tbuckley/cabot-search huggingface dataset:
Abstract 14373: Treatment Trends Among High Cardiovascular Disease Risk Patients Treated With Lipid-lowering Therapies: A United States Real-world Study
Authors: Ruben G Quek, Kathleen M Fox, Li Wang, Lu Li, Shravanthi R Gandra, Nathan D Wong
Journal: Circulation (2015)

Introduction: Strong evidence exists linking LDL-C as a causal factor of atherosclerotic CVD. Statins are the cornerstone for lipid lowering therapy (LLT) so it is important to understand treatment trends in light of current guidelines. Objective: To evaluate LLT trends in a US real-world setting. Methods: Patients (aged ≥18y) who initiated LLT (statins and/or ezetimibe) from 01/01/2007-06/30/2011 were retrospectively identified from IMS commercial claims. Patients were classified into two cohorts: 1) Prior CVD and 2) Prior CHD RE conditions [Definitions in Figure 1] and stratified by age group (&lt;65 and ≥65y). Eligible patients had continuous health plan enrollment for ≥1 year pre- and post-index date (LLT initiation date). The following were assessed: index statin intensity (defined by ACC/AHA 2013 guidelines), first treatment modification (e.g., switch, re-initiation after temporary discontinuation of &gt;60 days, permanent discontinuation of all LLT) and time-to-first treatment modification. Results: A total of 41,934 patients with prior CVD (mean age: 58y) and 170,344 patients with CHD RE (mean age: 57y) were analyzed. From 2007-2011, 66.6-77.8% and 8.8-25.1% of the cohorts were prescribed moderate-intensity and high-intensity statins, respectively, on the index date. Among the CVD and CHD RE cohorts, 18.8% and 26.2% reinitiated index LLT, 11.6% and 13.2% permanently discontinued all LLT and 19.5% and 13.6% switched to a different statin, respectively, as the first treatment modification (Figure 1). A similar trend was observed among patients aged ≥65y. Average number of days to first treatment modification was 130-399 days. Conclusion: With 79% of patients modifying their index LLT, of which 12-13% permanently discontinuing all LLT, such treatment modifications may potentially be indicative of index statin intolerability and/or ineffectiveness. High-intensity statin therapy initiation is low, potentially resulting in residual risk of CVD.
How Do Symptoms And Comorbidities Affect Healthcare Costs In Patients With COPD? Results From The New German Cosyconet Cohort
Authors: Margarethe E. Wacker, Rudolf A. Jörres, Holger Schulz, Joachim Heinrich, Stefan Karrasch, Annika Karch, Armin Koch, Reiner Leidl, Claus Vogelmeier, Rolf Holle
Journal: American Journal of Respiratory and Critical Care Medicine (2016)
Systematic review and meta-analysis of the effect of pre-operative PET/PET-CT in the management of patients with potentially resectable colorectal cancer liver metastasis.
Authors: Pablo Emilio Serrano Aybar, Julian Felipe Daza, Natalie Solis, Sameer Parpia, Steven Gallinger, Carolanne Moulton
Journal: Journal of Clinical Oncology (2018)

591 Background: It has been proposed that PET with 18F-fluorodeoxyglucose alone or combined with CT improves detection of extra hepatic disease in the setting of colorectal cancer liver metastasis (CRLM). However, there remains conflicting evidence on the added benefit of PET/PET-CT prior to liver resection, and its effect on long-term survival. Thus, we set out to perform a systematic review of literature and meta-analysis. Methods: From 2000 to April 2017, MEDLINE, EMBASE, and CENTRAL were searched for studies (prospective and retrospective) investigating the preoperative use of PET/PET-CT in the management of patients with CRLM. We excluded studies in which neoadjuvant chemotherapy was given 2 weeks prior to PET/PET-CT. Screening, data abstraction, and quality assessment was performed in duplicate. Primary outcome was overall survival (OS). Secondary outcomes included disease-free survival (DFS), pre-operative change in surgical management, and open-close surgery. Random effect models were used to pool treatment effects. The protocol was published in PROSPERO. Results: Of 4034 articles reviewed, 37 met the inclusion criteria and were analyzed, and 8 compared PET/PET-CT to conventional imaging. All studies included PET (n=18), PET-CT (n=17), or both (n=2). OS for all patients was similar whether or not pre-operative staging included PET/PET-CT (HR 0.94, 95% CI 0.69-1.26). A similar effect was seen in the subgroup of patients who underwent surgery (HR 0.92, 95% CI 0.72-1.17). DFS in patients who underwent surgery was not different either (HR 0.93, 95% CI 0.81-1.08). PET/PET-CT reduced the odds of undergoing an open-close surgery (OR 0.52, 95% CI 0.35-0.76) and changed the surgical management of 23.4% patients (95% CI 19.33-27.47), however heterogeneity (I 2 =100%). Conclusions: Pre-operative PET/PET-CT may have a meaningful impact on surgical decision making in CRLM, however heterogeneity between studies is high, likely due to different study designs. It may also reduce the rate of open-close surgeries. The addition of PET/PET-CT to routine pre-operative imaging does not improve OS or DFS.
Institutional practice patterns for the use of neoadjuvant systemic therapy for breast cancer: A retrospective analysis.
Authors: Lara Zibdawi, Demetrios Simos, Shaqil Nadirali Kassam, Amira Rana, Farrah Kassam, Yasmin Rahim
Journal: Journal of Clinical Oncology (2018)

