tbuckley/cabot-search huggingface dataset:
New HIV diagnoses among adults aged 50 years or older in 31 European countries, 2004–15: an analysis of surveillance data
Authors: Lara Tavoschi, Joana Gomes Dias, Anastasia Pharris, Daniela Schmid, André Sasse, Dominique Van Beckhoven, Tonka Varleva, Tatjana Nemeth Blazic, Linos Hadjihannas, Maria Koliou, Marek Maly, Susan Cowan, Kristi Rüütel, Kirsi Liitsola, Mika Salminen, Françoise Cazein, Josiane Pillonel, Florence Lot, Barbara Gunsenheimer-Bartmeyer, Stavros Patrinos, Dimitra Paraskeva, Maria Dudas, Haraldur Briem, Gudrun Sigmundsdottir, Derval Igoe, Kate O'Donnell, Darina O'Flanagan, Barbara Suligoi, Šarlote Konova, Sabine Erne, Irma Caplinskiene, Aurélie Fischer, Jackie Maistre Melillo, Tanya Melillo, Eline Op de Coul, Hans Blystad, Magdalena Rosinska, Isabel Aldir, Helena Gomes Dias, Mariana Mardarescu, Peter Truska, Irena Klavs, Asunción Díaz, Maria Axelsson, Valerie Delpech
Journal: The Lancet HIV (2017)
Updated efficacy and safety of the j-alex study comparing alectinib (ALC) with crizotinib (CRZ) in ALK-inhibitor naïve <i>ALK</i> fusion positive non-small cell lung cancer (<i>ALK+</i> NSCLC).
Authors: Yuichi Takiguchi, Toyoaki Hida, Hiroshi Nokihara, Masashi Kondo, Young Hak Kim, Koichi Azuma, Takashi Seto, Makoto Nishio, Hiroshige Yoshioka, Fumio Imamura, Katsuyuki Hotta, Satoshi Watanabe, Koichi Goto, Kazuhiko Nakagawa, Tetsuya Mitsudomi, Nobuyuki Yamamoto, Hiroshi Kuriki, Naohito Inagaki, Tomohiro Tanaka, Tomohide Tamura
Journal: Journal of Clinical Oncology (2017)

9064 Background: ALC is a highly selective, CNS-active ALK tyrosine kinase inhibitor. In the J-ALEX study, ALC proved superior efficacy and tolerability compared to CRZ at the pre-planned interim analysis at 83 progression free survival (PFS) events (51% of target events) . Here we report the updated data with a further 10 months of follow up. Methods: Patients with advanced ALK+ NSCLC were randomized 1:1 to receive ALC 300 mg b.i.d or CRZ 250 mg b.i.d and stratified by ECOG PS, treatment line, and clinical stage. Study Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was PFS according to the blinded independent review. Secondary endpoints included investigator-assessed PFS, overall survival, objective response rate and safety. Results: From Nov 2013 to Aug 2015, 207 patients were enrolled. Data cut off for the present analysis was Sep 2016. Median durations of PFS follow up were 20.5 months in the ALC arm and 20.4 months in the CRZ arm with 116 events by independent review observed. The updated PFS HR was 0.38 (95% CI: 0.26-0.55, p&lt; 0.0001). Median PFS was 25.9 months (95% CI: 20.3-not estimated) with ALC and 10.2 months (95% CI: 8.3-12.0) with CRZ. For patients without brain metastasis at baseline (n = 164), ALC prevented CNS metastasis onset compared to CRZ (HR = 0.19, 95% CI: 0.07-0.53). For patients with brain metastasis at baseline (n = 43), ALC also prevented CNS progression compared to CRZ (HR = 0.51, 95% CI: 0.16-1.64). Adverse events (AEs) with frequency of more than 30% were constipation (37.9%) and nasopharyngitis (32.0%) in the ALC arm, while in the CRZ arm nausea (76.0%), diarrhea (74.0%), vomiting (57.7%), visual disturbance (54.8%), dysgeusia (51.9%), constipation (46.2%), increased ALT (32.7%), and increased AST (31.7%) were observed. Grade 3-4 AEs occurred with greater frequency in the CRZ arm (ALC: 32.0% vs CRZ: 56.7%). There were no Grade 5 AEs in either arm. Conclusions: In the updated analysis, ALC consistently showed superior efficacy compared to CRZ in systemic disease and prevention of CNS progression. ALC was also associated with a more favorable tolerability profile than CRZ. Clinical trial information: JapicCTI-132316.
Opioid Overdose Outbreak — West Virginia, August 2016
Authors: Joel Massey, Michael Kilkenny, Samantha Batdorf, Sarah K. Sanders, Debra Ellison, John Halpin, R. Matthew Gladden, Danae Bixler, Loretta Haddy, Rahul Gupta
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

