Durvalumab with or without tremelimumab versus the EXTREME regimen as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck: KESTREL, a randomized, open-label, phase III study.

BACKGROUND: Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis. The phase III KESTREL study evaluated the efficacy of durvalumab [programmed death-ligand 1 (PD-L1) antibody] with or without tremelimumab [cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody], versus the EXTREME regimen in patients with R/M HNSCC. PATIENTS AND METHODS: Patients with HNSCC who had not received prior systemic treatment for R/M disease were randomized (2 : 1 : 1) to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W (up to four doses), durvalumab monotherapy 1500 mg Q4W, or the EXTREME regimen (platinum, 5-fluorouracil, and cetuximab) until disease progression. Durvalumab efficacy, with or without tremelimumab, versus the EXTREME regimen in patients with PD-L1-high tumors and in all randomized patients was assessed. Safety was also assessed. RESULTS: Durvalumab and durvalumab plus tremelimumab were not superior to EXTREME for overall survival (OS) in patients with PD-L1-high expression [median, 10.9 and 11.2 versus 10.9 months, respectively; hazard ratio (HR) = 0.96; 95% confidence interval (CI) 0.69-1.32; P = 0.787 and HR = 1.05; 95% CI 0.80-1.39, respectively]. Durvalumab and durvalumab plus tremelimumab prolonged duration of response versus EXTREME (49.3% and 48.1% versus 9.8% of patients remaining in response at 12 months), correlating with long-term OS for responding patients; however, median progression-free survival was longer with EXTREME (2.8 and 2.8 versus 5.4 months). Exploratory analyses suggested that subsequent immunotherapy use by 24.3% of patients in the EXTREME regimen arm contributed to the similar OS outcomes between arms. Grade 3/4 treatment-related adverse events (TRAEs) for durvalumab, durvalumab plus tremelimumab, and EXTREME were 8.9%, 19.1%, and 53.1%, respectively. CONCLUSIONS: In patients with PD-L1-high expression, OS was comparable between durvalumab and the EXTREME regimen. Durvalumab alone, and with tremelimumab, demonstrated durable responses and reduced TRAEs versus the EXTREME regimen in R/M HNSCC.

"I have failed to separate my HIV from this pain": the challenge of managing chronic pain among people with HIV.

Pain is a highly prevalent and burdensome symptom among people with HIV (PWH). This study aims to identify how the experience of living with HIV and chronic pain influences pain beliefs, health-seeking and pain management. Thirty-nine purposively sampled PWH with chronic pain (sample characteristics = 61% women, 79% Black, Asian and minority ethnic groups, 18% men who have sex with men, 45-54 median age category) participated in focus groups in London. Focus groups were co-facilitated with community members. Transcripts wereanalysed using a thematic approach. Findings revealed that HIV stigma, fractured care pathways, and general practitioners' lack of HIV training are barriers to supported pain management. Unaddressed pain results in poorer mental health and reduced quality of life, which has important clinical implications for HIV treatment adherence. Creating HIV-specific pain resources, activating social networks, and pain self-management techniques are potential solutions. Person-centred assessment and HIV training is needed to help clinicians identify PWH with chronic pain. Clear guidelines need to be developed to identify which health service providers are responsible for chronic pain management in PWH. This study generated a refined version of the Fear Avoidance Model that introduces a dimension of HIV-specific behaviours that impact PWHs seeking chronic pain management.

The Global Task Force for Chronic Pain in People with HIV (PWH): Developing a research agenda in an emerging field.

Chronic pain is a common comorbidity in people with HIV (PWH), with prevalence estimates of 25-85%. Research in this area is growing, but significant gaps remain. A Global Task Force of HIV experts was organized to brainstorm a scientific agenda and identify measurement domains critical to advancing research in this field. Experts were identified through literature searches and snowball sampling. Two online questionnaires were developed by Task Force members. Questionnaire 1 asked participants to identify knowledge gaps in the field of HIV and chronic pain and identify measurement domains in studies of chronic pain in PWH. Responses were ranked in order of importance in Questionnaire 2, which was followed by a group discussion. 29 experts completed Questionnaire 1, 25 completed Questionnaire 2, and 21 participated in the group. Many important clinical and research priorities emerged, including the need to examine etiologies of chronic pain in PWH. Pain-related measurement domains were discussed, with a primary focus on domains that could be assessed in a standardized manner across various cohorts that include PWH in different countries. We collaboratively identified clinical and research priorities, as well as gaps in standardization of measurement domains, that can be used to move the field forward.

