tbuckley/cabot-search huggingface dataset:
Patients with private health insurance are asked to help out cash strapped NHS
Authors: Caroline White
Journal: BMJ (2016)

Two clinical commissioning groups (CCGs) in England have admitted that they are encouraging GPs to ask patients with private medical insurance to think about using it to obtain treatment in an effort to reduce NHS costs.

As reported by the GP magazine Pulse ,1 since November 2015 NHS Mid Essex CCG has been asking GPs to discuss with privately insured patients how they might be able to use their policies for medical treatment since November 2015.

The move has resulted in a 6% increase in referrals to private healthcare for the first six months of this year when compared with …
Medication Review After a Fracture—Absolutely Essential
Authors: Sarah D. Berry, Douglas P. Kiel
Journal: JAMA Internal Medicine (2016)

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Stress activates pronociceptive endogenous opioid signalling in DRG neurons during chronic colitis
Authors: Raquel Guerrero-Alba, Eduardo E Valdez-Morales, Nestor N Jimenez-Vargas, Cintya Lopez-Lopez, Josue Jaramillo-Polanco, Takanobu Okamoto, Yasmin Nasser, Nigel W Bunnett, Alan E Lomax, Stephen J Vanner
Journal: Gut (2016)

Psychological stress accompanies chronic inflammatory diseases such as IBD, and stress hormones can exacerbate pain signalling. In contrast, the endogenous opioid system has an important analgesic action during chronic inflammation. This study examined the interaction of these pathways.Mouse nociceptive dorsal root ganglia (DRG) neurons were incubated with supernatants from segments of inflamed colon collected from patients with chronic UC and mice with dextran sodium sulfate (cDSS)-induced chronic colitis. Stress effects were studied by adding stress hormones (epinephrine and corticosterone) to dissociated neurons or by exposing cDSS mice to water avoidance stress. Changes in excitability of colonic DRG nociceptors were measured using patch clamp and Ca2+ imaging techniques.Supernatants from patients with chronic UC and from colons of mice with chronic colitis caused a naloxone-sensitive inhibition of neuronal excitability and capsaicin-evoked Ca2+ responses. Stress hormones decreased signalling induced by human and mouse supernatants. This effect resulted from stress hormones signalling directly to DRG neurons and indirectly through signalling to the immune system, leading to decreased opioid levels and increased acute inflammation. The net effect of stress was a change endogenous opioid signalling in DRG neurons from an inhibitory to an excitatory effect. This switch was associated with a change in G protein-coupled receptor excitatory signalling to a pathway sensitive to inhibitors of protein kinase A-protein, phospholipase C-protein and G protein βϒ subunits.Stress hormones block the inhibitory actions of endogenous opioids and can change the effect of opioid signalling in DRG neurons to excitation. Targeting these pathways may prevent heavy opioid use in IBD.
Impact of chemoradiotherapy (CRT) on local control and time without treatment in patients with locally advanced pancreatic cancer (LAPC) included in the international phase III LAP 07 study.
Authors: Florence Huguet, Pascal Hammel, Dewi Vernerey, David Goldstein, Jean Luc Van Laethem, Bengt Glimelius, Nigel Spry, Sophie Paget-Bailly, Franck Bonnetain, Christophe Louvet
Journal: Journal of Clinical Oncology (2014)

