tbuckley/cabot-search huggingface dataset:
Factors Influencing Physician Practices' Adoption of Behavioral Health Integration in the United States
Authors: Angèle Malâtre-Lansac, Charles C. Engel, Lea Xenakis, Lindsey Carlasare, Kathleen Blake, Carol Vargo, Christopher Botts, Peggy G. Chen, Mark W. Friedberg
Journal: Annals of Internal Medicine (2020)

Behavioral health integration is uncommon among U.S. physician practices despite recent policy changes that may encourage its adoption.To describe factors influencing physician practices' implementation of behavioral health integration.Semistructured interviews with leaders and clinicians from physician practices that adopted behavioral health integration, supplemented by contextual interviews with experts and vendors in behavioral health integration.30 physician practices, sampled for diversity on specialty, size, affiliation with parent organizations, geographic location, and behavioral health integration model (collaborative or co-located).47 physician practice leaders and clinicians, 20 experts, and 5 vendors.Qualitative analysis (cyclical coding) of interview transcripts.Four overarching factors affecting physician practices' implementation of behavioral health integration were identified. First, practices' motivations for integrating behavioral health care included expanding access to behavioral health services, improving other clinicians' abilities to respond to patients' behavioral health needs, and enhancing practice reputation. Second, practices tailored their implementation of behavioral health integration to local resources, financial incentives, and patient populations. Third, barriers to behavioral health integration included cultural differences and incomplete information flow between behavioral and nonbehavioral health clinicians and billing difficulties. Fourth, practices described the advantages and disadvantages of both fee-for-service and alternative payment models, and few reported positive financial returns.The practice sample was not nationally representative and excluded practices that did not implement or sustain behavioral health integration, potentially limiting generalizability.Practices currently using behavioral health integration face cultural, informational, and financial barriers to implementing and sustaining behavioral health integration. Tailored, context-specific technical support to guide practices' implementation and payment models that improve the business case for practices may enhance the dissemination and long-term sustainability of behavioral health integration.American Medical Association and The Commonwealth Fund.
Impact of antibiotics on residual cancer burden and pathologic response rates during neoadjuvant pembrolizumab in breast cancer (BC).
Authors: Amit Kulkarni, Patricia Jewett, Anne Hudson Blaes, Douglas Yee
Journal: Journal of Clinical Oncology (2020)

e12622 Background: Antibiotic exposure during immunotherapy has been shown to negatively affect clinical outcomes in metastatic melanoma and non-small cell lung cancer. We tested whether antibiotics exposure during neoadjuvant pembrolizumab (NA-P) affects residual cancer burden (RCB) and pathologic complete response rate (pCR) in the pembrolizumab-4 arm of the ISPY-2 trial. Methods: I-SPY2 is an adaptively-randomized, ph-II trial in patients with high-risk, stage II/III breast cancer (BC). In pembrolizumab-4 arm patients with HER2-negative BC received NA-P 200mg every 3 weeks for four cycles concurrently with 80mg/m 2 paclitaxel weekly for 12 weeks, followed by four cycles of 60mg/m 2 doxorubicin plus 600mg/m2 cyclophosphamide every 2 weeks. Data on antibiotic use during NA-P was reviewed. Patients who received at least one dose of systemic antibiotics were included in the antibiotic exposure group (ATB+). All other patients were included in the no exposure group (ATB-). RCB index was used to evaluate RCB as a continuous variable. A higher RCB index indicated higher RCB. RCB index and pCR rates were compared between ATB+ and ATB- groups. Association of antibiotic use with RCB and pCR rates was evaluated using linear regression and logistic regression respectively. Clinical variables for adjustment were age, stage and hormone receptor (HR) status. Results: 69 patients received NA-P with chemotherapy. All patients had HER2-negative BC. One patient was excluded due to missing data on antibiotics. 68 patients were included in the final analysis. 19/68 (28%) patients were in the ATB+ group. Antibiotic use in HR+ and HR- patients were 9/19 (47%) and 31/49 (63%) respectively ( P=0.23). Compared to ATB- group, patients in the ATB+ group had higher mean RCB index (1.05 vs 1.80, P=0.04) and lower pCR rate (53.1% vs 26.3%, P=0.05). Antibiotic use was associated with higher probability of RCB in univariate analysis (Coefficient estimate CE: 0.75, 95% CI 0.01-1.48, P=0.04) and multivariable analysis (CE: 0.89, 95% CI 0.11-1.65, P=0.02). HR positivity was independently associated with higher probability of RCB (CE: 1.07, 95% CI 0.38-1.77 P=0.002). Antibiotic use was associated with higher probability of not having pCR (Odds ratio 3.17, 95% CI 0.99-10.15, P=0.05). Conclusions: Patients with antibiotic exposure during NA-P in HER2-negative early stage BC were associated with higher RCB and lower pCR rates. Further validation in a larger independent cohort is needed to confirm these findings.
Intratumoral drug distribution of adavosertib in patients with glioblastoma: Interim results of phase I study.
Authors: Carlos G Romo, Brian Michael Alexander, Nathalie Agar, Manmeet Singh Ahluwalia, Arati Suvas Desai, Jorg Dietrich, Thomas Joseph Kaley, David M. Peereboom, Naoko Takebe, Serena Desideri, Joy D. Fisher, Megan Sims, Xiaobu Ye, Keith L. Ligon, Louis B. Nabors, Patrick Y. Wen, Stuart A. Grossman, Jeffrey G. Supko, Eudocia Quant Lee
Journal: Journal of Clinical Oncology (2020)

