Effect of a biomimetic pathogen adsorbing device on inflammatory biomarkers in COVID-19 patients.

INTRODUCTION: The Seraph 100 Microbind Affinity blood filter eliminate bacteria, viruses, fungi and toxins from blood stream. METHODS: This is a prospective multicenter observational biomarker trial in PCR-positive SARS-CoV-2 patients with acute respiratory failure. Biomarkers were sequentially tested at three time points. RESULTS: Forty-two patients with SARS-CoV-2 detected by PCR with acute respiratory failure were included. When receiving hemoperfusion treatment, 27 (64%) patients were on mechanical ventilation, 41 (98%) patients were treated in the ICU. The 3-month survival was 52%. After one hemoperfusion treatment cycle, D-dimer (p = 0.014), hemoglobin (p = 0.003) and LDH (p = 0.001) concentrations were significantly reduced 4 days after treatment. From the multiplex assay IL-1b, CXCL8/ IL-8, IL-10, IL-13, IL-15, CCL11/Eotaxin, G-CSF, and CXCL10/IP-10 were significantly reduced 1 h after treatment, however not 4 days later. CONCLUSION: Hemoperfusion with Seraph 100 Microbind Affinity Filter in patients with severe COVID-19 can transiently reduce several inflammatory biomarkers in the blood.

Digital manufacturing techniques and the in vitro biocompatibility of acrylic-based occlusal device materials.

OBJECTIVES: Material chemistry and workflow variables associated with the fabrication of dental devices may affect the biocompatibility of the dental devices. The purpose of this study was to compare digital and conventional workflow procedures in the manufacturing of acrylic-based occlusal devices by assessing the cytotoxic potential of leakage products. METHODS: Specimens were manufactured by 3D printing (stereolithography and digital light processing), milling, and autopolymerization. Print specimens were also subjected to different post-curing methods. To assess biocompatibility, a human tongue epithelial cell line was exposed to material-based extracts. Cell viability was measured by MTT assay while Western blot assessed the expression level of selected cytoprotective proteins. RESULTS: Extracts from the Splint 2.0 material printed with DLP technology and post-cured with the Asiga Flash showed the clearest loss of cell viability. The milled and autopolymerized materials also showed a significant reduction in cell viability. However, by storing the autopolymerized material in dH2O for 12 h, no significant viability loss was observed. Increased levels of cytoprotective proteins were seen in cells exposed to extracts from the print materials and the autopolymerized material. Similarly to the effect on viability loss, storing the autopolymerized material in dH2O for 12 h reduced this effect. CONCLUSIONS/CLINICAL RELEVANCE: Based on the biocompatibility assessments, clinical outcomes of acrylic-based occlusal device materials may be affected by the choice of manufacturing technique and workflow procedures.

The capability approach in rehabilitation: developing capability care.

PURPOSE: To develop a multidisciplinary outpatient rehabilitation intervention for people with neuromuscular diseases (NMD) based on the capability approach: capability care for persons with NMD. MATERIALS AND METHODS: The development process is described using a framework of actions for intervention development. It has been an iterative process consisting of a design phase based on theoretical insights and project group discussions, and a refine phase involving input from relevant stakeholders. RESULTS: Multidisciplinary efforts have resulted in the development of capability care for rehabilitation of persons with NMD. It can focus both on facilitating and achieving functionings (beings and doings), as well as looking for alternative functionings that fulfil the same underlying value, thereby contributing to the persons' well-being. To facilitate a conversation on broader aspects that impact on well-being, persons with NMD receive a preparation letter and healthcare professionals are provided with guiding questions and practical tools to use. CONCLUSIONS: We have shown that it is possible to develop a healthcare intervention based on the capability approach. We hope that rehabilitation professionals will be encouraged to use capability care and that other medical professionals will be inspired to develop capability care in their respective fields. REGISTRATION: Registered at trialregister.nl NL8946.

The capability approach can be used for development of healthcare interventions.Capability care in rehabilitation focuses on realising what is of real value to the person.The capability approach and the ICF are complementary and can both be used in rehabilitation.

Interactive exploration of adverse events and multimorbidity in CKD.

