructive sleep apnea and gastroesophageal reflux disease.

PubMed

Jaimchariyatam, Nattapong; Tantipornsinchai, Warangkana; Desudchit, Tayard; Gonlachanvit, Sutep

2016-06-01

Literature has addressed the increased prevalence of gastroesophageal reflux disease (GERD) in obstructive sleep apnea (OSA). Significant improvement of GERD has been found after OSA treatment. However, precise mechanisms underlying this correlation remain unclear. We examined the association between nocturnal gastroesophageal reflux (GER) and sleep events in patients with coexisting OSA and GERD. A case-crossover study among 12 patients with coexisting moderate-severe OSA and GERD was conducted. Participants underwent simultaneous polysomnography and esophageal impedance and pH monitoring. GER subtypes (ie, acid reflux, non-acid reflux) were defined as outcomes. Respective control time points were selected in all eligible control periods. Each sleep event was assessed individually. Estimated odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed. A p-value of < 0.05 was considered significant. Patients were determined as moderate to severe OSA (respiratory disturbance index of 42.66 [±22.09]). There were a total of 50 GER episodes, 22 acid reflux and 28 non-acid reflux. Arousals and awakenings were significantly associated with subsequent GER events. The OR for GER following an arousal was 2.31 (95% CI 1.39-3.68; p < 0.001) and following an awakening was 3.71 (95% CI 1.81-7.63; p < 0.001). GER events were significantly less likely to occur after other respiratory events (OR 0.38 [95% CI 0.18-0.82]; p = 0.01). No sleep events followed GER events (p > 0.05). Both awakening and arousal appear to precipitate any subtype of GER events in patients with coexisting GERD and moderate to severe OSA. However, GER events were significantly less likely to occur after other respiratory events and did not appear to cause sleep-related events. Copyright © 2016 Elsevier B.V. All rights reserved.

Eradication of hepatitis C virus and non-liver-related non-acquired immune deficiency syndrome-related events in human immunodeficiency virus/hepatitis C virus coinfection.

PubMed

Berenguer, Juan; Rodríguez-Castellano, Elena; Carrero, Ana; Von Wichmann, Miguel A; Montero, Marta; Galindo, María J; Mallolas, Josep; Crespo, Manuel; Téllez, María J; Quereda, Carmen; Sanz, José; Barros, Carlos; Tural, Cristina; Santos, Ignacio; Pulido, Federico; Guardiola, Josep M; Rubio, Rafael; Ortega, Enrique; Montes, María L; Jusdado, Juan J; Gaspar, Gabriel; Esteban, Herminia; Bellón, José M; González-García, Juan

2017-08-01

We assessed non-liver-related non-acquired immunodeficiency syndrome (AIDS)-related (NLR-NAR) events and mortality in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with interferon (IFN) and ribavirin (RBV), between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and nonresponders. Fine and Gray regression analysis was conducted to determine the adjusted subhazard rate (sHR) of NLR deaths and NLR-NAR events considering death as the competing risk. The NLR-NAR events analyzed included diabetes mellitus, chronic renal failure, cardiovascular events, NLR-NAR cancer, bone events, and non-AIDS-related infections. The variables for adjustment were age, sex, past AIDS, HIV transmission category, nadir CD4 + T-cell count, antiretroviral therapy, HIV RNA, liver fibrosis, HCV genotype, and exposure to specific anti-HIV drugs. Of the 1,625 patients included, 592 (36%) had a sustained viral response (SVR). After a median 5-year follow-up, SVR was found to be associated with a significant decrease in the hazard of diabetes mellitus (sHR, 0.57; 95% confidence interval [CI], 0.35-0.93; P = 0.024) and decline in the hazard of chronic renal failure close to the threshold of significance (sHR, 0.43; 95% CI, 0.17-1.09; P = 0.075). Our data suggest that eradication of HCV in coinfected patients is associated not only with a reduction in the frequency of death, HIV progression, and liver-related events, but also with a reduced hazard of diabetes mellitus and possibly of chronic renal failure. These findings argue for the prescription of HCV therapy in coinfected patients regardless of fibrosis stage. (Hepatology 2017;66:344-356). © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

The relation of stress and depression to interdialytic weight gain in hemodialysis patients.

PubMed

Everett, K D; Brantley, P J; Sletten, C; Jones, G N; McKnight, G T

1995-01-01

Nonadherence to fluid restrictions is a common problem with serious health consequences for patients with end-stage renal disease (ESRD). For the present study, the authors evaluated psychological variables of stress, as measured by major and minor life events, and depression. They sought to determine the role of these events in patients' failure to adhere to fluid restrictions as measured by increased interdialytic weight gain. Forty-two hemodialysis patients completed inventories assessing major life events, daily stressful events, and depression on three consecutive dialysis sessions. Fluid adherence was measured by interdialytic weight gain. A path analysis model found daily minor stress to have a direct effect on nonadherence, whereas there was a direct inverse effect of depression on nonadherence. Possible mechanisms and implications for future studies are discussed.

Perception of binary acoustic events associated with the first heart sound

NASA Technical Reports Server (NTRS)

Spodick, D. H.

1977-01-01

The resolving power of the auditory apparatus permits discrete vibrations associated with cardiac activity to be perceived as one or more events. Irrespective of the vibratory combinations recorded by conventional phonocardiography, in normal adults and in most adult patients auscultators tend to discriminate only two discrete events associated with the first heart sound S1. It is stressed that the heart sound S4 may be present when a binary acoustic event associated with S1 occurs in the sequence 'low pitched sound preceding high pitched sound', i.e., its components are perceived by auscultation as 'dull-sharp'. The question of S4 audibility arises in those individuals, normal and diseased, in whom the major components of S1 ought to be, at least clinically, at their customary high pitch and indeed on the PCG appear as high frequency oscillations. It is revealed that the apparent audibility of recorded S4 is not related to P-R interval, P-S4 interval, or relative amplitude of S4. The significant S4-LFC (low frequency component of S1) differences can be related to acoustic modification of the early component of S1.

What We Are Watching—Top Global Infectious Disease Threats, 2013-2016: An Update from CDC's Global Disease Detection Operations Center

PubMed Central

Iuliano, A. Danielle; Uyeki, Timothy M.; Mintz, Eric D.; Nichol, Stuart T.; Rollin, Pierre; Staples, J. Erin; Arthur, Ray R.

2017-01-01

To better track public health events in areas where the public health system is unable or unwilling to report the event to appropriate public health authorities, agencies can conduct event-based surveillance, which is defined as the organized collection, monitoring, assessment, and interpretation of unstructured information regarding public health events that may represent an acute risk to public health. The US Centers for Disease Control and Prevention's (CDC's) Global Disease Detection Operations Center (GDDOC) was created in 2007 to serve as CDC's platform dedicated to conducting worldwide event-based surveillance, which is now highlighted as part of the “detect” element of the Global Health Security Agenda (GHSA). The GHSA works toward making the world more safe and secure from disease threats through building capacity to better “Prevent, Detect, and Respond” to those threats. The GDDOC monitors approximately 30 to 40 public health events each day. In this article, we describe the top threats to public health monitored during 2012 to 2016: avian influenza, cholera, Ebola virus disease, and the vector-borne diseases yellow fever, chikungunya virus, and Zika virus, with updates to the previously described threats from Middle East respiratory syndrome-coronavirus (MERS-CoV) and poliomyelitis. PMID:28805465

What We Are Watching-Top Global Infectious Disease Threats, 2013-2016: An Update from CDC's Global Disease Detection Operations Center.

PubMed

Christian, Kira A; Iuliano, A Danielle; Uyeki, Timothy M; Mintz, Eric D; Nichol, Stuart T; Rollin, Pierre; Staples, J Erin; Arthur, Ray R

To better track public health events in areas where the public health system is unable or unwilling to report the event to appropriate public health authorities, agencies can conduct event-based surveillance, which is defined as the organized collection, monitoring, assessment, and interpretation of unstructured information regarding public health events that may represent an acute risk to public health. The US Centers for Disease Control and Prevention's (CDC's) Global Disease Detection Operations Center (GDDOC) was created in 2007 to serve as CDC's platform dedicated to conducting worldwide event-based surveillance, which is now highlighted as part of the "detect" element of the Global Health Security Agenda (GHSA). The GHSA works toward making the world more safe and secure from disease threats through building capacity to better "Prevent, Detect, and Respond" to those threats. The GDDOC monitors approximately 30 to 40 public health events each day. In this article, we describe the top threats to public health monitored during 2012 to 2016: avian influenza, cholera, Ebola virus disease, and the vector-borne diseases yellow fever, chikungunya virus, and Zika virus, with updates to the previously described threats from Middle East respiratory syndrome-coronavirus (MERS-CoV) and poliomyelitis.

The chronic obstructive pulmonary disease assessment test improves the predictive value of previous exacerbations for poor outcomes in COPD.

PubMed

Miravitlles, Marc; García-Sidro, Patricia; Fernández-Nistal, Alonso; Buendía, María Jesús; Espinosa de Los Monteros, María José; Esquinas, Cristina; Molina, Jesús

2015-01-01

Chronic obstructive pulmonary disease (COPD) exacerbations have a negative impact on the quality of life of patients and the evolution of the disease. We have investigated the prognostic value of several health-related quality of life questionnaires to predict the appearance of a composite event (new ambulatory or emergency exacerbation, hospitalization, or death) over a 1-year follow-up. This was a multicenter, prospective, observational study. Patients completed four questionnaires after recovering from an exacerbation (COPD Assessment Test [CAT], a Clinical COPD Questionnaire [CCQ], COPD Severity Score [COPDSS], and Airways Questionnaire [AQ20]). Patients were followed-up until the appearance of the composite event or for 1 year, whichever came first. A total of 497 patients were included in the study. The majority of them were men (89.7%), with a mean age of 68.7 (SD 9.2) years, and a forced expiratory volume in 1 second of 47.1% (SD 17.5%). A total of 303 (61%) patients experienced a composite event. Patients with an event had worse mean scores of all questionnaires at baseline compared to patients without event: CAT=12.5 vs 11.3 (P=0.028); CCQ=2.2 vs 1.9 (P=0.013); COPDSS=12.3 vs 10.9 (P=0.001); AQ20=8.3 vs 7.5 (P=0.048). In the multivariate analysis, only previous history of exacerbations and CAT score ≥13.5 were significant risk factors for the composite event. A CAT score ≥13.5 increased the predictive value of previous exacerbations with an area under the receiver operating characteristic curve of 0.864 (95% CI: 0.829-0.899; P=0.001). The predictive value of previous exacerbations significantly increased only in one of the four trialled questionnaires, namely in the CAT questionnaire. However, previous history of exacerbations was the strongest predictor of the composite event.

First and recurrent ischaemic heart disease events continue to decline in New Zealand, 2005-2015.

PubMed

Grey, Corina; Jackson, Rod; Wells, Susan; Wu, Billy; Poppe, Katrina; White, Harvey; Chan, Wing Cheuk; Kerr, Andrew J

2018-01-01

To examine recent trends in first and recurrent ischaemic heart disease (IHD) deaths and hospitalisations. Using anonymous patient-linkage of routinely collected data, all New Zealanders aged 35-84 years who experienced an International Statistical Classification of Diseases and Related Health Problems I(CD)-coded IHD hospitalisation and/or IHD death between 1 January 2005 and 31 December 2015 were identified. A 10-year look-back period was used to differentiate those experiencing first from recurrent events. Age-standardised hospitalisation and mortality rates were calculated for each calendar year and trends compared by sex and age. 160 109 people experienced at least one IHD event (259 678 hospitalisations and 35 548 deaths) over the 11-year study period, and there was a steady decline in numbers (from almost 24 000 in 2005 to just over 16 000 in 2015) and in age-standardised rates each year. With the exception of deaths in younger (35-64 years) women with prior IHD, there was a significant decline in IHD events in men and women of all ages, with and without a history of IHD. The decline in IHD mortality was greater for those experiencing a first rather than recurrent IHD event (3.8%-5.2% vs 0%-3.7% annually on average). In contrast, the decline in IHD hospitalisations was greater for those experiencing a recurrent compared with a first IHD event (5.6%-7.3% vs 3.2%-5.7% annually on average). The substantial decline in IHD hospitalisations and mortality observed in New Zealanders with and without prior IHD between 2005 and 2015 suggests that primary and secondary prevention efforts have been effective in reducing the occurrence of IHD events. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Mitochondrial oxidative stress and cardiac ageing.

PubMed

Martín-Fernández, Beatriz; Gredilla, Ricardo

According with different international organizations, cardiovascular diseases are becoming the first cause of death in western countries. Although exposure to different risk factors, particularly those related to lifestyle, contribute to the etiopathogenesis of cardiac disorders, the increase in average lifespan and aging are considered major determinants of cardiac diseases events. Mitochondria and oxidative stress have been pointed out as relevant factors both in heart aging and in the development of cardiac diseases such as heart failure, cardiac hypertrophy and diabetic cardiomyopathy. During aging, cellular processes related with mitochondrial function, such as bioenergetics, apoptosis and inflammation are altered leading to cardiac dysfunction. Increasing our knowledge about the mitochondrial mechanisms related with the aging process, will provide new strategies in order to improve this process, particularly the cardiovascular ones. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

From Science to Finance-A Tool for Deriving Economic Implications from the Results of Dietary Supplement Clinical Studies.

PubMed

Shanahan, Christopher J; de Lorimier, Robert

2016-01-01

This article examines evidence showing that the use of key dietary supplements can reduce overall disease treatment-related hospital utilization costs associated with coronary heart disease (CHD) in the United States among those at a high risk of experiencing a costly, disease-related event. Results show that the potential avoided hospital utilization costs related to the use of omega-3 supplements at preventive intake levels among the target population can be as much as $2.06 billion on average per year from 2013 to 2020. The potential net savings in avoided CHD-related hospital utilization costs after accounting for the cost of omega-3 dietary supplements at preventive daily intake levels would be more than $3.88 billion in cumulative health care cost savings from 2013 to 2020. Furthermore, the use of folic acid, B6, and B12 among the target population at preventive intake levels could yield avoided CHD-related hospital utilization costs savings of an average savings of $1.52 billion per year from 2013 to 2020. The potential net savings in avoided CHD-related health care costs after accounting for the cost of folic acid, B6, and B12 utilization at preventive daily intake levels would be more than $5.23 billion in cumulative health care cost net savings during the same period. Thus, targeted dietary supplement regimens are recommended as a means to help control rising societal health care costs, and as a means for high-risk individuals to minimize the chance of having to deal with potentially costly events and to invest in increased quality of life.

Heat and emergency room admissions in the Netherlands.

PubMed

van Loenhout, Joris Adriaan Frank; Delbiso, Tefera Darge; Kiriliouk, Anna; Rodriguez-Llanes, Jose Manuel; Segers, Johan; Guha-Sapir, Debarati

2018-01-05

Due to a global warming-related increase in heatwaves, it is important to obtain detailed understanding of the relationship between heat and health. We assessed the relationship between heat and urgent emergency room admissions in the Netherlands. We collected daily maximum temperature and relative humidity data over the period 2002-2007. Daily urgent emergency room admissions were divided by sex, age group and disease category. We used distributed lag non-linear Poisson models, estimating temperature-admission associations. We estimated the relative risk (RR) for urgent hospital admissions for a range of temperatures compared to a baseline temperature of 21 °C. In addition, we compared the impact of three different temperature scenarios on admissions using the RR. There is a positive relationship between increasing temperatures above 21 °C and the RR for urgent emergency room admissions for the disease categories 'Potential heat-related diseases' and 'Respiratory diseases'. This relationship is strongest in the 85+ group. The RRs are strongest for lag 0. For admissions for 'circulatory diseases', there is only a small significant increase of RRs within the 85+ age group for moderate heat, but not for extreme heat. The RRs for a one-day event with extreme heat are comparable to the RRs for multiple-day events with moderate heat. Hospitals should adjust the capacity of their emergency departments on warm days, and the days immediately thereafter. The elderly in particular should be targeted through prevention programmes to reduce harmful effects of heat. The fact that this increase in admissions already occurs in temperatures above 21 °C is different from previous findings in warmer countries. Given the similar impact of three consecutive days of moderate heat and one day of extreme heat on admissions, criteria for activation of national heatwave plans need adjustments based on different temperature scenarios.

Association of stressful life events with incident falls and fractures in older men: the Osteoporotic Fractures in Men (MrOS) Study

PubMed Central

Fink, Howard A.; Kuskowski, Michael A.; Marshall, Lynn M.

2014-01-01

Background: small, retrospective studies suggest that major life events and/or sudden emotional stress may increase fall and fracture risk. The current study examines these associations prospectively. Methods: a total of 5,152 men aged ≥65 years in the Osteoporotic Fractures in Men study self-reported data on stressful life events for 1 year prior to study Visit 2. Incident falls and fractures were ascertained for 1 year after Visit 2. Fractures were centrally confirmed. Results: a total of 2,932 (56.9%) men reported ≥1 type of stressful life event. In men with complete stressful life event, fall and covariate data (n = 3,949), any stressful life event was associated with a 33% increased risk of incident fall [relative risk (RR) 1.33, 95% confidence interval (CI) 1.19–1.49] and 68% increased risk of multiple falls (RR = 1.68, 95% CI = 1.40–2.01) in the year following Visit 2 after adjustment for age, education, Parkinson's disease, diabetes, stroke, instrumental activities of daily living (IADL) impairment, chair stand time, walk speed, multiple past falls, depressive symptoms and antidepressant use. Risk increased with the number of types of stressful life events. Though any stressful life event was associated with a 58% increased age-adjusted risk for incident fracture, this association was attenuated and no longer statistically significant after additional adjustment for total hip bone mineral density, fracture after age 50, Parkinson's disease, stroke and IADL impairment. Conclusions: in this cohort of older men, stressful life events significantly increased risk of incident falls independent of other explanatory variables, but did not independently increase incident fracture risk. PMID:24002237

75 FR 43990 - Agency Information Collection Activities; Proposed Collection; Comment Request; Pet Event...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-27

... outbreaks in companion animals or contamination incidents concerning pet food or animals feed, which they... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. 2010-N-0368... Network--State, Federal Cooperation to Prevent Spread of Pet Food Related Diseases AGENCY: Food and Drug...

Social Stress and Mortality Among Nonwhite Males

ERIC Educational Resources Information Center

Dennis, Ruth E.

1977-01-01

The leading causes of death for young black males are accidents, homicide and suicide. Stress arising from socioeconomic conditions precipitates these events. Heart disease and cancer, other major causes of death, are also thought to be environmentally related. The author proposes the development of new types of social institutions to remedy the…

Manual B-mode versus automated radio-frequency carotid intima-media thickness measurements.

PubMed

Dogan, Soner; Plantinga, Yvonne; Dijk, Joke M; van der Graaf, Yolanda; Grobbee, Diederick E; Bots, Michiel L

2009-10-01

Carotid intima-media thickness (CIMT) serves as an indicator of atherosclerosis and cardiovascular risk. Manual measurements of B-mode ultrasound images are the most applied method. Automated measurements with radiofrequency (RF) ultrasound have been suggested as an alternative. The aim of this study was to compare these methods in terms of risk-factor relations and associations with future events. Data from participants of the Second Manifestations of Arterial Disease (SMART) study were used. Far wall common CIMT was measured online with manual B-mode and automated RF ultrasound. Measurements were performed by a group of 6 sonographers. Risk-factor information was obtained. All participants were followed for the occurrence of vascular events (mean follow-up, 2.1 years). CIMT was related to risk factors with linear regression models and to future events with Cox proportional-hazards models. Data were available for 2,146 participants. Agreement between the methods was modest (intraclass correlation coefficient = 0.34). Risk-factor relations with age and systolic blood pressure were stronger for B-mode than for RF ultrasound. Association with future events was better for B-mode than for RF ultrasound (vascular death, 1.27 vs 1.00; ischemic stroke, 1.45 vs 1.03). In participants with CIMT < 0.9 mm (without plaque), the intraclass correlation between the measures was 0.50. In addition, in that subgroup, RF ultrasound showed a stronger association with future events than B-mode ultrasound (all events, 1.59 vs 1.09; vascular death, 1.72 vs 0.93; coronary ischemic events, 1.65 vs 1.05). The preference for either B-mode or RF measurements may be driven by the type of study population, the expected presence of local atherosclerotic abnormalities, and the main aim of the study (assessing risk factors or events). However, in this study, as in many others, the B-mode approach was shown to be robust in risk-factor relations and the prediction of events.

Epidemiological transition in a rural community of northern India: 18-year mortality surveillance using verbal autopsy.

PubMed

Kumar, Rajesh; Kumar, Dinesh; Jagnoor, J; Aggarwal, Arun K; Lakshmi, P V M

2012-10-01

Information on causes of death is vital for planning of health services. However, vital events registration systems are weak in developing countries. Therefore, verbal autopsy (VA) tools were incorporated in a community-based surveillance system to track causes of death. Trained fieldworker identified all deaths and interviewed a living relative of those who had died during 1992-2009, using VA, in eight villages of Haryana (11,864 populations). These field reports detailing events preceding death were reviewed by two trained physicians, who independently assigned an International Classification of Disease-10 code to each death. Discrepancies were resolved through reconciliation and, if necessary, adjudication. Non-communicable conditions were the leading causes of death (47.6%) followed by communicable diseases including maternal, perinatal and nutritional conditions (34.0%), and injuries (11.4%). Cause of death could not be determined in 6.9% cases. Deaths due to cardiovascular diseases showed a significant rise, whereas deaths due to diarrhoeal diseases have declined (p<0.01). Majority (90.0%) of the deceased had contacted a healthcare provider during illness but only 11.5% were admitted in hospital before death. Rising trend of cardiovascular diseases observed in a rural community of Haryana in India calls for reorientation of rural healthcare delivery system for prevention and control of chronic diseases.

Multi-event capture–recapture modeling of host–pathogen dynamics among European rabbit populations exposed to myxoma and Rabbit Hemorrhagic Disease Viruses: common and heterogeneous patterns

PubMed Central

2014-01-01

Host–pathogen epidemiological processes are often unclear due both to their complexity and over-simplistic approaches used to quantify them. We applied a multi-event capture–recapture procedure on two years of data from three rabbit populations to test hypotheses about the effects on survival of, and the dynamics of host immunity to, both myxoma virus and Rabbit Hemorrhagic Disease Virus (MV and RHDV). Although the populations shared the same climatic and management conditions, MV and RHDV dynamics varied greatly among them; MV and RHDV seroprevalences were positively related to density in one population, but RHDV seroprevalence was negatively related to density in another. In addition, (i) juvenile survival was most often negatively related to seropositivity, (ii) RHDV seropositives never had considerably higher survival, and (iii) seroconversion to seropositivity was more likely than the reverse. We suggest seropositivity affects survival depending on trade-offs among antibody protection, immunosuppression and virus lethality. Negative effects of seropositivity might be greater on juveniles due to their immature immune system. Also, while RHDV directly affects survival through the hemorrhagic syndrome, MV lack of direct lethal effects means that interactions influencing survival are likely to be more complex. Multi-event modeling allowed us to quantify patterns of host–pathogen dynamics otherwise difficult to discern. Such an approach offers a promising tool to shed light on causative mechanisms. PMID:24708296

Cardiovascular risk factors and events in women with androgen excess.

PubMed

Macut, D; Antić, I B; Bjekić-Macut, J

2015-03-01

Androgen excess (AE) was approximated to be present in 7% of the adult population of women. Polycystic ovary syndrome (PCOS) is the most prevalent among them, followed by idiopathic hirsutism (IH), congenital adrenal hyperplasia (CAH), hyperandrogenic insulin-resistant acanthosis nigricans (HAIRAN) syndrome, and androgen-secreting neoplasms (ASNs). Increased cardiovascular risk was implicated in women with AE. Serum testosterone independently increases risk for cardiovascular disease (CVD), and correlates even with indices of subclinical atherosclerosis in various populations of postmenopausal women. Hyperandrogenism in PCOS is closely related to the aggravation of abdominal obesity, and together with insulin resistance forming the metabolic core for the development of CVD. However, phenotypic variability of PCOS generates significant influence on the cardiometabolic risks. Numerous risk factors in PCOS lead to 5-7 times higher risk for CVD and over 2-fold higher risk for coronary heart disease and stroke. However, issue on the cardiometabolic risk in postmenopausal women with hyperandrogenic history is still challenging. There is a significant overlapping in the CVD characteristics of women with PCOS and variants of CAH. Relevant clinical data on the prevalence and cardiometabolic risk and events in women with IH, HAIRAN syndrome or ASNs are scarce. The effects of various oral contraceptives (OCs) and antiandrogenic compounds on metabolic profile are varying, and could be related to the selected populations and different therapy regiments mainly conducted in women with PCOS. It is assumed relation of OCs containing antiandrogenic progestins to the increased risk of cardiovascular and thromboembolic events.

Rotigotine Transdermal Patch in Parkinson’s Disease: A Systematic Review and Meta-Analysis

PubMed Central

Zhou, Chang-Qing; Li, Shan-Shan; Chen, Zhong-Mei; Li, Feng-Qun; Lei, Peng; Peng, Guo-Guang

2013-01-01

Background and Methods The efficacy and safety of rotigotine transdermal patch in Parkinson’s disease (PD) were studied in some clinical trials. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy, tolerability, and safety of rotigotine transdermal patch versus placebo in PD. Results Six randomized controlled trials (1789 patients) were included in this meta-analysis. As compared with placebo, the use of rotigotine resulted in greater improvements in Unified Parkinson’s Disease Rating Scale activities of daily living score (weighted mean difference [WMD] –1.69, 95% confidence interval [CI] –2.18 to –1.19), motor score (WMD –3.86, 95% CI –4.86 to –2.86), and the activities of daily living and motor subtotal score (WMD –4.52, 95% CI –5.86 to –3.17). Rotigotine was associated with a significantly higher rate of withdrawals due to adverse events (relative risk [RR] 1.82, 95% CI 1.29–2.59), and higher rates of application site reactions (RR 2.92, 95% CI 2.29–3.72), vomiting (RR 5.18, 95% CI 2.25–11.93), and dyskinesia (RR 2.52, 95% CI 1.47–4.32) compared with placebo. No differences were found in the relative risks of headache, constipation, back pain, diarrhea, or serious adverse events. Conclusions Our meta-analysis showed that the use of rotigotine can reduce the symptoms of PD. However, rotigotine was also associated with a higher incidence of adverse events, especially application site reactions, compared with placebo. PMID:23936090

Relation between Kidney Length and Cardiovascular and Renal Risk in High-Risk Patients

PubMed Central

van der Sande, Nicolette G.C.; Visseren, Frank L.J.; van der Graaf, Yolanda; Nathoe, Hendrik M.; de Borst, Gert Jan; Leiner, Tim

2017-01-01

Background and objectives Kidney length is often measured during routine abdominal ultrasonography and may be of use to identify patients at high vascular and renal risk. We aimed to explore patient characteristics related to kidney length, from which reference values were derived, and evaluate the relationship between kidney length and the risk of cardiovascular events and ESRD in high-risk patients. Design, setting, participants, & measurements The study population consisted of 10,251 patients with clinical manifest arterial disease or vascular risk factors included in the Second Manifestations of ARTerial disease (SMART) Study cohort between 1996 and 2014. Linear regression was used to explore patient characteristics of kidney length. The relationship between kidney length and cardiovascular events (myocardial infarction, stroke, and cardiovascular mortality), all-cause mortality, and ESRD was analyzed using Cox regression. Kidney length was analyzed in tertiles, using the second tertile as the reference category. Results Kidney length was strongly correlated with body surface area (2.04 mm; 95% confidence interval [95% CI], 1.95 to 2.13 per 0.1 m2 increase) and eGFR (1.62 mm; 95% CI, 1.52 to 1.73 per 10 ml/min per 1.73 m2 increase). During the median follow-up of 6.3 years, 1317 patients experienced a cardiovascular event, including 711 myocardial infarctions, 369 strokes, and 735 vascular cause deaths. A total of 1462 patients died of any cause and 52 patients developed ESRD. Irrespective of eGFR, patients in the third tertile of kidney length (11.7–16.1 cm) were at higher risk of cardiovascular mortality (hazard ratio, 1.33; 95% CI, 1.05 to 1.67) and cardiovascular events (hazard ratio, 1.28; 95% CI, 1.09 to 1.50). Patients in the first tertile of kidney length (7.8–10.8 cm) were not at higher risk of cardiovascular adverse events. Conclusions Large kidney length is related to higher risk of cardiovascular events and mortality in high-risk patients, irrespective of eGFR. Kidney length may serve as a clinical marker to further identify patients at high cardiovascular risk. PMID:28487344

Relation between Kidney Length and Cardiovascular and Renal Risk in High-Risk Patients.