2568 Background: Wee1 is a key regulator of the G2/M checkpoint and is frequently overexpressed in glioblastoma (GB). Adavosertib is a first-in-class oral, small molecule inhibitor of Wee1 that acts primarily as a DNA damage sensitizer. A phase I clinical trial was conducted to evaluate its safety and establish the recommended phase II dosing. Studies were undertaken to evaluate whether potentially therapeutic concentrations of the drug are achieved in recurrent tumor and adjacent non-enhancing brain regions with presumed intact blood-brain barrier (BBB). Methods: Twelve patients received five daily doses of adavosertib pre-operatively at either the maximum tolerated dose (MTD) for concurrent radiation or adjuvant temozolomide. Tissue from contrast enhancing (CE) and non-enhancing (NE) brain regions was obtained for analysis during surgical resection. A second stage is being conducted using microdialysis (MD) to facilitate continuous sampling of extracellular fluid (ECF) and measuring free drug concentrations in: normal-appearing brain, contrast enhancing tumor, and a peritumoral T2 hyperintense area. The concentration of total adavosertib in plasma and tissue homogenates and free drug in ECF were determined by validated LC/MS/MS methods. Results: Geometric mean concentrations of adavosertib after a 200 mg dose were 644 ng/mL and 119 ng/mL in CE and NE tissue specimens, respectively (6 patients). At the 425 mg dose, the mean concentrations were 3,576 ng/mL in CE tissue and 885 ng/mL in NE tissue (6 patients). MD was performed in 2 patients. Samples from functional MD catheters were collected from NE brain in patient no. 1 and from two NE areas and a FLAIR hyperintense region in patient no. 2, with the following results in the table. Conclusions: The total drug concentration in tissue samples was notably lower in regions of the brain with a relatively intact BBB as compared to contrast enhancing tissue. Concentrations of adavosertib measured by MD vary markedly depending on catheter location. Free drug levels in ECF within brain with a functional BBB, although considerably lower than total drug levels in tissue, were 2-10 times below the previously reported IC 50 for antiproliferative activity against sensitive GB cell lines (127 ng/mL). Whether or not the target of the drug is effectively inhibited at these concentrations remains to be demonstrated. Clinical trial information: NCT01849146 . [Table: see text]
Brain delivery and activity of a lysosomal enzyme using a blood-brain barrier transport vehicle in mice
Authors: Julie C. Ullman, Annie Arguello, Jennifer A. Getz, Akhil Bhalla, Cathal S. Mahon, Junhua Wang, Tina Giese, Catherine Bedard, Do Jin Kim, Jessica R. Blumenfeld, Nicholas Liang, Ritesh Ravi, Alicia A. Nugent, Sonnet S. Davis, Connie Ha, Joseph Duque, Hai L. Tran, Robert C. Wells, Steve Lianoglou, Vinay M. Daryani, Wanda Kwan, Hilda Solanoy, Hoang Nguyen, Timothy Earr, Jason C. Dugas, Michael D. Tuck, Jennifer L. Harvey, Michelle L. Reyzer, Richard M. Caprioli, Sejal Hall, Suresh Poda, Pascal E. Sanchez, Mark S. Dennis, Kannan Gunasekaran, Ankita Srivastava, Thomas Sandmann, Kirk R. Henne, Robert G. Thorne, Gilbert Di Paolo, Giuseppe Astarita, Dolores Diaz, Adam P. Silverman, Ryan J. Watts, Zachary K. Sweeney, Mihalis S. Kariolis, Anastasia G. Henry
Journal: Science Translational Medicine (2020)

