tbuckley/cabot-search huggingface dataset:
Factors associated with adjuvant endocrine therapy adherence in non-metastatic breast cancer.
Authors: Joan Marie Neuner, Aaron N Winn, Liliana E Pezzin, Purushottam W. Laud, Ann B Nattinger, Nicole Fergestrom
Journal: Journal of Clinical Oncology (2020)

533 Background: Over 50% of breast cancer patients prescribed adjuvant endocrine therapy (ET) are nonadherent during the recommended 5-year course of therapy. We investigated the role of cancer medication delivery on adherence, including mail order pharmacy use, number of pharmacies and copays. Methods: We conducted a retrospective cohort study of 15,769 commercially insured breast cancer patients age 18-64 with newly diagnosed breast cancer in 2007-2015 that initiated ET. Incident breast cancer was identified by a validated algorithm which identifies mainly non-metastatic breast cancer. We examined the association between 12-month AET adherence (proportion of days covered by fills ≥0.80) and mail order pharmacy use, number of pharmacies, and AET copays. We used Poisson regression to estimate nonadherence risk ratios and adjusted for demographics (age, income, race, urbanicity), comorbidities, total medications, primary cancer treatments (surgery, radiation, chemo, and ET initiated), and generic AI availability. Sensitivity analyses were conducted using alternate specifications for independent variables. To test whether any observed differences were due to self-selection, we also conducted a negative control analysis. Results: Most patients were white (74.4%) and age 55-64 (43.3%). Only 16% of patients used a mail order pharmacy for ET fills, most patients only used one pharmacy (58.8%) and 25.2% had a co-pay of $20 or more. In the primary analysis, mail order patients were more likely to be adherent to their ET (aRR 1.21; 95% CI 1.18-1.24), patients using one pharmacy were more likely to be adherent (1 vs 3+: aRR 1.09; 95% CI 1.06-1.13), and patients with lower copays were more likely to be adherent (quartile 1 vs 4: aRR 1.04; 95% CI 1.01-1.08). Results were consistent across sensitivity analyses, and there was no association between mail order and copays and the negative control outcome of any pneumonia diagnoses. Conclusions: Medication delivery factors are associated with adherence to breast cancer AET. Future work should investigate whether interventions to streamline medication delivery could improve adherence for this population.
痛性眼肌麻痹综合征一例
Authors: 包成月
Journal: BMJ (2011)

患者女,21岁,因头痛2个月,右眼睑下垂2周,于2010年8月19日入本院神经内科.患者2个月来无明显诱因出现头痛,伴间断恶心、呕吐,呈非喷射状,呕吐物为胃内容物,每天呕吐1-2次,晨起为著.在外院就诊,诊断为神经性头痛,给予口服米格来宁、神衰果素片(豆腐果苷片)、氟桂利嗪,症状未见好转.近2周出现右侧眼睑下垂,视物成双.无发热,无言语不利及肢体活动障碍.既往:6岁时诊断结核性脑膜炎,治愈.体检:生命体征平稳,神志清楚,言语流利,右眼内收及上视均受限,复视.双侧瞳孔不等大,右侧直径4 mm,对光反射迟钝.左侧直径3 mm,对光反射灵敏.双侧鼻唇沟对称,伸舌居中,咽反射好,四肢肌力、肌张力正常,腱反射对称正常,双侧病理反射阴性,共济运动良好,感觉系统正常.颈无抵抗,克氏征阴性.心、肺听诊未见异常.实验室检查:血常规、血糖、血脂、电解质、肾功、肝功、结核抗体、动态红细胞沉降率、C反应蛋白、免疫全项均未见异常。
内科治疗肝脓肿41例分析
Authors: 潘朝霞, 何权瀛
Journal: BMJ (2008)

