Category: Congenital disorders

The global hydrocephalus shunts market was valued at $291.00 million in 2019 and is projected to reach $322.01 million by 2027, registering a CAGR of 2.8% from 2020 to 2027. Growth in the number of hydrocephalic patients across the world majorly drives the growth of the hydrocephalus shunts market. For instance, according to the National Institute of Neurological Disorders and Stroke, in 2020, 1 to 2 of every 1000 babies are born with hydrocephalus, globally. Thus, considering the total number of newborns per year, the prevalence of hydrocephalus is all set to increase in the future. Furthermore, a rise in cases of neurological disorders, owing to congenital abnormalities and lifestyle diseases as well as a rise in incidences of brain and nerve injuries, boosts the demand for hydrocephalic shunts. In addition, the use of advanced programmable valves helps neurosurgeons to externally adjust valve pressure used in shunts during the treatment. Hydrocephalus is a neurological disorder caused due to abnormal accumulation of cerebrospinal fluid or CSF in the brain cavities called ventricles. The human body produces approximately 500 ml of CSF on daily basis, with the continuous replacement of the fluid as it is reabsorbed. In normal conditions, there is a subtle balance in between the amount of fluid produced and the rate at which it is absorbed within the body. Hydrocephalus occurs when there is a disruption in this balance. As ventricles produce CSF continuously, this disruption results in the accumulation of fluid, causing ventricles to enlarge and increase pressure on the brain tissues. Download Free Sample of This Strategic Report: https://reportocean.com/industry-verticals/sample-request?report_id=AMR1319 This thereby helps in controlling over-draining and under-draining issues associated with fixed pressure valves, which, in turn, is expected to drive the growth of the hydrocephalic shunts market. In addition, the use of programmable valves in treating hydrocephalus is anticipated to gain popularity in the coming years as most the medical professionals are opting for programmable shunts to reduce infections and malfunctions caused due to repetitive shunt surgeries. However, serious damages caused by infections and malfunctions of existing shunts greatly limit market growth. Some deleterious complications include irreversible brain injuries, meningitis, endocarditis, traumatic perforation, tricuspid regurgitation, heart failure, pulmonary hypertension, and others. On the contrary, advancements in shunt technology for reducing shunt complications are projected to create lucrative opportunities for market growth. This condition is commonly treated by surgical procedures, performed by neurosurgeons, which involves implanting a tube “shunt” into the human brain. This shunt is responsible for channeling and diverting the fluid from ventricles to other parts of the body, wherein it can be reabsorbed and transported back to the bloodstream. Surgical procedure controls hydrocephalus in most patients, however, implanting a shunt does not cure the condition. It is a life-long disorder, accompanied by several long-term complications. Moreover, if these complications are left untreated or undiagnosed, they cause severe brain damages and could be life-threatening. The global hydrocephalus shunts market is segmented on the basis of type, age group, and region. By type, the market is classified into ventriculo-peritoneal shunts, ventriculo-atrial shunts, ventriculo-pleural shunts, and lumbo-peritoneal shunts. By age group, the hydrocephalus shunts market is categorized into infants, children, and adults. Region-wise, the market is analyzed across North America, Europe, Asia-Pacific, and LAMEA. The healthcare sector is vital to both national economies and people all across the world. One of the industries with the fastest growth rates is this one. There is a correlation between income levels and healthcare spending across nations because healthcare spending accounts for more than 10% of the GDP of the majority of developed countries. According to the Centers for Medicare and Medicaid Services, US healthcare spending increased by 4.6% in 2019 to reach US$ 3.8 trillion, or US$ 11,582 per person and represented 17.7% of GDP. Additionally, households paid for 28.4% of all health expenditures, followed by the federal government for 29.0%. 16.1% of all healthcare costs were paid for by state and municipal governments, while 7.5% came from other private sources. Download Free Sample of This Strategic Report: https://reportocean.com/industry-verticals/sample-request?report_id=AMR1319 Due to advancements spurred by AI/ML, the impact of digital health technology will grow. Data from the Department for Promotion of Industry and Internal Trade show that FDI in the medicines and medication sector totaled US$19.12 billion (DPIIT). KEY BENEFITS FOR STAKEHOLDERS ? This report provides a detailed quantitative analysis of the current market trends and future estimations from 2019 to 2027, which assists to identify the prevailing market opportunities.? An in-depth analysis of various regions is anticipated to provide a detailed understanding of the current trends to enable stakeholders to formulate region-specific plans.? A comprehensive analysis of the factors that drive and restrain the growth of the global hydrocephalus shunt market is provided.? An extensive analysis of various regions provides insights that allow companies to strategically plan their business moves. KEY MARKET PLAYERS– Christoph Miethke GmbH & Co. KG– G. Surgiwear Ltd.