PubMed

van der Sande, Nicolette G C; Visseren, Frank L J; van der Graaf, Yolanda; Nathoe, Hendrik M; de Borst, Gert Jan; Leiner, Tim; Blankestijn, Peter J

2017-06-07

Kidney length is often measured during routine abdominal ultrasonography and may be of use to identify patients at high vascular and renal risk. We aimed to explore patient characteristics related to kidney length, from which reference values were derived, and evaluate the relationship between kidney length and the risk of cardiovascular events and ESRD in high-risk patients. The study population consisted of 10,251 patients with clinical manifest arterial disease or vascular risk factors included in the Second Manifestations of ARTerial disease (SMART) Study cohort between 1996 and 2014. Linear regression was used to explore patient characteristics of kidney length. The relationship between kidney length and cardiovascular events (myocardial infarction, stroke, and cardiovascular mortality), all-cause mortality, and ESRD was analyzed using Cox regression. Kidney length was analyzed in tertiles, using the second tertile as the reference category. Kidney length was strongly correlated with body surface area (2.04 mm; 95% confidence interval [95% CI], 1.95 to 2.13 per 0.1 m 2 increase) and eGFR (1.62 mm; 95% CI, 1.52 to 1.73 per 10 ml/min per 1.73 m 2 increase). During the median follow-up of 6.3 years, 1317 patients experienced a cardiovascular event, including 711 myocardial infarctions, 369 strokes, and 735 vascular cause deaths. A total of 1462 patients died of any cause and 52 patients developed ESRD. Irrespective of eGFR, patients in the third tertile of kidney length (11.7-16.1 cm) were at higher risk of cardiovascular mortality (hazard ratio, 1.33; 95% CI, 1.05 to 1.67) and cardiovascular events (hazard ratio, 1.28; 95% CI, 1.09 to 1.50). Patients in the first tertile of kidney length (7.8-10.8 cm) were not at higher risk of cardiovascular adverse events. Large kidney length is related to higher risk of cardiovascular events and mortality in high-risk patients, irrespective of eGFR. Kidney length may serve as a clinical marker to further identify patients at high cardiovascular risk. Copyright © 2017 by the American Society of Nephrology.

Patients with mild cognitive impairment have an abnormal upper-alpha event-related desynchronization/synchronization (ERD/ERS) during a task of temporal attention.

PubMed

Caravaglios, Giuseppe; Muscoso, Emma Gabriella; Di Maria, Giulia; Costanzo, Erminio

2015-03-01

There are several evidences indicating that an impairment in attention-executive functions is present in prodromal Alzheimer's disease and predict future global cognitive decline. In particular, the issue of temporal orienting of attention in patients with mild cognitive impairment (MCI) due to Alzheimer's disease has been overlooked. The present research aimed to explore whether subtle deficits of cortical activation are present in these patients early in the course of the disease. We studied the upper-alpha event-related synchronization/desynchronization phenomenon during a paradigm of temporal orientation of attention. MCI patients (n = 27) and healthy elderly controls (n = 15) performed a task in which periodically omitted tones had to be predicted and their virtual onset time had to be marked by pressing a button. Single-trial responses were measured, respectively, before and after the motor response. Then, upper-alpha responses were compared to upper-alpha power during eyes-closed resting state. The time course of the task was characterized by two different behavioral conditions: (1) a pre-event epoch, in which the subject awaited the virtual onset of the omitted tone, (2) a post-event epoch (after button pressing), in which the subject was in a post-motor response condition. The principal findings are: (1) during the waiting epoch, only healthy elderly had an upper-alpha ERD at the level of both temporal and posterior brain regions; (2) during the post-motor epoch, the aMCI patients had a weaker upper-alpha ERS on prefrontal regions; (3) only healthy elderly showed a laterality effect: (a) during the waiting epoch, the upper-alpha ERD was greater at the level of the right posterior-temporal lead; during the post-motor epoch, the upper alpha ERS was greater on the left prefrontal lead. The relevance of these findings is that the weaker upper-alpha response observed in aMCI patients is evident even if the accuracy of the behavioral performance (i.e., button pressing) is still spared. This abnormal upper-alpha response might represent an early biomarker of the attention-executive network impairment in MCI due to Alzheimer's disease.

A multifaceted strategy using mobile technology to assist rural primary healthcare doctors and frontline health workers in cardiovascular disease risk management: protocol for the SMARTHealth India cluster randomised controlled trial.

PubMed

Praveen, Devarsetty; Patel, Anushka; McMahon, Stephen; Prabhakaran, Dorairaj; Clifford, Gari D; Maulik, Pallab K; Joshi, Rohina; Jan, Stephen; Heritier, Stephane; Peiris, David

2013-11-25

Blood Pressure related disease affected 118 million people in India in the year 2000; this figure will double by 2025. Around one in four adults in rural India have hypertension, and of those, only a minority are accessing appropriate care. Health systems in India face substantial challenges to meet these gaps in care, and innovative solutions are needed. We hypothesise that a multifaceted intervention involving capacity strengthening of primary healthcare doctors and non-physician healthcare workers through use of a mobile device-based clinical decision support system will result in improved blood pressure control for individuals at high risk of a cardiovascular disease event when compared with usual healthcare. This intervention will be implemented as a stepped wedge, cluster randomised controlled trial in 18 primary health centres and 54 villages in rural Andhra Pradesh involving adults aged ≥40 years at high cardiovascular disease event risk (approximately 15,000 people). Cardiovascular disease event risk will be calculated based on World Health Organisation/International Society of Hypertension's region-specific risk charts. Cluster randomisation will occur at the level of the primary health centres. Outcome analyses will be conducted blinded to intervention allocation. The primary study outcome is the difference in the proportion of people meeting guideline-recommended blood pressure targets in the intervention period vs. the control period. Secondary outcomes include mean reduction in blood pressure levels; change in other cardiovascular disease risk factors, including body mass index, current smoking, reported healthy eating habits, and reported physical activity levels; self-reported use of blood pressure and other cardiovascular medicines; quality of life (using the EQ-5D); and cardiovascular disease events (using hospitalisation data). Trial outcomes will be accompanied by detailed process and economic evaluations. The findings are likely to inform policy on a scalable strategy to overcome entrenched inequities in access to effective healthcare for under-served populations in low and middle income country settings. Clinical Trial Registry India CTRI/2013/06/003753.

Permanent work disability before and after ischaemic heart disease or stroke event: a nationwide population-based cohort study in Sweden.

PubMed

Ervasti, Jenni; Virtanen, Marianna; Lallukka, Tea; Friberg, Emilie; Mittendorfer-Rutz, Ellenor; Lundström, Erik; Alexanderson, Kristina

2017-09-29

We examined the risk of disability pension before and after ischaemic heart disease (IHD) or stroke event, the burden of stroke compared with IHD and which factors predicted disability pension after either event. A population-based cohort study with follow-up 5 years before and after the event. Register data were analysed with general linear modelling with binary and Poisson distributions including interaction tests for event type (IHD/stroke). All people living in Sweden, aged 25‒60 years at the first event year, who had been living in Sweden for 5 years before the event and had no indication of IHD or stroke prior to the index event in 2006‒2008 were included, except for cases in which death occurred within 30 days of the event. People with both IHD and stroke were excluded, resulting in 18 480 cases of IHD (65%) and 9750 stroke cases (35%). Disability pension. Of those going to suffer IHD or stroke event, 25% were already on disability pension a year before the event. The adjusted OR for disability pension at first postevent year was 2.64-fold (95% CI 2.25 to 3.11) for people with stroke compared with IHD. Economic inactivity predicted disability pension regardless of event type (OR=3.40; 95% CI 2.85 to 4.04). Comorbid mental disorder was associated with the greatest risk (OR=3.60; 95% CI 2.69 to 4.83) after an IHD event. Regarding stroke, medical procedure, a proxy for event severity, was the largest contributor (OR=2.27, 95% CI 1.43 to 3.60). While IHD event was more common, stroke involved more permanent work disability. Demographic, socioeconomic and comorbidity-related factors were associated with disability pension both before and after the event. The results help occupational and other healthcare professionals to identify vulnerable groups at risk for permanent labour market exclusion after such an event. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Multiple risk factor control, mortality and cardiovascular events in type 2 diabetes and chronic kidney disease: a population-based cohort study

PubMed Central

Gulliford, Martin C

2018-01-01

Objectives This study aimed to evaluate the effectiveness of multiple risk factor control (MRFC) at reducing mortality and cardiovascular events in diabetes and chronic kidney disease (CKD) in clinical practice. Design Population-based cohort study. Setting Primary care database in the UK, linked with inpatient and mortality data. Participants Participants aged 40–79 years with type 2 diabetes and valid serum creatinine measurements, including 11 431 participants with CKD (estimated glomerular filtration rate: eGFR 15–59 mL/min/1.73 m2) and 36 429 participants with non-CKD (eGFR ≥60 mL/min/1.73 m2). Exposures MRFC consisted of four components: Haemoglobin A1c (HbA1c) <53 mmol/mol (<7.0%), blood pressure <140/90 mm Hg, total cholesterol <5 mmol/L and no smoking. The main exposure variable was the number of risk factors controlled at baseline. Outcome measures All-cause and cardiovascular mortality in the overall participants. Cardiovascular events, including coronary heart disease and stroke, in participants limited to those without a history of cardiovascular diseases at baseline. Results In participants with CKD, 37% or 13% met three or four MRFC criteria, respectively. Increasing numbers of risk factors controlled were associated with lower relative hazards for all outcomes studied compared with those meeting no or one criterion. For participants with CKD meeting four criteria, the adjusted HR for all-cause mortality was 0.60 (95% CI 0.53 to 0.69) and the adjusted subdistribution HR for cardiovascular mortality was 0.60 (95% CI 0.50 to 0.70), considering a competing risk of non-cardiovascular death. Participants meeting four criteria also had lower relative hazards for coronary heart disease (adjusted subdistribution HR 0.73, 95% CI 0.59 to 0.91) and stroke (0.63, 95% CI 0.45 to 0.89), considering death as a competing risk. Conclusions MRFC may lower the increased risks for mortality and cardiovascular events in people with diabetes and CKD. Further research is needed to evaluate appropriateness of MRFC according to individual participants’ health status for improved management of cardiovascular risks in this population. PMID:29739781

Stress, coping and support needs of patients with ulcerative colitis or Crohn's disease: a qualitative descriptive study.

PubMed

Larsson, Kjerstin; Lööf, Lars; Nordin, Karin

2017-03-01

To examine disease-related stress, coping strategies and the need for information and support in patients with inflammatory bowel disease (ulcerative colitis or Crohn's disease). Psychological stress is an important factor in ulcerative colitis and Crohn's disease, and therefore, coping strategies and support needs should be considered in routine clinical practice. This is a qualitative study using a descriptive interview-based approach. Fifteen patients with ulcerative colitis (n = 7) or Crohn's disease (n = 8) were interviewed. The interviews were analysed with content analysis. The informants largely focused on disease-related stress (e.g. access to a toilet, symptoms and worries) and relations to other people (various reactions from others and social situations). Behavioural strategies (i.e. taking actions and the need for making plans, prepare and adapt), social strategies (seeking help and information and sharing feelings about the disease with others) and emotional strategies (distraction, positive attitude and acceptance) were adopted to cope with the stress associated with the disease. The need for information and support concerned instrumental support (disease-related information) and emotional support (to talk about disease management). Faecal urgency and the fear of losing bowel control are important stressors for patients with inflammatory bowel disease. The patients handle this problem using various coping strategies depending on the type of stressful events. Both instrumental and emotional support were requested which primarily occurred at the time of diagnosis and disease flare-ups. Patients with ulcerative colitis or Crohn's disease ask for information and psychosocial support that are tailored to their individual needs and at different stages in the disease trajectory to improve everyday life and strengthen self-management strategies. © 2016 John Wiley & Sons Ltd.

[Radiation-related heart toxicity: Update in women].

PubMed

Marlière, S; Vautrin, E; Saunier, C; Chaikh, A; Gabelle-Flandin, I

2016-12-01

Breast cancer is a common diagnosis in women and thus women are at risk of radiation-induced heart disease, in particular during radiotherapy for left breast cancer and when the internal mammary chain is included. Rates of major cardiac events increase with younger age at the time of irradiation, diagnosis before 1990s, higher radiation doses, coexisting cardiovascular risk factors and adjuvant cardiotoxic chemotherapy. Radiation-induced heart disease comprises a spectrum of cardiac pathologies, including pericardial disease, cardiomyopathy, coronary artery disease and valvular disease. The cardiac injury can appear a long time after radiotherapy and can consist of complex lesions with poor prognosis. The disciplines of cardiology and oncology have increasingly recognized the benefits of collaborating in the care of cancer patients with cardiac disease, developing guidelines for the assessment and management of radiation-related cardiovascular disease. We could consider screening patients with previous chest radiation every 5 years with transthoracic echocardiography and functional imaging. However, prevention remains the primary goal, using cardiac sparing doses and avoidance techniques in radiotherapy to improve patient survival. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77 917 Individuals.

PubMed

Aung, Theingi; Halsey, Jim; Kromhout, Daan; Gerstein, Hertzel C; Marchioli, Roberto; Tavazzi, Luigi; Geleijnse, Johanna M; Rauch, Bernhard; Ness, Andrew; Galan, Pilar; Chew, Emily Y; Bosch, Jackie; Collins, Rory; Lewington, Sarah; Armitage, Jane; Clarke, Robert

2018-03-01

Current guidelines advocate the use of marine-derived omega-3 fatty acids supplements for the prevention of coronary heart disease and major vascular events in people with prior coronary heart disease, but large trials of omega-3 fatty acids have produced conflicting results. To conduct a meta-analysis of all large trials assessing the associations of omega-3 fatty acid supplements with the risk of fatal and nonfatal coronary heart disease and major vascular events in the full study population and prespecified subgroups. This meta-analysis included randomized trials that involved at least 500 participants and a treatment duration of at least 1 year and that assessed associations of omega-3 fatty acids with the risk of vascular events. Aggregated study-level data were obtained from 10 large randomized clinical trials. Rate ratios for each trial were synthesized using observed minus expected statistics and variances. Summary rate ratios were estimated by a fixed-effects meta-analysis using 95% confidence intervals for major diseases and 99% confidence intervals for all subgroups. The main outcomes included fatal coronary heart disease, nonfatal myocardial infarction, stroke, major vascular events, and all-cause mortality, as well as major vascular events in study population subgroups. Of the 77 917 high-risk individuals participating in the 10 trials, 47 803 (61.4%) were men, and the mean age at entry was 64.0 years; the trials lasted a mean of 4.4 years. The associations of treatment with outcomes were assessed on 6273 coronary heart disease events (2695 coronary heart disease deaths and 2276 nonfatal myocardial infarctions) and 12 001 major vascular events. Randomization to omega-3 fatty acid supplementation (eicosapentaenoic acid dose range, 226-1800 mg/d) had no significant associations with coronary heart disease death (rate ratio [RR], 0.93; 99% CI, 0.83-1.03; P = .05), nonfatal myocardial infarction (RR, 0.97; 99% CI, 0.87-1.08; P = .43) or any coronary heart disease events (RR, 0.96; 95% CI, 0.90-1.01; P = .12). Neither did randomization to omega-3 fatty acid supplementation have any significant associations with major vascular events (RR, 0.97; 95% CI, 0.93-1.01; P = .10), overall or in any subgroups, including subgroups composed of persons with prior coronary heart disease, diabetes, lipid levels greater than a given cutoff level, or statin use. This meta-analysis demonstrated that omega-3 fatty acids had no significant association with fatal or nonfatal coronary heart disease or any major vascular events. It provides no support for current recommendations for the use of such supplements in people with a history of coronary heart disease.

Adverse events and the relation with quality of life in adults with intellectual disability and challenging behaviour using psychotropic drugs.

PubMed

Scheifes, Arlette; Walraven, Sanne; Stolker, Joost Jan; Nijman, Henk L I; Egberts, Toine C G; Heerdink, Eibert R

2016-01-01

Psychotropic drugs are prescribed to approximately 30-40% of adults with intellectual disability (ID) and challenging behaviour, despite the limited evidence of effectiveness and the potential of adverse events. To assess the prevalence of adverse events in association with psychotropic drug use in adults with ID and challenging behaviour and to examine the relation of these adverse events with the person's quality of life. The presence of adverse events was measured with a questionnaire that had to be filled in by the physicians of the participants. Movement disorders were measured separately with a standardised protocol. The strength of the association between adverse events and Intellectual Disability Quality of Life-16 (IDQOL-16), and daily functioning was investigated using linear regression analyses, taking into account the severity of disease (CGI-S) as potential confounder. Virtually all of 103 adults with ID and challenging behaviour had at least one adverse event (84.4%) and almost half had ≥3 adverse events (45.6%) across different subclasses. Using psychotropic drugs increased the prevalence of adverse events significantly. Respectively 13% of the patients without psychotropic drugs and 61% of the patients with ≥2 psychotropic drugs had ≥3 adverse events. Having adverse events had a significantly negative influence on the quality of life. A large majority of all patients had at least one adverse event associated with psychotropic drug use. More attention is needed for these adverse events and their negative influence on the quality of life of these patients, taking into account the lack of evidence of effectiveness of psychotropic drugs for challenging behaviour. Copyright © 2015. Published by Elsevier Ltd.

Event Rates, Hospital Utilization, and Costs Associated with Major Complications of Diabetes: A Multicountry Comparative Analysis

PubMed Central

Clarke, Philip M.; Glasziou, Paul; Patel, Anushka; Chalmers, John; Woodward, Mark; Harrap, Stephen B.; Salomon, Joshua A.

2010-01-01

Background Diabetes imposes a substantial burden globally in terms of premature mortality, morbidity, and health care costs. Estimates of economic outcomes associated with diabetes are essential inputs to policy analyses aimed at prevention and treatment of diabetes. Our objective was to estimate and compare event rates, hospital utilization, and costs associated with major diabetes-related complications in high-, middle-, and low-income countries. Methods and Findings Incidence and history of diabetes-related complications, hospital admissions, and length of stay were recorded in 11,140 patients with type 2 diabetes participating in the Action in Diabetes and Vascular Disease (ADVANCE) study (mean age at entry 66 y). The probability of hospital utilization and number of days in hospital for major events associated with coronary disease, cerebrovascular disease, congestive heart failure, peripheral vascular disease, and nephropathy were estimated for three regions (Asia, Eastern Europe, and Established Market Economies) using multiple regression analysis. The resulting estimates of days spent in hospital were multiplied by regional estimates of the costs per hospital bed-day from the World Health Organization to compute annual acute and long-term costs associated with the different types of complications. To assist, comparability, costs are reported in international dollars (Int$), which represent a hypothetical currency that allows for the same quantities of goods or services to be purchased regardless of country, standardized on purchasing power in the United States. A cost calculator accompanying this paper enables the estimation of costs for individual countries and translation of these costs into local currency units. The probability of attending a hospital following an event was highest for heart failure (93%–96% across regions) and lowest for nephropathy (15%–26%). The average numbers of days in hospital given at least one admission were greatest for stroke (17–32 d across region) and heart failure (16–31 d) and lowest for nephropathy (12–23 d). Considering regional differences, probabilities of hospitalization were lowest in Asia and highest in Established Market Economies; on the other hand, lengths of stay were highest in Asia and lowest in Established Market Economies. Overall estimated annual hospital costs for patients with none of the specified events or event histories ranged from Int$76 in Asia to Int$296 in Established Market Economies. All complications included in this analysis led to significant increases in hospital costs; coronary events, cerebrovascular events, and heart failure were the most costly, at more than Int$1,800, Int$3,000, and Int$4,000 in Asia, Eastern Europe, and Established Market Economies, respectively. Conclusions Major complications of diabetes significantly increase hospital use and costs across various settings and are likely to impose a high economic burden on health care systems. Please see later in the article for the Editors' Summary PMID:20186272

Four ECG left ventricular hypertrophy criteria and the risk of cardiovascular events and mortality in patients with vascular disease.

PubMed

van Kleef, Monique E A M; Visseren, Frank L J; Vernooij, Joris W P; Nathoe, Hendrik M; Cramer, Maarten-Jan M; Bemelmans, Remy H H; van der Graaf, Yolanda; Spiering, Wilko

2018-06-06

The relation between different electrocardiographic left ventricular hypertrophy (ECG-LVH) criteria and cardiovascular risk in patients with clinical manifest arterial disease is unclear. Therefore, we determined the association between four ECG-LVH criteria: Sokolow-Lyon, Cornell product, Cornell/strain index and Framingham criterion; and risk of cardiovascular events and mortality in this population. Risk of cardiovascular events was estimated in 6913 adult patients with clinical manifest arterial disease originating from the Secondary Manifestations of ARTerial disease (SMART) cohort. Cox proportional regression analysis was used to estimate the risk of the four ECG-LVH criteria and the primary composite outcome: myocardial infarction (MI), stroke or cardiovascular death; and secondary outcomes: MI, stroke and all-cause mortality; adjusted for confounders. The highest prevalence of ECG-LVH was observed for Cornell product (10%) and Cornell/strain index (9%). All four ECG-LVH criteria were associated with an increased risk of the primary composite endpoint: Sokolow-Lyon (hazard ratio 1.37, 95% CI 1.13-1.66), Cornell product (hazard ratio 1.54, 95% CI 1.30-1.82), Cornell/strain index (hazard ratio 1.70, 95% CI 1.44-2.00) and Framingham criterion (hazard ratio 1.78, 95% CI 1.21-2.62). Cornell product, Cornell/strain index and Framingham criterion ECG-LVH were additionally associated with an elevated risk of secondary outcomes. Cardiovascular risk increased whenever two, or three or more ECG-LVH criteria were present concurrently. All four ECG-LVH criteria are associated with an increased risk of cardiovascular events. As Cornell/strain index is both highly prevalent and carries a high cardiovascular risk, this is likely the most relevant ECG-LVH criterion for clinical practice.

CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea.

PubMed

McEvoy, R Doug; Antic, Nick A; Heeley, Emma; Luo, Yuanming; Ou, Qiong; Zhang, Xilong; Mediano, Olga; Chen, Rui; Drager, Luciano F; Liu, Zhihong; Chen, Guofang; Du, Baoliang; McArdle, Nigel; Mukherjee, Sutapa; Tripathi, Manjari; Billot, Laurent; Li, Qiang; Lorenzi-Filho, Geraldo; Barbe, Ferran; Redline, Susan; Wang, Jiguang; Arima, Hisatomi; Neal, Bruce; White, David P; Grunstein, Ron R; Zhong, Nanshan; Anderson, Craig S

2016-09-08

Obstructive sleep apnea is associated with an increased risk of cardiovascular events; whether treatment with continuous positive airway pressure (CPAP) prevents major cardiovascular events is uncertain. After a 1-week run-in period during which the participants used sham CPAP, we randomly assigned 2717 eligible adults between 45 and 75 years of age who had moderate-to-severe obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care (CPAP group) or usual care alone (usual-care group). The primary composite end point was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack. Secondary end points included other cardiovascular outcomes, health-related quality of life, snoring symptoms, daytime sleepiness, and mood. Most of the participants were men who had moderate-to-severe obstructive sleep apnea and minimal sleepiness. In the CPAP group, the mean duration of adherence to CPAP therapy was 3.3 hours per night, and the mean apnea-hypopnea index (the number of apnea or hypopnea events per hour of recording) decreased from 29.0 events per hour at baseline to 3.7 events per hour during follow-up. After a mean follow-up of 3.7 years, a primary end-point event had occurred in 229 participants in the CPAP group (17.0%) and in 207 participants in the usual-care group (15.4%) (hazard ratio with CPAP, 1.10; 95% confidence interval, 0.91 to 1.32; P=0.34). No significant effect on any individual or other composite cardiovascular end point was observed. CPAP significantly reduced snoring and daytime sleepiness and improved health-related quality of life and mood. Therapy with CPAP plus usual care, as compared with usual care alone, did not prevent cardiovascular events in patients with moderate-to-severe obstructive sleep apnea and established cardiovascular disease. (Funded by the National Health and Medical Research Council of Australia and others; SAVE ClinicalTrials.gov number, NCT00738179 ; Australian New Zealand Clinical Trials Registry number, ACTRN12608000409370 .).

Bringing Antonovsky's salutogenic theory to life: A qualitative inquiry into the experiences of young people with congenital heart disease.

PubMed

Apers, Silke; Rassart, Jessica; Luyckx, Koen; Oris, Leen; Goossens, Eva; Budts, Werner; Moons, Philip

2016-01-01

Antonovsky coined sense of coherence (SOC) as the central concept of his salutogenic theory focusing on the origins of well-being. SOC captures the degree to which one perceives the world as comprehensible, manageable, and meaningful. Life events and resources are considered to be the building blocks of a person's SOC. However, mainly quantitative studies have looked into the role of life events and resources. Therefore, the present study aims to gain a deeper insight into the experiences of patients with congenital heart disease (CHD) regarding resources and life events. For this qualitative study, patients were selected from the sample of a preceding study on development of SOC (n = 429). In total, 12 young individuals with CHD who had either a weak (n = 6) or strong SOC (n = 6) over time were interviewed (8 women, median age of 20 years). Data analysis was based on the constant comparative method as detailed in the Qualitative Analysis Guide of Leuven. Commonalities and differences between patients from both groups were explored. The following themes emerged: (1) self-concept; (2) social environment; (3) daytime activities; (4) life events and disease-related turning points; (5) stress and coping; and (6) illness integration. Additionally, the degree of personal control was identified as an overarching topic that transcended the other themes when comparing both groups of patients. These results may have implications for the structure and content of interventions improving well-being in young people with CHD.

Immune defenses of healthy, bleached and diseased Montastraea faveolata during a natural bleaching event.

PubMed

Mydlarz, Laura D; Couch, Courtney S; Weil, Ernesto; Smith, Garriet; Harvell, C Drew

2009-11-16

One prominent hypothesis regarding climate change and scleractinian corals is that thermal stress compromises immune competence. To test this hypothesis we tracked how the immune defenses of bleached, apparently healthy and yellow band disease (YBD) diseased Montastraea faveolata colonies varied with natural thermal stress in southwestern Puerto Rico. Colonies were monitored for 21 mo from the peak of the bleaching event in October 2005 to August 2007. Since sea surface temperature was significantly higher in summer and fall 2005 than 2006, year of collection was used as a proxy for temperature stress, and colony fragments collected in 2005 were compared with those collected in 2006. Mortality rate was high (43% overall) and all colonies (except one) either died or became infected with YBD by August 2007. YBD-infected tissue did not bleach (i.e. expel zooxanthellae) during the 2005 bleaching event, even when healthy tissue of these colonies bleached. Immune activity was assayed by measuring prophenoloxidase (PPO), peroxidase (POX), lysozyme-like (LYS) and antibacterial (AB) activity. Immune activity was variable between all coral samples, but there was a significant elevation of PPO activity in bleached colonies collected in 2005 relative to apparently healthy and YBD-diseased corals in 2006. In YBD-diseased colonies, LYS and AB activity were elevated in both healthy and infected tissue, indicating a systemic response; activity levels in these colonies were higher compared to those that appeared healthy. In both these immune parameters, there was a trend for suppression of activity in corals that were bleached in 2005. These data, while complicated by between-genet variability, illustrate the complex interaction between disease and temperature stress on immune function.

In Vivo Hyperthermic Stress Model: An Easy Tool to Study the Effects of Oxidative Stress on Neuronal Tau Functionality in Mouse Brain.

PubMed

Chauderlier, Alban; Delattre, Lucie; Buée, Luc; Galas, Marie-Christine

2017-01-01

Oxidative damage is an early event in neurodegenerative disorders such as Alzheimer disease. To increase oxidative stress in AD-related mouse models is essential to study early mechanisms involved in the physiopathology of these diseases. In this chapter, we describe an experimental mouse model of transient and acute hyperthermic stress to induce in vivo an increase of oxidative stress in the brain of any kind of wild-type or transgenic mouse.

Glycemic control and macrovascular disease in types 1 and 2 diabetes mellitus: Meta-analysis of randomized trials.

PubMed

Stettler, Christoph; Allemann, Sabin; Jüni, Peter; Cull, Carole A; Holman, Rury R; Egger, Matthias; Krähenbühl, Stephan; Diem, Peter

2006-07-01

Uncertainty persists concerning the effect of improved long-term glycemic control on macrovascular disease in diabetes mellitus (DM). We performed a systematic review and meta-analysis of randomized controlled trials comparing interventions to improve glycemic control with conventional treatment in type 1 and type 2 diabetes. Outcomes included the incidence rate ratios for any macrovascular event, cardiac events, stroke, and peripheral arterial disease, and the number needed to treat intensively during 10 years to prevent one macrovascular event. The analysis was based on 8 randomized comparisons including 1800 patients with type 1 DM (134 macrovascular events, 40 cardiac events, 88 peripheral vascular events, 6 cerebrovascular events, 11293 person-years of follow-up) and 6 comparisons including 4472 patients with type 2 DM (1587 macrovascular events, 1197 cardiac events, 87 peripheral vascular events, 303 cerebrovascular events, 43607 person-years). Combined incidence rate ratios for any macrovascular event were 0.38 (95% CI 0.26-0.56) in type 1 and 0.81 (0.73-0.91) in type 2 DM. In type 1 DM, effect was mainly based on reduction of cardiac and peripheral vascular events and, in type 2 DM, due to reductions in stroke and peripheral vascular events. Effects appear to be particularly important in younger patients with shorter duration of diabetes. Our data suggest that attempts to improve glycemic control reduce the incidence of macrovascular events both in type 1 and type 2 DM. In absolute terms, benefits are comparable, although effects on specific manifestations of macrovascular disease differ.

