Sex- and gender-related risk factor burden in patients with premature acute coronary syndrome

BACKGROUND Few contemporary data exist on traditional (TRF) and non-TRF (NTRF) burden in patients with premature acute coronary syndrome (ACS). METHODS Prevalence of TRFs and NTRFs were measured in 1015 young (55 years old or younger) ACS patients recruited from 26 centres in Canada, the United States, and Switzerland. Risk factors were compared across sex and family history categories, and against a sample of the general Canadian population based on the 2000-2001 Canadian Community Health Survey. The 10- and 30-year risks of cardiovascular disease (CVD) were estimated using Framingham Risk Scores. RESULTS Risk factors were more prevalent in premature ACS patients compared with the general population. Young women with a family history of coronary artery disease showed the greatest risk factor burden including TRFs of hypertension (67%), dyslipidemia (67%), obesity (53%), smoking (42%), and diabetes (33%), and NTRFs of anxiety (55%), low household income (44%), and depression (37%). The estimated median 10-year risk of CVD was 7% (interquartile range [IQR], 3%-9%) in women and 13% (IQR, 7%-17%) in men, whereas the 30-year risk of CVD was 36% (IQR, 22%-49%) in women and 44% (IQR, 31%-57%) in men. CONCLUSIONS Patients with premature ACS, especially women with a positive family history, are characterized by a very high risk factor burden that is poorly captured by 10-year risk estimates but better captured by 30-year estimates. Consideration of NTRFs and use of 30-year risk estimates might better estimate risk in young individuals and improve the prevention of premature ACS.

Risk factors for potentially avoidable readmissions due to end-of-life care issues

BACKGROUND Repeated hospitalizations are frequent toward the end of life, where each admission should be an opportunity to initiate advance-care planning to high-risk patients. OBJECTIVE To identify the risk factors for having a 30-day potentially avoidable readmission due to end-of-life care issues among all medical patients. DESIGN Nested case-control study. SETTING/PATIENTS All 10,275 consecutive discharges from any medical service of an academic tertiary medical center in Boston, Massachusetts between July 1, 2009 and June 30, 2010. MEASUREMENTS A random sample of all the potentially avoidable 30-day readmissions was independently reviewed by 9 trained physicians to identify the ones due to end-of-life issues. RESULTS Among 534, 30-day potentially avoidable readmission cases reviewed, 80 (15%) were due to an end-of-life care issue. In multivariable analysis, the following risk factors were significantly associated with a 30-day potentially avoidable readmission due to end-of-life care issues: number of admissions in the previous 12 months (odds ratio [OR]: 1.10 per admission, 95% confidence interval [CI]: 1.02-1.20), neoplasm (OR: 5.60, 95% CI: 2.85-10.98), opiate medications at discharge (OR: 2.29, 95% CI: 1.29-4.07), Elixhauser comorbidity index (OR: 1.16 per 5-point increase, 95% CI: 1.10-1.22). The discrimination of the model (C statistic) was 0.85. CONCLUSIONS In a medical population, we identified 4 main risk factors that were significantly associated with 30-day potentially avoidable readmission due to end-of-life care issues, producing a model with very good to excellent discrimination. Patients with these risk factors might benefit from palliative care consultation prior to discharge in order to improve end-of-life care and possibly reduce unnecessary rehospitalizations.

At risk or not at risk? A meta-analysis of the prognostic accuracy of psychometric interviews for psychosis prediction

