arti

Bile Acid Signaling in Metabolic and Inflammatory Diseases and Drug Development [Review Article]

Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates biliary secretion of lipids, endogenous metabolites, and xenobiotics. In intestine, bile acids facilitate the digestion and absorption of dietary lipids and fat-soluble vitamins. Through activation of nuclear receptors and G protein-coupled receptors and interaction with gut microbiome, bile acids critically regulate host metabolism and innate and adaptive immunity and are involved in the pathogenesis of cholestasis, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, type-2 diabetes, and inflammatory bowel diseases. Bile acids and their derivatives have been developed as potential therapeutic agents for treating chronic metabolic and inflammatory liver diseases and gastrointestinal disorders.

Significance Statement

Bile acids facilitate biliary cholesterol solubilization and dietary lipid absorption, regulate host metabolism and immunity, and modulate gut microbiome. Targeting bile acid metabolism and signaling holds promise for treating metabolic and inflammatory diseases.




arti

Drug-Drug Interactions and Synergy: From Pharmacological Models to Clinical Application [Review Article]

This review explores the concept of synergy in pharmacology, emphasizing its importance in optimizing treatment outcomes through the combination of drugs with different mechanisms of action. Synergy, defined as an effect greater than the expected additive effect elicited by individual agents according to specific predictive models, offers a promising approach to enhance therapeutic efficacy while minimizing adverse events. The historical evolution of synergy research, from ancient civilizations to modern pharmacology, highlights the ongoing quest to understand and harness synergistic interactions. Key concepts, such as concentration-response curves, additive effects, and predictive models, are discussed in detail, emphasizing the need for accurate assessment methods throughout translational drug development. Although various mathematical models exist for synergy analysis, selecting the appropriate model and software tools remains a challenge, necessitating careful consideration of experimental design and data interpretation. Furthermore, this review addresses practical considerations in synergy assessment, including preclinical and clinical approaches, mechanism of action, and statistical analysis. Optimizing synergy requires attention to concentration/dose ratios, target site localization, and timing of drug administration, ensuring that the benefits of combination therapy detected bench-side are translatable into clinical practice. Overall, the review advocates for a systematic approach to synergy assessment, incorporating robust statistical analysis, effective and simplified predictive models, and collaborative efforts across pivotal sectors, such as academic institutions, pharmaceutical companies, and regulatory agencies. By overcoming critical challenges and maximizing therapeutic potential, effective synergy assessment in drug development holds promise for advancing patient care.

Significance Statement

Combining drugs with different mechanisms of action for synergistic interactions optimizes treatment efficacy and safety. Accurate interpretation of synergy requires the identification of the expected additive effect. Despite innovative models to predict the additive effect, consensus in drug-drug interactions research is lacking, hindering the bench-to-bedside development of combination therapies. Collaboration among science, industry, and regulation is crucial for advancing combination therapy development, ensuring rigorous application of predictive models in clinical settings.




arti

Glatiramer Acetate for the Treatment of Multiple Sclerosis: From First-Generation Therapy to Elucidation of Immunomodulation and Repair [Review Article]

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS), with a putative autoimmune origin and complex pathogenesis. Modification of the natural history of MS by reducing relapses and slowing disability accumulation was first attained in the 1990 s with the development of the first-generation disease-modifying therapies. Glatiramer acetate (GA), a copolymer of L-alanine, L-lysine, L-glutamic acid, and L-tyrosine, was discovered due to its ability to suppress the animal model of MS, experimental autoimmune encephalomyelitis. Extensive clinical trials and long-term assessments established the efficacy and the safety of GA. Furthermore, studies of the therapeutic processes induced by GA in animal models and in MS patients indicate that GA affects various levels of the innate and the adaptive immune response, generating deviation from proinflammatory to anti-inflammatory pathways. This includes competition for binding to antigen presenting cells; driving dendritic cells, monocytes, and B-cells toward anti-inflammatory responses; and stimulating T-helper 2 and T-regulatory cells. The immune cells stimulated by GA reach the CNS and secrete in situ anti-inflammatory cytokines alleviating the pathological processes. Furthermore, cumulative findings reveal that in addition to its immunomodulatory effect, GA promotes neuroprotective repair processes such as neurotrophic factors secretion, remyelination, and neurogenesis. This review aims to provide an overview of MS pathology diagnosis and treatment as well as the diverse mechanism of action of GA.

