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Puropse We evaluated the efficacy and safety of Nuvastatic™ in improving cancer-related fatigue (CRF) among cancer patients. Methods This multicenter randomized double-blind placebo-controlled phase-2 trial included 110 solid malignant tumor patients (stage I–IV) undergoing chemotherapy. They were randomly selected and provided oral Nuvastatic™ 1000 mg (N = 56) or placebo (N = 54) thrice daily for 9 weeks. The primary outcomes were fatigue (Brief Fatigue Inventory [BFI]) and Visual Analog Scale for Fatigue [VAS-F]) scores measured before and after intervention at baseline and weeks 3, 6, and 9. The secondary outcomes were mean group difference in the vitality subscale of the Medical Outcome Scale Short Form-36 (SF-36) and urinary F2-isoprostane concentration, Eastern Cooperative Oncology Group scores, and biochemical and hematologic parameters. Clinical outcomes were assessed using two-way repeated-measures analysis of variance on intention-to-treat population. Results The Nuvastatic™ group exhibited an overall decreased fatigue score compared with the placebo group. The BFI estimated mean difference (eMD) was 15.29 (95% CI: 12.77–17.82) and VAS-F eMD was 11.19 (95% CI: 8.06–14.32) were significantly different between two groups at week 9 (p

The wettest portion of the interior of western North America centers on the mountainous region spanning western Montana, Idaho, British Columbia, and Alberta. Inland ranges there capture the remnants of Pacific storms. Steep east–west hydroclimate gradients make the region sensitive to changes in inland-penetrating moisture that may have varied greatly during the Holocene. To investigate potential hydroclimate change, we produced a 7600-yr lake-level reconstruction from Silver Lake, located on the Montana–Idaho border. Ground-penetrating radar profiles and a transect of four shallow-water sediment cores that were dated using radiocarbon dating and tephrachronology revealed substantial changes in moisture through time. An organic-rich mud unit indicating wet and similar to modern conditions prior to 7000 cal yr BP is overlain by an erosional surface signifying drier than modern conditions from 7000–2800 cal yr BP. A subsequent time-transgressive increase in water levels from 2800–2300 cal yr BP is indicated by a layer of late Holocene muds, and is consistent with glacier expansion and increases in the abundance of mesic tree taxa in the region. Millennial-scale trends were likely driven by variations in orbital-scale forcing during the Holocene, but the regional outcomes probably depended upon factors such as the strength of the Aleutian Low, Pacific sea-surface temperature variability, and the frequency of atmospheric rivers over western North America.

OBJECTIVE To evaluate the prevalence of elevations of anti-cyclic citrullinated peptide-3 (anti-CCP3) antibody, rheumatoid factor IgM (RF-IgM) and serum calprotectin (sCP) in pre-rheumatoid arthritis (RA) as well as the diagnostic accuracies of these biomarkers for the timing of diagnosis of future RA. METHODS A total of 215 RA cases, each with approximately three pre-RA diagnoses and one post-RA diagnosis serum sample, and controls were identified from the Department of Defense Serum Repository. All case samples and a single sample from each control subject were tested for anti-CCP3 (IgG), RF-IgM, and sCP. The diagnostic accuracies of biomarkers for future RA were evaluated. RESULTS Anti-CCP3, RF-IgM, and sCP were elevated in pre-RA, with anti-CCP3 and sCP significantly elevated compared with RF-IgM at the earliest time points. Within the cases, the combination of anti-CCP3 and RF-IgM positivity had a positive predictive value (PPV) of 35.6% for a diagnosis of RA in 3 years or less, which is significantly higher than the PPV of 18.7% for anti-CCP3 positivity alone (P < 0.001). A combination of anti-CCP3, RF-IgM, and sCP had the highest PPV (53.0%) for a diagnosis of RA in 3 years or less; however, this was not significantly higher than the PPV for anti-CCP3 and RF-IgM positivity (P = 0.248). CONCLUSION Anti-CCP3, RF-IgM, and sCP are elevated in pre-RA; furthermore, combinations of elevations of these biomarkers are more commonly seen in the period of less than or equal to 3 years to diagnosis. This may be considered in creating inclusion criteria in prevention trials in RA. In addition, the biologic relationships of these biomarkers in pre-RA need exploration.

