tbuckley/cabot-search huggingface dataset:
How Would You Manage This Patient With Gout?
Authors: Risa B. Burns, C. Christopher Smith, Robert H. Shmerling, Anjala Tess
Journal: Annals of Internal Medicine (2018)

Gout is the most common form of inflammatory arthritis. In 2012, the American College of Rheumatology (ACR) issued a guideline, which was followed in 2017 by one from the American College of Physicians (ACP). The guidelines agree on treating acute gout with a corticosteroid, nonsteroidal anti-inflammatory drug, or colchicine and on not initiating long-term urate-lowering therapy (ULT) for most patients after a first gout attack and in those whose attacks are infrequent (<2 per year). However, they differ on treatment of both recurrent gout and problematic gout. The ACR advocates a “treat-to-target” approach, and the ACP did not find enough evidence to support this approach and offered an alternative strategy that bases intensity of ULT on the goal of avoiding recurrent gout attacks (“treat-to-avoid-symptoms”) with no monitoring of urate levels. They also disagree on the role of a gout-specific diet. Here, a general internist and a rheumatologist discuss these guidelines; they debate how they would manage an acute attack of gout, if and when to initiate ULT, and the goals for ULT. Lastly, they offer specific advice for a patient who is uncertain about whether to begin this therapy.
Health-related quality of life (HRQoL) in MONARCH 2: Abemaciclib plus fulvestrant in women with HR+, HER2- advanced breast cancer (ABC) who progressed on endocrine therapy.
Authors: Peter A. Kaufman, Masakazu Toi, Patrick Neven, Joohyuk Sohn, Gregory L Price, Yong Lin, Mark Boye, Li Li, Jonathon Gable, Gebra Cuyun Carter, George W. Sledge
Journal: Journal of Clinical Oncology (2018)

1049 Background: Compared to placebo (P) + fulvestrant (F), the MONARCH 2 HR+, HER2- ABC trial showed abemaciclib + F significantly improved PFS and ORR with a generally tolerable safety profile. Here, patient-reported HRQoL, functioning, and symptoms are reported. Methods: Study details were previously reported (Sledge et al. 2017). Data from the modified Brief Pain Inventory short form (mBPI-sf), EORTC QLQ-C30 and EORTC BR23 were collected at baseline, cycle 2 (C2), every 2 cycles from C3 - C13, and then every 3 cycles until short term follow up. Time to worsening (TTW) of pain (≥2 point increase of "worst pain" or ≥ 1 level increase of WHO analgesic class) were analyzed by Cox model. Change from baseline for EORTC QLQ-C30 and BR23 subscales and mBPI-sf were analyzed by mixed model. Differences of change from baseline (for each and across all visits) between arms were analyzed. Results: PRO completion rates were > 85% for baseline and on-treatment visits; duration of treatment was longer for abemaciclib + F patients (median 15 vs 9 cycles). The TTW for pain was similar between abemaciclib + F and P + F arms (HR = 0.900; p = .4005). No clinical and statistical significance was observed in the EORTC QLQ-C30 and BR23 function and symptom scales or the mBPI-sf; exceptions were higher diarrhea, appetite loss (AL) and nausea/vomiting (N/V) in the abemaciclib + F arm, which were consistent with reported adverse events (AE). The by-cycle analysis showed these higher mean symptom scores were transient for AL and NV, which increased in the first few cycles then gradually returned to near-baseline after cycle 7. Mean diarrhea scores returned to near-baseline levels post-therapy. Conclusions: In addition to significantly improved PFS and ORR, abemaciclib + F did not show statistically significant and clinically meaningful differences in patient-reported global health, functioning, or most symptoms compared to P + F. Increased GI-related symptoms were transient and consistent with the manageable, reversible AE profile; the highest symptom burden was reported during early visits. Clinical trial information: NCT02107703.
Cost‐effectiveness analysis of imaging strategy for an intensive follow‐up of patients with American Joint Committee on Cancer stage <scp>IIB</scp> , <scp>IIC</scp> and <scp>III</scp> malignant melanoma
Authors: S. Podlipnik, D. Moreno‐Ramírez, C. Carrera, A. Barreiro, E. Manubens, L. Ferrandiz‐Pulido, M. Sánchez, S. Vidal‐Sicart, J. Malvehy, S. Puig
Journal: British Journal of Dermatology (2018)