Significance Statement

Understanding the complex MS immune pathogenesis provided multiple targets for therapeutic intervention, resulting in a plethora of agents, with various mechanisms of action, efficacy, and safety profiles. However, promoting repair beyond the body’s limited spontaneous extent is still a major challenge. GA, one of the first approved disease-modifying therapies, induces diverse immunomodulatory effects. Furthermore, GA treatment results in elevated neurotrophic factors secretion, remyelination and neurogenesis, supporting the notion that immunomodulatory treatment can support in situ a growth-promoting and repair environment.




arti

Roles of Individual Human Cytochrome P450 Enzymes in Drug Metabolism [Review Article]

Our knowledge of the roles of individual cytochrome P450 (P450) enzymes in drug metabolism has developed considerably in the past 30 years, and this base has been of considerable use in avoiding serious issues with drug interactions and issues due to variations. Some newer approaches are being considered for "phenotyping" metabolism reactions with new drug candidates. Endogenous biomarkers are being used for noninvasive estimation of levels of individual P450 enzymes. There is also the matter of some remaining "orphan" P450s, which have yet to be assigned reactions. Practical problems that continue in drug development include predicting drug-drug interactions, predicting the effects of polymorphic and other P450 variations, and evaluating interspecies differences in drug metabolism, particularly in the context of "metabolism in safety testing" regulatory issues ["disproportionate (human) metabolites"].

Significance Statement

Cytochrome P450 enzymes are the major catalysts involved in drug metabolism. The characterization of their individual roles has major implications in drug development and clinical practice.




arti

Deep Learning-Based Reconstruction of 3D T1 SPACE Vessel Wall Imaging Provides Improved Image Quality with Reduced Scan Times: A Preliminary Study [ARTIFICIAL INTELLIGENCE]

BACKGROUND AND PURPOSE:

Intracranial vessel wall imaging is technically challenging to implement, given the simultaneous requirements of high spatial resolution, excellent blood and CSF signal suppression, and clinically acceptable gradient times. Herein, we present our preliminary findings on the evaluation of a deep learning–optimized sequence using T1-weighted imaging.

MATERIALS AND METHODS:

Clinical and optimized deep learning–based image reconstruction T1 3D Sampling Perfection with Application optimized Contrast using different flip angle Evolution (SPACE) were evaluated, comparing noncontrast sequences in 10 healthy controls and postcontrast sequences in 5 consecutive patients. Images were reviewed on a Likert-like scale by 4 fellowship-trained neuroradiologists. Scores (range, 1–4) were separately assigned for 11 vessel segments in terms of vessel wall and lumen delineation. Additionally, images were evaluated in terms of overall background noise, image sharpness, and homogeneous CSF signal. Segment-wise scores were compared using paired samples t tests.

RESULTS:

The scan time for the clinical and deep learning–based image reconstruction sequences were 7:26 minutes and 5:23 minutes respectively. Deep learning–based image reconstruction images showed consistently higher wall signal and lumen visualization scores, with the differences being statistically significant in most vessel segments on both pre- and postcontrast images. Deep learning–based image reconstruction had lower background noise, higher image sharpness, and uniform CSF signal. Depiction of intracranial pathologies was better or similar on the deep learning–based image reconstruction.

CONCLUSIONS:

Our preliminary findings suggest that deep learning–based image reconstruction–optimized intracranial vessel wall imaging sequences may be helpful in achieving shorter gradient times with improved vessel wall visualization and overall image quality. These improvements may help with wider adoption of intracranial vessel wall imaging in clinical practice and should be further validated on a larger cohort.




arti

Artificial Intelligence Efficacy as a Function of Trainee Interpreter Proficiency: Lessons from a Randomized Controlled Trial [RESEARCH]

BACKGROUND AND PURPOSE:

Recently, artificial intelligence tools have been deployed with increasing speed in educational and clinical settings. However, the use of artificial intelligence by trainees across different levels of experience has not been well-studied. This study investigates the impact of artificial intelligence assistance on the diagnostic accuracy for intracranial hemorrhage and large-vessel occlusion by medical students and resident trainees.