Modes of relating to contingency: An exploration of experiences in advanced cancer patients.

PubMed

Kruizinga, Renske; Hartog, Iris D; Scherer-Rath, Michael; Schilderman, Hans; Van Laarhoven, Hanneke

2017-08-01

Throughout their lives, people are confronted with unexpected life events, which can be difficult to incorporate into their life narratives. Such a confrontation can result in an experience of contingency. Different ways of relating to contingency have been described by Wuchterl: denying, acknowledging, and "encounter with the Other." In the present article, we aim to trace these theoretical distinctions in real-life experiences of patients. We analyzed 45 interviews using the constant comparative method with a directed content analysis approach in the Atlas.ti coding program. The interviews originated from a randomized controlled trial evaluating an assisted reflection on life events and ultimate life goals. Seven spiritual counselors from six hospitals in the Netherlands conducted the interviews from July of 2014 to March of 2016. All 45 patients had advanced cancer. We found four different modes into which relating to contingency can be classified: denying, acknowledging, accepting, and receiving. With denying, patients did not mention any impact of the life event on their lives. In acknowledging, the impact was recognized and a start was made to incorporate the event into their life. In accepting, patients went through a process of reinterpretation of the event. In receiving, patients talked about receiving insights from their illness and living a more conscious life. Our study is the first to investigate the different ways of relating to contingency in clinical practice. The defined modes will improve our understanding of the various ways in which cancer patients relate to their disease, allowing caregivers to better target and shape individual care.

Disease distribution and medical resources during the Beijing 2008 Olympic and Paralympic Games.

PubMed

Liang, Xue-Ya; Lan, Ling; Chen, Wei-Na; Zhang, Ai-Ping; Lü, Chao-Ying; Lü, Yan-Wei; Dai, Jian-Ping

2011-04-01

Appropriate planning and staffing for medical services at large-scale athletic events is essential to provide for a safe and successful competition. There are few well-documented accounts describing the demand for such services. The present study provided the data from the Beijing 2008 Olympics and Paralympics, with a view to provide the guidance for planning future events. A total of 22 029 and 8046 patients, who received medical care from a physician at an Olympic or Paralympic medical station, were included. The patient proportion among different personnel, various disease proportions at different kinds of venues, and the disease spectrum at specified venues at the Olympics and Paralympics were analyzed. At both games, the patient proportion varied by accreditation status. The staff accounted for the largest number of visits at the Olympics (44.83%) and Paralympics (36.95%), with respiratory diseases the most common. Various disease spectrums were discovered at the different kinds of venues. Surgical diseases were the most frequently listed reason for visits, both at competition and non-competition venues, especially during the Paralympics. The sport-related injuries accounted for a majority of the surgical cases during both games. At training venues, ear nose and throat diseases accounted for the greatest number of visits during both games. During both games, people contracted different diseases at different venues. Adequate surgeons should be designated to offer assistance mostly in trauma situations. Appropriate numbers of physicians in respiratory diseases and otorhinolaryngology is of great importance.

Vedolizumab Therapy in Severe Pediatric Inflammatory Bowel Disease.

PubMed

Conrad, Máire A; Stein, Ronen E; Maxwell, Elizabeth C; Albenberg, Lindsey; Baldassano, Robert N; Dawany, Noor; Grossman, Andrew B; Mamula, Petar; Piccoli, David A; Kelsen, Judith R

2016-10-01

Vedolizumab is effective for inducing and maintaining remission in adults with inflammatory bowel disease (IBD); however, there is limited pediatric data. This study aimed to describe the adverse events and clinical response to vedolizumab in refractory pediatric IBD. Disease activity indices, clinical response, concomitant medication use, and adverse events were measured over 22 weeks in an observational prospective cohort study of children with refractory IBD who had failed anti-tumor necrosis factor therapy and subsequently initiated vedolizumab therapy. Twenty-one subjects, 16 with Crohn disease, received vedolizumab. Clinical response was observed in 6/19 (31.6%) of the evaluable subjects at week 6 and in 11/19 (57.9%) by week 22. Before induction, 15/21 (71.4%) participants were treated with systemic corticosteroids, as compared with 7/21 (33.3%) subjects at 22 weeks. Steroid-free remission was seen in 1/20 (5.0%) subjects at 6 weeks, 3/20 (15.0%) at 14 weeks, and 4/20 (20.0%) at 22 weeks. There was statistically significant improvement in serum albumin and hematocrit; however, C-reactive protein increased by week 22 (P < 0.05). There were no infusion reactions. Vedolizumab was discontinued in 2 patients because of severe colitis, requiring surgical intervention. There is limited experience with vedolizumab therapy in pediatric IBD. There seems to be a marked number of subjects with clinical response in the first 6 weeks that increases further by week 22 despite the severity of disease in this cohort. Adverse events may not be directly related to vedolizumab. This study is limited by small sample size, and larger prospective studies are warranted.

Circulating Wnt inhibitory factor 1 levels are associated with development of cardiovascular disease.

PubMed

Ress, Claudia; Paulweber, Mariya; Goebel, Georg; Willeit, Karin; Rufinatscha, Kerstin; Strobl, Anna; Salzmann, Karin; Kedenko, Ludmilla; Tschoner, Alexander; Staudacher, Gabriele; Iglseder, Bernhard; Tilg, Herbert; Paulweber, Bernhard; Kaser, Susanne

2018-03-29

Wnt signaling is involved in atherosclerotic plaque formation directly and indirectly by modulating cardiovascular risk factors. We investigated whether circulating concentrations of Wnt inhibitors are associated with cardiovascular events in subjects with intermediate cardiovascular risk. 904 non-diabetic subjects participating in the SAPHIR study were assessed. In the SAPHIR study, middle-aged women without overt atherosclerotic disease at study entry were followed up for 10 years. 88 patients of our study cohort developed cardiovascular disease at follow-up (CVD group). Subjects of the CVD group were 1:2 case-control matched for age, sex, BMI and smoking behavior with subjects without overt cardiovascular disease after a 10 year-follow-up (control group). 18 patients of the CVD group and 19 subjects of the control group were retrospectively excluded due to fulfilling exclusion criteria. Baseline circulating sclerostin, dickkopf (DKK)-1, secreted frizzled-related protein (SFRP)-1 and Wnt inhibitory factor (WIF)-1 levels were assessed by ELISA. Baseline systemic SFRP-1 and WIF-1 levels were significantly higher in patients with cardiovascular events (n = 70) when compared to healthy controls (n = 157) while DKK-1 and sclerostin levels were similar in both groups. Logistic regression analysis revealed WIF-1 as a significant predictor of future cardiovascular events. Our data suggest that increased SFRP-1 and WIF-1 levels precede the development of symptomatic atherosclerotic disease. Assessment of systemic WIF-1 levels, which turned out to be independently associated with CVD, might help to early identify patients at intermediate cardiovascular risk. Copyright © 2018 Elsevier B.V. All rights reserved.

Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes.

PubMed

Wanner, Christoph; Inzucchi, Silvio E; Lachin, John M; Fitchett, David; von Eynatten, Maximilian; Mattheus, Michaela; Johansen, Odd Erik; Woerle, Hans J; Broedl, Uli C; Zinman, Bernard

2016-07-28

Diabetes confers an increased risk of adverse cardiovascular and renal events. In the EMPA-REG OUTCOME trial, empagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes at high risk for cardiovascular events. We wanted to determine the long-term renal effects of empagliflozin, an analysis that was a prespecified component of the secondary microvascular outcome of that trial. We randomly assigned patients with type 2 diabetes and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m(2) of body-surface area to receive either empagliflozin (at a dose of 10 mg or 25 mg) or placebo once daily. Prespecified renal outcomes included incident or worsening nephropathy (progression to macroalbuminuria, doubling of the serum creatinine level, initiation of renal-replacement therapy, or death from renal disease) and incident albuminuria. Incident or worsening nephropathy occurred in 525 of 4124 patients (12.7%) in the empagliflozin group and in 388 of 2061 (18.8%) in the placebo group (hazard ratio in the empagliflozin group, 0.61; 95% confidence interval, 0.53 to 0.70; P<0.001). Doubling of the serum creatinine level occurred in 70 of 4645 patients (1.5%) in the empagliflozin group and in 60 of 2323 (2.6%) in the placebo group, a significant relative risk reduction of 44%. Renal-replacement therapy was initiated in 13 of 4687 patients (0.3%) in the empagliflozin group and in 14 of 2333 patients (0.6%) in the placebo group, representing a 55% lower relative risk in the empagliflozin group. There was no significant between-group difference in the rate of incident albuminuria. The adverse-event profile of empagliflozin in patients with impaired kidney function at baseline was similar to that reported in the overall trial population. In patients with type 2 diabetes at high cardiovascular risk, empagliflozin was associated with slower progression of kidney disease and lower rates of clinically relevant renal events than was placebo when added to standard care. (Funded by the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance; EMPA-REG OUTCOME ClinicalTrials.gov number, NCT01131676.).

All-Atom Simulations Reveal How Single-Point Mutations Promote Serpin Misfolding

NASA Astrophysics Data System (ADS)

Wang, Fang; Orioli, Simone; Ianeselli, Alan; Spagnolli, Giovanni; a Beccara, Silvio; Gershenson, Anne; Faccioli, Pietro; Wintrode, Patrick L.

2018-05-01

Protein misfolding is implicated in many diseases, including the serpinopathies. For the canonical inhibitory serpin {\\alpha}1-antitrypsin (A1AT), mutations can result in protein deficiencies leading to lung disease, and misfolded mutants can accumulate in hepatocytes leading to liver disease. Using all-atom simulations based on the recently developed Bias Functional algorithm we elucidate how wild-type A1AT folds and how the disease-associated S (Glu264Val) and Z (Glu342Lys) mutations lead to misfolding. The deleterious Z mutation disrupts folding at an early stage, while the relatively benign S mutant shows late stage minor misfolding. A number of suppressor mutations ameliorate the effects of the Z mutation and simulations on these mutants help to elucidate the relative roles of steric clashes and electrostatic interactions in Z misfolding. These results demonstrate a striking correlation between atomistic events and disease severity and shine light on the mechanisms driving chains away from their correct folding routes.

Fault tree analysis of the causes of waterborne outbreaks.

PubMed

Risebro, Helen L; Doria, Miguel F; Andersson, Yvonne; Medema, Gertjan; Osborn, Keith; Schlosser, Olivier; Hunter, Paul R

2007-01-01

Prevention and containment of outbreaks requires examination of the contribution and interrelation of outbreak causative events. An outbreak fault tree was developed and applied to 61 enteric outbreaks related to public drinking water supplies in the EU. A mean of 3.25 causative events per outbreak were identified; each event was assigned a score based on percentage contribution per outbreak. Source and treatment system causative events often occurred concurrently (in 34 outbreaks). Distribution system causative events occurred less frequently (19 outbreaks) but were often solitary events contributing heavily towards the outbreak (a mean % score of 87.42). Livestock and rainfall in the catchment with no/inadequate filtration of water sources contributed concurrently to 11 of 31 Cryptosporidium outbreaks. Of the 23 protozoan outbreaks experiencing at least one treatment causative event, 90% of these events were filtration deficiencies; by contrast, for bacterial, viral, gastroenteritis and mixed pathogen outbreaks, 75% of treatment events were disinfection deficiencies. Roughly equal numbers of groundwater and surface water outbreaks experienced at least one treatment causative event (18 and 17 outbreaks, respectively). Retrospective analysis of multiple outbreaks of enteric disease can be used to inform outbreak investigations, facilitate corrective measures, and further develop multi-barrier approaches.

What predicts depression in cardiac patients: sociodemographic factors, disease severity or theoretical vulnerabilities?

PubMed

Doyle, F; McGee, H M; Conroy, R M; Delaney, M

2011-05-01

Depression is associated with increased cardiovascular risk in acute coronary syndrome (ACS) patients, but some argue that elevated depression is actually a marker of cardiovascular disease severity. Therefore, disease indices should better predict depression than established theoretical causes of depression (interpersonal life events, reinforcing events, cognitive distortions, type D personality). However, little theory-based research has been conducted in this area. In a cross-sectional design, ACS patients (n = 336) completed questionnaires assessing depression and psychosocial vulnerabilities. Nested logistic regression assessed the relative contribution of demographic or vulnerability factors, or disease indices or vulnerabilities to depression. In multivariate analysis, all vulnerabilities were independent significant predictors of depression (scoring above threshold on any scale, 48%). Demographic variables accounted for <1% of the variance of depression status, with vulnerabilities accounting for significantly more (pseudo R² = 0.16, χ²(change) = 150.9, df = 4, p < 0.001). Disease indices accounted for 7% of the variance in depression (pseudo R² = 0.07, χ² = 137.9, p < 0.001). However, adding the vulnerabilities increased the overall variance explained to 22% (pseudo R² = 0.22, χ² = 58.6, df = 4, p < 0.001). Theoretical vulnerabilities predicted depression status better than did either demographic or disease indices. The presence of these proximal causes of depression suggests that depression in ACS patients is not simply a result of cardiovascular disease severity.

The gender gap in heart disease: lessons from Eastern Europe.

PubMed

Weidner, Gerdi; Cain, Virginia S

2003-05-01

Why are men more susceptible to heart disease than women? Traditional risk factors cannot explain the gender gap in coronary heart disease (CHD) or the rapid increase in CHD mortality among middle-aged men in many of the newly independent states of Eastern Europe. However, Eastern European men score higher on stress-related psychosocial factors than men living in the West. Comparisons between the sexes also reveal differences in psychosocial and behavioral coronary risk factors favoring women, indicating that women's coping with stressful events may be more cardioprotective. Men's greater susceptibility to heart disease, particularly observable in many Eastern European countries, poses unique threats to public health and points to solutions in the behavioral and social arena.

Successful reinstitution of agalsidase beta therapy in Fabry disease patients with previous IgE-antibody or skin-test reactivity to the recombinant enzyme.

PubMed

Bodensteiner, David; Scott, C Ronald; Sims, Katherine B; Shepherd, Gillian M; Cintron, Rebecca D; Germain, Dominique P

2008-05-01

To determine if enzyme replacement therapy, involving intravenous infusions of recombinant human alpha-galactosidase A (agalsidase beta; Fabrazyme), could be safely continued in patients with Fabry disease who had been withdrawn from a previous clinical trial as a precautionary, protocol-specified measure due to detection of serum IgE antibodies or skin-test reactivity to agalsidase beta. The rechallenge infusion protocol specified strict patient monitoring conditions and graded dosing and infusion-rate schemes that were adjusted according to each patient's tolerance to the infusion. Six males (age: 26-66 years) were enrolled. During rechallenge, five patients received between 4 and 27 infusions; one patient voluntarily withdrew after one infusion because of recurrence of infusion-associated reactions. No anaphylactic reactions occurred. All adverse events, including four serious adverse events, were mild or moderate in intensity. Most treatment-related adverse events occurred during infusions (most commonly urticaria, vomiting, nausea, chills, pruritus, hypertension) and were resolved by infusion rate reductions and/or medication. After participation in the study, all patients, including the one who withdrew after one infusion, transitioned to commercial drug. Agalsidase beta therapy can be successfully reinstated in patients with Fabry disease who have developed IgE antibodies or skin test reactivity to the recombinant enzyme.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, R. C. G., E-mail: rcmart03@gwise.louisville.ed; Howard, J.; Tomalty, D.

PurposeTo evaluate the predictors of toxicity of drug-eluting beads loaded with irinotecan (DEBIRI) in the treatment of hepatic malignancies.Materials and MethodsA total of 330 patients were enrolled in a prospective, open-label, multicenter, multinational, single-arm study administering two types of drug-eluting beads (DEBIRI and drug-eluting beads loaded with doxorubicin). Complications were graded by Cancer Therapy Evaluation Program's Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. All events requiring additional physician treatment or requiring extended hospital stay or readmission within 30 days were included.ResultsA total of 109 patients received 187 DEBIRI treatments (range 1 to 5 per patient). The most commonmore » histology was metastatic colorectal cancer in 76% of patients, cholangiocarcinoma in 7% of patients, and other metastatic disease in 17% of patients. There were 35 patients (19%) with irinotecan treatments who sustained 158 treatment-related adverse events, with the median CTCAE event grade being CTCAE grade 2 (range 1 to 5). The most common adverse events were postembolic symptoms (42%). Multivariate analysis identified pretreatment and treatment-related risk factors as follows: lack of pretreatment with hepatic arterial lidocaine (p = 0.005), {>=}3 treatments (p = 0.05), achievement of complete stasis (p = 0.04), treatment with >100 mg DEBIRI in 1 treatment (p = 0.03), and bilirubin >2.0 {mu}g/dl with >50% liver involvement (p = 0.05). These factors were predictive of adverse events and significantly greater hospital length of stay.ConclusionsDEBIRI is safe when appropriate technique and treatment are used. Adverse events can be predicted based on pretreatment- and treatment-related factors, and their occurrence can become part of the informed consent process. Continued standardization of this treatment will lead to fewer adverse events and improved patient quality of life.« less

Event-based surveillance in north-western Ethiopia: experience and lessons learnt in the field

PubMed Central

Ota, Masaki; Beyene, Belay Bezabih

2015-01-01

This study piloted an event-based surveillance system at the health centre (HC) level in Ethiopia. The system collects rumours in the community and registers them in rumour logbooks to record events of disease outbreaks and public health emergencies. Descriptive analysis was conducted on the events captured at the 59 study HCs in the Amhara Region in north-western Ethiopia between October 2013 and November 2014. A total of 126 rumours were registered at two thirds of the HCs during the study period. The average event reporting time was 3.8 days; response time of the HCs was 0.6 days, resulting in a total response time of 4.4 days. The most commonly reported rumours were measles-related (n = 90, 71%). These rumours followed a similar pattern of measles cases reported in the routine surveillance system. The largest proportion of rumours were reported by community members (n = 38, 36%) followed by health post workers (n = 36, 29%) who were normally informed by the community members about the rumours. This surveillance system was established along with an existing indicator-based surveillance system and was simple to implement. The implementation cost was minimal, requiring only printing and distribution of rumour logbooks to the HCs and brief orientations to focal persons. In countries where routine surveillance is still weak, an event-based surveillance system similar to this should be considered as a supplementary tool for disease monitoring. PMID:26668763

Stressful life events and leucocyte telomere length: Do lifestyle factors, somatic and mental health, or low grade inflammation mediate this relationship? Results from a cohort of Danish men born in 1953.

PubMed

Osler, Merete; Bendix, Laila; Rask, Lene; Rod, Naja Hulvej

2016-11-01

Exposure to psychosocial stress is associated with increased risk of a number of somatic and mental disorders with relation to immune system functioning. We aimed to explore whether stressful events in early and recent life was associated with leucocyte telomere length (TL), which is assumed to reflect the accumulated burden of inflammation and oxidative stress occurring during the life course. We specifically aimed to address whether childhood constitutes a sensitive period and how much of the relation between stressful life events and TL is mediated through somatic and mental health, lifestyle, and markers of low-grade inflammation. A cohort of Danish men born in 1953 has been followed since birth in the Metropolit Cohort. These men underwent a health examination including blood sampling in 2010 and a subset of 324 also had a quantitative PCR-based measurement of TL. The relation between stressful life events and TL was analysed using structural equation modelling, which also provided an estimate of the proportion of the total effect mediated by somatic and mental health (cardiovascular disease, body mass and depressive mood), lifestyle factors, and low grade inflammation (C-reactive protein (CRP), interleukin (IL)-6 and IL-10). Total number of stressful events experienced during the life course was not associated with TL. In terms of sensitive periods, we found that number of stressful events in childhood was associated with shorter TL (β per number stressful events in childhood =-0.02(SE=-0.02); P=0.05). This relation was particularly strong for being placed away from home (β=-0.16; P<0.000). Thirty percent of the total effect of stressful events in childhood on TL was mediated by the included variables, with the largest proportion being mediated through depressive mood (16%) and CRP (9%). This study suggests that stressful events in childhood are associated with shorter TL in middle-aged men and that part of this relation is explained by depressive mood and low grade inflammation. Copyright © 2016 Elsevier Inc. All rights reserved.

Health related vulnerability due to chronic diseases: Impact on clinical services across emergency shelters in mass disasters

NASA Astrophysics Data System (ADS)

Koleva, Yordanka Nikolova

Chronic diseases are increasingly recognized as major contributors to the global burden of disease. Individuals with chronic disease are particularly vulnerable during mass emergencies as they may suffer an interruption in their therapeutic programs, leading to life-threatening conditions and complications. Based on the individual and community risk factors framework, three categories are defined as the most vulnerable to extreme natural events: physically, psychologically, and socially vulnerable. Complex emergencies that occurred in the recent decade have provided evidence that these groups suffer more pronounced effects than others. Individuals seeking community support during emergencies have been predominantly medically dependent, elderly, children, people with chronic health conditions, and lower socioeconomic status. The purpose of this study was to investigate the effect of health-related vulnerability on shelter operations, and to estimate the burden of chronic disease on community resources following catastrophic events. A comprehensive survey data collection conducted by the United States Public Health Service in 2005 was used to evaluate clinical services for populations with health conditions accommodated by Louisiana temporary disaster shelters. Correlation and multiple regression analyses determined the relationship between shelter characteristics and the factors predicting shelters' needs for short-term assistance. Significant predictors were identified in all three explored domains: structural shelter characteristics (sponsor, interpreter needed); clinical characteristics (access to health providers, clinic on site, staff had no days off); population characteristics (census, compromised mental health alone, or in combination with chronic conditions and diseases with epidemic potential). Shelters sponsored by faith-based organizations were less likely to be in risk of rapid resource depletion. Shelters with large census demonstrated association with the need of short-term assistance to maintain operations, as larger census was positively correlated with large numbers of individuals with vulnerabilities. Combined health-related vulnerability factor (chronic conditions, psycho-social disorders, and epidemic diseases) influenced significantly the risk of resource depletion. This study provides cross-sectional evidence that large concentration of populations with health-related vulnerabilities during disaster recovery phase is associated with increased demand for medical services. Chronic diseases with high prevalence and incidence like psycho-social disorders, diabetes, and cardiovascular conditions diagnosed during screenings could predict the overall burden on the health network.

Abrupt and unexpected stressful life events are followed with increased disease activity in spondyloarthritis: a two years web-based cohort study.

PubMed

Luo, Guanguan; Boelle, Pierre Yves; Turbelin, Clément; Costantino, Félicie; Kerneis, Solen; Nahal, Roula Said; Breban, Maxime; Hanslik, Thomas

2018-06-05

The contribution of environmental factors to spondyloarthritis (SpA) course remains poorly characterized. We previously reported a possible triggering of disease flares by stressful life events and vaccination. The objective of the present study was to specify the types of vaccine and life event that may influence disease activity. A prospective cohort of adult SpA was followed for two years. Patients logged on to a secured website every month to complete a standardized auto-questionnaire. They reported whether they had been exposed to stressful life events, vaccinations or other environmental factors. Patients were asked to rate the distress resulting from exposure to life events on a numerical rating scale (NRS: 0-10). Primary outcome variable was the variation of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) measured on two consecutive connections. Months where an event occurred were compared to months without events. The cutoff value of 1 is defined as the minimal clinically important variation for the BASDAI. The 272 enrolled SpA patients returned 3,388 questionnaires. Months where an abrupt and unexpected traumatic event occurred were associated with a significant increase of BASDAI of 0.57 [95%CI: 0.29; 0.85] (p<0.001). The higher the rating of distress, the larger the impact on BASDAI, reaching a clinically meaningful increase of 0.99 [0.17; 1.82] for a VNS ≥9. The effect of stressful events on BASDAI persisted during a median of 3 months. No other environmental factor was significantly associated with BASDAI variations. Among stressful life events, abrupt and unexpected events were associated with transient worsening of disease activity in SpA, which reached a clinically meaningful increase for the highest rating of distress. Association between vaccines and disease flare was not confirmed. Copyright © 2018. Published by Elsevier Masson SAS.

Safety Outcomes of Apixaban Compared With Warfarin in Patients With End-Stage Renal Disease.

PubMed

Sarratt, Stefanie C; Nesbit, Ross; Moye, Robert

2017-06-01

Current guidelines make no specific recommendations on the selection of direct oral anticoagulants for the prevention and treatment of venous thromboembolism in patients with end-stage renal disease (ESRD) receiving hemodialysis. Based on these guidelines, warfarin remains the anticoagulant of choice in these patients. To compare bleeding rates in patients receiving apixaban or warfarin with ESRD undergoing chronic hemodialysis. This was a single-center, retrospective, institutional review board-approved cohort analysis. Patients with ESRD undergoing chronic hemodialysis and receiving anticoagulation therapy with either apixaban or warfarin were included in this study. All data were collected from paper charts and electronic medical records and included documentation of bleeding events and related interventions. The primary outcome of this study was clinically relevant major bleeding events. Secondary outcomes included clinically relevant nonmajor bleeding events and minor bleeding events. A total of 160 patients were included in this study (warfarin group, n = 120; apixaban group, n = 40). There were 7 major bleeding events in the warfarin group compared with zero in the apixaban group ( P = 0.34). There were similar rates of clinically relevant nonmajor bleeding events (12.5% vs 5.8%, P = 0.17) and minor bleeding (2.5% vs 2.5%, P = 0.74) events in patients receiving apixaban and warfarin. There were no observed differences in bleeding rates in patients receiving apixaban compared with those receiving warfarin. Apixaban may be a cautious consideration in hemodialysis patients until there is further insight into the effect of subsequent, multiple doses on drug accumulation and clinical outcomes.

Coffee consumption and risk of cardiovascular events and all-cause mortality among women with type 2 diabetes

PubMed Central

Zhang, W.L.; Lopez-Garcia, E.; Li, T. Y.; Hu, F. B.; van Dam, R. M.

2009-01-01

Aims/hypothesis Coffee has been linked to both beneficial and harmful health effects, but data on its relation with cardiovascular disease and mortality in patients with type 2 diabetes are sparse. Methods This is a prospective cohort study including 7,170 women with diagnosed type 2 diabetes but free of cardiovascular disease or cancer at baseline. Coffee consumption was assessed in 1980 and then every 2 to 4 years through validated questionnaires. A total of 658 incident cardiovascular events (434 coronary heart disease and 224 stroke) and 734 deaths from all causes were documented between 1980 and 2004. Results After adjustment for age, smoking, and other cardiovascular risk factors, the relative risks (RRs) were 0.76 (95% CI, 0.50 to 1.14) for cardiovascular diseases (p trend = 0.09) and 0.80 (95% CI, 0.55 to 1.14) for all-cause mortality (p trend = 0.05) for the consumption of ≥ 4 cups/day caffeinated coffee as compared with nondrinkers. Similarly, multivariable RRs were 0.96 (95% CI, 0.66 to 1.38) for cardiovascular diseases (p trend = 0.84) and 0.76 (95% CI, 0.54 to 1.07) for all-cause mortality (p trend = 0.08) for the consumption of ≥ 2 cups/day decaffeinated coffee as compared with nondrinkers. Higher decaffeinated coffee consumption was associated with lower concentrations of glycosylated hemoglobin (6.2% for ≥ 2 cups/d versus 6.7% for < 1 cup/mo; p trend = 0.02). Conclusions These data provides evidence that habitual coffee consumption is not associated with increased risk for cardiovascular diseases or premature mortality among diabetic women. PMID:19266179

Incidence and predictors of obstetric and fetal complications in women with structural heart disease.

PubMed

van Hagen, Iris M; Roos-Hesselink, Jolien W; Donvito, Valentina; Liptai, Csilla; Morissens, Marielle; Murphy, Daniel J; Galian, Laura; Bazargani, Nooshin Mohd; Cornette, Jérôme; Hall, Roger; Johnson, Mark R

2017-10-01

Women with cardiac disease becoming pregnant have an increased risk of obstetric and fetal events. The aim of this study was to study the incidence of events, to validate the modified WHO (mWHO) risk classification and to search for event-specific predictors. The Registry Of Pregnancy And Cardiac disease is a worldwide ongoing prospective registry that has enrolled 2742 pregnancies in women with known cardiac disease (mainly congenital and valvular disease) before pregnancy, from January 2008 up to April 2014. Mean age was 28.2±5.5 years, 45% were nulliparous and 33.3% came from emerging countries. Obstetric events occurred in 231 pregnancies (8.4%). Fetal events occurred in 651 pregnancies (23.7%). The mWHO classification performed poorly in predicting obstetric (c-statistic=0.601) and fetal events (c-statistic=0.561). In multivariable analysis, aortic valve disease was associated with pre-eclampsia (OR=2.6, 95%CI=1.3 to 5.5). Congenital heart disease (CHD) was associated with spontaneous preterm birth (OR=1.8, 95%CI=1.2 to 2.7). Complex CHD was associated with small-for-gestational-age neonates (OR=2.3, 95%CI=1.5 to 3.5). Multiple gestation was the strongest predictor of fetal events: fetal/neonatal death (OR=6.4, 95%CI=2.5 to 16), spontaneous preterm birth (OR=5.3, 95%CI=2.5 to 11) and small-for-gestational age (OR=5.0, 95%CI=2.5 to 9.8). The mWHO classification is not suitable for prediction of obstetric and fetal events in women with cardiac disease. Maternal complex CHD was independently associated with fetal growth restriction and aortic valve disease with pre-eclampsia, potentially offering an insight into the pathophysiology of these pregnancy complications. The increased rates of adverse obstetric and fetal outcomes in women with pre-existing heart disease should be highlighted during counselling. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Lifetime trauma exposure and prospective cardiovascular events and all-cause mortality: findings from the Heart and Soul Study.