Uterine fibroids and risk of hypertensive disorders of pregnancy - results from a racially diverse high-risk cohort.

Study Question: What is the impact of the presence of uterine fibroids on the risk of developing hypertensive disorders of pregnancy (HDP) in a predominantly urban, low-income, Black, and Hispanic population of women with ultrasound or clinically diagnosed uterine fibroids with rich phenotypic data to carefully control for potential confounders? Summary answers: The odds of HDP were 39% higher in women with uterine fibroids compared to those without when controlled for age at delivery, race, prepregnancy BMI, education, parity, and smoking status; neither fibroid location or size modified this risk. What is known already: Studies are conflicting regarding the impact of uterine fibroids on risk of HDP; limitations of prior studies include primarily Western European populations and lack of measurement of potential confounders. Study design size and duration: A total of 7030 women from the Boston Birth Cohort (a racially diverse cohort recruited from 1998 to 2018) that had clinical and ultrasound data regarding uterine fibroid status were included in this analysis. Participants/materials setting and methods: Four hundred eighty-nine women with uterine fibroids and 6541 women without were included. Hypertensive disorders of pregnancy were ascertained from medical records. Logistic regression was performed to assess the risk of HDP in women with and without uterine fibroids. Covariates adjusted for included age at delivery, race, pre-pregnancy BMI, education, parity, and smoking status during pregnancy. Sub-analyses were performed to assess the impact of specific fibroid location and overall fibroid volume burden. Main results and the role of chance: The incidence of uterine fibroids in the cohort was 7% (N=489). Twelve percent of women without uterine fibroids and 17% of women with fibroids developed HDP; in multivariate analyses adjusted for the potential confounders above, the odds of HDP were 39% higher in women with uterine fibroids compared to those without (p=0.03). Women with a uterine fibroid diagnosis based on ICD code (n=297) versus asymptomatic incidental ultrasound diagnosis (n=192) had a significantly greater chance of developing HDP (20 vs 15%, p=0.006). There did not appear to be an association between number of fibroids or total fibroid volume and the risk of developing HDP. Limitations, reasons for caution: This study has a relatively small sample size. While post-hoc power calculation determined that there was adequate power to detect a 4.6% difference in the incidence of development of HDP between participants with uterine fibroids and those without, the sub-analyses based on fibroid size, location, and method of diagnosis were underpowered to determine a similar level of difference. Wider implications of the findings: In a racially diverse cohort, presence of uterine fibroids was a significant risk factor for developing HDP, regardless of uterine fibroid size or location. This may have implications for additional monitoring and risk stratification in women with uterine fibroids. Study funding/competing interests: KC supported by WRHR NIH NICHD Award # K12 HD103036, PI Andrew Satin, RD James Segars. The Boston Birth Cohort (the parent study) was supported in part by the National Institutes of Health (NIH) grants (2R01HD041702, R01HD098232, R01ES031272, R01ES031521, and U01 ES034983); and the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) (UT7MC45949). This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by any funding agencies. Trial registration number: The BBC is registered under clinicaltrials.gov NCT03228875 .

Serum biomarker levels for musculoskeletal disease in two- and three-year-old racing Thoroughbred horses: A prospective study of 130 horses.

