The development of transforming growth factor βreceptor inhibitors (TGFβRi) as new medicines has been affected by cardiac valvulopathy and arteriopathy toxicity findings in nonclinical toxicology studies. PF-06952229 (MDV6058) selected using rational drug design is a potent and selective TGFβRI inhibitor with a relatively clean off-target selectivity profile and good pharmacokinetic properties across species. PF-06952229 inhibited clinically translatable phospho-SMAD2 biomarker (≥60%) in human and cynomolgus monkey peripheral blood mononuclear cells, as well as in mouse and rat splenocytes. Using an optimized, intermittent dosing schedule (7-day on/7-day off/cycle; 5 cycles), PF-06952229 demonstrated efficacy in a 63-day syngeneic MC38 colon carcinoma mouse model. In the pivotal repeat-dose toxicity studies (rat and cynomolgus monkey), PF-06952229 on an intermittent dosing schedule (5-day on/5-day off cycle; 5 cycles, 28 doses) showed no cardiac-related adverse findings. However, new toxicity findings related to PF-06952229 included reversible hepatocellular (hepatocyte necrosis with corresponding clinically monitorable transaminase increases) and lung (hemorrhage with mixed cell inflammation) findings at ≥ targeted projected clinical efficacious exposures. Furthermore, partially reversible cartilage hypertrophy (trachea and femur in rat; femur in monkey) and partially to fully reversible, clinically monitorable decreases in serum phosphorus and urinary phosphate at ≥ projected clinically efficacious exposures were observed. Given the integral role of TGFβ in endochondral bone formation, cartilage findings in toxicity studies have been observed with other TGFβRi classes of compounds. The favorable cumulative profile of PF-06952229 in biochemical, pharmacodynamic, pharmacokinetic, and nonclinical studies allowed for its evaluation in cancer patients using the intermittent dosing schedule (7-day on/7-day off) and careful protocol-defined monitoring.

The diagnostic work-up of patients with fever of unknown origin (FUO) begins with a thorough history and physical examination, complete blood count with differential, chest x-ray, urinalysis and culture, electrolyte panel, liver enzymes, erythrocyte sedimentation rate, and C-reactive protein level. Additional imaging procedures, including nuclear medicine tests, are generally used as second-line procedures, with ¹⁸F-FDG PET and PET/CT assuming increasingly important roles in the diagnostic work-up. The Society of Nuclear Medicine and Molecular Imaging, the Infectious Diseases Society of America, and the American College of Nuclear Medicine convened an autonomous expert work group to comprehensively review the published literature for nuclear imaging in adults and children with FUO and establish appropriate use criteria (AUC). This process was performed in accordance with the Protecting Access to Medicare Act of 2014, which requires that all referring physicians consult AUC by using a clinical decision support mechanism before ordering advanced diagnostic imaging services. The complete findings and discussions of the work group were published on January 8, 2023, and are available at https://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=15666. The AUC in the final document are intended to assist referring health care providers in appropriate use of nuclear medicine imaging procedures in patients with FUO. The work group noted limitations in the current literature on nuclear medicine imaging for FUO, with the need for well-designed prospective multicenter investigations. Consensus findings from published data and expert opinions were used to create recommendations in common clinical scenarios for adults and children. Included in the complete document is a discussion of inflammation of unknown origin (IUO), a recently described entity. In view of the fact that the criteria for FUO and IUO are similar (except for fever > 38.3°C [100.9°F]) and that the most common etiologies of these 2 entities are similar, it is the expert opinion of the work group that the recommendations for nuclear medicine imaging of FUO are also applicable to IUO. These recommendations are included in the full guidance document. This summary reviews rationale, methodology, and main findings and refers the reader to the complete AUC document.

Rare genetic conditions are challenging for the primary care provider to manage without proper guidelines. This clinical review is designed to assist the pediatrician, family physician, or internist in the primary care setting to manage the complexities of 16p11.2 deletion syndrome. A multidisciplinary medical home with the primary care provider leading the care and armed with up-to-date guidelines will prove most helpful to the rare genetic patient population. A special focus on technology to fill gaps in deficits, review of case studies on novel medical treatments, and involvement with the educational system for advocacy with an emphasis on celebrating diversity will serve the rare genetic syndrome population well.

Metastatic porocarcinomas (PCs) are vanishingly rare, highly aggressive skin adnexal tumors with mortality rates exceeding 70%. Their rarity has precluded the understanding of their disease pathogenesis, let alone the conduct of clinical trials to evaluate treatment strategies. There are no effective agents for unresectable PCs. Here, we successfully demonstrate how functional precision medicine was implemented in the clinic for a metastatic PC with no known systemic treatment options. Comprehensive genomic profiling of the tumor specimen did not yield any actionable genomic aberrations. However, ex vivo drug testing predicted pazopanib efficacy, and indeed, administration of pazopanib elicited remarkable clinicoradiological response. Pazopanib and its class of drugs should be evaluated for efficacy in other cases of PC, and the rationale for efficacy should be determined when PC tumor models become available. A functional precision medicine approach could be useful to derive effective treatment options for rare cancers.

