Antiphospholipid autoantibodies as blood biomarkers for detection of early stage Alzheimer's disease

A robust blood biomarker is urgently needed to facilitate early prognosis for those at risk for Alzheimer's disease (AD). Redox reactive autoantibodies (R-RAAs) represent a novel family of antibodies detectable only after exposure of cerebrospinal fluid (CSF), serum, plasma or immunoglobulin fractions to oxidizing agents. We have previously reported that R-RAA antiphospholipid antibodies (aPLs) are significantly decreased in the CSF and serum of AD patients compared to healthy controls (HCs). These studies were extended to measure R-RAA aPL in serum samples obtained from Alzheimer's Disease Neuroimaging Initiative (ADNI). Serum samples from the ADNI-1 diagnostic groups from participants with mild cognitive impairment (MCI), AD and HCs were blinded for diagnosis and analyzed for R-RAA aPL by ELISA. Demographics, cognitive data at baseline and yearly follow-up were subsequently provided by ADNI after posting assay data. As observed in CSF, R-RAA aPL in sera from the AD diagnostic group were significantly reduced compared to HC. However, the sera from the MCI population contained significantly elevated R-RAA aPL activity relative to AD patient and/or HC sera. The data presented in this study indicate that R-RAA aPL show promise as a blood biomarker for detection of early AD, and warrant replication in a larger sample. Longitudinal testing of an individual for increases in R-RAA aPL over a previously established baseline may serve as a useful early sero-epidemiologic blood biomarker for individuals at risk for developing dementia of the Alzheimer's type

Impact of self-reported Gastroesophageal reflux disease in subjects from COPDGene cohort

Abstract Background The coexistence of gastroesophageal reflux disease (GERD) and COPD has been recognized, but there has been no comprehensive evaluation of the impact of GERD on COPD-related health status and patient-centered outcomes. Methods Cross-sectional and longitudinal study of 4,483 participants in the COPDGene cohort who met GOLD criteria for COPD. Physician-diagnosed GERD was ascertained by questionnaire. Clinical features, spirometry and imaging were compared between COPD subjects without versus with GERD. We evaluated the relationship between GERD and symptoms, exacerbations and markers of microaspiration in univariate and multivariate models. Associations were additionally tested for the confounding effect of covariates associated with a diagnosis of GERD and the use of proton-pump inhibitor medications (PPIs). To determine whether GERD is simply a marker for the presence of other conditions independently associated with worse COPD outcomes, we also tested models incorporating a GERD propensity score. Results GERD was reported by 29% of subjects with female predominance. Subjects with GERD were more likely to have chronic bronchitis symptoms, higher prevalence of prior cardiovascular events (combined myocardial infarction, coronary artery disease and stroke 21.3% vs. 13.4.0%, p < 0.0001). Subjects with GERD also had more severe dyspnea (MMRC score 2.2 vs. 1.8, p < 0.0001), and poorer quality of life (QOL) scores (St. George’s Respiratory Questionnaire (SGRQ) total score 41.8 vs. 34.9, p < 0.0001; SF36 Physical Component Score 38.2 vs. 41.4, p < 0.0001). In multivariate models, a significant relationship was detected between GERD and SGRQ (3.4 points difference, p < 0.001) and frequent exacerbations at baseline (≥2 exacerbation per annum at inclusion OR 1.40, p = 0.006). During a mean follow-up time of two years, GERD was also associated with frequent (≥2/year exacerbations OR 1.40, p = 0.006), even in models in which PPIs, GERD-PPI interactions and a GERD propensity score were included. PPI use was associated with frequent exacerbator phenotype, but did not meaningfully influence the GERD-exacerbation association. Conclusions In COPD the presence of physician-diagnosed GERD is associated with increased symptoms, poorer QOL and increased frequency of exacerbations at baseline and during follow-up. These associations are maintained after controlling for PPI use. The PPI-exacerbations association could result from confounding-by-indication.http://deepblue.lib.umich.edu/bitstream/2027.42/109476/1/12931_2014_Article_1500.pd

Risk factors for occurrence of displaced abomasum and their relation to nutritional management of Holstein dairy cattle