REASON FOR PERFORMING STUDY: Biomarkers have shown some in vivo promise for the detection of musculoskeletal injuries, but further study to assess biomarker levels in clinical orthopaedic disease is required. OBJECTIVE: To assess 7 serum biomarkers for the detection of musculoskeletal injuries. METHODS: Two- and 3-year-old racehorses were entered into the study (n = 238). Exit criteria were lack of training for >30 days, or completion of 10 study months. Data from horses with solitary musculoskeletal injuries and completion of >2 months were analysed. Musculoskeletal injury was considered intra-articular fragmentation (IAF), tendon or ligamentous injury (TL), stress fractures (SF) and dorsal metacarpal disease (DMD). Monthly lameness examination and serum collection were performed. Serum was analysed for glycosaminoglycan (GAG), type I and II collagen degradation (C1, 2C), type II collagen synthesis (CPII), type II collagen degradation (Col CEQ), aggrecan synthesis (CS846), osteocalcin (OC) as a marker of bone formation and (C-terminal telopeptide of type I collagen) CTX as a marker of bone degradation. RESULTS: Of the 238 horses 59 injured and 71 uninjured control horses met the analysis criteria. Based on injury no significant differences in the proportions were observed for age, gender or lesion type, although a higher proportion of injuries occurred at the beginning of the study. Of injured horses, 16 (27%) sustained an IAF, 17 (29%) a TL injury, 7 (12%) SF and 19 (32%) were diagnosed with DMD. There were significant changes seen in biomarkers based on the injury incurred when longitudinal samples were assessed. Furthermore, based on the serum biomarkers collected prior to injury, horses could be correctly classified as injured or uninjured 73.8% of the time. CONCLUSIONS: A unique biomarker pattern occurred before each injury and this was beneficial in classifying horses as injured or uninjured. POTENTIAL RELEVANCE: Biomarkers have the potential to be used as a screening aid prior to musculoskeletal injury.

The Oldest Highlands of Mars May Be Massive Dust Fallout Deposits.

The oldest terrains of Mars are cratered landscapes, in which extensive valleys and basins are covered by ubiquitous fluvial plains. One current paradigm maintains that an impact-generated megaregolith underlies these sediments. This megaregolith was likely largely generated during the Early Noachian (~4.1 to ~3.94 Ga) when most Martian impact basins formed. We examined the geologic records of NW Hellas and NW Isidis, which include this epoch's most extensive circum-basin outcrops. Here, we show that these regions include widespread, wind-eroded landscapes, crater rims eroded down by several hundred meters, pitted plains, and inverted fluvial and crater landforms. These surfaces exhibit few fresh craters, indicating geologically recent wind erosion. The deep erosion, topographic inversions, and an absence of dunes on or near talus across these regions suggest that sediments finer than sand compose most of these highland materials. We propose that basin-impact-generated hurricane-force winds created sediment-laden atmospheric conditions, and that muddy rains rapidly settled suspended sediments to construct extensive Early Noachian highlands. The implied high abundance of fine-grained sediments before these impacts suggests large-scale glacial silt production and supports the previously proposed Noachian "icy highlands" hypothesis. We suggest that subglacial meltwater interactions with the sedimentary highlands could have promoted habitability, particularly in clay strata.

The spokane flood controversy and the martian outflow channels.

In a series of papers published between 1923 and 1932, J Harlen Bretz described an enormous plexus of proglacial stream channels eroded into the loess and basalt of the Columbia Plateau, eastern Washington. He argued that this region which he called the Channeled Scabland, was the product of a cataclysmic flood, which he called the Spokane flood. Considering the nature and vehemence of the opposition to his hypothesis, which was considered outrageous, its eventual scientific verification constitutes one of the most fascinating episodes in the history of modern science. The discovery of probable catastrophic flood channels on Mars has given new relevance to Bretz's insights.

Paleohydrology of late pleistocene superflooding, altay mountains, siberia.

Cataclysmic flooding is a geomorphological process of planetary significance. Landforms of flood origin resulted from late Pleistocene ice-dammed lake failures in the Altay Mountains of south-central Siberia. Peak paleoflows, which exceeded 18 x 10(6) cubic meters per second, are comparable to the largest known terrestrial discharges of freshwater and show a hydrological scaling relation to floods generated by catastrophic dam failures. These seem to have been Earth's greatest floods, based on a variety of reconstructed paleohydraulic parameters.

Paleoflood hydrology.

The difficult task of estimating recurrence intervals for large floods has long plagued hydrologists because statistical measures fail when return intervals of floods exceed the length of historical data sets. Sediments deposited in the backwaters of large floods may accumulate thick sequences in tributary mouths. Stratigraphic and sedimentologic studies of these sequences combined with radiocarbon dating have established a 10,000-year paleoflood record for the lower Pecos and Devils rivers in southwestern Texas. This technique is rapid and relatively inexpensive and can be used where historical records are short or entirely absent.

A 5000-year record of extreme floods and climate change in the southwestern United States.