Pilocytic astrocytomas are the most common pediatric brain tumors, typically presenting as low-grade neoplasms. We report two cases of pilocytic astrocytoma with atypical tumor progression. Case 1 involves a 12-yr-old boy with an unresectable suprasellar tumor, negative for BRAF rearrangement but harboring a BRAF p.V600E mutation. He experienced tumor size reduction and stable disease following dabrafenib treatment. Case 2 describes a 6-yr-old boy with a thalamic tumor that underwent multiple resections, with no actionable driver detected using targeted next-generation sequencing. Whole-genome and RNA-seq analysis identified an internal tandem duplication in FGFR1 and RAS pathway activation. Future management options include FGFR1 inhibitors. These cases demonstrate the importance of escalating molecular diagnostics for pediatric brain cancer, advocating for early reflexing to integrative whole-genome sequencing and transcriptomic profiling when targeted panels are uninformative. Identifying molecular drivers can significantly impact treatment decisions and improve patient outcomes.

BackgroundThere has been significant investment in pharmacists working in UK general practice to improve the effective and safe use of medicines. However, evidence of how to optimise collaboration between GPs and pharmacists in the context of polypharmacy (multiple medication) is lacking.AimTo explore GP and pharmacist views and experiences of in-person, interprofessional collaborative discussions (IPCDs) as part of a complex intervention to optimise medication use for patients with polypharmacy in general practice.Design and settingA mixed-method process evaluation embedded within the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) trial conducted in Bristol and the West Midlands, between February 2021 and September 2023.MethodAudio-recordings of IPCDs between GPs and pharmacists, along with individual semi-structured interviews to explore their reflections on these discussions, were used. All recordings were transcribed verbatim and analysed thematically.ResultsA total of 14 practices took part in the process evaluation from February 2022 to September 2023; 17 IPCD meetings were audio-recorded, discussing 30 patients (range 1–6 patients per meeting). In all, six GPs and 13 pharmacists were interviewed. The IPCD was highly valued by GPs and pharmacists who described benefits, including: strengthening their working relationship; gaining in confidence to manage more complex patients; and learning from each other. It was often challenging, however, to find time for the IPCDs.ConclusionThe model of IPCD used in this study provided protected time for GPs and pharmacists to work together to deliver whole-patient care, with both professions finding this beneficial. Protected time for interprofessional liaison and collaboration, and structured interventions may facilitate improved patient care.

The usual challenges of conducting primary care research, including randomized trials, have been exacerbated, and new ones identified, during the COVID-19 pandemic. HOMER (Home versus Office for Medication Enhanced Recovery; subsequently, Comparing Home, Office, and Telehealth Induction for Medication Enhanced Recovery) is a pragmatic, comparative-effectiveness research trial that aims to answer a key question from patients and clinicians: What is the best setting in which to start treatment with buprenorphine for opioid use disorder for this patient at this time? In this article, we describe the difficult journey to find the answer. The HOMER study began as a randomized trial comparing treatment outcomes in patients starting treatment with buprenorphine via induction at home (unobserved) vs in the office (observed, synchronous). The study aimed to enroll 1,000 participants from 100 diverse primary care practices associated with the State Networks of Colorado Ambulatory Practices and Partners and the American Academy of Family Physicians National Research Network. The research team faced unexpected challenges related to the COVID-19 pandemic and dramatic changes in the opioid epidemic. These challenges required changes to the study design, protocol, recruitment intensity, and funding conversations, as well as patience. As this is a participatory research study, we sought, documented, and responded to practice and patient requests for adaptations. Changes included adding a third study arm using telehealth induction (observed via telephone or video, synchronous) and switching to a comprehensive cohort design to answer meaningful patient-centered research questions. Using a narrative approach based on the Greek myth of Homer, we describe here the challenges and adaptations that have provided the opportunity for HOMER to thrive and find the way home. These clinical trial strategies may apply to other studies faced with similar cultural and extreme circumstances.

PURPOSE

Meeting scholarly activity requirements continues to be a challenge in many family medicine (FM) residency programs. Studies comprehensively describing FM resident scholarship have been limited. We sought to identify institutional factors associated with increased scholarly output and meeting requirements of the Accreditation Council for Graduate Medical Education (ACGME).