PubMed

Hendrickson, Carolyn M; Neylan, Thomas C; Na, Beeya; Regan, Mathilda; Zhang, Qian; Cohen, Beth E

2013-01-01

Little is known about the effect of cumulative psychological trauma on health outcomes in patients with cardiovascular disease. The objective of this study was to prospectively examine the association between lifetime trauma exposure and recurrent cardiovascular events or all-cause mortality in patients with existing cardiovascular disease. A total of 1021 men and women with cardiovascular disease were recruited in 2000 to 2002 and followed annually. Trauma history and psychiatric comorbidities were assessed at baseline using the Computerized Diagnostic Interview Schedule for DSM-IV. Health behaviors were assessed using standardized questionnaires. Outcome data were collected annually, and all medical records were reviewed by two independent, blinded physician adjudicators. We used Cox proportional hazards models to evaluate the association between lifetime trauma exposure and the composite outcome of cardiovascular events and all-cause mortality. During an average of 7.5 years of follow-up, there were 503 cardiovascular events and deaths. Compared with the 251 participants in the lowest trauma exposure quartile, the 256 participants in the highest exposure quartile had a 38% greater risk of adverse outcomes (hazard ratio = 1.38, 95% confidence interval = 1.06-1.81), adjusted for age, sex, race, income, education, depression, posttraumatic stress disorder, generalized anxiety disorder, smoking, physical inactivity, and illicit drug abuse. Cumulative exposure to psychological trauma was associated with an increased risk of recurrent cardiovascular events and mortality, independent of psychiatric comorbidities and health behaviors. These data add to a growing literature showing enduring effects of repeated trauma exposure on health that are independent of trauma-related psychiatric disorders such as depression and posttraumatic stress disorder.

Endothelial dysfunction, vascular disease and stroke: the ARTICO study.

PubMed

Roquer, J; Segura, T; Serena, J; Castillo, J

2009-01-01

Endothelial dysfunction is a fundamental step in the atherosclerotic disease process. Its presence is a risk factor for the development of clinical events, and may represent a marker of atherothrombotic burden. Also, endothelial dysfunction contributes to enhanced plaque vulnerability, may trigger plaque rupture, and favors thrombus formation. The assessment of endothelial vasomotion is a useful marker of atherosclerotic vascular disease. There are different methods to assess endothelial function: endothelium-dependent vasodilatation brachial flow-mediated dilation, cerebrovascular reactivity to L-arginine, and the determination of some biomarkers such as microalbuminuria, platelet function, and C-reactive protein. Endothelial dysfunction has been observed in stroke patients and has been related to stroke physiopathology, stroke subtypes, clinical severity and outcome. Resting ankle-brachial index (ABI) is also considered an indicator of generalized atherosclerosis, and a low ABI is associated with an increase in stroke incidence in the elderly. Despite all these data, there are no studies analyzing the predictive value of ABI for new cardiovascular events in patients after suffering an acute ischemic stroke. ARTICO is an ongoing prospective, observational, multicenter study being performed in 50 Spanish hospitals. The aim of the ARTICO study is to evaluate the prognostic value of a pathological ABI (

Ankle-brachial index and cardiovascular outcomes in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial.

PubMed

Abbott, J Dawn; Lombardero, Manuel S; Barsness, Gregory W; Pena-Sing, Ivan; Buitrón, L Virginia; Singh, Premranjan; Woodhead, Gail; Tardif, Jean-Claude; Kelsey, Sheryl F

2012-10-01

Peripheral arterial disease increases cardiovascular risk in many patient populations. The risks associated with an abnormal ankle-brachial index (ABI) in patients with type 2 diabetes and stable coronary artery disease have not been well described with respect to thresholds and types of cardiovascular events. We examined 2,368 patients in the BARI 2D trial who underwent ABI assessment at baseline. Death and major cardiovascular events (death, myocardial infarction and stroke) during follow-up (average 4.3 years) were assessed across the ABI spectrum and by categorized ABI: low (≤0.90), normal (0.91-1.3), high (>1.3), or noncompressible. A total of 12,568 person-years were available for mortality analysis. During follow-up, 316 patients died, and 549 had major cardiovascular events. After adjustment for potential confounders, with normal ABI as the referent group, a low ABI conferred an increased risk of death (relative risk [RR] 1.6, CI 1.2-2.2, P = .0005) and major cardiovascular events (RR 1.4, CI 1.1-1.7, P = .004). Patients with a high ABI had similar outcomes as patients with a normal ABI, but risk again increased in patients with a noncompressible ABI with a risk of death (RR 1.9, CI 1.3-2.8, P = .001) and major cardiovascular event (RR 1.5, CI 1.1-2.1, P = .01). In patients with coronary artery disease and type 2 diabetes, ABI screening and identification of ABI abnormalities including a low ABI (<1.0) or noncompressible artery provide incremental prognostic information. Copyright © 2012 Mosby, Inc. All rights reserved.

Extended Duration Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With Peripheral Arterial Disease: A Meta-Analysis.

PubMed

Ling, Hua; Andrews, Ebony; Ombengi, David; Li, Fang

2018-06-01

Patients with peripheral arterial disease (PAD) undergoing percutaneous coronary intervention (PCI) are at elevated risk of ischemic and bleeding events. However, the optimal duration of dual antiplatelet therapy (DAPT) after PCI in patients with PAD remains unclear. A systematic literature search was performed through June 2017 using PubMed, EMBASE and Cochrane databases with the following key terms: "dual antiplatelet therapy", "P2Y12 inhibitor", "myocardial infarction", "percutaneous coronary intervention", "stent", "peripheral arterial disease", and "ankle-brachial index". The analysis was restricted to randomized trials published in English in patients with PAD receiving extended DAPT (> 12-month) after PCI. Overall analysis was performed using Review Manager 5.3 with the Mantel-Haenszel method. Two randomized controlled trials involving 895 patients were included in this review. Compared to the placebo group, there was no statistical significance in the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients receiving extended DAPT (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.37 - 1.57; P = 0.46). The results were associated with substantial heterogeneity (I 2 = 71%, P = 0.07). Extended DAPT was not significantly associated with increased moderate/severe bleeding events (OR 1.63, 95% CI 0.84 - 3.18; P = 0.15; I 2 = 0%, P = 0.59). The extended DAPT was associated with 82% relative risk reduction in the events of definite/probably stent thrombosis. Among patients with PAD, extended DAPT after PCI resulted in a non-significant difference in ischemic and bleeding events compared to placebo, respectively. The routine use of extended DAPT in this cohort should be carefully evaluated.

Relation of Carotid Artery Plaque to Coronary Heart Disease and Stroke in Chinese Patients: Does Hyperglycemia Status Matter?

PubMed

Zhou, Huanhuan; Wang, Xiaoyun; Zhu, Junya; Fish, Anne; Kong, Weimin; Li, Fan; Liu, Lin; Yuan, Xiaodan; Gao, Xin; Lou, Qingqing

2018-03-01

To examine the association of carotid artery plaque with the incident coronary heart disease and stroke events in Chinese patients and explore whether the association differs between patients with and without hyperglycemia. We evaluated plaque, and blood pressure, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting serum insulin, fasting plasma glucose, 2 h postprandial glucose and Homeostasis model assessment of insulin resistance in 253 Chinese patients. T-test and X 2 test were used to compare the clinical characteristics and Binary logistic regression was applied to analyze the association of coronary heart disease and stroke between patients with and without hyperglycemia. Among 253 patients, 162 patients had hyperglycemia (i. e., diabetes, impaired glucose regulation and stress induced hyperglycemia) and 155 (61.3%) patients had plaque. Fasting plasma glucose, 2 h postprandial glucose and Homeostasis model assessment of insulin resistance, triglycerides, plaque were significantly higher in the hyperglycemia group than non-hyperglycemia. The incident coronary heart disease and stroke events in patients with plaque were 2.254 (95%CI,1.203-4.224) and 2.437 (95%CI,1.042-5.701) times higher than those without plaque, respectively. Among hyperglycemia subgroup, plaque was an independent risk factor for coronary heart disease (OR,3.075,95%CI,1.353-6.992) and stroke (OR,3.571,95%CI,1.460-8.737). The slopes (associations between coronary heart disease/stroke and plaque) were steeper in the hyperglycemia group than those in the non-hyperglycemia group (coronary heart disease OR,3.075 vs. 2.614; stroke OR,3.571 vs. 3.307). The incident coronary heart disease and stroke events in patients with plaque were higher than those without plaque, and this difference was more pronounced for patients with hyperglycemia vs. those without hyperglycemia. © Georg Thieme Verlag KG Stuttgart · New York.

Hypertension Control in Adults With Diabetes Mellitus and Recurrent Cardiovascular Events: Global Results From the Trial Evaluating Cardiovascular Outcomes With Sitagliptin.

PubMed

Navar, Ann Marie; Gallup, Dianne S; Lokhnygina, Yuliya; Green, Jennifer B; McGuire, Darren K; Armstrong, Paul W; Buse, John B; Engel, Samuel S; Lachin, John M; Standl, Eberhard; Van de Werf, Frans; Holman, Rury R; Peterson, Eric D

2017-11-01

Systolic blood pressure (SBP) treatment targets for adults with diabetes mellitus remain unclear. SBP levels among 12 275 adults with diabetes mellitus, prior cardiovascular disease, and treated hypertension were evaluated in the TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) randomized trial of sitagliptin versus placebo. The association between baseline SBP and recurrent cardiovascular disease was evaluated using multivariable Cox proportional hazards modeling with restricted cubic splines, adjusting for clinical characteristics. Kaplan-Meier curves by baseline SBP were created to assess time to cardiovascular disease and 2 potential hypotension-related adverse events: worsening kidney function and fractures. The association between time-updated SBP and outcomes was examined using multivariable Cox proportional hazards models. Overall, 42.2% of adults with diabetes mellitus, cardiovascular disease, and hypertension had an SBP ≥140 mm Hg. The association between SBP and cardiovascular disease risk was U shaped, with a nadir ≈130 mm Hg. When the analysis was restricted to those with baseline SBP of 110 to 150 mm Hg, the adjusted association between SBP and cardiovascular disease risk was flat (hazard ratio per 10-mm Hg increase, 0.96; 95% confidence interval, 0.91-1.02). There was no association between SBP and risk of fracture. Above 150 mm Hg, higher SBP was associated with increasing risk of worsening kidney function (hazard ratio per 10-mm Hg increase, 1.10; 95% confidence interval, 1.02-1.18). Many patients with diabetes mellitus have uncontrolled hypertension. The U-shaped association between SBP and cardiovascular disease events was largely driven by those with very high or low SBP, with no difference in cardiovascular disease risk between 110 and 150 mm Hg. Lower SBP was not associated with higher risks of fractures or worsening kidney function. © 2017 American Heart Association, Inc.

Increasing cardiopulmonary emergency visits by long-range transported Asian dust storms in Taiwan.

PubMed

Chan, Chang-Chuan; Chuang, Kai-Jen; Chen, Wen-Jone; Chang, Wei-Tien; Lee, Chung-Te; Peng, Chi-Ming

2008-03-01

This study aims to explore whether Asian dust storms can affect health after 4000 km long-range transport from their origins to downwind areas. Asian dust storms reaching Taipei, Taiwan are tracked by satellite images and confirmed by backward trajectory analysis and ground air pollution monitoring between 1995 and 2002. Our outcome variables include emergency visits for ischaemic heart diseases (ICD-9-CM 410-411, 414), cerebrovascular diseases (ICD-9-CM 430-437), and chronic obstructive pulmonary diseases (COPD) (ICD-9-CM 493, 496) from the National Taiwan University Hospital (NTUH). We use simple paired t-test and Poisson regression models to compare difference in emergency visits, air pollution levels and meteorological conditions for the pairs of Asian dust events and pre-dust periods. There were 39 high dust events with PM(10) greater than 90 microg/m(3) and another 46 low dust events with PM(10) less than 90 microg/m(3). Compared to their pre-dust periods, PM(10) concentrations are significantly increased by 77 microg/m(3) per event for the high dust events. Asian dust storms increase cardiopulmonary emergency visits during storm-affecting periods in Taipei when ambient PM(10) concentrations are above 90 microg/m(3). Compared to their pre-dust periods, emergency visits for ischaemic heart diseases, cerebrovascular diseases, and COPD during high dust events are increased by 0.7 case (35%), 0.7 case (20%), and 0.9 case (20%) per event, respectively, by paired t-tests. By comparing the model-predicted to the observed emergency visits, we find emergency visits for cardiovascular diseases (ICD-9-CM 410-411, 414, 430-437) were significantly increased by 2.9 cases (67%) per event for the 39 high Asian dust events.

Association of bariatric surgery with risk of acute care use for hypertension-related disease in obese adults: population-based self-controlled case series study.

PubMed

Shimada, Yuichi J; Tsugawa, Yusuke; Iso, Hiroyasu; Brown, David F M; Hasegawa, Kohei

2017-08-23

Hypertension carries a large societal burden. Obesity is known as a risk factor for hypertension. However, little is known as to whether weight loss interventions reduce the risk of hypertension-related adverse events, such as acute care use (emergency department [ED] visit and/or unplanned hospitalization). We used bariatric surgery as an instrument for investigating the effect of large weight reduction on the risk of acute care use for hypertension-related disease in obese adults with hypertension. We performed a self-controlled case series study of obese patients with hypertension who underwent bariatric surgery using population-based ED and inpatient databases that recorded every bariatric surgery, ED visit, and hospitalization in three states (California, Florida, and Nebraska) from 2005 to 2011. The primary outcome was acute care use for hypertension-related disease. We used conditional logistic regression to compare each patient's risk of the outcome event during sequential 12-month periods, using pre-surgery months 13-24 as the reference period. We identified 980 obese patients with hypertension who underwent bariatric surgery. The median age was 48 years (interquartile range, 40-56 years), 74% were female, and 55% were non-Hispanic white. During the reference period, 17.8% (95% confidence interval [CI], 15.4-20.2%) had a primary outcome event. The risk remained unchanged in the subsequent 12-month pre-surgery period (18.2% [95% CI, 15.7-20.6%]; adjusted odds ratio [aOR] 1.02 [95% CI, 0.83-1.27]; P = 0.83). In the first 12-month period after bariatric surgery, the risk significantly decreased (10.5% [8.6-12.4%]; aOR 0.58 [95% CI, 0.45-0.74]; P < 0.0001). Similarly, the risk remained significantly reduced in the 13-24 months after bariatric surgery (12.9% [95% CI, 10.8-15.0%]; aOR 0.71 [95% CI, 0.57-0.90]; P = 0.005). By contrast, there was no significant reduction in the risk among obese patients who underwent non-bariatric surgery (i.e., cholecystectomy, hysterectomy, spinal fusion, or mastectomy). In this population-based study of obese adults with hypertension, we found that the risk of acute care use for hypertension-related disease decreased by 40% after bariatric surgery. The data provide the best evidence on the effectiveness of substantial weight loss on hypertension-related morbidities, underscoring the importance of discussing options for weight reduction when treating obese patients with hypertension.

Using the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey to Predict the Occurrence of Short-Term Coronary Heart Disease Events in Women.

PubMed

McSweeney, Jean C; Cleves, Mario A; Fischer, Ellen P; Pettey, Christina M; Beasley, Brittany

Few instruments capture symptoms that predict cardiac events in the short-term. This study examines the ability of the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey to predict acute cardiac events within 3 months of administration and to identify the prodromal symptoms most associated with short-term risk in women without known coronary heart disease. The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey was administered to 1,097 women referred to a cardiologist for initial coronary heart disease evaluation. Logistic regression models were used to examine prodromal symptoms individually and in combination to identify the subset of symptoms most predictive of an event within 3 months. Fifty-one women had an early cardiac event. In bivariate analyses, 4 of 30 prodromal symptoms were significantly associated with event occurrence within 90 days. In adjusted analyses, women reporting arm pain or discomfort and unusual fatigue were more likely (OR, 4.67; 95% CI, 2.08-10.48) to have a cardiac event than women reporting neither. The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey may assist in predicting short-term coronary heart disease events in women without known coronary heart disease. Copyright © 2017 Jacobs Institute of Women's Health. All rights reserved.

Differences in the health-related quality of life, affective status, and personality between irritable bowel syndrome and inflammatory bowel disease patients.

PubMed

Tkalcić, Mladenka; Hauser, Goran; Stimac, Davor

2010-07-01

To investigate differences in the health-related quality of life (HRQoL), number of stressful life events, affective status, and some personality characteristics between patients with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) as well as their possible role in disease activity. Fifty-six IBS outpatients, age range 25-75 years (mean = 48.64; SD = 13.04) and 43 outpatients with IBD, age range 19-74 years (mean = 42.90; SD = 15.44), participated in this study. Patients filled out the following questionnaires: Short-Form 36 Health Survey, Beck Depression Inventory, Spielberger's Trait-Anxiety Inventory, Big Five Inventory, and Stressful Life Events Questionnaire. There were significant differences in the physical component (F = 10.80, P<0.001) of the general HRQoL as well as in anxiety (F = 7.23, P<0.01) and neuroticism (F = 8.90, P<0.01) between patients with IBS and IBD. IBS patients showed a significantly higher level of anxiety and neuroticism and better physical aspects of general HRQoL compared with IBD patients. The results of standard regression analyses indicated that a significant predictor (beta = -0.44, P<0.01) for the perceived disease activity in IBS was neuroticism as a personality trait. The results of this study show that the patients with IBS are more prone to the effect of psychosocial variables on gastrointestinal symptoms compared with patients with organic gastrointestinal diseases such as IBD. IBS patients experienced a higher level of anxiety and expressed a higher level of neuroticism as a personality trait compared with IBD patients.

Sepsis in Poland: Why Do We Die?

PubMed Central

Rorat, Marta; Jurek, Tomasz

2015-01-01

Objective To investigate the adverse events and potential risk factors in patients who develop sepsis. Subjects and Methods Fifty-five medico-legal opinion forms relating to sepsis cases issued by the Department of Forensic Medicine, Wroclaw, Poland, between 2004 and 2013 were analyzed for medical errors and risk factors for adverse events. Results The most common causes of medical errors were a lack of knowledge in recognition, diagnosis and therapy as well as ignorance of risk. The common risk factors for adverse events were deferral of a diagnostic or therapeutic decision, high-level anxiety of patients or their families about the patient's health and actively seeking for help. The most significant risk factors were communication errors, not enough medical staff, stereotype-based thinking about diseases and providing easy explanations for serious symptoms. Conclusion The most common cause of adverse events related to sepsis in the Polish health-care system was a lack of knowledge about the symptoms, diagnosis and treatment as well as the ignoring of danger. A possible means of improving safety might be through spreading knowledge and creating medical management algorithms for all health-care workers, especially physicians. PMID:25501966

Inflammatory bowel disease and venous thromboembolism during pregnancy and the postpartum period.

PubMed

Hansen, A T; Erichsen, R; Horváth-Puhó, E; Sørensen, H T

2017-04-01

Essentials Risk of pregnancy-related venous thromboembolism may be increased in inflammatory bowel disease. We performed a study on inflammatory bowel disease and pregnancy-related venous thromboembolism. Inflammatory bowel disease is a risk factor for pregnancy-related venous thromboembolism. Proper disease control before conception is pivotal to avoid venous thromboembolism. Background The incidence of inflammatory bowel disease (IBD) increases, and thus is more common, in pregnant women. IBD is a risk factor for venous thromboembolism (VTE) but it is not clear whether IBD predisposes women to an excess risk of VTE during pregnancy and the postpartum period. Methods This was a nationwide population-based cohort study of all deliveries during 1980-2013 in Denmark, using data from two nationwide health registries: the Danish National Patient Registry and the Medical Birth Registry. We computed incidence rates (IRs) per 1000 person-years, and crude and adjusted relative risks (RRs) with 95% confidence intervals (CIs) for VTE during pregnancy and the first 12 postpartum weeks in women with and without IBD. Results We included 1 046 754 women with 1 978 701 deliveries. We identified 3465 VTE events during pregnancy and 1302 VTE events postpartum. The IR for VTE during pregnancy was 4.20 (95% CI, 2.83-5.58) in IBD patients and 2.41 (95% CI, 2.33-2.50) in women without IBD, corresponding to an RR of 1.72 (95% CI, 1.22-2.43). Adjustment for maternal age and smoking (pregnancies during 1991-2013) yielded an adjusted RR of 1.67 (95% CI, 1.15-2.41). IBD flare was associated with an RR of 2.64 (95% CI, 1.69-4.14) for VTE during pregnancy. The IR for postpartum VTE was 7.03 (95% CI, 3.87-10.20) among IBD patients and 2.88 (95% CI, 2.72-3.04) in women without IBD, corresponding to an adjusted RR of 2.10 (95% CI, 1.33-3.30). Conclusions IBD is a risk factor for VTE during pregnancy and postpartum. © 2017 International Society on Thrombosis and Haemostasis.

Chronic stress and calcium oxalate stone disease: influence on blood cortisol and urine composition.

PubMed

Arzoz-Fàbregas, Montserrat; Ibarz-Servio, Luis; Fernández-Castro, Jordi; Valiente-Malmagro, Manuel; Roca-Antonio, Josep; Edo-Izquierdo, Sílvia; Buisan-Rueda, Oscar

2013-12-01

To evaluate the influence of chronic stress (CS) on urine composition of calcium oxalate (CaOx) stone patients and controls. This case-control study enrolled 128 patients during a period of 20 months. The cases were CaOx stone formers with a recent stone episode. Controls were matched by sex and age. Dimensions of CS were evaluated in cases and controls by validated self-report questionnaires measuring stressful life events, perceived stress, anxiety, depression, burnout, and satisfaction with life. Blood and urine samples were collected to determine cortisol levels and urinary composition. More relations between CS dimensions and blood and urine parameters were observed in cases than in controls. In cases, the blood cortisol level was related positively with the number of stressful life events (P = .03), intensity of these events (P = .04), and anxiety (P = .04). In addition, urinary magnesium (P = .03) and pyrophosphate (P = .05) levels were positively related with satisfaction with life and burnout, respectively. In contrast, urinary magnesium levels were negatively related with perceived stress (P = .01), anxiety (P = .016), and depression (P = .03). In controls, the number of stressful life events and the intensity of stressful life events was related positively with magnesium (P = .06, P = .02) levels and negatively with blood cortisol levels (P = .03, P = .004). Based on the variation between cases and controls in relations between CS dimensions and biochemical parameters, we hypothesize that CS may trigger a differential biological response in CaOx stone formers and controls, which in turn may promote or protect against CaOx stone formation. Copyright © 2013 Elsevier Inc. All rights reserved.

The Organization and Anatomy of Narrative Comprehension and Expression in Lewy Body Spectrum Disorders

PubMed Central

Ash, Sharon; Xie, Sharon; Gross, Rachel Goldmann; Dreyfuss, Michael; Boller, Ashley; Camp, Emily; Morgan, Brianna; O’Shea, Jessica; Grossman, Murray

2012-01-01

Objective Patients with Lewy body spectrum disorders (LBSD) such as Parkinson’s disease (PD), Parkinson’s disease with dementia (PDD), and dementia with Lewy bodies (DLB) exhibit deficits in both narrative comprehension and narrative expression. The present research examines the hypothesis that these impairments are due to a material-neutral deficit in organizational executive resources rather than to impairments of language per se. We predicted that comprehension and expression of narrative would be similarly affected and that deficits in both expression and comprehension of narrative would be related to the same anatomic distribution of prefrontal disease. Method We examined 29 LBSD patients and 26 healthy seniors on their comprehension and expression of narrative discourse. For comprehension, we measured accuracy and latency in judging events with high and low associativity from familiar scripts such as “going fishing.” The expression task involved maintaining the connectedness of events while narrating a story from a wordless picture book. Results LBSD patients were impaired on measures of narrative organization during both comprehension and expression relative to healthy seniors. Measures of organization during narrative expression and comprehension were significantly correlated with each other. These measures both correlated with executive measures but not with neuropsychological measures of lexical semantics or grammar. Voxel-based morphometry revealed overlapping regressions relating frontal atrophy to narrative comprehension, narrative expression, and measures of executive control. Conclusions Difficulty with narrative discourse in LBSD stems in part from a deficit of organization common to comprehension and expression. This deficit is related to prefrontal cortical atrophy in LBSD. PMID:22309984

Spatio-temporal dynamics of pneumonia in bighorn sheep

USGS Publications Warehouse

Cassirer, E. Frances; Plowright, Raina K.; Manlove, Kezia R.; Cross, Paul C.; Dobson, Andrew P.; Potter, Kathleen A.; Hudson, Peter J.

2013-01-01

Bighorn sheep mortality related to pneumonia is a primary factor limiting population recovery across western North America, but management has been constrained by an incomplete understanding of the disease. We analysed patterns of pneumonia-caused mortality over 14 years in 16 interconnected bighorn sheep populations to gain insights into underlying disease processes. 2. We observed four age-structured classes of annual pneumonia mortality patterns: all-age, lamb-only, secondary all-age and adult-only. Although there was considerable variability within classes, overall they differed in persistence within and impact on populations. Years with pneumonia-induced mortality occurring simultaneously across age classes (i.e. all-age) appeared to be a consequence of pathogen invasion into a naïve population and resulted in immediate population declines. Subsequently, low recruitment due to frequent high mortality outbreaks in lambs, probably due to association with chronically infected ewes, posed a significant obstacle to population recovery. Secondary all-age events occurred in previously exposed populations when outbreaks in lambs were followed by lower rates of pneumonia-induced mortality in adults. Infrequent pneumonia events restricted to adults were usually of short duration with low mortality. 3. Acute pneumonia-induced mortality in adults was concentrated in fall and early winter around the breeding season when rams are more mobile and the sexes commingle. In contrast, mortality restricted to lambs peaked in summer when ewes and lambs were concentrated in nursery groups. 4. We detected weak synchrony in adult pneumonia between adjacent populations, but found no evidence for landscape-scale extrinsic variables as drivers of disease. 5. We demonstrate that there was a >60% probability of a disease event each year following pneumonia invasion into bighorn sheep populations. Healthy years also occurred periodically, and understanding the factors driving these apparent fade-out events may be the key to managing this disease. Our data and modelling indicate that pneumonia can have greater impacts on bighorn sheep populations than previously reported, and we present hypotheses about processes involved for testing in future investigations and management.

Reducing the Blood Pressure-Related Burden of Cardiovascular Disease: Impact of Achievable Improvements in Blood Pressure Prevention and Control.

PubMed

Hardy, Shakia T; Loehr, Laura R; Butler, Kenneth R; Chakladar, Sujatro; Chang, Patricia P; Folsom, Aaron R; Heiss, Gerardo; MacLehose, Richard F; Matsushita, Kunihiro; Avery, Christy L

2015-10-27

US blood pressure reduction policies are largely restricted to hypertensive populations and associated benefits are often estimated based on unrealistic interventions. We used multivariable linear regression to estimate incidence rate differences contrasting the impact of 2 pragmatic hypothetical interventions to reduce coronary heart disease, stroke, and heart failure (HF) incidence: (1) a population-wide intervention that reduced systolic blood pressure by 1 mm Hg and (2) targeted interventions that reduced the prevalence of unaware, untreated, or uncontrolled blood pressure above goal (per Eighth Joint National Committee treatment thresholds) by 10%. In the Atherosclerosis Risk in Communities Study (n=15 744; 45 to 64 years at baseline, 1987-1989), incident coronary heart disease and stroke were adjudicated by physician panels. Incident HF was defined as the first hospitalization with discharge diagnosis code of "428." A 10% proportional reduction in unaware, untreated, or uncontrolled blood pressure above goal resulted in ≈4.61, 3.55, and 11.01 fewer HF events per 100,000 person-years in African Americans, and 3.77, 1.63, and 4.44 fewer HF events per 100 000 person-years, respectively, in whites. In contrast, a 1 mm Hg population-wide systolic blood pressure reduction was associated with 20.3 and 13.3 fewer HF events per 100 000 person-years in African Americans and whites, respectively. Estimated event reductions for coronary heart disease and stroke were smaller than for HF, but followed a similar pattern for both population-wide and targeted interventions. Modest population-wide shifts in systolic blood pressure could have a substantial impact on cardiovascular disease incidence and should be developed in parallel with interventions targeting populations with blood pressure above goal. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Immuno-virological discordance and the risk of non-AIDS and AIDS events in a large observational cohort of HIV-patients in Europe.