A 5000-year regional paleoflood chronology, based on flood deposits from 19 rivers in Arizona and Utah, reveals that the largest floods in the region cluster into distinct time intervals that coincide with periods of cool, moist climate and frequent El Niño events. The floods were most numerous from 4800 to 3600 years before present (B.P.), around 1000 years B.P., and after 500 years B.P., but decreased markedly from 3600 to 2200 and 800 to 600 years B.P. Analogous modern floods are associated with a specific set of anomalous atmospheric circulation conditions that were probably more prevalent during past flood epochs.

Magellan: initial analysis of venus surface modification.

Initial Magellan observations reveal a planet with high dielectric constant materials exposed preferentially in elevated regions with high slopes, ejecta deposits extending up to 1000 kilometers to the west of several impact craters, windblown deposits and features in areas where there are both obstacles and a source of particulate material, and evidence for slow, steady degradation by atmosphere-surface interactions and mass movements.

The 1997 Mars Pathfinder Spacecraft Landing Site: Spillover Deposits from an Early Mars Inland Sea.

The Martian outflow channels comprise some of the largest known channels in the Solar System. Remote-sensing investigations indicate that cataclysmic floods likely excavated the channels ~3.4 Ga. Previous studies show that, in the southern circum-Chryse region, their flooding pathways include hundreds of kilometers of channel floors with upward gradients. However, the impact of the reversed channel-floor topography on the cataclysmic floods remains uncertain. Here, we show that these channel floors occur within a vast basin, which separates the downstream reaches of numerous outflow channels from the northern plains. Consequently, floods propagating through these channels must have ponded, producing an inland sea, before reaching the northern plains as enormous spillover discharges. The resulting paleohydrological reconstruction reinterprets the 1997 Pathfinder landing site as part of a marine spillway, which connected the inland sea to a hypothesized northern plains ocean. Our flood simulation shows that the presence of the sea would have permitted the propagation of low-depth floods beyond the areas of reversed channel-floor topography. These results explain the formation at the landing site of possible fluvial features indicative of flow depths at least an order of magnitude lower than those apparent from the analyses of orbital remote-sensing observations.

Safety and efficacy of paramedic treatment of regular supraventricular tachycardia: a randomised controlled trial.

INTRODUCTION: Supraventricular tachycardias (SVTs) are a common cause of acute hospital presentations. Adenosine is an effective treatment. To date, no studies have directly compared paramedic-with hospital-delivered treatment of acute SVT with adenosine. METHOD: Randomised controlled trial comparing the treatment of SVT and discharge by paramedics with conventional emergency department (ED)-based care. Patients were excluded if they had structural heart disease or contraindication to adenosine. Discharge time, follow-up management, costs and patient satisfaction were compared. RESULTS: Eighty-six patients were enrolled: 44 were randomised to paramedic-delivered adenosine (PARA) and 42 to conventional care (ED). Of the 37 patients in the PARA group given adenosine, the tachycardia was successfully terminated in 81%. There was a 98% correlation between the paramedics' ECG diagnosis and that of two electrophysiologists. No patients had any documented adverse events in either group. The discharge time was lower in the PARA group than in the ED group (125 min (range 55-9513) vs 222 min (range 72-26 153); p=0.01), and this treatment strategy was more cost-effective (£282 vs £423; p=0.01). The majority of patients preferred this management approach. Being treated and discharged by paramedics did not result in the patients being less likely to receive ongoing management of their arrhythmia and cardiology follow-up. CONCLUSIONS: Patients with SVT can effectively and safely be treated with adenosine delivered by trained paramedics. Implementation of paramedic-delivered acute SVT care has the potential to reduce healthcare costs without compromising patient care. TRIAL REGISTRATION NUMBER: NCT02216240.

An investigation into the relationship between input-output nonlinearities and rate-induced nonlinearities of click-evoked otoacoustic emissions recorded using maximum length sequences.

