tbuckley/cabot-search huggingface dataset:
Opioid Prescribing After Surgery in the United States, Canada, and Sweden
Authors: Karim S. Ladha, Mark D. Neuman, Gabriella Broms, Jennifer Bethell, Brian T. Bateman, Duminda N. Wijeysundera, Max Bell, Linn Hallqvist, Tobias Svensson, Craig W. Newcomb, Colleen M. Brensinger, Lakisha J. Gaskins, Hannah Wunsch
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Small studies and anecdotal evidence suggest marked differences in the use of opioids after surgery internationally; however, this has not been evaluated systematically across populations receiving similar procedures in different countries. <h3>Objective</h3> To determine whether there are differences in the frequency, amount, and type of opioids dispensed after surgery among the United States, Canada, and Sweden. <h3>Design, Setting, and Participants</h3> This cohort study included patients without previous opioid prescriptions aged 16 to 64 years who underwent 4 low-risk surgical procedures (ie, laparoscopic cholecystectomy, laparoscopic appendectomy, arthroscopic knee meniscectomy, and breast excision) between January 2013 and December 2015 in the United States, between July 2013 and March 2016 in Canada, and between January 2013 and December 2014 in Sweden. Data analysis was conducted in all 3 countries from July 2018 to October 2018. <h3>Main Outcomes and Measures</h3> The main outcome was postoperative opioid prescriptions filled within 7 days after discharge; the percentage of patients who filled a prescription, the total morphine milligram equivalent (MME) dose, and type of opioid dispensed were compared. <h3>Results</h3> The study sample consisted of 129 379 patients in the United States, 84 653 in Canada, and 9802 in Sweden. Overall, 52 427 patients (40.5%) in the United States were men, with a mean (SD) age of 45.1 (12.7) years; in Canada, 25 074 patients (29.6%) were men, with a mean (SD) age of 43.5 (13.0) years; and in Sweden, 3314 (33.8%) were men, with a mean (SD) age of 42.5 (13.0). The proportion of patients in Sweden who filled an opioid prescription within the first 7 days after discharge for any procedure was lower than patients treated in the United States and Canada (Sweden, 1086 [11.1%]; United States, 98 594 [76.2%]; Canada, 66 544 [78.6%];<i>P</i> &lt; .001). For patients who filled a prescription, the mean (SD) MME dispensed within 7 days of discharge was highest in United States (247 [145] MME vs 169 [93] MME in Canada and 197 [191] MME in Sweden). Codeine and tramadol were more commonly dispensed in Canada (codeine, 26 136 patients [39.3%]; tramadol, 12 285 patients [18.5%]) and Sweden (codeine, 170 patients [15.7%]; tramadol, 315 patients [29.0%]) than in the United States (codeine, 3210 patients [3.3%]; tramadol, 3425 patients [3.5%]). <h3>Conclusions and Relevance</h3> The findings indicate that the United States and Canada have a 7-fold higher rate of opioid prescriptions filled in the immediate postoperative period compared with Sweden. Of the 3 countries examined, the mean dose of opioids for most surgical procedures was highest in the United States.
P14.102 Cerebellar atrophy patterns in paraneoplastic cerebellar degeneraiton and spinocerebellar ataxia 1 (SCA1)
Authors: C Vialatte de Pémille, D Psimaras, I Adanyegu, F Graus, A Dürr, J Honnorat, J Delattre, A Alentorn
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Brain and more specifically cerebellar atrophy is a major radiological finding in both Paraneoplastic Cerebellar Degeneration (PCD) with anti-Yo antibodies and Spinocerebellar Ataxia type 1 (SCA1).We sought to analyze the different brain volumetric patterns of cerebellar atrophy in these diseases. MATERIAL AND METHODS We performed a retrospective multicentric study (Paris, Lyon, Barcelona reference centres) with either anti-Yo PCD (n=16) or SCA1 (n=17) and 30 healthy subjects paired by age. We used VolBrain and CERES algorithms to obtain the brain and cerebellum segmentation, respectively as well as the cortical thickness. We used a Sparse Canonical Correlation Analysis (SCCAN) and Voxel Brain Morphometry (VBM) with family wise error correction to analyze volumetric differences between the different conditions. RESULTS SCA patients were younger than PCD patients (p&lt;0.05, ANOVA). In univariate analysis, most of the atrophic regions (p&lt;0.05) were common between PCD and SCA1 compared to controls. Isolated cortical thickness and grey matter analysis showed predominant atrophy in PCD patients. Multivariate analysis using SCCAN and VBM confirmed these results. We identified a particular atrophy pattern in PCD patients involving lobules III to VII. We observed a more diffuse atrophy distribution in SCA1 patients and a lower cortical atrophy in PCD patients. CONCLUSION We described the specific pattern of topographic cerebellar atrophy in PCD and SCA1 patients. The cerebellar atrophy in PCD is mainly localized in the neocerebellum.
Effect of donor type and conditioning regimen intensity on allogeneic transplantation outcomes in patients with sickle cell disease: a retrospective multicentre, cohort study
Authors: Mary Eapen, Ruta Brazauskas, Mark C Walters, Françoise Bernaudin, Khalid Bo-Subait, Courtney D Fitzhugh, Jane S Hankins, Julie Kanter, Joerg J Meerpohl, Javier Bolaños-Meade, Julie A Panepinto, Damiano Rondelli, Shalini Shenoy, Joi Williamson, Teonna L Woolford, Eliane Gluckman, John E Wagner, John F Tisdale
Journal: The Lancet Haematology (2019)
Survival and safety of monosialotetrahexosylganglioside in GI cancer patients with oxaliplatin-induced peripheral neurotoxicity-result from TJMUCH-GI-001 trial.
Authors: Zhou Likun, Dingzhi Huang, Rui Liu, Hongli Li, Tao Ning, Le Zhang, Shaohua Ge, Ming Bai, Xia Wang, Rubing Han, Yuchong Yang, XinYi Wang, Xinyun Chen, Zhiying Gao, Kaijun Niu, Laizhi Luo, Xi Wu, Ting Deng, Yuanquan Yang, Yi Ba
Journal: Journal of Clinical Oncology (2019)