On August 15, 2016, the Mayor's Office of Drug Control Policy in Huntington, West Virginia, notified the CabellHuntington Health Department (CHHD) of multiple calls regarding opioid overdose received
Recombinant humanised anti-PD-1 monoclonal antibody (JS001) treatment for patients with refractory or metastatic nasopharyngeal carcinoma: preliminary results of an open-label, phase 1b/2, clinical study
Authors: Ruihua Xu, Fenghua Wang, Qi Li, Jianhua Shi, Lin Shen, Qingyuan Zhang, Xianglin Yuan, Yi Jiang, Nong Xu, Ye Chen, Xichun Hu, Xiaoyan Lin, Shujun Yang, Chao Ren
Journal: The Lancet Oncology (2017)
Assessment of treatment response with fulvestrant (F) 500 mg in standard clinical practice through a retrospective study: NCT01509625.
Authors: Isabel Blancas, Manuel Ruiz-Borrego, Javier Salvador Bofill, Veronica Conde, Francisco Carabantes, Juan L. Bayo, Ana Jaen, Elisabeth Perez Ruiz, María del Mar Santiago, Jose Manuel Baena, Vicente Villareal, Antonia Martinez Guisado, Luis de la Cruz Merino, Pedro Rodriguez, Evelyn Reyes, Rosana Cajal, Mayte Delgado, Encarnacion Gonzalez Flores, Angel Inoriza, Pedro Sanchez Rovira
Journal: Journal of Clinical Oncology (2013)

e11583 Background: The CONFIRM study showed greater efficacy of F500 as compared to F250.Based on these results a dosage change was authorized in Spain.The aim of this study is to describe the efficacy of F500 (progression free survival(PFS) and clinical benefit rate(CBR) in Spanish patients (P) with estrogen receptor (ER+) Metastatic Breast Cancer (MBC) through a retrospective data collection. Methods: After written informed consent, data collection was recorded from clinical records of P who previously had progressed on hormonal treatment and who received at any time F 500 from 1 st January 2010 to 31 st October 2011. Results: 102 P in 14 centers were included in the study, 93 P were evaluable.Median age was 65 (39-88). Histology: 80.6% ductal ;15% lobulillar. Hormonal receptors: ER+/ PgR+ 77.4%; ER+/PgR- 21.6 %. HER2 status was documented in 80P, 15% of them were HER2+. 45.4% were Ki67 +. Mean from diagnosis to metastatic disease:3.7 years, 19.3% of P had de novo metastatic disease. 21.5% of P had visceral metastases.82.8% of P had good PS (0-1) when F started.F received as 1 st line in 7.5%, as 2 nd line in 52.7% and 3 rd or more in 39.8% of the P. Average cycles administered: 10(3-48). With a median follow up of 16 months (m) since F treatment (1.4-34.4), median PFS was 10.6 m[8.3-13.0]. CBR was 59.1% (12.9%CR, 12.9 PR and 33.3% SD≥ 24 weeks). Median PFS in P with or without CB was 23.3 m and 5.6 m respectively. Median PFS in P with F in 1 st line was 10.3 m, 11.6 m in 2nd line and 9 m in 3rd line or more. No significant differences in CBR were observed between P with or without visceral metastases (58.9 vs 60%). There was a trend in the CBR between HER –ve and +ve groups (64.7% vs 33.3% p = 0.0565). 1-year survival rate was 86% (77.3-92.3). Median Overall Survival was not calculated because only 20 P had died when data were analyzed. More frequent toxicities were: local injection site pain (11.8%), hot flushes (11.8%) and gastrointestinal disorders (8.6%). Conclusions: F500 in real life setting showed a PFS of 10.6 m and got CB in 2/3 of P with a good toxicity profile, in line with phase III trials. In P who achieve a CB the median PFS was almost two years. P with visceral metastases may benefit from F same as those with non visceral involvement.
Infographic: We have the programme, what next? Developing a plan of action to implement injury prevention exercise programmes in community sport
Authors: Sheree Bekker, Alex Donaldson, Caroline F Finch
Journal: British Journal of Sports Medicine (2017)