BACKGROUND Idiopathic intracranial hypertension (IIH) mostly affects overweight and obese women. Severe obesity is associated with poorer visual outcomes in IIH, and weight gain can precipitate IIH and increase the risk of recurrence. Conversely, weight loss can decrease intracranial pressure and is an effective IIH treatment. Therefore, accurate monitoring of weight and body mass index (BMI) is important to help guide the management of IIH patients. Our goal was to compare estimated and measured BMI among patients with presumed IIH and non-IIH controls to determine whether these vital signs should be systematically measured when evaluating patients for IIH. METHODS A retrospective chart review was performed of consecutive patients with reported and measured weight and height seen in one ophthalmology-based neuro-ophthalmology clinic for IIH between January 2, 2018 and September 10, 2018. Patients with IIH or presumed IIH were compared to non-IIH controls, matched according to age (±5 years), BMI (±5 kg/m unless ≥40 kg/m), sex, and race. Patients with confirmed IIH were asked to self-report their weight when seen in follow-up and they were weighed to compare their self-reported vs measured percent weight change. RESULTS We included 379 subjects (140 patients; 239 controls) among whom 75 of the IIH patients were matched to non-IIH controls. Patients with presumed or definite IIH accurately estimated their height and generally underestimated their weight by a median of 1.8 kg (4 lb), resulting in a median BMI underestimate of 0.9 kg/m. There was no difference in BMI underestimation when comparing presumed or definite IIH patients to matched non-IIH controls while controlling for insurance status, smoking, diabetes, and vascular disease (P = 0.66). As BMI increased, all subjects underestimated their BMI more (by 0.9% per 10 measured BMI unit increase), when controlling for age, sex, and race (P < 0.003). Sixteen confirmed IIH patients were seen in follow-up. At initial neuro-ophthalmology consultation, these subjects underestimated their weight by a mean of 3.2%. At last follow-up they underestimated their weight by only 1.2% (P = 0.03). CONCLUSIONS There was no evidence that IIH or presumed IIH patients had a different perception of their weight than non-IIH controls at initial neuro-ophthalmology consultation. Both patients and matched controls tended to underestimate their weight by the same amount, resulting in an overall BMI underestimation of approximately 1% per 10 measured BMI unit increase. Heavier subjects tended to underestimate their body weight and resultant BMI more, and IIH patients tended to estimate their weight more accurately at follow-up. Our results emphasize the need to systematically objectively measure the weight of presumed IIH patients seen in an ophthalmology clinic.

Objective To evaluate patterns of elevations of isotypes of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) pre-rheumatoid arthritis (RA) diagnosis and post-RA diagnosis. Methods Using the Department of Defense Serum Repository we identified 214 RA cases and 210 matched controls. Up to 3 pre-RA diagnosis and 1 post-RA diagnosis serum samples per subject were tested for RF and for IgA, IgG, and IgM ACPAs. The timing and trajectories of elevations of autoantibodies were evaluated. Results Autoantibody levels were elevated in cases versus controls a mean of 17.9 years before RA diagnosis for IgG ACPA, 14.2 years for IgA-RF, 7.2 years for IgM-RF, 6.2 years for IgA ACPA, and 5.0 years for both IgM ACPA and IgG-RF (P 2 years post-RA diagnosis; P = 0.04). All autoantibody levels demonstrated an early initial elevation, a period of stability, then an increase immediately before RA diagnosis. A pre-RA endotype of early elevation of autoantibodies was associated with increased use of biologic therapy, and a higher prevalence of sicca symptoms and lung disease post-RA diagnosis. Conclusion Differences in patterns of elevations of autoantibody isotypes have implications for understanding the pathophysiology of RA development. These include understanding what factors drive initial autoantibody elevations compared to what factors (including mucosal) drive later increases in autoantibody levels and a transition to clinically apparent RA, and how pre-RA endotypes may influence post-RA diagnosis phenotypes.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) primarily affects the lungs, causing respiratory symptoms. However, the infection clearly affects all organ systems including the gastrointestinal system. Acute pancreatitis associated with coronavirus disease 2019 (COVID-19) has been widely reported Recent studies have discussed pancreatic compromise incidentally in asymptomatic patients, or in a form of clinical symptoms such as abdominal pain, nausea, or vomiting, which is further reflected in some cases with abnormal serum lipase and amylase levels It was suggested that upregulation of angiotensin-converting enzyme II cell receptors or inflammatory cytokines play a major role in predisposing pancreatic injury in SARS-CoV-2 positive patients To date, there is insufficient data to establish the causality of acute pancreatitis in SARS-CoV-2 infected cases. In this paper, we organize recent studies conducted to observe the frequency of acute pancreatitis associated with COVID-19 cases while highlighting present hypotheses, predisposing factors, and their effect on the outcome, and point to gaps in our knowledge.