Many follow‐up guidelines for patients with high‐risk melanoma include expensive imaging studies, serum biomarkers and regular visits to the dermatologist, with little attention to cost‐effectiveness. To establish the cost‐effectiveness of chest–abdomen–pelvis computed tomography (CT) and brain magnetic resonance imaging (MRI) in a follow‐up protocol for patients at high risk of relapse. This was a prospective single‐centre cohort study of 290 patients with clinicopathological American Joint Committee on Cancer (AJCC) stage IIB, IIC and III melanoma. Patients had a body CT scan and brain MRI every 6 months and were withdrawn from the study after completing a 5‐year follow‐up or when metastases were detected. A cost‐effectiveness analysis for each follow‐up radiological procedure was performed. Patients underwent 1805 body CT scans and 1683 brain MRIs. Seventy‐six metastases (26·2%) were identified by CT or MRI. CT scan was cost‐effective in the first 4 years (cost‐effectiveness ratio €4710·70–€14 437·10/patient with metastasis); brain MRI was cost‐effective during the first year (cost‐effectiveness ratio €14 090·60/patient with metastasis). Limitations included lack of survival analysis and comparisons with willingness‐to‐pay thresholds. Six‐monthly CT scan of the chest, abdomen and pelvis is a cost‐effective technique for the early detection of metastases in the first 4 years of follow‐up in patients with AJCC stage IIC and III melanoma, and in the first 3 years in patients with AJCC stage IIB melanoma. In addition, brain MRI has been shown to be cost‐effective only in the first year of follow‐up in patients with AJCC stage IIC and III melanoma.
PE-PCR, a novel method for detection of mutations in blood-cell-free DNA.
Authors: Ovidiu Platica, Mikhail Khazan, Manuel Martinez
Journal: Journal of Clinical Oncology (2012)

e12016 Background: During the past few years, the “personalized” therapy based on specific tumor molecular alterations has become the standard of care of cancer patients . Recently, it has been shown that blood DNA is released from normal as well as tumor cells as a high molecular weight nucleic acid and carries the same genetic abnormalities as the cells of origin. However, the identification of these DNA alterations is difficult since the blood tumor DNA is found in very low concentration and it is mixed with a huge amount of normal homologous DNA. Therefore, most methods able to detect such abnormalities in cells are not applicable for blood cell free DNA. We report here a simple novel technology for mutation detection in blood DNA. Methods: The serum DNA is subject to two PCR rounds; in the first round, only DNA fragments containing the mutation are amplified by an extension primer encoding the mutation at its 3’ terminus. The DNA is then re-amplified by nested PCR for 40 cycles and the extension of mutated primer is detected by gel electrophoresis. The method was tested with DNA from the human lung cancer cell line A549 (ATCC # CCL-185) and was found to detect mutations in the presence of 10 12 [OP1] fold excess of normal DNA. Results: The sera from 10 patients with localized and metastatic lung (6) and pancreatic carcinomas (4) were tested for the presence of mutations in Kras and P53 genes. Seven patients had a mutation in a least one gene. Eleven patients without any clinical evidence of cancer tested negative. Conclusions: PE-PCR is a simple sensitive method for mutation detection in blood cell-free DNA, requiring only one ml blood and less than a 48 hour work. This method can potentially be used for mutation detection in most of the genes of clinical interest, as a non-invasive research tool, for early detection of tumor recurrence and possibly for early diagnosis of cancer when surgery can be curative.
Comparison of chemotherapy use, cost, and survival in patients with metastatic colorectal cancer in Western Washington and British Columbia.
Authors: Todd Yezefski, Dan Le, Leo Chen, Jeremy Snider, Caroline Speers, Sharlene Gill, Hagen F. Kennecke, Veena Shankaran
Journal: Journal of Clinical Oncology (2018)