细菌性肝脓肿是发生于肝脏的一种继发性感染.典型的肝脓肿根据临床表现诊断不难,但当早期轻症、有原有基础疾病、合并其他疾病时可能造成误漏诊.本研究通过对北京大学人民医院内科系统1996年1月至2007年6月间收治的细菌性肝脓肿41例进行回顾性分析,旨在提高对细菌性肝脓肿的诊断水平。
Synthetic-lethal interactions between ATR inhibition and functional genetic and proteomic biomarkers to predict responses in endometriosis-associated cancers.
Authors: Oren Gilad, Dansu Li, Erin George, Rakesh Chettier, Fiona Simpkins, Kenneth Ward, Eric J Brown
Journal: Journal of Clinical Oncology (2020)

e18000 Background: Endometriosis is a common gynecologic disorder proven to be a precursor to several cancer types. We developed a potent and selective inhibitor (ATRN-119) of a critical DNA damage response (DDR) protein kinase: the ataxia telangiectasia and Rad3-related protein (ATR). Treatment with ATRN-119 is synthetically lethal with multiple cancer-associated changes in DDR pathways, representing a new and effective strategy to treat cancer. The objective of this study is to evaluate the overlap of DDR genes that respond to ATRN-119 and those mutated in endometriosis. Methods: We sequenced the exomes of 2,932 unrelated women with surgically-confirmed endometriosis (GERMLINE) and 274 tissue blocks containing endometriosis lesions (LESION). DNA was extracted using standard methods. Missense and truncation variants were analyzed. These data were compared to analysis of a whole proteome screen for factors that respond to exposure to ATRN-119 and may influence responsiveness to treatment. Factors observed in both methods were considered high-priority biomarker candidates and were experimentally tested for synthetic lethality with ATRN-119 treatment. Results: Analysis of endometriosis patients found 89% of the LESION samples had 2 or more DDR mutations vs 83% of the GERMLINE samples. There is an excess of DDR mutations per sample in LESION (5.5 mutations) vs GERMLINE (3.89 mutations) [p = 4.66x10-6, Mann Whitney test]. In parallel, we identified 92 genes as protein responders to ATRN-119 treatment. Mutations in 21 of these 92 genes show nominal association with surgical endometriosis (p &lt; 0.05). However, of these responsive genes, 18 are known TIER 1 cancer-driver genes and well-characterized mutations were found in three dominant genes in the LESION tissue (ATM, DDB1, and ARID1A). Overall 20% of the patients who’s LESION we examined subsequently developed an endometriosis-associated cancer. Both in vitro and in vivo studies confirmed synthetic-lethal interactions between ATRN-119 treatment and alteration of these genes. Conclusions: The overlap between DDR genes responding to ATRN-119 and those mutated in endometriosis-associated cancer suggest that genetic markers underlying response and resistance will be critical to extend the use of these drugs while increasing efficacy and minimizing toxicities. Furthermore, our data support the inclusion of endometriosis-associated cancer patients in planned ATRN-119 clinical trials.
Three-year follow-up of overlap syndrome
Authors: Jin-zhi Tan, Shu-ping Feng
Journal: BMJ (2008)

Objective To analyze the clinical features of overlap syndromes(OS),I.e.,chronic obstructive pulmonary disease(COPD)complicated with obstructive sleep apnea hypoventilation syndrome (OSAHS).Methods Frequency of episodes of acute exacerbation,severity,quality of life,exercise endurance,complications and three-year survival rate were investigated in eight patients with OS and 10 patients with pure COPD.Results Both quality of life and exercise endurance in OS group were lower than those in COPD group(P＜0.05).Annual frequency of acute exacerbation episodes and severity were more and three-year survival rate was lower in OS group than those in COPD group(P＜0.05).Complications of hypertension,diabetes,erythrocythemia,respiratory failure and heart failure were all more frequent in OS group than those in COPD group.Among all the above clinical features,increased frequency of acute exacerbation episodes was the most significant.Conclusions OS is clinically more severe than pure COPD,so more attention should be paid to it.Survival for patients with OS can not extended by nocturnal oxygen therapy alone,which may be beneficial when combined with biphasic positive airway pressure(BiPAP)or continuous positive airway pressure(CPAP)ventilation.