Idiopathic intracranial hypertension (IIH) mostly affects overweight and obese women. Severe obesity is associated with poorer visual outcomes in IIH, and weight gain can precipitate IIH and increase the risk of recurrence. Conversely, weight loss can decrease intracranial pressure and is an effective IIH treatment. Therefore, accurate monitoring of weight and body mass index (BMI) is important to help guide the management of IIH patients. Our goal was to compare estimated and measured BMI among patients with presumed IIH and non-IIH controls to determine whether these vital signs should be systematically measured when evaluating patients for IIH.A retrospective chart review was performed of consecutive patients with reported and measured weight and height seen in one ophthalmology-based neuro-ophthalmology clinic for IIH between January 2, 2018 and September 10, 2018. Patients with IIH or presumed IIH were compared to non-IIH controls, matched according to age (±5 years), BMI (±5 kg/m unless ≥40 kg/m), sex, and race. Patients with confirmed IIH were asked to self-report their weight when seen in follow-up and they were weighed to compare their self-reported vs measured percent weight change.We included 379 subjects (140 patients; 239 controls) among whom 75 of the IIH patients were matched to non-IIH controls. Patients with presumed or definite IIH accurately estimated their height and generally underestimated their weight by a median of 1.8 kg (4 lb), resulting in a median BMI underestimate of 0.9 kg/m. There was no difference in BMI underestimation when comparing presumed or definite IIH patients to matched non-IIH controls while controlling for insurance status, smoking, diabetes, and vascular disease (P = 0.66). As BMI increased, all subjects underestimated their BMI more (by 0.9% per 10 measured BMI unit increase), when controlling for age, sex, and race (P0.003). Sixteen confirmed IIH patients were seen in follow-up. At initial neuro-ophthalmology consultation, these subjects underestimated their weight by a mean of 3.2%. At last follow-up they underestimated their weight by only 1.2% (P = 0.03).There was no evidence that IIH or presumed IIH patients had a different perception of their weight than non-IIH controls at initial neuro-ophthalmology consultation. Both patients and matched controls tended to underestimate their weight by the same amount, resulting in an overall BMI underestimation of approximately 1% per 10 measured BMI unit increase. Heavier subjects tended to underestimate their body weight and resultant BMI more, and IIH patients tended to estimate their weight more accurately at follow-up. Our results emphasize the need to systematically objectively measure the weight of presumed IIH patients seen in an ophthalmology clinic.

The aim of this note is to bring to wider attention a painting, entitled The Temptation of Saint Anthony, by Roelandt Savery sold at Sotheby’s London on 7th December 2016. This work of c.16...

To explore the influence of contextual factors on health-related quality of life (HRQoL), which is sometimes used as an indicator of quality of care, we examined the association of neighborhood socioeconomic status (NSES) and trajectories of HRQoL after hospitalization for acute coronary syndromes (ACS).We studied 1481 patients hospitalized with acute coronary syndromes in Massachusetts and Georgia querying HRQoL via the mental and physical components of the 36-item short-form health survey (SF-36) (MCS and PCS) and the physical limitations and angina-related HRQoL subscales of the Seattle Angina Questionnaire (SAQ) during hospitalization and at 1-, 3-, and 6-month postdischarge. We categorized participants by tertiles of the neighborhood deprivation index (a residence-census tract-based measure) to examine the association of NSES with trajectories of HRQoL after adjusting for individual socioeconomic status (SES) and clinical characteristics.Participants had mean age 61.3 (SD, 11.4) years; 33% were female; 76%, non-Hispanic white; 11.2% had household income below the federal poverty level. During 6 months postdischarge, living in lower NSES neighborhoods was associated with lower mean PCS scores (1.5 points for intermediate NSES; 1.8 for low) and SAQ scores (2.4 and 4.2 points) versus living in high NSES neighborhoods. NSES was more consequential for patients with lower individual SES. Individuals living below the federal poverty level had lower average MCS and SAQ physical scores (3.7 and 7.7 points, respectively) than those above.Neighborhood deprivation was associated with worse health status. Using HRQoL to assess quality of care without accounting for individual SES and NSES may unfairly penalize safety-net hospitals.