An enzyme transport vehicle enables brain delivery of lysosomal enzymes across the blood-brain barrier in mice.
Implementation and impact of the first two years of a systemwide molecular tumor board at Henry Ford Health System (HFHS).
Authors: Igor I. Rybkin, Nadia Z Haque, Kristen Collins, Louisa Laidlaw, Tom Mikkelsen
Journal: Journal of Clinical Oncology (2020)

e19266 Background: HFHS implemented clinically-oriented Precision Medicine Program (PMP) in 2016. As part of the program, multidisciplinary molecular tumor board (MTB) was created to review complex molecular cases, providing guidance to treating medical oncologist in selecting targeted therapies and clinical trials. In some cases MTB recommended genetic counseling or recommended against/for additional molecular testing. MTB consists of oncologists, molecular pathologists, clinical trial staff, and genetic counselors. MTB was designed as teaching platform engaging hematology-oncology fellows into cases analysis and presentation. Here we present preliminary analysis of the impact of the MTB on the HFHS oncology practice. Methods: From 09/08/2017 to 12/31/2019 MTB reviewed 120 cases, 116 cases were used for this analysis. Data was abstracted using Syapse precision oncology platform, MTB recommendation note, electronic medical record (EMR), and molecular test results. Results: Out of 116 pts 83 (72%) were Caucasian, 25 (22%) African American, 4 (3%) Asian, 1 (1%) American Indian. Fifty-two % (n = 21) had an ECOG performance status of 1. Most common primary disease sites were lung (39%, n = 45) brain (12%, n = 15), and hematologic cancers (9%; n = 10), followed by breast (5%, n = 6), prostate (4%, n = 5), colon (3%, n = 4), and others (28%, n = 31). The most common genetic abnormalities discussed were atypical EGFR (n = 15), non-V600 BRAF (n = 10), KRAS (n = 8), BRCA2 (n = 5), NF2 (n = 4), PTEN (n = 4), CSF3R (n = 3), IDH1 (n = 3), TP53 (n = 3), and 29 less common mutations. Thirty five (30%) pts out of 116 total were recommended clinical trials, although only 3 patients (10% of recommended) were enrolled into trials. 31 pts (27%) were recommended off-label therapy, although trials were preferred. 18% of pts (n = 21) were recommended genetics referral, although only 3 have seen Geneticist, with two undergoing germline testing. One pt was discovered to have a germline RET V804M mutation which was originally detected in the cancer. Conclusions: The first two years of data demonstrate the utility of the MTB and provide a basis for ongoing analysis. Through multidisciplinary approach, MTB encourages care coordination and collaboration. MTB resulted in genetics referrals, clinical trial recommendations, and identification of targeted therapy options, including off label. In many cases, MTB recommendations prevented futile therapies and/or additional molecular testing.
Anti-Müllerian hormone levels in polycystic ovarian syndrome patients with insulin resistance after metformin treatment
Authors: Chunxia Fang, Qin Zhu, Xia Liu, Liping Wang, Wenwei Cai
Journal: BMJ (2017)

