Biallelic PKP2 loss of function variants are associated with a lethal perinatal-onset biventricular dilated cardiomyopathy with excessive trabeculations and ventricular septal defects.

Homozygous plakophilin-2 (PKP2) variants have been identified as a cause of a lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET) in three cases. We report three more cases from two families with homozygous pathogenic PKP2 variants and perinatal-onset, lethal DCM-ET. Identification of the genetic abnormalities played a key role in decision-making and family counselling in these cases. This case series supports the published evidence that biallelic loss of function PKP2 variants cause a lethal, perinatal-onset cardiomyopathy.

Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism.

Recent studies have identified both recessive and dominant forms of mitochondrial disease that result from ATAD3A variants. The recessive form includes subjects with biallelic deletions mediated by non-allelic homologous recombination. We report five unrelated neonates with a lethal metabolic disorder characterized by cardiomyopathy, corneal opacities, encephalopathy, hypotonia, and seizures in whom a monoallelic reciprocal duplication at the ATAD3 locus was identified. Analysis of the breakpoint junction fragment indicated that these 67 kb heterozygous duplications were likely mediated by non-allelic homologous recombination at regions of high sequence identity in ATAD3A exon 11 and ATAD3C exon 7. At the recombinant junction, the duplication allele produces a fusion gene derived from ATAD3A and ATAD3C, the protein product of which lacks key functional residues. Analysis of fibroblasts derived from two affected individuals shows that the fusion gene product is expressed and stable. These cells display perturbed cholesterol and mitochondrial DNA organization similar to that observed for individuals with severe ATAD3A deficiency. We hypothesize that the fusion protein acts through a dominant-negative mechanism to cause this fatal mitochondrial disorder. Our data delineate a molecular diagnosis for this disorder, extend the clinical spectrum associated with structural variation at the ATAD3 locus, and identify a third mutational mechanism for ATAD3 gene cluster variants. These results further affirm structural variant mutagenesis mechanisms in sporadic disease traits, emphasize the importance of copy number analysis in molecular genomic diagnosis, and highlight some of the challenges of detecting and interpreting clinically relevant rare gene rearrangements from next-generation sequencing data.

Left ventricular noncompaction cardiomyopathy and short QT syndrome due to primary carnitine deficiency.

We report the case of a 13-year-old female patient presenting with presyncope and palpitations. Her electrocardiogram revealed an abbreviation of the rate-corrected QT interval with imaging showing significant left ventricular dysfunction. Carnitine levels were measured as part of her diagnostic workup, discovering a rare, reversible cause of short QT syndrome (SQTS) and associated cardiomyopathy-primary carnitine deficiency (PCD) caused by a homozygous mutation in the SLC22A5 gene, leading to an in-frame deletion mutation (NP_003051.1:p.Phe23del) affecting the organic cation transporter 2 (OCTN2) protein. Following the treatment with oral carnitine supplementation, her QT interval returned to within the normal range with significant improvement in left ventricular function.

The role of the advanced clinical practitioner in arthroplasty care.

Demand for joint arthroplasty surgery in the UK has increased significantly over the past 10 years. Advanced clinical practitioner (ACP) roles in arthroplasty care, typically fulfilled by expert nurses or physiotherapists, have been developed to alleviate service pressures and facilitate care for the growing number of patients undergoing arthroplasty surgery. There are numerous different models of ACP-led services both in the UK and internationally, driven by local service and population needs. ACPs in arthroplasty care will be involved throughout the patient journey, including pre-operative assessment, peri-operative care and long-term surveillance. ACPs in arthroplasty care will develop expertise across all four pillars of advanced clinical practice and have the potential to influence and contribute to the development of guidance and policy for the future of arthroplasty care delivery, ensuring best quality, evidence-based practice is achieved.

Expanding ACTA2 genotypes with corresponding phenotypes overlapping with smooth muscle dysfunction syndrome.