4001^ Background: In the LAP07 multicenter randomized study, administration of CRT in patients with LAPC controlled with induction chemotherapy (CT) was not superior to continuing CT alone in terms of overall survival. However, whether CRT should have an impact on locoregional tumor control remains unknown. Methods: LAPC patients were first randomized to gemcitabine or gemcitabine plus erlotinib. Patients with controlled disease after 4 months of CT were then randomized to two additional months of CT or CRT 54 Gy and concurrent capecitabine. A quality control for radiotherapy was done using validation by a dummy run and assessment of treated patients. Primary objective was overall survival (OS) in patients who acceded to the second randomization. Survivals were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: Among the 442 included patients, 269 patients had tumor control after 4 months of induction CT and were randomized to either the CRT arm (n=133) or the CT arm (n=136). The OS was not significantly different between the two arms (15.2 vs 16.5 months, p=0.8). At the time of analysis, 238 patients had a tumor progression, which was locoregional in 96 patients (50.5%) and metastatic in 97 patients (49.5%). In the CRT arm, patients had significantly less local tumor progression compared to the CT arm (34% vs 65%, p<0.0001). Median time without treatment (i.e. reintroduction of chemotherapy) was longer in the CRT arm compared to the CT arm (159 vs 96 days, respectively, p=0.05). Conclusions: Even though the OS was not improved in the CRT arm, patients with non-progressive LAPC after 4 months of induction CT had a longer time without treatment in the CRT arm with significantly less local tumor progression which could translate into a better quality of life. Clinical trial information: NCT00634725.
Intermediate Dose Methotrexate in Low-Risk Acute Lymphoblastic Leukemia. Results of the FRALLE 93A Protocol.
Authors: Yves Perel, Hervé Chambost, Virginie Gandemer, Thierry Leblanc, Schneider Pascale, Schmitt Claudine, Mariane Debré, Christiane Vermylen, Gérard Couillault, Jean-Paul Lamagnere, Marie-Françoise Auclerd, Guy Leverger, André Baruchel
Journal: Blood (2004)
Activated Sumoylation Is a Hallmark Of Burkitt's Lymphoma and MYC Driven Cancer Leading To Synthetic Lethal Interactions With Sumoylation Inhibitors
Authors: Alexander Hoellein, Sabine Steidle, Mohammad Fellahi, Stephanie Schoeffmann, Martina Rudelius, Christian Peschel, John L Cleveland, Ulrich Keller
Journal: Blood (2013)
Re-discovering NK cell allo-reactivity in the therapy of solid tumors
Authors: Luca Castagna, Domenico Mavilio
Journal: Journal for ImmunoTherapy of Cancer (2016)

Currently, refractory lymphoma or advanced solid tumors have an unfavorable prognosis as conventional therapies are often not curative while providing high levels of toxicity. Indeed, the overall survival of these patients is relatively short with a poor quality of life. This clinical evidence
Canagliflozin Slows Progression of Renal Function Decline Independently of Glycemic Effects
Authors: Hiddo J. L. Heerspink, Mehul Desai, Meg Jardine, Dainius Balis, Gary Meininger, Vlado Perkovic
Journal: Journal of the American Society of Nephrology (2016)

Sodium-glucose cotransporter 2 inhibition with canagliflozin decreases HbA1c, body weight, BP, and albuminuria, implying that canagliflozin confers renoprotection. We determined whether canagliflozin decreases albuminuria and reduces renal function decline independently of its glycemic effects in a secondary analysis of a clinical trial in 1450 patients with type 2 diabetes receiving metformin and randomly assigned to either once-daily canagliflozin 100 mg, canagliflozin 300 mg, or glimepiride uptitrated to 6-8 mg. End points were annual change in eGFR and albuminuria over 2 years of follow-up. Glimepiride, canagliflozin 100 mg, and canagliflozin 300 mg groups had eGFR declines of 3.3 ml/min per 1.73 m2 per year (95% confidence interval [95% CI], 2.8 to 3.8), 0.5 ml/min per 1.73 m2 per year (95% CI, 0.0 to 1.0), and 0.9 ml/min per 1.73 m2 per year (95% CI, 0.4 to 1.4), respectively (P<0.01 for each canagliflozin group versus glimepiride). In the subgroup of patients with baseline urinary albumin-to-creatinine ratio ≥30 mg/g, urinary albumin-to-creatinine ratio decreased more with canagliflozin 100 mg (31.7%; 95% CI, 8.6% to 48.9%; P=0.01) or canagliflozin 300 mg (49.3%; 95% CI, 31.9% to 62.2%; P<0.001) than with glimepiride. Patients receiving glimepiride, canagliflozin 100 mg, or canagliflozin 300 mg had reductions in HbA1c of 0.81%, 0.82%, and 0.93%, respectively, at 1 year and 0.55%, 0.65%, and 0.74%, respectively, at 2 years. In conclusion, canagliflozin 100 or 300 mg/d, compared with glimepiride, slowed the progression of renal disease over 2 years in patients with type 2 diabetes, and canagliflozin may confer renoprotective effects independently of its glycemic effects.
Breast-feeding: time to teach what we preach
Authors: A. Lenihan
Journal: JAMA (1993)