e12637 Background: Neoadjuvant systemic therapy (NAST) has traditionally been used in patients (pts) with locally advanced breast cancer (LABC). An increasing number of pts with early-stage operable breast cancer (ESOBC) possessing high risk features (triple negative, HER2+) are now being offered the option of NAST. There is a paucity of real life data describing the contemporary use of NAST for ESOBC and LABC pts. Objectives: To describe the institutional practice patterns on the use of NAST and to determine if there has been a meaningful change in practice at a large Canadian Community Cancer Centre. Methods: A retrospective chart analysis of all pts diagnosed with breast cancer (BC) between May 1, 2010 and October 31, 2016 who went on to receive NAST. Descriptive statistics were used to summarize and present data. Results: 1,979 pts with a new diagnosis of BC were identified, 154 (7.8%) had NAST and 146 (94.8%) were eligible for data extraction and analysis. The proportion of pts receiving NAST increased from 4.5% in 2010 to 7.1% in 2016. Of the 146 pts receiving NAST, 6.2% were identified as having ESOBC. Pts who received NAST were generally younger, had fewer comorbidities, larger primary tumors, axillary adenopathy, higher tumor grade, and hormone receptor (HR) positive disease. Pathological complete response rates were as follows: 56.3% in HR-/HER2+, 37.9% in HR+/HER2+, 29.3% in triple negative, and 5.0% in HR+/HER2-. Breast conserving surgery (BCS) increased modestly over the study time period, with 17.1% receiving this limited surgery. However, there was a 36.4% decrease in the rate of axillary lymph node dissection (ALND) for pts with clinical N1 (cN1) disease. Conclusions: There has been a modest increase in the use of NAST at our institution over the study period. We believe this is likely a reflection of increasing case discussions at our multidisciplinary meetings. In our data set, the rate of post-NAST mastectomies has changed little but more women appear to have been spared from undergoing more extensive axillary surgery.
Child obesity plan must include legal action on junk food advertising and discounts, say MPs
Authors: Adrian O’Dowd
Journal: BMJ (2018)

Tougher action is needed as part of fresh efforts to reduce childhood obesity, including a wider approach across government departments and more direct interventions such as restrictions on advertising and price promotions, MPs have said.

In a report published on 30 May,1 MPs on the parliamentary health and social care committee emphasised the need for childhood obesity to be seen as everyone’s business. Current estimates suggest that almost a third of children aged 2 to 15 are overweight or obese in the UK and that younger generations are becoming obese earlier and staying obese for longer.

A refreshed version of the childhood obesity plan first published in 20162 is expected to be published by the …
The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer’s disease
Authors: Paul J. Cheng-Hathaway, Erin G. Reed-Geaghan, Taylor R. Jay, Brad T. Casali, Shane M. Bemiller, Shweta S. Puntambekar, Victoria E. von Saucken, Roxanne Y. Williams, J. Colleen Karlo, Miguel Moutinho, Guixiang Xu, Richard M. Ransohoff, Bruce T. Lamb, Gary E. Landreth
Journal: Molecular Neurodegeneration (2018)

