Proceedings of the annual meeting of the European Consortium of Lipodystrophies (ECLip), Pisa, Italy, 28-29 September 2023.

Lipodystrophy syndromes are rare diseases primarily affecting the development or maintenance of the adipose tissue but are also distressing indirectly multiple organs and tissues, often leading to reduced life expectancy and quality of life. Lipodystrophy syndromes are multifaceted disorders caused by genetic mutations or autoimmunity in the vast majority of cases. While many subtypes are now recognized and classified, the disease remains remarkably underdiagnosed. The European Consortium of Lipodystrophies (ECLip) was founded in 2014 as a non-profit network of European centers of excellence working in the field of lipodystrophies aiming at promoting international collaborations to increase basic scientific understanding and clinical management of these syndromes. The network has developed a European Patient Registry as a collaborative research platform for consortium members. ECLip and ECLip registry activities involve patient advocacy groups to increase public awareness and to seek advice on research activities relevant from the patients perspective. The annual ECLip congress provides updates on the research results of various network groups members.

Effect of Exhausted Coffee Ground Particle Size on Metal Ion Adsorption Rates and Capacities.

Spent coffee grounds (SCGs) are common waste products that can be used as low-cost adsorbents to remove contaminants from water. SCGs come in a range of particle sizes based on how they were ground to brew coffee. However, few studies have investigated how SCG particle size influences the adsorption rate and capacities of metal ions. In this study, SCGs were washed under alkaline conditions, creating exhausted coffee grounds (ECGs). ECGs were sieved into four particle size ranges (106-300, 300-500, 500-710, and 710-1000 µm). Monocomponent batch adsorption experiments were conducted with each size fraction using 0.3 mM Pb2+, Cu2+, Zn2+, and Ni2+ at pH 5.5 to examine the effect of particle size on the adsorption rates and capacities. The initial adsorption rates for all the four metal ions were 8-12 times higher for the smallest ECGs compared to the largest ECGs. Slower initial adsorption rates with increasing particle size were due to intraparticle diffusion of metal ions into the porous structure of ECGs. However, the equilibrium adsorption capacities for each metal ion and the surface acidic group concentrations were similar across the range of particle sizes studied, suggesting that grinding ECGs does not substantially change the number of adsorption sites. The equilibrium adsorption capacities for Cu2+ and Pb2+ were 0.18 and 0.17 mmol g-1, respectively. Zn2+ and Ni2+ had lower adsorption capacities of 0.12 and 0.10 mmol g-1, respectively. The time needed to reach equilibrium ranged from less than 2 h for Zn2+ and Ni2+ adsorption onto the smallest ECGs to several hours for Pb2+ or Cu2+ adsorption onto the largest ECGs. Future adsorption studies should consider the effect of ECG particle size on reported adsorption capacities, particularly for shorter experiments that have not yet reached equilibrium.

Proceedings of the annual meeting of the European Consortium of Lipodystrophies (ECLip) Cambridge, UK, 7-8 April 2022.

Lipodystrophy syndromes are rare diseases with defects in the development or maintenance of adipose tissue, frequently leading to severe metabolic complications. They may be genetic or acquired, with variable clinical forms, and are largely underdiagnosed. The European Consortium of Lipodystrophies, ECLip, is a fully functional non-profit network of European centers of excellence working in the field of lipodystrophies. It provides a favorable environment to promote large Europe-wide and international collaborations to increase the basic scientific understanding and clinical management of these diseases. It works with patient advocacy groups to increase public awareness. The network also promotes a European Patient Registry of lipodystrophies, as a collaborative research platform for consortium members. The annual congress organized gives an update of the findings of network research groups, highlighting clinical and fundamental aspects. The talks presented during the meeting in Cambridge, UK, in 2022 are summarized in these minutes.

Assessment of inequity in bicyclist crashes using bivariate Bayesian copulas.

