Risk Indicators For Development Research Articles

Meta-Analysis of Cognition in Parkinson's Disease Mild Cognitive Impairment and Dementia Progression.

Mild cognitive changes, including executive dysfunction, are seen in Parkinson's Disease (PD). Approximately 30% of individuals with PD develop Parkinson's disease dementia (PDD). Mild cognitive impairment (MCI) has been identified as a transitional state between normal cognition and dementia. Although PD-MCI and its cognitive correlates have been increasingly studied as a risk indicator for development of PDD, investigations into the PD-MCI construct have yielded heterogeneous findings. Thus, a typical PD-MCI cognitive profile remains undefined. The present meta-analysis examined published cross-sectional studies of PD-MCI and cognitively normal PD (PD-CN) groups to provide aggregated effect sizes of group test performance by cognitive domain. Subsequently, longitudinal studies examining PD-MCI to PDD progression were meta-analyzed. Ninety-two cross-sectional articles of PD-MCI vs. PD-CN were included; 5 longitudinal studies of PD-MCI conversion to PDD were included. Random effects meta-analytic models were constructed resulting in effect sizes (Hedges' g) for cognitive domains. Overall performance across all measures produced a large effect size (g = 0.83, 95% CI [0.79, 0.86], t2 = 0.18) in cross-sectional analyses, with cognitive screeners producing the largest effect (g = 1.09, 95% CI [1.00, 1.17], t2 = 0.19). Longitudinally, overall measures produced a moderate effect (g = 0.47, 95% CI [0.40, 0.53], t2 = 0.01), with measures of executive functioning exhibiting the largest effect (g = 0.70, 95% CI [0.51, 0.89], t2 = 0.01). Longitudinal effects were made more robust by low heterogeneity. This report provides the first comprehensive meta-analysis of PD-MCI cognitive outcomes and predictors in PD-MCI conversion to PDD. Limitations include heterogeneity of cross-sectional effect sizes and the potential impact of small-study effects. Areas for continued research include visuospatial skills and visual memory in PD-MCI and longitudinal examination of executive dysfunction in PD-MCI.

The use of equine faecal volatile organic compounds as an indicator of risk for development of laminitis in pastured animals

The use of equine faecal volatile organic compounds as an indicator of risk for development of laminitis in pastured animals

Social impact assessment of investment activities in the China–Pakistan economic corridor

In order to analyze potential social risks, and achieve smooth implementation of investment activities in the China–Pakistan economic corridor (CPEC), we attempt to establish social impact and risk indicators. Both the impacts on the projects and the impacts of the projects are used to develop risk indicators in accordance with the literature review, reality and international standard principles. Using an analytic hierarchy process (AHP) and average value to analyze questionnaires of both Chinese and Pakistani respondents, we identify the importance of various risk indicators. The primary social risks of the western high mountain region include tribal obstacles and religious extremism. The social risks to the southeast coastal plains include preserving the historical and cultural heritage of the area and international protection of national parks. The social risks in north Kashmir include disputes, extremist threats, religious and cultural differences, and the protection of natural reserves. The social risks of the Xinjiang region primarily involve social issues faced by ethnic minorities and environmental pressures.

Clonality of HTLV-1-infected T cells as a risk indicator for development and progression of adult T-cell leukemia.

Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) that develops along a carcinogenic process involving 5 or more genetic events in infected cells. The lifetime incidence of ATL among HTLV-1-infected individuals is approximately 5%. Although epidemiologic studies have revealed risk factors for ATL, the molecular mechanisms that determine the fates of carriers remain unclear. A better understanding of clonal composition and related longitudinal dynamics would clarify the process of ATL leukemogenesis and provide insights into the mechanisms underlying the proliferation of a malignant clone. Genomic DNA samples and clinical information were obtained from individuals enrolled in the Joint Study for Predisposing Factors for ATL Development, a Japanese prospective cohort study. Forty-seven longitudinal samples from 20 individuals (9 asymptomatic carriers and 11 patients with ATL at enrollment) were subjected to a clonality analysis. A method based on next-generation sequencing was used to characterize clones on the basis of integration sites. Relationships were analyzed among clonal patterns, clone sizes, and clinical status, including ATL onset and progression. Among carriers, those exhibiting an oligoclonal or monoclonal pattern with largely expanded clones subsequently progressed to ATL. All indolent patients who progressed to acute-type ATL exhibited monoclonal expansion. In both situations, the major expanded clone after progression was derived from the largest pre-existing clone. This study has provided the first detailed information regarding the dynamics of HTLV-1-infected T-cell clones and collectively suggests that the clonality of HTLV-1-infected cells could be a useful predictive marker of ATL onset and progression.

