Publications by authors named "Richard Keen"
Current and future perspectives on pregnancy and lactation-associated osteoporosis.
Front Endocrinol (Lausanne)
December 2024
Normal pregnancy and lactation have a marked physiological impact on maternal bone metabolism. This impact is usually temporary and reversible, but some women sustain fragility fractures whilst pregnant or lactating, termed pregnancy and lactation-associated osteoporosis (PLO). These fractures have severe negative consequences on their quality of life, at what is a crucial stage in a mother's life.
View Article and Find Full Text PDFArticle Synopsis
- Paget's disease of bone (PDB) makes bones grow and change shape in a messy way, which can lead to problems like pain, deafness, and broken bones.
- A study with 168 people found that about 73% of them had musculoskeletal pain, mainly because of osteoarthritis in joints away from the PDB affected areas.
- The research showed that pain was more common in older folks and women, and highlighted the need to check each person's pain to treat it correctly.
Introduction: Osteogenesis imperfecta (OI) is a heritable skeletal disorder and comprises various subtypes that differ in clinical presentation, with Type I considered the least severe and Types III/IV the most severe forms. The study aim was to understand the OI patient diagnostic and treatment journey across Europe.
Methods: We conducted a qualitative, descriptive study to understand the OI patient journey.
Article Synopsis
- Fibrodysplasia ossificans progressiva (FOP) is a rare disorder causing painful flare-ups and abnormal bone growth, known as heterotopic ossification (HO).
- In a clinical trial, patients receiving the anti-activin A antibody garetosmab experienced fewer severe and lengthy flare-ups compared to those given a placebo, leading to a notable difference in quality of life.
- The study found that 71% of placebo patients had flare-ups linked to new HO lesions, while garetosmab reduced the severity, duration, and frequency of these flare-ups throughout the trial.
Unlabelled: We assessed multiple components of muscle function in ten adults with X-linked hypophosphatemia (XLH) receiving burosumab treatment. Lower limb power (+ 9%), short physical performance battery (SPPB) score (+ 1.2 points), and physical activity (+ 65%) increased following 6 months of treatment, and hand grip increased (+ 10%) between 6 and 12 months of treatment.
View Article and Find Full Text PDFArticle Synopsis
- Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic disorder that often presents with congenital great toe abnormalities (CBHV), intermittent swelling, and abnormal bone growth.
- A case report describes a three-month-old girl with CBHV whose condition raised concerns for FOP, but comprehensive genetic testing revealed no typical markers for the disorder.
- The findings emphasize the importance of CBHV as an early diagnostic sign for FOP, while also suggesting that affected infants should be carefully evaluated and monitored before confirming a diagnosis.
We report two studies that tested the effects of caffeine, the world's most widely used psychoactive drug, on temporal perception. We trained Wistar rats using the Bisection Procedure (Experiment 1) or the Stubbs' Procedure (Experiment 2) to discriminate between short and long light stimuli. Once training finished, we administered caffeine orally (0, 9.
View Article and Find Full Text PDFReal-world non-interventional post-authorization safety study of long-term use of burosumab in children and adolescents with X-linked hypophosphatemia: first interim analysis.
Ther Adv Chronic Dis
May 2024
Article Synopsis
- - X-linked hypophosphatemia (XLH) is a rare disorder caused by high levels of FGF23, leading to phosphate loss and decreased vitamin D production, while burosumab is a treatment that helps restore phosphate levels by inhibiting FGF23.
- - This post-authorization safety study (PASS) monitors the long-term safety of burosumab in children and adolescents aged 1-17 years, with this first interim analysis focusing on the initial safety outcomes based on registry data.
- - The analysis involved 67 participants, with 37.3% reporting at least one adverse event, primarily musculoskeletal issues; however, there were no serious adverse events or treatment withdrawals, indicating that the safety profile of
Article Synopsis
- The background discusses the challenges of designing clinical trials for ultra-rare diseases like Fibrodysplasia ossificans progressiva (FOP) and highlights the role of palovarotene, a selective retinoic acid receptor gamma agonist, in this research.