PubMed

Zoufaly, Alexander; Cozzi-Lepri, Alessandro; Reekie, Joanne; Kirk, Ole; Lundgren, Jens; Reiss, Peter; Jevtovic, Djordje; Machala, Ladislav; Zangerle, Robert; Mocroft, Amanda; Van Lunzen, Jan

2014-01-01

The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated. Patients in EuroSIDA starting at least 1 new antiretroviral drug with CD4<350 cells/µl and viral load (VL)>500 copies/mL were followed-up from the first day of VL< = 50 copies/ml until a new fatal/non-fatal non-AIDS/AIDS event. Considered non-AIDS events included non-AIDS malignancies, pancreatitis, severe liver disease with hepatic encephalopathy (>grade 3), cardio- and cerebrovascular events, and end-stage renal disease. Patients were classified over time according to whether current CD4 count was above (non-ID) or below (ID) baseline level. Relative rates (RR) of events were calculated for ID vs. non-ID using adjusted Poisson regression models. 2,913 patients contributed 11,491 person-years for the analysis of non-AIDS. 241 pre-specified non-AIDS events (including 84 deaths) and 89 AIDS events (including 10 deaths) occurred. The RR of developing pre-specified non-AIDS events for ID vs. non-ID was 1.96 (95% CI 1.37-2.81, p<0.001) in unadjusted analysis and 1.43 (0.94-2.17, p = 0.095) after controlling for current CD4 count. ID was not associated with the risk of AIDS events (aRR 0.76, 95% CI 0.41-1.38, p = 0.361). Compared to CD4 responders, patients with immuno-virological discordance may be at increased risk of developing non-AIDS events. Further studies are warranted to establish whether in patients with ID, strategies to directly modify CD4 count response may be needed besides the use of ART.

Neuromuscular complications of immune checkpoint inhibitor therapy.

PubMed

Kolb, Noah A; Trevino, Christopher R; Waheed, Waqar; Sobhani, Fatemeh; Landry, Kara K; Thomas, Alissa A; Hehir, Mike

2018-01-17

Immune checkpoint inhibitor (ICPI) therapy unleashes the body's natural immune system to fight cancer. ICPIs improve overall cancer survival, however, the unbridling of the immune system may induce a variety of immune-related adverse events. Neuromuscular immune complications are rare but they can be severe. Myasthenia gravis and inflammatory neuropathy are the most common neuromuscular adverse events but a variety of others including inflammatory myopathy are reported. The pathophysiologic mechanism of these autoimmune disorders may differ from that of non-ICPI-related immune diseases. Accordingly, while the optimal treatment for ICPI-related neuromuscular disorders generally follows a traditional paradigm, there are important novel considerations in selecting appropriate immunosuppressive therapy. This review presents 2 new cases, a summary of neuromuscular ICPI complications, and an approach to the diagnosis and treatment of these disorders. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

A lower baseline glomerular filtration rate predicts high mortality and newly cerebrovascular accidents in acute ischemic stroke patients.

PubMed

Dong, Kai; Huang, Xiaoqin; Zhang, Qian; Yu, Zhipeng; Ding, Jianping; Song, Haiqing

2017-02-01

Chronic kidney disease (CKD) is gradually recognized as an independent risk factor for cardiovascular and cardio-/cerebrovascular disease. This study aimed to examine the association of the estimated glomerular filtration rate (eGFR) and clinical outcomes at 3 months after the onset of ischemic stroke in a hospitalized Chinese population.Totally, 972 patients with acute ischemic stroke were enrolled into this study. Modified of Diet in Renal Disease (MDRD) equations were used to calculate eGFR and define CKD. The site and degree of the stenosis were examined. Patients were followed-up for 3 months. Endpoint events included all-cause death and newly ischemic events. The multivariate logistic model was used to determine the association between renal dysfunction and patients' outcomes.Of all patients, 130 patients (13.4%) had reduced eGFR (<60 mL/min/1.73 m), and 556 patients had a normal eGFR (≥90 mL/min/1.73 m). A total of 694 patients suffered from cerebral artery stenosis, in which 293 patients only had intracranial artery stenosis (ICAS), 110 only with extracranial carotid atherosclerotic stenosis (ECAS), and 301 with both ICAS and ECAS. The patients with eGFR <60 mL/min/1.73m had a higher proportion of death and newly ischemic events compared with those with a relatively normal eGFR. Multivariate analysis revealed that a baseline eGFR <60 mL/min/1.73 m increased the risk of mortality by 3.089-fold and newly ischemic events by 4.067-fold. In further analysis, a reduced eGFR was associated with increased rates of mortality and newly events both in ICAS patients and ECAS patients. However, only an increased risk of newly events was found as the degree of renal function deteriorated in ICAS patients (odds ratio = 8.169, 95% confidence interval = 2.445-14.127).A low baseline eGFR predicted a high mortality and newly ischemic events at 3 months in ischemic stroke patients. A low baseline eGFR was also a strong independent predictor for newly ischemic events in ICAS patients.

Monitoring emerging diseases of fish and shellfish using electronic sources.

PubMed

Thrush, M A; Dunn, P L; Peeler, E J

2012-10-01

New and emerging fish and shellfish diseases represent an important constraint to the growth and sustainability of many aquaculture sectors and have also caused substantial economic and environmental impacts in wild stocks. This paper details the results of 8 years of a monitoring programme for emerging aquatic animal diseases reported around the world. The objectives were to track global occurrences and, more specifically, to identify and provide advanced warning of disease threats that may affect wild and farmed fish stocks in the UK. A range of electronic information sources, including Internet newsletters, alerting services and news agency releases, was systematically searched for reports of new diseases, new presentations of known pathogens and known diseases occurring in new geographic locations or new host species. A database was established to log the details of key findings, and 250 emerging disease events in 52 countries were recorded during the period of study. These included 14 new diseases and a further 16 known diseases in new species. Viruses and parasites accounted for the majority of reports (55% and 24%, respectively), and known diseases occurring in new locations were the most important emerging disease category (in which viruses were dominant). Emerging diseases were reported disproportionally in salmonid species (33%), in farmed populations (62%) and in Europe and North America (80%). The lack of reports from some regions with significant aquaculture or fishery production may indicate that emerging diseases are not being recognized in these areas owing to insufficient surveillance or testing or that these events are being under-reported. The results are discussed in relation to processes underpinning disease emergence in the aquatic environment. © 2011 Crown Copyright. Reproduced with the permission of the Controller of Her Majesty’s Stationery Office and Centre for Environment Fisheries & Aquaculture Science.

Disease-related mortality exceeds treatment-related mortality in patients with chronic myeloid leukemia on second-line or later therapy.

PubMed

Pearson, Edward; McGarry, Lisa; Gala, Smeet; Nieset, Christopher; Nanavaty, Merena; Mwamburi, Mkaya; Levy, Yair

2016-04-01

Treatment of newly-diagnosed patients with chronic-phase chronic myeloid leukemia (CP-CML) with tyrosine kinase inhibitors (TKIs) results in near-normal life expectancy. However, CP-CML patients resistant to initial TKIs face a poorer prognosis and significantly higher CML-related mortality. We conducted a systematic literature review to evaluate the specific causes of deaths (diseases progression versus drug-related) in CP-CML patients receiving second- or third-line therapy. We identified eight studies based on our criteria that reported causes of death. Overall, 5% of second-line and 10% of third-line patients died during the study follow-up period. For second-line, (7 studies, n=1926), mortality was attributed to disease progression for 41% of deaths, 2% to treatment-related causes, 3% were treatment-unrelated, and 50% were unspecified adverse events (AEs), not likely related to study drug. In third-line, (2 studies, n=144), 71% deaths were attributed to disease progression, 7% treatment-related AEs, 14% treatment-unrelated and 7% unspecified AEs. Annual death rates for second- and third-line therapy were significantly higher than for general population in similar age group. Our findings suggest death attributed to disease progression is approximately 10 times that due to treatment-related AEs in patients with CP-CML receiving second- or third-line therapy. Therefore, the potential benefits of effective treatment for these patients with the currently available TKIs outweigh the risks of treatment-induced AEs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Serum C-reactive protein in the prediction of cardiovascular diseases: Overview of the latest clinical studies and public health practice.

PubMed

Avan, Amir; Tavakoly Sany, Seyedeh Belin; Ghayour-Mobarhan, Majid; Rahimi, Hamid Reza; Tajfard, Mohammad; Ferns, Gordon

2018-06-22

Cardiovascular disease is the most common cause of morbidity and mortality globally. Epidemiological studies using high-sensitivity assays for serum C-reactive protein have shown a consistent association between cardiovascular disease risk and serum C-reactive protein concentrations. C-reactive protein is a biomarker for inflammation, and has been established in clinical practice as an independent risk factor for cardiovascular disease events. There is evidence that serum C-reactive protein is an excellent biomarker of cardiovascular disease and is also an independent and strong predictor of adverse cardiovascular events. Further characterization of the impact and influence of lifestyle exposures and genetic variation on the C-reactive protein response to cardiovascular disease events may have implications for the therapeutic approaches to reduce cardiovascular disease events. This review summarizes the studies that have examined the association between serum C-reactive protein and the risk of cardiovascular disease. We also discuss the impact of independent factors and C-reactive protein genetic polymorphisms on baseline plasma C-reactive protein levels. © 2018 Wiley Periodicals, Inc.

Google Calendar Enhances Prospective Memory in Alzheimer's Disease: A Case Report.

PubMed

El Haj, Mohamad; Gallouj, Karim; Antoine, Pascal

2017-01-01

We investigated whether an external memory aid (i.e., Google Calendar) would alleviate prospective memory compromise in a patient with mild Alzheimer's disease. The patient was asked in the baseline phase to perform three prospective targeted events (e.g., attending her weekly bridge game at the community club) and three prospective control events (e.g., buying her weekly magazine). The same six prospective events were assessed in the intervention phase but the targeted-events were cued by Google Calendar while the control-events were not. Results showed less omission of the targeted events in the training phase than in the baseline phase, suggesting a positive effect of Google Calendar. This case report offers a unique view into how smartphone calendars may alleviate prospective memory compromise in patients with mild Alzheimer's disease.

Computationally predicted Adverse Outcome Pathway networks for liver-related diseases using publicly available data sources: Case studies and lessons learned

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework summarizes key information about mechanistic events leading to an adverse health or ecological outcome. In recent years computationally predicted AOPs (cpAOP) making use of publicly available data have been proposed as a means of accele...

A novel Coltivirus-related virus isolated from free-tailed bats from Côte d'Ivoire is able to infect human cells in vitro.

PubMed

Weiss, Sabrina; Dabrowski, Piotr Wojtek; Kurth, Andreas; Leendertz, Siv Aina J; Leendertz, Fabian H

2017-09-18

Zoonotic transmission events play a major role in the emergence of novel diseases. While such events are virtually impossible to predict, wildlife screening for potential emerging pathogens can be a first step. Driven by recent disease epidemics like severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Ebola, bats have gained special interest as reservoirs of emerging viruses. As part of a bigger study investigating pathogens in African bats we screened animals for the presence of known and unknown viruses. We isolated and characterised a novel reovirus from blood of free-tailed bats (Chaereophon aloysiisabaudiae) captured in 2006 in Côte d'Ivoire. The virus showed closest relationship with two human pathogenic viruses, Colorado tick fever virus and Eyach virus, and was able to infect various human cell lines in vitro. The study shows the presence of a coltivirus-related virus in bats from Sub-Sahara Africa. Serological studies could help to assess its impact on humans or wildlife health.

Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: a noninferiority trial.

PubMed

Carbonell-Estrany, Xavier; Simões, Eric A F; Dagan, Ron; Hall, Caroline B; Harris, Brian; Hultquist, Micki; Connor, Edward M; Losonsky, Genevieve A

2010-01-01

Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by approximately 50% compared with placebo. We compared the efficacy and safety of motavizumab, an investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies, with palivizumab. This randomized, double-blind, multinational, phase 3, noninferiority trial assessed safety and RSV hospitalization in 6635 preterm infants aged

Accidental drug deaths in Fulton County, Georgia, 2002: characteristics, case management and certification issues.

PubMed

Graham, Jason K; Hanzlick, Randy

2008-09-01

Historically, the duty of the medical examiner in assigning cause and manner of death in drug-related death cases has been fraught with controversial challenges. The lack of standardization in certifying drug-related deaths may involve differences among practicing forensic pathologists in their approach to such cases. The central objectives of the present study include characterization of current drug death patterns and the variability among medical examiners with respect to autopsy performance and death certification practices in one county medical examiner's office. Death certificates, scene information/investigative reports, autopsy reports, and toxicological laboratory results for each of the 100 cases of drug-related death occurring in 2002 in Fulton County, Georgia were reviewed. Comparison of overall autopsy rates and autopsy rates in drug-related death cases for each medical examiner individually and for the group collectively was performed. In examining cocaine-related deaths (most common), statistical analysis was performed for comparison of drug concentrations (cocaine and benzoylecgonine) between deaths certified as cocaine toxicity (poisoning) versus cocaine-complicating disease or causing an adverse event such as cerebral hemorrhage. Causes of accidental drug deaths included cocaine 40%, mixed drug intoxication 37%, opioids 10%, ethanol 7%, and prescription medication (nonopioid) 5%. Overall total autopsy rates in 2002 for each of the 6 independent medical examiners ranged from 51% to 69% (mean 64%), whereas autopsy rates in drug-related death ranged from 55% to 91% (mean 81%). In review of the subset of 40 cocaine-related deaths, 25% were certified as cocaine toxicity (poisoning), with the remaining 75% certified as cocaine-complicating disease or causing and adverse event. Autopsy rates in cocaine-related deaths were as follows: cocaine toxicity 80%, cocaine-complicating disease 77.3%, and cocaine causing adverse event 62.5%. Thirty-eight percent of cocaine-related deaths were considered to be of "low suspicion" for drug involvement at the time the death was reported to the medical examiner with the remaining 62% being of "high suspicion". Autopsy rates were somewhat lower in the low suspicion group (67%) versus the high suspicion group (72%). Comparison of drug levels between cocaine-related death certification groups was performed. No statistically significant difference was shown in drug levels (cocaine, P > 0.3; benzoylecgonine, P > 0.2) between deaths certified as cocaine toxicity versus those certified as cocaine-complicating disease or causing adverse event. In Fulton County, accidental drug deaths in 2002 most often involved cocaine either alone or in combination with opiates and/or alcohol. Cocaine, opiates, or both were involved in greater than three-fourths (77%) of all drug-related deaths. The majority of all decedents were black (57%) and male (76%) with an average age of 42.2 years. Cocaine and ethanol were more frequently detected in black decedents, whereas opiates and polydrug abuse were more common in white decedents throughout the period studied. Preliminary investigation showed a high index of suspicion for the specific drug involved in virtually all opiate and alcohol cases, and in 62% of cocaine-related cases. Overall, the 100 accidental drug deaths in 2002 accounted for 7.5% of all deaths investigated and certified by the Fulton County Medical Examiner's Office. Our study provides further evidence to support the lack of correlation between serum drug levels and the mechanism of drug toxicity in cocaine-related deaths. No statistically significant differences were shown in parent cocaine or benzoylecgonine concentrations between those cases certified as toxicities or poisonings versus those cases certified as aggravating underlying disease or causing an adverse event. In addition, 62% of the cocaine-related death cases were considered initially to be of high suspicion for drug-related death, thus emphasizing the strong importance of scene information/investigative reports in evaluating drug-death cases and in formulating plans of action to handle each individual case. Among the drug-death cases handled by 6 staff medical examiners at the Fulton County Medical Examiner's Office, variation existed in autopsy performance and death certification practices. These issues are discussed in the context of the National Association of Medical Examiners' (NAME) Position Paper on Cocaine, NAME Forensic Autopsy Performance Standards, and other relevant literature. Most variations relate to completeness of the cause-of-death statement (whether or not comorbid conditions are included) rather than classification of manner of death within the office. However, specific wording in the cause of death may have significant ramifications regarding drug-related mortality statistics processed by the vital statistics system, with possible under-representation of drug-related deaths in single-cause mortality data.

Feasibility, Drug Safety, and Effectiveness of Etiological Treatment Programs for Chagas Disease in Honduras, Guatemala, and Bolivia: 10-Year Experience of Médecins Sans Frontières

PubMed Central

Yun, Oliver; Lima, M. Angeles; Ellman, Tom; Chambi, Wilma; Castillo, Sandra; Flevaud, Laurence; Roddy, Paul; Parreño, Fernando; Albajar Viñas, Pedro; Palma, Pedro Pablo

2009-01-01

Background Chagas disease (American trypanosomiasis) is a zoonotic or anthropozoonotic disease caused by the parasite Trypanosoma cruzi. Predominantly affecting populations in poor areas of Latin America, medical care for this neglected disease is often lacking. Médecins Sans Frontières/Doctors Without Borders (MSF) has provided diagnostic and treatment services for Chagas disease since 1999. This report describes 10 years of field experience in four MSF programs in Honduras, Guatemala, and Bolivia, focusing on feasibility protocols, safety of drug therapy, and treatment effectiveness. Methodology From 1999 to 2008, MSF provided free diagnosis, etiological treatment, and follow-up care for patients <18 years of age seropositive for T. cruzi in Yoro, Honduras (1999–2002); Olopa, Guatemala (2003–2006); Entre Ríos, Bolivia (2002–2006); and Sucre, Bolivia (2005–2008). Essential program components guaranteeing feasibility of implementation were information, education, and communication (IEC) at the community and family level; vector control; health staff training; screening and diagnosis; treatment and compliance, including family-based strategies for early detection of adverse events; and logistics. Chagas disease diagnosis was confirmed by testing blood samples using two different diagnostic tests. T. cruzi-positive patients were treated with benznidazole as first-line treatment, with appropriate counseling, consent, and active participation from parents or guardians for daily administration of the drug, early detection of adverse events, and treatment withdrawal, when necessary. Weekly follow-up was conducted, with adverse events recorded to assess drug safety. Evaluations of serological conversion were carried out to measure treatment effectiveness. Vector control, entomological surveillance, and health education activities were carried out in all projects with close interaction with national and regional programs. Results Total numbers of children and adolescents tested for T. cruzi in Yoro, Olopa, Entre Ríos, and Sucre were 24,471, 8,927, 7,613, and 19,400, respectively. Of these, 232 (0.9%), 124 (1.4%), 1,475 (19.4%), and 1,145 (5.9%) patients, respectively, were diagnosed as seropositive. Patients were treated with benznidazole, and early findings of seroconversion varied widely between the Central and South American programs: 87.1% and 58.1% at 18 months post-treatment in Yoro and Olopa, respectively; 5.4% by up to 60 months in Entre Ríos; and 0% at an average of 18 months in Sucre. Benznidazole-related adverse events were observed in 50.2% and 50.8% of all patients treated in Yoro and Olopa, respectively, and 25.6% and 37.9% of patients in Entre Ríos and Sucre, respectively. Most adverse events were mild and manageable. No deaths occurred in the treatment population. Conclusions These results demonstrate the feasibility of implementing Chagas disease diagnosis and treatment programs in resource-limited settings, including remote rural areas, while addressing the limitations associated with drug-related adverse events. The variability in apparent treatment effectiveness may reflect differences in patient and parasite populations, and illustrates the limitations of current treatments and measures of efficacy. New treatments with improved safety profiles, pediatric formulations of existing and new drugs, and a faster, reliable test of cure are all urgently needed. PMID:19582142

Chelation therapy to treat atherosclerosis, particularly in diabetes: is it time to reconsider?

PubMed

Lamas, Gervasio A; Ergui, Ian

2016-08-01

Case reports and case series have suggested a possible beneficial effect of chelation therapy in patients with atherosclerotic disease. Small randomized trials conducted in patients with angina or peripheral artery disease, however, were not sufficiently powered to provide conclusive evidence on clinical outcomes. The Trial to Assess Chelation Therapy (TACT) was the first randomized trial adequately powered to detect the effects of chelation therapy on clinical endpoints. We discuss results and future research. Expert commentary: Chelation reduced adverse cardiovascular events in a post myocardial infarction (MI) population. Patients with diabetes demonstrated even greater benefit, with a number needed to treat of 6.5 patients to prevent a cardiac event over 5 years, with a 41% relative reduction in risk of a cardiac event (p = 0.0002). These results led to the revision of the ACC/AHA guideline recommendations for chelation therapy, changing its classification from class III to class IIb. TACT2, a replicative trial, will assess the effects of chelation therapy on cardiovascular outcomes in diabetic patients with a prior myocardial infarction. We are seeking participating sites for TACT2.

[Perioperative adverse events related to antidepressive agents use].

PubMed

Rozec, B; Cinotti, R; Blanloeil, Y

2011-11-01

Depression is the most common psychiatric disease, which is treated by the use of antidepressive agents possessing various mechanisms of action. Thus, the use in preoperative period of antidepressive agents is frequent (7% of patients scheduled for surgery). The objective of this review was to update the knowledge on the drug interactions between antidepressive agents and drugs used in perioperative period. (i) Medline and Ovid databases using combination of antidepressive agent and perioperative period as keywords; (ii) national and European epidemiologic database; (iii) expert recommendation and official French health agency; (iv) reference book chapters. The clinical practice showed a limited risk of adverse event related to antidepressant agents interaction with perioperative used drugs. In the two past decades, few relevant observations of adverse event related with imipramine and monoamine oxidase inhibitors use was reported. The most recent antidepressive agents had no serious adverse interaction. Nevertheless, the serotonin syndrome has to be known as far as it is more and more reported. In case of hypotension, the use of vasopressive agent has to be careful because of excessive response. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Online surveillance of media health event reporting in Nepal: digital disease detection from a One Health perspective.

PubMed

Schwind, Jessica S; Norman, Stephanie A; Karmacharya, Dibesh; Wolking, David J; Dixit, Sameer M; Rajbhandari, Rajesh M; Mekaru, Sumiko R; Brownstein, John S

2017-09-21

Traditional media and the internet are crucial sources of health information. Media can significantly shape public opinion, knowledge and understanding of emerging and endemic health threats. As digital communication rapidly progresses, local access and dissemination of health information contribute significantly to global disease detection and reporting. Health event reports in Nepal (October 2013-December 2014) were used to characterize Nepal's media environment from a One Health perspective using HealthMap - a global online disease surveillance and mapping tool. Event variables (location, media source type, disease or risk factor of interest, and affected species) were extracted from HealthMap. A total of 179 health reports were captured from various sources including newspapers, inter-government agency bulletins, individual reports, and trade websites, yielding 108 (60%) unique articles. Human health events were reported most often (n = 85; 79%), followed by animal health events (n = 23; 21%), with no reports focused solely on environmental health. By expanding event coverage across all of the health sectors, media in developing countries could play a crucial role in national risk communication efforts and could enhance early warning systems for disasters and disease outbreaks.

Planning for climate change: the need for mechanistic systems-based approaches to study climate change impacts on diarrheal diseases

PubMed Central

Levy, Karen; Zimmerman, Julie; Elliott, Mark; Bartram, Jamie; Carlton, Elizabeth; Clasen, Thomas; Dillingham, Rebecca; Eisenberg, Joseph; Guerrant, Richard; Lantagne, Daniele; Mihelcic, James; Nelson, Kara

2016-01-01

Increased precipitation and temperature variability as well as extreme events related to climate change are predicted to affect the availability and quality of water globally. Already heavily burdened with diarrheal diseases due to poor access to water, sanitation and hygiene facilities, communities throughout the developing world lack the adaptive capacity to sufficiently respond to the additional adversity caused by climate change. Studies suggest that diarrhea rates are positively correlated with increased temperature, and show a complex relationship with precipitation. Although climate change will likely increase rates of diarrheal diseases on average, there is a poor mechanistic understanding of the underlying disease transmission processes and substantial uncertainty surrounding current estimates. This makes it difficult to recommend appropriate adaptation strategies. We review the relevant climate-related mechanisms behind transmission of diarrheal disease pathogens and argue that systems-based mechanistic approaches incorporating human, engineered and environmental components are urgently needed. We then review successful systems-based approaches used in other environmental health fields and detail one modeling framework to predict climate change impacts on diarrheal diseases and design adaptation strategies. PMID:26799810

Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks

PubMed Central

Aung, Theingi; Halsey, Jim; Kromhout, Daan; Gerstein, Hertzel C.; Marchioli, Roberto; Tavazzi, Luigi; Geleijnse, Johanna M.; Rauch, Bernhard; Ness, Andrew; Galan, Pilar; Chew, Emily Y.; Bosch, Jackie; Collins, Rory; Lewington, Sarah; Armitage, Jane

2018-01-01

Importance Current guidelines advocate the use of marine-derived omega-3 fatty acids supplements for the prevention of coronary heart disease and major vascular events in people with prior coronary heart disease, but large trials of omega-3 fatty acids have produced conflicting results. Objective To conduct a meta-analysis of all large trials assessing the associations of omega-3 fatty acid supplements with the risk of fatal and nonfatal coronary heart disease and major vascular events in the full study population and prespecified subgroups. Data Sources and Study Selection This meta-analysis included randomized trials that involved at least 500 participants and a treatment duration of at least 1 year and that assessed associations of omega-3 fatty acids with the risk of vascular events. Data Extraction and Synthesis Aggregated study-level data were obtained from 10 large randomized clinical trials. Rate ratios for each trial were synthesized using observed minus expected statistics and variances. Summary rate ratios were estimated by a fixed-effects meta-analysis using 95% confidence intervals for major diseases and 99% confidence intervals for all subgroups. Main Outcomes and Measures The main outcomes included fatal coronary heart disease, nonfatal myocardial infarction, stroke, major vascular events, and all-cause mortality, as well as major vascular events in study population subgroups. Results Of the 77 917 high-risk individuals participating in the 10 trials, 47 803 (61.4%) were men, and the mean age at entry was 64.0 years; the trials lasted a mean of 4.4 years. The associations of treatment with outcomes were assessed on 6273 coronary heart disease events (2695 coronary heart disease deaths and 2276 nonfatal myocardial infarctions) and 12 001 major vascular events. Randomization to omega-3 fatty acid supplementation (eicosapentaenoic acid dose range, 226-1800 mg/d) had no significant associations with coronary heart disease death (rate ratio [RR], 0.93; 99% CI, 0.83-1.03; P = .05), nonfatal myocardial infarction (RR, 0.97; 99% CI, 0.87-1.08; P = .43) or any coronary heart disease events (RR, 0.96; 95% CI, 0.90-1.01; P = .12). Neither did randomization to omega-3 fatty acid supplementation have any significant associations with major vascular events (RR, 0.97; 95% CI, 0.93-1.01; P = .10), overall or in any subgroups, including subgroups composed of persons with prior coronary heart disease, diabetes, lipid levels greater than a given cutoff level, or statin use. Conclusions and Relevance This meta-analysis demonstrated that omega-3 fatty acids had no significant association with fatal or nonfatal coronary heart disease or any major vascular events. It provides no support for current recommendations for the use of such supplements in people with a history of coronary heart disease. PMID:29387889

Serum 25-hydroxyvitamin D, mortality, and incident cardiovascular disease, respiratory disease, cancers, and fractures: a 13-y prospective population study.

PubMed

Khaw, Kay-Tee; Luben, Robert; Wareham, Nicholas

2014-11-01

Vitamin D is associated with many health conditions, but optimal blood concentrations are still uncertain. We examined the prospective relation between serum 25-hydroxyvitamin D [25(OH)D] concentrations [which comprised 25(OH)D3 and 25(OH)D2] and subsequent mortality by the cause and incident diseases in a prospective population study. Serum vitamin D concentrations were measured in 14,641 men and women aged 42-82 y in 1997-2000 who were living in Norfolk, United Kingdom, and were followed up to 2012. Participants were categorized into 5 groups according to baseline serum concentrations of total 25(OH)D <30, 30 to <50, 50 to <70, 70 to <90, and ≥ 90 nmol/L. The mean serum total 25(OH)D was 56.6 nmol/L, which consisted predominantly of 25(OH)D3 (mean: 56.2 nmol/L; 99% of total). The age-, sex-, and month-adjusted HRs (95% CIs) for all-cause mortality (2776 deaths) for men and women by increasing vitamin D category were 1, 0.84 (0.74, 0.94), 0.72 (0.63, 0.81), 0.71 (0.62, 0.82), and 0.66 (0.55, 0.79) (P-trend < 0.0001). When analyzed as a continuous variable and with additional adjustment for body mass index, smoking, social class, education, physical activity, alcohol intake, plasma vitamin C, history of cardiovascular disease, diabetes, or cancer, HRs for a 20-nmol/L increase in 25(OH)D were 0.92 (0.88, 0.96) (P < 0.001) for total mortality, 0.96 (0.93, 0.99) (P = 0.014) (4469 events) for cardiovascular disease, 0.89 (0.85, 0.93) (P < 0.0001) (2132 events) for respiratory disease, 0.89 (0.81, 0.98) (P = 0.012) (563 events) for fractures, and 1.02 (0.99, 1.06) (P = 0.21) (3121 events) for incident total cancers. Plasma 25(OH)D concentrations predict subsequent lower 13-y total mortality and incident cardiovascular disease, respiratory disease, and fractures but not total incident cancers. For mortality, lowest risks were in subjects with concentrations >90 nmol/L, and there was no evidence of increased mortality at high concentrations, suggesting that a moderate increase in population mean concentrations may have potential health benefit, but <1% of the population had concentrations >120 nmol/L.