Radiographic subchondral bone trabecular integrity predicts osteoarthritis structural outcomes after anterior cruciate ligament rupture

Purpose: The course of post-traumatic osteoarthritis (OA) is an invaluable paradigm for discovery of markers of the very earliest stages of the OA disease process. Subchondral bone trabecular integrity (BTI) predicts structural progression of radiographic knee OA based on radiographic and MRI outcomes. The goal of this study was to determine if the BTI in a knee injury cohort, measured within 5 weeks after an anterior cruciate ligament (ACL) tear, is an early indicator of risk for development of OA over the subsequent 5 years. We hypothesized that thinning and loss of the subchondral vertical bone trabeculae, detected by BTI, would predict joint space width and joint space area loss. Methods: Bone trabecular integrity (BTI) of the medial tibial plateau was determined from analysis of knee radiographs from the completed randomized controlled KANON clinical trial (http://www.controlled-trials.com; ISRCTN 84752559), designed to compare rehabilitation plus early ACL reconstruction (ACLR, n = 61) versus rehabilitation plus optional delayed ACLR (n = 60) with follow-up out to 5 years. The KANON study enrolled 121 young active adults (aged 18–35 yrs) with acute ACL rupture within the prior 5 weeks to a previously uninjured knee. There was no loss to follow-up at 2 years and only 1 individual lost to follow-up at 5 years; none of the index knees had radiographic OA at baseline. Weight bearing knee radiographs, obtained at baseline (at time of enrollment), 2 years and 5 years using a modified Lyon-Schuss protocol, were analyzed using KneeAnalyzer software (Optasia Medical Ltd, Manchester, UK) to obtain fractal dimensions for computing BTI, minimum medial joint space width (mJSW), and medial joint space area (JSA). Multivariable regression models, adjusted for age, gender and body mass index, were used to evaluate the ability of baseline (BL) BTI parameters of index knees to predict the change in mJSW and JSA between BL and 2 y and 5 y after injury. Results: Based on BTI profiles injured knees on average showed thinning of vertical trabeculae over 2 years with further thinning between 2 and 5 years. Horizontal trabeculae showed thickening over 2 years with little further change to 5 years. Baseline BTI parameters were statistically significantly associated with change in mJSW over 2 (R2 0.19, p = 0.036) and 5 (R2 0.16, p = 0.04) years, and change in JSA over 5 (R2 0.22, p = 0.004), but not 2 (R2 0.13, p = 0.16) years. Conclusions: The qualitative changes in BTI parameters over time after injury, reflecting vertical and horizontal trabecular structure, were similar to changes earlier reported over similar time intervals in knee OA progressors. The remarkable finding that baseline BTI predicted subsequent changes in mJSW and JSA suggests that acute injury leads to dramatic acute alterations in bone structure, and/or, that pre-injury BTI identifies and perhaps contributes to, risk of knee injury. Longitudinal surveillance, initiated prior to injury, is needed to determine if BTI might identify individuals at high-risk for post-injury OA and who could be targeted with interventions to prevent subsequent development of OA.