The R47H variant of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) confers greatly increased risk for Alzheimer's disease (AD), reflective of a central role for myeloid cells in neurodegeneration. Understanding how this variant confers AD risk promises to provide important insights into how myeloid cells contribute to AD pathogenesis and progression.In order to investigate this mechanism, CRISPR/Cas9 was used to generate a mouse model of AD harboring one copy of the single nucleotide polymorphism (SNP) encoding the R47H variant in murine Trem2. TREM2 expression, myeloid cell responses to amyloid deposition, plaque burden, and neuritic dystrophy were assessed at 4 months of age.AD mice heterozygous for the Trem2 R47H allele exhibited reduced total Trem2 mRNA expression, reduced TREM2 expression around plaques, and reduced association of myeloid cells with plaques. These results were comparable to AD mice lacking one copy of Trem2. AD mice heterozygous for the Trem2 R47H allele also showed reduced myeloid cell responses to amyloid deposition, including a reduction in proliferation and a reduction in CD45 expression around plaques. Expression of the Trem2 R47H variant also reduced dense core plaque number but increased plaque-associated neuritic dystrophy.These data suggest that the AD-associated TREM2 R47H variant increases risk for AD by conferring a loss of TREM2 function and enhancing neuritic dystrophy around plaques.
Concussion in sport: best from Berlin, direction from Dublin and gems from gridiron
Authors: Michael Makdissi, Jon Patricios
Journal: British Journal of Sports Medicine (2018)

Sports-related concussion (SRC) is one of the most important medical issues in contact and collision sports around the world. The NFL Head, Neck and Spine Committee’s Concussion Diagnosis and Management Protocols, published in this edition of the BJSM , represent a comprehensive approach to concussion management in professional sport.1 The protocols highlight how much the approach to SRC has evolved, particularly since the first International Conference on Concussion in Sport held in Vienna in November 2001.2 This evolution has been driven largely by concerns (both medical and public) regarding potential short-term and long-term adverse outcomes following SRC, and have been underpinned by evolving concepts from five international consensus meetings, and an explosion of research on SRC over the past decade.

The fifth International Conference on Concussion in Sport was held in Berlin in October 2016. The meeting involved more than 18 months of active planning, 10 scientific committee members, 23 additional expert panellists and 420 participants representing 24 countries.3 The output included 12 comprehensive systematic reviews (which collectively screened nearly 60 000 articles), 202 additional conference scientific abstracts, a consensus paper4 and revised standardised concussion recognition and assessment tools (SCAT5, ChildSCAT5 and CRT5). The output from the Berlin meeting provides a blueprint of 11 key principles of concussion management (the 11 ‘R’s’).4 Translation and implementation of these principles …
Effects of climate shocks on human fertility in Indonesia: a retrospective, panel analysis of household survey and climate data
Authors: Samuel Sellers, Clark Gray
Journal: The Lancet Planetary Health (2018)

BackgroundClimate change is likely to induce a large range of household-level responses, including changes in human fertility behaviours and outcomes. These responses might have important implications for human and economic development, women's empowerment, and environmental sustainability. However, to date, few studies have explored the associations between climate change and fertility intentions, family planning use, and births.MethodsDrawing on the literature linking climate variability to rice production in Indonesia, we used large-scale, longitudinal household survey data and high-resolution climate data to explore changes in childbearing preferences, family planning use, and births after community-level climate anomalies (timing of monsoon onset and temperature) in Indonesia between 1993 and 2015. Analyses were done with a series of fixed-effects, logistic regression models. We also assessed parallel shifts in household wellbeing, as measured by expenditure on rice, food, and non-food products.FindingsWe found that, in the short term (climate anomalies occurring 1–12 months before surveys), fertility desires increased and family planning use declined in response to delays in monsoon onset, particularly in wealthier populations. Delays in monsoon onset were also associated with substantially reduced expenditure on food and non-food products among households without farm businesses and high levels of education. In the medium term (climate anomalies occurring 1–60 months before surveys), fertility desires declined and family planning use increased in response to high temperatures, particularly in poorer populations.InterpretationThese results suggest that fertility desires, family planning use, and births are affected by climate shocks. Provision of high-quality family planning services can serve as an important climate change adaptation tool for vulnerable populations.FundingNone.
Response to: ’Not all drugs (and routes) are same' by Zanwar and Gandhi
Authors: Pierre Charles, Loic Guillevin
Journal: Annals of the Rheumatic Diseases (2018)