PURPOSE

Despite being key to better health outcomes for patients from racial and ethnic minority groups, the proportion of underrepresented in medicine (URiM) physicians remains low in the US health care system. This study linked a nationally representative sample of family physicians (FPs) with Medicaid claims data to explore the relative contributions to care of Medicaid populations by FP race and ethnicity.

PURPOSE

Currently, 40% of counties in the United States do not have an obstetrician or midwife, and in rural areas the likelihood of childbirth being attended to by a family medicine (FM) physician is increasing. We sought to characterize the effect of the FM presence on unit culture and a key perinatal quality metric in Iowa hospital intrapartum units.

The respiratory literature, both written and in online formats, is growing exponentially. Capturing quality content, to meet the learning needs of those working in all fields of respiratory medicine and delivering it in a palatable, accessible format is challenging but paramount. In this article we discuss ways to determine the information content and review different methods of delivering this content to those who need it.

Medically evacuating an astronaut from space is difficult and expensive, and a new model predicts that one in three long-duration moon missions may require it

Stay up to date on the latest AI technology advancements and learn about the challenges and opportunities AI presents

The 2024 Nobel prize in physiology or medicine has gone to Victor Ambros and Gary Ruvkun for their discovery that tiny pieces of RNA called microRNAs play a key role in controlling genes

Israeli airstrikes killed at least 46 people in the Gaza Strip in the past day, medics said. In Lebanon, warplanes struck Beirut's southern suburbs and killed 33 people in the country on Tuesday.

Dhaka (AFP) Nov 7, 2024
Bangladesh is struggling to tamp down a surge in dengue cases as climate change turns the disease into a year-round crisis, leaving some paediatric wards packed with children squeezed two to a bed. The Aedes mosquito that spreads dengue - identifiable by its black and white striped legs - breeds in stagnant pools, and cases once slowed after the monsoon rains faded. "Normally, around t

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

In an effort to strengthen the regulatory activities for medical devices in the country, the Union health ministry has framed and finalised rules regulating the method of recruitment to various posts under the Central

The Department of Pharmaceuticals (DoP) has released the operational guidelines for the newly announced central sector scheme for Strengthening of Medical Device Industry (SMDI), aiming at providing

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Nvision Biomedical Technologies and Invibio Biomaterial Solutions have announced that the FDA has granted clearance of the first 3D-Printed PEEK Interbody System made from PEEK-OPTIMA.

Placon, an innovator in the medical packaging market, announced the release of a new stock line of BargerGard TPU pouches and tip protectors.

TekniPlex Healthcare is set to unveil its strongest-ever reinforced paper for medical device packaging applications at Pack Expo 2024, 3-6 November in Chicago.

PolyNovo UK – a UK medical devices company specialising in the development of surgical solutions using the patented polymer technology NovoSorb will be exhibiting at MEDICA 2024.

Schultz Medical, a single use instrument company based in Southport, Merseyside have announced they will be exhibiting at MEDICA 2024 in Germany and on the UK Pavilion in Hall 15 hosted by Medilink UK.

The Association of British HealthTech Industries (ABHI) is excited to unveil a diverse delegation of UK HealthTech innovators at MEDICA 2024, one of the world's largest and most influential medical trade fairs.

Brightmark CEO Bob Powell discusses Plastics Renewal technology and how to bring sustainability into the medical industry.

Ampacet has introduced ProVital+ Gamma-Protect, a medical-grade additive designed to preserve mechanical and optical properties of polypropylene-based medical and pharmaceutical articles during gamma and e-beam sterilisation processes.

Regulatory experts LFH Regulatory have announced their attendance at MEDICA 2024 to provide insights and support to healthcare innovators facing the complexities of the UK and EU markets.

Mike Hodgin, director of strategic applications, Meridian Electronics Division discusses enabling and protecting vital medical implants with epoxies.

Surgical Holdings, a British manufacturer and repairer of medical devices, will return to MEDICA 2024 for the third consecutive year, focused on strengthening its partnerships across Europe and expanding its reach in key markets.

Syensqo, previously part of Solvay Group and a global provider of advanced performance materials and chemical solutions, is making its debut at Compamed 2024.

Dr Euan McBrearty, head of commerical & innovation, Wideblue shares five steps to successful medical device development.

Trelleborg Medical Solutions showcases its comprehensive polymer-based solutions and capabilities for the medical technology and biopharmaceutical industries at Compamed 2024 in Dusseldorf from November 11 to 14, at stand F02 in hall 8A.

Researchers at the University of Waterloo in Canada have developed plant-based microrobots that are intended to pave the way for medical robots that can enter the body and perform tasks, such as obtaining a biopsy or performing a surgical procedure. The robots consist of a hydrogel material that is biocompatible and the composite contains cellulose […]