Pathogenic variants in ACTA2, encoding smooth muscle α-actin, predispose to thoracic aortic aneurysms and dissections. ACTA2 variants altering arginine 179 predispose to a more severe, multisystemic disease termed smooth muscle dysfunction syndrome (SMDS; OMIM 613834). Vascular complications of SMDS include patent ductus arteriosus (PDA) or aortopulmonary window, early-onset thoracic aortic disease (TAD), moyamoya-like cerebrovascular disease, and primary pulmonary hypertension. Patients also have dysfunction of other smooth muscle-dependent systems, including congenital mydriasis, hypotonic bladder, and gut hypoperistalsis. Here, we describe five patients with novel heterozygous ACTA2 missense variants, p.Arg179Gly, p.Met46Arg, p.Thr204Ile, p.Arg39Cys, and p.Ile66Asn, who have clinical complications that align or overlap with SMDS. Patients with the ACTA2 p.Arg179Gly and p.Thr204Ile variants display classic features of SMDS. The patient with the ACTA2 p.Met46Arg variant exhibits exclusively vascular complications of SMDS, including early-onset TAD, PDA, and moyamoya-like cerebrovascular disease. The patient with the ACTA2 p.Ile66Asn variant has an unusual vascular complication, a large fusiform internal carotid artery aneurysm. The patient with the ACTA2 p.Arg39Cys variant has pulmonary, gastrointestinal, and genitourinary complications of SMDS but no vascular manifestations. Identifying pathogenic ACTA2 variants associated with features of SMDS is critical for aggressive surveillance and management of vascular and nonvascular complications and delineating the molecular pathogenesis of SMDS.

Initial results from an enhanced recovery program for pediatric cardiac surgical patients.

BACKGROUND: Over recent years, a number of enhanced recovery programs have appeared in first, adult colorectal surgery, and subsequently many other adult surgical specialties. Increasing interest in this approach to perioperative management in children culminated in the recent development of the first enhanced recovery pathway for pediatric intestinal surgery, endorsed by Enhanced Recovery after Surgery Society (ERAS®). In parallel, there has been increasing interest in the refinement of perioperative management of selected pediatric cardiac surgical patients, invariably referred to as "fast track" management. Initiatives have largely focused on duration of postoperative ventilation rather than on a much wider range of perioperative interventions to optimize recovery and ensure timely discharge after surgery. In our institution, a "Level 1" pediatric cardiac surgical center, we assembled a multidisciplinary team to design a comprehensive enhanced recovery pathway, based on ERAS® methodology, for selected cardiac surgical patients. After a lengthy period of planning, staff education, and preparation, we implemented the pathway at the end of November 2019. METHODS: We conducted a prospective audit of the perioperative management and outcomes of the first 88 patients managed according to this enhanced recovery pathway over a 25-month period in our institution. RESULTS: The mean age of the patients was 5.8 years (range 0.5-17.9), and the mean weight was 22.4 kg (range 6.6-57.2). Sixty-eight of the 88 patients were cardiopulmonary bypass cases. A total of 54% of patients received all four defined intraoperative anesthetic interventions (intravenous paracetamol, non-steroidal anti-inflammatory drug, antiemetic if aged more than 4 years, and use of a local anesthetic technique). A total of 89% of patients met the target extubation time of 6 h after administration of protamine. Median postoperative intensive care unit length of stay was 23.5 h (range 15.2-89.5). When compared to a historic control group, this represented a 22% reduction in median intensive care unit stay, although the total hospital length of stay remained unchanged. A total of 83% of patients met the target hospital discharge target of the fifth postoperative day. CONCLUSIONS: These preliminary results suggest that enhanced recovery pathway implementation for selected pediatric cardiac surgical patients is feasible, with acceptable outcomes. They suggest areas for further development and the potential for wider implementation.

Vertebral Fractures in Ireland: A Sub-analysis of the DXA HIP Project.