MATERIALS AND METHODS:

This prospective study was conducted between March 2023 and October 2023. Medical students and resident trainees were asked to identify intracranial hemorrhage and large-vessel occlusion in 100 noncontrast head CTs and 100 head CTAs, respectively. One group received diagnostic aid simulating artificial intelligence for intracranial hemorrhage only (n = 26); the other, for large-vessel occlusion only (n = 28). Primary outcomes included accuracy, sensitivity, and specificity for intracranial hemorrhage/large-vessel occlusion detection without and with aid. Study interpretation time was a secondary outcome. Individual responses were pooled and analyzed with the t test; differences in continuous variables were assessed with ANOVA.

RESULTS:

Forty-eight participants completed the study, generating 10,779 intracranial hemorrhage or large-vessel occlusion interpretations. With diagnostic aid, medical student accuracy improved 11.0 points (P < .001) and resident trainee accuracy showed no significant change. Intracranial hemorrhage interpretation time increased with diagnostic aid for both groups (P < .001), while large-vessel occlusion interpretation time decreased for medical students (P < .001). Despite worse performance in the detection of the smallest-versus-largest hemorrhages at baseline, medical students were not more likely to accept a true-positive artificial intelligence result for these more difficult tasks. Both groups were considerably less accurate when disagreeing with the artificial intelligence or when supplied with an incorrect artificial intelligence result.

CONCLUSIONS:

This study demonstrated greater improvement in diagnostic accuracy with artificial intelligence for medical students compared with resident trainees. However, medical students were less likely than resident trainees to overrule incorrect artificial intelligence interpretations and were less accurate, even with diagnostic aid, than the artificial intelligence was by itself.




arti

Common clonal origin of three distinct hematopoietic neoplasms in a single patient: B-cell lymphoma, T-cell lymphoma, and polycythemia vera [RESEARCH ARTICLE]

The potential for more than one distinct hematolymphoid neoplasm to arise from a common mutated stem or precursor cell has been proposed based on findings in primary human malignancies. Particularly, angioimmunoblastic T-cell lymphoma (AITL), which shares a somatic mutation profile in common with other hematopoietic malignancies, has been reported to occur alongside myeloid neoplasms or clonal B-cell proliferations, with identical mutations occurring in more than one cell lineage. Here we report such a case of an elderly woman who was diagnosed over a period of 8 years with diffuse large B-cell lymphoma, polycythemia vera, and AITL, each harboring identical somatic mutations in multiple genes. Overall, at least five identical nucleotide mutations were shared across multiple specimens, with two identical mutations co-occurring at variable variant allele frequencies in all three specimen types. These findings lend credence to the theory that a common mutated stem cell could give rise to multiple neoplasms through parallel hematopoietic differentiation pathways.




arti

ITPR1-associated spinocerebellar ataxia with craniofacial features--additional evidence for germline mosaicism [RESEARCH ARTICLE]

Inositol 1,4,5-triphosphate receptor type 1 (ITPR1) is an endoplasmic reticulum–bound intracellular inositol triphosphate receptor involved in the regulation of intracellular calcium. Pathogenic variants in ITPR1 are associated with spinocerebellar ataxia (SCA) types 15/16 and 29 and have recently been implicated in a facial microsomia syndrome. In this report, we present a family with three affected individuals found to have a heterozygous missense c.800C > T (predicted p.Thr267Met) who present clinically with a SCA29-like syndrome. All three individuals presented with varying degrees of ataxia, developmental delay, and apparent intellectual disability, as well as craniofacial involvement—an uncommon finding in patients with SCA29. The variant was identified using clinical exome sequencing and validated with Sanger sequencing. It is presumed to be inherited via parental germline mosaicism. We present our findings to provide additional evidence for germline mosaic inheritance of SCA29, as well as to expand the clinical phenotype of the syndrome.




arti

De novo TRPM3 missense variant associated with neurodevelopmental delay and manifestations of cerebral palsy [RESEARCH ARTICLE]

We identified a de novo heterozygous transient receptor potential cation channel subfamily M (melastatin) member 3 (TRPM3) missense variant, p.(Asn1126Asp), in a patient with developmental delay and manifestations of cerebral palsy (CP) using phenotype-driven prioritization analysis of whole-genome sequencing data with Exomiser. The variant is localized in the functionally important ion transport domain of the TRPM3 protein and predicted to impact the protein structure. Our report adds TRPM3 to the list of Mendelian disease–associated genes that can be associated with CP and provides further evidence for the pathogenicity of the variant p.(Asn1126Asp).




