tbuckley/cabot-search huggingface dataset:
Accountability in malaria prevention and treatment programmes: a review of current challenges
Authors: Georges Danhoundo, Mary Wiktorowicz, Rachel Gorman
Journal: The Lancet Global Health (2017)

BackgroundSound governance is a fundamental tenet of financial aid programmes for malaria prevention and treatment in low-income countries, yet their limited effectiveness in reducing the prevalence of malaria suggests weaknesses in the underlying accountability frameworks. Despite heightened global attention since the Roll Back Malaria Partnership was launched in 1998, 214 million new cases and 438 000 deaths due to malaria were reported in 2015. Millions of people lack access to malaria prevention and treatment services in Africa, where 80% of malaria deaths occur. We aimed to clarify accountability frameworks and mechanisms that underlie malaria prevention and treatment programmes in sub-Saharan African countries.MethodsTo clarify accountability mechanisms in maternal and child health malaria programmes in Benin, Burkina Faso, and Mali, we reviewed policy reports and studies published between Jan 1, 2000, and Aug 1, 2016, and undertook semi-structured key informant interviews with national ministries of health, non-governmental organisations, WHO, and the Global Fund to fight AIDS, Tuberculosis and Malaria. We triangulated results with findings from interviews with local health professionals and pregnant women done in 2015–16. We analysed recorded and transcribed interviews through framework analysis using NVivo software.FindingsWe included 15 reports, 60 studies, and 118 individual interviews in analysis. Our analysis of accountability frameworks identified general indicators of programme implementation success such as antenatal physician visit attendance. However, important limitations in programmes were also identified. These included insufficient delineation and measurement of operational aspects of programme implementation and a lack of specific measures within local health systems used to ensure target groups' access to malaria prevention and treatment. The manner in which preventable health system deficiencies, such as medication shortages, were to be addressed and evaluated were absent from current accountability frameworks. We also noted that global accountability measures were "glocalised" by national actors, since policy adoption was infused with local customs and practices.InterpretationNational health leadership is a key driver in successful health outcomes. Changes in accountability frameworks to foster sound national health governance and leadership could support development of a more comprehensive array of practices to specifically address challenges in programme implementation, including how preventable local health system deficiencies will be alleviated to meet programme goals. Country-specific programme goals should be harmonised with the goals of national health leaders.FundingYork University, ON, Canada.
Quality, clinician and information technology (IT) partnership for metric reporting.
Authors: Andrea Segura Smith, Julie Porter, Amogh Badwe, Eileen F Kiamanesh, Douglas W. Blayney
Journal: Journal of Clinical Oncology (2017)

128 Background: Reporting of physician defined quality metrics, using manual data abstraction, is labor intensive and not always timely. We developed a multidisciplinary team to develop a metric reporting system. Methods: The Senior Quality Consultant (SQC) partnered with the Research Data Analyst using data extracted from the electronic data warehouse, Bone Marrow Transplant Registry, Cancer Registry, Aria (Varian, Palo Alto) and Epic (Verona, WI) and the Social Security Death index. The Plan, Do, Check Act model was used to guide the team. Results: Fourteen metrics were developed in a seven-month period. Sample of metrics: Blood Marrow Transplant patient referral to Survivorship by Day 100; Genetic counseling referral for ovarian cancer; Cytogenetic testing of acute leukemia, myeloma; Chemotherapy in the last two weeks of life; Hospice enrollment at death; &gt; 10 radiation fractions for bone metastases palliation. Conclusions: The PDCA model created a shared framework for metric development. Standard definitions were developed and applied to promote consistent design. 72% (10/14) of the metrics are on a reporting system for automated data extraction and reporting. The limitation of the project is negative results are reviewed manually by the SQC because not all data elements are discrete and may require review of items (ex. progress notes or media). [Table: see text]
Effect of mutations in distinct components of the PI3K/AKT/mTOR pathway on sensitivity to endocrine therapy in estrogen receptor (ER)-positive breast cancer.
Authors: Suleiman Alfred Massarweh, Juliann Chmielecki, James Sun, Rachel Lauren Stewart, Emily Van Meter Dressler, Vera Kadamyan, Mara D. Chambers, Craig Horbinski, Murtaza Mehdi, Esther P. Black, Edward H. Romond
Journal: Journal of Clinical Oncology (2015)

