tbuckley/cabot-search huggingface dataset:
Understanding the Impact of Rainfall on Diarrhea: Testing the Concentration-Dilution Hypothesis Using a Systematic Review and Meta-Analysis
Authors: Alicia N. M. Kraay, Olivia Man, Morgan C. Levy, Karen Levy, Edward Ionides, Joseph N. S. Eisenberg
Journal: Environmental Health Perspectives (2020)

Background: Projected increases in extreme weather may change relationships between rain-related climate exposures and diarrheal disease. Whether rainfall increases or decreases diarrhea rates is unclear based on prior literature. The concentration-dilution hypothesis suggests that these conflicting results are explained by the background level of rain: Rainfall following dry periods can flush pathogens into surface water, increasing diarrhea incidence, whereas rainfall following wet periods can dilute pathogen concentrations in surface water, thereby decreasing diarrhea incidence. Objectives: In this analysis, we explored the extent to which the concentration-dilution hypothesis is supported by published literature. Methods: To this end, we conducted a systematic search for articles assessing the relationship between rain, extreme rain, flood, drought, and season (rainy vs. dry) and diarrheal illness. Results: A total of 111 articles met our inclusion criteria. Overall, the literature largely supports the concentration-dilution hypothesis. In particular, extreme rain was associated with increased diarrhea when it followed a dry period [incidence rate ratio (IRR)=1.26; 95% confidence interval (CI): 1.05, 1.51], with a tendency toward an inverse association for extreme rain following wet periods, albeit nonsignificant, with one of four relevant studies showing a significant inverse association (IRR=0.911; 95% CI: 0.771, 1.08). Incidences of bacterial and parasitic diarrhea were more common during rainy seasons, providing pathogen-specific support for a concentration mechanism, but rotavirus diarrhea showed the opposite association. Information on timing of cases within the rainy season (e.g., early vs. late) was lacking, limiting further analysis. We did not find a linear association between nonextreme rain exposures and diarrheal disease, but several studies found a nonlinear association with low and high rain both being associated with diarrhea. Discussion: Our meta-analysis suggests that the effect of rainfall depends on the antecedent conditions. Future studies should use standard, clearly defined exposure variables to strengthen understanding of the relationship between rainfall and diarrheal illness. https://doi.org/10.1289/EHP6181
Inclusion of pregnant women in COVID-19 treatment trials: a review and global call to action
Authors: Melanie M Taylor, Loulou Kobeissi, Caron Kim, Avni Amin, Anna E Thorson, Nita B Bellare, Vanessa Brizuela, Mercedes Bonet, Edna Kara, Soe Soe Thwin, Hamsadvani Kuganantham, Moazzam Ali, Olufemi T Oladapo, Nathalie Broutet
Journal: The Lancet Global Health (2020)

Inclusion of pregnant women in COVID-19 clinical trials would allow evaluation of effective therapies that might improve maternal health, pregnancy, and birth outcomes, and avoid the delay of developing treatment recommendations for pregnant women. We explored the inclusion of pregnant women in treatment trials of COVID-19 by reviewing ten international clinical trial registries at two timepoints in 2020. We identified 155 COVID-19 treatment studies of non-biological drugs for the April 7-10, 2020 timepoint, of which 124 (80%) specifically excluded pregnant women. The same registry search for the July 10-15, 2020 timepoint, yielded 722 treatment studies, of which 538 (75%) specifically excluded pregnant women. We then focused on studies that included at least one of six drugs (remdesivir, lopinavir-ritonavir, interferon beta, corticosteroids, chloroquine and hydroxychloroquine, and ivermectin) under evaluation for COVID-19. Of 176 such studies, 130 (74%) listed pregnancy as an exclusion criterion. Of 35 studies that evaluated high-dose vitamin treatment for COVID-19, 27 (77%) excluded pregnant women. Despite the surge in treatment studies for COVID-19, the proportion excluding pregnant women remains consistent. Exclusion was not well justified as many of the treatments being evaluated have no or low safety concerns during pregnancy. Inclusion of pregnant women in clinical treatment trials is urgently needed to identify effective COVID-19 treatment for this population.
QOL-14. A BIOPSYCHOSOCIAL APPROACH TO BRAIN INJURY REHABILITATION FOLLOWING TREATMENT FOR PAEDIATRIC BRAIN TUMOURS: CAN PHARMACOTHERAPY AID NEUROPSYCHOLOGICAL OUTCOME?
Authors: Jo Phillips, Mark Brougham
Journal: Neuro-Oncology (2020)