The objectives of this longitudinal study were to examine differences between whites and blacks, and across two geographical regions, in the socio-demographic, clinical, and psychosocial characteristics, hospital treatment practices, and post-discharge mortality for hospital survivors of an acute coronary syndrome (ACS). In this prospective cohort study, we performed in-person interviews and medical record abstractions for patients discharged from the hospital after an ACS at participating sites in Central Massachusetts and Central Georgia during 2011–2013. Among the 1143 whites in Central Massachusetts, 514 whites in Central Georgia, and 277 blacks in Central Georgia, we observed a gradient of socioeconomic position with whites in Central Massachusetts being the most privileged, followed by whites and then blacks from Central Georgia; similar gradients pertained to psychosocial vulnerability (e.g., 10.7%, 25.1%, and 49.1% had cognitive impairment, respectively) and to the hospital receipt of all 4 evidence-based cardiac medications (35.5%, 18.1%, and 14.4%, respectively) used in the acute management of patients hospitalized with an ACS. Multivariable adjusted odds ratios (95% confidence intervals) for the receipt of a percutaneous coronary intervention for whites and blacks in Georgia vs. whites in Massachusetts were 0.57 (0.46–0.71) and 0.40(0.30–0.52), respectively. Thirty-day and one-year mortality risks exhibited a similar gradient. The results of this contemporary clinical/epidemiologic study in a diverse patient cohort suggest that racial and geographic disparities continue to exist for patients hospitalized with an ACS., Highlights • We observed a gradient of socio-economic position, treatment practices, and dying. • Interplay of race and place with treatment practices and post discharge outcomes. • Racial and geographic disparities continue to exist for patients after an ACS.

Objectives Oral anticoagulants are the cornerstone of stroke prevention in high-risk patients with atrial fibrillation (AF). Geriatric elements, such as cognitive impairment and frailty, commonly occur in these patients and are often cited as reasons for not prescribing oral anticoagulants. We sought to systematically assess geriatric impairments in patients with AF and determine whether they were associated with oral anticoagulant prescribing. Design Cross-sectional analysis of baseline data from the ongoing Systematic Assessment of Geriatric Elements in Atrial Fibrillation (SAGE-AF) prospective cohort study. Setting Multicenter study with site locations in Massachusetts and Georgia that recruited participants from cardiology, electrophysiology, and primary care clinics from 2016 to 2018. Participants Participants with AF age 65 years or older, CHA2 DS2 -VASc (congestive heart failure; hypertension; aged ≥75 y [doubled]; diabetes mellitus; prior stroke, transient ischemic attack, or thromboembolism [doubled]; vascular disease; age 65-74; female sex) score of 2 or higher, and no oral anticoagulant contraindications (n = 1244). Measurements A six-component geriatric assessment included validated measures of frailty, cognitive function, social support, depressive symptoms, vision, and hearing. Oral anticoagulant use was abstracted from the medical record. Results A total of 1244 participants (mean age = 76 y; 49% female; 85% white) were enrolled; 42% were cognitively impaired, 14% frail, 53% pre-frail, 12% socially isolated, and 29% had depressive symptoms. Oral anticoagulants were prescribed to 86% of the cohort. Oral anticoagulant prescribing did not vary according to any of the geriatric elements (adjusted odds ratios [ORs] for oral anticoagulant prescribing and cognitive impairment: OR = .75; 95% confidence interval [CI] = .51-1.09; frail OR = .69; 95% CI = .35-1.36; social isolation OR = .90; 95% CI = .52-1.54; depression OR = .79; 95% CI = .49-1.27; visual impairment OR = .98; 95% CI = .65-1.48; and hearing impairment OR = 1.05; 95% CI = .71-1.54). Conclusion Geriatric impairments, particularly cognitive impairment and frailty, were common in our cohort, but treatment with oral anticoagulants did not differ by impairment status. These geriatric impairments are commonly cited as reasons for not prescribing oral anticoagulants, suggesting that prescribers may either be unaware or deliberately ignoring the presence of these factors in clinical settings. J Am Geriatr Soc 68:147-154, 2019.