Exercise programmes to prevent injuries, such as lower-limb injuries that are common in community Australian Football,1 exist but are not widely used. Often, such programmes are developed using research evidence and clinical best practice without consideration of real-world implementation factors. This means that work still needs to be done to make them suitable for use in community sports settings.2 Implementing evidence-based injury prevention exercise programmes into ‘real world’ practice remains challenging.2 A ‘plan of action’ to implement such interventions seems to help coaches use them. However, there is little guidance about how best to create such a plan. Donaldson and colleagues3 describe how researchers developed a ‘plan of action’ for implementing the …
Features and Outcomes of Methamphetamine-associated Pulmonary Arterial Hypertension
Authors: Roham T. Zamanian, Haley Hedlin, Paul Greuenwald, David M. Wilson, Joshua I. Segal, Michelle Jorden, Kristina Kudelko, Juliana Liu, Andrew Hsi, Allyson Rupp, Andrew J. Sweatt, Rubin Tuder, Gerald J. Berry, Marlene Rabinovitch, Ramona L. Doyle, Vinicio de Jesus Perez, Steven M. Kawut
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Although amphetamines are recognized as "likely" agents to cause drug- and toxin-associated pulmonary arterial hypertension (PAH), (meth)amphetamine-associated PAH (Meth-APAH) has not been well described.To prospectively characterize the clinical presentation, histopathology, and outcomes of Meth-APAH compared with those of idiopathic PAH (iPAH).We performed a prospective cohort study of patients with Meth-APAH and iPAH presenting to the Stanford University Pulmonary Hypertension Program between 2003 and 2015. Clinical, pulmonary angiography, histopathology, and outcomes data were compared. We used data from the Healthcare Cost and Utilization Project to estimate the epidemiology of PAH in (meth)amphetamine users hospitalized in California.The study sample included 90 patients with Meth-APAH and 97 patients with iPAH. Patients with Meth-APAH were less likely to be female, but similar in age, body mass index, and 6-minute-walk distance to patients with iPAH. Patients with Meth-APAH reported more advanced heart failure symptoms, had significantly higher right atrial pressure (12.7 ± 6.8 vs. 9.8 ± 5.1 mm Hg; P = 0.001), and had lower stroke volume index (22.2 ± 7.1 vs. 25.5 ± 8.7 ml/m2; P = 0.01). Event-free survival in Meth-APAH was 64.2%, 47.2%, and 25% at 2.5, 5, and 10 years, respectively, representing more than double the risk of clinical worsening or death compared with iPAH (hazard ratio, 2.04; 95% confidence interval, 1.28-3.25; P = 0.003) independent of confounders. California data demonstrated a 2.6-fold increase in risk of PAH diagnosis in hospitalized (meth)amphetamine users.Meth-APAH is a severe and progressive form of PAH with poor outcomes. Future studies should focus on mechanisms of disease and potential therapeutic considerations.
Multi-level differential network analysis of COPD exacerbations
Authors: Guillaume Noell, Borja G. Cosío, Rosa Faner, Eduard Monsó, German Peces-Barba, Alfredo de Diego, Cristobal Esteban, Joaquim Gea, Robert Rodriguez-Roisin, Marian Garcia-Nuñez, Francisco Pozo-Rodriguez, Susana G. Kalko, Alvar Agustí
Journal: European Respiratory Journal (2017)