LBA3579 Background: Few studies have directly compared health care utilization, costs, and outcomes between geographically similar patients (pts) treated in the U.S.’ multi-payer health system versus Canada’s single-payer system. Using cancer registry and claims data, we assessed systemic therapy (ST) use, cost, and survival for metastatic colorectal cancer (mCRC) pts in Western Washington (WW) and British Columbia (BC). Methods: Pts age ≥ 18 diagnosed with mCRC in 2010 and later were identified from 1) the BC Cancer Agency database and 2) a regional database linking WW SEER to claims from two large commercial insurers. Demographic and treatment characteristics for the two populations were compared using two-sample T tests. ST costs (first-line and lifetime) were expressed as mean per patient per month costs; Canadian costs were expressed in US dollars using the Purchasing Power Parity for Health in 2009. Median survival was reported for both populations. Results: 1622 BC pts and 575 WW pts were included in the analysis. BC pts were more likely to be older (median age 60 vs 66) and male (57% vs 48%, p = &lt; 0.01). A greater proportion of WW versus BC pts received ST (79% vs. 68%, p &lt; 0.01). FOLFIRI plus bevacizumab was the most common first-line regimen in BC (32%) while FOLFOX was the most common first-line regimen in WW (39%). The mean monthly cost of first-line therapy per patient was significantly higher in WW than BC ($12,345 vs $6,195, p = &lt; 0.01), and this was true for all regimens assessed. Mean lifetime monthly ST costs were significantly higher in WW ($7,883 vs $4,830, p = &lt; 0.01). There was no difference in median overall survival between populations among those receiving ST (21.4 months (95% CI 18.0-26.2) in WW and 22.1 months (20.5-23.7) in BC) or among those not receiving ST (5.4 months (2.4-7.7) WW versus 6.3 months (5.2-7.3) BC). Conclusions: Utilization and cost of ST for mCRC was significantly higher for patients in WW compared to BC without differences in overall survival in treated and untreated patients.
Anesthesia Care Handovers and Risk of Adverse Outcomes
Authors: Jesse M. Ehrenfeld, Jonathan P. Wanderer, Warren S. Sandberg
Journal: JAMA (2018)

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Chemoprevention of esophageal cancer with esomeprazole and aspirin therapy: Efficacy and safety in the phase III randomized factorial ASPECT trial.
Authors: Janusz Jankowski, John de Caestecker, Sharon Love, Gavin Reilly, Yeng Ang, Krish Ragunath, Arthur Tucker, Ian Penman, Colin Rodgers, Emma Roffe, Claire E. Brooks, Stephen Attwood, Danielle Morris, Rebecca Harrison, Pradeep Bhandari, Peter Watson, Scott Sanders, Hugh Barr, Paul Moayyedi, James Neale
Journal: Journal of Clinical Oncology (2018)

LBA4008 Background: Esophageal adenocarcinoma (EA) is the sixth most common cause of global cancer death. We rely on endoscopy screening to identify and monitor patients with Barrett’s esophagus (BE) and find neoplastic lesions early enough to manage their EA. This approach has a modest effect on EA supported by low quality evidence. We evaluated the efficacy of aspirin and high dose acid suppression in preventing EA in patients with BE. Methods: We recruited patients with ≥ 1cm of BE and no high grade dysplasia (HGD) or EA at baseline in UK and Canadian hospitals. To conceal allocation, a central trials unit randomized patients using a computer-generated schedule. Patients were randomized unblinded 1:1:1:1 in a 2X2 factorial design to high dose (40mg twice daily) or low dose (20mg once daily) esomeprazole proton pump inhibitor acid suppression (PPI), alone or combined with low dose aspirin 300mg/day (330mg in Canada). The primary composite endpoint was time to all-cause mortality or EA or HGD analyzed using accelerated failure time modelling adjusting for minimization factors (age, length of Barrett’s esophagus and presence of intestinal metaplasia). Results: We recruited 2563 Barrett’s patients followed-up for a median of 8.9 years (interquartile range 8.2-9.8) with 20,095 years of follow up. There were 313 events of the composite primary endpoint. High dose PPI was statistically significantly superior to low dose PPI (p = 0.037, N = 2535, time ratio (TR) 1.27, 95% CI = 1.01-1.58). Aspirin therapy showed a trend to benefit but was not statistically significant (p = 0.068, N = 2280, TR = 1.24, 95% CI = 0.98 – 1.57). The combination of aspirin with high dose PPI had the strongest effect compared to low dose PPI with no aspirin (TR = 1.59, 95% CI = 1.14 to 2.23, p = 0.007). There were few serious adverse events reported (1.0% of patients), with 99.9% data collected. Conclusions: This is the largest randomized controlled chemoprevention trial in patients with Barrett’s esophagus. We have shown that PPI high dose and aspirin chemoprevention therapy, especially in combination significantly reduces rates of death, EA or HGD occurrence and is safe. Clinical trial information: 2004-003836-77.
Aerobic Exercise and Resting Blood Pressure in Older Adults: A Meta-Analytic Review of Randomized Controlled Trials
Authors: George A. Kelley, Kristi S. Kelley
Journal: Circulation (2001)