– HLL Lifecare Limited– HpBio Prteses, Inc.– Integra Life Sciences– Kaneka Medix Corporation– Medtronic plc– Natus Medical Incorporated– Spiegelberg GmbH & CO. KG– Tokibo Co., Ltd. KEY MARKET SEGMENTS– By Typeo Ventriculo-peritonealo Ventriculo-atrialo Ventriculo-pleuralo Lumbo-peritoneal You Can Browse The Request Full Report here: https://reportocean.com/industry-verticals/sample-request?report_id=AMR1319 – By Age Groupo Infantso Childreno Adults – By Regiono North America? U.S.? Canada? Mexicoo Europe? Germany? UK? France? Italy? Spain? Rest of Europeo Asia-Pacific? Japan? China? India? Australia? South Korea? Rest of Asia-Pacifico LAMEA? Brazil? Saudi Arabia? South Africa? Rest of LAMEA Table of Content: Report Overview Global Growth Trends Competition Landscape by Key Players Data Segments North America Market Analysis Europe Market Analysis Asia-Pacific Market Analysis Latin America Market Analysis Middle East & Africa Market Analysis Key Players Profiles Market Analysis Analysts Viewpoints/Conclusions Appendix Reasons to Buy This Report: This file will help the peruses with appreciation the opposition interior the ventures and structures for the serious local weather to improve the feasible benefit. The document moreover facilities round the cutthroat scene of the market, and provides exhaustively the piece of the pie, industry positioning, contender organic system, market execution, new object advancement,

Welcome back to Diagnosis, a vertical that focuses on the crossroads of health care policy and politics. ___ — Budgetary matters — Gov. Ron DeSantis may spend a lot of time on the campaign trail, but we also expected him to roll out his budget for 2024 in the next several days. Senate committees have already scheduled Dec. 6 to hear presentations from DeSantis’ budget staff in several areas, including the Governor’s budget recommendations on health care spending and key agencies such as the Agency for Health Care Administration (AHCA) and the Department of Health (DOH). DeSantis must submit his spending plan to state legislators at least 30 days before the scheduled Jan. 9 opening day of Session. The timeline laid out by the Senate suggests the Governor will release it between now and next Tuesday. Session is approaching, time for Florida to pay its tab. This will be the sixth set of budget recommendations outlined by DeSantis, but unlike the last several years, he has yet to give a lot of hints or spelled out many of his top priorities ahead of time. Given the state’s continued budget surplus, DeSantis has suggested he will probably ask for a fresh round of tax cuts. Still, he needs to outline many other significant spending items. One item of interest will be the state’s Medicaid budget and how much state money will need to be set aside for the program funded jointly with the federal government. State economists have projected the caseload will continue to drop from a peak during the COVID-19 emergency as state officials continue to trim the rolls even as outside groups and even the federal government raise alarm bells at the rate. Medicaid enrollment during the calendar year has dropped from 5.77 million at the end of April to 5.10 million at the end of October. Economists had previously projected that Medicaid enrollment would dip to about 5.02 million by the end of June 2024. ___ I welcome your feedback, questions and especially your tips. You can email me at [email protected] or call me at 850-251-2317. — Grand jury update — Nearly a year ago, at DeSantis’ urging, the Florida Supreme Court agreed to impanel a statewide grand jury to look at pharmaceutical companies and others involved in developing and distributing COVID-19 vaccines. But so far, the grand jury has issued no reports or given any updates on its work and, at some point, the clock will tick down. Statewide grand juries are appointed for one year. However, the court can extend the term by six months if petitioned by a majority of the statewide grand jury or by the legal adviser to the statewide grand jury. A grand jury looking at immigration issues, for example, asked for and was granted an extension until April 2024. The clock is ticking for a grand jury to look into vaccine production. The one-year mark, however, is not tied to the court’s order but to when the grand jury itself is seated, according to a representative for the Supreme Court. That date appears to have been later in the spring of 2023. A key question remains whether the grand jury will produce findings that DeSantis can tout on the presidential campaign trail. The Iowa caucuses are Jan. 15, and the DeSantis campaign is counting on a solid showing for momentum in his challenge to former President Donald Trump. DeSantis, who early on promoted the use of vaccines only to express skepticism on their effectiveness later, filed a petition in December 2022 asking the court to bless the creation of a grand jury to look into the safety and efficacy of vaccines, adding that “an investigation is warranted to determine whether the pharmaceutical industry has engaged in fraudulent practices.” During his presidential bid, DeSantis faulted Trump for sticking by top medical adviser Anthony Fauci. So, any adverse findings from the grand jury might aid the Governor’s criticisms of Trump. The COVID-19 vaccine grand jury is currently presided over by the chief judge of Hillsborough County, with jurors selected from five different circuits in central and southwest Florida. — Achtung, Weida — According to social media sites, AHCA Secretary Jason Weida has been in Germany as part of the state’s trade mission, attending a health technology trade show and meeting with German health care officials and physicians. Weida led Florida’s mission to the @MEDICATradeFair in Germany. ABHI, an acronym for the Association of British HealthTech Industries, sponsored the four-day trade show. Achtung, baby. Meanwhile, the state Commerce Department posted on X that dozens of Florida medical companies displayed “cutting-edge, high-quality medical products and services.” Weida also met with the Bavarian State Ministry of Health, which oversees the health care system for Bavaria’s 13 million residents. Weida posted on X that the meeting “focused on hospital regulation, pharmaceutical pricing, and demographic changes and challenges.” He also met with Klinikum Rechts der Isar CEO and medical director Dr. Martin Siess. “Among other things, we discussed cancer treatment and innovation in the field of nuclear medicine with the head of the hospital’s department, Dr. Wolfgang Weber. I look forward to continuing our discussion of cancer innovation and connecting them with thought leaders in Florida,” Weida wrote on X. Germany has universal health coverage provided by Statutory Health Insurance (SHI) and private health insurance (PHI). SHI is mandatory unless a person earns enough to opt out and purchase the PHI. Approximately 88% of the population receives primary coverage through SHI and 11% have PHI, according to The CommonWealth Fund. — Naloxone confusion — A Senate health panel next week is expected to advance legislation establishing June 6 as Naloxone Awareness Day. SB 66 creates in statute “Victoria’s Law,” which encourages the DOH to hold events to “raise awareness of the dangers of opioid overdose and the availability and safe use of naloxone as an effective way to rapidly reverse the effects of opioid overdose.” But there is a battle of sorts going on between providers

By Iram Ramzan Published: 19:27 EST, 29 November 2023 | Updated: 19:27 EST, 29 November 2023

Abstract Oculocutaneous albinism is an inherited disorder of melanin biosynthesis, characterized by absent or reduced pigmentation of the skin, hair, and eyes. Molecular alterations of genes that cause non-syndromic albinism in Asian Indians are poorly characterized. This information would be useful for developing therapies for this disorder. We analyzed 164 persons with non-syndromic albinism, belonging to unrelated families from all parts of India, for molecular changes in the causative genes. Subjects with white hair, white skin, and red iris had their tyrosinase gene sequenced and were also tested by MLPA for deletions/duplications. Subjects with negative results or with darker skin, golden/brown or darker hair had sequencing of TYR, P, TYRP1, SLC45A2 and GPR143 genes. Pathogenic variants in TYR (OCA1) were observed in 139 (84.7%) patients, in the P gene (OCA2) in 20 (12.2%), in TYRP1 (OCA3) in two (1.2%), in SLC45A2 (OCA 4) in one (0.61%), and in GPR143 (X-linked ocular albinism) in two (1.2%) patients. Of 278 alleles with variants in TYR, 179 (64.3%) alleles had (p.R278*) alteration, suggesting the possibility of therapy with a stop codon readthrough molecule. We report 20 patients with 13 disease associated variants in the P gene and 18 novel pathogenic variants in TYR, P, TYRP1, SLC45A2 and GPR143 genes. The data are compared with those reported from India, Pakistan and rest of the world. The therapeutic options in albinism are briefly described, opening this field for future therapies. 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The variants are submitted to LOVD V3.0 as individual # 00435430, 00435573, 00435574, 00435575, 00436615, 00436616, 00436617, 00436618, 00436619, 00436620, 00436621, 00436622, 00436624, 00436625,00436626,00436627,00436636,00436637,00436638,00436639,00436640,00436641,00436642,00436643,00466644,00436645,00436666,00436667,00436668,00436669,00436670,00436671,00436675,00436676,00436777,00436778,00436784,00436785,00436786,00436787,00436788. References OMIM®Online Mendelian Inheritance in Man. Johns Hopkins University, Baltimore, MD; 1985. Albinism, Oculocutaneous, Type IA; OCA1A. # 203100; 6/2/1986 [Updated 01/27/2021]. Available from: https://www.omim.org/entry/203100. Summers CG, Albinism. In: Lambert SR, Lyons CJ, editors. Taylor and Hoyt’s pediatric ophthalmology and strabismus. 6th ed. USA: Elsevier Inc; 2022. 403–10. Kromberg JGR, Kerr R. Oculocutaneous albinism in southern Africa: historical background, genetic, clinical and psychosocial issues. Afr J Disabil. 2022;11:877. Article PubMed PubMed Central Google Scholar The Lancet Child Adolescent Health. Albinism: myths and reality. Lancet Child Adolesc Health. 2019;3:511. Article CAS PubMed Google Scholar Jeevan Trust. Raising awareness about albinism in India. India, 2016. Available from https://www.thebetterindia.com/50960/jeevan-trust-albinism-awareness/. Gupta A. Albinism India Group. Available from: https://www.facebook.com/groups/139027856116032. Verma IC, Anand NK, Modi UJ, Bharucha BA. Study of malformations and Down syndrome in India–a multi-centric study. Mumbai: Department of Atomic Energy, and Trombay, Bhabha Atomic Research Center; 1998). Master-Notani P, Kolah PJ, Sanghvi LD. Congenital malformations in the new born in Bombay II. Acta Genet Stat Med. 1968;18:193–205. CAS PubMed Google Scholar Chaki M, Mukhopadhyay A, Chatterjee S, Das M, Samanta S, Ray K. Higher prevalence of OCA1 in an ethnic group of eastern India is due to a founder mutation in the tyrosinase gene. Mol Vis. 2005;11:531–4. CAS PubMed Google Scholar Chaki M, Sengupta M, Mukhopadhyay A, Subba Rao I, Majumder PP, Das M, et al. OCA1 in different ethnic groups of India is primarily due to founder mutations in the tyrosinase gene. Ann Hum Genet. 