Bank Behaviour and Risks in Chaps Following the Collapse of Lehman Brothers

We use payments data for the period 2006-09 to study the impact of the global financial crisis on payment patterns in CHAPS, the United Kingdom’s large-value wholesale payments system. CHAPS functioned smoothly throughout the crisis and all CHAPS settlement banks continued to meet their payment obligations. However, the data show that in the two months following the Lehman Brothers failure, banks did, on average, make payments at a slower pace than before the failure. Our analysis suggests this was partly explained by concerns about counter-party default risk as well as system-wide risk. The ratio of payments made to liquidity used was 30% lower in the period from 15 September 2008 to 30 September 2009 than in the period preceding the default of Lehman Brothers. This was due initially to payment delay, but later was due to banks making more payments with their own liquidity, probably because quantitative easing increased the amount of reserves in the system. To assess the economic significance of the observed delays in the value of payments settled, we develop risk indicators, based on Markov models, to quantify the theoretical liquidity impact of delays during an operational outage. We find that payment delays in the months following the failure of Lehman Brothers led to a statistically significant but economically modest increase in these risk measures.

Plasma Biomarkers for Prediction of Sudden Cardiac Death

Sudden cardiac death (SCD) accounts for most cardiovascular deaths in the United States, claiming an estimated 300 000 lives per year.1 Despite intense efforts to develop resuscitation techniques, survival rates are still low, at ≈5%.2 This has led to a renewed focus in this field directed toward optimizing risk prediction to identify the candidate that would qualify for prophylactic or preventive interventions.3 At present, the clinical risk stratification is largely limited to the use of left ventricular ejection fraction (LVEF) for identifying primary prophylaxis candidates, but specificity of this predictor is modest.4 Moreover, the absolute numbers of these high-risk patients in the general population are low. Instead, the highest prevalence of SCD is likely observed among previously asymptomatic individuals, even though it is well-known that coronary artery disease (CAD) is present in most SCD cases.5 This underscores the need for the development of risk stratification models that can be applied to the general population where the largest health benefit is likely to be realized. The underpinnings of SCD are complex, and it is reasonable to believe that the risk stratification instrument of the future is likely to involve other components beyond clinical risk markers. Novel genomic variants show promise but are still in early phases of development as risk stratification targets. However, the “unbiased” approaches made possible through genomewide association studies have led to the recent identification of specific genetic variants that could predict SCD.6,7 This has reignited the interest in plasma biomarkers as a means for risk stratification. This article will review the emerging evidence and role of plasma biomarkers in predicting SCD in the general population and suggest a blueprint for future studies of potential utility. ### Uniform Definition of SCD Given the complexity and dynamic nature of the condition, there has been some variability …

Risk indicators for major hazards on offshore installations

Major hazards risk indicators are proposed for offshore installations, based on what has been used by the Petroleum Safety Authority Norway for the Risk Level approach in the Norwegian offshore petroleum industry. Since 2002 also leading indicators are used, in the sense that indicators for barrier performance are included together with the lagging indicators. There are individual indicators for a number of barrier functions, including fire and gas detection, a number of safety valves, active fire protection and mustering of personnel. The performance of the leading indicators during several years of data collection as well as lessons learned from the project are discussed. This is followed by a review of how indicators may be used by individual companies, and how the lessons may be utilised by individual companies to develop risk indicators for individual installations as well as company wide indicators.

Risk indicators for development of headache during dipyridamole treatment after cerebral ischaemia of arterial origin

A considerable proportion of patients discontinue dipyridamole therapy because of headache. Risk indicators for the development of dipyridamole induced headache were identified by means of an exploratory analysis of data...

P2-223: Analysis of clinical and dosimetric factors associated with severe radiation pneumonitis in locally advanced Non–Small–Cell–Lung–Cancer patients treated with concurrent chemotherapy and intensity–modulated radiotherapy (IMRT)