Twenty eight polycystic ovarian syndrome (PCOS) patients complicated with insulin resistance, whose testosterone and luteinizing hormone levels were normal, received metformin treatment (500 mg b. i.d ) for 3 months. Blood anti-Mullerian hormone (AMH) levels, endocrine and metabolic parameters were measured before and after treatment. The mean levels of AMH were not significantly changed after 3 months of treatment [(8.4±3.2) vs.( 8.5±3.2) μg/L, P=0.148]. However, the BMI[(27.6±4.1) vs. (29.3±4.4)kg/m2], fast glucose[(5.32±0.47) vs. (5.55±0.71)mmol/L], fast insulin [(93.3±17.8) vs. (147.7±44.1)pmol/L] and homeostasis model assessment of insulin resistance (HOMA-IR) (3.17±0.71 vs. 5.27±1.85) were significantly decreased after treatment (all P<0.05). The results indicate that metformin treatment may not significantly affect serum AMH levels, although it can improve the insulin resistance and reduce the BMI value in PCOS patients.


Key words: 
Polycystic ovary syndrome; Metformin; Anti-Mullerian hormone
First-line apatinib plus chemotherapy in extensive-stage small-cell lung cancer.
Authors: Jian Shi, Jiayin Liu, Xiaoyang Duan, Guanglei Huang, Lixing Wang, Yan Zhao
Journal: Journal of Clinical Oncology (2020)

e21104 Background: Angiogenesis plays a critical role in the growth, progression, and metastasis of numerous solid tumor types. Apatinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR2), which is inhibits tumor angiogenesis. Etoposide plus cisplatin is a standard chemotherapy regimen for Extensive-Stage Small-Cell Lung Cancer (SCLC). Combining apatinib with chemotherapy may have a synergistic effect and improve efficacy. Methods: Eligible patients were adults with histologically or cytologically confirmed extensive-stage small-cell lung cancer, excluded patients with symptomatic brain metastases. Measurable extensive-stage small-cell lung cancer according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Eligible patients were received six 21-day cycles of apatinib (250mg, orally daily) and chemotherapy (etoposide:100 mg/m 2 , ivgtt d1-3 of each cycle; cisplatin: 80 mg/m 2 , ivgtt d1 of each cycle), followed by local radiotherapy, apatinib (250mg, orally daily) maintenance therapy. For patients who have received treatment less than 6 cycles have disease progression, change the chemotherapy regimen combined with local radiotherapy. Primary endpoint: 6-month ORR. Secondary endpoints: 6-month DCR, PFS, safety. Results: We enrolled 40 patients between November 15, 2017 and April 18, 2019. Median age was 56 (range 28-67), 92.5% had an ECOG PS of 0. At the data cutoff (December 31, 2019), 27 patients were evaluated. In 27 patients who received apatinib for 4-26 months, with average of 10.6 months. The 6-month ORR was 63%, DCR was 85% [17 PR, 6 SD]. 9 patients (33.3%) achieved PFS, of which 8 patients progressed within 9 months and 1 patient progressed within 22 months. Patients who progressed within 6 months, the average duration of apatinib was 5.1 months. During the therapy, adverse events (AEs) were mostly Common grade 1-2 related AE, hypertension (37%), hand-foot syndrome (3.7%), and Hepatic Insufficiency (7.4%). Conclusions: Our study suggests that oral apatinib plus chemotherapy should be considered an active and safe treatment in patients with first-line treatment of extensive-stage small-cell lung cancer.
腹外疝嵌顿合并腹内疝嵌顿二例
Authors: 韦浩俊, 胡世堂, 葛丽娟
Journal: BMJ (2005)