arti

Clinical and functional analysis of the germline TP53 p.K164E acetylation site variant [RESEARCH ARTICLE]

TP53 plays a critical role as a tumor suppressor by controlling cell cycle progression, DNA repair, and apoptosis. Post-translational modifications such as acetylation of specific lysine residues in the DNA binding and carboxy-terminus regulatory domains modulate its tumor suppressor activities. In this study, we addressed the functional consequences of the germline TP53 p.K164E (NM_000546.5: c.490A>G) variant identified in a patient with early-onset breast cancer and a significant family history of cancer. K164 is a conserved residue located in the L2 loop of the p53 DNA binding domain that is post-translationally modified by acetylation. In silico, in vitro, and in vivo analyses demonstrated that the glutamate substitution at K164 marginally destabilizes the p53 protein structure but significantly impairs sequence-specific DNA binding, transactivation, and tumor cell growth inhibition. Although p.K164E is currently considered a variant of unknown significance by different clinical genetic testing laboratories, the clinical and laboratory-based findings presented here provide strong evidence to reclassify TP53 p.K164E as a likely pathogenic variant.




arti

Leukemic presentation and progressive genomic alterations of MCD/C5 diffuse large B-cell lymphoma (DLBCL) [RESEARCH ARTICLE]

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous group of lymphoid malignancies. Based on gene expression profiling, it has been subdivided into germinal center (GC)-derived and activated B-cell (ABC) types. Advances in molecular methodologies have further refined the subclassification of DLBCL, based on recurrent genetic abnormalities. Here, we describe a distinct case of DLBCL that presented in leukemic form. DNA sequencing targeting 275 genes revealed pathogenically relevant mutations of CD79B, MyD88, TP53, TBL1XR1, and PIM1 genes, indicating that this lymphoma would be best classified as MCD/C5 DLBCL, an ABC subtype. Despite an initial good clinical response to BTK inhibitor ibrutinib, anti-CD20 antibody rituxan, alkylating agent bendamustine, and hematopoietic stem-cell transplant, the lymphoma relapsed, accompanied by morphologic and molecular evidence of disease progression. Specifically, the recurrent tumor developed loss of TP53 heterozygosity (LOH) and additional chromosomal changes central to ABC DLBCL pathogenesis, such as PRDM1 loss. Acquired resistance to ibrutinib and rituxan was indicated by the emergence of BTK and FOXO1 mutations, respectively, as well as apparent activation of alternative cell-activation pathways, through copy-number alterations (CNAs), detected by high-resolution chromosomal microarrays. In vitro, studies of relapsed lymphoma cells confirmed resistance to standard BTK inhibitors but sensitivity to vecabrutinib, a noncovalent inhibitor active against both wild-type as well as mutated BTK. In summary, we provide in-depth molecular characterization of a de novo leukemic DLBCL and discuss mechanisms that may have contributed to the lymphoma establishment, progression, and development of drug resistance.




arti

HBO Boss on Working With George R.R. Martin: ‘Marriages Can Be Difficult’



HBO's Casey Bloys was asked about the Game of Thrones author's spicy take on House of the Dragon season two.



  • Television
  • Game of Thrones
  • George RR Martin
  • HBO
  • House of the Dragon


arti

Alan Wake 2’s The Lake House is a dark, brilliant parable on the devaluation of art and artists

There must be hundreds of typewriters in the hall, their collective clacks a tidal wave of soulless automation, rising up to greet agent Kiran Estevez as she enters, pistol and flashlight in hands. Exploring rooms to the side, Alan Wake 2: The Lake House’s star finds whiteboards and documents revealing the typewriter’s purpose: to mimic Wake’s writing. Pages are graded along criteria such as ‘style’, ‘tone’, and ‘content’, then “fed into the algorithm” as references until “near-identical stories” to Wake’s can be produced.