BACKGROUND AND HYPOTHESIS: Persons with chronic kidney disease (CKD) are at increased risk of adverse events, early mortality, and multimorbidity. A detailed overview of adverse event types and rates from a large CKD cohort under regular nephrological care is missing. We generated an interactive tool to enable exploration of adverse events and their combinations in the prospective, observational German CKD (GCKD) study. METHODS: The GCKD study enrolled 5217 participants under regular nephrological care with an estimated glomerular filtration rate of 30-60 or >60 mL/min/1.73m2 and an overt proteinuria. Cardio-, cerebro- and peripheral vascular, kidney, infection, and cancer events, as well as deaths were adjudicated following a standard operation procedure. We summarized these time-to-event data points for exploration in interactive graphs within an R shiny app. Multivariable adjusted Cox models for time to first event were fitted. Cumulative incidence functions, Kaplan-Meier curves and intersection plots were used to display main adverse events and their combinations by sex and CKD etiology. RESULTS: Over a median of 6.5 years, 10 271 events occurred in total and 680 participants (13.0%) died while 2947 participants (56.5%) experienced any event. The new publicly available interactive platform enables readers to scrutinize adverse events and their combinations as well as mortality trends as a gateway to better understand multimorbidity in CKD: incident rates per 1000 patient-years varied by event type, CKD etiology, and baseline characteristics. Incidence rates for the most frequent events and their recurrence were 113.6 (cardiovascular), 75.0 (kidney), and 66.0 (infection). Participants with diabetic kidney disease and men were more prone to experiencing events. CONCLUSION: This comprehensive explorative tool to visualize adverse events (https://gckd.diz.uk-erlangen.de/), their combination, mortality, and multimorbidity among persons with CKD may manifest as a valuable resource for patient care, identification of high-risk groups, health services, and public health policy planning.

Phylogenomics and the rise of the angiosperms.

Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods1,2. A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome3,4. Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins5-7. However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes8. This 15-fold increase in genus-level sampling relative to comparable nuclear studies9 provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.

Trisomy silencing by XIST: translational prospects and challenges.

XIST RNA is heavily studied for its role in fundamental epigenetics and X-chromosome inactivation; however, the translational potential of this singular RNA has been much less explored. This article combines elements of a review on XIST biology with our perspective on the translational prospects and challenges of XIST transgenics. We first briefly review aspects of XIST RNA basic biology that are key to its translational relevance, and then discuss recent efforts to develop translational utility of XIST for chromosome dosage disorders, particularly Down syndrome (DS). Remarkably, it was shown in vitro that expression of an XIST transgene inserted into one chromosome 21 can comprehensively silence that chromosome and "dosage compensate" Trisomy 21, the cause of DS. Here we summarize recent findings and discuss potential paths whereby ability to induce "trisomy silencing" can advance translational research for new therapeutic strategies. Despite its common nature, the underlying biology for various aspects of DS, including cell types and pathways impacted (and when), is poorly understood. Recent studies show that an inducible iPSC system to dosage-correct chromosome 21 can provide a powerful approach to unravel the cells and pathways directly impacted, and the developmental timing, information key to design pharmacotherapeutics. In addition, we discuss prospects of a more far-reaching and challenging possibility that XIST itself could be developed into a therapeutic agent, for targeted cellular "chromosome therapy". A few rare case studies of imbalanced X;autosome translocations indicate that natural XIST can rescue an otherwise lethal trisomy. The potential efficacy of XIST transgenes later in development faces substantial biological and technical challenges, although recent findings are encouraging, and technology is rapidly evolving. Hence, it is compelling to consider the transformative possibility that XIST-mediated chromosome therapy may ultimately be developed, for specific pathologies seen in DS, or other duplication disorders.

Treatment Approaches for Altered Facial Expression: A Systematic Review in Facioscapulohumeral Muscular Dystrophy and Other Neurological Diseases.

Background: Facial weakness is a key feature of facioscapulohumeral muscular dystrophy (FSHD) and may lead to altered facial expression and subsequent psychosocial impairment. There is no cure and supportive treatments focus on optimizing physical fitness and compensation of functional disabilities. Objective: We hypothesize that symptomatic treatment options and psychosocial interventions for other neurological diseases with altered facial expression could be applicable to FSHD. Therefore, the aim of this review is to collect symptomatic treatment approaches that target facial muscle function and psychosocial interventions in various neurological diseases with altered facial expression in order to discuss the applicability to FSHD. Methods: A systematic search was performed. Selected studies had to include FSHD, Bell's palsy, Moebius syndrome, myotonic dystrophy type 1, or Parkinson's disease and treatment options which target altered facial expression. Data was extracted for study and patients' characteristics, outcome assessment tools, treatment, outcome of facial expression and or psychosocial functioning. Results: Forty studies met the inclusion criteria, of which only three studies included FSHD patients exclusively. Most, twenty-one, studies were performed in patients with Bell's palsy. Studies included twelve different therapy categories and results were assessed with different outcomes measures. Conclusions: Five therapy categories were considered applicable to FSHD: training of (non-verbal) communication compensation strategies, speech training, physical therapy, conference attendance, and smile restoration surgery. Further research is needed to establish the effect of these therapies in FSHD. We recommend to include outcome measures in these studies that cover at least cosmetic, functional, communication, and quality of life domains.