An accurate detection of individuals at clinical high risk (CHR) for psychosis is a prerequisite for effective preventive interventions. Several psychometric interviews are available, but their prognostic accuracy is unknown. We conducted a prognostic accuracy meta-analysis of psychometric interviews used to examine referrals to high risk services. The index test was an established CHR psychometric instrument used to identify subjects with and without CHR (CHR+ and CHR-). The reference index was psychosis onset over time in both CHR+ and CHR- subjects. Data were analyzed with MIDAS (STATA13). Area under the curve (AUC), summary receiver operating characteristic curves, quality assessment, likelihood ratios, Fagan's nomogram and probability modified plots were computed. Eleven independent studies were included, with a total of 2,519 help-seeking, predominately adult subjects (CHR+: N=1,359; CHR-: N=1,160) referred to high risk services. The mean follow-up duration was 38 months. The AUC was excellent (0.90; 95% CI: 0.87-0.93), and comparable to other tests in preventive medicine, suggesting clinical utility in subjects referred to high risk services. Meta-regression analyses revealed an effect for exposure to antipsychotics and no effects for type of instrument, age, gender, follow-up time, sample size, quality assessment, proportion of CHR+ subjects in the total sample. Fagan's nomogram indicated a low positive predictive value (5.74%) in the general non-help-seeking population. Albeit the clear need to further improve prediction of psychosis, these findings support the use of psychometric prognostic interviews for CHR as clinical tools for an indicated prevention in subjects seeking help at high risk services worldwide.

Prospective longitudinal voxel-based morphometry study of major depressive disorder in young individuals at high familial risk

BACKGROUND Previous neuroimaging studies indicate abnormalities in cortico-limbic circuitry in mood disorder. Here we employ prospective longitudinal voxel-based morphometry to examine the trajectory of these abnormalities during early stages of illness development. METHOD Unaffected individuals (16-25 years) at high and low familial risk of mood disorder underwent structural brain imaging on two occasions 2 years apart. Further clinical assessment was conducted 2 years after the second scan (time 3). Clinical outcome data at time 3 was used to categorize individuals: (i) healthy controls ('low risk', n = 48); (ii) high-risk individuals who remained well (HR well, n = 53); and (iii) high-risk individuals who developed a major depressive disorder (HR MDD, n = 30). Groups were compared using longitudinal voxel-based morphometry. We also examined whether progress to illness was associated with changes in other potential risk markers (personality traits, symptoms scores and baseline measures of childhood trauma), and whether any changes in brain structure could be indexed using these measures. RESULTS Significant decreases in right amygdala grey matter were found in HR MDD v. controls (p = 0.001) and v. HR well (p = 0.005). This structural change was not related to measures of childhood trauma, symptom severity or measures of sub-diagnostic anxiety, neuroticism or extraversion, although cross-sectionally these measures significantly differentiated the groups at baseline. CONCLUSIONS These longitudinal findings implicate structural amygdala changes in the neurobiology of mood disorder. They also provide a potential biomarker for risk stratification capturing additional information beyond clinically ascertained measures.

Prospective longitudinal study of subcortical brain volumes in individuals at high familial risk of mood disorders with or without subsequent onset of depression

Subcortical volumetric brain abnormalities have been observed in mood disorders. However, it is unknown whether these reflect adverse effects predisposing to mood disorders or emerge at illness onset. Magnetic resonance imaging was conducted at baseline and after two years in 111 initially unaffected young adults at increased risk of mood disorders because of a close family history of bipolar disorder and 93 healthy controls (HC). During the follow-up, 20 high-risk subjects developed major depressive disorder (HR-MDD), with the others remaining well (HR-well). Volumes of the lateral ventricles, caudate, putamen, pallidum, thalamus, hippocampus and amygdala were extracted for each hemisphere. Using linear mixed-effects models, differences and longitudinal changes in subcortical volumes were investigated between groups (HC, HR-MDD, HR-well). There were no significant differences for any subcortical volume between groups controlling for multiple testing. Additionally, no significant differences emerged between groups over time. Our results indicate that volumetric subcortical brain abnormalities of these regions using the current method appear not to form familial trait markers for vulnerability to mood disorders in close relatives of bipolar disorder patients over the two-year time period studied. Moreover, they do not appear to reduce in response to illness onset at least for the time period studied.