The aim of the present study was to identify nutritional risk factors for the occurrence of displaced abomasum (DA) in Holstein dairy cattle raised in regions with highly variable nutritional management. Feeding program data were collected from 30 dairy farms throughout Kosovo via use of a standardized questionnaire, and an AgriNIR™ Analyser was used to analyze the nutrient composition of forage (hay, corn silage) fed to cattle on those farms. A diagnosis of DA was made via auscultation/percutation in the area of the last rib and hearing of a ping sound. Multivariate linear regression models were used to determine risk factors associated with the incidence of DA. The overall incidence of DA in this study was 4.9% (38 cases among 769 cows). Of cows diagnosed with DA, 81.6% (31/38) had left side DA and 18.4% (7/38) had right side DA. Nearly all DA occurred during the first month of the postpartum period - 92.1% (35/38); only 7.9% (3/38) were observed in the pre-partum period. Risk factors that elevated the occurrence of DA included increased intake of concentrate feed after parturition (P\u3c0.002), increased body condition score at calving (P\u3c0.01), larger herd size (P\u3c0.021), and increased daily consumption of corn silage in the pre-partum transition period (P\u3c0.051). An increase in daily consumption of grass hay in the pre-partum transition period decreased (P\u3c0.014) the incidence of DA. The results of this study are useful for developing enhanced nutritional management protocols to reduce the incidence of DA in Holstein dairy cattle

Interviewer versus self-administered health-related quality of life questionnaires - Does it matter?

<p>Abstract</p> <p>Background</p> <p>Patient-reported outcomes are measured in many epidemiologic studies using self- or interviewer-administered questionnaires. While in some studies differences between these administration formats were observed, other studies did not show statistically significant differences important to patients. Since the evidence about the effect of administration format is inconsistent and mainly available from cross-sectional studies our aim was to assess the effects of different administration formats on repeated measurements of patient-reported outcomes in participants with AIDS enrolled in the Longitudinal Study of Ocular Complications of AIDS.</p> <p>Methods</p> <p>We included participants enrolled in the Longitudinal Study of Ocular Complications in AIDS (LSOCA) who completed the Medical Outcome Study [MOS] -HIV questionnaire, the EuroQol, the Feeling Thermometer and the Visual Function Questionnaire (VFQ) 25 every six months thereafter using self- or interviewer-administration. A large print questionnaire was available for participants with visual impairment. Considering all measurements over time and adjusting for patient and study site characteristics we used linear models to compare HRQL scores (all scores from 0-100) between administration formats. We defined adjusted differences of ≥0.2 standard deviations [SD]) to be quantitatively meaningful.</p> <p>Results</p> <p>We included 2,261 participants (80.6% males) with a median of 43.1 years of age at enrolment who provided data on 23,420 study visits. The self-administered MOS-HIV, Feeling Thermometer and EuroQol were used in 70% of all visits and the VFQ-25 in 80%. For eight domains of the MOS-HIV differences between the interviewer- and self- administered format were < 0.1 SD. Differences in scores were highest for the social and role function domains but the adjusted differences were still < 0.2 SD. There was no quantitatively meaningful difference between administration formats for EuroQol, Feeling Thermometer and VFQ-25 domain scores. For ocular pain (VFQ-25), we found a statistically significant difference of 3.5 (95% CI 0.2, 6.8), which did, however, not exceed 0.2 SD. For all instruments scores were similar for the large and standard print formats with all adjusted differences < 0.2 SD.</p> <p>Conclusions</p> <p>Our large study provides evidence that administration formats do not have a meaningful effect on repeated measurements of patient-reported outcomes. As a consequence, longitudinal studies may not need to consider the effect of different administration formats in their analyses.</p

Barriers Preventing Liver Transplantation in Canadians with HIV Infection – Perceptions of HIV Specialists