Osteoporosis is an important global health problem resulting in fragility fractures. The vertebrae are the commonest site of fracture resulting in extreme illness burden, and having the highest associated mortality. International studies show that vertebral fractures (VF) increase in prevalence with age, similarly in men and women, but differ across different regions of the world. Ireland has one of the highest rates of hip fracture in the world but data on vertebral fractures are limited. In this study we examined the prevalence of VF and associated major risk factors, using a sample of subjects who underwent vertebral fracture assessment (VFA) performed on 2 dual-energy X-ray absorptiometry (DXA) machines. A total of 1296 subjects aged 40 years and older had a valid VFA report and DXA information available, including 254 men and 1042 women. Subjects had a mean age of 70 years, 805 (62%) had prior fractures, mean spine T-score was - 1.4 and mean total hip T-scores was - 1.2, while mean FRAX scores were 15.4% and 4.8% for major osteoporotic fracture and hip fracture, respectively. Although 95 (7%) had a known VF prior to scanning, 283 (22%) patients had at least 1 VF on their scan: 161 had 1, 61 had 2, and 61 had 3 or more. The prevalence of VF increased with age from 11.5% in those aged 40-49 years to > 33% among those aged ≥ 80 years. Both men and women with VF had significantly lower BMD at each measured site, and significantly higher FRAX scores, P < 0.01. These data suggest VF are common in high risk populations, particularly older men and women with low BMD, previous fractures, and at high risk of fracture. Urgent attention is needed to examine effective ways to identify those at risk and to reduce the burden of VF.

Osteoporotic Vertebral Fractures are Common in Hip Fracture Patients and are Under-recognized.

INTRODUCTION: The vertebrae are the most common site for osteoporotic fracture. While they can result in disability and increased mortality, only one-third present clinically. People with multiple fractures are at greater risk of future fractures. Most hip fracture patients are neither diagnosed nor treated for their underlying osteoporosis. Computed tomography (CT) studies are often performed on hospitalised patients, can be used to diagnose osteoporosis and are gaining popularity for opportunistic osteoporosis screening by measuring BMD and other bone strength indices. The aim of this study was to assess the prevalence of vertebral fractures on CT pulmonary angiograms (CTPA) in a cohort of hip fracture patients and whether this increased their diagnosis and treatment rates. METHODS: We retrospectively identified all hip fractures admitted to our institution between 2010 and 2017 to identify those who underwent CTPA scans. An independent, blinded consultant musculoskeletal radiologist reviewed the images for vertebral fractures and quantified severity using Genant criteria. Results were compared to the original radiology report, discharge diagnoses and treatment rates for osteoporosis. RESULTS: Eleven percent (225/2122) of patients had CTPA images available. Seventy percent (158) were female with a mean age of 78 years (SD: 11). The median length of stay for all patients was 16 days (1-301). Forty percent (90) of patients had at least one vertebral fracture present and 20% (46) had more than one fracture. Only one in 5 radiology reports noted the fractures. 24% of subjects had osteoporosis treatment recorded at hospital discharge and there was no difference between those with vertebral fractures to those without. CONCLUSION: Many hip fracture patients have undiagnosed spine fractures. A screening strategy which evaluates CT scans for fractures has potential to increase diagnosis and treatment rates of osteoporosis. However, more work is needed to increase awareness.

High-performing physicians are more likely to participate in a research study: findings from a quality improvement study.