例1 男,46 岁.因右腹股沟可复性包块2年,不能还纳6 h,于1986年3月9日入院.既往无外伤及手术史.查体:生命体征正常,心肺听诊未见异常,腹稍胀、软,脐周轻压痛,无反跳痛,未扪及包块,可闻及气过水声,右侧腹股沟可扪及6 cm×5 cm包块,触痛.辅助检查:血常规、心电图、肝功能、肾功能均正常。
Cancerbiome: Defining a healthy microbiome for therapeutic targeting.
Authors: Hari S Babu, Robert Mason, Nicholas P West, Ben Gunawan, Amanda J Cox, Tiffanie M Nelson, Ping Zhang, Allan W Cripps, Jasotha Sanmugarajah
Journal: Journal of Clinical Oncology (2020)

e15152 Background: The gut microbiome has been shown to modify the efficacy of cancer immunotherapy. Currently, there is little understanding of how the microbiome in advanced cancer patients responding to immunotherapy compares to healthy individuals. The aim of this study was to characterise the intestinal microbiome in patients with advanced solid organ tumours that have a durable response to programmed-death-protein-1 inhibitors (PD-1) with healthy individuals. Methods: Ten patients (mean age 69 ± 11; 60% female) with metastatic melanoma, renal cell carcinoma or non-small cell lung cancer and durable response for greater than one year to anti-PD-1 antibodies and ten healthy age and sex matched individuals (mean age 69 ± 9.2; 60% female) were recruited. Clinical data and a three-day diet diary were collected, with faecal sample analysed via shallow shotgun sequencing (CoreBiome, Minneapolis, USA). Results: Duration of response to immunotherapy was 786 ± 282 days. Responders had a significantly higher body mass index (28 ± 5.5 kg/m 2 v 23.3 ± 2.65 kg/m 2 , p = 0.005; mean ± SD) than the healthy group. There was a significantly higher intake of total fat and fibre in the healthy group. The responder group had significantly higher diversity metrics, exhibiting a greater diversity in the number (OTUs) and the richness of species than the healthy group. At the phylum level, the microbiome in the responder group was significantly abundant in proteobacteria and had a significantly lower abundance of Bacteroidetes compared to the healthy group. At the genus level, the microbiome in the responder group was significantly enriched in Desulfovibrio, Acideminococcus, Klebsiella, Enterococcus and Faecalitalea compared to Ruminococcus, Veillonella and Roseburia in the healthy group. Species that were abundantly higher in the cancer group were associated with glycolysis, the TCA cycle, sugar metabolism and amino acid metabolism. Five Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologues were significantly enriched in the responder group, mostly relating to transport systems for minerals and nitrogen fixation, but also mismatch repair proteins and cell cycle activity. Conclusions: Our findings suggest that compositional and functional differences in the faecal microbiome exist between advanced cancer patients responding to immunotherapy and healthy individuals, suggesting not only potential mechanisms of durable response but also targets for future therapy.
Bisphosphonate-related osteonecrosis of the jaw
Authors: 王小磊, 鞠文龙, 丁晓玲
Journal: BMJ (2010)

双膦酸盐相关性颌骨坏死(bisphosphonate-related osteonecrosis of the jaw,BRONJ)于2003年首次在美国 报道,描述了36例癌症患者为预防骨骼事件(骨转移、高钙血症、骨痛)的发生,在静脉应用双膦酸盐治疗后发生了颌骨缺血坏死[1].之后此类的报道越来越多,引起了人们的关注。
Association between naturally occurring anti-amyloid β autoantibodies and medial temporal lobe atrophy in Alzheimer's disease
Authors: Kimura Akio, Takemura Masao, Saito Kuniaki, Yoshikura Nobuaki, Hayashi Yuichi, Inuzuka Takashi, 周波
Journal: BMJ (2017)

背景
既往研究已发现，健康人血清和脑脊液中存在淀粉样β（Aβ）肽的天然自身抗体。而近期则有研究报道在阿尔茨海默病（AD）患者的轻度认知障碍（MCI）阶段，给予静脉注射免疫球蛋白治疗可以减少脑萎缩程度。


目的
探讨天然存在的抗Aβ自身抗体与认知功能障碍患者脑萎缩之间的关系。


方法
对68例认知功能障碍患者的血清和脑脊液抗Aβ抗体以及脑脊液生物标志物水平进行了评价，其中包括44例AD、19例遗忘型MCI患者和5例非AD型痴呆。针对脑萎缩程度的评估则采用基于体素的分析方法，感兴趣区（VOI）为内侧颞叶结构，包括整个海马、内嗅皮质和杏仁核。