Liver transplantation is a life-saving procedure with demonstrated utility. There are accumulating data indicating that this procedure is helpful in HIV-infected patients as well. Liver transplantation is currently largely unavailable to those living with HIV in Canada. Understanding the obstacles to this procedure is the first step to increasing access. Between August 2005 and November 2005, HIV physicians, one from each Canadian HIV Trials Network site, were asked to complete a quantitative questionnaire on adult liver transplant access and need. Forty-six per cent (16 of 35) of sites responded. A median 20% of the nearly 12,700 HIV patients followed at these sites had concurrent liver disease (20% caused by hepatitis C virus, 5% caused by hepatitis B virus and 5% were alcohol-related). On average, two patients per site were thought to be appropriate candidates for liver transplant evaluation. Eighty per cent of respondents anticipated increased need for liver transplantation over the next five years. Organ supply was universally identified as the chief obstacle to transplantation in patients with HIV. Other key issues included risk of hepatitis C virus reinfection and transplant surgical team willingness. Based on these data, it is believed that these issues should be the focus of efforts designed to increase access to transplantation in Canadians with end-stage liver disease and concurrent HIV.</jats:p

Čimbenici rizika za pojavu dislokacije sirišta i njihova povezanost s uvjetima hranidbe kod mliječnih goveda holštajnske pasmine

The aim of the present study was to identify nutritional risk factors for the occurrence of displaced abomasum (DA) in Holstein dairy cattle raised in regions with highly variable nutritional management. Feeding program data were collected from 30 dairy farms throughout Kosovo via use of a standardized questionnaire, and an AgriNIR™ Analyser was used to analyze the nutrient composition of forage (hay, corn silage) fed to cattle on those farms. A diagnosis of DA was made via auscultation/percutation in the area of the last rib and hearing of a ping sound. Multivariate linear regression models were used to determine risk factors associated with the incidence of DA. The overall incidence of DA in this study was 4.9% (38 cases among 769 cows). Of cows diagnosed with DA, 81.6% (31/38) had left side DA and 18.4% (7/38) had right side DA. Nearly all DA occurred during the first month of the postpartum period - 92.1% (35/38); only 7.9% (3/38) were observed in the pre-partum period. Risk factors that elevated the occurrence of DA included increased intake of concentrate feed after parturition (P<0.002), increased body condition score at calving (P<0.01), larger herd size (P<0.021), and increased daily consumption of corn silage in the pre-partum transition period (P<0.051). An increase in daily consumption of grass hay in the pre-partum transition period decreased (P<0.014) the incidence of DA. The results of this study are useful for developing enhanced nutritional management protocols to reduce the incidence of DA in Holstein dairy cattleCilj istraživanja bio je identificirati čimbenike rizika u hranidbi koji doprinose pojavi dislokacije sirišta (DS) kod mliječnih goveda holštajnske pasmine, uzgajanih u područjima s različitim uvjetima hranidbe. Podatci o programu hranidbe prikupljeni su pomoću standardnog upitnika na 30 farmi za proizvodnju mlijeka širom Kosova, a analiza nutritivnog sastava u krmivima (sijeno, kukuruzna silaža) koja su na tim farmama korištena za hranidbu goveda obavljena je AgriNIR™ analizatorom. Dislokacija sirišta dijagnosticirana je osluškivanjem timpaničnog zvuka, uz primjenu metoda auskultacije/perkusije u području posljednjeg rebra. Modeli multivarijantne linearne regresije korišteni su za određivanje čimbenika rizika koji su povezani s incidencijom dislokacije sirišta. Ukupna incidencija dislokacije sirišta u ovom istraživanju bila je 4,9 % (38 slučajeva od 769 krava). Među kravama s dijagnosticiranom dislokacijom sirišta 81,6 % (31/38) krava imalo je dislokaciju u lijevu stranu, a 18,4 % (7/38) u desnu stranu. Gotovo sve dislokacije (92,1 %; 35/38) dogodile su se tijekom prvog mjeseca nakon teljenja, a samo 7,9 % (3/38) u razdoblju prije teljenja. Čimbenici rizika koji doprinose pojavnosti dislokacije sirišta uključivali su povećani unos koncentriranih krmiva nakon teljenja (P<0,002), višu ocjenu tjelesne kondicije pri teljenju (P<0,01), veću veličinu stada (P<0,021) i povećano dnevno uzimanje kukuruzne silaže u tranzicijskom razdoblju prije teljenja (P<0,051). Povećanje dnevnog uzimanja sijena od trava u tranzicijskom razdoblju prije teljenja doprinijelo je sniženju incidencije dislokacije sirišta (P<0,014). Rezultati ovog istraživanja korisni su za razvijanje boljih protokola u upravljanju hranidbom kojima bi se smanjila incidencija dislokacije sirišta u mliječnih goveda holštajnske pasmine