INTRODUCTION: Physical activity associated with active transport modes such as bicycling has major health benefits and can help to reduce health concerns related to sedentary lifestyles, such as cardiovascular disease, Type II diabetes, and obesity, as well as risks of colon and breast cancer, high blood pressure, lipid disorders, osteoporosis, depression, and anxiety. However, as a vulnerable user group, bicyclists experience negative health impacts of transportation policies and infrastructure, such as traffic crashes and exposure to air and noise pollution that is disproportionately distributed within low-income and underserved areas. METHOD: This study used aggregated (block-group) bicyclist crash data from Harris County, Texas, to analyze how various equity measures are associated with both fatal and injury (FI) and no injury (property damage only) bicyclist crashes that occurred from 2010 to 2017. We used Bayesian bivariate copula-based random effects regression analysis to evaluate these associations. In contrast to more traditional univariate analysis, this novel methodology can consider the effects of factors of interest across different severity levels or crash types to fully understand their effects and how they may differ across categories. RESULTS: The analysis results indicate that the bicyclist exposure, vehicle exposure, population demographics, population density, the percentage of African-Americans, and households below the poverty level are associated with both FI and PDO bicyclist crashes. CONCLUSIONS: Although more location and context-specific analyses are required, this study's overall results once again conform with the findings and assumptions in bicycling safety literature that the low-income and racially diverse communities are prone to experience more bicyclist crashes. PRACTICAL APPLICATIONS: The findings of this study may have implications for future transportation and planning policies. These findings can be used to guide the policies and strategies targeting the elimination of inequity in transportation-related health concerns.

Towards a predictive model of COVID-19 vaccine hesitancy among American adults.

Designing effective public health campaigns to combat COVID-19 vaccine hesitancy requires an understanding of i) who the vaccine hesitant population is, and ii) the determinants of said population's hesitancy. While researchers have identified a number of variables associated with COVID-19 vaccine hesitancy that could inform such campaigns, little is known about the cumulative or relative predictive power of these factors. In this article, we employ a machine learning model to analyze online survey data collected from 3353 respondents. The model incorporates an array of variables that have been shown to impact vaccine hesitancy, allowing us to i) test how well we can predict vaccine hesitancy, and ii) compare the relative predictive impact of each covariate. The model allows us to correctly classify individuals that are vaccine acceptant with 97% accuracy, and those that are vaccine hesitant with 72% accuracy. Trust in and knowledge about vaccines is, by far, the strongest predictor of vaccination choice. While our results demonstrate that public health campaigns designed to increase vaccination rates must find a way to increase public trust in COVID-19 vaccines, our results cannot speak to the malleability of such beliefs, nor how to enhance trust.

Preparing for a Career in Pediatric Hospital Medicine: A Needs Assessment and Recommendations for Individualized Curricula.

OBJECTIVES: The individualized curriculum within residency programs allows residents to tailor their elective time toward future career goals and interests. Our objective was to identify experiences and activities that would foster resident interest and enhance preparation for a career in pediatric hospital medicine (PHM). METHODS: Electronic surveys were distributed to pediatric hospitalists, PHM fellowship directors, and graduating PHM fellows. These stakeholders were asked to identify key experiences for residents to explore before entering fellowship or practice. Descriptive statistics and thematic analysis were performed on survey responses. RESULTS: Forty-six percent of PHM fellows (16 of 35), 42% of pediatric hospitalists (149 of 356), and 58% of fellowship program directors (35 of 60) completed the survey. All 3 groups identified complex care as the most important clinical experience to gain in residency. Other highly valued clinical experiences included pain management, surgical comanagement, and palliative care. Lumbar puncture, electrocardiograph interpretation, and airway management were identified as essential procedural skills. Nonclinical experiences that were deemed important included quality improvement, development of teaching skills, and research methodology. All groups agreed that these recommendations should be supplemented with effective mentorship. CONCLUSIONS: Identification of key clinical experiences, nonclinical activities, and mentorship for residents interested in PHM may assist with tailoring the individualized curriculum to personal career goals. Incorporating these suggested experiences can improve preparedness of residents entering PHM.

Experiences and Perspectives of Patients with Non-HIV-Associated Lipodystrophies and Their Caregivers: A Qualitative Study.