Patients with chronic obstructive pulmonary disease (COPD) often suffer episodes of exacerbation (ECOPD) that impact negatively the course of their disease. ECOPD are heterogeneous events of unclear pathobiology and non-specific diagnosis. Network analysis is a novel research approach that can help unravelling complex biological systems. We hypothesised that the comparison of multi-level ( i.e. , clinical, physiological, biological, imaging and microbiological) correlation networks determined during ECOPD and convalescence can yield novel patho-biologic information . In this proof-of-concept study we included 86 patients hospitalised because of ECOPD in a multicentre study in Spain. Patients were extensively characterised both during the first 72 h of hospitalisation and during clinical stability, at least 3 months after hospital discharge. We found that 1) episodes of ECOPD are characterised by disruption of the network correlation observed during convalescence; and 2) a panel of biomarkers that include increased levels of dyspnoea, circulating neutrophils and C-reactive protein (CRP) has a high predictive value for ECOPD diagnosis (AUC 0.97). We conclude that ECOPD 1) are characterised by disruption of network homeokinesis that exists during convalescence; and 2) can be identified objectively by using a panel of three biomarkers (dyspnoea, circulating neutrophils and CRP levels) frequently determined in clinical practice.
Evaluation of the change in structural radiographic sacroiliac joint damage after 2 years of etanercept therapy (EMBARK trial) in comparison to a contemporary control cohort (DESIR cohort) in recent onset axial spondyloarthritis
Authors: Maxime Dougados, Walter P Maksymowych, Robert B M Landewé, Anna Moltó, Pascal Claudepierre, Manouk de Hooge, Robert G Lambert, Randi Bonin, Jack F Bukowski, Heather E Jones, Isabelle Logeart, Ron Pedersen, Annette Szumski, Bonnie Vlahos, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2017)

Objective To compare 2 years of radiographic sacroiliac joint (SIJ) changes in patients with recent onset axial spondyloarthritis (axSpA) receiving etanercept in a clinical trial (EMBARK) to similar patients not receiving biologics in a cohort study (DESIR). Methods Endpoints were changes at week 104 per the modified New York (mNY) grading system in total SIJ score (primary endpoint) and net percentage of patients with progression defined three ways. Treatment effect was analysed with and without adjustment for baseline covariates. Results At 104 weeks, total SIJ score improved in the etanercept group (n=154, adjusted least-squares mean change: –0.14) and worsened in the control group (n=182, change: 0.08). The adjusted difference between groups (etanercept minus control) was –0.22 (95% CI –0.38 to –0.06), p=0.008. The net percentage of patients with progression was significantly lower in the etanercept versus the control group for two of three binary endpoints: –1.9% versus 1.6% (adjusted difference for etanercept minus control: –4.7%,95% CI –9.9 to 0.5, p=0.07) for change in mNY criteria; –1.9% versus 7.8% (adjusted difference: –18.2%,95% CI –30.9 to –5.6, p=0.005) for change ≥1 grade in ≥1 SIJ; and –0.6% versus 6.7% (adjusted difference: –16.4%,95% CI –27.9 to –5.0, p=0.005) for change ≥1 grade in ≥1 SIJ, with shift from 0 to 1 or 1 to 0 considered no change. Conclusion Despite the slow radiographic SIJ progression rate over 2 years in axSpA, this study suggests a lower rate of progression in the SIJ with etanercept than without anti-tumour necrosis factor therapy. Trial registration numbers NCT01258738 , NCT01648907 ; Post-results.
The Finest Traditions of My Calling: One Physician’s Search for the Renewal of Medicineby Abraham M. Nussbaum, M.D. New Haven, Conn., Yale University Press, 2016, 320 pp., $28.50 (hardcover).
Authors: Michael Redinger
Journal: American Journal of Psychiatry (2017)