“If Jules could simply cut the painter open and pull the painting out of him, he would,” reads one of the real Alan’s typewritten pages. That’s Jules Marmont, the obsessive head of the titular FBC centre. The Marmonts - Jules and his wife Diana - are running experiments to forcibly and synthetically create works of art, aiming to mimic creative passion convincingly enough for the paranatural entity inside Cauldron Lake to respond, as it has in the past.

Read more




arti

Twitter chat: How the gun control debate mirrors larger issues of partisanship in America

Participants with One Million Moms for Gun Control, a gun control group formed in the wake of the Newtown, Connecticut, school mass shooting, march across the Brooklyn Bridge on Jan. 21, 2013, in New York City. Photo by Spencer Platt/Getty Images

What would it take to turn Texas, a Republican stronghold, into a blue state? According to data from SurveyMonkey, just remove all the gun owners from the Lone Star State and it would have gone to Hillary Clinton in 2016. You can do the same thing in liberal California. Remove all the non-gun owners and the state would have voted for Donald Trump.

That’s how divisive the issue of gun control is in American politics.

SurveyMonkey found that no other demographic — not race, religion or gender — so perfectly divided voters. In the 2016 election, 47 percent of Trump supporters said gun control was an issue important enough to influence their vote. That’s compared to just 27 percent of voters who supported Hillary Clinton.

But what does this divide mean? How is it impacting gun control policy, and how might this issue change in light of recent mass shootings like Las Vegas, Orlando and Newtown? To discuss the data, join a PBS NewsHour-hosted Twitter chat at 1 p.m. EDT Thursday with data journalist Dante Chinni (@Dchinni), professor and chairman of political science at the University of Kansas Don Haider-Markel (@dhmarkel), and Washington Post correspondent Philip Bump (@pbump).

Have questions? Tweet them using #NewsHourChats.

The post Twitter chat: How the gun control debate mirrors larger issues of partisanship in America appeared first on PBS NewsHour.




arti

Martin Lewis issues warning to anyone with a Tesco Clubcard as £18m savings at risk



Martin Lewis has warned Tesco customers of a piece of small print that could see £18m worth of Clubcard points wasted.




arti

The AI expert who says artificial general intelligence is nonsense

Artificial intelligence has more in common with ants than humans, says Neil Lawrence. Only by taking a more nuanced view of intelligence can we see how machines will truly transform society




arti

How E. coli infections wreak havoc on the body, causing dangerous disease — particularly in kids

Certain strains of E. coli are capable of causing severe disease, by rapidly spreading through the human digestive system, wreaking havoc throughout the bloodstream, and eventually damaging the delicate kidneys. That's the situation right now during a large outbreak in Alberta, with hundreds of children now affected.




arti

Artificial intelligence is being used in university classes. How it's being used matters, say profs

As artificial intelligence becomes more common in university classrooms, some professors are weighing the benefits — and downsides — of students using it for research projects.



  • News/Canada/Nova Scotia

arti

Can the free market ensure artificial intelligence won't wipe out human workers?

People keep predicting that each wave of new technology will mean humans can put their feet up. It hasn't happened yet. Some economists and anthropologists who study the subject say even with the arrival of artificial intelligence, humans will remain integral to making the world go round.




arti

Raul Torras Martinez killed at Isle of Man TT





arti

Allies providing Sudan's warring parties with weapons are 'enabling the slaughter,' UN official says




arti

From Prolonging Wallaby Pregnancies to Disorienting Hatchling Turtles, 11 Ways Artificial Lights Affect Animals

From the busy cities to ocean waters, our need to illuminate the world has had some strange and tragic consequences




arti

Ricky Martin on Pandemic-Induced Anxiety and Promoting Social Justice for His Kids

The Puerto Rican singer covers the latest issue of 'Out' magazine.

[[ This is a content summary only. Visit my website for full links, other content, and more! ]]




arti

Martin Garrix set to perform in ‘world’s biggest Holi celebration’ in India

Tickets for the event will go on sale on November 10, 2024, via BookMyShow




arti

Lead melam artiste Satheesan Marar gears up for Kerala’s annual temple festival season

Peruvanam Satheesan Marar recalls his initiation into the percussion ensemble and how he gained expertise in playing different instruments




arti

Mesopotamia Artifacts Help Explain How Language Evolved from Pictures to Words

By comparing early markings used for business purposes to 'proto' cuneiform, we can say language transitioned from symbols to writing.