BACKGROUND: Lipodystrophy comprises a group of conditions characterized by loss of functional adipose tissue, resulting in severe metabolic complications and a complex range of symptoms. OBJECTIVE: This study sought to gain a holistic understanding of the impact of congenital or non-human immunodeficiency virus acquired lipodystrophies on the quality of life of patients and their caregivers and to capture the impact of lipodystrophy on quality of life using a standard instrument. METHODS: Ten patients with lipodystrophies and five caregivers from the USA and UK were recruited through convenience sampling and interviewed using a semi-structured questionnaire containing open-ended questions about disease symptoms and attributes and numerical rating scales to prompt discussion of symptom prevalence and impact. After the interview, participants filled out the 36-Item Short Form (SF-36) survey instrument. Conventional conceptual content analysis methods were used to analyze the anonymized transcripts. RESULTS: Four concepts were developed: diagnostic journey and symptom management, burden of disease, healthcare resource utilization, and support and advocacy. Participants described lengthy diagnostic journeys and frequent interactions with healthcare systems. Many participants became experts on lipodystrophy through the diagnostic journey and described difficulties accessing effective treatment, even after diagnosis. Both patients and caregivers emphasized the ongoing burden of living with lipodystrophy and the accompanying sense of isolation. Participants turned to disease-specific support groups to cope, engaging in knowledge sharing with other patients and caregivers and developing friendships based on shared experiences. Ten participants completed the SF-36, with a mean (standard deviation) SF-36 score of 0.6 (0.2). CONCLUSIONS: Currently, there are no qualitative studies that describe the experiences of patients with lipodystrophy and their caregivers. While additional research is needed, educational work like this study is a promising first step that could lead to early diagnosis and access to treatment and support.

The belief that politics drive scientific research & its impact on COVID-19 risk assessment.

We use survey data collected from 12,037 US respondents to examine the extent to which the American public believes that political motives drive the manner in which scientific research is conducted and assess the impact that such beliefs have on COVID-19 risk assessments. We find that this is a commonly held belief and that it is negatively associated with risk assessments. Public distrust in scientists could complicate efforts to combat COVID-19, given that risk assessments are strongly associated with one's propensity to adopt preventative health measures.

Quality Initiative to Reduce High-Flow Nasal Cannula Duration and Length of Stay in Bronchiolitis.

OBJECTIVES: High-flow nasal cannula (HFNC) use in bronchiolitis may prolong length of stay (LOS) if weaned more slowly than medically indicated. We aimed to reduce HFNC length of treatment (LOT) and inpatient LOS by 12 hours in 0- to 18-month-old patients with bronchiolitis on the pediatric hospital medicine service. METHODS: After identifying key drivers of slow weaning, we recruited a multidisciplinary "Wean Team" to provide education and influence provider weaning practices. We then implemented a respiratory therapist-driven weaning protocol with supportive sociotechnical interventions (huddles, standardized orders, simplification of protocol) to reduce LOT and LOS and promote sustainability. RESULTS: In total, 283 patients were included: 105 during the baseline period and 178 during the intervention period. LOT and LOS control charts revealed special cause variation at the start of the intervention period; mean LOT decreased from 48.2 to 31.2 hours and mean LOS decreased from 84.3 to 60.9 hours. LOT and LOS were less variable in the intervention period compared with the baseline period. There was no increase in PICU transfers or 72-hour return or readmission rates. CONCLUSIONS: We reduced HFNC LOT by 17 hours and LOS by 23 hours for patients with bronchiolitis via multidisciplinary collaboration, education, and a respiratory therapist-driven weaning protocol with supportive interventions. Future steps will focus on more judicious application of HFNC in bronchiolitis.

Erenumab and OnabotulinumtoxinA Combination Therapy for the Prevention of Intractable Chronic Migraine without Aura: A Retrospective Analysis.