To the Editor.  —Dr Freed's recent article on breast-feeding 1 brings attention to a long-neglected resource needed to assist in reaching the Healthy People 2000  2 goals for promotion of breast-feeding.  However, we regret there is an error in the Women, Infants, and Children (WIC) program costs for infants and breast-feeding women provided in the article. The actual yearly cost to the North Carolina WIC program for bottle-feeding infants is $932 (cost of infant food package and non— breast-feeding postpartum food package). This is more than twice the cost of $396 to WIC for breast-feeding women (cost of breast-feeding food package).  The critical issue to be emphasized is that there are still significant cost savings to the WIC program, and thus the taxpayer, for every woman who breast-feeds an infant.
Brain Metastases in Breast Cancer Network Germany (BMBC, GBG 79): Treatment patterns and clinical outcome of more than 1000 patients with brain metastases from breast cancer.
Authors: Volkmar Mueller, Sibylle Loibl, Elena Laakmann, Doris Augustin, Felix Flock, Hans Hermann Dohmen, Strittmatter Hans-Joachim, Matthias Frank, Tobias Hesse, Atanas Ignatov, Thorsten Kuehn, Tjoung-Won Park-Simon, Marcus Schmidt, Florian Wuerschmidt, Tanja N. Fehm, Volker Moebus, Gunter Von Minckwitz, Nicole Burchardi, Isabell Witzel
Journal: Journal of Clinical Oncology (2016)

