Search

Discrimination statistics describe the ability of a survival model to assign higher risks to individuals who experience earlier events: examples are Harrell's C-index and Royston and Sauerbrei's D, which we call the D-index. Prognostic covariates whose distributions are controlled by the study design (e.g. age and sex) influence discrimination and can make it difficult to compare model discrimination between studies. Although covariate adjustment is a standard procedure for quantifying disease-risk factor associations, there are no covariate adjustment methods for discrimination statistics in censored survival data.To develop extensions of the C-index and D-index that describe the prognostic ability of a model adjusted for one or more covariate(s).We define a covariate-adjusted C-index and D-index for censored survival data, propose several estimators, and investigate their performance in simulation studies and in data from a large individual participant data meta-analysis, the Emerging Risk Factors Collaboration.The proposed methods perform well in simulations. In the Emerging Risk Factors Collaboration data, the age-adjusted C-index and D-index were substantially smaller than unadjusted values. The study-specific standard deviation of baseline age was strongly associated with the unadjusted C-index and D-index but not significantly associated with the age-adjusted indices.The proposed estimators improve meta-analysis comparisons, are easy to implement and give a more meaningful clinical interpretation.? 2014 The Author. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Use of distal protection in renal artery stenting entails overcoming challenges unique to renal artery anatomy. We used 3D image reconstruction to review high-spatial-resolution MDCT angiographic data to better characterize the anatomy of stenotic renal arteries.A total of 218 abdominal MDCT angiograms from a single tertiary care referral center were reviewed. The subjects were 108 patients who had 127 arteries with more than 50% ostial atherosclerotic renal artery stenosis. Vessel analysis software was used to measure renal artery length, cross-sectional area, and maximum diameter. Differences between mean values for women and men and for left and right renal arteries were measured with a two-tailed Student's t test.Significant differences for men and women were found in average maximum cross-sectional area distal to the point of stenosis (0.3 +/- 0.19 vs 0.23 +/- 0.09 cm2, p = 0.006) and the corresponding maximum diameter (6.9 +/- 1.7 vs 6.1 +/- 1.1 cm2, p = 0.003). Average lengths of the main renal artery did not differ significantly for men and women. Differences for the left and right main renal arteries were found in minimum area (i.e., area of maximum stenosis, 0.08 +/- 0.04 vs 0.06 +/- 0.03 cm2, p = 0.03), area proximal to the bifurcation (0.26 +/- 0.11 cm2 vs 0.23 +/- 0.07 cm2, p = 0.02), and length (38.5 +/- 12.6 vs 48.7 +/- 16.2 mm, p = 0.0002).Significant anatomic differences exist between the left and right renal arteries, between the renal arteries in men and those in women, and from one person to the next. Many of these differences are relevant to the design and use of distal protection devices in stenting of the renal arteries.

To examine the feasibility of screening for alcohol problems in a representative flow sample of patients attending a busy UK emergency department. To compare two methods of identifying alcohol related problems in the emergency department.Brief interview administered by the same interviewer to a representative flow sample of 429 patients attending a single accident and emergency department over a six week period. Measures included a CAGE questionnaire and assessments by the patient and staff as to whether the attendance was alcohol related.413 patients (96%) were successfully screened. Of these, 115 (28%) patients were considered to have an alcohol related attendance on the basis of the CAGE questionnaire or the staff assessment. Head injuries and psychiatric presentations were particularly likely to be associated with alcohol misuse. Compared with those identified by staff, patients scoring above threshold on the CAGE were more likely to attend during routine working hours and recognise they had an alcohol problem.Emergency departments may provide an opportunity for the early prevention of alcohol related difficulties. However, patients with alcohol problems who present to the emergency department are not a homogenous group. Different screening methods identify different groups of patients, who in turn may respond to different forms of intervention. Further research examining the efficacy and feasibility of different alcohol treatment approaches is needed to enable us to target specific interventions to those patients who might most benefit.