Erenumab is a monoclonal antibody that mediates calcitonin-gene-related peptide (CGRP), a pro-inflammatory polypeptide implicated in migraine pathology, by targeting its receptor. To date, no clinical trial has evaluated combination therapy with both erenumab and onabotulinumtoxinA therapy for the treatment of chronic migraine. We conducted a retrospective chart review of 78 patients to investigate if the addition of erenumab to patients with chronic migraines receiving onabotulinumtoxinA had a decrease in their total monthly headache days (MHDs) and monthly migraine days (MMD). At baseline, while on onabotulinumtoxinA, mean MHDs were 22.5 ± 8.7 and mean MMDs were 15.8 ± 8.3, and 65 patients (83.3%) failed at least three preventative therapies. Our results demonstrated a significant reduction in MHDs and MMDs at 30- (-6.8 MHDs; p < 0.001, -7.0 MMDs; p < 0.001), 60- (-7.2 MHDs; p < 0.001, -6.7 MMDs; p < 0.001), and 90 days (-8.1 MHDs; p < 0.001, -7.4 MMDs; p < 0.001). Thus, the results of this study suggest favorable outcomes with the addition of erenumab to patients who were still suffering while receiving onabotulinumtoxinA therapy. Additional investigation is needed to determine if erenumab in combination with onabotulinumtoxinA has an enhanced effect on the modulation of CGRP release from peripheral unmyelinated C fibers while also blocking CGRP receptors in the myelinated A-delta fibers.

Prospects for Realizing International Women's Rights Law Through Local Governance: the Case of Cities for CEDAW.

How best to realize international human rights law in practice has proved a vexing problem. The challenge is compounded in the USA, which has not ratified several treaties including the Convention on the Elimination of All Forms of Discrimination against Women (CEDAW). The Cities for CEDAW movement addresses this deficit by encouraging cities to endorse and implement CEDAW norms. In doing so, it seeks to catalyze a local boomerang effect, whereby progressive political momentum at the local level generates internal pressure from below to improve gender equity outcomes across the country and eventually, at the national level. In this article, we trace the diffusion of Cities for CEDAW activism with attention to the case of Cincinnati and analyze its implications for advancing women's rights principles. We argue that while Cities for CEDAW has potential to enhance respect for women's rights in local jurisdictions, its impact on national policy remains limited.

Pain medicine fellow neuromodulation surgical skill assessment tool: a pilot.

OBJECTIVE: Spinal cord stimulation (SCS) is an evidence-based therapy for the treatment of refractory pain. Current American College of Graduate Medical Education requirements for pain medicine fellowship graduation include observation of five neuromodulation cases. Matriculating fellows have varying degrees of technical skill, training, and experience. The purpose of this study was to use an innovative skill-based assessment tool using the validated Zwisch scale to evaluate fellow surgical performance during SCS cases. DESIGN: Cross-sectional survey SETTING: Mayo Clinic, Rochester, Minnesota. SUBJECTS: Consultant faculty (10) in the Division of Pain Medicine and pain medicine fellows (5). METHODS: A list of faculty-driven neuromodulation surgical objectives was formed and a rubric was created that focused on technical approach, imaging, epidural access and wound closure. Consultants who perform surgical cases were instructed to use the Zwisch scale as a guide to evaluate fellow surgical performance during a neuromodulation case. Faculty and fellows were surveyed before and after implementation of the tool to determine their satisfaction with use of the skill assessment tool. RESULTS: The consultants reported they were more satisfied, consistent, and efficient with feedback provided to the trainee on every aspect of neuromodulation surgical cases. The improvement was most significant during the fellows' intraoperative skill assessment. The fellows indicated increased satisfaction, improved communication, and increased efficiency of feedback when the tool was utilized. The fellows reported greater intraoperative skill assessment and consistency of feedback provided. CONCLUSIONS: The diverse nature of primary specialty backgrounds observed in pain medicine fellowship training offers a unique opportunity to assess and improve fellow skill and surgical competence in the field of neuromodulation. Both faculty and fellows reported improved satisfaction, consistency and efficiency with feedback provided. Importantly, this pilot project observed that implementation of a skill assessment tool was beneficial for both the faculty and fellow as the feedback received was viewed as strongly beneficial to the educational experience.

Improving the standardization of mRNA measurement by RT-qPCR.

Human health and safety depend on reliable measurements in medical diagnosis and on tests that support the selection and evaluation of therapeutic intervention and newly discovered molecular biomarkers must pass a rigorous evaluation process if they are to be of benefit to patients. Measurement standardization helps to maximize data quality and confidence and ultimately improves the reproducibility of published research. Failure to consider how a given experiment may be standardized can be costly, both financially as well as in time and failure to perform and report pre-clinical research in an appropriately rigorous manner will hinder the development of diagnostic methods. Hence standardization is a crucial step in maintaining the integrity of scientific studies and is a key feature of robust investigation.

