Search

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis, characterized by asthma, eosinophilia and granulomatous or vasculitic involvement of several organs. The diagnosis and management of EGPA are often challenging and require an integrated, multidisciplinary approach. Current practice relies on recommendations and guidelines addressing the management of ANCA-associated vasculitis and not specifically developed for EGPA. Here, we present evidence-based, cross-discipline guidelines for the diagnosis and management of EGPA that reflect the substantial advances that have been made in the past few years in understanding the pathogenesis, clinical subphenotypes and differential diagnosis of the disease, as well as the availability of new treatment options. Developed by a panel of European experts on the basis of literature reviews and, where appropriate, expert opinion, the 16 statements and five overarching principles cover the diagnosis and staging, treatment, outcome and follow-up of EGPA. These recommendations are primarily intended to be used by healthcare professionals, pharmaceutical industries and drug regulatory authorities, to guide clinical practice and decision-making in EGPA. These guidelines are not intended to limit access to medications by healthcare agencies, nor to impose a fixed order on medication use.

Heart regeneration is a remarkable process whereby regrowth of damaged cardiac tissue rehabilitates organ anatomy and function. Unfortunately, the human heart is highly resistant to regeneration, which creates a shortage of cardiomyocytes in the wake of ischemic injury, and explains, in part, why coronary artery disease remains a leading cause of death worldwide. Luckily, a detailed blueprint for achieving therapeutic heart regeneration already exists in nature because several lower vertebrate species successfully regenerate amputated or damaged heart muscle through robust cardiomyocyte proliferation. A growing number of species are being interrogated for cardiac regenerative potential, and several commonalities have emerged between those animals showing high or low innate capabilities. In this review, we provide a historical perspective on the field, discuss how regenerative potential is influenced by cardiomyocyte properties, mitogenic signals, and chromatin accessibility, and highlight unanswered questions under active investigation. Ultimately, delineating why heart regeneration occurs preferentially in some organisms, but not in others, will uncover novel therapeutic inroads for achieving cardiac restoration in humans.

Few performance measures assess presurgical value (quality and utilization).Using carpal tunnel syndrome (CTS) as a case study: (1) develop a model to evaluate presurgical quality and utilization and (2) identify opportunities for value improvement.A retrospective cohort study utilizing Veterans Affairs (VA) national administrative data.Patients who were evaluated in a VA primary care clinic on at least 1 occasion for CTS and received carpal tunnel release over a 7-year period.We modeled facility-level performance on 2 outcomes: surgical delay (marker of quality) and number of presurgical encounters (utilization) for CTS, and examined association between patient, facility, and care process variables and performance.Among 41,912 Veterans undergoing carpal tunnel release at 127 VA medical centers, the median facility-level predicted probability of surgical delay was 48%, with 16 (13%) facilities having significantly less delay than the median and 13 (10%) facilities having greater delay. The median facility-level predicted number of presurgical encounters was 8.8 visits, with 22 (17%) facilities having significantly fewer encounters and 22 (17%) facilities having more. Care processes had a stronger association with both outcomes than structural variables included in the models. Processes associated with the greatest deviations in predicted delay and utilization included receipt of repeat electrodiagnostic testing, use of 2 or more nonoperative treatments, and community referral outside of VA.Using CTS as a test case, this study demonstrates the potential to assess presurgical value and identify modifiable care processes associated with presurgical delay and utilization performance.

The aim of this work was 2-fold: (1) to evaluate current knowledge and identify key directions in the study of sluggish cognitive tempo (SCT); and (2) to arrive at a consensus change in terminology for the construct that reflects the current science and may be more acceptable to researchers, clinicians, caregivers, and patients.An international Work Group was convened that, in early 2021, compiled an online archive of all research studies on SCT and summarized the current state of knowledge, noted methodological issues, and highlighted future directions, and met virtually on 10 occasions in 2021 to discuss these topics and terminology.Major progress has been made over the last decade in advancing our understanding of SCT across the following domains of inquiry: construct measurement and stability; genetic, environmental, pathophysiologic, and neuropsychological correlates; comorbid conditions; functional impairments; and psychosocial and medication interventions. Findings across these domains are summarized, and potential avenues to pursue in the next generation of SCT-related research are proposed. Following repeated discussions on terminology, the Work Group selected "cognitive disengagement syndrome" (CDS) to replace "SCT" as the name for this construct. This term was deemed to best satisfy considerations that should apply when selecting terms for a condition or syndrome, as it does not overlap with established terms for other constructs, is not offensive, and reflects the current state of the science.It is evident that CDS (SCT) has reached the threshold of recognition as a distinct syndrome. Much work remains to further clarify its nature (eg, transdiagnostic factor, separate disorder, diagnostic specifier), etiologies, demographic factors, relations to other psychopathologies, and linkages to specific domains of functional impairment. Investigators are needed with interests and expertise spanning basic, clinical, and translational research to advance our understanding and to improve the lives of individuals with this unique syndrome.