11596 Background: TJMUCH-GI-001 Trial was a randomized, double-blind, placebo-controlled phase III trial to study the efficacy of Monosialotetrahexosylganglioside (GM1) for oxaliplatin-induced peripheral neurotoxicity (OIPN) in GI cancer patients. Majority patients (&gt; 80%) in both arms continued receiving oxaliplatin on the trial. The results showed GM1 effectively reduced OIPN in GI cancer patients. Here we report the survival and safety results of this trial. Methods: Patients were randomized in a 1:1 ratio to receive GM1 or placebo. Patients with OIPN &gt; = G2 by CTCAE 4.03 persisting during or after oxaliplatin-based chemotherapy were eligible. The patients who remained on oxaliplatin after enrollment, received concurrent placebo or GM1 x 7 days with each chemotherapy cycle. The patients who stopped taking oxaliplatin, were treated with placebo or GM1 x 14 days every 3 weeks. GM1 was dosed at 60mg daily for every 3-week or 40mg daily for every 2-week schedule. Trial was continued until modified EORTC QLQ-CIPN20 ( MCIPN) increased by 30% or stayed unchanged after two more treatments beyond completion of oxaliplatin. Survival data for the treatment arms were compared using a log-rank test and Chi-square tests were used for safety analysis. Results: From May 2015 to Dec 2017, 73 patients were enrolled in GM1 and 72 in placebo arm. The median follow-up was 16.6 months (0.8-43.1 months) as of Dec.2018. Four patients lost to follow up. There was no deleterious impact of GM1 on survival. As a matter of fact, receiving GM1 was associated with a trend toward improved PFS and OS (HR=0.74,95%CI, 0.469 - 1.156 for PFS and HR=0.76, 95%CI0.469 - 1.156 for OS). The most frequent Grade 3 or 4 adverse events included neutropenia (8 patients in GM1 group VS. 4 in placebo group) and hypoleukemia (4 patients in GM1 group VS. 1 in placebo group). Other 3 or 4 adverse events (all less than 3 patients) included anorexia, hypercalcemia, nausea, vomiting, proteinuria, hyperbilirubinemia, hypokalemia, hypertension and appendicitis. All the 3 or 4 adverse events were related to chemotherapy, not to GM1. Conclusion: In this placebo-controlled phase III trial, GM1 showed acceptable toxicity with trends favorable PFS and OS in GI cancer patients. Clinical trial information: NCT02486198.
Is there a shift in use of subacute rehabilitation (SAR) instead of hospice referral since immunotherapy became available?
Authors: Jonathan Yeh, Louise Knight, Joyce M. Kane, Danielle Doberman, Arjun Gupta, Thomas J. Smith
Journal: Journal of Clinical Oncology (2019)