Stroke, coronary and peripheral artery disease survey on antithrombotic treatment (START IT)

QUESTIONS UNDER STUDY: To determine the perception of primary care physicians regarding the risk of subsequent atherothrombotic events in patients with established cardiovascular (CV) disease, and to correlate this perception with documented antithrombotic therapy. METHODS: In a cross-sectional study of the general practice population in Switzerland, 381 primary care physicians screened 127 040 outpatients during 15 consecutive workdays in 2006. Perception of subsequent atherothrombotic events in patients with established CV disease was assessed using a tick box questionnaire allowing choices between low, moderate, high or very high risk. Logistic regression models were used to determine the relationship between risk perception and antithrombotic treatment. RESULTS: Overall, 13 057 patients (10.4%) were identified as having established CV disease and 48.8% of those were estimated to be at high to very high risk for subsequent atherothrombotic events. Estimated higher risk for subsequent atherothrombotic events was associated with a shift from aspirin monotherapy to clopidogrel, vitamin K antagonist or aspirin plus clopidogrel (p <0.001 for trend). Clopidogrel (12.7% vs 6.8%, p <0.001), vitamin K antagonist (24.5% vs 15.6%, p <0.001) or aspirin plus clopidogrel (10.2% vs 4.2%, p <0.001) were prescribed in patients estimated to be at high to very high risk more often than in those at low to moderate risk. CONCLUSIONS: Perception of primary care physicians regarding risk of subsequent atherothrombotic events varies in patients with CV disease, and as a result antithrombotic therapy is altered in patients with anticipated high to very high risk even though robust evidence and clear guidelines are lacking.

Significance of Periodontal Risk Assessment in the recurrence of periodontitis and tooth loss

Aim: To investigate the association of the Periodontal Risk Assessment (PRA) model categories with periodontitis recurrence and tooth loss during supportive periodontal therapy (SPT) and to explore the role of patient compliance. Material and Methods: In a retrospective cohort, PRA was performed for 160 patients after active periodontal therapy (APT) and after 9.5 ± 4.5 years of SPT. The recurrence of periodontitis and tooth loss were analysed according to the patient's risk profile (low, moderate or high) after APT and compliance with SPT. The association of risk factors with tooth loss and recurrence of periodontitis was investigated using logistic regression analysis. Results: In 18.2% of patients with a low-risk profile, in 42.2% of patients with a moderate-risk profile and in 49.2% of patients with a high-risk profile after APT, periodontitis recurred. During SPT, 1.61 ± 2.8 teeth/patient were lost. High-risk profile patients lost significantly more teeth (2.59 ± 3.9) than patients with moderate- (1.02 ± 1.8) or low-risk profiles (1.18 ± 1.9) (Kruskal–Wallis test, p=0.0229). Patients with erratic compliance lost significantly (Kruskal–Wallis test, p=0.0067) more teeth (3.11 ± 4.5) than patients compliant with SPT (1.07 ± 1.6). Conclusions: In multivariate logistic regression analysis, a high-risk patient profile according to the PRA model at the end of APT was associated with recurrence of periodontitis. Another significant factor for recurrence of periodontitis was an SPT duration of more than 10 years.

Preoperative mapping of arterial spinal supply using 3.0-T MR angiography with an intravasal contrast medium and high-spatial-resolution steady-state

Preoperative mapping of the arterial spinal supply prior to thoracoabdominal aortic aneurysm repair is highly relevant because of high risk for postoperative ischemic spinal cord injuries such as paraparesis or paraplegia.