532 Background: Aberrations of the PI3K/AKT/mTOR pathway are common in ER-positive breast cancer and may be associated with endocrine-resistance. We hypothesized that, since the majority of ER-positive breast cancers are actually sensitive to endocrine therapy, the most prevalent aberration in this pathway will more likely be associated with endocrine-sensitivity rather than resistance. Methods: We studied 28 tumors from patients enrolled on protocol NCT00570921 using fulvestrant and everolimus after aromatase inhibitor failure; 19 from 13 patients with endocrine-sensitive disease and 9 from 8 patients with resistant tumors. Resistance was defined as relapse within 3 years of adjuvant use or progression within 6 months in the metastatic setting. DNA was extracted from FFPE tumor tissue and subjected to next-generation-based comprehensive genomic profiling using the FoundationOne assay and alterations were then compared. Results: 10 of 13 patients with endocrine-sensitive tumors (77%) had at least one alteration in the PI3K/AKT/mTOR pathway vs. 6 of 8 patients with resistant disease (75%). PIK3CA mutations were more frequent in the sensitive group; 9/13 (69%) vs. 2/8 (25%) in the resistant group (p = 0.08). Interestingly, aberrations of pathway components other than PIK3CA were present in only 1 of 13 patients (8%) with sensitive disease vs. 4 of 8 patients (50%) with resistant disease (p = 0.0475). These aberrations were 1 activating AKT1 mutation in the sensitive group and 2 each of AKT1 activating mutations and PTEN loss in the resistant group. Further analysis of additional alterations will be presented in greater detail. Conclusions: Alterations in the PI3K/AKT/mTOR pathway are common in both endocrine-sensitive as well as resistant breast cancer but mutations of specific pathway components may distinguish sensitive from disease that is more likely to be resistant. PIK3CA mutations, which are relatively common, may be associated with more estrogen-dependent tumor biology while non-PIK3CA mutations are potentially associated with endocrine-resistance in ER-positive breast cancer. Further investigation of these findings is warranted.
Frequency, predictors and medical record documentation of chemical coping among advanced cancer patients.
Authors: Kimberson Tanco, Jung Hye Kwon, Ji Chan Park, Angelique Wong, Lisa Seo, Diane D Liu, Gary B. Chisholm, Janet L. Williams, David Hui, Eduardo Bruera
Journal: Journal of Clinical Oncology (2015)

e20595 Background: Chemical coping, defined as using prescribed opioids to control non-nociceptive symptoms, is one of the major challenges in the management of cancer pain. In this prospective study, we determined the frequency of opioid-related chemical coping among advanced cancer patients as diagnosed by palliative medicine specialists. We also determined predictors for chemical coping and the concordance between the physician's diagnosis and documentation in the medical records. Methods: Palliative medicine specialists evaluated and diagnosed consecutive patients seen for chemical coping. The proportion of patients identified as chemically coping was compared to the proportion documented in the medical records. Demographic data, cancer diagnosis, history of smoking, substance abuse, and psychiatric disease, morphine equivalent daily dosage (MEDD), CAGE (Cut-down, Annoyed, Guilty, Eye-opener) questionnaire scores, and Edmonton Symptom Assessment System (ESAS) scores were also collected. Results: 432 patients were evaluated. 76 patients (18%, 14%-21%) were diagnosed as chemically coping. Documentation of chemical coping in the medical records was reported in only 15 patients (4%, 2%-6%). CAGE positivity (OR 2.89), younger age (OR 0.97 per year), better performance status (OR 0.68 per point), pain (OR 1.20 per point) and well-being (OR 1.28 per point) were found to be significant predictors of chemical coping by protocol definition. After recursive partitioning, 21/50 patients (42%) who were CAGE positive and ECOG ≤ 2 were diagnosed as chemically coping. Conclusions: Approximately 18% of palliative care patients seen were diagnosed as chemically coping by palliative medicine specialists. The frequency of documentation in the medical records was significantly lower. Better and safer ways for physicians to assess and report chemical coping are needed.
Phase II trial of tamoxifen and interferon alpha in patients with metastatic or recurrent soft tissue sarcoma
Authors: M. J. Kyasa
Journal: Journal of Clinical Oncology (2004)