ephemeral, elusive and largely unknown" (p. 7).Kelly does use a number of archival case records to partially fill this gap and also describes current efforts to use other materials to get closer to the voices and thoughts of patients.The book's last two chapters focus on developments in this century and the future of psychiatry in Ireland.A crucial advance in the past 30 years has been the rapid growth of mental health advocacy organizations so that Ireland is now a world leader in recipients of mental health services and in families effectively participating at the highest levels in the development, implementation, and review of such services.While this masterful work is about the history of psychiatry in Ireland (supplemented by references to parallel developments in other countries), it reflects and documents humankind's historical and continuing grappling with the reality and impact of mental illness.Kelly openly deals with the good, the bad, and the ugly-"the therapeutic enthusiasm, with all the triumph and tragedy, hubris and humility that such enthusiasm brings" (p.1)-as well as the neglect, isolation, exclusion, mismanagement and, at times, cruelty suffered by those we call patients.There is much to learn about such matters in this book that can benefit us all.As Kelly concludes, "We must do better" (p.306).
Reply to Goetz et al.
Authors: Rakesh Kalapala, Radhika Chavan, Zaheer Nabi, Sundeep Lakhtakia, D. Reddy
Journal: Endoscopy (2017)

See also:Reverse bougienage of the major papilla via the minor papilla followed by conventional sphincterotomyEndoscopy 2017; 49(10): 1013-1013DOI: 10.1055/s-0043-117407
Antitumor activity of bevacizumab in human gastric cancer xenografts.
Authors: Yoriko Yamashita, Kaori Fujimoto-Ouchi, Keigo Yorozu, Kazushige Mori
Journal: Cancer Research (2008)

2913  Objective: Bevacizumab (BV), a humanized antibody to VEGF, has been reported to show clinical benefit in the patients with CRC, BC, and NSCLC. Bevacizumab is also expected for showing efficacy in gastric cancers, then we examined the antitumor activity of BV on human gastric cancer xenograft models as a single agent or in combination with chemotherapies.  Methods: Five gastric cancer cell lines of various histological types were inoculated into nude mice, and treated with 1-25 mg/kg of BV or human IgG once a week for 3 weeks. Capecitabine (CAPE,239 mg/kg/day, orally, daily for 14 days, and 7 day’s rest) or cisplatin (CDDP,5 mg/kg, intravenously, once a week for 3 weeks)were administered in combination with BV in a GXF-97 model. Tumor growth inhibition rate (TGI%) was determined after 3 weeks treatment.  Results: BV showed antitumor activity in tubular adenocarcinoma GXF-97 and MKN-28, mucinous adenocarcinoma SC-08-JCK, and solid type of poorly differentiated adenocarcinoma 4-1ST and MKN-45. TGI% of BV at 5 mg/kg of BV were 62%,56%,75%,68%, and 73%, respectively. Combination of BV with CAPE and CDDP in the GXF-97 model showed significantly more potent antitumor activity than CAPE + CDDP or BV alone. (BV: 78%, CAPE: 63%, CDDP: 73%, CAPE + CDDP: 106%, BV + CAPE + CDDP: 122%).  Conclusion: Bevacizumab as a single agent showed antitumor activity in various histological types of gastric cancers, and more potent antitumor activity in the combination with capecitabine and cisplatin. Evaluation of the efficacy and safety of bevacizumab in clinical gastric cancers would be warranted.
Abstract 081: Liganded Cannabinoid Receptors Suppress Cardiac Myocyte Hypertrophy by AMP-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) signaling
Authors: Yan Lu, Hope Anderson
Journal: Circulation Research (2013)