Mortality from road traffic accidents in Switzerland: longitudinal and spatial analyses

Road traffic accidents (RTA) are an important cause of premature death. We examined socio-demographic and geographical determinants of RTA mortality in Switzerland by linking 2000 census data to RTA mortality records 2000-2005 (ICD-10 codes V00-V99). Data from 5.5 million residents aged 18-94 years, 1744 study areas, and 1620 RTA deaths were analyzed, including 978 deaths (60.4%) in motor vehicle occupants, 254 (15.7%) in motorcyclists, 107 (6.6%) in cyclists, and 259 (16.0%) in pedestrians. Weibull survival models and Bayesian methods were used to calculate hazard ratios (HR), and standardized mortality ratios (SMR) across study areas. Adjusted HR comparing women with men ranged from 0.04 (95% CI 0.02-0.07) in motorcyclists to 0.43 (95% CI 0.32-0.56) in pedestrians. There was a u-shaped relationship with age in motor vehicle occupants and motorcyclists. In cyclists and pedestrians, mortality increased after age 55 years. Mortality was higher in individuals with primary education (HR 1.53; 95% CI 1.29-1.81), and higher in single (HR 1.24; 95% CI 1.05-1.46), widowed (HR 1.31; 95% CI 1.05-1.65) and divorced individuals (HR 1.62; 95% CI 1.33-1.97), compared to persons with tertiary education or married persons. The association with education was particularly strong for pedestrians (HR 1.87; 95% CI 1.20-2.91). RTA mortality increased with decreasing population density of study areas for motor vehicle occupants (test for trend p<0.0001) and motorcyclists (p=0.0021) but not for cyclists (p=0.39) or pedestrians (p=0.29). SMR standardized for socio-demographic and geographical variables ranged from 82 to 190. Prevention efforts should aim to reduce inequities across socio-demographic and educational groups, and across geographical areas, with interventions targeted at high-risk groups and areas, and different traffic users, including pedestrians.

Relationship between the logistic EuroSCORE and the Society of Thoracic Surgeons Predicted Risk of Mortality score in patients implanted with the CoreValve ReValving system--a Bern-Rotterdam Study

Background Surgical risk scores, such as the logistic EuroSCORE (LES) and Society of Thoracic Surgeons Predicted Risk of Mortality (STS) score, are commonly used to identify high-risk or “inoperable” patients for transcatheter aortic valve implantation (TAVI). In Europe, the LES plays an important role in selecting patients for implantation with the Medtronic CoreValve System. What is less clear, however, is the role of the STS score of these patients and the relationship between the LES and STS. Objective The purpose of this study is to examine the correlation between LES and STS scores and their performance characteristics in high-risk surgical patients implanted with the Medtronic CoreValve System. Methods All consecutive patients (n = 168) in whom a CoreValve bioprosthesis was implanted between November 2005 and June 2009 at 2 centers (Bern University Hospital, Bern, Switzerland, and Erasmus Medical Center, Rotterdam, The Netherlands) were included for analysis. Patient demographics were recorded in a prospective database. Logistic EuroSCORE and STS scores were calculated on a prospective and retrospective basis, respectively. Results Observed mortality was 11.1%. The mean LES was 3 times higher than the mean STS score (LES 20.2% ± 13.9% vs STS 6.7% ± 5.8%). Based on the various LES and STS cutoff values used in previous and ongoing TAVI trials, 53% of patients had an LES ≥15%, 16% had an STS ≥10%, and 40% had an LES ≥20% or STS ≥10%. Pearson correlation coefficient revealed a reasonable (moderate) linear relationship between the LES and STS scores, r = 0.58, P < .001. Although the STS score outperformed the LES, both models had suboptimal discriminatory power (c-statistic, 0.49 for LES and 0.69 for STS) and calibration. Conclusions Clinical judgment and the Heart Team concept should play a key role in selecting patients for TAVI, whereas currently available surgical risk score algorithms should be used to guide clinical decision making.