Abstract Long term survival following paediatric brain tumours has vastly improved in recent decades. Consequently there is a drive towards improved quality of survivorship. Brain tumours, surgical resection and adjuvant therapies represent mechanisms for brain injury and can therefore negatively impact a child’s neuropsychological trajectory; affecting cognition, behaviour, emotional and adaptive functioning and educational/occupational outcomes. A biopsychosocial approach to rehabilitation should target each of these domains through supported remediation, environmental modification and psychoeducation for young people and the key systems around them (e.g. families, education). There is a growing evidence base for the role of concordant psychopharmacologies to improve neuropsychological outcome. Since 2015 children treated at RHSC Edinburgh for brain tumours have been offered pharmacotherapy alongside usual rehabilitation approaches if they demonstrate significant difficulties with Attention, Processing Speed and/or Executive Function on formal neuropsychological assessment. Patients are referred to a Consultant Psychiatrist or Paediatrician (as per local protocol) for medication selection, titration and monitoring. A short case series (N=14) is presented outlining brain tumour pathologies, treatment modalities, neuropsychological profile and rationale for recommending pharmacotherapy. Approximately 50% of patients took up the offer. The treatment/s offered and self or parents reported outcomes is summarised. Pharmacotherapy was broadly effective; “it’s been like night and day”, although for one case (N=1) the side effects outweighed any benefit; “she became even more emotional”. Findings indicate that pharmacotherapy should be considered alongside conventional neurorehabilitation techniques for CYP with specific cognitive difficulties following treatment for paediatric brain tumours.
Abstract 19298: Age-related Decline of the Adaptive Proteostasis Gene Program in Cardiac Myocytes
Authors: Anup V Sarakki, Erik A Blackwood, Khalid M Azizi, Shirin Doroudgar, Christopher C Glembotski
Journal: Circulation (2017)

Introduction: Proteostasis is the ability of the cell to balance the requirement of folding nascent proteins and degrading terminally misfolded ones in an efficient manner. A major site of proteost...
Cost-effectiveness of alcohol use treatments in patients with alcohol-related cirrhosis
Authors: Anton L.V. Avanceña, Nicholas Miller, Sarah E. Uttal, David W. Hutton, Jessica L. Mellinger
Journal: Journal of Hepatology (2020)

Alcohol use treatment such as medication-assisted therapies (MATs) and counseling are available and effective in promoting alcohol abstinence. We sought to explore the cost-effectiveness of different alcohol use treatments among patients with compensated alcohol-related cirrhosis (AC).We simulated a cohort of patients with compensated AC receiving care from a hepatology clinic over their lifetimes. We estimated costs (in 2017 US$) and benefits in terms of quality-adjusted life years (QALYs) gained from healthcare and societal perspectives. Transition probabilities, costs, and health utility weights were taken from the literature. Treatment effects of FDA-approved MATs (acamprosate and naltrexone) and non-FDA approved MATs (baclofen, gabapentin, and topiramate) and counseling were based on a study of employer-insured patients with AC. We calculated incremental cost-effectiveness ratios (ICERs) and performed one-way and probabilistic sensitivity analyses to understand the impact of parameter uncertainty.Compared to a do-nothing scenario, MATs and counseling were found to be cost-saving from a healthcare perspective, which means that they provide more benefits with less costs than no intervention. Compared to other interventions, acamprosate and naltrexone cost the least and provide the most QALYs. If the effectiveness of MATs and counseling decreased, these interventions would still be cost-effective based on the commonly used $100,000 per QALY gained threshold. Several sensitivity and scenario analyses showed that our main findings are robust.Among patients with compensated AC, MATs and counseling are extremely cost-effective, and in some cases cost-saving, interventions to prevent decompensation and improve health. Health policies (e.g. payer reimbursement) should emphasize and appropriately compensate for these interventions.Alcohol use treatments, including physician counseling and medication-assisted therapies (MATs), improve the outcomes of patients with compensated alcohol-related cirrhosis, though use and access have remained suboptimal. In this study, we found that counseling and MATs are extremely cost-effective, and in some cases cost-saving, interventions to help patients with alcohol-related cirrhosis abstain from alcohol and improve their health. Wider use of these interventions should be encouraged.
NCMP-21. REVERSIBLE MOTOR NEURON SYNDROME IN THE SETTING OF CANCER
Authors: Ditte Primdahl, Brad Beinlich, Megan Albertson
Journal: Neuro-Oncology (2020)