2070 Background: In order to improve knowledge about treatment and outcome of breast cancer patients with brain metastases (BM) we initiated the registry Brain Metastases in Breast Cancer Network Germany (BMBC, GBG79). Methods: Patients diagnosed with BM since 2000 were included retrospectively and prospectively. 1105 patients from 54 centers were analyzed. Results: Median age at diagnosis of BM was 51 years (20 – 87 years). 49.0 % of patients (472/1105) had HER2-pos., 20.5% (198/1005) triple-neg. and 30.5% (294/1005) luminal primary tumors. One year survival rate from diagnosis of BM was 35.7 % (CI95%: 32.6 – 38.8). Median time from first diagnosis of BM to death in the entire cohort was 7.1 month (CI95%: 5.8 – 7.9). HER2-positive patients had the longest median survival with 12.1 mo. (CI95%: 10.2 – 13.7) compared to 5.5 mo. (CI95%: 4.1 – 7.1) for luminal primary tumors and 4.1 mo. (CI95%: 3.1 – 4.8) for triple-negative patients (p < 0.001). Median OS of patients with BM diagnosed between 2000 and 2006 was 7.2 mo. (CI95%: 5.3 - 9.6) compared to 6.7 mo. (CI95%: 5.5 -8.1) of patients diagnosed between 2007 and 2012 (p = 0.848). No relevant OS improvements were observed in these time intervals for luminal (5.1 mo. [CI95%: 2.7-10.4] vs. 5.8 mo. [CI95%: 4.1 -8.0]; p = 0.541), triple negative (4.6 months [CI95%: 3.3 -7.4] vs. 4.0 mo [CI95%: 2.4 - 5.4]; p = 0.558) or HER2-pos. patients (10.7 mo. [CI95% 7.7- 13.5] vs. 12.6 [CI95% 9.4 – 15.5]; p = 0.320). 32.8% of HER2-pos. patients received HER2-directed therapies beyond the diagnosis of BM (55.5% trastuzumab, 53.5% lapatinib, 19.4% T-DM1 and 11.0% trastuzumab and pertuzumab). Those HER2-pos. patients receiving HER2-directed therapy after the diagnosis of BM lived longer than those without (median 17.7, CI95%: 15.0 – 22.0 vs. 12.9 mo., CI95%: 10.5 – 17.1, p = 0.015). Conclusions: Patients that received HER2-directed therapy after diagnosis of BM had an improved survival. However, we could not observe improvement of survival over the study period in any tumor subtype. These findings underline the high need for the development of new treatment strategies in patients with BM from breast cancer.
Induction of Remission Prior to Transplantation Improves the Disease-Free Survival (DFS) of Patients with Advanced Myelodysplastic Syndromes (MDS) Treated with Myeloablative T-Cell Depleted (TCD) Stem Cell Transplants (SCT) from HLA Identical Siblings.
Authors: H.R. Castro-Malaspina, Ann A. Jakubowski, Esperanza B. Papadopoulos, Farid Boulad, James W. Young, Nancy A. Kernan, Miguel A. Perales, Trudy N. Small, Katharina C. Hsu, Michelle Chiu, Glenn Heller, Marcel van den Brink, Stephen D. Nimer, Richard J. O’Reilly
Journal: Blood (2005)
Reflectance confocal microscopy as a noninvasive complementary tool in the diagnosis of psoriatic balanitis
Authors: E. Arzberger, A. Oliveira, C. Massone, P. Komericki, I. Zalaudek, R. Hofmann-Wellenhof
Journal: British Journal of Dermatology (2016)

Genital lesions are estimated to occur in 30-40% of patients with psoriasis with a slight predominance in men. Less frequently they are the first, and rarely the sole presentation of this common inflammatory disease in only 2-5% of affected patients.1 Therefore, its differential diagnosis can be wide, including mainly inflammatory diseases.

This article is protected by copyright. All rights reserved.
PF-05280014, a potential biosimilar to trastuzumab: Overview and clinical development in Japan
Authors: Chiho Ono, Tomofumi Ishikawa, Yoshinori Nishizawa, Charles M Zacharchuk, Donghua Yin, Xu Meng, Ruifeng Li, Ira A. Jacobs
Journal: Annals of Oncology (2015)
A systematic review of the effectiveness of discharge care bundles for patients with COPD
Authors: Maria B Ospina, Kelly Mrklas, Lesly Deuchar, Brian H Rowe, Richard Leigh, Mohit Bhutani, Michael K Stickland
Journal: Thorax (2016)

<h3>Background</h3> A COPD discharge bundle is a set of evidence-based practices aimed at improving patient outcomes after discharge from acute care settings following an exacerbation. We conducted a systematic review on the effectiveness of COPD discharge bundles and summarised their individual care elements. <h3>Methods</h3> Biomedical electronic databases and clinical trial registries were searched from database inception through April 2016 to identify experimental studies evaluating care bundles offered to patients with COPD at discharge. Random-effects meta-analyses of clinical trials data were conducted for hospital readmissions, mortality, and quality of life (QoL). <h3>Results</h3> The review included 14 studies (5 clinical trials, 7 uncontrolled trials, and 2 interrupted time series). A total of 26 distinct elements of care were included in the bundles of individual studies. Evidence from four clinical trials with moderate-to-high risk of bias showed that COPD discharge bundles reduced hospital readmissions (pooled risk ratio (RR): 0.80; 95% CI 0.65 to 0.99). There was insufficient evidence that care bundles influence long-term mortality (RR: 0.74; 95% CI 0.43 to 1.28; four trials) or QoL (mean difference in St. George9s Respiratory Questionnaire: 1.84; 95% CI −2.13 to 5.8). <h3>Conclusions</h3> Discharge bundles for patients with COPD led to fewer readmissions but did not significantly improve mortality or QoL. Future studies should employ higher quality research methods, fully report care bundle elements, implementation strategies and intervention fidelity to better evaluate the effectiveness of packaging evidence-based interventions together to improve outcomes of patients with COPD discharged from acute care settings.
Controversial Practices in Allergy
Authors: Donald J. Nalebuff
Journal: JAMA (1983)