Risk stratification of normotensive patients with acute symptomatic pulmonary embolism

Treatment guidelines recommend strong consideration of thrombolysis in patients with acute symptomatic pulmonary embolism (PE) that present with arterial hypotension or shock because of the high risk of death in this setting. For haemodynamically stable patients with PE, the categorization of risk for subgroups may assist with decision-making regarding PE therapy. Clinical models [e.g. Pulmonary Embolism Severity Index (PESI)] may accurately identify those at low risk of overall death in the first 3 months after the diagnosis of PE, and such patients might benefit from an abbreviated hospital stay or outpatient therapy. Though some evidence suggests that a subset of high-risk normotensive patients with PE may have a reasonable risk to benefit ratio for thrombolytic therapy, single markers of right ventricular dysfunction (e.g. echocardiography, spiral computed tomography, or brain natriuretic peptide testing) and myocardial injury (e.g. cardiac troponin T or I testing) have an insufficient positive predictive value for PE-specific mortality to drive decision-making toward such therapy. Recommendations for outpatient treatment or thrombolytic therapy for patients with PE necessitate further development of prognostic models and conduct of clinical trials that assess various treatment strategies.

Occurrence, risk factors, diagnosis and treatment of syphilis in the prospective observational Swiss HIV Cohort Study

Background: Annual syphilis testing was reintroduced in the Swiss HIV Cohort Study (SHCS) in 2004. We prospectively studied occurrence, risk factors, clinical manifestations, diagnostic approaches and treatment of syphilis. Methods: Over a period of 33 months, participants with positive test results for Treponema pallidum hemagglutination assay were studied using the SHCS database and an additional structured case report form. Results: Of 7244 cohort participants, 909 (12.5%) had positive syphilis serology. Among these, 633 had previously been treated and had no current signs or symptoms of syphilis at time of testing. Of 218 patients with newly detected untreated syphilis, 20% reported genitooral contacts as only risk behavior and 60% were asymptomatic. Newly detected syphilis was more frequent among men who have sex with men (MSM) [adjusted odds ratio (OR) 2.8, P < 0.001], in persons reporting casual sexual partners (adjusted OR 2.8, P < 0.001) and in MSM of younger age (P = 0.05). Only 35% of recommended cerebrospinal fluid (CFS) examinations were performed. Neurosyphilis was diagnosed in four neurologically asymptomatic patients; all of them had a Venereal Disease Research Laboratory (VDRL) titer of 1:≥32. Ninety-one percent of the patients responded to treatment with at least a four-fold decline in VDRL titer. Conclusion: Syphilis remains an important coinfection in the SHCS justifying reintroduction of routine screening. Genitooral contact is a significant way of transmission and young MSM are at high risk for syphilis. Current guidelines to rule out neurosyphilis by CSF analysis are inconsistently followed in clinical practice. Serologic treatment response is above 90% in the era of combination antiretroviral therapy.

Health care use of long-term survivors of childhood cancer: the British Childhood Cancer Survivor Study

Purpose Survivors of childhood cancer are at high risk of chronic conditions, but few studies investigated whether this translates into increased health care utilization. We compared health care service utilization between childhood cancer survivors and the general British population and investigated potential risk factors. Methods We used data from the British Childhood Cancer Survivor Study, a population-based cohort of 17,981 individuals diagnosed with childhood cancer (1940-1991) and surviving ≥ 5 years. Frequency of talks to a doctor, hospital outpatient visits, and day-patient and inpatient hospitalizations were ascertained by questionnaire in 10,483 survivors and were compared with the General Household Survey 2002 data by using logistic regression. Results Among survivors, 16.5% had talked to a doctor in the last 2 weeks, 25.5% had attended the outpatient department of a hospital in the last 3 months, 11.9% had been hospitalized as a day patient in the last 12 months, and 9.8% had been hospitalized as an inpatient in the last 12 months. Survivors had talked slightly more often to a doctor than the general population (odds ratio [OR], 1.2; 95% CI, 1.1 to 1.3) and experienced increased hospital outpatient visits (OR, 2.5; 95% CI, 2.3 to 2.8), day-patient hospitalizations (OR, 1.4; 95% CI, 1.3 to 1.6) and inpatient hospitalizations (OR, 1.9; 95% CI, 1.7 to 2.2). Survivors of Hodgkin's lymphoma, neuroblastoma, and Wilms tumor had the highest ORs for day-patient care, whereas survivors of CNS tumors and bone sarcomas had the highest OR for outpatient and inpatient care. The OR of health care use did not vary significantly with age of survivor. Conclusion We have quantified how excess morbidity experienced by survivors of childhood cancer translates into increased use of health care facilities.