To retrospectively evaluate clinical and dosimetric factors associated with severe (grade≥3) radiation pneumonitis in patients after concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). We retrospectively analyzed 94 locally advanced NSCLC patients treated with concurrent chemotherapy and IMRT between May 2005 and September 2006. Radiation pneumonitis was graded according to Common Terminology Criteria for Adverse Events version 3.0. The following clinical parameters were considered: gender, age, smoking and diabetes history, history of chronic obstructive pulmonary disease (COPD), induction chemotherapy, concurrent chemotherapy regimens, performance status and forced expiratory volume in 1 second (FEV1). Dosimetric factors including mean lung dose (Dmean), rV5-V60 relative volumes of lung receiving more than a threshold dose D of radiation (rVD), where values of D considered were 5°C 60 Gy in increments of 5 Gy), prescribed dose (63GY/35f/7w vs 60Gy/30f/6w), and normal tissue complication probability (NTCP) values were analysed. DVHs data and NTCP values were collected for both lungs considered as a parallel organ. Pearson Chi-Square test was performed to compare clinical parameters between patients who developed severe RP and those who did not. Univariate and multivariate logistic regression analyses were performed to evaluate data for association between clinical and dosimetric factors and severe RP. The study was approved by the institutional reviewboard. Of 94 patients, 11 (11.7%) develop severe (grade≥3) radiation pneumonitis; 6 (6.4%), grade 3; 2(2.1%), grade 4; and 3 (3.2%)grade 5. Univariate analyses show that Sex, age (≤60vs>60), smoking and diabetes history, induction chemotherapy, concurrent chemotherapy regimens, PS(≤70vs>70) and prescribed dose did not significantly differ between patients who developed severe RP and those who did not. However, NTCP, MLD, rV5-V60, COPD and FEV1 were associated with severe RP (p<0.05). In multivariate analysis, NTCP (p=0.001) and rV10(p=0.015) was the most significant factors associated with severe (grade≥3) radiation pneumonitis. The incidences of Grade≥3 pneumonitis in the group with NTCP>4.2% and NTCP <4.2% were 43.5% and 1.4%, respectively (p<0.01). The incidences of Grade≥3 pneumonitis in the group with rV10 <51.2% and rV10 >51.2% were 5.6% and 30.4%, respectively (p<0.01). NTCP and rV10 is useful indicator of risk for development of severe (grade≥3) radiation pneumonitis in NSCLC patients after concurrent chemotherapy and intensity -modulated radiotherapy (IMRT).

Dose-volumetric Parameters for Predicting Severe Radiation Pneumonitis after Three-dimensional Conformal Radiation Therapy for Lung Cancer

To retrospectively evaluate dose-volumetric parameters for association with risk of severe (grade >/=3) radiation pneumonitis (RP) in patients after three-dimensional (3D) conformal radiation therapy for lung cancer. The study was approved by the institutional review board, which did not require informed consent. Data from 76 patients (66 men, 10 women; median age, 60 years; range, 35-79 years) with histologically proved lung cancer treated curatively with 3D conformal radiation therapy between August 2001 and October 2002 were retrospectively analyzed. Twenty patients underwent surgery before radiation therapy; 57 patients received chemotherapy. Median total radiation dose of 60 Gy (range, 54-66 Gy) was delivered in 30 (range, 27-33) fractions over 6 weeks. RP was scored by using Radiation Therapy Oncology Group criteria. Clinical parameters were analyzed. Dose-volumetric parameters analyzed were percentage of lung volume that received a dose of 20 Gy or more (V20), 30 Gy or more (V30), 40 Gy or more (V40), or 50 Gy or more (V50); mean lung dose (MLD); normal tissue complication probability (NTCP); and total dose. Fisher exact test was performed to compare clinical parameters between patients who developed severe RP and those who did not. Univariate and multivariate logistic regression analyses were performed to evaluate data for association between dose-volumetric parameters and severe RP. Pearson chi(2) test was used to assess data for correlations among dose-volumetric parameters. P < or = .05 was considered to indicate statistically significant difference. Of 76 patients, 30 (39%) did not develop RP; 23 (30%) developed RP of grade 1; 11 (14%), grade 2; 11 (14%), grade 3; and 1 (1%), grade 4. None had grade 5 RP. Age (< 60 vs > or =60), sex, Karnofsky performance status (< 70 vs > or =70), forced expiratory volume in 1 second, presence of weight loss, preexisting lung disease, history of thoracic surgery, and history of chemotherapy did not significantly differ between patients who developed severe RP and those who did not. In univariate analyses, MLD, V20, V30, V40, V50, and NTCP were associated with severe RP (P < .05). In multivariate analysis, MLD was the only variable associated with severe RP. MLD is a useful indicator of risk for development of severe RP after 3D conformal radiation therapy in patients with lung cancer.