Key words: 
Lung diseases,obstructive;  Sleep apnea syndromes;  Quality of life;  Survival rate
Prevalence of Bullying Among Youth Classified as LGBTQ Who Died by Suicide as Reported in the National Violent Death Reporting System, 2003-2017
Authors: Kirsty A. Clark, Susan D. Cochran, Anthony J. Maiolatesi, John E. Pachankis
Journal: JAMA Pediatrics (2020)

multifaceted treatment approach, including questioning for premorbid symptoms, limiting exposure to stimuli that increase symptoms, short-course pharmacotherapy, and referrals to other types of therapies. 4econd, adolescents set academic goals including catching up on schoolwork, improving grades, and attending classes regularly.A recent systematic review suggests that 35% to 73% of children and adolescents require academic accommodations and/or experience difficulty in school after sportsassociated concussion. 3Clinicians can educate patients, families, and school staff about return-to-learn guidelines and assessments for risk factors that may indicate the need for ongoing adolescent academic support. 3hird, adolescents also desired to return to their sports and physical activity regimens.For adolescents with PPCS, considerable restrictions in lifestyle and exercise can contribute to ongoing symptoms.Clinicians can support adolescents in a closely monitored, active rehabilitation program. 6ourth, adolescents wanted help with mood regulation and mental health issues that frequently arise with concussion.A range of treatment options may be helpful, such as pediatricians or other clinicians providing informal support for mental health needs and connecting adolescents to local mental health resources that offer more structured therapies and psychopharmacological support.
Outcomes of children with Phenylketonuria detected by newborn screening program
Authors: Ling Zhu, Jianping Yang, Qin Dong, Wenjuan Mu, Xiaogang Zhang, Liang Yu, Hongmei Zhang, Baojun Yang, Jie Yu
Journal: BMJ (2018)

Objective
To evaluate the outcomes of children with Phenylketonuria (PKU) detected by newborn screening program.


Methods
One hundred and two children with PKU were detected and diagnosed in Shanxi Newborn Screening Center from June 2004 to September 2014. All children with PKU were followed up until December 2015. During the follow-up, the Phenylalanine (Phe) levels, physical and intellectual development, nutrition status of those children were monitored.


Results
Among 102 PKU children, there were 96 (94.12 %)with normal physical development, and 93 (91.18%)with normal DQ/IQ. The average DQ or IQ score in children who started the therapy before 1 month was higher than that in those who started after 1 month old(93.07±9.50 vs. 87.39±10.99, t=3.09, P=0.00). Among these children 82.47%(80/97)had zinc deficiency and 31.46%(28/89)had dyslipidemia; and the normal Phe concentration rate was (59.73±19.03)%. The intellectual development level was negatively correlated with the age of starting therapy (r=-0.25, P=0.01), positively correlated with the education levels of his/her father (r=0.21, P=0.03) and mother (r=0.23, P=0.02). And the intellectual development was better in urban areas than that in rural areas.


Conclusions
With the standardized treatment, the physical and intellectual development of children with PKU can basically reach normal levels, and the earlier treatment can make better therapeutic effect.


Key words: 
Phenylketonurias; Neonatal screening; Intelligence
Prediabetes and progression to diabetes among adult survivors of childhood cancer in the St. Jude Lifetime Cohort.
Authors: Stephanie Dixon, Lu Lu, Carmen Louise Wilson, John L. Jefferies, Thomas E. Merchant, Rebecca M. Howell, Kirsten K. Ness, Deo Kumar Srivastava, Melissa M. Hudson, Leslie L. Robison, Wassim Chemaitilly, Gregory T. Armstrong
Journal: Journal of Clinical Oncology (2020)