Objective The disease process in rheumatoid arthritis (RA) starts years before the clinical diagnosis is made, and elevated levels of disease-specific autoantibodies can be detected during this period. Early responses to known or novel autoantigens likely drive the eventual production of pathogenic autoimmunity. Importantly, the presence of disease-specific autoantibodies can identify individuals who are at high risk of developing RA but who do not currently have arthritis. The goal of the current study was to characterize plasmablasts from individuals at risk of developing RA. Methods We investigated antibody-secreting plasmablasts derived from a well-characterized cohort of individuals who were at risk of developing RA, based on RA-related serum autoantibody positivity, as compared to patients with early (

The prevalence of obesity is increasing in young people in the United States. Lately, low-grade inflammation is recognized as accompanying obesity, a known risk factor for type 2 diabetes. Autonomic dysfunction is a prominent feature of adult diabetes, but its prevalence in adolescents in prediabetic states or with diabetes risk factors is unknown. We undertook to study obesity, inflammation, insulin resistance, and autonomic dysfunction together in a population of adolescents aged 13-18 years.Subjects gave a blood sample for cytokine analysis and a 5-min resting EKG for analysis of resting heart rate variability. TNF-α, IL-6, c-reactive protein (CRP), MCP-1, and IL-10 were analyzed by enzyme-linked immunosorbent assay, and Fourier Transform was applied to electrocardiographic recordings of R-R intervals for analysis in frequency space. The HOMA calculation was used as an index of insulin sensitivity.TNF-α, IL-6, CRP, MCP-1, HOMA, and insulin levels, but not serum glucose or IL-10, were higher in the obese subjects. Low-frequency (0.04-0.15 Hz) and high-frequency (0.15-0.4 Hz) fluctuations of R-R intervals were lower in the obese subjects, but the normalized low-frequency power was not different, suggesting proportional reduction in variability in both ranges and impairment of both sympathetic and parasympathetic systems.Chronic low-grade inflammation, insulin resistance, and autonomic dysfunction are present at an early age in obese youths; early detection of inflammation may facilitate meaningful lifestyle changes in this high-risk group.

Background As adults live longer, multiple chronic conditions have become more prevalent over the past several decades. We describe the prevalence of, and patient characteristics associated with, cardiac- and non-cardiac-related multimorbidities in patients discharged from the hospital after an acute coronary syndrome. Methods We studied 2174 patients discharged from the hospital after an acute coronary syndrome at 6 medical centers in Massachusetts and Georgia between April 2011 and May 2013. Hospital medical records yielded clinical information including presence of eight cardiac-related and eight non-cardiac-related morbidities on admission. We assessed multiple psychosocial characteristics during the index hospitalization using standardized in-person instruments. Results The mean age of the study sample was 61 years, 67% were men, and 81% were non-Hispanic whites. The most common cardiac-related morbidities were hypertension, hyperlipidemia, and diabetes (76%, 69%, and 31%, respectively). Arthritis, chronic pulmonary disease, and depression (20%, 18%, and 13%, respectively) were the most common noncardiac morbidities. Patients with ≥4 morbidities (37% of the population) were slightly older and more frequently female than those with 0-1 morbidity; they were also heavier and more likely to be cognitively impaired (26% vs 12%), have symptoms of moderate/severe depression (31% vs 15%), high perceived stress (48% vs 32%), a limited social network (22% vs 15%), low health literacy (42% vs 31%), and low health numeracy (54% vs 42%). Conclusion Multimorbidity, highly prevalent in patients hospitalized with an acute coronary syndrome, is strongly associated with indices of psychosocial deprivation. This emphasizes the challenge of caring for these patients, which extends well beyond acute coronary syndrome management.