2017 update on pain management in patients with chronic kidney disease

The prevalence of pain has been reported to be \u3e60–70% among patients with advanced and end-stage kidney disease. Although the underlying etiologies of pain may vary, pain per se has been linked to lower quality of life and depression. The latter is of great concern given its known association with reduced survival among patients with end-stage kidney disease.We herein discuss and update the management of pain in patients with chronic kidney disease with and without requirement for renal replacement therapy with the focus on optimizing pain control while minimizing therapy-induced complications

Detecting and removing sample contamination in phylogenomic data: an example and its implications for Cicadidae phylogeny (Insecta Hemiptera).

Contamination of a genetic sample with DNA from one or more nontarget species is a continuing concern of molecular phylogenetic studies, both Sanger sequencing studies and next-generation sequencing studies. We developed an automated pipeline for identifying and excluding likely cross-contaminated loci based on the detection of bimodal distributions of patristic distances across gene trees. When contamination occurs between samples within a data set, a comparison between a contaminated sample and its contaminant taxon will yield bimodal distributions with one peak close to zero patristic distance. This new method does not rely on a priori knowledge of taxon relatedness nor does it determine the causes(s) of the contamination. Exclusion of putatively contaminated loci from a data set generated for the insect family Cicadidae showed that these sequences were affecting some topological patterns and branch supports, although the effects were sometimes subtle, with some contamination-influenced relationships exhibiting strong bootstrap support. Long tip branches and outlier values for one anchored phylogenomic pipeline statistic (AvgNHomologs) were correlated with the presence of contamination

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation. the GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Computing, Ethics and the Public Interest - What does this even mean?

Presented on November 21, 2019 at 12:00 p.m. in the Technology Square Research Building, Banquet Hall.Kathy Pham is a product leader, computer scientist, and founder who has held roles in product management, software engineering, data science, consulting, and leadership in the private, non-profit, and public sector. Her work has spanned Google, IBM, Harris Healthcare, and the federal government at the United States Digital Service at the White House, where she was a founding product and engineering member. At the Harvard Kennedy School, Kathy created and teaches Product Management and Society, and launched Product and Society. Kathy is an Affiliate at the Harvard Berkman Klein Center where she leads the Ethical Tech working group, and focuses on ethics in technology, with an emphasis on engineering culture and computer science curricula.Runtime: 63:05 minutesThe talk will range from ethics and responsibility in computer science, to honoring expertise across disciplines, to applying computer science and engineering skills to the civic and public sector. Georgia Tech and the College of Computing prepared Kathy Pham for broad impact across large tech companies, government, and the public sector. This talk will touch on opportunities for deep impact in society using our computing skills, and the many different ways a degree from Georgia Tech lays a strong foundation for the impact. Kathy will pull from her experience at Google, IBM, and the White House, and share observations from the current landscape of computing, ethics, and the public interest

Inflammatory Profiles and Immune Responses to High-Altitude Acclimatization

High altitude is a physiologically stressful environment due to oxygen limitation and low atmospheric pressure. Despite these conditions, over 160 million people live, work, or travel to high altitude annually. Several systemic physiological changes in response to hypoxia promote acclimatization to high altitude. However, even in acclimatized individuals, there is still a significant risk of developing high-altitude illnesses (HAIs), such as acute mountain sickness, high-altitude pulmonary edema, or high-altitude cerebral edema. While it is clear that HAIs result from high altitude/hypoxia, gaps in our knowledge remain regarding the underlying mechanisms that drive the development of these pathologies. The molecular pathways that control hypoxia responses are evolutionary conserved and have significant crosstalk to essential mechanisms that drive inflammation. While these responses may be key for acute adaptation to hypoxia, they may become maladaptive if not properly mediated. For example, native highlanders show evidence of natural selection for traits that promote adaptation to chronic hypoxia, but different native high-altitude populations display distinct adaptations. However, not all these adaptations are beneficial. Most notably, Andean highlanders have a high prevalence of Chronic Mountain Sickness (CMS), an incapacitating syndrome induced by lifelong exposure to hypoxia. The underlying mechanisms behind CMS are also unknown, however it has been suspected that inflammation may play a role in CMS pathogenesis. The goal of my dissertation research was to determine how high-altitude hypoxia induces changes in inflammatory profiles and immune cell populations. Furthermore, I aimed to investigate if immune cells at high altitude are sensitized to inflammatory stimuli, and if these responses are dependent on hypoxia inducible factor (HIF) activity. To accomplish these goals, I employed several techniques such as multi-parameter flow cytometry, multiplex immunoassays, in vitro stimulation experiments, and an unbiased transcriptomic approach. These studies demonstrate that acute high-altitude exposure increases inflammatory expression, as well as promotes a pro-inflammatory immunophenotype. Furthermore, HIF plays a role in immune cell surface markers, most notably CD14. As sojourners acclimatize, the inflammatory profile favors an anti-inflammatory phenotype. Overall, these studies provide important insights into the role of inflammation in high altitude acclimatization and characterize a potential mechanism underlying hypoxia-induced immune sensitization