Epidural Hematoma Following Interlaminar Epidural Injection in Patient Taking Aspirin.

OBJECTIVE: We present a case report of a patient who developed an epidural hematoma following an interlaminar epidural steroid injection with no risk factors aside from old age and aspirin use for secondary prevention. CASE REPORT: A 79-year-old man developed an epidural hematoma requiring surgical treatment following an uncomplicated interlaminar epidural steroid injection performed for neurogenic claudication. In the periprocedural period, he continued aspirin for secondary prophylaxis following a myocardial infarction. CONCLUSIONS: For patients taking aspirin for primary or secondary prophylaxis, the American Society of Regional Anesthesia and Pain Medicine antiplatelet and anticoagulation guidelines for spine and pain procedures recommend a shared assessment and risk stratification when deciding to hold the medication for intermediate-risk neuraxial procedures. Cases such as this serve to highlight the importance of giving careful consideration to medical optimization of a patient even when a low- or intermediate-risk procedure is planned.

Utilization of Leads After Permanent Implant in Spinal Cord Stimulator Systems.

OBJECTIVE: The goal of this study was to determine the frequency and clinical indications associated with implantation of single vs. dual percutaneous lead spinal cord stimulator (SCS) systems and to look further into how these leads are utilized for treatment. MATERIALS AND METHODS: A retrospective cohort analysis of all patients undergoing SCS implantation between January 2001 and December 2013 with a minimum of 2 years of clinical follow-up was performed. Number of trial leads and implanted leads was recorded. For patients with dual-lead systems, it was noted if and when the second lead was used, along with the clinical indication for lead activation. RESULTS: In the 259-patient cohort, 15.8% (n = 41) patients underwent placement of a single-lead system, 83.0% (n = 215) underwent placement of a dual-lead system, and 1.2% (n = 3) underwent placement of 3-lead systems. Placement of dual-lead systems was similar among all indication groups. Of those patients with a dual-lead system in place, 88.1% utilized both leads and average time to programming of the second lead was 2.3 months. The most common reason to activate the second lead was inadequate stimulation coverage. Five of the 41 patients with single-lead systems underwent an additional surgery to implant a second lead due to inadequate stimulation with 1 lead. CONCLUSIONS: To our knowledge this is the first descriptive analysis of the frequency of single- and dual-lead SCS systems. This report indicates that dual-lead systems are most often placed and both leads are required for optimal patient therapy.

Latent analysis of Complete Streets and traffic safety along an urban corridor.

BACKGROUND: To evaluate Complete Street implementations that covary, the present paper aims to: 1) explore the development of typologies of intersections; and 2) examine how these typologies relate to traffic safety. METHODS: The study site is a five-mile segment in Los Angeles County, California. Multiple indicators of environmental features were collected in 2012 and were included in a latent analysis. Latent classes were then analyzed as a predictor of the number of pedestrian injuries/fatalities and injuries/fatalities for all modes in separate models using negative binomial regression and controlling for exposures. Injuries/fatalities represent the most recent 3 years of crash data available surrounding the environmental data collection (2009-2014). We also examined the role of alcohol. RESULTS: For a relatively short segment of an urban corridor, we identified two distinct classes of intersections. One class was more complete with respect to pedestrian features but was also associated with indicators of increased potential conflict and was predictive of higher overall injuries/fatalities for all modes. This class also had higher pedestrian volumes but was not predictive of higher pedestrian injuries/fatalities in the final models. The alcohol involvement in crash injuries at these locations did not differ by intersection class but was positively associated with injuries/fatalities for all modes and with severe/fatal injuries for pedestrians in the final models. CONCLUSIONS: Identifying typologies can be used to understand the combination of features and prioritize locations for treatment. While Complete Streets may help counter pedestrian injury trends, the efforts captured in this data are insufficient for municipalities aiming for Vision Zero. Ideally, future research can examine these intersections after the implementation of additional improvements in order to isolate treatment effects. These findings suggest additional intersection countermeasures are needed, in addition to efforts to address social problems such as alcohol use and traffic safety.

Outcomes of C1-2 joint injections.