BACKGROUND: Participants in voluntary research present a different demographic profile than those who choose not to participate, affecting the generalizability of many studies. Efforts to evaluate these differences have faced challenges, as little information is available from non-participants. Leveraging data from a recent randomized controlled trial that used health administrative databases in a jurisdiction with universal medical coverage, we sought to compare the quality of care provided by participating and non-participating physicians prior to the program's implementation in order to assess whether participating physicians provided a higher baseline quality of care. METHODS: We conducted clustered regression analyses of baseline data from provincial health administrative databases. Participants included all family physicians who were eligible to participate in the Improved Delivery of Cardiovascular Care (IDOCC) project, a quality improvement project rolled out in a geographically defined region in Ontario (Canada) between 2008 and 2011. We assessed 14 performance indicators representing measures of access, continuity, and recommended care for cancer screening and chronic disease management. RESULTS: In unadjusted and patient-adjusted models, patients of IDOCC-participating physicians had higher continuity scores at the provider (Odds Ratio (OR) [95% confidence interval]: 1.06 [1.03-1.09]) and practice (1.06 [1.04-1.08]) level, lower risk of emergency room visits (Rate Ratio (RR): 0.93 [0.88-0.97]) and hospitalizations (RR:0.87 [0.77-0.99]), and were more likely to have received recommended diabetes tests (OR: 1.25 [1.06-1.49]) and cancer screening for cervical cancer (OR: 1.32 [1.08-1.61] and breast cancer (OR: 1.32 [1.19-1.46]) than patients of non-participating physicians. Some indicators remained statistically significant in the model after adjusting for provider factors. CONCLUSIONS: Our study demonstrated a participation bias for several quality indicators. Physician characteristics can explain some of these differences. Other underlying physician or practice attributes also influence interest in participating in quality improvement initiatives and existing quality levels. The standard for addressing participation bias by controlling for basic physician and practice level variables is inadequate for ensuring that results are generalizable to primary care providers and practices.

The use of electronic consultations is associated with lower specialist referral rates: a cross-sectional study using population-based health administrative data.

Background: The referral-consultation process can be difficult to navigate. Electronic consultations (eConsults) can help streamline referrals by facilitating inter-provider communication. Objective: We evaluated the potential effect of eConsult on specialist referral rates in Ontario among family physicians providing comprehensive care. Methods: We conducted a retrospective 1:3 matched cohort study examining total referrals and referrals to all available medical specialties from primary care providers between 1 April 2014 and 31 March 2015. We used multivariable random effects Poisson regression analysis to compare referral rates between eConsult and non-eConsult users while adjusting for relevant patient and provider characteristics. Referral rates were expressed per physician, per 100 patients and per 100 patient encounters. Results: There were 113197 referrals across all medical specialties made by 119 eConsult physicians and 352 matched controls. Referral rates per physician were significantly lower in the eConsult group for all specialty groupings [unadjusted rate ratio (RR) = 0.87, 95% confidence interval (CI) = 0.80-0.95; adjusted RR = 0.92, 95% CI = 0.85-1.00]. Referral rates per patient were lower among eConsult physicians (unadjusted RR = 0.91, 95% CI = 0.84-0.98) but this difference was not statistically significant after adjustment (adjusted RR = 0.96, 95% CI = 0.90-1.02). No statistically significant difference was observed when referrals were expressed per 100 patient encounters. Conclusion: This is the first Canadian study to examine the potential effect of eConsult on overall referrals at a population level. Our findings demonstrate that using eConsult service is associated with fewer referrals from primary to specialist care, with considerable potential for cost savings to our single-payer system.

Withdrawn: A Randomized Controlled Trial Comparing Modular and Nonmodular Neck Versions of a Titanium Stem.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Who Uses eConsult? Investigating Physician Characteristics Associated with Usage (and Nonusage).

BACKGROUND: The Champlain BASE™ eConsult Service was developed in a Local Health Integration Network (LHIN) in Ontario, Canada in 2010 to reduce wait times and improve access to specialist care. The service allows primary care providers to receive advice from specialists via a secure electronic platform without necessarily requiring a face-to-face consultation. INTRODUCTION: As of 2015, over half of the LHIN's family physicians were registered and trained to use the service. However, 24% of registrants never went on to submit a case. The purpose of this study is to examine the demographic characteristics associated with usage. MATERIALS AND METHODS: Usage data for the pool of physicians registered between January 1, 2011 and September 30, 2015 were linked to physician characteristics retrieved from the College of Physicians and Surgeons of Ontario database. Probit regressions were estimated to determine characteristics associated with usage. RESULTS: Neither sex, being an international medical school graduate-documented predictors of electronic medical records adoption-nor proximity to specialists were found to explain usage. Only length of time in practice was found to be predictive. Being out of medical school an additional 10 years was estimated to decrease the probability of ever using eConsult by five percentage points (p < 0.01). CONCLUSION: Lower use by veteran physicians may reflect their lower need for services like eConsult given their well-established specialist networks, or their greater confidence in practicing medicine. Future work should explore the reasons and barriers for not registering, or not using eConsult, with an aim toward increasing the appropriate use of this cost-effective and innovative service.