9031 Background: Management of patients with advanced soft tissue sarcoma (STS) is difficult and often disappointing. We evaluated the role of Tamoxifen (T) and Interferon alpha 2b (I) for their anti-angiogenic properties in metastatic or recurrent STS. Methods: Patients with advanced STS who had failed at least one prior systemic therapy, with performance status of 0–2 on ECOG scale, and adequate organ functions were enrolled on this study between October 1999 and June 2003.Patients received 20 mg of Tamoxifen daily and subcutaneous Interferon alpha 2b (Schering-Plough) 3 million-unit/square meters three times weekly .Patients were evaluated for response at 8 weeks and at 6 months, and those with stable or responsive disease continued treatment up to 26 weeks after which treatment was discontinued and patients were followed. Results: Seventeen patients were enrolled on the study. All patients had received at east one prior chemotherapy regimen and 8 patients had received prior radiotherapy. Median age 56 years (27–76), Male/Female 11/6, 12 Caucasians. Median follow-up was 24 weeks (2–126 weeks). Two of the seventeen patients were not started on treatment due to rapidly deteriorating condition, 4 patients developed early severe toxicity and eventually were taken off protocol. Out of the 11 evaluable study patients, There was 1(7%) Complete remission with 70 weeks duration of response, no partial responses, and 2(13%) stable disease of 84 and 45 weeks duration, 8(53%) had progressive disease. Encountered Grade 3 and 4 toxicities included thrombocytopenia (1), neutropenia (1), abnormal LFTs (1) and non-Q wave myocardial infarction. No treatment related deaths were encountered. Conclusions: The combination of interferon and tamoxifen has activity in advanced STS, which warrants further evaluation. No significant financial relationships to disclose.
Sudden Unexpected Death in Epilepsy Among Patients With Benign Childhood Epilepsy With Centrotemporal Spikes
Authors: Kyra Doumlele, Daniel Friedman, Jeffrey Buchhalter, Elizabeth J. Donner, Jay Louik, Orrin Devinsky
Journal: JAMA Neurology (2017)

Children with benign epilepsy with centrotemporal spikes (BECTS) have traditionally been considered to have a uniformly good prognosis. However, benign may be a misnomer because BECTS is linked to cognitive deficits, a more severe phenotype with intractable seizures, and the potential for sudden unexpected death in epilepsy (SUDEP).To determine if cases of BECTS are present in the North American SUDEP Registry (NASR).The NASR is a clinical and biospecimen repository established in 2011 to promote SUDEP research. The NASR database, which includes medical records, results of electroencephalographic tests, and interviews with family members of patients with epilepsy who died suddenly without other identifiable causes of death, was queried from June 3, 2011, to June 3, 2016, for cases of BECTS. The patients with epilepsy had died suddenly without other identifiable causes of death (eg, drowning, trauma, exposure to toxic substances, or suicide); SUDEP classification was determined by the consensus of 2 epileptologists.Cases of SUDEP among children who received a diagnosis of BECTS among patients reported in the NASR.Three boys (median age at death, 12 years; range, 9-13 years) who received a diagnosis of BECTS by their pediatric epileptologist or neurologists were identified among 189 cases reported in the NASR. The median age of epilepsy onset was 5 years (range, 3-11 years), and the median duration of epilepsy was 4 years (range, 1-10 years). Two deaths were definite SUDEP, and 1 was probable SUDEP. Independent review of clinical and electroencephalographic data supported the diagnosis of BECTS in all 3 patients. None of the patients was prescribed antiseizure drugs, either owing to physician recommendation or mutual decision by the physician and parents. All 3 patients were found dead in circumstances typical of SUDEP. The 3 patients spanned the spectrum of BECTS severity: 1 had only a few seizures, 1 had more than 30 focal motor seizures, and 1 had 4 witnessed generalized tonic-clonic seizures and approximately 30 suspected generalized tonic-clonic seizures.Sudden unexpected death in epilepsy is a very rare outcome in BECTS that clinicians should consider discussing in appropriate circumstances and possibly factoring into treatment decisions.
Association of <i>POLE</i>-mutated and MSI endometrial cancers with an elevated number of tumor-infiltrating and peritumoral lymphocytes and higher expression of PD-L1.
Authors: Brooke E. Howitt, Lynette M. Sholl, Lauren Ritterhouse, Jaclyn C Watkins, Scott J. Rodig, Kyle Strickland, Alan D. D'Andrea, Ursula Matulonis, Panagiotis Konstantinopoulos
Journal: Journal of Clinical Oncology (2015)