DEPRESSIVE SYMPTOMS AFTER BREAST CANCER SURGERY: RELATIONSHIPS WITH GLOBAL, CANCER-RELATED, AND LIFE EVENT STRESS

PubMed Central

GOLDEN-KREUTZ, DEANNA M.; ANDERSEN, BARBARA L.

2007-01-01

SUMMARY For women with breast cancer, rates of depression are the third highest of any cancer diagnostic group. Stress, defined as life events or perceptions of stress, is associated with depressive symptoms. However, little is known about the relationships between different types of stress and these symptoms in women with breast cancer. This relationship was tested in 210 women assessed after initial surgical treatment for regional breast cancer. Using Hierarchical Multiple Regression, three types of stress were examined: the occurrence of five stressful life events in the year prior to cancer diagnosis, perceptions of global stress, and perceptions of cancer-related traumatic stress. Other potentially relevant correlates of depressive symptoms were also examined, including the personality trait neuroticism, sociodemographics, and disease/treatment characteristics. Fifty-three percent of the variance in depressive symptoms was accounted for by three stress variables (perceptions of global and cancer-related traumatic stress and the life event-major financial difficulty) and two control variables (neuroticism and racial group). Specifically, global stress perceptions coupled with cancer-related intrusive thoughts and financial concerns along with the tendency towards negativity (neuroticism) may conspire to heighten a women’s risk for depressive symptoms. Assessing multiple sources of stress would improve our ability to identify women ‘at risk’ for depressive symptoms and provide appropriate intervention. PMID:15022156

A randomized study of coconut oil versus sunflower oil on cardiovascular risk factors in patients with stable coronary heart disease.

PubMed

Vijayakumar, Maniyal; Vasudevan, D M; Sundaram, K R; Krishnan, Sajitha; Vaidyanathan, Kannan; Nandakumar, Sandya; Chandrasekhar, Rajiv; Mathew, Navin

2016-01-01

Coronary artery disease (CAD) and its pathological atherosclerotic process are closely related to lipids. Lipids levels are in turn influenced by dietary oils and fats. Saturated fatty acids increase the risk for atherosclerosis by increasing the cholesterol level. This study was conducted to investigate the impact of cooking oil media (coconut oil and sunflower oil) on lipid profile, antioxidant mechanism, and endothelial function in patients with established CAD. In a single center randomized study in India, patients with stable CAD on standard medical care were assigned to receive coconut oil (Group I) or sunflower oil (Group II) as cooking media for 2 years. Anthropometric measurements, serum, lipids, Lipoprotein a, apo B/A-1 ratio, antioxidants, flow-mediated vasodilation, and cardiovascular events were assessed at 3 months, 6 months, 1 year, and 2 years. Hundred patients in each arm completed 2 years with 98% follow-up. There was no statistically significant difference in the anthropometric, biochemical, vascular function, and in cardiovascular events after 2 years. Coconut oil even though rich in saturated fatty acids in comparison to sunflower oil when used as cooking oil media over a period of 2 years did not change the lipid-related cardiovascular risk factors and events in those receiving standard medical care. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Family history does not predict angiographic localization or severity of coronary artery disease.

PubMed

Banerjee, Amitava; Lim, Chris C S; Silver, Louise E; Heneghan, Carl; Welch, Sarah J V; Mehta, Ziyah; Banning, Adrian P; Rothwell, Peter M

2012-04-01

Family history of MI is an established risk factor for coronary artery disease and subclinical atherosclerosis. Maternal MI and maternal stroke are more common in females than males presenting with acute coronary syndromes (ACS), suggesting sex-specific heritability, but the effects of family history on location and extent of coronary artery disease are unknown. In a prospective, population-based study (Oxford Vascular Study) of all patients with ACS, family history data for stroke and MI were analysed by sex of proband and affected first degree relatives (FDRs), and coronary angiograms were reviewed, where available. Of 835 probands with one or more ACS, 623 (420 males) had incident events and complete family history data. 351 patients with incident events (56.3%; 266 males) underwent coronary angiography. Neither angiographic disease localization nor severity were associated with sex-of-parent/sex-of-offspring in men or women. Sex-specific family history data do not predict angiographic localization of coronary disease in patients presenting with ACS. Maternal stroke and maternal MI probably affect ACS in females by a mechanism unrelated to atherosclerosis or coronary anatomy. However, family history data may still be useful in risk prediction and prognosis of ACS. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Ipilimumab retreatment in patients with pretreated advanced melanoma: the expanded access programme in Italy

PubMed Central

Chiarion-Sileni, V; Pigozzo, J; Ascierto, P A; Simeone, E; Maio, M; Calabrò, L; Marchetti, P; De Galitiis, F; Testori, A; Ferrucci, P F; Queirolo, P; Spagnolo, F; Quaglino, P; Carnevale Schianca, F; Mandalà, M; Di Guardo, L; Del Vecchio, M

2014-01-01

Background: Retreatment with ipilimumab has been shown to re-establish disease control in some patients with disease progression. Here, we report the efficacy and safety of retreatment with ipilimumab 3 mg kg−1 among patients participating in an expanded access programme in Italy. Methods: Patients who achieved disease control during induction therapy were retreated with ipilimumab upon progression (3 mg kg−1 every 3 weeks for up to four doses), providing they had not experienced toxicity that precluded further dosing. Tumour assessments were conducted after retreatment, and patients were monitored throughout for adverse events. Results: Of 855 patients treated with ipilimumab, 51 were retreated upon disease progression. Of these, 28 (55%) regained disease control upon retreatment and 42% were alive 2 years after the first induction dose of ipilimumab; median overall survival was 21 months. Eleven patients (22%) had a treatment-related adverse event of any grade during retreatment. These were generally mild-to-moderate and resolved within a median of 4 days. No new types of toxicity were reported. Conclusions: For patients who meet predefined criteria, retreatment with ipilimumab is generally well tolerated and can translate into clinical benefit. This strategy should be compared with other therapeutic options in randomised controlled trials. PMID:24619072

Classic and new animal models of Parkinson's disease.

PubMed

Blesa, Javier; Phani, Sudarshan; Jackson-Lewis, Vernice; Przedborski, Serge

2012-01-01

Neurological disorders can be modeled in animals so as to recreate specific pathogenic events and behavioral outcomes. Parkinson's Disease (PD) is the second most common neurodegenerative disease of an aging population, and although there have been several significant findings about the PD disease process, much of this process still remains a mystery. Breakthroughs in the last two decades using animal models have offered insights into the understanding of the PD disease process, its etiology, pathology, and molecular mechanisms. Furthermore, while cellular models have helped to identify specific events, animal models, both toxic and genetic, have replicated almost all of the hallmarks of PD and are useful for testing new neuroprotective or neurorestorative strategies. Moreover, significant advances in the modeling of additional PD features have come to light in both classic and newer models. In this review, we try to provide an updated summary of the main characteristics of these models as well as the strengths and weaknesses of what we believe to be the most popular PD animal models. These models include those produced by 6-hydroxydopamine (6-OHDA), 1-methyl-1,2,3,6-tetrahydropiridine (MPTP), rotenone, and paraquat, as well as several genetic models like those related to alpha-synuclein, PINK1, Parkin and LRRK2 alterations.

Should tumour necrosis factor antagonist safety information be applied from patients with rheumatoid arthritis to psoriasis? Rates of serious adverse events in the prospective rheumatoid arthritis BIOBADASER and psoriasis BIOBADADERM cohorts.

PubMed

García-Doval, I; Hernández, M V; Vanaclocha, F; Sellas, A; de la Cueva, P; Montero, D

2017-03-01

Information on the safety of tumour necrosis factor (TNF) antagonists frequently arises from their use in rheumatic diseases, their first approved indications, and is later applied to psoriasis. Whether the risk of biological therapy is similar in psoriasis and rheumatoid arthritis has been considered a priority research question. To compare the safety profile of anti-TNF drugs in patients with rheumatoid arthritis and psoriasis. We compared two prospective safety cohorts of patients with rheumatoid arthritis and psoriasis that share methods (BIOBADASER and BIOBADADERM). There were 1248 serious or mortal adverse events in 16 230 person-years of follow-up in the rheumatoid arthritis cohort (3171 patients), and 124 in the 2760 person-years of follow-up of the psoriasis cohort (946 patients). Serious and mortal adverse events were less common in patients with psoriasis than in rheumatoid arthritis (incidence rate ratio of serious adverse events in psoriasis/rheumatoid arthritis: 0·6, 95% confidence interval 0·5-0·7). This risk remained after adjustment for sex, age, treatment, disease, hypertension, diabetes, hypercholesterolaemia and simultaneous therapy with methotrexate (hazard ratio 0·54, 95% confidence interval 0·47-0·61), and after excluding patients receiving corticosteroids. Patients with rheumatoid arthritis showed a higher rate of infections, cardiac disorders, respiratory disorders and infusion-related reactions, whereas patients with psoriasis had more skin and subcutaneous tissue disorders and hepatobiliary disorders. Patients with rheumatoid arthritis clinical practice have almost double the risk of serious adverse events compared with patients with psoriasis, with a different pattern of adverse events. Safety data from rheumatoid arthritis should not be fully extrapolated to psoriasis. These differences are likely to apply to other immune-mediated inflammatory diseases. © 2016 British Association of Dermatologists.

The quantified self during travel: mapping health in a prospective cohort of travellers.

PubMed

Farnham, Andrea; Furrer, Reinhard; Blanke, Ulf; Stone, Emily; Hatz, Christoph; Puhan, Milo A

2017-09-01

Travel medicine research has remained relatively unchanged in the face of rapid expansion of international travel and is unlikely to meet health challenges beyond infectious diseases. Our aim was to identify the range of health outcomes during travel using real-time monitoring and daily reporting of health behaviours and outcomes and identify traveller subgroups who may benefit from more targeted advice before and during travel. We recruited a prospective cohort of travellers ≥ 18 years and planning travel to Thailand for <5 weeks from the travel clinics in Zurich and Basel (Switzerland). Participants answered demographic, clinical and risk behaviour questionnaires pre-travel and a daily health questionnaire each day during travel using a smartphone application. Environmental and location data were collected passively by GPS. Classification trees were used to identify predictors of health behaviour and outcomes during travel. Non-infectious disease events were relatively common, with 22.7% (17 out of 75 travellers) experiencing an accident, 40.0% ( n  = 30) a wound or cut and 14.7% ( n  = 11) a bite or lick from an animal. Mental health associated events were widely reported, with 80.0% ( n  = 60) reporting lethargy, 34.7% ( n  = 26) anxiety and 34.7% ( n  = 26) feeling tense or irritable. Classification trees identified age, trip length, previous travel experience and having experienced a sports injury in the past year as the most important discriminatory variables for health threats. Our study offers a revolutionary look at an almost real-time timeline of health events and behaviours during travel using mHealth technology. Non-infectious disease related health issues were common in this cohort, despite being largely unaddressed in traditional travel medicine research and suggest a substantial potential for improving evidence-based travel medicine advice. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Gla-rich protein function as an anti-inflammatory agent in monocytes/macrophages: Implications for calcification-related chronic inflammatory diseases

PubMed Central

Viegas, Carla S. B.; Costa, Rúben M.; Santos, Lúcia; Videira, Paula A.; Silva, Zélia; Araújo, Nuna; Macedo, Anjos L.; Matos, António P.; Vermeer, Cees; Simes, Dina C.

2017-01-01

Calcification-related chronic inflammatory diseases are multifactorial pathological processes, involving a complex interplay between inflammation and calcification events in a positive feed-back loop driving disease progression. Gla-rich protein (GRP) is a vitamin K dependent protein (VKDP) shown to function as a calcification inhibitor in cardiovascular and articular tissues, and proposed as an anti-inflammatory agent in chondrocytes and synoviocytes, acting as a new crosstalk factor between these two interconnected events in osteoarthritis. However, a possible function of GRP in the immune system has never been studied. Here we focused our investigation in the involvement of GRP in the cell inflammatory response mechanisms, using a combination of freshly isolated human leucocytes and undifferentiated/differentiated THP-1 cell line. Our results demonstrate that VKDPs such as GRP and matrix gla protein (MGP) are synthesized and γ-carboxylated in the majority of human immune system cells either involved in innate or adaptive immune responses. Stimulation of THP-1 monocytes/macrophages with LPS or hydroxyapatite (HA) up-regulated GRP expression, and treatments with GRP or GRP-coated basic calcium phosphate crystals resulted in the down-regulation of mediators of inflammation and inflammatory cytokines, independently of the protein γ-carboxylation status. Moreover, overexpression of GRP in THP-1 cells rescued the inflammation induced by LPS and HA, by down-regulation of the proinflammatory cytokines TNFα, IL-1β and NFkB. Interestingly, GRP was detected at protein and mRNA levels in extracellular vesicles released by macrophages, which may act as vehicles for extracellular trafficking and release. Our data indicate GRP as an endogenous mediator of inflammatory responses acting as an anti-inflammatory agent in monocytes/macrophages. We propose that in a context of chronic inflammation and calcification-related pathologies, GRP might act as a novel molecular mediator linking inflammation and calcification events, with potential therapeutic application. PMID:28542410

Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes

PubMed Central

Radolf, Justin D.; Caimano, Melissa J.; Stevenson, Brian; Hu, Linden T.

2012-01-01

In little more than 30 years, Lyme disease, which is caused by the spirochaete Borrelia burgdorferi, has risen from relative obscurity to become a global public health problem and a prototype of an emerging infection. During this period, there has been an extraordinary accumulation of knowledge on the phylogenetic diversity, molecular biology, genetics and host interactions of B. burgdorferi. In this Review, we integrate this large body of information into a cohesive picture of the molecular and cellular events that transpire as Lyme disease spirochaetes transit between their arthropod and vertebrate hosts during the enzootic cycle. PMID:22230951

Sleep Apnea, Sleep Duration and Brain MRI Markers of Cerebral Vascular Disease and Alzheimer's Disease: The Atherosclerosis Risk in Communities Study (ARIC).

PubMed

Lutsey, Pamela L; Norby, Faye L; Gottesman, Rebecca F; Mosley, Thomas; MacLehose, Richard F; Punjabi, Naresh M; Shahar, Eyal; Jack, Clifford R; Alonso, Alvaro

2016-01-01

A growing body of literature has suggested that obstructive sleep apnea (OSA) and habitual short sleep duration are linked to poor cognitive function. Neuroimaging studies may provide insight into this relation. We tested the hypotheses that OSA and habitual short sleep duration, measured at ages 54-73 years, would be associated with adverse brain morphology at ages 67-89 years. Included in this analysis are 312 ARIC study participants who underwent in-home overnight polysomnography in 1996-1998 and brain MRI scans about 15 years later (2012-2013). Sleep apnea was quantified by the apnea-hypopnea index and categorized as moderate/severe (≥15.0 events/hour), mild (5.0-14.9 events/hour), or normal (<5.0 events/hour). Habitual sleep duration was categorized, in hours, as <7, 7 to <8, ≥8. MRI outcomes included number of infarcts (total, subcortical, and cortical) and white matter hyperintensity (WMH) and Alzheimer's disease signature region volumes. Multivariable adjusted logistic and linear regression models were used. All models incorporated inverse probability weighting, to adjust for potential selection bias. At the time of the sleep study participants were 61.7 (SD: 5.0) years old and 54% female; 19% had moderate/severe sleep apnea. MRI imaging took place 14.8 (SD: 1.0) years later, when participants were 76.5 (SD: 5.2) years old. In multivariable models which accounted for body mass index, neither OSA nor abnormal sleep duration were statistically significantly associated with odds of cerebral infarcts, WMH brain volumes or regional brain volumes. In this community-based sample, mid-life OSA and habitually short sleep duration were not associated with later-life cerebral markers of vascular dementia and Alzheimer's disease. However, selection bias may have influenced our results and the modest sample size led to relatively imprecise associations.

Ferric maltol therapy for iron deficiency anaemia in patients with inflammatory bowel disease: long-term extension data from a Phase 3 study.

PubMed

Schmidt, C; Ahmad, T; Tulassay, Z; Baumgart, D C; Bokemeyer, B; Howaldt, S; Stallmach, A; Büning, C

2016-08-01

Ferric maltol was effective and well-tolerated in iron deficiency anaemia patients with inflammatory bowel disease during a 12-week placebo-controlled trial. To perform a Phase 3 extension study evaluating long-term efficacy and safety with ferric maltol in inflammatory bowel disease patients in whom oral ferrous therapies had failed to correct iron deficiency anaemia. After 12 weeks of randomised, double-blind treatment, patients with iron deficiency anaemia and mild-to-moderate ulcerative colitis or Crohn's disease received open-label ferric maltol 30 mg b.d. for 52 weeks. 111 patients completed randomised treatment and 97 entered the open-label ferric maltol extension. In patients randomised to ferric maltol ('continued'; n = 50), mean ± s.d. haemoglobin increased by 3.07 ± 1.46 g/dL between baseline and Week 64. In patients randomised to placebo ('switch'; n = 47), haemoglobin increased by 2.19 ± 1.61 g/dL. Normal haemoglobin was achieved in high proportions of both continued and switch patients (89% and 83% at Week 64, respectively). Serum ferritin increased from 8.9 μg/L (baseline) to 26.0 μg/L (Week 12) in ferric maltol-treated patients, and to 57.4 μg/L amongst all patients at Week 64. In total, 80% of patients reported ≥1 adverse event by Week 64. Adverse events considered related to ferric maltol were recorded in 27/111 (24%) patients: 8/18 discontinuations due to adverse events were treatment-related. One patient was withdrawn due to increased ulcerative colitis activity. Normal haemoglobin was observed in ≥80% of patients from weeks 20-64 of long-term ferric maltol treatment, with concomitant increases in iron storage parameters. Ferric maltol was well-tolerated throughout this 64-week study. © 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

[Oxidative Stress Derived from Airborne Fine and Ultrafine Particles and the Effects on Brain-Nervous System: Part 2].

PubMed

Sagai, Masaru; Tin Win-Shwe, Tin

2015-01-01

Traffic-related air pollution is a major contributor to urban air pollution. Diesel exhaust (DE) is its most important component of near-road and urban air pollutions and is commonly used as a surrogate model of air pollution in health effects studies. In particular, diesel exhaust particles (DEPs) and nanoparticles in DEPs are the components considered hazardous for health. It is widely known that exposure to DEPs is associated with mortality caused by respiratory and cardiovascular diseases. Recently, evidence has been accumulating showing that DEPs and nanoparticles may cause neurodegenerative disorders. Here, we introduce evidence suggesting their association with these disorders. The chemical components and the translocation of DEPs and nanoparticles to the brain are described in part 1. In part 2, we introduce the mechanism of development of neurodegenerative diseases such as stroke, Alzheimer's disease, and Parkinson's disease via oxidative stress and inflammatory events. Furthermore, there are many lines of epidemiological evidence showing that the particulates impair cognitive function and ability of memory through oxidative and inflammatory events in the brain. These lines of evidences are supported by many animal experiments on neurological disorders.

Microhemorrhage is an Early Event in the Pulmonary Fibrotic Disease of PECAM-1 Deficient FVB/n Mice

PubMed Central

Young, Lena C.; Woods, Steven J.; Groshong, Steven D.; Basaraba, Randall J.; Gilchrist, John M.; Higgins, David M.; Gonzalez-Juarrero, Mercedes; Bass, Todd A.; Muller, William A.; Schenkel, Alan R.

2014-01-01

Platelet Endothelial Cell Adhesion Molecule 1 (PECAM-1) deficient mice in the FVB/n strain exhibit fatal chronic pulmonary fibrotic disease. The illness occurs in the absence of a detectable pro-inflammatory event. PECAM-1 is vital to the stability of vascular permeability, leukocyte extravasation, clotting of platelets, and clearance of apoptotic cells. We show here that the spontaneous development of fibrotic disease in PECAM-1 deficient FVB/n mice is characterized by early loss of vascular integrity in pulmonary capillaries, resulting in spontaneous microbleeds. Hemosiderin-positive macrophages were found in interstitial spaces and bronchoalveolar lavage (BAL) fluid in relatively healthy animals. We also observed a gradually increasing presence of hemosiderin-positive macrophages and fibrin deposition in the advanced stages of disease, corresponding to the accumulation of collagen, IL-10 expression, and myofibroblasts expressing alpha smooth muscle actin (SMA). Together with the growing evidence that pulmonary microbleeds and coagulation play an active part in human pulmonary fibrosis, this data further supports our hypothesis that PECAM-1 expression is necessary for vascular barrier function control and regulation of homeostasis specifically, in the pulmonary environment. PMID:24972347

Failure of fertility therapy and subsequent adverse cardiovascular events

PubMed Central

Udell, Jacob A.; Lu, Hong; Redelmeier, Donald A.

2017-01-01

BACKGROUND: Infertility may indicate an underlying predisposition toward premature cardiovascular disease, yet little is known about potential long-term cardiovascular events following fertility therapy. We investigated whether failure of fertility therapy is associated with subsequent adverse cardiovascular events. METHODS: We performed a population-based cohort analysis of women who received gonadotropin-based fertility therapy between Apr. 1, 1993, and Mar. 31, 2011, distinguishing those who subsequently gave birth and those who did not. Using multivariable Poisson regression models, we estimated the relative rate ratio of adverse cardiovascular events associated with fertility therapy failure, accounting for age, year, baseline risk factors, health care history and number of fertility cycles. The primary outcome was subsequent treatment for nonfatal coronary ischemia, stroke, transient ischemic attack, heart failure or thromboembolism. RESULTS: Of 28 442 women who received fertility therapy, 9349 (32.9%) subsequently gave birth and 19 093 (67.1%) did not. The median number of fertility treatments was 3 (interquartile range 1–5). We identified 2686 cardiovascular events over a median 8.4 years of follow-up. The annual rate of cardiovascular events was 19% higher among women who did not give birth after fertility therapy than among those who did (1.08 v. 0.91 per 100 patient-years, p < 0.001), equivalent to a 21% relative increase in the annual rate (95% confidence interval 13%–30%). We observed no association between event rates and number of treatment cycles. INTERPRETATION: Fertility therapy failure was associated with an increased risk of long-term adverse cardiovascular events. These women merit surveillance for subsequent cardiovascular events. PMID:28385819

The relation of early experienced negative life events and current itch. A longitudinal study among adolescents in Oslo, Norway.

PubMed

Lien, Lars; Halvorsen, Jon Anders; Haavet, Ole Rikard; Dalgard, Florence

2012-03-01

Negative life events have impact on mental health and skin diseases among adults. Itch is a common, disabling skin symptom. The aim was to describe negative life events associated with current itch and to analyze the impact of number of negative life events on symptoms of itch, controlling for possible confounders. This school-based longitudinal survey was conducted among 15 and 18 years old high-school students in Oslo, Norway. From a baseline cohort of 3811 students, 2489 (65%) participants were followed-up after three years later. They completed questionnaires at baseline and follow-up. Current itch was measured with a validated instrument asking for symptoms on a four point Likert scale at follow-up. More girls than boys reported itch. There were no gender differences in number of negative life events. Death among close relative/friend was the most common negative life event among boys and girls. All negative life experiences before 15 years of age were statistically significantly associated with itch, but after 15 years only half of the negative life events were associated with itch. The bivariate association between number of negative life events and itch was statistically significant, and only when adjusting for mental distress at baseline there was a considerable drop in the Odds Ratio. There is a clear association between number of negative life events at baseline and itch at follow-up three years later among adolescents. It is therefore important to discuss possible adverse experiences with adolescents presenting with severe symptoms of itch. Copyright © 2011 Elsevier Inc. All rights reserved.

Health Benefits of Fasting and Caloric Restriction.

PubMed

Golbidi, Saeid; Daiber, Andreas; Korac, Bato; Li, Huige; Essop, M Faadiel; Laher, Ismail

2017-10-23

Obesity and obesity-related diseases, largely resulting from urbanization and behavioral changes, are now of global importance. Energy restriction, though, is associated with health improvements and increased longevity. We review some important mechanisms related to calorie limitation aimed at controlling of metabolic diseases, particularly diabetes. Calorie restriction triggers a complex series of intricate events, including activation of cellular stress response elements, improved autophagy, modification of apoptosis, and alteration in hormonal balance. Intermittent fasting is not only more acceptable to patients, but it also prevents some of the adverse effects of chronic calorie restriction, especially malnutrition. There are many somatic and potentially psychologic benefits of fasting or intermittent calorie restriction. However, some behavioral modifications related to abstinence of binge eating following a fasting period are crucial in maintaining the desired favorable outcomes.

Autoantibodies in myositis.

PubMed

McHugh, Neil J; Tansley, Sarah L

2018-04-20

The discovery of novel autoantigen systems related to idiopathic inflammatory myopathies (collectively referred to as myositis) in adults and children has had major implications for the diagnosis and management of this group of diseases across a wide range of medical specialties. Traditionally, autoantibodies found in patients with myositis are described as being myositis-specific autoantibodies (MSAs) or myositis-associated autoantibodies (MAAs), depending on their prevalence in other, related conditions. However, certain MSAs are more closely associated with extramuscular manifestations, such as skin and lung disease, than with myositis itself. It is very rare for more than one MSA to coexist in the same individual, underpinning the potential to use MSAs to precisely define genetic and disease endotypes. Each MSA is associated with a distinctive pattern of disease or phenotype, which has implications for diagnosis and a more personalized approach to therapy. Knowledge of the function and localization of the autoantigenic targets for MSAs has provided key insights into the potential immunopathogenic mechanisms of myositis. In particular, evidence suggests that the alteration of expression of a myositis-related autoantigen by certain environmental influences or oncogenesis could be a pivotal event linking autoantibody generation to the development of disease.

Concepts of dental caries and their consequences for understanding the disease.

PubMed

Fejerskov, O

1997-02-01

The way in which we conceptually consider dental caries determines our choice of preventive and treatment strategy. In this paper the definition of dental caries is discussed and the related problems concerning causality are addressed. Dental caries reflects symptoms of ongoing and past disease--not the disease itself. As such, it is important to record early stages of signs of the disease, i.e. non-cavitated stages of lesion development. The dynamic nature of the processes leading to net loss of mineral (hence a lesion) is emphasized, and appreciating that caries is ubiquitous in populations around the world and initiation and progression of lesions continues lifelong leads to the logical conclusion that we can control dental caries through a variety of measures--but not truly prevent the disease. We can prevent cavities by controlling the patho-physiological events which may result in a net loss of mineral. The relative role of dental plaque in caries control is discussed in relation to the role of the many determinants which influence the likelihood for lesion development. It is concluded that several paradigms about the nature of dental caries should be reconsidered to provide the most cost-effective dental services.

Analyzing semi-competing risks data with missing cause of informative terminal event.

PubMed

Zhou, Renke; Zhu, Hong; Bondy, Melissa; Ning, Jing

2017-02-28

Cancer studies frequently yield multiple event times that correspond to landmarks in disease progression, including non-terminal events (i.e., cancer recurrence) and an informative terminal event (i.e., cancer-related death). Hence, we often observe semi-competing risks data. Work on such data has focused on scenarios in which the cause of the terminal event is known. However, in some circumstances, the information on cause for patients who experience the terminal event is missing; consequently, we are not able to differentiate an informative terminal event from a non-informative terminal event. In this article, we propose a method to handle missing data regarding the cause of an informative terminal event when analyzing the semi-competing risks data. We first consider the nonparametric estimation of the survival function for the terminal event time given missing cause-of-failure data via the expectation-maximization algorithm. We then develop an estimation method for semi-competing risks data with missing cause of the terminal event, under a pre-specified semiparametric copula model. We conduct simulation studies to investigate the performance of the proposed method. We illustrate our methodology using data from a study of early-stage breast cancer. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

[Gender aspects of socioeconomic and psychosocial risk factors of cardiovascular diseases].

PubMed

Dorner, Thomas; Kiefer, Ingrid; Kunze, Michael; Rieder, Anita

2004-09-01

Socioeconomic and psychosocial factors exert influence on health as well as the development, the progression and the prevention of diseases. Social factors regarding cardiovascular diseases have been widely researched. Whilst characteristics of classic type A behaviour increase cardiovascular risk among men, characteristics of type B behaviour represent a protective value, especially among women. Depression--a disease that is particularly prevalent among women and is associated with socioeconomic factors--negatively influences the development of cardiovascular diseases, triggers cardiovascular events and influences rehabilitation. Lifestyle factors, which are positively or negatively correlated with cardiovascular disease, show a gender-specific prevalence and are related to psychosocial factors. More women than men report healthy nutrition, whereas more men report partaking in physical exercise. Obesity is--depending on the occupational group and the social level--more prevalent among women compared to men.

Relationship satisfaction reduces the risk of maternal infectious diseases in pregnancy: the Norwegian Mother and Child Cohort Study.