Endocannabinoids are bioactive lipids that signal through CB1 and CB2 cannabinoid receptors. Despite an effort to avoid the psychoactive side effects mediated by central CB1 receptors, we previously found that selective activation of CB2 receptors is not sufficient to prevent cardiac myocyte hypertrophy. Thus, the objective of this study is to determine the effects of CB13, a peripherally-restricted agonist of CB1/CB2 receptors, on hypertrophy. The effects of CB-13 on endothelin-1 (ET1)-induced hypertrophy were determined using isolated neonatal rat myocytes. Hypertrophic indicators included myocyte enlargement, protein synthesis by [3H]-leucine incorporation, and fetal gene expression as brain natriuretic peptide (BNP) mRNA levels. AMPK and eNOS signaling were assessed by immunoblotting. ET1 increased myocyte size (122±4% vs. control; p&lt;0.01), BNP expression (426±88% vs. control; p&lt;0.01) and [3H]-leucine incorporation (147±13% vs. control; p&lt;0.05). CB13 attenuated all three hypertrophic indicators (respectively, 104±3%, 210±32%, 90±8% vs. control; not significant). We next queried whether the anti-hypertrophic actions of CB13 were mediated by AMPK. CB13 increased total expression (222±45% vs. control; p&lt;0.05) and phosphorylation (354±58% vs. control; p&lt;0.01) of AMPK. Also, pretreatment with a chemical inhibitor of AMPK, compound C, attenuated the anti-hypertrophic actions of CB-13. AMPK is a regulator of cellular energy, so we determined that ET-1-induced mitochondrial depolarization, as assessed using the potential-sensitive dye, JC-1, was prevented by CB-13. In addition, CB-13 increased eNOS phosphorylation (237±51%; p&lt;0.01), which suggests that AMPK-eNOS crosstalk, through anti-growth nitric oxide signaling, plays a role. These findings support the notion that agonism of CB1 and CB2 receptors by CB13, a synthetic endocannabinoid with poor brain-blood barrier penetration, prevents hypertrophy and mitochondrial dysfunction. These CB13 actions rely on AMPK signaling, and are associated with eNOS activation. In conclusion, cannabinoid-based treatment of heart disease remains a viable goal with therapeutic potential and warrants further study.
Burden of salmonellosis, campylobacteriosis and listeriosis: a time series analysis, Belgium, 2012 to 2020
Authors: Charline Maertens de Noordhout, Brecht Devleesschauwer, Juanita A Haagsma, Arie H Havelaar, Sophie Bertrand, Olivier Vandenberg, Sophie Quoilin, Patrick T Brandt, Niko Speybroeck
Journal: Eurosurveillance (2017)

Salmonellosis, campylobacteriosis and listeriosis are food-borne diseases. We estimated and forecasted the number of cases of these three diseases in Belgium from 2012 to 2020, and calculated the corresponding number of disability-adjusted life years (DALYs). The salmonellosis time series was fitted with a Bai and Perron two-breakpoint model, while a dynamic linear model was used for campylobacteriosis and a Poisson autoregressive model for listeriosis. The average monthly number of cases of salmonellosis was 264 (standard deviation (SD): 86) in 2012 and predicted to be 212 (SD: 87) in 2020; campylobacteriosis case numbers were 633 (SD: 81) and 1,081 (SD: 311); listeriosis case numbers were 5 (SD: 2) in 2012 and 6 (SD: 3) in 2014. After applying correction factors, the estimated DALYs for salmonellosis were 102 (95% uncertainty interval (UI): 8–376) in 2012 and predicted to be 82 (95% UI: 6–310) in 2020; campylobacteriosis DALYs were 1,019 (95% UI: 137–3,181) and 1,736 (95% UI: 178–5,874); listeriosis DALYs were 208 (95% UI: 192–226) in 2012 and 252 (95% UI: 200–307) in 2014. New actions are needed to reduce the risk of food-borne infection with Campylobacter spp. because campylobacteriosis incidence may almost double through 2020.