Abstract 60 year old female was admitted with difficulty swallowing, slurred speech and gait instability resulting in multiple falls worsening over 2-3 weeks. Her exam revealed subtle spastic dysarthric speech, spasticity in all four extremities (lower &amp;gt; upper and right &amp;gt; left), hyperreflexia, and bilateral Babinksi and Hoffman signs consistent with pure upper motor neuron syndrome. An MRI brain and total spine were without evidence of neurological pathology but revealed an incidental finding of lymphadenopathy concerning for neoplastic process. Her symptoms continued to worsen over the next few weeks and she developed severe, nearly continuous, extensor spasms of BLE (right &amp;gt; left) with stimulus sensitivity causing inability to walk. She was started on baclofen, tizanidine and diazepam for spasticity with only mild improvement. An MRI cervical spine was repeated (please see below) and revealed hyperintense T2 signal in lateral corticospinal tract (right &amp;gt; left) without enhancement and no cord compression. Given strong clinical concern for paraneoplastic process patient received 0.4 g/kg IVIG for 5 days and concurrent 1000 mg methylprednisolone for 3 days with dramatic improvement within days. Cervical lymph node biopsy lead to diagnosis of nodal marginal zone lymphoma. A CT abdomen revealed an ovarian mass concerning for teratoma vs dermoid cyst (pending resection and final pathology). She was treated with weekly boosters of IVIG and IV methylprednisolone and was started on Rituximab for her Lymphoma. When seen in clinic a month post discharge nearly all of her symptoms had resolved. Neurological exam showed subtle residual spasticity making this presentation most consistent with a reversible pure upper motor neuron syndrome.
CSIG-12. HDACs-Sp1-BMI1 PATHWAY IS INVOLVED IN THE ATTENUATION OF STRESS- AND THERAPY-INDUCED DEATH IN GLIOMA
Authors: Wei-Lun Lo, Yu-Ting Tsai, Jian-Ying Chuang
Journal: Neuro-Oncology (2020)

Abstract BMI-1 is a transcriptional repressor and overexpresses in various human cancer tissues, which is also known to involve in the maintenance of “stem cell” features in a cell sub-population within the tumor. Here, we investigate the roles of BMI1 oncogene in brain tumors, notably involving drug-resistant metabolism. Interestingly, microarray datasets in OMCOMINE indicated that BMI1 is not commonly increased in clinical brain tumors, and survival plots in PROGgeneV2 also showed that BMI1 expression is not statistically associated with glioma patients. However, stressful serum starvation and anchorage independence growth conditions enabled to induce upregulation of BMI1. Further investigation, we identified HDAC-Sp1 is a stress-responsive pathway, critically promoting BMI1 expression. HDAC inhibition via vorinostat treatment prevented the binding of Sp1 to BMI1 promoter, leading to decreased BMI1 expression and attenuated tumor growth of TMZ-resistant glioma xenografts. Importantly, increased expression of the HDAC-Sp1-BMI1 axis but not BMI1 alone showed an increased risk of death in both high- and low-grade glioma. Thus, the HDAC-Sp1-BMI1 axis is critical to attenuate stress- and therapy-induced death in glioma cells and the axis inhibition may prevent the recurrence of malignant cells persisting after primary therapy.
ERK1/2 inhibition reduces vascular calcification by activating miR-126-3p-DKK1/LRP6 pathway
Authors: Peng Zeng, Jie Yang, Lipei Liu, Xiaoxiao Yang, Zhi Yao, Chuanrui Ma, Haibo Zhu, Jiamin Su, Qian Zhao, Ke Feng, Shu Yang, Yan Zhu, Xiaoju Li, Wenguang Wang, Yajun Duan, Jihong Han, Yuanli Chen
Journal: Theranostics (2020)