A guide to barley mutants.

BACKGROUND: Mutants have had a fundamental impact upon scientific and applied genetics. They have paved the way for the molecular and genomic era, and most of today's crop plants are derived from breeding programs involving mutagenic treatments. RESULTS: Barley (Hordeum vulgare L.) is one of the most widely grown cereals in the world and has a long history as a crop plant. Barley breeding started more than 100 years ago and large breeding programs have collected and generated a wide range of natural and induced mutants, which often were deposited in genebanks around the world. In recent years, an increased interest in genetic diversity has brought many historic mutants into focus because the collections are regarded as valuable resources for understanding the genetic control of barley biology and barley breeding. The increased interest has been fueled also by recent advances in genomic research, which provided new tools and possibilities to analyze and reveal the genetic diversity of mutant collections. CONCLUSION: Since detailed knowledge about phenotypic characters of the mutants is the key to success of genetic and genomic studies, we here provide a comprehensive description of mostly morphological barley mutants. The review is closely linked to the International Database for Barley Genes and Barley Genetic Stocks ( bgs.nordgen.org ) where further details and additional images of each mutant described in this review can be found.

External Validation of the 2023 Duke-International Society for Cardiovascular Infectious Diseases Diagnostic Criteria for Infective Endocarditis.

BACKGROUND: The 2023 Duke-International Society of Cardiovascular Infectious Diseases (ISCVID) criteria for infective endocarditis (IE) were introduced to improve classification of IE for research and clinical purposes. External validation studies are required. METHODS: We studied consecutive patients with suspected IE referred to the IE team of Amsterdam University Medical Center (from October 2016 to March 2021). An international expert panel independently reviewed case summaries and assigned a final diagnosis of "IE" or "not IE," which served as the reference standard, to which the "definite" Duke-ISCVID classifications were compared. We also evaluated accuracy when excluding cardiac surgical and pathologic data ("clinical" criteria). Finally, we compared the 2023 Duke-ISCVID with the 2000 modified Duke criteria and the 2015 and 2023 European Society of Cardiology (ESC) criteria. RESULTS: A total of 595 consecutive patients with suspected IE were included: 399 (67%) were adjudicated as having IE; 111 (19%) had prosthetic valve IE, and 48 (8%) had a cardiac implantable electronic device IE. The 2023 Duke-ISCVID criteria were more sensitive than either the modified Duke or 2015 ESC criteria (84.2% vs 74.9% and 80%, respectively; P < .001) without significant loss of specificity. The 2023 Duke-ISCVID criteria were similarly sensitive but more specific than the 2023 ESC criteria (94% vs 82%; P < .001). The same pattern was seen for the clinical criteria (excluding surgical/pathologic results). New modifications in the 2023 Duke-ISCVID criteria related to "major microbiological" and "imaging" criteria had the most impact. CONCLUSIONS: The 2023 Duke-ISCVID criteria represent a significant advance in the diagnostic classification of patients with suspected IE.

Towards a validated glossary of usability attributes for the evaluation of wearable robotic devices.

BACKGROUND: Despite technical advances in the field of wearable robotic devices (WRD), there is still limited user acceptance of these technologies. While usability often comes as a key factor influencing acceptance, there is a scattered landscape of definitions and scopes for the term. To advance usability evaluation, and to integrate usability features as design requirements during technology development, there is a need for benchmarks and shared terminology. These should be easily accessible and implementable by developers. METHODS: An initial set of usability attributes (UA) was extracted from a literature survey on usability evaluation in WRD. The initial set of attributes was enriched and locally validated with seven developers of WRD through an online survey and a focus group. The locally validated glossary was then externally validated through a globally distributed online survey. RESULTS: The result is the Robotics Usability Glossary (RUG), a comprehensive glossary of 41 UA validated by 70 WRD developers from 17 countries, ensuring its generalizability. 31 of the UA had high agreement scores among respondents and 27 were considered highly relevant in the field, but only 11 of them had been included as design criteria by the respondents. CONCLUSIONS: Multiple UA ought to be considered for a comprehensive usability assessment. Usability remains inadequately incorporated into device development, indicating a need for increased awareness and end-user perspective. The RUG can be readily accessed through an online platform, the Interactive Usability Toolbox (IUT), developed to provide context-specific outcome measures and usability evaluation methods. Overall, this effort is an important step towards improving and promoting usability evaluation practices within WRD. It has the potential to pave the way for establishing usability evaluation benchmarks that further endorse the acceptance of WRD.