Migraines affect approximately one billion individuals worldwide. Implanted nerve stimulator devices can provide relief to some individuals who have chronic migraines refractory to other treatments. This study defines the change in headache pain severity and headache frequency following implanted nerve stimulator treatment in chronic migraineurs. A PRISMA-compliant systematic review of six databases was performed to identify all clinical trials treating at least 10 chronic migraineurs with an implanted nerve stimulator. Inverse variance random effects meta-analyses were performed to define the relative change in headache pain severity and headache frequency as compared to baseline. Nine studies met criteria, including 5 randomized controlled clinical trials and 4 uncontrolled clinical trials, and treated 559 individuals. Among studies that reported gender, 306 females and 154 males were treated. Mean patient ages ranged from 45 to 50 years. All included studies targeted the greater occipital nerve with an implanted nerve stimulator. Implanted nerve stimulator treatment reduced pain severity at 1 month by 36.42% (95%-CI: 28.35-44.49, I2 = 55%) and 3 months by 50.04% (95%-CI: 39.67-60.42%, I2 = 26%). Implanted nerve stimulators reduced headache frequency by 49.86% (95%-CI: 31.49-68.23, I2 = 92%) at 1 to 3 months and 27.43% (95%-CI: 17.68-37.18, I2 = 63%) at 6 to 97 months. Implanted nerve stimulator devices provide clinically and statistically significant improvements in headache severity and frequency in individuals with chronic migraines.

Background: Prenatal diagnosis of bicuspid aortic valve is challenging. Bicuspid aortic valve is often associated with aortic dilation. Methods: Fetuses with postnatally confirmed bicuspid aortic valve were gestational age-matched with normal controls. Complex lesions were excluded. Aortic valve and arch measurements by two blinded investigators were compared. Results: We identified 27 cases and 27 controls. Estimated fetal weight percentile was lower in cases than controls. Seven cases had one or more significant lesions including perimembranous ventricular septal defects (n = 2), isolated annular hypoplasia (n = 2), and/or arch hypoplasia/coarctation (n = 4). Fetuses with bicuspid aortic valves had significantly smaller median z-scores of the aortic annulus (–1.60 versus –0.53, p < 0.001) and root (–1.10 versus –0.53, p = 0.040), and larger ratios of root to annulus (1.32 versus 1.21, p < 0.001), sinotubular junction to annulus (1.07 versus 0.99, p < 0.001), ascending aorta to annulus (1.29 versus 1.18, p < 0.001), and transverse aorta to annulus (1.04 versus 0.96, p = 0.023). Leaflets were “doming” in 11 cases (41%) and 0 controls (p = 0.010), “thickened” in 10 cases (37%) and 0 controls (p = 0.002). We noted similar findings in the subgroup without significant additional cardiac defects. Conclusions: The appearance of doming or thickened aortic valve leaflets on fetal echocardiogram is associated with bicuspid aortic valve. Compared to controls, fetuses with bicuspid aortic valve had smaller aortic annulus sizes (possibly related to smaller fetal size) without proportionally smaller aortic measurements, resulting in larger aortic dimension to annulus ratios. Despite inherent challenges of diagnosing bicuspid aortic valve prenatally, these findings may increase suspicion and prompt appropriate postnatal follow-up.