Rationale: Vascular microcalcification increases the risk of rupture of vulnerable atherosclerotic lesions. Inhibition of ERK1/2 reduces atherosclerosis in animal models while its role in vascular calcification and the underlying mechanisms remains incompletely understood. Methods: Levels of activated ERK1/2, DKK1, LRP6 and BMP2 in human calcific aortic valves were determined. ApoE deficient mice received ERK1/2 inhibitor (U0126) treatment, followed by determination of atherosclerosis, calcification and miR-126-3p production. C57BL/6J mice were used to determine the effect of U0126 on Vitamin D3 (VD3)-induced medial arterial calcification. HUVECs, HAECs and HASMCs were used to determine the effects of ERK1/2 inhibitor or siRNA on SMC calcification and the involved mechanisms. Results: We observed the calcification in human aortic valves was positively correlated to ERK1/2 activity. At cellular and animal levels, U0126 reduced intimal calcification in atherosclerotic lesions of high-fat diet-fed apoE deficient mice, medial arterial calcification in VD3-treated C57BL/6J mice, and calcification in cultured SMCs and arterial rings. The reduction of calcification was attributed to ERK1/2 inhibition-reduced expression of ALP, BMP2 and RUNX2 by activating DKK1 and LRP6 expression, and consequently inactivating both canonical and non-canonical Wnt signaling pathways in SMCs. Furthermore, we determined ERK1/2 inhibition activated miR-126-3p production by facilitating its maturation through activation of AMPKα-mediated p53 phosphorylation, and the activated miR-126-3p from ECs and SMCs played a key role in anti-vascular calcification actions of ERK1/2 inhibition. Conclusions: Our study demonstrates that activation of miR-126-3p production in ECs/SMCs and interactions between ECs and SMCs play an important role in reduction of vascular calcification by ERK1/2 inhibition.
NFB-08. PHASE II STUDY OF AXITINIB IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 2 AND PROGRESSIVE VESTIBULAR SCHWANNOMAS
Authors: Sheetal Phadnis, Mari Hagiwara, Anna Yaffe, Carole Mitchell, Theodore Nicolaides, Srivandana Akshintala, Tsivia Hochman, Judith Goldberg, Jeffrey Allen, Matthias Karajannis
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), and c-KIT represent clinically and/or preclinically validated molecular targets in vestibular schwannomas. We conducted a single institution, prospective, open-label, two-stage phase II study (ClinicalTrials.gov identifier NCT02129647) to estimate the response rate to axitinib, an oral multi-receptor tyrosine kinase inhibitor targeting VEGFR, PDGFR and c-KIT, in neurofibromatosis type 2 (NF2) patients with progressive vestibular schwannomas (VS). METHODS NF2 patients older than 5 years with at least one volumetrically measurable, progressive VS were eligible. The primary endpoint was to estimate the objective volumetric response rates to axitinib. Axitinib was given continuously in 28-day cycles for up to of 12 cycles. Response was assessed every 3 months with MRI using 3-D volumetric tumor analysis and audiograms. Volumetric response and progression were defined as ≥20% decrease or increase in VS volume, respectively. RESULTS Twelve eligible patients (ages: 14–56 years) were enrolled on this study. Seven of twelve patients completed 12 cycles (range: 2 to 12 cycles). We observed two imaging and three hearing responses. Best volumetric response was -53.9% after nine months on axitinib. All patients experienced drug-related toxicities, the most common adverse events were diarrhea, hematuria and skin toxicity, not exceeding grade 2 and hypertension, not exceeding grade 3. CONCLUSIONS While axitinib has modest anti-tumor activity in NF2 patients, it is more toxic and appears to be less effective compared to bevacizumab. Based on these findings, further clinical development of axitinib for this indication does not appear warranted.
Development and external validation study combining existing models and recent data into an up-to-date prediction model for evaluating kidneys from older deceased donors for transplantation
Authors: Chava L. Ramspek, Mostafa El Moumni, Eelaha Wali, Martin B.A. Heemskerk, Robert A. Pol, Meindert J. Crop, Nichon E. Jansen, Andries Hoitsma, Friedo W. Dekker, M. van Diepen, Cyril Moers
Journal: Kidney International (2020)