A 53 year old man had a long history of rheumatoid arthritis (RA) necessitating hip, knee and elbow replacements. Hand deformity and pain progressed (right worse), particularly at the metacarpophalangeal (MCP) joints. However, he had congenital short …

The NHANES I Epidemiologic Followup Study (NHEFS) was jointly initiated by the National Center for Health Statistics and the National Institute on Aging in collaboration with other National Institutes of Health and Public Health Service agencies. The goal of NHEFS is to examine the relationship of baseline clinical, nutritional, and behavioral factors assessed in the first National Health and Nutrition Examination Survey (NHANES I-1971-75) to subsequent morbidity and mortality. Data collection for the initial phase of followup took place between 1982 and 1984 and included tracing of all NHANES I participants, determining their vital status, conducting in-depth interviews with surviving participants or with proxies for those who were deceased or incapacitated, conducting selected physical measurements, obtaining facility records for stays in hospitals or nursing homes that occurred during the period of followup, and obtaining death certificates for decedents. Ninety-three percent of the original cohort was successfully traced. Interviews were conducted for 93 percent of traced, surviving participants and 84 percent of traced, surviving participants and 84 percent of traced, deceased subjects. Physical measurements were obtained for approximately 95 percent of surviving, interviewed subjects. Death certificates are available for more than 95 percent of the decedents, and 18,136 facility records were received for 6,477 subjects.

An epidemiologic follow-up of the first National Health and Nutrition Examination Survey (NHANES I), being conducted from 1982 to 1984, is expected to provide estimates of the risks of certain health conditions for a sample of the U.S. population and to make it possible to relate these conditions to the nutritional, social, demographic, and behavioral characteristics of the sample. As part of the followup study, the baseline data obtained in NHANES I have been reviewed to define hypotheses and to identify pertinent variables that can be used in studying changes over time and the relationships of these variables to outcome measures. Because the followup study provides cohort data on a large sample of the U.S. population, it presents a unique opportunity for epidemiologists.

AThe phenomenon of rapid expulsion (RE) of Nippostrongylus brasiliensis was examined in Wistar rats. Within 4 hr of intraduodenal challenge with 4 day old N. Brasiliensis greater than 85% of the worms were expelled from rats immunized by infection 18 days previously with 4000-6000 third stage larvae. Rapid expulsion was unaffected by the challenge dose but waned with time after primary infection. Histological observations suggested that the parasites were excluded from their predilection site between the villi in immune rats and that they were separated from the mucosa by a superficial layer of mucus. A newly developed intestinal wash-out technique demonstrated that the 70%-80% of worms in previously uninfected controls were adherent to the mucosa whereas in immune rats 28%-36% of the parasites were adherent and 3%-23% were trapped in mucus. These experiments establish that immune exclusion and mucus trapping are early events in the expulsion process. The possible mechanisms controlling these phenomena are discussed.

The systemic secretion of a serine protease, rat mast-cell protease II (RMCPII), a major product of rat mucosal mast cells (MMC), was measured by a sensitive enzyme-linked immunosorbent assay (ELISA) in the sera of naive and primed rats challenged with the nematode N. brasiliensis. The systemic secretion of RMCPII was both time- and dose-dependent in primed rats (1-3 micrograms RMCPII/ml serum, 1 hr after challenge). Systemic release of RMCPII was slower and less pronounced in naive rats following intraduodenal challenge with 5-day-old worms. No RMCPII was detected in the sera of naive rats challenged with 4-day-old N. brasiliensis. Soluble worm antigen had no effect in naive rats, but when it was given intraduodenally or intravenously to primed rats, the serum levels of RMCPII 1 hr later were 10.5 micrograms/ml and 122 micrograms/ml, respectively. Few morphological changes were detected in MMC following worm challenge and the jejunal content of RMCPII was unaltered. A substantial reduction in the number of MMC occurred following intravenous injection of worm antigen, and the remaining cells were vacuolated and pale-staining, although granule exocytosis was not observed. Significant reduction in the jejunal content of RMCPII was also evident. These results demonstrate, unequivocally, that MMC are activated in response to N. brasiliensis challenge infection or to parasite antigens. In addition, the ability to detect secreted RMCPII in the sera of test animals provides a highly sensitive and uniquely selective assay to determine the participation of MMC in pathological reactions at mucosal surfaces.