The maximum length sequence (MLS) technique allows otoacoustic emissions (OAEs) to be recorded using clicks presented at very high presentation rates. It has previously been found that increasing the click presentation rate leads to increasing suppression (termed "rate-suppression") of the MLS evoked OAE (Hine, J.E., Thornton, A.R.D., 1997. Transient evoked otoacoustic emissions recorded using maximum length sequences as a function of stimulus rate and level. Ear Hear. 18, 121-128). It has been suggested that the source of rate-suppression arises from the same nonlinear processes that give rise to the well-known nonlinear growth of OAEs. Based on this assumption, a simple model of rate-suppression (Kapadia, S., Lutman, M.E., 2001. Static input-output nonlinearity as the source of nonlinear effects in maximum length sequence click-evoked OAEs. Br. J. Audiol. 35, 103-112) predicts that both input-output (I/O) nonlinearity and rate-suppression can be unified by characterising the stimulus in terms of its acoustic power which, at high rates, is proportional to the click presentation rate. The objective of this study was to test this simple model by recording MLS OAEs from a group of normally hearing adults over a range of stimulus rates from 40 to 5000 clicks/s, and of stimulus levels from 45 to 70dB peSPL. The results are broadly in agreement with the predictions from the model, though there appears to be some tendency for the model to slightly overestimate the degree of rate-suppression for a given degree of I/O nonlinearity. It is also suggested that the model may break down more significantly in the presence of spontaneous OAEs.

Nonlinear properties of otoacoustic emissions in normal and impaired hearing.

Click-evoked otoacoustic emissions (CEOAEs) exhibit nonlinearities in amplitude and time domains. The first objective of this study was to investigate whether there is any correlation between the temporal and amplitude nonlinearities of CEOAEs in normals. Additionally there is evidence that pathology affects the normal cochlear nonlinearity. The second objective was to investigate whether pathology affects the temporal nonlinear components. Conventional and maximum length sequence (MLS) CEOAEs were recorded in normal subjects and in patients with mild hearing loss. The slope of the input-output (I/O) function of the conventional CEOAE measured the amplitude nonlinearity. Two measures of temporal nonlinearity were the magnitude of the suppression that occurs with increase in stimulus rate and the amplitudes of the second and third order temporal interaction components (Volterra slices). The amplitude nonlinearity is well correlated with both the magnitude of the rate suppression and the amplitudes of the Volterra slices. The 'linear' CEOAE amplitude showed no differences between the normal and patient groups but the differences in the Volterra slices were substantial. This suggests that the first sign of damage to the cochlea is that the system becomes more linear. Hence the Volterra slices may provide a sensitive measure of cochlear damage.

Telomere shortening and telomerase activity in ischaemic cardiomyopathy patients - Potential markers of ventricular arrhythmia.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) reduce mortality in patients with ischaemic cardiomyopathy at high risk of ventricular arrhythmias (VA). However, the current indication for ICD prescription needs improvement. Telomere and telomerase in leucocytes have been shown to associate with biological ageing and pathogenesis of cardiovascular diseases. We hypothesised that leucocyte telomere length, load-of-short telomeres and/or telomerase activity are associated with VA occurrence in ischaemic cardiomyopathy patients. METHODS AND RESULTS: 90 ischaemic cardiomyopathy patients with primary prevention ICDs were recruited. 35 had received appropriate therapy from the ICD for potentially-fatal VA while the remaining 55 patients had not. No significant differences in baseline demographic data relevant to telomere biology were seen between the two groups. There was no significant difference in the age and sex adjusted mean telomere length analysed by qPCR between the groups (p=0.88). In contrast, the load-of-short telomeres assessed by Universal-STELA method and telomerase activity by TRAP assay were both higher in patients who had appropriate ICD therapy and were significantly associated with incidence of ICD therapy (p=0.02, p=0.02). ROC analyses demonstrated that the sensitivity and specificity of these telomere dynamics in predicting potentially-fatal VA was higher than the current gold-standard - left ventricular ejection fraction (AUC 0.82 versus 0.47). CONCLUSION: The load-of-short telomeres and telomerase activity had a significant association with ICD therapy (for VA) in ischaemic cardiomyopathy patients. These biomarkers should be tested in prospective studies to assess their clinical utility in predicting VA after myocardial infarction and guiding primary prevention ICD prescription.

Bryostatin induces changes in protein kinase C location and activity without altering c-myc gene expression in human promyelocytic leukemia cells (HL-60).