Blood Metal Ion Levels Have Limited Utility in the Surveillance of Asymptomatic Large-Head Metal-on-Metal Total Hip Arthroplasties.

BACKGROUND: Blood cobalt (Co) and chromium (Cr) ion levels have been used as surveillance tools for adverse reaction to metal debris (ARMD) in metal-on-metal (MoM) articulations with varying thresholds in different countries. The aim of our study is to present the serial 12-year blood Co and Cr levels in a cohort of MoM total hip arthroplasties (THAs) with femoral head size ≥36 mm and analyze their utility in asymptomatic patients at current thresholds. METHODS: A total of 256 patients with unilateral MoM THA with femoral head size ≥36 mm were included in this study with data collected prospectively. The implants used were Birmingham hip resurfacing cup-Freeman stem (BHR-F) or an Articular Surface Resurfacing cup-Corail/S-ROM stem. Annual follow-up with blood Co and Cr measurements was done as per Medicines and Healthcare Products Regulatory Agency (MHRA) of the United Kingdom guidelines. Receiver operating characteristic curve was plotted based on the sensitivity and specificity of blood metal ion values to detect ARMD. The metal ion levels in asymptomatic patients were analyzed separately. RESULTS: Receiver operating characteristic curves showed poor discriminatory ability for both Co and Cr values in predicting ARMD at 7 µg/L. The sensitivity of Co and Cr was 82.1% and 53.5%, respectively, and their positive predictive values were 43.8% and 67.6%, respectively. After 7 years, there was no significant change in Co values, and there was a decline in Cr value after 9 years in asymptomatic patients. CONCLUSION: To the best of our knowledge, this is the first study to describe the behavior of serial blood metal ion levels in asymptomatic large-diameter MoM THA. We suggest that annual blood Co and Cr have limited discriminant capacity in diagnosing the occurrence of metallosis and their measurement beyond 7 years is of limited utility in asymptomatic patients.

Finding covert fluid: methods for detecting volume overload in children on dialysis.

BACKGROUND: Lung ultrasound is a novel technique for detecting generalized fluid overload in children and adults with end-stage renal disease (ESRD). Echocardiography and bioimpedance spectroscopy are established methods, albeit variably adopted in clinical practice. We compared the practicality and accuracy of lung ultrasound with current objective techniques for detecting fluid overload in children with ESRD. METHODS: A prospective observational study was performed to compare lung ultrasound B-lines, echocardiographic measurement of inferior vena cava parameters and bioimpedance spectroscopy in the assessment of fluid overload in children with ESRD on dialysis. The utility of each technique in predicting fluid overload, based on short-term weight gain, was assessed. Multiple linear regression models to predict fluid overload by weight were explored. RESULTS: A total of 22 fluid assessments were performed in 13 children (8 on peritoneal dialysis, 5 on haemodialysis) with a median age of 4.0 (range 0.8-14.0) years. A significant linear correlation was observed between the number of B-lines detected by lung ultrasound and fluid overload by weight (r = 0.57, p = 0.005). A non-significant positive linear correlation was observed between fluid overload by weight and bioimpedance spectroscopy (r = 0.43, p = 0.2), systolic blood pressure (r = 0.19, p = 0.4) and physical examination measurements (r = 0.19, p = 0.4), while a non-significant negative linear relationship was found between the inferior vena cava collapsibility index and fluid overload by weight (r = -0.24, p = 0.3). In multiple linear regression models, a combination of three fluid parameters, namely lung ultrasound B-lines, clinical examination and systolic blood pressure, best predicted fluid overload (R 2 = 0.46, p = 0.05). CONCLUSIONS: Lung ultrasound may be superior to echocardiographic methods and bioimpedance spectroscopy in detecting volume overload in children with ESRD. Given the practicality and sensitivity of this new technique, it can be adopted alongside clinical examination and blood pressure in the routine assessment of fluid status in children with ESRD.