- The methods outline three key studies: a natural history study (PVO-1A-001), a randomized phase II trial (PVO-1A-201), and its open-label extension (PVO-1A-202), detailing their designs, treatment regimens, and assessment of disease progression and flare-up outcomes.
- The results emphasized the recruitment of participants, with significant insights reported from the studies on the suitability of endpoints and the effectiveness of imaging
Article Synopsis
- - Fibrodysplasia ossificans progressiva (FOP) is a rare condition that causes painful heterotopic ossification in connective tissues, leading to disability.
- - In the LUMINA-1 phase 2 trial, adults with FOP were given either garetosmab (an activin A-blocking antibody) or a placebo over two 28-week periods, focusing on safety and effects on HO lesions.
- - Although the primary efficacy endpoint was not met in the first period, garetosmab significantly reduced the development of new HO lesions in the second period compared to placebo, with ongoing investigations into its effectiveness.
Article Synopsis
- X-linked hypophosphatemia (XLH) is a rare genetic disorder that causes phosphate wasting in the kidneys and is linked to increased levels of the hormone FGF23; its rarity can lead to delayed diagnosis, worsening patient outcomes.
- The International XLH Registry was launched in 2017 to gather data on XLH patients of all ages, with an interim analysis reporting on 579 participants as of March 2021, highlighting a longer diagnosis time for older adults compared to children.
- Data collected included family histories and genetic testing, revealing that a significant proportion of patients had biological relatives also affected by XLH, while most had a confirmed genetic mutation related to the disorder.
Article Synopsis
- The study examines the effects of continuing burosumab treatment on adults with X-linked hypophosphataemia after a 96-week phase 3 study, focusing on lab tests, patient-reported outcomes, and walking ability.
- Results showed sustained improvements in serum phosphate levels, vitamin D levels, and overall physical health during the 48-week extension.
- An analysis indicated that stopping burosumab led to a loss of benefits, highlighting that ongoing treatment is essential for maintaining clinical improvements.
Article Synopsis
- Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder that causes abnormal bone growth, and the MOVE trial tested the drug palovarotene to see if it could effectively treat this condition.
- The trial involved 97 patients receiving palovarotene and compared results with 101 untreated patients from a natural history study, showing a 60% reduction in new abnormal bone growth for those on palovarotene.
- While the drug showed promise, all participants experienced side effects, with a significant number of younger patients facing serious adverse events like premature closure of growth plates.
Purpose: We report the first prospective, international, natural history study of the ultra-rare genetic disorder fibrodysplasia ossificans progressiva (FOP). FOP is characterized by painful, recurrent flare-ups, and disabling, cumulative heterotopic ossification (HO) in soft tissues.
Methods: Individuals aged ≤65 years with classical FOP (ACVR1 variant) were assessed at baseline and over 36 months.
Article Synopsis
- X-linked hypophosphataemia (XLH) is a rare genetic disorder characterized by elevated FGF23 levels, leading to phosphate-wasting and various bone-related issues.
- Traditional treatments like oral phosphate and vitamin D supplements don't fully address the root causes or all symptoms of the disease.
- A new study (PASS) is assessing the long-term safety of burosumab, a monoclonal antibody treatment for XLH, using data from a global registry over the next decade.
Article Synopsis
- * A subgroup analysis of data from a phase 3 study involving 134 adults revealed no significant differences in treatment benefits among 14 clinically relevant subgroups, including variations in sex, pain levels, and physical function.
- * Overall, burosumab consistently showed better outcomes compared to placebo, suggesting it is beneficial for all symptomatic adults with active XLH, although some treatment effects were small and not statistically significant across subgroups. *
Article Synopsis
- - Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder that causes abnormal bone growth, leading to reduced mobility and life expectancy; this study tested a drug called palovarotene to see if it could prevent this bone growth during flare-ups.