2006;70:623–30. Article CAS PubMed Google Scholar Ullah MI. Clinical and mutation spectrum of autosomal recessive non-syndromic oculocutaneous albinism (nsOCA) in Pakistan: a review. Genes. 2022;13:1072. Article CAS PubMed PubMed Central Google Scholar Ma EZ, Zhou AE, Hoegler KM, Khachemoune A. Oculocutaneous albinism: epidemiology, genetics, skin manifestation, and psychosocial issues. Arch Dermatol Res. 2023;315:107–16. Article PubMed Google Scholar Tripathi RK, Bundey S, Musarella MA, Droetto S, Strunk KM, Holmes SA, et al. Mutations of the tyrosinase gene in Indo-Pakistani patients with type I (tyrosinase-deficient) oculocutaneous albinism (OCA). Am J Hum Genet. 1993;53:1173–9. CAS PubMed PubMed Central Google Scholar Sundaresan P, Sil AK, Philp AR, Randolph MA, Natchiar G, Namperumalsamy P. Genetic analysis of oculocutaneous albinism type 1 (OCA1) in Indian families: two novel frameshift mutations in the TYR Gene. Mol Vis. 2004;10:1005–10. CAS PubMed Google Scholar Miyamura Y, Verma IC, Saxena R, Hoshi M, Murase A, Nakamura E, et al. Five novel mutations in tyrosinase gene of Japanese and Indian patients with oculocutaneous albinism type I (OCA1). J Invest Dermatol. 2005;125:397–8. Article CAS PubMed Google Scholar Sengupta M, Mondal M, Jaiswal P, Sinha S, Chaki M, Samanta S, et al. Comprehensive analysis of the molecular basis of oculocutaneous albinism in Indian patients lacking a mutation in the tyrosinase gene. Br J Dermatol. 2010;163:487–94. Article CAS PubMed Google Scholar Chiang PW, Spector E, Scheuerle A. A case of Asian Indian OCA3 patient. Am J Med Genet A. 2009;149A:1578–80. Article CAS PubMed Google Scholar Sengupta M, Chaki M, Arti N, Ray K. SLC45A2 variations in Indian oculocutaneous albinism patients. Mol Vis. 2007;13:1406–11. CAS PubMed Google Scholar Mondal M, Sengupta M, Samanta S, Sil A, Ray K. Molecular basis of albinism in India: evaluation of seven potential candidate genes and some new findings. Gene. 2012;511:470–4. Article CAS PubMed Google Scholar Dhangar S, Panchal

Gene dosage mechanisms are required to maintain the expression of haploinsufficient genes properly, which, if misregulated, can lead to many developmental disorders. For the first time, researchers from the Max Planck Institute of Immunobiology and Epigenetics have shown that a protein called MSL2 can recognize these dosage-sensitive genes and ensure they are expressed in both forms in the right tissue or stage of development. Understanding how MSL2, an epigenetic regulator, keeps certain dosage-sensitive genes expressed on both alleles opens the door to studying other factors that play a part in allelic dosage compensation in mammalian cells. This has important implications for human health conditions linked to haploinsufficiency, including congenital disorders and neurodevelopmental diseases. The research article “MSL2 ensures biallelic gene expression in mammals” was published in Nature. MSL2 is an evolutionarily conserved epigenetic dosage-sensor In sexually reproducing organisms, each parent contributes one copy of a chromosome, resulting in the offspring’s somatic cells being diploid. Most genes show balanced expression resulting from both maternal and paternal alleles. Genes that are haploinsufficient show obligate biallelic expression because they need two copies of the gene to make enough protein to work. The loss of expression of one of a haploinsufficient gene’s two alleles can result in disease. In flies and mammals, males are the heterogametic sex exhibiting hemizygosity of X-linked genes. Dosage compensation is required to adjust the allelic expression of X-linked genes to compensate for differences in gene dosage between the sexes. In mammals, one of the X chromosomes is turned off in females. But in flies, the MSL complex—a histone acetyltransferase—increases transcription of the single male X chromosome to match the expression levels of the two X chromosomes in females. Whether and how a biallelic or monoallelic state is determined at individual loci in different cell types and stages of development has been challenging to unravel. This study found a role for MSL2 in regulating allelic expression in a cell-type-specific manner in mammals. If you do not have MSL2, a group of genes goes from having two copies to only one copy. One allele stays active, keeping histone modifications and transcription factor binding, while the other allele is turned off, losing promoter-enhancer contacts and gaining DNA methylation. The fact that MSL2-knockout mice die before birth and have different phenotypes during embryonic development lends credence to the idea that MSL2 regulates gene dosage. This concept of MSL2-regulated gene dosage is evolutionarily conserved and extends to humans. For example, haploinsufficiency of the MSL2 target gene BCL11A is associated with Dias-Logan syndrome, resulting in variable neurological phenotypes. This discovery opens up new avenues for further research into the modulation of gene dosage within our cells. MSL2 may be just one example of an allelic regulator, implying the existence of other factors playing similar roles. This newfound knowledge has far-reaching implications for understanding diseases and holds great promise for developing potential treatments.