Expand and extend postpartum Medicaid to support maternal and child health.

Most early maternal deaths are preventable, with many occurring within the first year postpartum (we use the terms "maternal" and "mother" broadly to include all individuals who experience pregnancy or postpartum and frame our recognition of need and policy recommendations in gender-neutral terms. To acknowledge limitations inherent in existing policy and the composition of samples in prior research, we use the term "women" when applicable). Black, Hispanic, and Native American individuals are at the most significant risk of pregnancy-related death. They are more commonly covered by Medicaid, highlighting likely contributions of structural racism and consequent social inequities. State-level length and eligibility requirements for postpartum Medicaid vary considerably. Federal policy requires 60 days of Medicaid continuation postpartum, risking healthcare coverage loss during a critical period of heightened morbidity and mortality risk. This policy position paper aims to outline urgent risks to maternal health, detail existing federal and state-level efforts, summarize proposed legislation addressing the issue, and offer policy recommendations for legislative consideration and future study. A team of maternal health researchers and clinicians reviewed and summarized recent research and current policy pertaining to postpartum Medicaid continuation coverage, proposing policy solutions to address this critical issue. Multiple legislative avenues currently exist to support and advance relevant policy to improve and sustain maternal health for those receiving Medicaid during pregnancy, including legislation aligned with the Biden-Harris Maternal Health Blueprint, state-focused options via the American Rescue Plan of 2021 (Public Law 117-2), and recently proposed acts (HR3407, S1542) which were last reintroduced in 2021. Recommendations include (i) reintroducing previously considered legislation requiring states to provide 12 months of continuous postpartum coverage, regardless of pregnancy outcome, and (ii) enacting a revised, permanent federal mandate equalizing Medicaid eligibility across states to ensure consistent access to postpartum healthcare offerings nationwide.

Many maternal deaths happen within the first year postpartum and can be prevented. Black, Hispanic, and Native American mothers are at more risk for many reasons, including unfair systems and insufficient healthcare coverage from government insurance (Medicaid). Rules for getting Medicaid can be very different across states and in postpartum compared to pregnancy. The US government only requires states to continue providing Medicaid for 60 days postpartum, after which it is up to each state. If mothers are required to re-qualify for Medicaid shortly after giving birth, they could lose healthcare when they are at more risk of dying or getting sick. In this policy position paper, a team of maternal health researchers and clinicians reviewed and summarized recent research and current laws related to postpartum Medicaid to propose future laws that could address these issues. Some proposed laws would expand Medicaid coverage during postpartum, but lawmakers have not recently discussed them. This position paper recommends that lawmakers (i) consider laws that require states to provide 12 months of postpartum healthcare coverage and (ii) have the US government make the same rules to qualify for postpartum Medicaid across all states.

Using the Seraph® 100 Microbind® Affinity blood filter under slow flow conditions through 18 G and 16 G central lines.

INTRODUCTION: The Seraph® 100 Microbind® Affinity blood filter (Seraph® 100) has been in use since 2019 for the treatment of fulminant or difficult to treat blood stream infections as an adjunct to pharmacotherapy. In 2020 the device received emergency use authorization by the US Food and Drug Administration for the treatment of critically ill COVID-19 patients with confirmed or imminent respiratory failure. Results of an international registry showed that the Seraph® 100 was operated under blood flow rates of 100-350 mL/min. As those conditions require a large bore central line, a dialysis catheter is currently considered indispensable to operate the Seraph® 100. The use of smaller catheter lumina has neither been evaluated in vitro nor in vivo. METHODS: In vitro pressure data before and after the Seraph® 100 at various blood pump rates (prepump line 16 G, postpump line 18 G) with saline and human plasma were obtained. Further, anecdotal flow and pressure data of two patients treated with the Seraph® 100 for a COVID-19 infection are reported. RESULTS: At a pump speed of 50 mL/min pre-Seraph® pressure using saline was -70 [-70 to -60] mm Hg. In comparison, using plasma pre-Seraph® pressure was lower at -120 [-120 to -105] mm Hg; p < 0.001 (t-test). The post-Seraph® pressure at 50 mL/min using saline of 120 [110-130] mm Hg was not different from plasma at 130 [120-140] mm Hg, p = 0.152 (t-test). Blood flow rates of 50 mL/min did not lead to preAP levels below -250 mm Hg in the two clinical cases. CONCLUSION: Seraph® 100 blood flow rate of 50 mL/min may be achieved using low flow vascular access, allowing to treat a blood volume 72 L in 24 h.