Response to: 'Not all drugs (and routes) are same' by Zanwar and Gandhi We would like to thank Zanwar and Gandhi 1 for their comments regarding our paper. 2We are aware of the long-term results of the European Vasculitis Society (EUVAS) trial: patients treated with daily oral (DO) cyclophosphamide experienced fewer relapses than those given pulse intravenous cyclophosphamide for induction therapy. 3At 18 months, no significant between-group differences were seen and long-term follow-up indicated fewer relapses only for the DO cyclophosphamide group.However, as mentioned by the authors, the study was retrospective and approximately 10% of the data were missing, which might have modified their results.The DO versus pulse difference in relapse rates could be explained by those groups' different cumulative (median (IQR) cyclophosphamide doses, respectively: 15.9 (11-22.5)g vs 8.2 (5.95-10.55)g).The excess relapses in the pulse arm were not associated with higher mortality or more renal damage.In light of the well-known increased risk of adverse events when DO cyclophosphamide is prescribed (infertility, malignancies, infections), we no longer recommend it as first-line therapy.Since the demonstration of rituximab non-inferiority to oral cyclophosphamide to induce antineutrophil cytoplasm antibody (ANCA)-associated vasculitis remission, 4 we have modified our cyclophosphamide use strategy.We prescribe DO cyclophosphamide only for patients with refractory disease, after pulse cyclophosphamide and rituximab have failed.In the MAINRITSAN2 trial, only one patient in the fixed-schedule infusion arm received oral cyclophosphamide for induction versus none in the individually tailored arm.Based on the post-hoc analysis of the RAVE trial data, Fussner et al 5 reported that higher antiproteinase-3 ANCA titres were associated with relapses only in patients who had received rituximab as induction therapy; this group of patients did not receive any maintenance therapy.No ANCA-titre-relapse association was found for patients taking DO cyclophosphamide followed by azathioprine.We do not think that their observed association could affect MAINRITSAN2 results because, after remission was obtained with different induction regimens, all patients received rituximab for maintenance at randomisation, thereby rendering the population homogeneous.
A computational tool to detect DNA alterations tailored to formalin-fixed paraffin-embedded samples in cancer clinical sequencing
Authors: Mamoru Kato, Hiromi Nakamura, Momoko Nagai, Takashi Kubo, Asmaa Elzawahry, Yasushi Totoki, Yuko Tanabe, Eisaku Furukawa, Joe Miyamoto, Hiromi Sakamoto, Shingo Matsumoto, Kuniko Sunami, Yasuhito Arai, Yutaka Suzuki, Teruhiko Yoshida, Katsuya Tsuchihara, Kenji Tamura, Noboru Yamamoto, Hitoshi Ichikawa, Takashi Kohno, Tatsuhiro Shibata
Journal: Genome Medicine (2018)

Advanced cancer genomics technologies are now being employed in clinical sequencing, where next-generation sequencers are used to simultaneously identify multiple types of DNA alterations for prescription of molecularly targeted drugs. However, no computational tool is available to accurately detect DNA alterations in formalin-fixed paraffin-embedded (FFPE) samples commonly used in hospitals. Here, we developed a computational tool tailored to the detection of single nucleotide variations, indels, fusions, and copy number alterations in FFPE samples. Elaborated multilayer noise filters reduced the inherent noise while maintaining high sensitivity, as evaluated in tumor-unmatched normal samples using orthogonal technologies. This tool, cisCall, should facilitate clinical sequencing in everyday diagnostics. It is available at https://www.ciscall.org .
Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease
Authors: Seung Pil Yun, Tae-In Kam, Nikhil Panicker, SangMin Kim, Yumin Oh, Jong-Sung Park, Seung-Hwan Kwon, Yong Joo Park, Senthilkumar S. Karuppagounder, Hyejin Park, Sangjune Kim, Nayeon Oh, Nayoung Alice Kim, Saebom Lee, Saurav Brahmachari, Xiaobo Mao, Jun Hee Lee, Manoj Kumar, Daniel An, Sung-Ung Kang, Yunjong Lee, Kang Choon Lee, Dong Hee Na, Donghoon Kim, Sang Hun Lee, Viktor V. Roschke, Shane A. Liddelow, Zoltan Mari, Ben A. Barres, Valina L. Dawson, Seulki Lee, Ted M. Dawson, Han Seok Ko
Journal: Nature Medicine (2018)
Intrinsic subtypes of HER2-positive breast cancer and their associations with pathologic complete response (pCR) and outcomes: Findings from NSABP B-41, a randomized neoadjuvant trial.
Authors: Sandra M. Swain, Gong Tang, Peter C. Lucas, Andre Robidoux, David Goerlitz, Brent T. Harris, Hanna Bandos, Charles E. Geyer, Priya Rastogi, Eleftherios P. Mamounas, Norman Wolmark
Journal: Journal of Clinical Oncology (2018)