Palliative care (PC) benefits patients undergoing hematopoietic stem cell transplantation (HSCT), but it remains underutilized. Although transplant physicians report concerns regarding how patients perceive PC, HSCT recipients’ perceptions about PC remain unaddressed. We conducted a multisite, cross-sectional survey of autologous and allogeneic HSCT recipients 3 to 12 months after transplant to assess their familiarity, knowledge, and perception of PC, as well as their unmet PC needs. We computed a composite score of patients’ perceptions of PC and used a generalized linear regression model to examine factors associated with these perceptions. We enrolled 69.6% (250/359) of potential participants (median age = 58.1; 63.1% autologous HSCT). Overall, 44.3.8% (109/249) reported limited knowledge about PC and 52% (127/245) endorsed familiarity with PC. Most patients felt hopeful (54%) and reassured (50%) when they heard the term PC; 83% saw referral as a sign their doctor cared about what was happening to them. In multivariate analyses, patients who were more knowledgeable about PC were more likely to have positive perceptions of PC (B = 7.54, standard error = 1.61, P < .001). Patients’ demographics, HSCT features, quality of life, and symptom burden were not significantly associated with perceptions of PC. HSCT recipients have positive perceptions of PC, though many have limited knowledge about its role. Patients who were more knowledgeable about PC were more likely to have positive perceptions of PC. These data do not support transplant physicians’ negative concerns about how patients perceive PC and underscore the need to further educate patients and transplant physicians about PC.

Aim: Socio-economic deprivation encompasses the relative disadvantage experienced by individuals or communities in relation to financial, material or social resources. Nature-based interventions (NBIs) are a public health approach that promote sustainable, healthy communities through engagement with nature and show potential to address inequalities experienced by socio-economically deprived communities. This narrative review aims to identify and evaluate the benefits of NBIs in socio-economically deprived communities. Method: A systematic literature search of six electronic publication databases (APA PsycInfo, CENTRAL, CDSR, CINAHL, Medline and Web of Science) was conducted on 5 February 2021 and repeated on 30 August 2022. In total, 3852 records were identified and 18 experimental studies (published between 2015 and 2022) were included in this review. Results: Interventions including therapeutic horticulture, care farming, green exercise and wilderness arts and craft were evaluated in the literature. Key benefits were observed for cost savings, diet diversity, food security, anthropometric outcomes, mental health outcomes, nature visits, physical activity and physical health. Age, gender, ethnicity, level of engagement and perception of environment safety influenced the effectiveness of the interventions. Conclusion: Results demonstrate there are clear benefits of NBIs on economic, environmental, health and social outcomes. Further research including qualitative analyses, more stringent experimental designs and use of standardised outcome measures is recommended.

Background:The scale of the 2022 global mpox (formerly known as monkeypox) outbreak has been unprecedented. In less than 6 months, non-endemic countries have reported more than 67 000 cases of a disease that had previously been rare outside of Africa. Mortality has been reported as rare but hospital admission has been relatively common. We aimed to describe the clinical and laboratory characteristics and outcomes of individuals admitted to hospital with mpox and associated complications, including tecovirimat recipients. Methods:In this cohort study, we undertook retrospective review of electronic clinical records and pathology data for all individuals admitted between May 6, and Aug 3, 2022, to 16 hospitals from the Specialist and High Consequence Infectious Diseases Network for Monkeypox. The hospitals were located in ten cities in England and Northern Ireland. Inclusion criteria were clinical signs consistent with mpox and MPXV DNA detected from at least one clinical sample by PCR testing. Patients admitted solely for isolation purposes were excluded from the study. Key outcomes included admission indication, complications (including pain, secondary infection, and mortality) and use of antibiotic and anti-viral treatments. Routine biochemistry, haematology, microbiology, and virology data were also collected. Outcomes were assessed in all patients with available data. Findings:156 individuals were admitted to hospital with complicated mpox during the study period. 153 (98%) were male and three (2%) were female, with a median age of 35 years (IQR 30–44). Gender data were collected from electronic patient records, which encompassed full formal review of clincian notes. The prespecified options for data collection for gender were male, female, trans, non-binary, or unknown. 105 (71%) of 148 participants with available ethnicity data were of White ethnicity and 47 (30%) of 155 were living with HIV with a median CD4 count of 510 cells per mm3(IQR 349–828). Rectal or perianal pain (including proctitis) was the most common indication for hospital admission (44 [28%] of 156). Severe pain was reported in 89 (57%) of 156, and secondary bacterial infection in 82 (58%) of 142 individuals with available data. Median admission duration was 5 days (IQR 2–9). Ten individuals required surgery and two cases of encephalitis were reported. 38 (24%) of the 156 individuals received tecovirimat with early cessation in four cases (two owing to hepatic transaminitis, one to rapid treatment response, and one to patient choice). No deaths occurred during the study period. Interpretation:Although life-threatening mpox appears rare in hospitalised populations during the current outbreak, severe mpox and associated complications can occur in immunocompetent individuals. Analgesia and management of superimposed bacterial infection are priorities for patients admitted to hospital.