With a rising demand for kidney transplantation, reliable pre-transplant assessment of organ quality becomes top priority. In clinical practice, physicians are regularly in doubt whether suboptimal kidney offers from older donors should be accepted. Here, we externally validate existing prediction models in a European population of older deceased donors, and subsequently developed and externally validated an adverse outcome prediction tool. Recipients of kidney grafts from deceased donors 50 years of age and older were included from the Netherlands Organ Transplant Registry (NOTR) and United States organ transplant registry from 2006-2018. The predicted adverse outcome was a composite of graft failure, death or chronic kidney disease stage 4 plus within one year after transplantation, modelled using logistic regression. Discrimination and calibration were assessed in internal, temporal and external validation. Seven existing models were validated with the same cohorts. The NOTR development cohort contained 2510 patients and 823 events. The temporal validation within NOTR had 837 patients and the external validation used 31987 patients in the United States organ transplant registry. Discrimination of our full adverse outcome model was moderate in external validation (C-statistic 0.63), though somewhat better than discrimination of the seven existing prediction models (average C-statistic 0.57). The model's calibration was highly accurate. Thus, since existing adverse outcome kidney graft survival models performed poorly in a population of older deceased donors, novel models were developed and externally validated, with maximum achievable performance in a population of older deceased kidney donors. These models could assist transplant clinicians in deciding whether to accept a kidney from an older donor.
PARE0010 THE VR DOCTOR – THE IDEAL DOCTOR’S APPOINTMENT
Authors: C. Helin Hollstrand, K. Nilke Nordlund
Journal: Annals of the Rheumatic Diseases (2020)

Background: With new technology available, health care is evolving quickly, and new solutions are constantly being presented. Although few of these solutions focus on patient-participation and patient empowerment. That’s what we wanted to create! Using virtual reality, we figured we could prepare and empower patients before meeting their doctor – and also giving doctor’s a chance to see what it’s like sitting across the table. Objectives: The main objective was to show an example of how an ideal visit to the doctor could look like, to empower patients. By knowing their rights and what kind of care they are entitled to, we wanted to make patients more prepared and feel safer and more comfortable before a doctor’s appointment. The experienced is based on the Swedish Patient Act. We also wanted to be able to show health care professionals what it’s like being a patient, and giving them the opportunity to try it out. Methods: We teamed up with fellow patient organizations Proud Bellies (Stolta Magar) and Youth with Psoriasis (Ung med Psoriasis), pharmaceutical company AbbVie and e-health company Cambio to create the virtual reality experience. Together we workshopped what the ideal doctor’s appointment would be like, based on the Swedish Patient Act, and wrote the script. Our example doctor’s visit is generic, meaning all of our three organizations could use it even though we represent different diseases and diagnoses. But we also created three other virtual reality experiences. They are disease specific, and one is for RA. In the film, you get to go inside the joint to see what happens when you have rheumatism, while a speaker explains it to you. Results: We launched the VR Doctor in January of 2019 with a great event. Patients, health care professionals, press and others were gathered and got to try a visit to the VR Doctor. It was very-well received, especially by other patients. Since then, we have used the tool during our member activities such as summer camps, to empower our members. And we have introduced the tool for health care professionals at several rheumatology clinics throughout Sweden. Conclusion: With new technology comes great opportunities to simplify complicated matters. The VR Doctor is essentially a crash course in the Swedish Patient Act, making it a very useful tool for both patients and health care professionals. By giving an example of what an ideal doctor’s appointment could be like, we are letting patients take matters into their own hands and bringing them a sense a power and control over a situation that normally could be tough and sometimes intimidating. With empowered patients who feel safe, we are one step closer full patient-participation and in the long run a better health care system for all. References: [1]https://vrdoktorn.se/ [2]https://ungareumatiker.se/vr-doktorn-starker-patienter-i-motet-med-varden/ [3]https://www.youtube.com/watch?v=FMw9XmyVh0g [4]https://www.youtube.com/watch?v=xz056alBBkc&amp;t=1s Disclosure of Interests: None declared