A mixed-methods study of the causes and impact of poor teamwork between junior doctors and nurses.

OBJECTIVES: This study aimed to collect and analyse examples of poor teamwork between junior doctors and nurses; identify the teamwork failures contributing to poor team function; and ascertain if particular teamwork failures are associated with higher levels of risk to patients. DESIGN: Critical Incident Technique interviews were carried out with junior doctors and nurses. SETTING: Two teaching hospitals in the Republic of Ireland. PARTICIPANTS: Junior doctors (n = 28) and nurses (n = 8) provided descriptions of scenarios of poor teamwork. The interviews were coded against a theoretical framework of healthcare team function by three psychologists and were also rated for risk to patients by four doctors and three nurses. RESULTS: A total of 33 of the scenarios met the inclusion criteria for analysis. A total of 63.6% (21/33) of the scenarios were attributed to 'poor quality of collaboration', 42.4% (14/33) to 'poor leadership' and 48.5% (16/33) to a 'lack of coordination'. A total of 16 scenarios were classified as high risk and 17 scenarios were classified as medium risk. Significantly more of the high-risk scenarios were associated with a 'lack of a shared mental model' (62.5%, 10/16) and 'poor communication' (50.0%, 8/16) than the medium-risk scenarios (17.6%, 3/17 and 11.8%, 2/17, respectively). CONCLUSION: Poor teamwork between junior doctors and nurses is common and places patients at considerable risk. Addressing this problem requires a well-designed complex intervention to develop the team skills of doctors and nurses and foster a clinical environment in which teamwork is supported.

Evolving Role of Viltolarsen for Treatment of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is one of the most prevalent X-linked inherited neuromuscular disorders, with an estimated incidence between 1 in 3500 and 5000 live male births. The median life expectancy at birth is around 30 years due to a rapid and severe disease progression. Currently, there is no cure for DMD, and the standard of care is mainly palliative therapy and glucocorticoids to mitigate symptoms and improve quality of life. Recent advances in phosphorodiamidate morpholino antisense oligonucleotide (PMO) technology has proven optimistic in providing a disease-modifying therapy rather than a palliative treatment option through correcting the primary genetic defect of DMD by exon skipping. However, as a result of the high variance in mutations of the dystrophin gene causing DMD, it has been challenging to tailor an effective therapy in most patients. Viltolarsen is effective in 8% of patients and accurately skips exon 53, reestablishing the reading frame and producing a functional form of dystrophin and milder disease phenotype. Results of recently concluded preclinical and clinical trials show significantly increased dystrophin protein expression, no severe adverse effects, and stabilization of motor function. In summary, viltolarsen has provided hope for those working toward giving patients a safe and viable treatment option for managing DMD. This review summarizes an overview of the presentation, pathophysiology, genetics, and current treatment guidelines of DMD, pharmacological profile of viltolarsen, and a summary of the safety and efficacy with additional insights using recent clinical trial data.

Laryngopharyngeal Reflux Pathophysiology, Clinical Presentation, and Management: A Narrative Review.

Laryngopharyngeal reflux (LPR) is a common and often misinterpreted clinical entity responsible for various symptoms affecting the upper aerodigestive tract. This narrative literature review aims to review the pathophysiology, symptoms, and management of LPR, emphasizing the emerging understanding of gastric content reflux in aerodigestive tissue irritation. Understanding the pathophysiology of LPR will allow general practitioners and specialists to accurately recognize and treat a condition that causes substantial morbidity in the affected patients. Using evidence-based findings from randomized controlled trials, clinical studies, and meta-analyses, the present investigation aims to outline and unify previous research into LPR. A review of anatomical structures, pathogenic mechanisms, endoscopic findings in LPR, and clinical manifestations and treatment options are also discussed. Though controversy around the diagnosis and management of LPR persists, emerging research in cellular damage and diagnostic tools promises to provide increasingly accurate and reliable modalities for characterizing LPR. Hopefully, future research will unify the field and provide overarching guidelines for both primary care and specialists. The present investigation provides an integrated perspective on LPR, a clinically prevalent and complex disease.