Polypharmacy has been linked to higher risks of hospitalisation and death in community samples. It is commonly present in people with dementia but these risks have rarely been studied in this population. We aimed to investigate associations between polypharmacy and emergency department attendance, any and unplanned hospitalisation, and mortality in patients with dementia. Using a large mental health care database in South London, linked to hospitalisation and mortality data, we assembled a retrospective cohort of patients diagnosed with dementia. We ascertained number of medications prescribed at the time of dementia diagnosis and conducted multivariate Cox regression analyses. Of 4668 patients with dementia identified, 1128 (24.2%) were prescribed 4–6 medications and 739 (15.8%) ≥7 medications. Compared to those using 0–3 medications, patients with dementia using 4–6 or ≥7 agents had an increased risk of emergency department attendance (hazard ratio 1.20/1.35), hospitalisation (hazard ratio 1.12/1.32), unplanned hospital admission (hazard ratio 1.12/1.25), and death within two years (hazard ratio 1.29/1.39) after controlling for potential confounders. We found evidence of a dose response relationship with each additional drug at baseline increasing the risk of emergency department attendance and mortality by 5% and hospitalisation by 3%. In conclusion, polypharmacy at dementia diagnosis is associated with a higher risk of adverse health outcomes. Future research is required to elucidate which specific agents underlie this relationship and if reduction of inappropriate prescribing is effective in preventing these outcomes in dementia. © 2018 Elsevier Inc.

Objective Depression is associated with increased mortality in community samples. The use of antidepressant medication may also increase mortality, however, it is still unclear whether taking antidepressants before or after a diagnosis of dementia influences survival. Design Retrospective. Setting A cohort with a diagnosis of Alzheimer disease (AD) from a large mental health and dementia care database in South London, linked to hospitalization and mortality data. Participants Mild dementia (Mini-Mental State Examination ≥18/30) at the point of diagnosis. Measurements We ascertained antidepressant prescription, either in the 6 months before or after dementia diagnosis, and used the HoNOS65+, a standard clinician-rated measure of patient well-being, to determine depression severity and other neuropsychiatric, physical health, and functional difficulties. We conducted a survival analysis, adjusted for potential confounders and addressed possible confounding by indication through adjusting for a propensity score. Results Of 5473 patients with AD, 22.8% were prescribed an antidepressant in a 1-year window around dementia diagnosis. Of these, 2415 (44.1%) died in the follow-up period [mean (standard deviation) 3.5 (2.4) years]. Prescription of an antidepressant, both before and after dementia diagnosis, was significantly associated with higher mortality after adjusting for a broad range of potential confounders including symptom severity, functional status, and physical illness (hazard ratio 1.22; 95% confidence interval 1.08–1.37 for prescription prior to dementia diagnosis; 95% confidence interval 1.04–1.45 for prescription post dementia diagnosis). In stratified analyses, risks remained significant in those without neuropsychiatric symptoms. Conclusions The prescription of antidepressants around the time of dementia diagnosis may be a risk factor for mortality. © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine

Objective To investigate whether polypharmacy is associated with a higher incidence of frailty in a large cohort of North Americans during 8 years of follow-up. Design Longitudinal study, follow-up of 8 years. Participants A total of 4402 individuals at high risk or having knee osteoarthritis free from frailty at baseline. Measurements Details regarding medication prescription were captured and categorized as 0–3, 4–6, and ≥7. Frailty was defined using the Study of Osteoporotic Fracture index as the presence of ≥2 out of (1) weight loss ≥5% between baseline and the subsequent follow-up visit; (2) inability to do 5 chair stands; and (3) low energy level according to the Study of Osteoporotic Fracture definition. Cox's regression models calculating a hazard ratio (HR) with 95% confidence intervals (CIs), adjusted for potential confounders, were undertaken. Results During the 8-year follow-up, from 4402 participants at baseline, 361 became frail. Compared with participants taking 0–3 medications, the incidence of frailty was approximately double in those taking 4–6 medications and 6 times higher in people taking ≥7 medications. After adjusting for 11 potential baseline confounders, participants using 4–6 medications had a higher risk of frailty of 55% (HR = 1.55; 95% CI 1.22–1.96; P