Early identification of patients with an acute coronary syndrome as assessed by dispatchers and the ambulance crew

This study was performed to evaluate the possibility of early identification of patients with an acute coronary syndrome who are transported by ambulance. All patients in the community of Göteborg who were transported by ambulance over a period of 3 months owing to symptoms raising any suspicion of an acute coronary syndrome were studied. In all 930 cases that were included in the survey, 130 (14%) had a final diagnosis of acute myocardial infarction (AMI) and 276 (30%) had a final diagnosis of an acute coronary syndrome. Independent risk indicators for development of AMI were: male sex (odds ratio 1.70; 95% confidence limits 1.02-2.84), cold and clammy on admission of the ambulance crew (odds ratio 2.07; 95% confidence limits 1.23-3.49) and showing electrocardiogram (ECG) signs of myocardial ischemia on admission to the emergency department (odds ratio 8.78; 95%confidence limits 5.28-14.61). Independent predictors for development of an acute coronary syndrome were: male sex (odds ratio 1.97; 95% confidence limits 1.30-2.99), a history of angina pectoris (odds ratio 3.41; 95% confidence limits 2.24-5.26), cold and clammy on admission of the ambulance crew (odds ratio 1.95; 95% confidence limits 1.21-3.15), and ECG signs of myocardial ischemia on admission to the emergency department (odds ratio 5.55; 95% confidence limits 3.63-8.58). Among patients seen by the ambulance crew with symptoms raising any suspicion of an acute coronary syndrome, predictors for that diagnosis included male sex, a history of angina pectoris, patients being cold and clammy on admission of the ambulance crew, and ECG signs of myocardial ischemia on admission to the emergency department. (Am J Emerg Med 2002;20:196-201. Copyright 2002, Elsevier Science (USA). All rights reserved.)

Five-year mortality in patients with acute chest pain in relation to smoking habits.

Smoking is one of the major risk indicators for development of coronary artery disease, and smokers develop acute myocardial infarction (AMI) approximately a decade earlier than nonsmokers. In smokers with established coronary artery disease, quitting smoking has been associated with a more favorable prognosis. However, most of these studies comprised younger patients, the majority of whom were males. The purpose of the study was to determine mortality, mode of death, and risk indicators of death in relation to smoking habits among consecutive patients admitted to the emergency department with acute chest pain. In all, 4,553 patients admitted with acute chest pain to the emergency department at Sahlgrenska University Hospital during a period of 21 months were included in the analyses and were prospectively followed for 5 years. Of these patients, 36% admitted current smoking. They were younger and had a lower prevalence of previous cardiovascular diseases than did nonsmokers. The 5-year mortality was 19.4% among smokers and 24.9% among non-smokers (p < 0.0001). However, when adjusting for difference in age, smoking was associated with an increased risk [relative risk (RR) 1.51; 95% confidence interval (CI) 1.32-1.74; p < 0.0001]. Among patients presenting originally with chest pain, the increased mortality for smokers was more pronounced in patients with non-acute than acute myocardial infarction (AMI). Among patients who died, death in smokers was less frequently associated with new-onset myocardial infarction (MI) and congestive heart failure. Among those who smoked at onset of symptoms and were alive 1 year later, 25% had stopped smoking. Patients with a confirmed AMI who continued smoking 1 year after onset of symptoms had a higher mortality (28.4%) during the subsequent 4 years than patients who stopped smoking (15.2%; p = 0.049). In consecutive patients admitted to the emergency department with acute chest pain, current smoking was significantly associated with an increased risk of death during 5 years of follow-up. Among patients who died, death in smokers was less frequently associated with new-onset MI and congestive heart failure than was death in nonsmokers.

Reducing pesticide risks to US food consumers: can agricultural research help?