5511 Background: TCGA identified two groups of endometrial cancers with high mutation frequency: an ultramutated group of tumors which harbored mutations in polymerase e (POLE) and a hypermutated group with microsatellite instability (MSI). We hypothesized that these hypermutated tumors may harbor more neoantigens and thus stimulate a stronger immune response compared to tumors with low mutation frequency. In this regard, we evaluated whether hypermutated tumors are associated with an elevated number of tumor-infiltrating lymphocytes (TILs) and peritumoral lymphocytes and higher expression of the immune modulatory molecule PD-L1. Methods: We evaluated 4 POLE-mutated (determined via Sanger sequencing of mutational hotspots), 28 MSI-tumors and 32 microsatellite stable (MSS) endometrioid endometrial tumors. MSI status was determined using immunohistochemistry (IHC). IHC was performed for CD3, CD4, CD8, CD20, PD-1 and PD-L1 using standard protocols. For evaluation of TILs, a photomicrograph (40X) of the area of maximum CD3+ intraepithelial lymphocytes was obtained with corresponding photomicrographs for the additional stains. For peritumoral lymphocytes, a semi-quantitative scoring method was utilized. Results: POLE-mutated and MSI tumors exhibited significantly elevated CD3+ (p = 0.001), CD4+ (p = 0.078) and CD8+ (p < 0.001) TILs compared to MSS tumors. CD20+ TILs were not statistically significantly different between MSI/POLE tumors and MSS tumors. Expression of PD-1 (p < 0.001) and PD-L1 (p = 0.022) was higher in TILs of POLE and MSI tumors compared to MSS tumors. Furthermore, POLE and MSI tumors harbored more peritumoral T-lymphocytes (p < 0.001) and higher expression of PD-1 (p = 0.001) and PD-L1 (p < 0.001) compared to MSS tumors. There were no significant differences in TILs, peritumoral lymphocytes and PD-1/PD-L1 expression between POLE-mutated and MSI tumors. Conclusions: POLE-mutated and MSI endometrial cancers are associated with an elevated number of TILs and peritumoral lymphocytes, and higher expression of PD-1 and PD-L1. These data support trials of immune-checkpoint inhibitors in hypermutated endometrial cancers.
춘계학술대회 발표 : 포스터전시 ; 장기간 Ursodeoxycholic Acid 치료로 완전 호전된 간의 결절성 재생증식 1예
Authors: 손병관, 손주현, 박윤경, 전용철, 한동수, 이민호, 이동후, 기춘석
Journal: Clinical and Molecular Hepatology (2006)
Development of a QOL module for head and neck cancer patients with enteral feeding tubes
Authors: J. Ringash, B. Lemon
Journal: Journal of Clinical Oncology (2004)

6153 Background: Head and neck cancer (HNC) patients frequently require enteral feeding (EF) during treatment, but how this affects quality of life (QOL) is unknown. We developed a QOL module for use with existing HNC disease-specific QOL questionnaires in patients with EF tubes. Methods: Literature review and a clinician focus group were used to generate QOL items. Items were formatted as statements rated on a 5 point Likert-type scale. The prototype was pilot tested in 12 HNC patients with current or recent EF tubes. The resulting beta version underwent item reduction in a non-overlapping sample of 36 HNC patients, who indicated the importance of each item. Items were kept if their summary importance scores were ranked above median by the whole group or by Chinese or female minority subgroups. Results: Items from the literature were provided to a focus group representing radiation oncology, interventional radiology, radiation therapy, nursing, and nutrition. Of 41 items generated, after pilot testing 15 were eliminated; 2 items identified by 2 or more patients, and 2 “positive” items suggested by investigators, were added. The item reduction study sample of 36 patients (mean age 57.5) included 20 Caucasian individuals, 9 Chinese, and 7 of other cultural background, with 12 females and 24 males. Cancer sites included nasopharynx (16), oropharynx (9), oral cavity (5), hypopharynx (2), unknown primary (2), larynx (1), and paranasal sinus (1). Overall, 17 items rated above median importance were kept. Among Chinese patients, 2 additional items were kept, and among women 1 additional item was kept. No additional write-in items were identified by 2 or more patients. Conclusions: We have developed a 20 item QOL module for HNC patients with EF tubes. The module is currently undergoing validity and reliability testing in a new sample of 75 patients with EF tubes. This instrument may be useful in trials comparing aggressive treatment strategies for HNC or different methods of EF. No significant financial relationships to disclose.
DAP-kinase positive tumor-associated macrophages induce apoptotic cell death in colorectal cancer cells
Authors: Regine Schneider-Stock, Dörthe Küster, Oliver Ullrich, Falk Mittag, Carsten Boltze, Brigitte Peters, Sabine Krüger, Frank Meyer, Cornelia Hintze, Roland Hartig, Albert Roessner
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