Josep Carreras Leukaemia Research Institute Blood vessels are responsible of the appropriate and efficient delivery of nutrients and oxygen to the whole body. To do so, they must grow and branch to reach every cell in a process called angiogenesis. The precise regulation of the sprouting and pruning of blood vessels is complex and partly unknown, but endothelial cells, those lining the inner part of the vessels, are known to play an important role. The growth and proliferation of endothelial cells is promoted by a protein known as mTORC1. Controlling its activity is important to organise a coherent branching of blood vessels and alterations in this process may lead to vascular malformations. New research from the Mariona Graupera’s lab (Josep Carreras Leukaemia Research Institute), published yesterday at the top journal Science Signaling, has just found that PI3K-C2b, a family member of the PI3K kinases, is responsible of the mTORC1 fine tuning through its inhibition. In a series of experiments using mice models and human cells, researchers found that animals with an inactive form of PI3K-C2a displayed aberrantly enlarged blood vessels. Similarly, when PI3K-C2b was transiently inactivated, endothelial cells appeared larger than usual. Both effects correlated with an increased expression of mTORC1 and were restored upon its external repression. The findings are important since mutations in components of the PI3K family of proteins are frequent in patients with congenital vascular disorders. Understanding the link between one and the other may be useful to find new therapeutic targets in the future. The present work was a collaborative initiative including researchers from the Josep Carreras Leukaemia Research Institute, the CNIO, the Universitätsmedizin Berlin, the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the University College London. Funders of the project were the Spanish Ministry for Science and Innovation, the PTEN Foundation, “La Caixa” Foundation, the Spanish Association Against Cancer and the BBVA Foundation. /Public Release. This material from the originating organization/author(s) might be of the point-in-time nature, and edited for clarity, style and length. Mirage.News does not take institutional positions or sides, and all views, positions, and conclusions expressed herein are solely those of the author(s).View in full here.

Your morning summary of digital health news, information and events to know about if you want to be “in the know”. 👇 News 😀 Bupa UK Insurance is rolling out a new suite of preventative and proactive wellbeing products and services to all its health insurance customers to help them stay healthy, identify potential risks earlier and ultimately take action towards better health. From January 2024, Bupa customers will be able to access online health and wellbeing services including over 1,500 digital gym classes, fitness programmes such as pilates, yoga and high intensity interval training (HIIT), alongside mindfulness sessions and comprehensive wellbeing resources. 👣 Revvity, Inc. has announced the launch of its EONIS Q system, a CE-IVD declared platform enabling laboratories in countries that accept the CE marking to adopt molecular testing for spinal muscular atrophy (SMA) and severe combined immunodeficiency (SCID) in newborns. For both inherited conditions, immediate detection is critical to advancing a positive outcome. For SMA, disease modifying therapies exist to stop progression of disease, and for SCID, immunoglobulin treatments combined with stem cell therapies can potentially cure a child, if intervention comes in time. However, to date, molecular testing for these and other congenital disorders is relatively low, due in part to cost restrictions and the technical expertise required to perform and interpret these tests. 📝 Recent board papers from Isle of Wight NHS Trust, Solent NHS Trust and Southern Health NHS Foundation Trust revolve around ‘Project Fusion’, which will see a number of their services brought together under a new trust; as part of their meeting, the boards discussed the new trust’s developing digital strategy and digital transition requirements, including plans to develop an EPR roadmap and priority areas of focus for digital. Through Project Fusion, all services from Solent and Southern Health will be brought together under a new NHS trust along with community, mental health and learning disability services provided from the Isle of Wight and child and adolescent mental health services (CAMHS) from Sussex Partnership NHS Trust, the Health Tech News reports. 🏃‍♀️ VentriJect, a Danish MedTech start-up seeking to revolutionise the way cardiorespiratory fitness (CRF) is measured, won the 2nd place award at the Healthcare Innovation World Cup earlier this month for its innovation that enables CRF to be estimated without the need for exercise and in less than three minutes. 🔊 Bournemouth University has teamed up with ImproveWell, a real-time feedback solution for staff to improve health and care, to use AI to turn NHS frontline workers’ feedback into digestible evidence to support decision-making for the first time. ImproveWell is a digital platform that collects real-time feedback from NHS workers on changes that could improve staff and patient experience. An Innovate UK grant has enabled Bournemouth University and ImproveWell to enter into a Knowledge Transfer Partnership (KTP) to develop bespoke AI models for the platform, building on existing data science and business intelligence capability. ❓ Did you know that? Starting a family is becoming more expensive than ever before. The squeeze on household budgets continue to dictate how families prioritise their money. Patients looking to start a family should always consider the financial implications which it entails. For couples undergoing fertility treatment, the added costs they carry during treatment is deterring a growing number of them to pause their plans of starting a family. Recent data shows 95% of fertility patients are concerned about the financial burden of the cost-of-living crisis, with 49% of respondents suspending their treatment in response to the pressures. 