To the Editor.—  In the SPECIAL COMMUNICATION by Grieco entitled Controversial Practices in Allergy (1982; 247:3106), Grieco raised issue with the clinical usefulness of the radioallergosorbent (RAST) test in general and our modification of the RAST 1 in particular. Using the data obtained from one report 2 and a short abstract, 3 he made two critical judgments regarding our system; that is, he repeated their concern regarding both the specificity of the modified RAST and the ability of the physician to use the score obtained as a guide in selecting a safe initial immunotherapy dose. A careful analysis of the reported data shows that such conclusions are not warranted.  In regard to the first matter, Grieco refers to the observation that a non-IgE-containing material was scored false-positive in one third (7/21) of the modified RAST assays. This is an error. The scores were actually reported as equivocal. He also failed
Prolonged vs Short Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With or Without Peripheral Arterial Disease
Authors: Anna Franzone, Raffaele Piccolo, Giuseppe Gargiulo, Sara Ariotti, Marcello Marino, Andrea Santucci, Andrea Baldo, Giulia Magnani, Aris Moschovitis, Stephan Windecker, Marco Valgimigli
Journal: JAMA Cardiology (2016)

Patients with concomitant peripheral arterial disease (PAD) experience worse cardiovascular outcomes after percutaneous coronary intervention (PCI).To assess the efficacy and safety of prolonged (24 months) vs short (≤6 months) dual antiplatelet therapy (DAPT) in patients with PAD undergoing PCI.This subanalysis of the randomized Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study (PRODIGY) trial assessed unselected patients from tertiary care hospitals with stable coronary artery disease or acute coronary syndromes with or without concomitant PAD from December 2006 to December 2008. Data analysis was performed from January 7 to April 4, 2016.Percutaneous coronary intervention.Rates of the primary efficacy end point, composite of death, myocardial infarction, or cerebrovascular accidents, and occurrence of the key safety end point, a composite of Bleeding Academic Research Consortium type 2, 3, or 5.This analysis comprised 246 and 1724 patients with and without PAD, respectively. In the patients with PAD, mean (SD) age was 73.2 (9.2) in the prolonged group and 75.7 (8.7) years in the short DAPT group, and 97 (82.2%) were male in the prolonged group and 92 (71.9%) were male in the short DAPT group. In the patients without PAD, mean (SD) age was 67.1 (11.2) years in the prolonged group and 66.8 (11.3) years in the short DAPT group, and 667 (76.8%) were male in the prolonged group and 655 (76.6%) were male in the short DAPT group. Status of PAD was associated with a higher risk of death and ischemic events (hazard ratio [HR], 2.80; 95% CI, 2.05-3.83; P < .001). Prolonged vs short DAPT conveyed a lower risk of the primary efficacy end point in patients with PAD (19 [16.1%] vs 35 [27.3%]; HR, 0.54; 95% CI, 0.31-0.95; P = .03) but not in patients without PAD (81 [9.3%] vs 63 [7.4%]; HR, 1.28; 95% CI, 0.92-1.77; P = .15), with positive interaction (P = .01). The risk of definite or probable stent thrombosis was significantly lower in patients with PAD treated with prolonged compared with short DAPT (HR, 0.07; 95% CI, 0-1.21; P = .01). Bleeding Academic Research Consortium type 2, 3, or 5 bleeding occurred in 6 patients with PAD (5.2%) receiving prolonged DAPT relative to 8 (6.9%) of those receiving short DAPT (HR, 0.77; 95% CI, 0.27-2.21; P = .62), with a significant interaction (P = .04) compared with patients without PAD.Peripheral artery disease confers a poor prognosis in patients undergoing PCI in the setting of stable coronary artery disease or acute coronary syndromes. Prolonged DAPT lowers the risk of ischemic events with no apparent bleeding liability in this high-risk group.clinicaltrials.gov Identifier: NCT00611286.
A Phase I/Ib study of MEK162 (binimetinib), a MEK inhibitor, in combination with carboplatin and pemetrexed in patients with non-squamous NSCLC.
Authors: Safiya Karim, Ronald Feld, Natasha B. Leighl, Frances A. Shepherd, Penelope Ann Bradbury, Geoffrey Liu, Donna M. Graham
Journal: Journal of Clinical Oncology (2016)