10548 Background: Cardiac death among survivors of childhood cancer occurs at &gt; 10 times the rate expected in the general population. Modifiable cardiovascular risk factors, including diabetes, increase risk for major cardiac events in a near multiplicative fashion. Thus, prevention of progression from prediabetes to diabetes could improve long-term cardiac morbidity and mortality. However, little is known about prediabetes in survivors. Methods: Prevalence of prediabetes (fasting glucose 100-125 mg/dL or HbA1c 5.7-6.4%) and diabetes were assessed in 3529 5+ year survivors ≥18 years of age and compared to 450 community controls stratified by age and matched for race/ethnicity, sex, and BMI using Chi-squared statistics. Logistic regression estimated risk factors for prediabetes and cox proportional hazards regression for progression from prediabetes to diabetes among survivors with multiple visits, reported as odds (OR) and hazard ratio (HR), respectively, with 95% confidence intervals (CI). Results: Among 3529 survivors (median age 30 years, range 18-65), the prevalence of prediabetes overall was 29.2% (95% CI 27.7-30.7) and diabetes was 6.5% (5.7-7.3). In each age strata, survivors had significantly higher prevalence of prediabetes and diabetes than controls with over 50% of middle-aged survivors (35-44 years) having prediabetes or diabetes (Table). In a multivariable model, therapy-related risk factors for prediabetes included high pancreatic tail dose (≥20 Gy: 2.9 [1.8-4.8]) and moderate prescribed cranial radiation dose (OR [95% CI] &gt; 0- &lt; 20 Gy: 1.4 [1.1-1.8], 20- &lt; 30 Gy: 1.4 [1.0-1.9]) independent of age, sex, race/ethnicity and BMI. Among 695 survivors with prediabetes and longitudinal follow-up, median 5.1 years, 68 (10%) progressed to diabetes. After adjustment for age, sex, race/ethnicity and BMI, risk of progression from prediabetes to diabetes was increased by the presence of insulin resistance (HR 4.9 [95% CI 2.3-10.6]) or prior treatment with hematopoietic cell transplant (HR 2.9 [1.1-7.7]) or total body irradiation (HR 4.6 [1.6-13.5]). Conclusions: Survivors of childhood cancer have a high prevalence of prediabetes and high rates of progression to diabetes. Strategies that prevent progression to diabetes should be considered to decrease diabetes risk and subsequent cardiac morbidity and mortality in this high-risk population. [Table: see text]
Analysis of knowledge and clinical skill competition results in general practitioners attending grass-roots health post training
Authors: Zejun Chen, Xiaoyang Liao, Jie Wu, Guangbin Zhao
Journal: BMJ (2019)

The knowledge and clinical skill competition scores of 331 general practitioners (GPs), who attended the grassroots health posts training in Sichuan Province and Chengdu Municipality in 2016 and 2017, were documented. The factors influencing the competition results were analyzed. The mean knowledge test score of 331 participants were higher than the clinical skill score [(76.89±6.56) vs. (54.13±10.91) , P 0.05). The levels of clinical skills of general practitioners at the grass-roots level need to be further improved, according to relevant influencing factors.


Key words: 
General practitioner; Clinical knowledge; Clinical skill
Burnout among oncology physician assistants (PAs) from 2015 to 2019.
Authors: Eric Daniel Tetzlaff, Heather Marie Hylton, Karen Ruth, Zachary Hasse, Michael J. Hall
Journal: Journal of Clinical Oncology (2020)