11530 Background: Immunotherapy has rapidly become mainstream treatment. Since the first drug approval in 2011, we have noted a decline in referrals from inpatient oncology to hospice, and an increase in referrals to sub-acute rehabilitation (SAR) facilities, possibly with the aim of “getting strong enough” for immunotherapy and other promising drugs. This study explores outcomes after discharge to SAR, including rates of cancer-directed therapy after SAR, overall survival, and hospice utilization. Methods: Electronic chart review of patients discharged from oncology units to SAR facilities from 2009-2017. Demographics, admission statistics, and post-discharge outcomes were gathered from discharge summaries and targeted chart searches. Results: SAR referrals increased from 28 in 2012 to 82 in 2016. Age 66, males 52%, solid tumors 58%. 358 patients were referred to SAR 413 times. 174 patients (49%) returned to the oncology clinic prior to re-admission or death, and only 117 (33%) ever received further cancer-directed treatment (chemotherapy, radiation, or immunotherapy). 219 of 358 (61%) died within 6 months. Only 3 individuals who were not on immunotherapy at time of admission went on to receive immunotherapy after discharge to SAR. Among all discharges, 28% led to readmissions within 30 days. 74 patients (21%) were deceased within 30 days, of whom only 31% were referred to hospice. Palliative care involvement resulted in more frequent do not resuscitate (DNR) code status (33 v 22%), documented goals of care (GOC) discussions (81 v 23%), and electronic advance directives (42 v 28%).(All p&lt;0.05). Conclusions: A growing number of oncology inpatients are being discharged to SAR, but two-thirds do not receive further cancer therapy at any point, including a substantial fraction that are re-admitted or deceased within 1 month. Many patients lose the opportunity to use hospice for optimal end of life care, as few SAR facilities offer this. These data can help guide decision-making and discharge planning that aligns with patients’ goals of care. More clinical data are needed to predict who is most likely to benefit from SAR and proceed to further cancer therapy.
<i>CYP2D6</i> genotype and adverse effects as indicators of plasma endoxifen in breast cancer patients taking tamoxifen.
Authors: Bavanthi Balakrishnar, Alexander M. Menzies, Sayed Sahanawaz Ali, Shang Heng Yeap, Bo Gao, Chris Liddle, Sally Coulter, Pamela Provan, Val Gebski, Rina Hui, Richard Kefford, Nicholas Wilcken, Rosemary L Balleine, Howard Gurney
Journal: Journal of Clinical Oncology (2012)

550 Background: Tamoxifen is a prodrug. Its principal active metabolite endoxifen is a product of cytochrome P450 2D6 (CYP2D6) metabolism. The CYP2D6 gene is highly polymorphic with a number of relatively common reduced function alleles. The aim of this study was to determine whether plasma endoxifen levels were reflected by CYP2D6 genotype or adverse effects in individuals taking tamoxifen. Methods: Plasma endoxifen was measured by High Performance Liquid Chromatography / Mass Spectroscopy in 90 breast cancer patients taking 20mg tamoxifen per day. Ten CYP2D6 single nucleotide polymorphisms were assessed to designate four putative CYP2D6 functional categories: ultra-rapid (UM), extensive (EM), intermediate (IM) and poor (PM) metabolizers. CYP2D6 inhibitor use and adverse effects were documented. The study was part of an ongoing Australian trial of tamoxifen dose escalation. Results: There was marked variation in plasma endoxifen levels across the cohort (mean 27.6 nM, SD 14.3). Endoxifen levels were significantly associated with metabolizer categories (p&lt;0.001, r= -0.44), but were not distinctive between categories. For example, in the EM category (n=46) endoxifen levels ranged from 3.8-72.2 nM (mean 32.6 nM) with levels in the lowest quartile (3.8-19.7 nM) substantially overlapping the PM category (n=11); 6.1-24.7 nM. Consistent with an impact of non-CYP2D6 genotype related factors on endoxifen levels, endoxifen was significantly lower in 18 patients taking CYP2D6 inhibitor medications (p=0.005). There was no association between endoxifen levels and vasomotor symptoms or other adverse effects of tamoxifen. Conclusions: Endoxifen levels were highly variable in patients taking standard dose tamoxifen, and not predicted by CYP2D6 genotype or adverse effects. Therapeutic monitoring of endoxifen levels may be a useful approach to assess tamoxifen activity.
Frederick Ephraim Dische
Authors: Geoffrey Dische
Journal: BMJ (2019)

After service in the Royal Air Force, Frederick Dische trained in pathology at the Canadian Red Cross Memorial Hospital, Taplow; Cambridge University; and St George’s Hospital, London. In 1958 he was appointed consultant pathologist to the Camberwell Hospitals Group, later merged into King’s.