Advancing Treatment in Atopic Dermatitis: A Comprehensive Review of Clinical Efficacy, Safety, and Comparative Insights Into Corticosteroids, Calcineurin Inhibitors, and Phosphodiesterase-4 Inhibitors as Topical Therapies.

Atopic dermatitis (AD) is a pervasive and multifaceted dermatological disorder causing daily distress to afflicted individuals worldwide. This comprehensive review synthesizes the historical and contemporary advancements in therapeutic strategies, offering a critical analysis of their efficacy, safety profiles, and adaptability. The enduring role of topical corticosteroids in managing AD is examined, acknowledging their potent anti-inflammatory properties alongside their potential adverse side effects, particularly in extended usage. The article explores the utilization of topical calcineurin inhibitors like tacrolimus and pimecrolimus, highlighting their novel anti-inflammatory pathways while also scrutinizing concerns over potential malignancies that relegate them to second-line therapy. The present investigation features the emergence of crisaborole, a phosphodiesterase four inhibitor. Its innovative mode of action, benign safety profile, and applicability to mild and moderate AD are thoroughly evaluated. The review also includes challenges, particularly cost considerations, which constrain accessibility and necessitate nuanced implementation in therapeutic regimens. This study underscores the need for persistent investigation, teamwork, and innovations in managing AD. In this regard, AD requires a united approach between clinicians, researchers, affected individuals, and policymakers to refine patient-focused treatment and develop precise, economical strategies to address this chronic and frequently life-altering health condition.

Ireland DXA-FRAX may differ significantly and substantially to Web-FRAX.

Appropriate use of FRAX reduces the number of people requiring DXA scans, while contemporaneously determining those most at risk. We compared the results of FRAX with and without inclusion of BMD. It suggests clinicians to carefully consider the importance of BMD inclusion in fracture risk estimation or interpretation in individual patients. PURPOSE: FRAX is a widely accepted tool to estimate the 10-year risk of hip and major osteoporotic fracture in adults. Prior calibration studies suggest this works similarly with or without the inclusion of bone mineral density (BMD). The purpose of the study is to compare within-subject differences between FRAX estimations derived using DXA and Web software with and without the inclusion of BMD. METHOD: A convenience cohort was used for this cross-sectional study, consisting of 1254 men and women aged between 40 and 90 years who had a DXA scan and complete validated data available for analysis. FRAX 10-year estimations for hip and major osteoporotic fracture were calculated using DXA software (DXA-FRAX) and the Web tool (Web-FRAX), with and without BMD. Agreements between estimates within each individual subject were examined using Bland-Altman plots. We performed exploratory analyses of the characteristics of those with very discordant results. RESULTS: Overall median DXA-FRAX and Web-FRAX 10-year hip and major osteoporotic fracture risk estimations which include BMD are very similar: 2.9% vs. 2.8% and 11.0% vs. 11% respectively. However, both are significantly lower than those obtained without BMD: 4.9% and 14% respectively, P < 0.001. Within-subject differences between hip fracture estimates with and without BMD were < 3% in 57% of cases, between 3 and 6% in 19% of cases, and > 6% in 24% of cases, while for major osteoporotic fractures such differences are < 10% in 82% of cases, between 10 and 20% in 15% of cases, and > 20% in 3% of cases. CONCLUSIONS: Although there is excellent agreement between the Web-FRAX and DXA-FRAX tools when BMD is incorporated, sometimes there are very large differences for individuals between results obtained with and without BMD. Clinicians should carefully consider the importance of BMD inclusion in FRAX estimations when assessing individual patients.