P98     OBJECTIVE: Use the meta-analytic approach to examine the  effects of aerobic exercise on resting systolic and diastolic blood  pressure in older adults. METHODS: Studies were retrieved from (1)  computer searches (MEDLINE, Current Contents, Sport Discus), (2)  cross-referencing from bibliographies of retrieved studies and review  articles, and (3) expert review of reference list. Inclusion criteria  for this study were (1) randomized trials, (2) aerobic activity as the  only intervention, (3) nonexercise control group included, (4) changes  in resting systolic and/or diastolic blood pressure assessed, (5)  within study ages of subjects ≥ 50 years, (6) English-language  studies published in journals between January 1966 and January 1998.  All studies were coded by both authors, independent of each other. The  authors then met and reviewed every item coded. Discrepancies were  resolved by consensus. Net changes in blood pressure were calculated as  the exercise minus control group difference. RESULTS: A total of 14  primary outcomes were derived from 7 studies. Using a random-effects  model, decreases of approximately 2% and 1% were found for resting  systolic and diastolic blood pressure, respectively, with only changes  in systolic blood pressure statistically significant (systolic,  mean ± SD = -2 ± 3 mmHg, 95% confidence interval  = -4 to -1; diastolic, mean ± SD = -1 ± 2 mmHg, 95%  confidence interval = -2 to 0 mmHg). No statistically significant  publication bias was observed for changes in either resting systolic or  diastolic blood pressure. Regression analyses revealed a statistically  significant association between changes in resting systolic blood  pressure and initial systolic blood pressure (R = 0.73, SEE =  0.57, p = 0.003). Changes in blood pressure were independent of  changes in body weight, body fat, and body mass index. CONCLUSIONS:  Aerobic exercise is efficacious for reducing resting  systolic blood pressure in older adults. However, a need exists for  additional studies that address the effectiveness of this  intervention for reducing resting blood pressure in older  adults.
Rare variants in Fanconi anemia genes are enriched in acute myeloid leukemia
Authors: Kyaw Ze Ya Maung, Paul J. Leo, Mahmoud Bassal, Debora A. Casolari, James X Gray, Sarah C. Bray, Stephen Pederson, Deepak Singhal, Saumya E. Samaraweera, Tran Nguyen, Gökhan Cildir, Mhairi Marshall, Adam Ewing, Emma L. Duncan, Matthew A. Brown, Russell Saal, Vinay Tergaonkar, Luen Bik To, Paula Marlton, Devinder Gill, Ian Lewis, Andrew J Deans, Anna L Brown, Richard J D’Andrea, Thomas J Gonda
Journal: Blood Cancer Journal (2018)

Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy caused by somatically acquired changes affecting a well-defined set of genes1. While rare high-risk variants affecting specific transcription factors account for a proportion of myelodysplastic syndrome (MDS) and AML associated with a family history, the contribution of other germline variants conferring low-intermediate risk has not yet been determined, partly because these are more difficult to identify from pedigree analysis. Here we use an Australian AML patient cohort to analyze rare, deleterious variants affecting genes involved in the rare recessive bone marrow failure syndrome Fanconi Anemia (FA). FA is caused by bi-allelic germline mutations in any of the 22 FANC genes (except for FANCB and FANCR which are X-linked and autosomal dominant), and is associated with profoundly increased risk of AML. The proteins encoded by the FANC genes participate in the removal of interstrand crosslinks (ICL) and the protection and resolution of stalled replication forks, an essential step for faithful DNA replication. Deficiency for these genes, combined with other mutations, results in pre-leukemia or leukemia in mouse models.
Comparison of two breast cancer survivorship treatment summary and care plan (TSCP) documents.
Authors: Eileen Williams, Andrew Borgert, Linda Kay Peterson, Leah L. Dietrich
Journal: Journal of Clinical Oncology (2018)