📖 What we’re reading AI is not new to health care – there have been efforts to harness its potential since the 1960s. But all of these failed to deliver on their promise, leading to a decades-long ‘AI winter’ in health care. Only now are we starting to see AI’s true potential reveal itself. Why is this? There are two reasons. First, it just needed time to get good. The new versions of AI are fundamentally different from what we’ve had before, and they’re improving every day. And the second reason is the health care ecosystem is ready to take advantage of the technology as never before. These factors combined mean we now find ourselves at a bit of a tipping point when it comes to the potential of health technology, writes Dr. Robert Wachter in this Health Foundation blog. 🚨 This week’s events 29 November 14:00-15:00 – Digital Health Webinar: The Next Evolution of AI: Fully automated clinical documentation 30 November 09:00-15:00 – Networks Exchange November: ICS Digital Priorities Unveiled – Shaping the Future of NHS Related Posts

Developed in Germany in the 1950s, thalidomide was originally used as a sedative or tranquiliser, but soon became widely promoted around the world as a morning sickness drug. As usage increased, so too did reports of birth defects – usually in the form of significantly shortened limbs. It was an Australian report in The Lancet medical journal that first warned the world of thalidomide’s dangers in 1961, and it was taken off the market soon after. By then an estimated 10,000 babies globally had been born with disabilities. For decades, survivors have fought for acknowledgments of wrongdoing and compensation. Canada introduced financial assistance for survivors in 1991, and in 2010 the UK issued a national apology to those affected. But it wasn’t until a landmark Senate inquiry in 2019 that Australia took action to support survivors. Its financial scheme provided a one-off payment of up to A$500,000 ($332,000; £261,000) to survivors, followed by annual payments of between A$5,000 and A$60,000. The programme was later closed to new applicants, but on Wednesday Mr Albanese reopened it “to ensure that anyone who may have missed the previous opportunity to apply does not miss out”. In East Germany, thalidomide was rejected by the Central Committee of Experts for the Drug Traffic in the GDR, and was never approved for use. There are no known thalidomide babies born in East Germany. Meanwhile, in West Germany, it took some time before the increase in dysmelia at the end of the 1950s was connected with thalidomide. In 1958, Karl Beck, a former pediatric doctor in Bayreuth, wrote an article in a local newspaper claiming a relationship between nuclear weapons testing and cases of dysmelia in children. Based on this, FDP whip Erich Mende requested an official statement from the federal government.[ For statistical reasons, the main data series used to research dysmelia cases started by chance at the same time as the approval date for thalidomide. After the Nazi regime with its Law for the Prevention of Hereditarily Diseased Offspring used mandatory statistical monitoring to commit various crimes, western Germany had been very reluctant to monitor congenital disorders in a similarly strict way. The parliamentary report rejected any relation with radioactivity and the abnormal increase of dysmelia. Also the DFG research project installed after the Mende request was not helpful. The project was led by pathologist Franz Büchner, who ran the project to propagate his teratological theory. Büchner saw lack of healthy nutrition and behavior of the mothers as being more important than genetic reasons. Furthermore, it took a while to appoint a Surgeon General in Germany; the Federal Ministry of Health was not founded until 1962, some months after thalidomide was banned from the market. In West Germany approximately 2,500 babies were born with birth defects from thalidomide. In the U.S., the FDA refused approval to market thalidomide, saying further studies were needed. ‘This reduced the impact of thalidomide in U.S. patients. The refusal was largely due to pharmacologist Frances Oldham Kelsey who withstood pressure from the Richardson-Merrell Pharmaceuticals Co. Although thalidomide was not approved for sale in the United States at the time, over 2.5 million tablets had been distributed to over 1,000 physicians during a clinical testing programme. It is estimated that nearly 20,000 patients, several hundred of whom were pregnant women, were given the drug to help alleviate morning sickness or as a sedative, and at least 17 children were consequently born in the United States with thalidomide-associated deformities. While pregnant, children’s television host Sherri Finkbine took thalidomide that her husband had purchased over-the-counter in Europe. When she learned that thalidomide was causing fetal deformities she wanted to abort her pregnancy, but the laws of Arizona allowed abortion only if the mother’s life was in danger. Finkbine traveled to Sweden to have the abortion. Thalidomide was found to have deformed the fetus. For denying the application despite the pressure from Richardson-Merrell Pharmaceuticals Co., Kelsey eventually received the President’s Award for Distinguished Federal Civilian Service at a 1962 ceremony with President John F. Kennedy. In September 2010, the FDA honored Kelsey with the first Kelsey award, given annually to an FDA staff member. This came 50 years after Kelsey, then a new medical officer at the agency, first reviewed the application from the William S. Merrell Pharmaceuticals Company of Cincinnati. Cardiologist Helen B. Taussig learned of the damaging effects of the drug thalidomide on newborns and in 1967, testified before Congress on this matter after a trip to Germany where she worked with infants with phocomelia (severe limb deformities). As a result of her efforts, thalidomide was banned in the United States and Europe.