580 Background: NSABP B-41, randomly assigned 529 patients with HER2 positive breast cancer to receive neoadjuvant trastuzumab, lapatinib, or the combination, with weekly paclitaxel following doxorubicin and cyclophosphamide x 4. No significant difference in pCR was found among three arms (Robidoux 2013), but overall survival was significantly increased for patients who obtained a pCR (Robidoux 2016). This study evaluated outcomes in B-41 based on intrinsic subtype. Methods: H&E slides were reviewed by study pathologist for areas of invasive carcinoma having > 10% tumor cells. RNA was isolated and hybridized to the "RUO-PAM50" CodeSet (NanoString Technologies). Intrinsic PAM50 subtype was determined for each sample. Contingence-table analyses were used to compare pCR breast and nodes (ypT0/is ypN0) among intrinsic subtypes and Kaplan-Meier estimates and Cox models were used to compare event-free survival and overall survival among subtypes. Results: Core biopsy samples from 276 patients, prior to therapy, were evaluated. Intrinsic subtype was determined in 271: 197 (73%) were HER2 enriched (E) (97 ER negative and 100 ER positive), 26 (10%) basal-like, 23 (8%) luminal A, and 25 (9%) luminal B. pCR was 61% in HER2-E (69% in ER negative and 53% in ER positive) and 26% in others (basal-like, luminal A/B) (p < 0.001). In HER2-E, patients on trastuzumab-based arms had higher pCR than those on the lapatinib arm (67% vs 49%, p = 0.02). Patients with basal-like tumors had higher pCR than those with luminal A/B tumors (38.5% vs 13% & 24%) but their long-term prognosis is poor, compared with other three subtypes: five-year EFS = 0.724 [0.506, 0.858] (p = 0.28) and five-year OS = 0.808 [0.598, 0.915] (p = 0.005). In HER2-E, EFS and OS were no different between the three arms. Conclusions: HER2-E subtype is a good marker for predicting benefit from HER2 targeted therapies, particularly if trastuzumab-based. Whether tumors with other subtypes are suitable for HER2 targeted therapies needs further investigation. Survival outcomes are limited by the small number of events and would benefit from meta-analysis with other similar studies. Clinical trial information: NCT00486668.
A Dosing Study of Bevacizumab for Retinopathy of Prematurity
Authors: David K. Wallace, Trevano W. Dean, Mary Elizabeth Hartnett, Lingkun Kong, Lois E. Smith, G. Baker Hubbard, Mary Lou McGregor, Catherine O. Jordan, Iason S. Mantagos, Edward F. Bell, Raymond T. Kraker
Journal: Ophthalmology (2018)
Intraoperative lumpectomy cavity margin analysis with far-red fluorescence to reduce volume of tissue excised during breast cancer lumpectomy surgery.
Authors: Conor Lanahan, Michele Gadd, Michelle Connolly Specht, Elena Brachtel, Jorge M. Ferrer, Anna Biernacka, Travis Rice-Stitt, Rong Tang, Upahvan Rai, Andrea Merrill, Barbara L. Smith
Journal: Journal of Clinical Oncology (2018)

e12605 Background: Obtaining clear margins in breast cancer lumpectomy surgery is made difficult by complex tumor geometry and lack of rapid, accurate approaches for intraoperative margin assessment. 20-40% of patients have positive margins that require second surgeries. These increase volume excised, worsen cosmetic outcomes and add to patient discomfort and cost. In a prospective Phase II trial we assessed the ability of the LUM2.6 Imaging System to obtain clear margins while reducing volume of breast tissue excised. Methods: Women with invasive breast cancer and/or ductal carcinoma in situ (DCIS) received an IV injection of LUM015, a cathepsin-activatable fluorescent dye, 4±2 hours prior to surgery. A standard lumpectomy was performed and lumpectomy cavity walls were evaluated intraoperatively with the technology. Complete shaved cavity margins and remaining areas of high fluorescence were excised, analyzed with standard histopathology and compared to LUM Imaging System results. Volume of tissue excised was calculated using specimen measurements. Results: 45 patients received IV LUM015 preoperatively and had their lumpectomy cavities imaged with the LUM2.6 Imaging System. Median age was 60 years (range 44-79). Mean tumor size was 1.2cm (0.06-3.5cm); 79% with invasive carcinoma +/- DCIS, and 21% with pure DCIS. We previously reported that the LUM Imaging System established a 100% negative predictive rate and 72% specificity for detection of tumor in lumpectomy cavity margins in this patient cohort. All patients had comprehensive shaved cavity margin specimens taken after lumpectomy excision, with an average volume of 16.1 cm3. When we modeled outcomes if only margins containing LUM015 signal had been excised, the average margin volume excised fell to 5.3 cm3, a 67% reduction in margin excision volume. Conclusions: The LUM015/LUM2.6 Imaging System allows for real-time identification of residual tumor in the lumpectomy cavity during breast cancer surgery and may reduce positive margin rates while also reducing volume of tissue excised. A multicenter, randomized pivotal clinical trial to address the impact of this technology is underway. Clinical trial information: NCT02438358.