arti

George RR Martin teases potential new Game of Thrones project with Maisie Williams

Williams played Arya Stark in Game of Thrones for eight seasons




arti

F1: Mercedes motorisera Alpine à partir de 2026

C'était une nouvelle attendue.




arti

Canadien 7, Sabres 5: «Les boys en avaient assez» – Martin St-Louis

Traverser une séquence de revers, ça n’a rien de plaisant. Surtout quand elle vous refoule jusqu’au dernier rang de la LNH.




arti

Artist José González is creating an underwater universe — with an iPad

José González is an illustrator, author and animator originally from Buenos Aires now living in English Harbour. González was selected to be one of the Artists in Residence at Business and Arts N.L. (Un)Common Threads Creativity and Innovation Summit happening on Nov. 7. In advance of the summit, González has been busy preparing for his installation, which will feature a large-scale fish tank with animated sea creatures brought to life through projections and augmented reality.




arti

'No happy paintings': Dozens of art works by Canadian war artist at Calgary exhibit

Bill MacDonnell's paintings are on display at the Military Museums in Calgary through Remembrance Day and into 2025.



  • News/Canada/Calgary

arti

Une ancienne boîte St-Hubert des années 70 retrouvée dans l’entretoit d’un chalet près de Stoneham et remise à la famille Martin en échange d'un don de 1000$

Une ancienne boîte de poulet St-Hubert, retrouvée par hasard dans l’entretoit d’un chalet, a été remise à la famille Martin en échange d'un don.




arti

PRIMEUR | Le PQ a choisi sa candidate pour la partielle dans Terrebonne

Le Parti Québécois misera sur sa présidente, Catherine Gentilcore, pour tenter de ravir la circonscription de Terrebonne à la CAQ.




arti

Indian health, pharma companies invited to participate in Iraq's 'Medico Expo' from Feb 5─8, 2025

The Embassy of India in Iraq has extended an invitation to Indian businesses to participate in the "Medico Expo," officially known as the Erbil International Health Exhibition. This prestigious event, set to be the




arti

DGTR releases list of registered parties on anti─dumping investigation on sodium citrate imports from China

The Directorate General of Trade Remedies (DGTR), under the ministry of commerce and industry, has released a list of registered interested parties regarding the ongoing Second Sunset Review anti─dumping




arti

Happy Martian New Year!

The Martian new year arrives with the Red Planet’s vernal equinox. Explaining why requires a deep dive into celestial mechanics and Earth’s calendrical history




arti

Mariana Oncology’s Radiopharm Platform Acquired By Novartis

Novartis recently announced the acquisition of Mariana Oncology, an emerging biotech focused on advancing a radioligand therapeutics platform, for up to $1.75 billion in upfronts and future milestones. The capstone of its three short years of operations, this acquisition represents

The post Mariana Oncology’s Radiopharm Platform Acquired By Novartis appeared first on LifeSciVC.




arti

Medicinal Chemistry In The Age Of Artificial Intelligence

By Peter Tummino, CSO of Nimbus Therapeutics, as part of the From The Trenches feature of LifeSciVC  “Over the next five to 10 years, our goal is to become a company that’s leading the world in personalized medicines, a company

The post Medicinal Chemistry In The Age Of Artificial Intelligence appeared first on LifeSciVC.




arti

Will Your Family Make You a Better Trial Participant?

It is becoming increasing accepted within the research community that patient engagement leads to a host of positive outcomes – most importantly (at least practically speaking) improved clinical trial recruitment and retention.

But while we can all agree that "patient engagement is good" in a highly general sense, we don't have much consensus on what the implications of that idea might be. There is precious little hard evidence about how to either attract engaged patients, or how we might effectively turn "regular patients" into "engaged patients".

That latter point - that we could improve trial enrollment and completion rates by converting the (very large) pool of less-engaged patient - is a central tenet of the mHealth movement in clinical trials. Since technology can now accompany us almost anywhere, it would seem that we have an unprecedented opportunity to reach out and connect with current and potential trial participants.

However, there are signs that this promised revolution in patient engagement hasn't come about. From the decline of new apps being downloaded to the startlingly high rate of people abandoning their wearable health devices, there's a growing body of evidence suggesting that we aren't in fact making very good progress towards increasing engagement. We appear to have underestimated the inertia of the disengaged patient.