- - The clinical trial involved 40 patients divided into groups receiving different doses of palovarotene or a placebo, with the main goal being to measure the effectiveness of the drug in reducing new bone formation after 6 and 12 weeks.
- - Results showed that palovarotene was well-tolerated, with high responder rates in both palovarotene groups compared to placebo, and significantly lower new bone growth volume at week 12
Background: Fibrodysplasia Ossificans Progressiva (FOP) is a genetic, progressive and devastating disease characterized by severe heterotopic ossification (HO), loss of mobility and early death. There are no FDA approved medications. The STOPFOP team identified AZD0530 (saracatinib) as a potent inhibitor of the ALK2/ACVR1-kinase which is the causative gene for this rare bone disease.
View Article and Find Full Text PDFArticle Synopsis
- Osteogenesis Imperfecta (OI) affects about 1 in 10,000 people and leads to significant musculoskeletal disorders and pain in adults, but there's limited understanding of their specific needs and access to therapy varies.
- A study analyzed 50 adults with OI attending a new clinic, revealing that 84% reported musculoskeletal pain, with 46% experiencing spine pain, and many faced challenges with mobility, self-care, and daily activities.
- The study found that 70% of patients received therapy advice or referrals during their consultations, with a notable 30% being referred to specialized rehabilitation services.
Introduction: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, severely disabling, autosomal dominant, congenital disease characterized by progressive multi-focal heterotopic ossification (HO) of skeletal muscle, ligaments, tendons, and fascia. Past FOP studies have focused on the clinical aspects of the disease; therefore, there is a paucity of qualitative research on the patient experience. Our objective was to better understand the experience of children and adolescents living with FOP from their and their parents' perspectives.
View Article and Find Full Text PDFFibrodysplasia ossificans progressiva (FOP) is an ultra-rare progressive genetic disease effecting one in a million individuals. During their life, patients with FOP progressively develop bone in the soft tissues resulting in increasing immobility and early death. A mutation in the gene was identified as the causative mutation of FOP in 2006.
View Article and Find Full Text PDFArticle Synopsis
- The study aimed to evaluate the effectiveness of burosumab on patient-reported outcomes (PROs) and walking ability in adults with X-linked hypophosphataemia (XLH) over 96 weeks.
- Adults with XLH were randomly assigned to receive either burosumab or a placebo; improvements in pain, fatigue, and physical function were measured at 24, 48, and 96 weeks.
- Results showed significant and meaningful improvements in PROs and walking distance for those treated with burosumab compared to the placebo group, indicating that the treatment effectively reduced the disease burden in patients with XLH.
When patients lack suitable superficial veins in the upper extremity to create an arteriovenous fistula, surgeons are faced with a decision between a synthetic graft or autologous fistula using deep veins, such as a brachial artery to brachial vein arteriovenous fistula. In patients with a high radial artery origin (or brachioradial artery) and inadequate superficial veins, arteriovenous fistula creation will be even more challenging. In the present report, we describe a technique used in three such patients who underwent successful staged brachioradial artery to brachioradial vein arteriovenous fistula creation.
View Article and Find Full Text PDFObjective: Techniques such as the use of nonpenetrating vascular clips for arteriovenous fistula (AVF) anastomotic creation have been developed in an effort to reduce fistula-related complications. However, the outcomes data for the use of clips have remained equivocal, and the cost evaluations to support their use have been largely theoretical. Therefore, the present study aimed to determine both the clinical and the cost outcomes of AVFs created with nonpenetrating vascular clips compared with the continuous suture technique during a 10-year period at a single institution.
View Article and Find Full Text PDFObjective: Mycotic aneurysms of the infrapopliteal vessels are rare, with few cases reported in the literature. Management strategies are diverse and should be tailored to the patient's presentation.
Methods: We describe the case of a 40-year-old male who presented with a painful left leg mass in the setting of bacteremia and infective endocarditis.