When human promyelocytic leukemia cells (HL-60) are induced by phorbol esters to differentiate to macrophages, the process is accompanied by immediate activation of protein kinase C (PK-C) in the cytoplasm and later changes in DNA and RNA synthesis. Although these events are temporarily related, it remains unclear how activation of this protein kinase leads to changes in nuclear transcription. In this study, we find that bryostatin, a macrocyclic lactone which does not induce differentiation of HL-60 cells but activates PK-C, mimics the effects of phorbol esters on protein phosphorylation and PK-C location. Treatment of HL-60 cells with bryostatin stimulates phosphorylation of the surface transferrin receptor and in the cytoplasm of five proteins having the molecular weights of 17-43 kDa over the same time course as that stimulated by phorbol esters. Similarly, prolonged treatment with bryostatin, like that with phorbol esters, causes the loss of all cellular PK-C activity. Unlike the phosphorylation studies, bryostatin treatment, over a 1-100 nM concentration range and for varying lengths of time, did not affect HL-60 c-myc RNA levels, while phorbol ester treatment rapidly decreased c-myc RNA levels. These data suggest that neither the activation of PK-C and the phosphorylation of specific substrates nor the loss of total cellular PK-C activity from HL-60 cells is sufficient to induce marked decreases in c-myc levels and differentiation of HL-60 cells.

Electrocardiogram of the humpback whale (Megaptera novaeangliae), with specific reference to atrioventricular transmission and ventricular excitation.

OBJECTIVES: The objective of the study was to record the electrocardiogram (ECG) of a large whale to obtain crucial data for comparative electrophysiologic analysis. BACKGROUND: The data were needed to establish the mismatch between heart size and PR interval and QRS duration in mammals. METHODS: In the waters off the coast of Newfoundland, in two humpback whales (Megaptera novaeangliae) with an estimated weight of 30,000 kg a 1-lead ECG was recorded, enabling reliable assessment of P waves and QRS complexes. RESULTS: It was found that both the PR interval (atrioventricular [AV] transmission time) and QRS duration (ventricular excitation) are extremely short for animals of this size. These findings are difficult, if not impossible, to explain on the basis of currently accepted electrophysiologic theories. However, the narrow QRS complex may be due to a very dense His-Purkinje network in the ventricular wall of whales. Alternative mechanisms that can explain the function of the mammalian AV node need to be considered and explored. CONCLUSIONS: The results of the study may be of value for the understanding of the ECG in humans.

Fecal hemoglobin excretion in elderly patients with atrial fibrillation: combined aspirin and low-dose warfarin vs conventional warfarin therapy.

BACKGROUND: Antithrombotic prophylaxis using combined aspirin and low-dose warfarin is under evaluation in several clinical trials. However, therapy may result in increased gastrointestinal blood loss and clinical bleeding vs conventional single-agent antithrombotic therapy. METHODS: To assess differences in gastrointestinal blood loss, we measured quantitative fecal hemoglobin equivalents (HemoQuant, Mayo Medical Laboratory, Rochester, Minn) in 117 patients, mean age 71 years, 1 month after initiation of assigned therapy in the Stroke Prevention in Atrial Fibrillation III Study. Sixty-three of these patients who had characteristics for high risk of stroke were randomly assigned to conventional adjusted-dose warfarin therapy (international normalized ratio, 2.0 to 3.0) or low-dose combined therapy (warfarin [international normalization ratio,<1.5] plus 325 mg/d of enteric-coated aspirin). The remaining 54 patients with low risk of stroke received 325 mg/d of enteric-coated aspirin. RESULTS: Among the 63 at high risk of stroke, abnormal values (>2mg of hemoglobin per gram of stool) were detected in 11% and values greater than 4 mg of hemoglobin per gram of stool were found in 8%. Mean ( +/- SD) values were more for those randomly assigned to receive combined therapy (1.7 +/- 3.3 mg of hemoglobin per gram of stool vs adjusted-dose warfarin therapy, 1.0 +/- 1.9 mg/g; P=.003). The 54 nonrandomized patients with low risk of stroke receiving aspirin alone had a mean (+/- SD) HemoQuant value of 0.8 +/- 0.7mg of hemoglobin per gram of stool 1 month after entry in the study. CONCLUSIONS: Abnormal levels of fecal hemoglobin excretion were common in elderly patients with high risk of atrial fibrillation 1 month after randomization to prophylactic antithrombotic therapy. Combined warfarin and aspirin therapy was associated with greater fecal hemoglobin excretion than standard warfarin therapy, suggesting the potential for increased gastrointestinal hemorrhage.