Recent pesticide policy initiatives focus on reducing risks through agricultural research on pest control alternatives. This paper illustrates how research resources could be targeted to reduce risks to food consumers from dietary pesticide residue intake. For 50 chemicals on 10 fruits and vegetables, we estimate consumers' dietary intake of pesticides and use those estimates to develop risk indicators, expressing dietary intake as a percentage of safe levels. These indicators show that risks are higher for small children. The indicators allow us to rank pesticides according to their contribution to risk for this vulnerable sub-population. We then trace these risks to four sources: onfarm pesticide use, post-harvest pesticide use, pesticides used on imported foods, and canceled pesticides that persist in the environment. For pesticides that are used mainly on-farm, we show that the development of alternatives for risk reduction could be targeted to particular regions and crops. However, research to develop on-farm pest control alternatives will not address all of the sources of pesticide residues in the diet.

A follow-up study of laboratory animal exposed workers: the influence of atopy for the development of occupational asthma.

In a 5-year follow-up study of 88 animal exposed laboratory technicians, the incidence of laboratory animal allergy (LAA), lung function, and the development of allergy test reactivity were investigated. Only two individuals developed test positive LAA rhinitis during the follow-up period. Furthermore, one subject who had previously had LAA rhinitis developed LAA asthma. In the remaining subjects the results of skin prick tests against laboratory animals and environmental allergens, total serum IgE levels, and lung function were unchanged. Atopy defined as parental and childhood allergy, raised total serum IgE levels, and positive skin prick tests against nonanimal environmental allergens and nonlaboratory animals (dog and horse) were risk indicators for development of test positive LAA asthma. The low incidence of LAA during the 5-year follow-up is interpreted as a result of an early LAA development in atopic subjects.

One‐year prognosis in patients hospitalized with a history of unstable angina pectoris

The prognosis during 1 year of follow-up in 715 patients admitted to one single hospital due to suspected acute myocardial infarction (AMI) with a history of unstable angina pectoris immediately preceding hospitalization is described. AMI developed in 192 patients (27%) during the first three days and in 255 patients (38%) during the first year. The mortality during hospitalization was 7% (50 patients) and during 1 year 19% (130 patients). Of the nonsurvivors, 54% died of AMI, 28% of congestive heart failure, and 20% of cardiogenic shock. Based on simple clinical parameters on admission to the emergency room, risk indicators for death during the following year could be identified as follows, in the order of significance: high age (p < 0.001), ST-segment depression on admission (p < 0.001), and a history of diabetes mellitus (p < 0.05). At admission to the emergency room, risk indicators for development of AMI during the following year were as follows: initial degree of suspicion of AMI (p < 0.001), electrocardiographic signs of acute ischemia on admission (p < 0.001), ST-segment elevation on admission (p < 0.01), age (p < 0.05), and lack of a previous history of chronic stable angina pectoris (p < 0.05). We conclude that, among patients admitted to hospital due to suspected AMI with a history of unstable angina pectoris immediately preceding hospitalization, 38% developed a confirmed infarction and 19% died during the following year.

Venous function in the leg after postoperative thrombosis diagnosed with 125I-fibrinogen uptake test.

The 125I-fibrinogen uptake test (FUT) has been widely used in the past decade to detect postoperative thrombosis. FUT has been shown to correlate well with phlebography, and positive FUT is associated with a high frequency of pulmonary embolism. The long-term venous function of the leg after FUT-detected postoperative thrombosis, however, is inadequately documented. In 179 patients who had been studied after operation with FUT, a follow-up evaluation of FUT as an indicator of risk for development of deep venous insufficiency was made four to five years later. The patients replied to a questionnaire, were clinically examined, and underwent venous strain-gauge plethysmography, venous pressure measurement, and, in some cases, phlebography. No statistically significant differences were found in any of the parameters between legs that had been FUT-positive and those that were FUT-negative at the time of the operation. The frequency of deep venous insufficiency thus was equal in FUT-positive and FUT-negative legs. It was also independent of the site of FUT-detected thrombus in the leg.