Apart from general histopathological reporting, biopsy work at Dulwich Hospital …
Mission accomplished? A scoping review and bibliometric analysis of the term “planetary health” in the peer-reviewed literature
Authors: Verena Rossa-Roccor, Emily Acheson, Federico Andrade-Rivas, Michelle Coombe, Saori Ogura, Laura Super, Andy Hong
Journal: The Lancet Planetary Health (2019)

BackgroundPlanetary health is an emerging holistic health field that aims to disrupt the boundaries of unidisciplinary research by fostering collaborations, integrating Indigenous knowledge, facilitating education, and driving public and policy engagement. To understand to what degree the field has been successful in meeting this mandate, we conducted a scoping review and bibliometric analysis of the term "planetary health" in the peer-reviewed literature.MethodsAn interdisciplinary research team conducted a systematic literature search in 14 databases. The search strategy examined the years 2005–18 with the term "planetary health" in title, abstract, or keywords; no limitations were used regarding language or geographical location. Search results were sorted into three different categories: commentaries, education, and original research. Results in the latter were categorised under the themes suggested by the Planetary Health Alliance. Obtained bibliographic data were analysed with the R bibliometrix package.FindingsOur inclusion criteria identified 180 articles. Preliminary analysis showed that most publications (n=153, 85%) were commentaries, calls to action or framework suggestions. 12 publications reported on educational content and 15 publications reported original research. The themes "nutrition" and "changing food systems" were most commonly discussed in the research papers while "urbanization" and "changing biochemical flows" were not discussed. Ten publications considered Indigenous knowledge and traditions. The number of publications remained low until 2014 but has tripled since 2017. The USA was the most productive country (32%), followed by the UK (16%), and Australia (9%). The most common keyword was "climate change", followed by "public health".InterpretationPlanetary health aims to bridge the gaps both between academic fields and beyond academia. However, based on the results of this study, the term is currently mostly used in commentary-like publications. We need to "spread the word" to better connect researchers, academic fields, and efforts worldwide and under the planetary health umbrella.FundingNone.
Fibroblast activation and ECM remodelling in genodermatoses
Authors: E. Chacón‐Solano, C. León, F. Díaz, F. García‐García, M. García, M.J. Escámez, S. Guerrero‐Aspizua, C.J. Conti, Á. Mencía, L. Martínez‐Santamaría, S. Llames, M. Pévida, J. Carbonell‐Caballero, J.A. Puig‐Butillé, R. Maseda, S. Puig, R. Lucas, E. Baselga, F. Larcher, J. Dopazo, M. Río
Journal: British Journal of Dermatology (2019)

Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and Xeroderma pigmentosum C (XPC) are three genetic skin diseases (i.e. genodermatoses) in which patients are at increased risk of developing cancer. The events leading to cancer in these diseases, including those taking place at the level of the skin, are still not well understood even though they are under intense investigation. To deepen the knowledge of these rare diseases with the ultimate goal of finding new treatments, the Spanish research group investigated the gene expression profile (signature) of a type of skin cell called dermal fibroblasts from patients with RDEB, KS and XPC. The researchers found that the fibroblasts from three genodermatoses share a large number of genes aberrantly (wrongly) expressed in a similar fashion. That in turn translates into what is defined as an activated phenotype and leads to changes in dermal (a skin layer) stiffness and an imbalance of the redox (a type of chemical reaction) status. This overlapping signature seems not to depend on the primary disease-causing deficiency defect (i.e. loss of type VII collagen, kindlin-1 or XPC) but rather the consequence of a common injury-responsive event not yet fully understood. In conclusion, this study adds to the current knowledge about the role played by dermal fibroblasts in RDEB, XPC and KS and highlights new targets for possible treatments.
Risk factors in pregnant women with an oncological diagnosis and their impact in the post-partum period.
Authors: Flavia Faccio, Chiara Ionio, Eleonora Mascheroni, Fedro Peccatori, Giulia Ongaro, Elena Cattaneo, Camilla Pisoni, Silvia von Wunster, Giuseppe Nastasi, Gabriella Pravettoni, Giordano D. Beretta, Lucia Bonassi
Journal: Journal of Clinical Oncology (2019)