49 Background: The 2005 Institute of Medicine report recommended providing a cancer TSCP, but barriers including time needed to complete these documents led to limited implementation. In 2014, in order to facilitate delivery, ASCO released a streamlined version of a TSCP. The current prospective, randomized study compares a Breast Cancer ASCO 2014 derived template (concise TSCP) with a facility derived Breast Cancer TSCP template based on the “old” ASCO version and NCCN guideline recommended elements (detailed TSCP). Methods: Female breast cancer survivors who completed therapy at Gundersen Health System were randomized between a concise TSCP and a detailed TSCP. Subjects received a survey prior to their survivorship visit assessing their baseline knowledge of their breast cancer diagnosis and treatment (pre visit knowledge). After the visit, participants completed the same survey (post visit knowledge) and a satisfaction survey. Pre and post visit knowledge survey scores, patient satisfaction scores and time needed to complete the TSCP were compared between the two study groups. Results: Both TSCP groups showed significant improvement in patient-specific disease and treatment knowledge scores (% of applicable knowledge questions answered correctly) after their survivorship visit. There was no significant difference between the concise and detailed groups’ pre-visit knowledge score (mean 78% vs. 79%, p=0.88). Calculated difference between the groups’ post knowledge scores met the pre-determined threshold for non-inferiority (p=0.013). Conclusions: Our study demonstrates the value of a cancer TSCP and Survivorship visit in improving breast cancer survivors’ knowledge of their disease characteristics and treatment. The concise version was found to be non-inferior to the detailed TSCP in terms of patient knowledge and satisfaction and required less time to complete. These results assist us and other institutions in choosing a more streamlined version of TSCP without compromising patient knowledge or satisfaction. [Table: see text]
The Impact of Targeted Rheumatoid Arthritis Pharmacologic Treatment on Mental Health
Authors: Faith Matcham, James Galloway, Matthew Hotopf, Emmert Roberts, Ian C. Scott, Sophia Steer, Sam Norton
Journal: Arthritis & Rheumatology (2018)

Rheumatoid arthritis ( RA ) pharmacotherapy may impact mental health outcomes by improving pain and stiffness, potentially by targeting inflammatory processes common to RA and depression. The objectives of this review were to ascertain the frequency of mental health assessments in RA pharmacotherapy trials, quantify the efficacy of RA pharmacotherapy for mental health outcomes, and explore the clinical and demographic factors related to mental health outcomes. Effective pharmacotherapy alone is unlikely to substantially improve mental health outcomes in most patients with RA. Integrated mental health care provided within routine clinical practice is essential to optimize mental and physical health outcomes.
Brief Report: Tubulointerstitial Damage in Lupus Nephritis: A Comparison of the Factors Associated With Tubulointerstitial Inflammation and Renal Scarring
Authors: Alejandra Londoño Jimenez, Wenzhu B. Mowrey, Chaim Putterman, Jill Buyon, Beatrice Goilav, Anna Broder
Journal: Arthritis & Rheumatology (2018)

To characterize and compare the factors associated with tubulointerstitial inflammation (TII) and tubulointerstitial scarring, defined as interstitial fibrosis and/or tubular atrophy (IF/TA), in patients with lupus nephritis (LN).We identified systemic lupus erythematosus patients who had renal biopsy results consistent with LN between 2005 and 2017. Clinical data were collected from medical records. Multivariable logistic regression models were fitted to assess factors associated with TII and with IF/TA (moderate-to-severe versus none/mild).Of 203 LN patients included, 41 (20%) had moderate-to-severe TII, 45 (22%) had moderate-to-severe IF/TA, and 21 (10%) had both. Multivariable logistic regression models showed that moderate-to-severe TII was associated with a shorter disease duration, African American race, proliferative LN, and an estimated glomerular filtration rate (eGFR) of <60 ml/minute/1.73 m2 at the time of biopsy. Hydroxychloroquine use was associated with significantly lower odds of moderate-to-severe TII (odds ratio 0.27 [95% confidence interval 0.10-0.70], P = 0.008). Similar to TII, factors associated with moderate-to-severe IF/TA included proliferative LN and eGFR <60 ml/minute/1.73 m2 at the time of biopsy. In addition, the presence of moderate-to-severe TII and older age was associated with moderate-to-severe IF/TA. None of the routinely available serologic markers-including anti-double-stranded DNA antibodies, anti-Ro/La antibodies, and low complement-were associated with tubulointerstitial damage.The use of hydroxychloroquine was strongly associated with less inflammation, while the presence of TII, proliferative LN, and low eGFR were major determinants of tubulointerstitial scarring. Identifying modifiable factors is critical for the development of better preventive and therapeutic strategies with the goal of improving survival in patients with lupus-related kidney disease.