11009 Background: Changes in the demand and delivery of healthcare have led to a significant increase in employment of PAs in Oncology (Onc). These changes may also increase PAs risk of burnout, a syndrome characterized by a high level of emotional exhaustion (EE) and/or depersonalization (DP). This study was initiated to explore temporal changes in burnout &amp; the PA workforce. Methods: Using the same methods from 2015, a national survey of Onc PAs was conducted in 2019. Survey items (n = 74) examined personal and professional characteristics, collaborative practice (CP), team structure, organizational context (OC), and burnout. OC was assessed using Areas of Worklife Survey (AWS) domains: workload, control, reward, community, fairness, &amp; values. Low AWS domain score indicated a workplace mismatch (WM). Burnout was assessed with the Maslach Burnout Inventory. Change in burnout was examined with repeated measures logistic regression. Results: 234 out of 917 PAs (25.5%) completed the full survey. Respondents were mostly female (86%), married/partnered (78%), in Med Onc (71%), and practicing in the outpatient setting (67%). Burnout increased from 34.8% in 2015 to 48.7% in 2019 [odds ratio for burnout, 2019 vs 2015 = 1.92 (95%CI 1.40-2.65), p &lt; .001]. Adjustment for workforce variables did not explain the increase in burnout. Among 2019 respondents, increased hours worked (p = .003), sub-specialty (P = .018), less time (%) spent on direct patient care (p = .007), practicing below full extent of education and training (p = .048), dissatisfaction with CP (p &lt; .001), and perceptions of poor collaborative physician leadership (p &lt; .001) were associated with higher rates of burnout. No difference in burnout was seen for personal or team characteristics, practice setting, years in onc, or # of patient visits. AWS scores were lower for PAs with burnout vs. without burnout (p &lt; .001). PAs with a WM had a higher rate of burnout for each AWS domain (p &lt; .001); most common WMs were fairness (44%) and workload (43%). Conclusions: The rate of burnout for Onc PAs has significantly increased and is now at levels of nearly 50%. Burnout in Onc PAs related to WM in workload is common, significant, &amp; not explained by patient volume alone. The causes of burnout are multifactorial and additional research is needed in this at risk group. [Table: see text]
Excess out‐of‐hospital deaths during the <scp>COVID</scp>‐19 outbreak: evidence of pulmonary embolism as a main determinant
Authors: Joseph Benzakoun, Ghazi Hmeydia, Tania Delabarde, Lilia Hamza, Jean‐François Meder, Bertrand Ludes, Alexandre Mebazaa
Journal: European Journal of Heart Failure (2020)
Barriers to goals of care discussion and early palliative care referral in patients with advanced cancer: A community oncology clinic survey.
Authors: Sandhya Maradana, Yugandhara Kate, Deepali Pandey, Masood Pasha Syed, Pruthvi Raj Velamala, Shekhar Patil, Ahmad Daniyal Siddiqui
Journal: Journal of Clinical Oncology (2020)

e19199 Background: Earlier discussion of end-of-life (EOL) preferences in patients with advanced cancer is associated with less aggressive EOL care. Most terminally-ill patients have not discussed their goals of care (GOC) with their healthcare providers before becoming acutely ill. Identifying various barriers in the outpatient setting might help improve GOC discussion and EOL experience for patients with advanced cancer. Methods: This cross sectional survey was designed after a thorough literature review and distributed to internal medicine residents, oncologists and oncology nurses involved in patient care in an outpatient cancer center at a community hospital. Barriers to GOC discussions and early palliative care (PC) referral were assessed on a 7-point Likert scale (1 = extremely unimportant; 7 = extremely important). Most important barrier was defined by people ranking it as very important or extremely important (6 or 7). A total of 33 health care providers were included in the final analysis. Trends were reported using descriptive statistics. Results: Patient/family related barriers were ranked the highest overall. 88% of respondents perceived patient’s difficulty in accepting prognosis as most important, followed by lack of agreement among family members (82%) and patient wanting to be 'aggressive' (82%). Among groups, 100% (6 of 6) oncologists perceived patient wanting to be ‘aggressive’ as the most important barrier, whereas disagreement among family members and patient’s difficulty in accepting poor prognosis was perceived as most important by 88% (7 of 8) nurses and 84% (16 of 19) residents respectively. Nurses also ranked patient's difficulty in understanding limitations of life sustaining treatments high. 67% of respondents, especially nurses and residents, perceived lack of training to have GOC conversations as the most important health care provider related barrier. Patient’s refusal for PC services was rated as the most important barrier for early PC referral by 61% of respondents, however, oncologists (100%) ranked lack of outpatient PC services the highest. Conclusions: These results emphasize the need for better resources to improve communication between health care providers and cancer patients in an outpatient setting. Initiatives such as formal training and targeted education in communication about GOC to health care providers can be instrumental in addressing these barriers. Integration of outpatient palliative care services into community-based oncology can be beneficial.
A phase I, first-in-human, open-label, dose-escalation study of MGD013, a bispecific DART molecule binding PD-1 and LAG-3, in patients with unresectable or metastatic neoplasms.
Authors: Jason J. Luke, Manish R. Patel, Erika Paige Hamilton, Bartosz Chmielowski, Susanna Varkey Ulahannan, Hedy L. Kindler, Shakeela Wazeen Bahadur, Philip R. Clingan, Girish Mallesara, Andrew James Weickhardt, Scott Currence, Linzhi Xu, Sanjeev Kaul, Francine Chen, Paul A. Moore, Ezio Bonvini, Brad Sumrow, George Blumenschein
Journal: Journal of Clinical Oncology (2020)