结果
在AD患者中脑脊液抗Aβ自身抗体水平与VOI萎缩的严重程度和VOI/灰质体积萎缩的比例均呈负相关，而在MCI或非AD痴呆患者中并未发现这一现象。血清抗Aβ自身抗体水平在所有的患者组中与上述这些参数均未发现相关。


结论
脑脊液中天然存在的抗Aβ自身抗体水平与AD患者内侧颞叶结构的萎缩程度存在着负相关，虽然相关机制目前尚不清楚，但这一结果提示在AD患者中脑脊液中天然存在的抗Aβ自身抗体可能参与了海马、内嗅皮层和杏仁核萎缩的演变过程。
Epidemiologic changes in bloodstream infections in Andalucía (Spain) during the last decade
Authors: P.M. Martínez Pérez-Crespo, L.E. López-Cortés, P. Retamar-Gentil, J.F. Lanz García, D. Vinuesa García, E. León, J.M. Sánchez Calvo, F. Galán-Sánchez, C. Natera Kindelan, A. del Arco Jiménez, A. Sánchez-Porto, C. Herrero Rodríguez, B. Becerril Carral, I.M. Reche Molina, J.M. Reguera Iglesias, I. Pérez Camacho, M. Guzman García, I. López-Hernández, J. Rodríguez-Baño
Journal: Clinical Microbiology and Infection (2020)

ObjectivesDuring the last decade, some changes in the epidemiology of invasive infections have been reported; however, specific studies with patient-level data are scarce. The aim of this study was to describe and evaluate the epidemiologic changes in bloodstream infections (BSI) during the last decade in Andalucía, Spain.MethodsData from two prospective cohorts of BSI in adults with the same methodology performed 10 years apart in 11 hospitals (eight tertiary and three community) in Andalucía, Spain, were compared; the 2006–7 cohort study was performed between October 2006 and March 2007, and the 2016–17 cohort study was performed between October 2016 and March 2017. Population-based incidence rates were calculated and extrapolated for 1 year. Relative risk ratios were calculated between the 2 periods. Multivariate analyses were performed by logistic regression.ResultsOverall, 1262 episodes of BSI were included, 563 (44.6%) in 2006–7 and 699 (55.3%) in 2016–17. Multivariate models selected the following changes in patients' features in 2016–17, after controlling for type of acquisition: higher age (odds ratio (OR) = 1.02; 95% confidence interval [CI] 1.01–1.03), lower urinary catheter (OR = 0.37; 95% CI, 0.26–0.48) and lower Pitt score (OR = 0.76; 95% CI, 0.71–0.82). Adjusted estimations considering patients' features and exposure to procedures showed a reduction in coagulase-negative staphylococci (OR = 0.47; 95% CI, 0.32–0.69), and an increase in Proteus spp. (OR = 3.12; 95% CI, 1.18–8.23) and Candida spp. (OR = 3.01; 95% CI, 1.03–8.86).ConclusionsWe found relevant epidemiologic changes in BSI in our area, including rates, frequency of acquisition types, changes in patient's profiles and aetiologic agents.
Progress of gastrointestinal involvement in systemic sclerosis
Authors: Hongyan Li, Lin Yang, Jingjing He, Yanru Wang
Journal: BMJ (2017)

Systemic sclerosis is an autoimmune disease characterized by skin thickening and tightness. Digestive system is the most commonly damaged system secondary to skin, and as to unspecific clinical manifestations, this complication is often ignored in the early, the prognosis and quality of life of patients will be affected. This article overviews the recent research developments on pathology, clinical features, management of systemic sclerosis with digestive system involvement, to draw attention to early diagnosis and treatment of this condition for the improvement of the prognosis.


Key words: 
Scleroderma, systemic; Digestive system; Disease attributes; Diagnosis; Therapeutics