Successful percutaneous management of hypothenar hammer syndrome with thrombosuction and catheter-directed intra-arterial thrombolysis.

Hypothenar hammer syndrome (HHS) is a rare vascular disorder leading to ulnar artery thrombosis or aneurysm and causing acute or chronic limb ischemia. The optimal approaches to managing this condition lack a definitive consensus and are essentially empirical, typically necessitating conservative methods for symptomatic relief, with surgical intervention reserved for cases for which conservative measures prove inadequate or when acute limb ischemia ensues. Limited data are available on percutaneous management for this condition. We present the case of a 36-year-old male powerlifter who developed acute digital ischemia due to HHS in the left hand that was managed successfully through an innovative approach using antegrade left brachial artery access and combining percutaneous thrombosuction and intra-arterial thrombolysis. This comprehensive approach resulted in restoration of blood flow and resolution of acute limb ischemia. The patient was subsequently prescribed short-term anticoagulation therapy and remained symptom free at 3 months of follow-up. This innovative strategy challenges traditional surgical approaches in HHS management, underscoring the importance of using minimally invasive techniques as a promising alternative and highlighting potential avenues for further research.

Racial-Ethnic Differences in Receipt of Past-Year Health Care Services Among Suicide Decedents: A Case-Control Study.

OBJECTIVE: Suicide remains an urgent public health crisis. Although some sociodemographic characteristics are associated with greater suicide risk in the general population, it is unclear whether individuals utilizing health care in the United States have similar suicide incidence patterns. The authors examined whether race-ethnicity is associated with suicide death among patients seeking health care and investigated health care utilization patterns. METHODS: Data were collected from electronic health records and government mortality records for patients seeking health care across nine health care systems in the United States. Patients who died by suicide (N=1,935) were matched with patients in a control group (N=19,350) within each health care system. RESULTS: Patients who died by suicide were significantly more likely to be White, older, male, living in low-education areas, living in rural areas, or diagnosed as having mental health conditions or were significantly less likely to have commercial insurance (p<0.05). Among most racial-ethnic groups, those who died by suicide had a higher number of past-year mental health, primary care, and total health care visits; for American Indian/Alaska Native patients, the number of health care visits tended to be lower among suicide decedents. CONCLUSIONS: These findings suggest that higher past-year health care utilization was associated with increased likelihood of suicide death across several racial-ethnic groups. This observation underscores the need for identifying and managing suicide risk in health care settings, including outside of mental health visits, among most racial-ethnic groups.

Respiratory function in LAMA2-related muscular dystrophy and SELENON-related congenital myopathy, a 1.5-year natural history study.

INTRODUCTION: LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON(SEPN1)-related congenital myopathy (SELENON-RM) are rare neuromuscular diseases with respiratory impairment from a young age. Prospective natural history studies are needed for prevalence estimations, respiratory characterization, optimizing clinical care and selecting outcome measures for trial readiness. METHODS: Our prospective 1.5-year natural history study included spirometry (forced vital capacity (FVC); difference between upright and supine vital capacity (dVC)), respiratory muscle strength tests (sniff nasal inspiratory pressure (SNIP)) (age≥5 years), and diaphragm ultrasound (thickness; thickening; echogenicity; all ages). RESULTS: Twenty-six LAMA2-MD patients (M = 8, median 21 [9; 31] years) and 11 SELENON-RM patients (M = 8, 20 [10; 33] years) were included. At baseline, 17 (85 %) LAMA2-MD (FVC%: 59 % [33; 68]) and all SELENON-RM patients (FVC%: 34 % [31; 46]) had an impaired respiratory function (FVC%<80 %). Nine (35 %) LAMA2-MD and eight (73 %) SELENON-RM patients received mechanical ventilation at baseline, and two additional SELENON-RM patients started during follow-up. Contrarily to LAMA2-MD, SELENON-RM patients had severe diaphragm atrophy (diaphragm thickness z-score: 2.5 [-3.1; -2.1]) and dysfunction (diaphragm thickness ratio: 1.2 [1.0; 1.7]; dVC: 30 % [7.7; 41]). SNIP was low in both neuromuscular diseases and correlated with motor function. In SELENON-RM, respiratory function decreased during follow-up. CONCLUSION: The majority of LAMA2-MD and all SELENON-RM patients had respiratory impairment. SELENON-RM patients showed lower respiratory function which was progressive, more prevalent mechanical ventilation, and more severe diaphragm atrophy and dysfunction than LAMA2-MD patients. Spirometry (FVC%, dVC) and respiratory muscle strength tests (SNIP) are useful in clinical care and as outcome measure in clinical trials. CLINICAL TRIAL NUMBER: NCT04478981.