3004 Background: MGD013 is an investigational, first-in-class, Fc-bearing bispecific tetravalent DART molecule designed to bind PD-1 and LAG-3 and sustain/restore the function of exhausted T cells. MGD013 demonstrates ligand blocking properties consistent with anti-PD-1 and anti-LAG-3 benchmark molecules, and improves T cell responses beyond that observed with benchmark or component antibodies alone or in combination. Methods: This study characterizes the safety, tolerability, dose-limiting toxicities, maximum tolerated dose (MTD), PK/PD, and antitumor activity of MGD013 in patients (pts) with advanced solid and hematologic malignancies. Sequential single-pt cohorts were treated with escalating flat doses of MGD013 (1-1200 mg IV every 2 weeks), followed by a 3+3 design. Tumor-specific expansion cohorts are being treated at the recommended Phase 2 dose of 600 mg. Results: At data-cutoff, 50 pts (46% checkpoint-experienced) were treated in Dose Escalation, and 157 pts (32% checkpoint-experienced) in Cohort Expansion. No MTD was defined. Treatment-related adverse events (TRAEs) occurred in 146/207 (70.5%) pts, most commonly fatigue (19%) and nausea (11%). The rate of Grade ≥ 3 TRAEs was 23.2%. Immune-related AEs were consistent with events observed with anti-PD-1 antibodies. Mean half-life was 11 days; peripheral blood flow cytometry analyses confirmed full and sustained on-target binding during treatment at doses ≥ 120 mg. Among 41 response-evaluable [RE] dose escalation pts, 3 confirmed partial responses [cPRs] (triple negative breast cancer [TNBC], mesothelioma, gastric cancer) per RECIST 1.1 were observed, while 21 pts had stable disease [SD]. Among select expansion cohorts, PRs have been observed in epithelial ovarian cancer (n=2; both cPRs, and 7 with SD among 15 RE pts) and TNBC (n=2; 1 cPR, 1 unconfirmed PR [uPR], and 5 with SD among 14 RE pts). In a cohort of pts with HER2+ tumors treated with MGD013 in combination with margetuximab (investigational anti-HER-2 antibody), 3 PRs have been observed (breast [n=2], colorectal [n=1]; 1 cPR, 2 uPRs) and 2 pts with SD among 6 RE pts. Objective responses have been observed in several pts after prior anti-PD-1 therapy. Investigations into potential correlative biomarkers including LAG-3 and PD-1 are ongoing. Conclusions: MGD013, a novel molecule designed to coordinately block PD-1 and LAG-3, has demonstrated an acceptable safety profile and encouraging early evidence of anti-tumor activity. Clinical trial information: NCT03219268 .