5532 

Background and Aims : The death-associated protein kinase (DAP-kinase) is a cytoskeleton-associated protein which is crucially involved in the induction of early apoptotic pathways. Aberrant hypermethylation of the DAP-kinase promotor plays a major role in tumorigenesis. We aimed to investigate the inactivation of DAP-kinase and its association with apoptotic cell death in 94 colorectal carcinomas. Methods : DAP-kinase promotor hypermethylation and mRNA expression were investigated using methylation-specific PCR and real-time RT-PCR, respectively. The immunohistochemical expression of DAP-kinase, Fas and Fas-ligand (FasL) proteins and TUNEL-positive tumor cells were studied by single, double and triple immunofluorescence using laser-scan confocal microscopy. Histopathological findings were confirmed functionally in a co-culture model of U937 monocytic cells and HCT-116 colorectal tumor cells. Results : We found an aberrant promotor hypermethylation in more than 50% of carcinomas resulting in DAP-kinase inactivation at the mRNA and protein level and decreased apoptosis in tumor cells. DAP-kinase protein was localized in tumor cells and specifically in invading tumor-associated macrophages. High DAP-kinase expression co-localized with FasL overexpression in tumor-associated macrophages. Co-culture experiments revealed that macrophageal DAP-kinase expression and Fas-L secretion were indeed required for apoptosis in human colorectal carcinoma cells. Conclusions : Our study provides the first evidence for a synergistic interaction between macrophages and colorectal tumor cells during apoptosis in vivo and in vitro . Moreover, DAP-kinase expression in tumor-associated macrophages is an important mechanism of FasL-mediated tumor cell apoptosis. Thus, targeting DAP-kinase might represent an interesting new therapeutic option in order to enhance anti-tumor defense by the innate immune system.
An evaluation of tuberculosis contact investigations against national standards
Authors: Sean M Cavany, Tom Sumner, Emilia Vynnycky, Clare Flach, Richard G White, H Lucy Thomas, Helen Maguire, Charlotte Anderson
Journal: Thorax (2017)

<h3>Background</h3> Contact tracing is a key element in England9s 2015 collaborative TB strategy, although proposed indicators of successful contact tracing remain undescribed. <h3>Methods</h3> We conducted descriptive and multivariable analyses of contact tracing of TB cases in London between 1 July 2012 and 31 December 2015 using cohort review data from London9s TB Register, identifying characteristics associated with improved indicators and yield. <h3>Results</h3> Of the pulmonary TB cases notified, 60% (2716/4561) had sufficient information for inclusion. Of these, 91% (2481/2716) had at least 1 contact (median: 4/case (IQR: 2–6)) identified, with 86% (10 251/11 981) of these contacts evaluated. 4.1% (177/4328), 1.3% (45/3421) and 0.70% (51/7264) of evaluated contacts of pulmonary smear-positive, pulmonary smear-negative and non-pulmonary cases, respectively, had active disease. Cases who were former prisoners or male were less likely to have at least one contact identified than those never imprisoned or female, respectively. Cases diagnosed at clinics with more directly observed therapy or social workers were more likely to have one or more contacts identified. Contacts screened at a different clinic to their index case or of male index cases were less likely to be evaluated than those screened at the same clinic or of women, respectively; yield of active disease was similar by sex. 10% (490/4850) of evaluated child contacts had latent TB infection. <h3>Conclusions</h3> These are the first London-wide estimates of TB contact tracing indicators which are important for monitoring the strategy9s success and informing risk assessment of index cases. Understanding why differences in indicators occur between groups could improve contact tracing outcomes.