PubMed

Henriksen, Roger Ekeberg; Torsheim, Torbjørn; Thuen, Frode

2015-01-01

The aims of this study were to explore the degree to which relationship satisfaction predicts the risk of infectious diseases during pregnancy and to examine whether relationship satisfaction moderates the association between stressful life events and the risk of infections. This was a prospective study based on data from the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. Pregnant women (n = 67,244) completed questionnaires concerning relationship satisfaction and nine different categories of infectious diseases as well as socioeconomic characteristics and stressful life events. Associations between the predictor variables and the infectious diseases were assessed by logistic regression analyses. A multiple regression analysis was performed to assess a possible interaction of relationship satisfaction with stressful life events on the risk for infectious diseases. After controlling for marital status, age, education, income, and stressful life events, high levels of relationship satisfaction at week 15 of gestation were found to predict a significantly lower risk for eight categories of infectious diseases at gestational weeks 17-30. No significant interaction effect was found between relationship satisfaction and stressful life events on the risk for infections.

Clinical presentation and risk factors of inflammatory bowel disease in Sri Lanka.

PubMed

Weerasekara, Deepaka; Fernando, Neluka; Meedin, F; Holton, John; Fernando, D

2011-01-01

There have been very few studies on inflammatory bowel disease (IBD) in Sri Lanka. This study was undertaken to determine the clinical presentation and whether a western style diet or infection with geo-helminths were associated with the condition. Three questionnaires were given to the patients: one relating to diet, one relating to clinical presentation and one relating to quality of life. The disease was confirmed endoscopically and histologically. Faeces were examined for parasites. Forty four patients were enrolled (43-ulcerative colitis; 1-Crohn's Disease). All but one had ulcerative colitis. Most had no family history of disease. The peak age of onset was 21-40 y and 63% gave a history of more than 6 months symptoms prior to diagnosis. Clinical presentation was similar to cases in western countries although milder with less severe life-events. None of them had undergone surgery. All patients ate a rice-based diet and none ate bread made of refined flour. Only 2 patient was infected with a geo-helminth. Eating bread made of refined flour is not related to development of IBD in these patients. The prevalence of geo-helminths in the study population corresponded to the general population average. Delay in diagnosis occurs because of an initial assumption that the cause of symptoms is infective. A National Register of non-infectious gastrointestinal disease would aid the epidemiology and allocation of funding to this inflammatory condition.

How artificial intelligence tools can be used to assess individual patient risk in cardiovascular disease: problems with the current methods.

PubMed

Grossi, Enzo

2006-05-03

In recent years a number of algorithms for cardiovascular risk assessment has been proposed to the medical community. These algorithms consider a number of variables and express their results as the percentage risk of developing a major fatal or non-fatal cardiovascular event in the following 10 to 20 years The author has identified three major pitfalls of these algorithms, linked to the limitation of the classical statistical approach in dealing with this kind of non linear and complex information. The pitfalls are the inability to capture the disease complexity, the inability to capture process dynamics, and the wide confidence interval of individual risk assessment. Artificial Intelligence tools can provide potential advantage in trying to overcome these limitations. The theoretical background and some application examples related to artificial neural networks and fuzzy logic have been reviewed and discussed. The use of predictive algorithms to assess individual absolute risk of cardiovascular future events is currently hampered by methodological and mathematical flaws. The use of newer approaches, such as fuzzy logic and artificial neural networks, linked to artificial intelligence, seems to better address both the challenge of increasing complexity resulting from a correlation between predisposing factors, data on the occurrence of cardiovascular events, and the prediction of future events on an individual level.

Use of drug treatment for secondary prevention of cardiovascular disease in urban and rural communities of China: China Kadoorie Biobank Study of 0.5 million people☆

PubMed Central

Chen, Yiping; Li, Liming; Zhang, Qiuli; Clarke, Robert; Chen, Junshi; Guo, Yu; Bian, Zheng; Pan, Xianhai; Peto, Richard; Tao, Ran; Shi, Kunxiang; Collins, Rory; Ma, Liangcai; Sun, Huarong; Chen, Zhengming

2014-01-01

Aims Relatively little is known about the use of medication for the secondary prevention of cardiovascular disease (CVD) events in China, and the relevance to it of socioeconomic, lifestyle and health-related factors. Methods and results We analysed cross-sectional data from the China Kadoorie Biobank (CKB) of 512,891 adults aged 30–79 years recruited from 1737 rural and urban communities in China. Information about doctor-diagnosed ischaemic heart disease (IHD) and stroke, and the use of medication for the secondary prevention of CVD events, were recorded by interview. Multivariate logistic regression was used to estimate odds ratios (ORs) for use of secondary preventive treatment, adjusting simultaneously for age, sex, area and education. Overall, 23,129 (4.5%) participants reported a history of CVD (3.0% IHD, 1.7% stroke). Among them, 35% reported current use of any of 6 classes of drug (anti-platelet, statins, diuretics, ACE-I, β-blockers or calcium-channel blockers) for the prevention of CVD events, with the rate of usage greater in those with older age, higher levels of income, education, BMI or blood pressure. The use of these agents was associated positively with history of diagnosed hypertension (OR 7.5; 95% confidence intervals: 7.08–8.06) and diabetes (1.40; 1.28–1.52) and inversely with self-rated health status, but there was no association with years since diagnosis. Conclusions Despite recent improvements in hospital care in China, only one in three individuals with prior CVD was routinely treated with any proven secondary preventive drugs. The treatment rates were correlated with the existence of other risk factors, in particular evidence of hypertension. PMID:24461961

Transcriptome Profiling Revealed Stress-Induced and Disease Resistance Genes Up-Regulated in PRSV Resistant Transgenic Papaya

PubMed Central

Fang, Jingping; Lin, Aiting; Qiu, Weijing; Cai, Hanyang; Umar, Muhammad; Chen, Rukai; Ming, Ray

2016-01-01

Papaya is a productive and nutritious tropical fruit. Papaya Ringspot Virus (PRSV) is the most devastating pathogen threatening papaya production worldwide. Development of transgenic resistant varieties is the most effective strategy to control this disease. However, little is known about the genome-wide functional changes induced by particle bombardment transformation. We conducted transcriptome sequencing of PRSV resistant transgenic papaya SunUp and its PRSV susceptible progenitor Sunset to compare the transcriptional changes in young healthy leaves prior to infection with PRSV. In total, 20,700 transcripts were identified, and 842 differentially expressed genes (DEGs) randomly distributed among papaya chromosomes. Gene ontology (GO) category analysis revealed that microtubule-related categories were highly enriched among these DEGs. Numerous DEGs related to various transcription factors, transporters and hormone biosynthesis showed clear differences between the two cultivars, and most were up-regulated in transgenic papaya. Many known and novel stress-induced and disease-resistance genes were most highly expressed in SunUp, including MYB, WRKY, ERF, NAC, nitrate and zinc transporters, and genes involved in the abscisic acid, salicylic acid, and ethylene signaling pathways. We also identified 67,686 alternative splicing (AS) events in Sunset and 68,455 AS events in SunUp, mapping to 10,994 and 10,995 papaya annotated genes, respectively. GO enrichment for the genes displaying AS events exclusively in Sunset was significantly different from those in SunUp. Transcriptomes in Sunset and transgenic SunUp are very similar with noteworthy differences, which increased PRSV-resistance in transgenic papaya. No detrimental pathways and allergenic or toxic proteins were induced on a genome-wide scale in transgenic SunUp. Our results provide a foundation for unraveling the mechanism of PRSV resistance in transgenic papaya. PMID:27379138

Small artery elasticity predicts future cardiovascular events in chinese patients with angiographic coronary artery disease.

PubMed

Wan, Zhaofei; Liu, Xiaojun; Wang, Xinhong; Liu, Fuqiang; Liu, Weimin; Wu, Yue; Pei, Leilei; Yuan, Zuyi

2014-04-01

Arterial elasticity has been shown to predict cardiovascular disease (CVD) in apparently healthy populations. The present study aimed to explore whether arterial elasticity could predict CVD events in Chinese patients with angiographic coronary artery disease (CAD). Arterial elasticity of 365 patients with angiographic CAD was measured. During follow-up (48 months; range 6-65), 140 CVD events occurred (including 34 deaths). Univariate Cox analysis demonstrated that both large arterial elasticity and small arterial elasticity were significant predictors of CVD events. Multivariate Cox analysis indicated that small arterial elasticity remained significant. Kaplan-Meier analysis showed that the probability of having a CVD event/CVD death increased with a decrease of small arterial elasticity (P < .001, respectively). Decreased small arterial elasticity independently predicts the risk of CVD events in Chinese patients with angiographic CAD.

Aldosterone, mortality, and acute ischaemic events in coronary artery disease patients outside the setting of acute myocardial infarction or heart failure.

PubMed

Ivanes, Fabrice; Susen, Sophie; Mouquet, Frédéric; Pigny, Pascal; Cuilleret, François; Sautière, Karine; Collet, Jean-Philippe; Beygui, Farzin; Hennache, Bernadette; Ennezat, Pierre Vladimir; Juthier, Françis; Richard, Florence; Dallongeville, Jean; Hillaert, Marieke A; Doevendans, Pieter A; Jude, Brigitte; Bertrand, Michel; Montalescot, Gilles; Van Belle, Eric

2012-01-01

Recent studies have demonstrated that aldosterone levels measured in patients with heart failure or acute myocardial infarction (MI) are associated with long-term mortality, but the association with aldosterone levels in patients with coronary artery disease (CAD) outside these specific settings remains unknown. In addition, no clear mechanism has been elucidated to explain these observations. The present study was designed to evaluate the relationship between the level of aldosterone and the risk of death and acute ischaemic events in CAD patients with a preserved left ventricular (LV) function and no acute MI. In 799 consecutive CAD patients referred for elective coronary angioplasty measurements were obtained before the procedure for: aldosterone (median = 25 pg/mL), brain natriuretic peptide (BNP) (median = 35 pg/mL), hsC-reactive protein (median = 4.17 mg/L), and left ventricular ejection fraction (mean = 58%). Patients with acute MI or coronary syndrome (ACS) who required urgent revascularization were not included in the study. The primary endpoint, cardiovascular death, occurred in 41 patients during a median follow-up period of 14.9 months. Secondary endpoints-total mortality, acute ischaemic events (acute MI or ischaemic stroke), and the composite of death and acute ischaemic events-were observed in 52, 54, and 94 patients, respectively. Plasma aldosterone was found to be related to BMI, hypertension and NYHA class, and inversely related to age, creatinine clearance, and use of beta-blockers. Multivariate Cox model analysis demonstrated that aldosterone was independently associated with cardiovascular mortality (P = 0.001), total mortality (P = 0.001), acute ischaemic events (P = 0.01), and the composite of death and acute ischaemic events (P = 0.004). Reclassification analysis, using integrated discrimination improvement (IDI) and net reclassification improvement (NRI), demonstrated incremental predictive value of aldosterone (P < 0.0001). Our results demonstrate that, in patients with CAD but without heart failure or acute MI, the level of aldosterone is strongly and independently associated with mortality and the occurrence of acute ischaemic events.

Immune-related adverse events associated with PD-1 and PD-L1 inhibitors for nonsmall cell lung cancer

PubMed Central

Sun, Xiaoying; Roudi, Raheleh; Chen, Shangya; Fan, Bin; Li, Hong Jin; Zhou, Min; Li, Xin; Li, Bin

2017-01-01

Abstract Introduction: Nonsmall cell lung cancer accounts for approximately 80% of all lung cancers, and approximately 75% of cases are diagnosed in the middle and late stages of disease. Unfortunately, limited treatment does not improve the prognosis of advanced disease. Monoclonal antibodies targeting programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) represent a new treatment paradigm for nonsmall cell lung cancer. Nevertheless, the immune-related adverse events (irAEs) associated with PD-1 and PD-L1 inhibitors are unique, and early recognition and treatment of these events are essential. Methods and Analysis: A systematic literature search will be performed using the EMBASE, MEDLINE, and Cochrane databases to identify relevant articles published in any language. Randomized clinical trials, case series, and case reports of PD-1 and PD-L1 inhibitors in the treatment of nonsmall cell lung cancer will be included. All meta-analyses will be performed using RevMan software. The quality of the studies will be evaluated using the guidelines listed in the Cochrane Handbook. If the necessary data are available, then subgroup analyses will be performed for high-, median-, and low-dose cohorts. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements will be followed until the findings of the systematic review and meta-analysis are reported. Conclusions: This will be the first systematic review and meta-analysis to describe previously reported irAEs related to PD-1 and PD-L1 inhibitors in the treatment of nonsmall cell lung cancer. PMID:29095271

Intrapartum electrocardiogram alteration in fetuses with congenital heart disease: a case-control study.

PubMed

Gay, Estelle; Bornallet, Géraldine; Gaucherand, Pascal; Doret, Muriel

2015-11-01

To assess if the fetal electrocardiogram especially ST segment is modified by congenital heart diseases: modifications in frequencies of the different ST events and modifications in signal quality. A retrospective case-control study, comparing frequencies of the different ST events and the quality of the signal between fetuses with congenital heart diseases and fetuses without congenital heart disease. From 2000 to 2011, fifty-eight fetuses with congenital heart disease had their heart rate recording using a STAN device during labor. Control group was fetuses who were born just before a case and had a STAN as a second line for intrapartum surveillance. Cases and controls were matched on parity, gestational age at birth, presence of growth restriction and umbilical artery pH. Frequencies of the different ST event and quality of the signal were first analyzed for the global labor recording, and then separately for the first and the second phase of labor. No statistically significant difference in ST event frequencies between fetuses with congenital heart disease and the control group was found. Regarding the quality of the signal, 11.49% (±18.82) of recording time is a signal loss for fetus with congenital heart disease whereas only 5.18% (±10.67) for the control group (p=0.028). This is the first study investigating for intrapartum electrocardiogram modification in fetus with congenital heart disease. Congenital heart diseases do not modify frequencies of ST events. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Large-scale impacts of sea star wasting disease (SSWD) on intertidal sea stars and implications for recovery

PubMed Central

Burnaford, Jennifer L.; Ambrose, Richard F.; Antrim, Liam; Bohlmann, Heath; Blanchette, Carol A.; Engle, John M.; Fradkin, Steven C.; Gaddam, Rani; Harley, Christopher D. G.; Miner, Benjamin G.; Murray, Steven N.; Smith, Jayson R.; Whitaker, Stephen G.; Raimondi, Peter T.

2018-01-01

Disease outbreaks can have substantial impacts on wild populations, but the often patchy or anecdotal evidence of these impacts impedes our ability to understand outbreak dynamics. Recently however, a severe disease outbreak occurred in a group of very well-studied organisms–sea stars along the west coast of North America. We analyzed nearly two decades of data from a coordinated monitoring effort at 88 sites ranging from southern British Columbia to San Diego, California along with 2 sites near Sitka, Alaska to better understand the effects of sea star wasting disease (SSWD) on the keystone intertidal predator, Pisaster ochraceus. Quantitative surveys revealed unprecedented declines of P. ochraceus in 2014 and 2015 across nearly the entire geographic range of the species. The intensity of the impact of SSWD was not uniform across the affected area, with proportionally greater population declines in the southern regions relative to the north. The degree of population decline was unrelated to pre-outbreak P. ochraceus density, although these factors have been linked in other well-documented disease events. While elevated seawater temperatures were not broadly linked to the initial emergence of SSWD, anomalously high seawater temperatures in 2014 and 2015 might have exacerbated the disease’s impact. Both before and after the onset of the SSWD outbreak, we documented higher recruitment of P. ochraceus in the north than in the south, and while some juveniles are surviving (as evidenced by transition of recruitment pulses to larger size classes), post-SSWD survivorship is lower than during pre-SSWD periods. In hindsight, our data suggest that the SSWD event defied prediction based on two factors found to be important in other marine disease events, sea water temperature and population density, and illustrate the importance of surveillance of natural populations as one element of an integrated approach to marine disease ecology. Low levels of SSWD-symptomatic sea stars are still present throughout the impacted range, thus the outlook for population recovery is uncertain. PMID:29558484

IL-6 blockade in systemic juvenile idiopathic arthritis - achievement of inactive disease and remission (data from the German AID-registry).

PubMed

Bielak, M; Husmann, E; Weyandt, N; Haas, J-P; Hügle, B; Horneff, G; Neudorf, U; Lutz, T; Lilienthal, E; Kallinich, T; Tenbrock, K; Berendes, R; Niehues, T; Wittkowski, H; Weißbarth-Riedel, E; Heubner, G; Oommen, P; Klotsche, J; Foell, Dirk; Lainka, E

2018-04-05

Systemic juvenile idiopathic arthritis (sJIA) is a complex disease with an autoinflammatory component of unknown etiology related to the innate immune system. A major role in the pathogenesis has been ascribed to proinflammatory cytokines like interleukin-6 (IL-6), and effective drugs inhibiting their signaling are being developed. This study evaluates sJIA patients treated with the IL-6 inhibitor tocilizumab (TCZ) concerning clinical response rate, disease course and adverse effects in a real-life clinical setting. In 2009 a clinical and research consortium was established, including an online registry for autoinflammatory diseases (AID) ( https://aid-register.de ). Data for this retrospective TCZ study were documented by 13 centers. From 7/2009 to 4/2014, 200 patients with sJIA were recorded in the AID-registry. Out of these, 46 (19 m, 27 f, age 1-18 years) received therapy with TCZ. Long term treatment (median 23 months) has been documented in 24/46 patients who were evaluated according to Wallace criteria (active disease 6/24, inactive disease 5/24, remission 13/24 cases). Under observation co-medication were used in 40/46 cases. Adverse events were reported in 11/46 patients. The clinical response rate (no clinical manifestation, no increased inflammation parameters) within the first 12 weeks of treatment was calculated to be 35%. Out of 200 sJIA children reported in the German AID-registry, 46 were treated with TCZ, showing a clinical response rate of 35% during the first 12 weeks, and inactive disease and/or remission under medication in 75% after one year. Adverse events were seen in 24% and severe adverse events in 4%. The AID-Registry is funded by the BMBF (01GM08104, 01GM1112D, 01GM1512D).

Extracellular matrix disruption is an early event in the pathogenesis of skeletal disease in mucopolysaccharidosis I.

PubMed

Heppner, Jonathan M; Zaucke, Frank; Clarke, Lorne A

2015-02-01

Progressive skeletal and connective tissue disease represents a significant clinical burden in all of the mucopolysaccharidoses. Despite the introduction of enzyme replacement strategies for many of the mucopolysaccharidoses, symptomatology related to bone and joint disease appears to be recalcitrant to current therapies. In order to address these unmet medical needs a clearer understanding of skeletal and connective tissue disease pathogenesis is required. Historically the pathogenesis of the mucopolysaccharidoses has been assumed to directly relate to progressive storage of glycosaminoglycans. It is now apparent for many lysosomal storage disorders that more complex pathogenic mechanisms underlie patients' clinical symptoms. We have used proteomic and genome wide expression studies in the murine mucopolysaccharidosis I model to identify early pathogenic events occurring in micro-dissected growth plate tissue. Studies were conducted using 3 and 5-week-old mice thus representing a time at which no obvious morphological changes of bone or joints have taken place. An unbiased iTRAQ differential proteomic approach was used to identify candidates followed by validation with multiple reaction monitoring mass spectrometry and immunohistochemistry. These studies reveal significant decreases in six key structural and signaling extracellular matrix proteins; biglycan, fibromodulin, PRELP, type I collagen, lactotransferrin, and SERPINF1. Genome-wide expression studies in embryonic day 13.5 limb cartilage and 5 week growth plate cartilage followed by specific gene candidate qPCR studies in the 5week growth plate identified fourteen significantly deregulated mRNAs (Adamts12, Aspn, Chad, Col2a1, Col9a1, Hapln4, Lum, Matn1, Mmp3, Ogn, Omd, P4ha2, Prelp, and Rab32). The involvement of biglycan, PRELP and fibromodulin; all members of the small leucine repeat proteoglycan family is intriguing, as this protein family is implicated in the pathogenesis of late onset osteoarthritis. Taken as a whole, our data indicates that alteration of the extracellular matrix represents a very early event in the pathogenesis of the mucopolysaccharidoses and implies that biomechanical failure of chondro-osseous tissue may underlie progressive bone and joint disease symptoms. These findings have important therapeutic implications. Copyright © 2014 Elsevier Inc. All rights reserved.

Pre-event Smallpox Vaccination for Healthcare Workers Revisited – the Need for a Carefully Screened Multidisciplinary Cadre

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malone, JD D.

2007-03-01

Abstract As healthcare institutions are a focus of smallpox transmission early in an epidemic, several mathematical models support pre-event smallpox vaccination of healthcare workers (HCWs). The deciding factor for HCW voluntary vaccination is the risk of disease exposure versus the risk of vaccine adverse events. In a United States military population, with careful screening to exclude atopic dermatitis/eczema and immunosuppression, over 1 million vaccinia vaccinations were delivered with 1 fatality attributed to vaccination. Among 37,901 U.S. civilian volunteer healthcare workers vaccinated, 100 serious adverse events were reported including 10 ischemic cardiac episodes and six myocardial infarctions – 2 were fatal.more » This older population had a higher rate of adverse events due to age related coronary artery disease. T-cell mediated inflammatory processes, induced by live vaccinia vaccination, may have a role in the observed acute coronary artery events. With exclusion of individuals at risk for coronary artery disease, atopic dermatitis/eczema, and immunosuppression, HCWs can be smallpox vaccinated with minimal risk. A smallpox pre-vaccinated multidisciplinary cadre (physician, nurse, infection control practitioner, technician) will supply leadership to deal with fear and uncertainty while limiting spread and initial mortality of smallpox. Stochastic – from the Greek meaning “skillful in aiming” – is currently interpreted as arising from chance and involving probability. This issue’s article “Containing a large bioterrorist smallpox attack: a computer simulation approach” by Longini et al. is a discrete time, stochastic computer simulation model that offers additional planning guidance for a smallpox (variola virus) outbreak (1). Although interpretation of the model’s information may differ, Longini’s article concludes “Given that surveillance and containment measures are in place, preemptive vaccination of hospital workers would further reduce the number of smallpox cases and deaths, but would require large numbers of prevaccinations” for the greatest effectiveness. In their simulation, the hospital has 686 workers (a relatively small facility compared to many tertiary care institutions) and 133 make close contact with smallpox cases prior to the initiation of isolation measures. Of 828 cases, 50% originated in the hospital and 13% of the contacts were untraceable. Preemptive smallpox (vaccinia virus) vaccination of 10% of the hospital workers, in addition to surveillance and containment, had a small effect on the average number of cases; however, preemptive vaccination of 50% of the hospital workers had a relatively large effect on case reduction. The larger number of preemptive vaccinations required less contact tracing and “ring” containment vaccinations. A delay of one day in fully implementing surveillance and containment resulted in a large epidemic.« less

Management of Patient Care in Hemodialysis While Focusing on Cardiovascular Disease Events and the Atypical Role of Hyper- and/or Hypotension: A Systematic Review

PubMed Central

Khan, Amer Hayat; Syed Sulaiman, Syed Azhar; Khan, Irfanullah

2016-01-01

Background. Hemodialysis related hemodynamic instability is a major but an underestimated issue. Moreover, cardiovascular events are the leading cause of morbidity and mortality associated with blood pressure in hemodialysis patients. However, there have been many controversies regarding the role and management of hyper- and/or hypotension during hemodialysis that needs to be addressed. Objective. To critically review the available published data on the atypical role of hyper- and/or hypotension in cardiovascular associated morbidity and mortality in patients on hemodialysis and to understand the discrepancies in this context. Methods. A comprehensive search of literature employing electronic as well as manual sources and screening 2783 papers published between Jan 1980 and Oct 2015 was conducted to collect, identify, and analyze relevant information through peer-reviewed research articles, systematic reviews, and other published works. The cardiovascular events, including accelerated atherosclerotic cardiovascular disease (ASCVD), stroke, heart failure, myocardial infarction, myocardial ischemia, and stress induced myocardial dysfunction, leading to death were considered relevant. Results. A total of 23 published articles met the inclusion criteria and were included for in-depth review and analysis to finalize a comprehensive systematic review article. All the studies showed a significant association between the blood pressure and cardiovascular disease events in hemodialysis patients. Conclusions. Both intradialytic hypertension/hypotension episodes are major risk factors for cardiovascular mortality with a high percentage of probable causality; however, clinicians are faced with a dilemma on how to evaluate blood pressure and treat this condition. PMID:27833921

Biopsychosocial Predictors of Fall Events among Older African Americans

PubMed Central

Nicklett, Emily Joy; Taylor, Robert Joseph; Rostant, Ola; Johnson, Kimson E.; Evans, Linnea

2016-01-01

This study identifies risk and protective factors for falls among older, community-dwelling African Americans. Drawing upon the biopsychosocial perspective (Engel, 1997), we conducted a series of sex- and age-adjusted multinomial logistic regression analyses to identify the correlates of fall events among older African Americans. Our sample consisted of 1,442 community-dwelling African Americans aged 65 and older, participating in the 2010-12 rounds of the Health and Retirement Study. Biophysical characteristics associated with greater relative risk of experiencing single and/or multiple falls included greater functional limitations, poorer self-rated health, poorer self-rated vision, chronic illnesses (high blood pressure, diabetes, cancer, lung disease, heart problems, stroke, and arthritis), greater chronic illness comorbidity, older age, and female sex. Physical activity was negatively associated with recurrent falls. Among the examined psychosocial characteristics, greater depressive symptoms were associated with greater relative risk of experiencing single and multiple fall events. Implications for clinicians and future studies are discussed. PMID:28285579

Sexual counselling for individuals with cardiovascular disease and their partners: a consensus document from the American Heart Association and the ESC Council on Cardiovascular Nursing and Allied Professions (CCNAP).

PubMed

Steinke, Elaine E; Jaarsma, Tiny; Barnason, Susan A; Byrne, Molly; Doherty, Sally; Dougherty, Cynthia M; Fridlund, Bengt; Kautz, Donald D; Mårtensson, Jan; Mosack, Victoria; Moser, Debra K

2013-11-01

After a cardiovascular event, patients and their families often cope with numerous changes in their lives, including dealing with consequences of the disease or its treatment on their daily lives and functioning. Coping poorly with both physical and psychological challenges may lead to impaired quality of life. Sexuality is one aspect of quality of life that is important for many patients and partners that may be adversely affected by a cardiac event. The World Health Organization defines sexual health as '… a state of physical, emotional, mental and social well-being in relation to sexuality; it is not merely the absence of disease, dysfunction or infirmity. Sexual health requires a positive and respectful approach to sexuality and sexual relationships, as well as the possibility of having pleasurable and safe sexual experiences ….'(1(p4)) The safety and timing of return to sexual activity after a cardiac event have been well addressed in an American Heart Association scientific statement, and decreased sexual activity among cardiac patients is frequently reported.(2) Rates of erectile dysfunction (ED) among men with cardiovascular disease (CVD) are twice as high as those in the general population, with similar rates of sexual dysfunction in females with CVD.(3) ED and vaginal dryness may also be presenting signs of heart disease and may appear 1-3 years before the onset of angina pectoris. Estimates reflect that only a small percentage of those with sexual dysfunction seek medical care;(4) therefore, routine assessment of sexual problems and sexual counselling may be of benefit as part of effective management by physicians, nurses, and other healthcare providers.

Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors.

PubMed

Carnevale-Schianca, Fabrizio; Caravelli, Daniela; Gallo, Susanna; Coha, Valentina; D'Ambrosio, Lorenzo; Vassallo, Elena; Fizzotti, Marco; Nesi, Francesca; Gioeni, Luisa; Berger, Massimo; Polo, Alessandra; Gammaitoni, Loretta; Becco, Paolo; Giraudo, Lidia; Mangioni, Monica; Sangiolo, Dario; Grignani, Giovanni; Rota-Scalabrini, Delia; Sottile, Antonino; Fagioli, Franca; Aglietta, Massimo

2017-03-01

Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors. GVHD prophylaxis included combination post-HCT cyclophosphamide 50 mg/kg (days +3 and +4) and tacrolimus/mofetil mycophenolate (T/MMF) (day +5 forward). The primary objective was the cumulative incidence of acute and chronic GVHD. Between March 2011 and May 2015, 35 consecutive patients received the proposed regimen. MMF was stopped in all patients at day +28; the median discontinuation of tacrolimus was day +113. Acute and chronic GVHD cumulative incidences were 17% and 7%, respectively, with no grade IV GVHD events, only 2 patients requiring chronic GVHD immunosuppression control, and no deaths from GVHD. Two-year NRM, overall survival, event-free survival, and chronic GVHD event-free survival rates were 3%, 77%, 54%, and 49%, respectively. The graft-versus-tumor effect was maintained as 5 of 15 patients (33%) who received HCT with evidence of disease experienced further disease response. A post-transplant cyclophosphamide + T/MMF combination strategy effectively prevented acute and chronic GVHD after alloPBSCT from HLA-matched donors and achieved an unprecedented low NRM without losing efficacy in disease control or impaired development of the graft-versus-tumor effect. This trial is registered at clinicaltrials.gov as NCT02300571. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Deciphering the functions of O-GlcNAc glycosylation in the brain: The role of site-specific quantitative O-GlcNAcomics.