Introduction Caregivers of disabled children are essential for maintaining and improving the health status of the affected child.1 As the disability of the affected individuals increases, the physical and psychological burden on their caregivers increases.2,3 Caregivers help the affected person in many activities, including bed mobility, transition to sitting, standing, mobility, toileting, bathing, dressing, eating, etc.4 Most of the time, the caregivers are parents of the affected children or family members in the case of affected adults. However, in some cases, relatives or friends become caregivers, and, in some situations, the role is taken by paid healthcare workers.5–7 Cerebral palsy is the name given to a group of disorders that affect a child’s movements and posture due to non-progressive damage that happens to the immature brain. Children affected with cerebral palsy (CP), Down syndrome, muscular dystrophies, congenital disorders, chromosomal conditions, or other disabilities require special care by their caregivers.8,9 There are many types of CP, including hypotonic, spastic, ataxic, athetoid, and mixed varieties.10,11 Irrespective of the type of CP, all affected children require special attention and care. The care needed by the child depends on many factors such as disease severity, general health status, functional capacity, financial level of the family, etc.12 Most relevant scientific literature commonly focuses on the affected people’s quality of life (QOL). However, the caregiver’s QOL is also critical for enhancing the health status of the affected individual. Since caregivers have taken on the extra burden of another individual, the resultant lack of time and energy for socializing and entertainment can affect their physical and mental health. Furthermore, they cannot leave that person and attend gatherings, trips, or holidays to improve their socialization. Wellbeing and understanding the caregiver’s QOL are also essential for positive development. There is a need for more studies pertaining to QOL information relating to the caregivers of children with CP in this region. The various factors influencing QOL also need to be understood to improve the QOL among caregivers of children with CP. Hence, we aim to identify the levels of QOL among caregivers of children with CP in the Asir region of Saudi Arabia. Moreover, we evaluate the effects of various demographic characteristics and socioeconomic factors on QOL among caregivers of children with CP. Materials and Methods This single cohort study complies with the Declaration of Helsinki and obtained certificated ethical clearance with approval number ECM#2023-612 from the ethical research committee of King Khalid University (HAPO-06-B-001). The sample size was assessed using the https://clincalc.com/Stats/SampleSize.aspx website. While calculating the sample size, the selected design for the study group was one study group versus the population, and the primary endpoint chosen was continuous means. The general population means, and standard deviation were obtained from a previous study conducted by Khoshhal et al,13 and the anticipated study group mean was chosen based on the known mean. The probability of type I error, ie, alpha, was selected at the level of 0.05, and the power of the study was maintained at 80%. We calculated a suitable sample size of 96, including a 10% dropout rate; the sample size was 106. The study was conducted at King Khalid University, Abha, and the duration of the study was one year. The investigators obtained permission letters and ethical approval and approached various hospitals and disability centers to collect the data. Convenience sampling was utilized to select the participants. The caregivers of children with cerebral palsy were approached specifically for the recruitment process, and the age of the child with cerebral palsy should be between two and 12 years. Caregivers with any other psychological disorders, difficulty reading and understanding Arabic, and who were not willing to participate were excluded from the study. Their written informed consent was obtained after the study procedure was explained to the caregivers. After receiving demographic characteristics, including age, gender, height, weight, and BMI, further specific questions were asked about their socioeconomic status, number of siblings for the affected child, their accommodation type, financial and social support received, etc. More information related to the affected children was also obtained, which includes the child’s age, gender, level of mobility, schooling capacity, etc. Additionally, the participating caregivers filled out the Arabic version of the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire. The full assessment was conducted either in paper-based format or online Google form. A therapist was available to address the participants’ queries during the completion of the examination, and the caregivers were informed that the collected data would be stored confidentially. Participants were not obliged to participate in the study and were free to withdraw their details at any time without affecting the care of their children. The collected data were analyzed to obtain the results. Details of the Outcome Measure The WHOQOL-BREF instrument contains 26 questions in total. The Arabic version of this questionnaire is freely available on the WHO website under the tools section, and it can be accessed from this URL, which is available here: https://www.who.int/tools/whoqol/whoqol-bref/docs/default-source/publishing-policies/whoqol-bref/arabic-whoqol-bref. Each question is rated on a 5-point Likert scale: 1 indicates poor QOL, and 5 means good quality of life. Among the 26 questions, questions 1 and 2 measure the subject’s overall perception of QOL and satisfaction with their health, respectively. The remaining questions are divided into four domains: physical health, psychological health, social relationships, and environment. Physical fitness was assessed by seven questions: 3, 4, 10, 15, 16, 17, and 18; this domain sets pain, discomfort, energy, fatigue, sleep, rest, dependence on medication, mobility, activities of daily living, and working capacity. Psychological health was evaluated by six questions: 5, 6, 7, 11, 19, and 26; this domain evaluates positive feelings, negative feelings, self-esteem, thinking, learning, memory, concentration, body image, spirituality, religion, and personal beliefs. Three questions examine the domain of social relationships: questions 20, 21, and 22 evaluating personal relationships, sexual life, and practical social support. The environment was analyzed by eight questions: 8, 9, 12, 13, 14, 23, 24, and 25, assessing financial resources, information and skills, recreation and leisure, home environment, access