So what can we do? We know people like their technology, but if they're not using it to engage with their healthcare decisions, we're no better off as a result.

Daniel Calvert, in a recent blog post at Parallel 6 offers an intriguing solution: he suggests we go beyond the patient and engage their wider group of loved ones. By engaging what Calvert calls the Support Circle - those people most likely to "encourage the health and well being of that patient as they undergo a difficult period of their life" - trial teams will find themselves with a more supported, and therefore more engaged, participant, with corresponding benefits to enrollment and retention. 

Calvert outlines a number of potential mechanisms to get spouses, children, and other loved ones involved in the trial process:
During the consent process the patient can invite their support team in with them. A mobile application can be put on their phones enabling encouraging messages, emails, and texts to be sent. Loved ones can see if their companion or family member did indeed take today’s medication or make last Monday’s appointment. Gamification offers badges or pop-ups: “Two months of consecutive appointments attended” or “perfect eDiary log!” Loved ones can see those notifications, like/comment, and constantly encourage the patients. 
Supporting materials can also be included in the Support Circle application. There are a host of unknown terms to patients and their team. Glossaries, videos, FAQs, contact now, and so much more can be made available at their fingertips.
I have to admit I'm fascinated by Calvert's idea. I want him to be right: the picture of supportive, encouraging, loving spouses and children standing by to help a patient get through a clinical trial is an attractive one. So is the idea that they're just waiting for us to include them - all we need to do is a bit of digital communication with them to get them fully on board as members of the study team.

The problem, however, remains: we have absolutely no evidence that this approach will work. There is no data showing that it is superior to other approaches to engage trial patients.

(In fact, we may even have some indirect evidence that it may hinder enrollment: in trials that require active caregiver participation, such as those in Alzheimer's Disease, caregivers are believed to often contribute to the barriers to patient enrollment).

Calvert's idea is a good one, and it's worthy of consideration. More importantly, it's worthy of being rigorously tested against other recruitment and retention approaches. We have a lot of cool new technologies, and even more great ideas - we're not lacking for those. What we're lacking is hard data showing us how these things perform. What we especially need is comparative data showing how new tactics work relative to other approaches.

Over 5 years ago, I wrote a blog post bemoaning the sloppy approaches we take in trial recruitment - a fact made all the more painfully ironic by the massive intellectual rigor of the trials themselves. I'm not at all sure that we've made any real progress in those 5 years.

In my next post, I'll outline what I believe are some of the critical steps we need to take to improve the current situation, and start bringing some solid evidence to the table along with our ideas.

[Photo credit: Flikr user Matthew G, "Love (of technology)"]







arti

CVS Health Exec: Payers Need to Stop Making Behavioral Health Providers Jump Through Hoops In Order to Participate in Value-Based Care

Value-based care contracting is especially difficult for behavioral health providers, Taft Parsons III, chief psychiatric officer at CVS Health/Aetna, pointed out during a conference this week.

The post CVS Health Exec: Payers Need to Stop Making Behavioral Health Providers Jump Through Hoops In Order to Participate in Value-Based Care appeared first on MedCity News.




arti

Pew Applauds Michigan for Enacting Bipartisan Legislation to Safely Reduce Jail Populations

The Pew Charitable Trusts today commended Michigan Governor Gretchen Whitmer (D), state Senate Majority Leader Mike Shirkey (R), and Lee Chatfield (R)—whose term as state House Speaker ended last month—for passing and signing a bipartisan package of bills aimed at protecting public safety while reducing the number of people in county jails.




arti

Data | How regional parties in India are funded?

Total income for the selected regional parties in FY20 amounted to ₹803.24 crore, of which 55% was from unknown sources




arti

Data | Anonymous donations to parties in FY21: Congress tops list, BJP close second

In FY21, national parties and regional parties received ₹427 crore and ₹264 crore worth of funds, respectively, from unknown sources




arti

Odisha political parties urge ECI to ensure neutrality of government machineries during elections

As many as 3.32 crore voters will cast their votes in 37,809 polling stations across State





arti

Conjoncture logement au 1er semestre 2015 : un march� soutenu par l'investissement locatif des particuliers, un march� qui repart ? - Les tendances du march� neuf

Les tendances du march� neuf