People with diagnosed HIV infection not attending for specialist clinical care: UK national review

BACKGROUND: Regular clinical care is important for the well-being of people with HIV. We sought to  audit and describe the characteristics of adults with diagnosed HIV infection not reported to be attending for clinical care in the UK. METHODS: Public Health England (PHE) provided clinics with lists of patients diagnosed or seen for specialist HIV care in 2010 but not linked to a clinic report or known to have died in 2011. Clinics reviewed case-notes of these individuals and completed questionnaires. A nested case–control analysis was conducted to compare those who had remained in the UK in 2011 while not attending care with individuals who received specialist HIV care in both 2010 and 2011. RESULTS: Among 74,418 adults living with diagnosed HIV infection in the UK in 2010, 3510 (4.7 %) were not reported as seen for clinical care or died in 2011. Case note reviews and outcomes were available for 2255 (64 %) of these: 456 (20.2 %) remained in the UK and did not attend care; 590 (26.2 %) left UK; 508 (22.6 %) received care in the UK: 73 (3.2 %) died and 628 (27.8 %) had no documented outcome. Individuals remaining in the UK and not attending care were more likely to be treatment naïve than those in care, but duration since HIV diagnosis was not significant. HIV/AIDS related hospitalisations were observed among non-attenders. CONCLUSION: Retention in UK specialist HIV care is excellent. Our audit indicates that the ‘true’ loss to follow up rate in 2011 was <2.5 % with no evidence of health tourism. Novel interventions to ensure high levels of clinic engagement should be explored to minimise disease progression among non-attenders

Relationship between quantitative CT metrics and health status and BODE in chronic obstructive pulmonary disease

Background The value of quantitative CT (QCT) to identify chronic obstructive pulmonary disease (COPD) phenotypes is increasingly appreciated. The authors hypothesised that QCT-defined emphysema and airway abnormalities relate to St George’s Respiratory Questionnaire (SGRQ) and Body-Mass Index, Airflow Obstruction, Dyspnea and Exercise Capacity Index (BODE). Methods 1200 COPDGene subjects meeting Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD with QCT analysis were included. Total lung emphysema was measured using the density mask technique with a 950 Hounsfield unit threshold. An automated programme measured mean wall thickness (WT), wall area percentage (WA%) and 10 mm lumenal perimeter (pi10) in six segmental bronchi. Separate multivariate analyses examined the relative influence of airway measures and emphysema on SGRQ and BODE. Results In separate models predicting SGRQ score, a 1 unit SD increase in each airway measure predicted higher SGRQ scores (for WT, 1.90 points higher, p=0.002; for WA%, 1.52 points higher, p=0.02; for pi10, 2.83 points higher p<0.001). The comparable increase in SGRQ for a 1 unit SD increase in emphysema percentage in these models was relatively weaker, significant only in the pi10 model (for emphysema percentage, 1.45 points higher, p=0.01). In separate models predicting BODE, a 1 unit SD increase in each airway measure predicted higher BODE scores (for WT, 1.07-fold increase, p<0.001; for WA%, 1.20-fold increase, p<0.001; for pi10, 1.16-fold increase, p<0.001). In these models, emphysema more strongly influenced BODE (range 1.24-1.26-fold increase, p<0.001). Conclusion Emphysema and airway disease both relate to clinically important parameters. The relative influence of airway disease is greater for SGRQ; the relative influence of emphysema is greater for BODE.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91946/1/2012 Thorax Relationship between quantitative CT metrics and health status and BODE in chronic obstructive pulmonary disease.pd