Equine CD4(+) CD25(high) T cells exhibit regulatory activity by close contact and cytokine-dependent mechanisms in vitro

Horses are particularly prone to allergic and autoimmune diseases, but little information about equine regulatory T cells (Treg) is currently available. The aim of this study therefore was to investigate the existence of CD4(+) Treg cells in horses, determine their suppressive function as well as their mechanism of action. Freshly isolated peripheral blood mononuclear cells (PBMC) from healthy horses were examined for CD4, CD25 and forkhead box P3 (FoxP3) expression. We show that equine FoxP3 is expressed constitutively by a population of CD4(+) CD25(+) T cells, mainly in the CD4(+) CD25(high) subpopulation. Proliferation of CD4(+) CD25(-) sorted cells stimulated with irradiated allogenic PBMC was significantly suppressed in co-culture with CD4(+) CD25(high) sorted cells in a dose-dependent manner. The mechanism of suppression by the CD4(+) CD25(high) cell population is mediated by close contact as well as interleukin (IL)-10 and transforming growth factor-beta1 (TGF-beta1) and probably other factors. In addition, we studied the in vitro induction of CD4(+) Treg and their characteristics compared to those of freshly isolated CD4(+) Treg cells. Upon stimulation with a combination of concanavalin A, TGF-beta1 and IL-2, CD4(+) CD25(+) T cells which express FoxP3 and have suppressive capability were induced from CD4(+) CD25(-) cells. The induced CD4(+) CD25(high) express higher levels of IL-10 and TGF-beta1 mRNA compared to the freshly isolated ones. Thus, in horses as in man, the circulating CD4(+) CD25(high) subpopulation contains natural Treg cells and functional Treg can be induced in vitro upon appropriate stimulation. Our study provides the first evidence of the regulatory function of CD4(+) CD25(+) cells in horses and offers insights into ex vivo manipulation of Treg cells.

Tumor budding score based on 10 high-power fields is a promising basis for a standardized prognostic scoring system in stage II colorectal cancer

Tumor budding is recognized by the World Health Organization as an additional prognostic factor in colorectal cancer but remains unreported in diagnostic work due to the absence of a standardized scoring method. This study aims to assess the most prognostic and reproducible scoring systems for tumor budding in colorectal cancer. Tumor budding on pancytokeratin-stained whole tissue sections from 105 well-characterized stage II patients was scored by 3 observers using 7 methods: Hase, Nakamura, Ueno, Wang (conventional and rapid method), densest high-power field, and 10 densest high-power fields. The predictive value for clinicopathologic features, the prognostic significance, and interobserver variability of each scoring method was analyzed. Pancytokeratin staining allowed accurate evaluation of tumor buds. Interobserver agreement for 3 observers was excellent for densest high-power field (intraclass correlation coefficient, 0.83) and 10 densest high-power fields (intraclass correlation coefficient, 0.91). Agreement was moderate to substantial for the conventional Wang method (κ = 0.46-0.62) and moderate for the rapid method (κ = 0.46-0.58). For Nakamura, moderate agreement (κ = 0.41-0.52) was reached, whereas concordance was fair to moderate for Ueno (κ = 0.39-0.56) and Hase (κ = 0.29-0.51). The Hase, Ueno, densest high-power field, and 10 densest high-power field methods identified a significant association of tumor budding with tumor border configuration. In multivariate analysis, only tumor budding as evaluated in densest high-power field and 10 densest high-power fields had significant prognostic effects on patient survival (P < .01), with high prognostic accuracy over the full 10-year follow-up. Scoring tumor buds in 10 densest high-power fields is a promising method to identify stage II patients at high risk for recurrence in daily diagnostics; it is highly reproducible, accounts for heterogeneity, and has a strong predictive value for adverse outcome.