Introduction Uremia is a symptom of the final stage of chronic renal failure, which is clinically characterized by aberrant water, electrolyte, acid, and base balance and increased blood levels of metabolites, such as creatinine and urea.1 The uremia stage is often associated with a number of secondary conditions and comorbidities of chronic kidney disease (CKD), including, but not limited to: decreased renal function and accumulation of metabolites; pathological changes in the circulatory system, including anemia, platelet dysfunction, and bleeding; neuromuscular dysfunction and cognitive impairment; vascular endothelial dysfunction and vascular disease progression; endocrine and metabolic disorders, such as insulin resistance, gonadal dysfunction, hyperparathyroidism, and CKD-mineral and bone metabolism disorder; congenital and adaptive immunological diseases characterized by inflammation and immune deficiency.1–3 Patients in uremia stage are associated with poor prognosis of High morbidity, high prevalence of cardiovascular disease, high mortality rates. The main therapeutic strategies for uremia are kidney transplantation or dialysis (including hemodialysis and peritoneal dialysis). However, the expensive treatment is a major economic burden for society and individuals. Thus, uremia is a major challenge to global health. Recently, the number of studies on uremia has markedly increased. However, the pathological mechanisms of uremia have not been elucidated. The elucidation of the molecular mechanism and the identification of targets for early intervention, which are common concerns of interdisciplinary research and challenging limitations, are the major focus of renal disease research.1–3 The dynamic regulatory effects of the uremic environment on the immune system are known as uremic inflammation and include immune activation and immunosuppression.4 The aberrant activation of the innate immune system, especially monocytes, is one of the features of uremic inflammation.5,6 Patients with end-stage renal disease treated with renal replacement therapy exhibit premature immunological aging of T cells, which may be the cause of uremia-related immune dysfunction.7 This study used bioinformatics methods to examine the correlation between immune-related genes (IRGs) and uremia and screen molecular markers that can aid in the diagnosis, elucidation of pathogenesis, and treatment of uremia. Materials and Methods Data Source The data of an independent uremia cohort (GSE37171) were obtained from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). The GSE37171 dataset comprised data of blood samples from 75 patients with uremia and 40 healthy subjects. The dataset was divided into training (20 healthy and 63 uremic samples) and validation (20 healthy and 12 uremic samples) sets.3 Additionally, the data of 1793 IRGs were retrieved from the ImmPort database (https://immport.niaid.nih.gov) (Supplementary File 1). Screening of Differentially Expressed Genes (DEGs) The DEGs between the uremia and control groups in the training set were screened using the limma package (|log fold-change| > 0.5; adj. p < 0.05).8 The screening results were visualized using the volcano plot and heatmap, which were plotted using the R language ggplot2 (version 3.3.6) package and pheatmap package (version 1.0.12), respectively.9 Identification of Differentially Expressed IRGs (DEIRGs) The clinical traits of the uremia and control groups in the training set were used to perform weighted gene co-expression network analysis (WGCNA) using the R package WGCNA to obtain key modules and key module genes.10 The outlier samples in the training set were filtered out using the Hclust function. Next, the soft threshold of data was determined and the adjacency was calculated. Gene modules were obtained using dynamic tree cutting with a minimum of 30 genes in each gene module, and similar modules were merged. The modules related to uremia were selected as key modules and key module genes for subsequent analysis. DEIRGs were obtained by intersecting the DEGs, key module genes, and 1793 IRGs using the VennDiagram package.11 Functional enrichment analysis of DEIRGs was performed using the R language clusterProfiler (p < 0.05).12 Protein-Protein Interaction (PPI) Network Protein interactions between DEIRGs associated with uremia were characterized using the STRING database (http://string-db.org) (score > 0.4). The topological properties of the PPI networks were analyzed using cytoHubba in the Cytoscape plugin.13 The maximal clique centrality (MCC), degree, and stress algorithms were applied to evaluate and select candidate genes. Identification and Validation of Biomarkers In the training set, three machine learning models (generalized linear model (GLM), support vector machine-recursive feature elimination (SVM-RFE), and random forest (RF)) were executed using the R package “DALEX” to plot the residual distribution and obtain the best model. The biomarkers were obtained from the best model. The receiving operating characteristic (ROC) curves of the biomarkers were generated using the survROC R package to evaluate the diagnostic value of the biomarkers.14 Next, the validation set was used to further assess the diagnostic power of the biomarkers. The expression of biomarkers in the training set and validation set was displayed. Construction and Verification of a Nomogram The nomogram of biomarkers in the training set was constructed using the R language rms package. The predictive power of the nomogram model was evaluated using clinical impact curves (CICs) and decision curve analysis (DCA).15 Evaluation of Infiltrating Immune Cell Landscape The distribution of immune cells in the training set was examined using the CIBERSORT algorithm.16 The differential distribution of immune cells in the uremia and control samples was compared using the Wilcox test.16 Next, Spearman correlation analysis was performed to explore the correlation between biomarkers and differentially abundant immune cells.17,18 Gene Set Enrichment Analyses (GSEA) and Ingenuity Pathway Analysis (IPA) Functional enrichment analysis of biomarkers in the training set was performed using the GSEA function of the R package clusterProfiler (p 1).19 The gene identifiers and corresponding expression values of the DEGs in the training set were uploaded to the IPA software, which was used to analyze the unique pathways of the biomarkers.20 Validation of Expression of Biomarkers The expression of biomarkers was verified using quantitative real-time polymerase chain reaction (qRT-PCR). We collected blood samples from 5 uremic patients and 5 healthy subjects for validation at the Guangxi International Zhuang Medical Hospital in February 2023. The 5 uremic patients met the following four conditions: (1) Age 18–90 years old, male or female; (2) Meet the diagnostic criteria for chronic kidney disease, with creatinine clearance <10mL/min; (3) Have been on