The Utility of Risk Factors to Define Complicated Staphylococcus aureus Bacteremia in a Setting With Low Methicillin-Resistant S. aureus Prevalence.

INTRODUCTION: Recommended duration of antibiotic treatment of Staphylococcus aureus bacteremia (SAB) is frequently based on distinguishing uncomplicated and complicated SAB, and several risk factors at the onset of infection have been proposed to define complicated SAB. Predictive values of risk factors for complicated SAB have not been validated, and consequences of their use on antibiotic prescriptions are unknown. METHODS: In a prospective cohort, patients with SAB were categorized as complicated or uncomplicated through adjudication (reference definition). Associations and predictive values of 9 risk factors were determined, compared with the reference definition, as was accuracy of Infectious Diseases Society of America (IDSA) criteria that include 4 risk factors, and the projected consequences of applying IDSA criteria on antibiotic use. RESULTS: Among 490 patients, 296 (60%) had complicated SAB. In multivariable analysis, persistent bacteremia (odds ratio [OR], 6.8; 95% confidence interval [CI], 3.9-12.0), community acquisition of SAB (OR, 2.9; 95% CI, 1.9-4.7) and presence of prosthetic material (OR, 2.3; 95% CI, 1.5-3.6) were associated with complicated SAB. Presence of any of the 4 risk factors in the IDSA definition of complicated SAB had a positive predictive value of 70.9% (95% CI, 65.5-75.9) and a negative predictive value of 57.5% (95% CI, 49.1-64.8). Compared with the reference, IDSA criteria yielded 24 (5%) false-negative and 90 (18%) false-positive classifications of complicated SAB. Median duration of antibiotic treatment of these 90 patients was 16 days (interquartile range, 14-19), all with favorable clinical outcome. CONCLUSIONS: Risk factors have low to moderate predictive value to identify complicated SAB and their use may lead to unnecessary prolonged antibiotic use.

Toward an Understanding of GSD5 (McArdle disease): How Do Individuals Learn to Live with the Metabolic Defect in Daily Life.

BACKGROUND: Glycogen storage disease type 5 (GSD) is an autosomal recessive inherited metabolic myopathy caused by a deficiency of the enzyme muscle glycogen phosphorylase. Individuals with GSD5 experience physical activity intolerance. OBJECTIVE: This patient-led study aimed to capture the daily life experiences of GSD5, with a focus on adapting to and coping with their physical activity intolerance. METHODS: An online survey was composed in close collaboration with patient organizations. It consisted of customized and validated questionnaires on demographics, general health and comorbidities, physical activity, psychosocial well-being and functioning, pain, fatigue and adapting to and coping with GSD5. RESULTS: One hundred sixty-two participants (16 countries) participated. The majority, n = 86 (69%) were from the Netherlands, USA or UK. We observed a high rate of misdiagnosis prior to GSD5 diagnosis (49%), surprisingly a relatively high proportion had not been diagnosed by DNA testing which is the gold standard. Being diagnosed had a strong impact on emotional status, daily life activities and important life choices. A large proportion had not received any rehabilitation (41%) nor medical treatment (57%) before diagnosis. Engagement in vigorous and moderate physical activity was reduced. Health related quality of life was low, most likely related to low physical health. The median Fatigue Severity Score was 4.3, indicating moderate to severe fatigue. Participants themselves had found various ways to adapt to and cope with their disability. The adaptations concerned all aspect of their life, including household chores, social and physical activities, and work. In addition to lack of support, participants reported limited availability of information sources. CONCLUSION: Participants have provided guidance for newly diagnosed people, including the advice to accept one's limited abilities and maintain an active lifestyle. We conclude that adequate counseling on ways of adapting and coping is expected to increase both health-related quality of life and physical activity.