TPS2609 Background: RAS is the most commonly mutated oncogene in lung cancer. While direct inhibitors of RAS have not yet been successfully developed, MEK inhibitors have shown activity in RAS mutated tumors including KRAS mutant NSCLC. Binimetinib (ARRAY, Boulder CO) is an oral highly selective inhibitor of MEK1/2 and has demonstrated preclinical and clinical activity. Distinct from other MEK inhibitors in clinical development, it has activity against NRAS mutant cancers, with improved PFS as a single agent in NRAS mutant melanoma compared to dacarbazine (NEMO). Methods: In this phase I/Ib study, binimetinib is combined with pemetrexed/carboplatin in advanced non-squamous NSCLC patients. Primary study objectives include determination of the RP2D of continuous binimetinib plus pemetrexed/carboplatin, safety (NCI CTCAE v. 4) of the combination and exploration of efficacy (ORR per RECIST v.1.1). Population PK is being characterized and potential relationships between RAS mutation subtypes and response explored. A 3+3 dose-escalation design with 3 treatment groups will be used to determine the maximum administered dose and RP2D of the combination. The cohort will be expanded at the RP2D to a total of 35 patients with stratification by genotype (RAS/RAF wild type (10), KRAS G12C mutant (10), non-G12C mutant (10), BRAF/NRAS mutant (5)). Binimetinib 30-45 mg BID daily (starting day -7 with a 48 hour break pre-chemotherapy) is combined with pemetrexed 500 mg/m2 IV and carboplatin AUC 5-6 mg*min/mL. Patients who have completed 4-6 cycles of chemotherapy may continue to receive MEK162 until disease progression. Patient population: Patients must be chemo-naïve with EGFR wild type, non-ALK rearranged non-squamous NSCLC, have ECOG PS 0/1, adequate organ, marrow, and normal cardiac function. Those with prior retinal vein occlusion, coronary syndromes, active infection and significant comorbidities are excluded. Patients with stable treated CNS metastases are permitted. Accrual to cohort 1 is ongoing. Clinical trial information: NCT02185690.
Total Hip Replacement
Authors: Mark G. Lazansky
Journal: JAMA (1970)

<h3>To the Editor.—</h3> How disappointing that the first article inThe Journal(<b>212</b>:611, 1970) to describe the striking progress in hip reconstruction being made with total hip replacement by Charnley, McKee, and Watson-Farrar and Ring in England should contain many inaccuracies. Picking only the most glaring of the errors in the article, I point out for your readers: The statement that Girdlestone's operation "may be expected to make weight bearing on the affected side impossible" is patently false and indicates that the author has had little occasion to observe patients who have had the procedure performed. While it scarcely leaves an elegant hip (rather one characterized by shortening of one to two inches, a pronounced limp, and need for a cane, though generally pain-free and mobile), weight bearing is hardly impossible. Charnley's present series of total hip replacements is closer to 4,000 than 8,000. The Charnley