e23166 Background: An oncological diagnosis during pregnancy, or the choice of motherhood following cancer may be accompanied by anxiety, distress and depression. The aim of the study is to explore the possible risk factors in the perinatal period in women who experienced an oncological diagnosis before or during pregnancy. Methods: 32 pregnant women (25 breast, 3 cervix, 1 lung, 1 Hodgkin's lymphoma, 1 perivascular epithelial cell neoplasia, 1 epatic PEComa) were assessed during their 3rd trimester (T1) and three months’ post-partum (T2). At T1 mood states and post-traumatic symptoms were evaluated, at T2 parenting stress and perceived quality of life (QoL). Results: Depression, anger and anxiety correlated with lower physical and psychological QoL in the post-partum. Moreover, mothers who expressed higher levels of fatigue and confusion during pregnancy are associated to lower levels of perceived psychological QoL. Women who manifested hypervigilance and hyperarousal during pregnancy were more likely to perceive lower psychological QoL three months after birth. Finally, post-traumatic symptoms of intrusiveness during pregnancy correlated with higher levels of parenting stress and higher risk of dysfunctional parenting, together with a stronger perception of having a child with a difficult temperament in the post-partum period. Conclusions: Mood states and post-traumatic symptoms can decrease the mother’s quality of life and heighten parental distress. These preliminary results suggest implementing psychological support for women with current or previous oncological diagnosis during pregnancy in order to prevent the onset of dysfunctional parenting and/or problem behaviours in their children. [Table: see text]
Mucosal IgG in inflammatory bowel disease – a question of (sub)class?
Authors: Tomas Castro-Dopico, Menna R. Clatworthy
Journal: Gut Microbes (2019)

Immunoglobulins (Igs) form a cornerstone of mucosal immunity. In the gastrointestinal tract, secretory IgA and IgM bind to commensal microorganisms within the intestinal lumen to prevent them from breaching the intestinal epithelium – a process known as immune exclusion. In recent years, there has been renewed interest in the role of IgG in intestinal immunity, driven in part by a genetic association of an affinity-lowering variant of an IgG receptor, FcγRIIA, with protection from ulcerative colitis (UC), a subclass of inflammatory bowel disease (IBD). We recently demonstrated a role for IgG and Fcγ receptor signalling in driving pathogenic IL-1β production by colonic mononuclear phagocytes and the subsequent induction of a local type 17 response in UC. Here, we discuss the potential relevance of our observations to the other major subclass of IBD – Crohn's disease (CD) – where the genetic association with FCGR variants is less robust and consider how this may impact therapeutic interventions in these disease subsets.
The Opportunity for Exercise to Improve Population Mental Health
Authors: Adam M. Chekroud, Alisa Trugerman
Journal: JAMA Psychiatry (2019)

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Dietary fat and the faecal microbiome: where collinearity may lead to incorrect attribution of effects to fat
Authors: Zaid S Ardalan, Miles P Sparrow, Jane G Muir, Peter R Gibson
Journal: Gut (2019)

We read with interest the study reported by Yi Wan and colleagues, who examined the relative effects of high-fat and low-fat diets on the gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors.1 The authors should be congratulated for the remarkable achievement of performing a feeding study on 217 young adults for 6 months with impressive retention rate. They concluded that higher fat consumption was associated with unfavourable changes in gut microbiota, faecal metabolomic profiles and systemic inflammation, and implied that difference in dietary fat was causally related to the changes observed, as evidenced by the title of the paper. While the study has been beautifully performed, we believe that the results have been misinterpreted.

The authors have overlooked the importance of the associated alterations in non-digestible carbohydrates. The …
MP calls for independent review of benefits and harms of statins
Authors: Elisabeth Mahase
Journal: BMJ (2019)

MP Norman Lamb, chair of the parliamentary Science and Technology Committee, has written to the Department of Health and Social Care to call for an independent review of all evidence relating to the effectiveness of statins and side effects they may cause.

The letter, addressed to chief scientific adviser Chris Whitty and seen by The BMJ , said the review must be independent of “scientists with personal or institutional ties to drug companies that manufacture statins.”

Lamb also pointed out that raw …