PubMed

Thompson, John W; Sorum, Alexander W; Hsieh-Wilson, Linda C

2018-06-23

The dynamic posttranslational modification O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain. Like phosphorylation, O-GlcNAcylation is inducible and plays important functional roles in both physiology and disease. Recent advances in mass spectrometry (MS) and bioconjugation methods are now enabling the mapping of O-GlcNAcylation events to individual sites in proteins. However, our understanding of which glycosylation events are necessary for regulating protein function and controlling specific processes, phenotypes, or diseases remains in its infancy. Given the sheer number of O-GlcNAc sites, methods are greatly needed to identify promising sites and prioritize them for time- and resource-intensive functional studies. Revealing sites that are dynamically altered by different stimuli or disease states will likely to go a long way in this regard. Here, we describe advanced methods for identifying O-GlcNAc sites on individual proteins and across the proteome, and for determining their stoichiometry in vivo. We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites. These cutting-edge technologies are beginning to bridge the gap between the high-throughput cataloging of O-GlcNAcylated proteins and the relatively low-throughput study of individual proteins. By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.

Vitamin E in the prevention of cardiovascular disease: the importance of proper patient selection

PubMed Central

Vardi, Moshe; Levy, Nina S.; Levy, Andrew P.

2013-01-01

Vitamin E is a naturally occurring fat-soluble antioxidant which has been proposed as a treatment for both primary and secondary protection against cardiovascular (CV) events. Promising data from observational epidemiological studies associating higher vitamin E dietary intake with lower risk of CV events have not been validated in randomized controlled clinical trials assessing the effect of vitamin E on CV outcomes. While the pendulum of medical opinion has swung to suggest that high dose vitamin E supplements have no place in the treatment and prevention of CV disease, new data is emerging that allows identification of a specific target population for this treatment, namely patients with diabetes mellitus and the haptoglobin genotype 2-2. This review details the scientific basis and clinical evidence related to the effect of vitamin E on CV outcomes, and the importance of proper patient selection in gaining therapeutic benefit from this intervention. PMID:23505320

Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy: final analysis of a multicentre, open-label, early-access protocol trial.

PubMed

Sternberg, Cora N; Castellano, Daniel; Daugaard, Gedske; Géczi, Lajos; Hotte, Sebastien J; Mainwaring, Paul N; Saad, Fred; Souza, Ciro; Tay, Miah H; Garrido, José M Tello; Galli, Luca; Londhe, Anil; De Porre, Peter; Goon, Betty; Lee, Emma; McGowan, Tracy; Naini, Vahid; Todd, Mary B; Molina, Arturo; George, Daniel J

2014-10-01

In the final analysis of the phase 3 COU-AA-301 study, abiraterone acetate plus prednisone significantly prolonged overall survival compared with prednisone alone in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. Here, we present the final analysis of an early-access protocol trial that was initiated after completion of COU-AA-301 to enable worldwide preapproval access to abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. We did a multicentre, open-label, early-access protocol trial in 23 countries. We enrolled patients who had metastatic castration-resistant prostate cancer progressing after taxane chemotherapy. Participants received oral doses of abiraterone acetate (1000 mg daily) and prednisone (5 mg twice a day) in 28-day cycles until disease progression, development of sustained side-effects, or abiraterone acetate becoming available in the respective country. The primary outcome was the number of adverse events arising during study treatment and within 30 days of discontinuation. Efficacy measures (time to prostate-specific antigen [PSA] progression and time to clinical progression) were gathered to guide treatment decisions. We included in our analysis all patients who received at least one dose of abiraterone acetate. This study is registered with ClinicalTrials.gov, number NCT01217697. Between Nov 17, 2010, and Sept 30, 2013, 2314 patients were enrolled into the early-access protocol trial. Median follow-up was 5·7 months (IQR 3·5-10·6). 952 (41%) patients had a grade 3 or 4 treatment-related adverse event, and grade 3 or 4 serious adverse events were recorded in 585 (25%) people. The most common grade 3 and 4 adverse events were hepatotoxicity (188 [8%]), hypertension (99 [4%]), cardiac disorders (52 [2%]), osteoporosis (31 [1%]), hypokalaemia (28 [1%]), and fluid retention or oedema (23 [1%]). 172 (7%) patients discontinued the study because of adverse events (64 [3%] were drug-related), as assessed by the investigator, and 171 (7%) people died. The funder assessed causes of death, which were due to disease progression (85 [4%]), an unrelated adverse experience (72 [3%]), and unknown reasons (14 [1%]). Of the 86 deaths not attributable to disease progression, 18 (<1%) were caused by a drug-related adverse event, as assessed by the investigator. Median time to PSA progression was 8·5 months (95% CI 8·3-9·7) and median time to clinical progression was 12·7 months (11·8-13·8). No new safety signals or unexpected adverse events were found in this early-access protocol trial to assess abiraterone acetate for patients with metastatic castration-resistant prostate cancer who progressed after chemotherapy. Future work is needed to ascertain the most effective regimen of abiraterone acetate to optimise patients' outcomes. Janssen Research & Development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Deciphering membrane-associated molecular processes in target tissue of autoimmune uveitis by label-free quantitative mass spectrometry.

PubMed

Hauck, Stefanie M; Dietter, Johannes; Kramer, Roxane L; Hofmaier, Florian; Zipplies, Johanna K; Amann, Barbara; Feuchtinger, Annette; Deeg, Cornelia A; Ueffing, Marius

2010-10-01

Autoimmune uveitis is a blinding disease presenting with autoantibodies against eye-specific proteins as well as autoagressive T cells invading and attacking the immune-privileged target tissue retina. The molecular events enabling T cells to invade and attack the tissue have remained elusive. Changes in membrane protein expression patterns between diseased and healthy stages are especially interesting because initiating events of disease will most likely occur at membranes. Since disease progression is accompanied with a break-down of the blood-retinal barrier, serum-derived proteins mask the potential target tissue-related changes. To overcome this limitation, we used membrane-enriched fractions derived from retinas of the only available spontaneous animal model for the disease equine recurrent uveitis, and compared expression levels by a label-free LC-MSMS-based strategy to healthy control samples. We could readily identify a total of 893 equine proteins with 57% attributed to the Gene Ontology project term "membrane." Of these, 179 proteins were found differentially expressed in equine recurrent uveitis tissue. Pathway enrichment analyses indicated an increase in proteins related to antigen processing and presentation, TNF receptor signaling, integrin cell surface interactions and focal adhesions. Additionally, loss of retina-specific proteins reflecting decrease of vision was observed as well as an increase in Müller glial cell-specific proteins indicating glial reactivity. Selected protein candidates (caveolin 1, integrin alpha 1 and focal adhesion kinase) were validated by immunohistochemistry and tissue staining pattern pointed to a significant increase of these proteins at the level of the outer limiting membrane which is part of the outer blood-retinal barrier. Taken together, the membrane enrichment in combination with LC-MSMS-based label-free quantification greatly increased the sensitivity of the comparative tissue profiling and resulted in detection of novel molecular pathways related to equine recurrent uveitis.

The relationship between complaints of night-time heartburn and sleep-related gastroesophageal reflux.

PubMed

Orr, W C; Goodrich, S; Estep, M E; Shepherd, K

2014-01-01

This study investigated whether the complaint of night-time heartburn (NHB) as opposed to daytime heartburn (DHB) is a reliable reflection of actual sleep-related reflux events. Three groups of individuals were studied: individuals with complaints of NHB at least twice per week (n = 24), individuals with complaints of DHB (n = 23), and normal participants without any complaints of regular heartburn during the day or night (n = 25). All three groups were studied on one occasion with combined pH monitoring and polysomnography, and subjective questionnaires about sleep disturbance and sleep quality were given to all participants. The NHB group had significantly more sleep-related reflux events compared with both DHB and control groups (P < 0.01). DHB subjects had significantly (P < 0.05) more sleep-related reflux events than normal controls. Total acid contact time (ACT) was significantly (P < 0.05) elevated in the NHB group compared with both the DHB and control group. Sleep-related ACT was also significantly (P < 0.05) elevated in the NHB group compared with the other two groups, while upright (daytime) ACT was not significantly different. The NHB group was significantly (P < 0.05) worse regarding measures of both objective and subjective sleep quality. Subjects with exclusively DHB do have sleep-related reflux that is greater than normal controls. Subjects with NHB have significantly more sleep-related reflux, and both objective and subjective sleep abnormalities compared with normal controls. Complaints of NHB reflect sleep-related reflux events and may be indicative of a more clinically significant condition. © 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Influenza preparedness and the bureaucratic reflex: anticipating and generating the 2009 H1N1 event.

PubMed

Barker, Kezia

2012-07-01

This paper draws together work on the event to problematise the generative implications of anticipatory governance in the management of emerging infectious disease. Through concerns for preparedness, the need to anticipate outbreaks of disease has taken on a new urgency. With the identification of the H1N1 virus circulating amongst human populations in 2009, public health measures and security practices at regional, national and international levels were rapidly put into play. However, as the ensuing event demonstrated, the social, political and economic disruptions of emerging infectious diseases can be matched by those of anticipatory actions. I argue that the event-making potential of surveillance practices and the pre-determined arrangements of influenza preparedness planning, when triggered by the H1N1 virus, caused an event acceleration through the hyper-sensitised global health security architecture. In the UK, this led to a bureaucratic reflex, a security response event that overtook the present actualities of the disease. This raises questions about the production of forms of insecurity by the security apparatus itself. Copyright © 2012. Published by Elsevier Ltd.

The Management of Chronic Disease: a Study of Employee Morbidity and Mortality at the NASA, Goddard Space Flight Center, 1966 - 1971

NASA Technical Reports Server (NTRS)

Villafana, C.; Mockbee, J.

1971-01-01

Several approaches to studying chronic disease patterns in the employee population at Goddard Space Flight Center from 1966 to 1970 are presented. Attempts were made to summarize preliminary data for 1971 and relate this data to specific programs and events which may have had some causative influence. Investigative data for the study cover records of periodic and return to work examinations, injury and illness visit reports, mortality data, and health trends with and without external influences.

[New guidelines for the assessment of mental disorders--from a standpoint of lawyer].

PubMed

Yamaguchi, Koichiro

2012-01-01

In the field of Workers' Compensation Law, new guidelines were issued by the Ministry of Health, Labour and Welfare (Circular 26 Dec. 2011). This article briefly explains its content and function. Compared with medical insurance, a worker's compensation solely covers the diseases arising "out of employment", and the guidelines prescribe the criteria in order to decide on a causal relationship (nessocausale) between work and a mental disorder. By doing so, the guidelines aim to secure the fair and appropriate administration of compensation. The guidelines set the "Table" by which the events at the workplace are evaluated. When the event is "strong", the compensation is to be given. There are several other events which are, by themselves, "strong" (ex., work-related death). In parallel with the events, the working time (especially overtime) is also measured as a factor showing the heaviness of the work.

Adapting biomarker technologies to adverse outcome pathways (AOPs) research: current thoughts on using in vivo discovery for developing in vitro target methods

EPA Science Inventory

Adverse outcome pathways (AOP) research is a relatively new concept in human systems biology for assessing the molecular level linkage from an initiating (chemical) event that could lead to a disease state. Although most implementations of AOPs are based on liquids analyses, the...

Perfectionism in Relation to Stress and Cardiovascular Disease among Gifted Individuals and the Need for Affective Interventions

ERIC Educational Resources Information Center

Corson, Ansley T.; Loveless, James P.; Mochrie, Kirk D.; Whited, Matthew C.

2018-01-01

Maladaptive perfectionism has the potential to put gifted individuals at an increased risk for cardiac events via the reduced heart rate variability that results from chronic negative affect and physiological stress reactions. As a result, implementing affective interventions into gifted programs may play a critical role in teaching gifted…

Treatment Needs and Adverse Events Related to Dental Treatment under General Anesthesia for Individuals with Autism

ERIC Educational Resources Information Center

Rada, Robert E.

2013-01-01

Individuals with autism can be quite challenging to treat in a routine dental-office setting, especially when extensive dental treatment and disruptive behavioral issues exist. Individuals with autism may also be at higher risk for oral disease. Frequently, general anesthesia is the only method to facilitate completion of the needed dental…

Efforts to Control by Children and Adults with the Type A Coronary-Prone Behavior Pattern.

ERIC Educational Resources Information Center

Matthews, Karen A.

1979-01-01

Examines the initial reactions of type A and type B boys and men to uncontrollable events. Type A individuals are characterized by extremes of competitive achievement striving, impatience, and aggression, a pattern of behavior implicated by recent research in the etiology of coronary heart disease. Type B individuals exhibit the relative absence…

Foodborne Botulism in the United States, 1990–2000

PubMed Central

Tucker, Nicole; Sulka, Alana; McLaughlin, Joseph; Maslanka, Susan

2004-01-01

Foodborne botulism, a potentially lethal neuroparalytic disease, is caused by ingesting preformed Clostridium botulinum neurotoxin. We reviewed surveillance data and reports from 1990 to 2000. Of 263 cases from 160 foodborne botulism events (episode of one or more related cases) in the United States, 103 (39%) cases and 58 events occurred in Alaska. Patients' median age was 48 years; 154 (59%) were female; the case-fatality rate was 4%. The median number of cases per event was 1 (range 1–17). Toxin type A caused 51% of all cases; toxin type E caused 90% of Alaska cases. A particular food was implicated in 126 (79%) events. In the lower 49 states, a noncommercial food item was implicated in 70 (91%) events, most commonly home-canned vegetables (44%). Two restaurant-associated outbreaks affected 25 persons. All Alaska cases were attributable to traditional Alaska Native foods. Botulism prevention efforts should be focused on those who preserve food at home, Alaska Natives, and restaurant workers. PMID:15498163

Evaluation of correlations between underlying disease and port complications.

PubMed

Teichgräber, U; Nagel, S N; Kausche, S

2014-05-01

Evaluation of correlations between underlying disease and port complications. Retrospective analysis of a data set of 3160 port systems, which had been interventionally implanted over a period of 10 years. Of these, 1393 were included in the final evaluation. The 7 most common underlying diseases and port-induced complications were considered. Port-related thrombotic events, port pocket infections as well as the port-induced sepsis were evaluated and classified as either early or late complications. In 1393 ports, 131 experienced complications. Of these, 22.1 % (n = 29) were early and 79.6 % (n = 102) late complications. The overall incidence rate of late complications was 0.253/1000 observed days. It differed significantly between the underlying diseases (p < 0.001) and was significantly lower in colon carcinoma when compared with pancreatic (p = 0.049), gastric (p = 0.012) and bronchial carcinoma (p = 0.042). The incidence rate of the port sepsis between the underlying diseases also differed significantly (p =  0.006) and had the highest rate in gastric and bronchial carcinoma. The occurrence of a thrombotic event also showed a significant difference in the incidence rates between the underlying diseases (p = 0.045) and was highest in pancreatic and gastric carcinoma. There are significant differences in the incidences of complications between the underlying diseases. Knowledge about this can help to improve the port-care and to take specific preventive measures. © Georg Thieme Verlag KG Stuttgart · New York.

Healthcare resource use and cost associated with varying dosages of extended corticosteroid exposure in a US population.

PubMed

Rice, J Bradford; White, Alan G; Johnson, Michaela; Wagh, Aneesha; Qin, Yimin; Bartels-Peculis, Laura; Ciepielewska, Gosia; Nelson, Winnie W

2018-05-23

To quantify healthcare resource use (HCRU) and costs associated with varying levels of corticosteroid exposure. Patients with a diagnosis of selected autoimmune and inflammatory diseases between 1 January 2006 and 30 September 2015 ("study period") were selected from a de-identified, privately-insured claims database. Patients were stratified into four treatment cohorts based on the dosing and duration of continuous corticosteroid use following disease diagnosis: intermittent use with <60 days of corticosteroid use and ≥60 days of corticosteroid use with low (≤7.5 mg/day), medium (>7.5-≤15 mg/day), or high (>15 mg/day) dosage. Patients were followed from the date of their highest dose episode of corticosteroid use ("treatment index date") until the earliest of the end of continuous corticosteroid use +30 days, disenrollment from health plan, or the end of the study period ("follow-up period"). HCRU and costs in the follow-up period were compared across treatment cohorts. Of 78,704 patients who were identified for study inclusion, 29% had extended corticosteroid use lasting ≥60 days, and 71% had intermittent use. On average, patients in the high-dose cohort incurred twice the cost of intermittent users ($68,408 vs $32,690 in annualized total all-cause healthcare costs, USD). Adverse event-related medical costs accounted for ∼40% of medical costs, and were higher than disease-related medical costs for all cohorts with extended corticosteroid exposure. Comparing the high-dose and low-dose cohorts, the smaller savings in disease-related prescriptions ($1,680) occurred along with a much larger cost in adverse event-related spend ($13,464). The impact of corticosteroids may be under-estimated because of conservative follow-up duration, and administrative data may contain inaccuracies in coding. Steroid use, especially at higher doses, is associated with higher HCRU and costs.

Financial strain predicts recurrent events among women with coronary artery disease.

PubMed

Georgiades, Anastasia; Janszky, Imre; Blom, May; László, Krisztina D; Ahnve, Staffan

2009-06-26

Although a number of epidemiological studies have found an association between socioeconomic status (SES) indices such as income and education and coronary morbidity and mortality, few have looked at health consequences arising from actually experiencing financial shortcomings. The objective of the present study was to examine whether financial strain predicts recurrent coronary artery disease (CAD) events among women with established CAD. Two hundred two women (mean age 62+/-9 years) hospitalized for an acute coronary event were followed over a period of 3.5 years. Demographic, socioeconomic, lifestyle-related, psychosocial and biological characteristics were obtained by means of questionnaires and clinical examination. Data on recurrent cardiac events were collected from the Swedish discharge and death registers. Women experiencing financial strain over the past year had an increased risk for recurrent events, i.e. the combination of all-cause mortality, new acute myocardial infarction and unstable angina pectoris during the follow-up with an unadjusted hazard ratio (HR) of 3.2 (95% CI 1.6-6.6), and a HR of 2.76 (95% CI 1.02-7.50) after controlling for education, household income, age, cohabiting status, inclusion diagnosis and rehabilitation therapy. Adjustment for potential mediators, i.e. psychosocial factors, lipids, diabetes mellitus, smoking, body-mass index, blood pressure, physical activity, alcohol consumption, participation in other cardiac rehabilitation programs did not alter the results significantly. Financial strain was a predictor for recurrent events among women with CAD, independently of commonly used SES indicators such as education and household income. Future studies will have to explore the mechanism behind this association.

A patient with stress-related onset and exacerbations of Graves disease.

PubMed

Vita, Roberto; Lapa, Daniela; Vita, Giuseppe; Trimarchi, Francesco; Benvenga, Salvatore

2009-01-01

An 18-year-old, nonsmoking woman presented to her general practitioner with a 1-week history of weakness, fatigue, palpitations, nervousness, tremors, insomnia, heat intolerance, and sudden enlargement of a thyroid goiter that had been detected 2 years earlier. The patient's symptoms had started shortly after she experienced emotional stress. Diagnostic work-up disclosed an avid radioactive iodine uptake by the goiter. On ultrasound examination, the thyroid gland was enlarged with a diffusely hypoechogenic structure and intense vascularization. Thyroid scintigraphy with (131)I; ultrasonography of the thyroid gland; and measurements of serum free T(3), free T(4), TSH levels and thyroid autoantibodies, including autoantibodies against thyroglobulin (TgAb), thyroperoxidase (TPOAb) and TSH receptor (TRAb). Graves disease, with stress-related onset and subsequent stress-related exacerbations. The patient was treated with methimazole to normalize levels of thyroid hormone and thyroid autoantibodies, and with bromazepam to help her cope with stress. The daily dose of methimazole was kept low during pregnancy. Over the 4 year period when the patient was taking methimazole, exacerbations of hyperthyroidism occurred twice: during her first pregnancy and 9 months after her first delivery. On all three occasions, symptoms were preceded by stressful life events. Further exacerbations were avoided by starting bromazepam treatment soon after the patient experienced stressful events.

Localized structural frustration for evaluating the impact of sequence variants

PubMed Central

Kumar, Sushant; Clarke, Declan; Gerstein, Mark

2016-01-01

Population-scale sequencing is increasingly uncovering large numbers of rare single-nucleotide variants (SNVs) in coding regions of the genome. The rarity of these variants makes it challenging to evaluate their deleteriousness with conventional phenotype–genotype associations. Protein structures provide a way of addressing this challenge. Previous efforts have focused on globally quantifying the impact of SNVs on protein stability. However, local perturbations may severely impact protein functionality without strongly disrupting global stability (e.g. in relation to catalysis or allostery). Here, we describe a workflow in which localized frustration, quantifying unfavorable local interactions, is employed as a metric to investigate such effects. Using this workflow on the Protein Databank, we find that frustration produces many immediately intuitive results: for instance, disease-related SNVs create stronger changes in localized frustration than non-disease related variants, and rare SNVs tend to disrupt local interactions to a larger extent than common variants. Less obviously, we observe that somatic SNVs associated with oncogenes and tumor suppressor genes (TSGs) induce very different changes in frustration. In particular, those associated with TSGs change the frustration more in the core than the surface (by introducing loss-of-function events), whereas those associated with oncogenes manifest the opposite pattern, creating gain-of-function events. PMID:27915290

Men's and women's health beliefs differentially predict coronary heart disease incidence in a population-based sample.

PubMed

Rom Korin, Maya; Chaplin, William F; Shaffer, Jonathan A; Butler, Mark J; Ojie, Mary-Jane; Davidson, Karina W

2013-04-01

To examine gender differences in the association between beliefs in heart disease preventability and 10-year incidence of coronary heart disease (CHD) in a population-based sample. A total of 2,688 Noninstitutionalized Nova Scotians without prior CHD enrolled in the Nova Scotia Health Study (NSHS95) and were followed for 10 years. Risk factors, health behaviors, and incident CHD were assessed. Participants responded "yes" or "no" to a question about heart disease preventability. Survival models, adjusted for age, income, total and high-density lipoprotein cholesterol, and systolic blood pressure, were used to estimate the relation between health belief and incident CHD. Gender differences in the relation between health beliefs and health behaviors were assessed. Gender was a significant moderator of the relation between belief and CHD incidence; specifically, women who believed heart disease could be prevented were less likely to have incident CHD events compared with women who believed heart disease could not be prevented (hazard ratio [HR] = 0.36, 95% confidence interval [CI] = 0.24-0.55, p < .001). This relation was not found for men. Belief was also related to smoking behavior for women (β = -0.70, odds ratio [OR] = 0.50, 95% CI = 0.33-0.74, p = .001) but not for men. Smoking significantly mediated the relation between health beliefs and incident CHD for women (z = -1.96, p = .05), but not for men. Health belief in prevention and subsequent smoking was an important independent predictor of incident CHD in women but not in men.

Association of aortic wall thickness on contrast-enhanced chest CT with major cerebro-cardiac events.

PubMed

Tresoldi, Silvia; Di Leo, Giovanni; Zoffoli, Elena; Munari, Alice; Primolevo, Alessandra; Cornalba, Gianpaolo; Sardanelli, Francesco

2014-11-01

There is a significant association between aortic atherosclerosis and previous major cardiovascular events. Particularly, thoracic aortic atherosclerosis is closely related to the degree of coronary and carotid artery disease. Thus, there is a rationale for screening the thoracic aorta in patients who undergo a chest computed tomography (CT) for any clinical question, in order to detect patients at increased risk of cerebro-cardiovascular (CCV) events. To estimate the association between either thoracic aortic wall thickness (AWT) or aortic total calcium score (ATCS) and CCV events. One hundred and forty-eight non-cardiac patients (78 men; 67 ± 12 years) underwent chest contrast-enhanced multidetector CT (MDCT). The AWT was measured at the level of the left atrium (AWTref) and at the maximum AWT (AWTmax). Correlation with clinical CCV patients' history was estimated. The value of AWTmax and of a semi-quantitative ATCS as a marker for CCV events was assessed using receiver-operating characteristic curve (ROC) analysis and multivariate regression analysis. Out of 148 patients, 59% reported sedentary lifestyle, 44% hypertension, 32% smoking, 23% hypercholesterolemia, 13% family history of cardiac disease, 12% diabetes, and 10% BMI ≥ 30 kg/m(2); 9% reported myocardial infarction, 8% aortic aneurism, 8% myocardial revascularization, and 2% ischemic stroke. Twenty-six percent of patients had a medium-to-high ATCS. Both AWTmax and AWTref correlated with hypertension and age (P < 0.002). At the ROC analysis, a 4.8 mm threshold was associated to a 90% specificity and an odds ratio of 6.3 (AUC = 0.735). Assuming as threshold the AWTmax median value (4.3 mm) of patients who suffered from at least one CCV event in their history, a negative predictive value of 90%, a RR of 3.6 and an OR of 6.3 were found. At the multivariate regression analysis, AWTmax was the only independent variable associated to the frequency of CCV events. Patients with increased thoracic AWTmax on chest MDCT could be considered at risk for CCV disease. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Urine neutrophil gelatinase-associated lipocalin and risk of cardiovascular disease and death in CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) Study.

PubMed

Liu, Kathleen D; Yang, Wei; Go, Alan S; Anderson, Amanda H; Feldman, Harold I; Fischer, Michael J; He, Jiang; Kallem, Radhakrishna R; Kusek, John W; Master, Stephen R; Miller, Edgar R; Rosas, Sylvia E; Steigerwalt, Susan; Tao, Kaixiang; Weir, Matthew R; Hsu, Chi-Yuan

2015-02-01

Chronic kidney disease is common and is associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about the risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration-based markers (such as serum creatinine or albuminuria). Cohort study, CRIC (Chronic Renal Insufficiency Cohort) Study. 3,386 participants with estimated glomerular filtration rate of 20 to 70mL/min/1.73m(2) enrolled from June 2003 through August 2008. Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration. Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March 2011. Urine NGAL measured at baseline with a 2-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories). There were 428 heart failure events (during 16,383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16,584 person-years of follow-up), and 522 deaths (during 18,214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors, and cardiac medications, higher urine NGAL levels remained associated independently with ischemic atherosclerotic events (adjusted HR for the highest [>49.5ng/mL] vs lowest [≤6.9ng/mL] quintile, 1.83 [95% CI, 1.20-2.81]; HR per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths. Urine NGAL was measured only once. Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were associated independently with future ischemic atherosclerotic events, but not with heart failure events or deaths. Copyright © 2015 National Kidney Foundation, Inc. All rights reserved.

Stroke is predicted by low visuospatial in relation to other intellectual abilities and coronary heart disease by low general intelligence.

PubMed

Kajantie, Eero; Räikkönen, Katri; Henriksson, Markus; Leskinen, Jukka T; Forsén, Tom; Heinonen, Kati; Pesonen, Anu-Katriina; Osmond, Clive; Barker, David J P; Eriksson, Johan G

2012-01-01

Low intellectual ability is associated with an increased risk of coronary heart disease and stroke. Most studies have used a general intelligence score. We studied whether three different subscores of intellectual ability predict these disorders. We studied 2,786 men, born between 1934 and 1944 in Helsinki, Finland, who as conscripts at age 20 underwent an intellectual ability test comprising verbal, visuospatial (analogous to Raven's progressive matrices) and arithmetic reasoning subtests. We ascertained the later occurrence of coronary heart disease and stroke from validated national hospital discharge and death registers. 281 men (10.1%) had experienced a coronary heart disease event and 131 (4.7%) a stroke event. Coronary heart disease was predicted by low scores in all subtests, hazard ratios for each standard deviation (SD) lower score ranging from 1.21 to 1.30 (confidence intervals 1.08 to 1.46). Stroke was predicted by a low visuospatial reasoning score, the corresponding hazard ratio being 1.23 (95% confidence interval 1.04 to 1.46), adjusted for year and age at testing. Adjusted in addition for the two other scores, the hazard ratio was 1.40 (1.10 to 1.79). This hazard ratio was little affected by adjustment for socioeconomic status in childhood and adult life, whereas the same adjustments attenuated the associations between intellectual ability and coronary heart disease. The associations with stroke were also unchanged when adjusted for systolic blood pressure at 20 years and reimbursement for adult antihypertensive medication. Stroke is predicted by low visuospatial reasoning scores in relation to scores in the two other subtests. This association may be mediated by common underlying causes such as impaired brain development, rather than by mechanisms associated with risk factors shared by stroke and coronary heart disease, such as socio-economic status, hypertension and atherosclerosis.

Neural network approach in multichannel auditory event-related potential analysis.

PubMed

Wu, F Y; Slater, J D; Ramsay, R E

1994-04-01

Even though there are presently no clearly defined criteria for the assessment of P300 event-related potential (ERP) abnormality, it is strongly indicated through statistical analysis that such criteria exist for classifying control subjects and patients with diseases resulting in neuropsychological impairment such as multiple sclerosis (MS). We have demonstrated the feasibility of artificial neural network (ANN) methods in classifying ERP waveforms measured at a single channel (Cz) from control subjects and MS patients. In this paper, we report the results of multichannel ERP analysis and a modified network analysis methodology to enhance automation of the classification rule extraction process. The proposed methodology significantly reduces the work of statistical analysis. It also helps to standardize the criteria of P300 ERP assessment and facilitate the computer-aided analysis on neuropsychological functions.