Equity and effectiveness of the medication therapy management (MTM) program in Medicare has been a policy focus since its inception. The objective of this study was to evaluate the cost-effectiveness of the Medicare MTM program in improving medication utilization quality across racial and ethnic groups.This study analyzed 2017 Medicare data linked to the Area Health Recourses File. A propensity score was used to match MTM enrollees and nonenrollees, and an incremental cost-effectiveness ratio between the 2 groups was calculated. Effectiveness was measured as the proportion of appropriate medication utilization based on medication utilization measures developed by Pharmacy Quality Alliance. Net monetary benefits were compared across racial and ethnic groups at various societal willingness-to-pay (WTP) thresholds. The 95% confidence intervals were obtained by nonparametric bootstrapping.MTM dominated non-MTM among the total sample (N = 699 992), as MTM enrollees had lower healthcare costs ($31 135.89 vs $32 696.69) and higher proportions of appropriate medication utilization (87.47% vs 85.31%) than nonenrollees. MTM enrollees had both lower medication costs ($10 681.21 vs $11 003.08) and medical costs ($20 454.68 vs $21 693.61) compared with nonenrollees. The cost-effectiveness of MTM was higher among Black patients than White patients across the WTP thresholds. For instance, at a WTP of $3006 per percentage point increase in effectiveness, the net monetary benefit for Black patients was greater than White patients by $2334.57 (95% confidence interval $1606.53-$3028.85).MTM is cost-effective in improving medication utilization quality among Medicare beneficiaries and can potentially reduce disparities between Black and White patients. Expansion of the current MTM program could maximize these benefits.

This article reports the outcome of an in silico analysis of more than 12,000 small molecule drugs and drug impurities, identifying the nitrosatable structures, assessing their potential to form nitrosamines under relevant conditions and the challenges to determine compound-specific AIs based on data available or read-across approaches for these nitrosamines and their acceptance by health authorities. Our data indicate that the presence of nitrosamines in pharmaceuticals is likely more prevalent than originally expected. In total, 40.4 % of the analyzed APIs and 29.6 % of the API impurities are potential nitrosamine precursors. Most structures identified through our workflow could form complex API-related nitrosamines, so-called nitrosamine drug substance related impurities (NDSRIs), although we also found structures that could release the well-known small and potent nitrosamines NDMA, NDEA, and others. Due to common structural motifs including secondary or tertiary amine moieties, whole essential drug classes such as beta blockers and ACE inhibitors are at risk. To avoid the risk of drug shortages or even the complete loss of therapeutic options, it will be essential that the well-established ICH M7 principles remain applicable for nitrosamines and that that the industry and regulatory authorities keep an open communication not only about the science but also to make sure there is a good balance between risk and benefit to patients.

Many antimicrobial stewardship programs (ASPs) focus on decreasing unnecessary antibiotics. We describe the impact of an outpatient ASP on choice, dose, and duration of antibiotics when used for common infections in pediatric urgent care (PUC) centers.We reviewed encounters at 4 PUC centers within our organization for patients 6 months to 18 years old with acute otitis media, group A streptococcal pharyngitis, community-acquired pneumonia, urinary tract infection, and skin and soft tissue infections who received systemic antibiotics. We determined appropriate antibiotic choice, dose, and duration for each diagnosis. Pearson's χ² test compared appropriate prescribing before ASP implementation (July 2017-July 2018) and postimplementation (August 2018-December 2020). Control charts trended improvement over time.Our study included 35,917 encounters. The percentage of prescriptions with the recommend agent at the appropriate dose and duration increased from a mean of 32.7% to 52.4%. The center lines for appropriate agent, dose, and duration all underwent upward shifts. The most substantial changes were seen in antibiotic duration (63.2%-80.5%), and appropriate dose (64.6%-77%).Implementation of an outpatient ASP improved prescribing patterns for choosing the appropriate agent, duration, and dose for many common infections in our PUCs.