OBJECTIVE: Intra-articular injections of the C1-2 joint are an effective therapeutic option for pain generated from degenerative and inflammatory conditions affecting the joint. Limited information exists about the adverse events (AEs) associated with these injections. The primary aim of this study is to describe the frequency and type of AEs associated with C1-2 joint injections. The secondary aim is to identify clinical factors associated with the occurrence of AEs of C1-2 joint injections. DESIGN/METHODS: A retrospective chart review was conducted on all C1-2 joint injections performed at the Mayo Pain Medicine Clinic in Rochester, MN, from January 1, 2005 through July 31, 2015. AE data were extracted from procedural and post-procedural clinical notes. Analysis was conducted to determine correlations between any AE and demographic and clinical characteristics. Using univariate and multivariate logistic regression analyses, associations were determined. RESULTS: From January 1, 2005 to July 31, 2015, 135 C1-2 injections were performed on 72 patients. Overall, at least 1 AE was reported in 18.5% of the injections. The most common AEs were post-procedural increase in pain and procedural vascular contrast uptake. There was a significant association between AE occurrence and greater pre-procedural maximum pain score. CONCLUSIONS: AEs from C1-2 joint injections occurred commonly, but there were no persistent or serious AEs associated with these injections. The data also demonstrate that patients with higher pre-procedural maximum pain scores are more likely to experience an AE.

An international comparability study on quantification of mRNA gene expression ratios: CCQM-P103.1.

Measurement of RNA can be used to study and monitor a range of infectious and non-communicable diseases, with profiling of multiple gene expression mRNA transcripts being increasingly applied to cancer stratification and prognosis. An international comparison study (Consultative Committee for Amount of Substance (CCQM)-P103.1) was performed in order to evaluate the comparability of measurements of RNA copy number ratio for multiple gene targets between two samples. Six exogenous synthetic targets comprising of External RNA Control Consortium (ERCC) standards were measured alongside transcripts for three endogenous gene targets present in the background of human cell line RNA. The study was carried out under the auspices of the Nucleic Acids (formerly Bioanalysis) Working Group of the CCQM. It was coordinated by LGC (United Kingdom) with the support of National Institute of Standards and Technology (USA) and results were submitted from thirteen National Metrology Institutes and Designated Institutes. The majority of laboratories performed RNA measurements using RT-qPCR, with datasets also being submitted by two laboratories based on reverse transcription digital polymerase chain reaction and one laboratory using a next-generation sequencing method. In RT-qPCR analysis, the RNA copy number ratios between the two samples were quantified using either a standard curve or a relative quantification approach. In general, good agreement was observed between the reported results of ERCC RNA copy number ratio measurements. Measurements of the RNA copy number ratios for endogenous genes between the two samples were also consistent between the majority of laboratories. Some differences in the reported values and confidence intervals ('measurement uncertainties') were noted which may be attributable to choice of measurement method or quantification approach. This highlights the need for standardised practices for the calculation of fold change ratios and uncertainties in the area of gene expression profiling.

Deep procedural sedation by a sedationist team for outpatient pediatric renal biopsies.

To date, no study has analyzed the use of deep PS for pediatric renal biopsies by a dedicated sedation team in an outpatient setting. Retrospective analysis of renal biopsies performed at CHOA from 2009 to 2013. Patient demographics, procedure success, and sedation-related events were analyzed. Logistic regression techniques were applied to identify characteristics associated with procedure safety and success. A total of 174 biopsies from 136 patients, aged 2-21 yr, were reviewed. Of the 174 biopsies, 63 of 174 (36%) were from native, and 111 of 174 (64%) were from transplanted kidneys, respectively. No deaths, allograft losses, or unanticipated hospital admissions occurred. The most commonly utilized interventions during sedation were blow-by oxygen (29.9%) and CPAP (12.1%). Children receiving the combination of F + P had significantly higher biopsy success rates vs. other drug combinations (96.1% vs. 79%; p = 0.014). There was no difference in complication rates regardless of drug combination or biopsy type (transplanted vs. native). The combination of F + P yields a high procedural success rate for outpatient native and transplanted kidney biopsies. We identified a number of sedation-related events that can be easily managed by a well-trained sedationist team.