bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyzwitterion-grafted decellularized bovine intercostal arteries as new substitutes of small-diameter arteries for vascular regeneration
Authors: Xia Yuan , Rao Zilong , Wu Simin , Huang Jiayao , Zhou Haiyun , Li Hanzhao , Zheng Hui , Guo Daxin , Quan Daping , Ou Jing-Song , Bai Ying , Liu Yunqi
Published: August 2024

Coronary artery bypass grafting is acknowledged as a major clinical approach for treatment of severe coronary artery atherosclerotic heart disease. This procedure typically requires autologous small-diameter vascular grafts. However, the limited availability of the donor vessels and associated trauma during tissue harvest underscore the necessity for artificial arterial alternatives. Herein, decellularized bovine intercostal arteries were successfully fabricated with lengths ranging from 15 to 30 cm, which also closely match the inner diameters of human coronary arteries. These decellularized arterial grafts exhibited great promise following poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) grafting from the inner surface. Such surface modification endowed the decellularized arteries with superior mechanical strength, enhanced anticoagulant properties and improved biocompatibility, compared to the decellularized bovine intercostal arteries alone, or even those decellularized grafts modified with both heparin and vascular endothelial growth factor. After replacement of the carotid arteries in rabbits, all surface-modified vascular grafts have shown good patency within 30 days post-implantation. Notably, strong signal was observed after α-SMA immunofluorescence staining on the PMPC-grafted vessels, indicating significant potential for regenerating the vascular smooth muscle layer and thereby restoring full structures of the artery. Consequently, the decellularized bovine intercostal arteries surface modified by PMPC can emerge as a potent candidate for small-diameter artificial blood vessels, and have shown great promise to serve as viable substitutes of arterial autografts.
From Europe to Caucasus: cryptic diversity and unexpected biogeographic history of a Western Palaearctic moss-inhabiting flea beetle (Chrysomelidae: Mniophila)
Authors: Damaška Albert František , Fikáček Martin , Daňková Klára , Čičovský Daniel , Smyčková Marie , Koštíř Vojtěch , Munclinger Pavel
Published: August 2024

The turbulent Tertiary and Quaternary history of Europe and the Ponto-Caucasus has had a strong impact on its biota, resulting in unusual patterns of speciation, diversification, and dispersal. Our study reveals the Late-Tertiary diversification and biogeographic history of Mniophila, a Western Palaearctic endemic moss-inhabiting flightless flea beetle distributed across Europe and the Ponto-Caucasus. We assembled samples across the whole range of the genus except Crimea. Based on a molecular phylogenetic analysis, we found that the diversification of Mniophila started in the Balkan Peninsula, and was followed by at least two independent colonizations of other parts of Europe. The Ponto-Caucasian species are all descendants of a single colonization from the Balkans, followed by species’ radiation. The Mniophila beetles are, therefore, one of the first-known cases of the colonization of the Caucasus from Europe. We integrated our DNA data with morphology, allowing us to uncover the cryptic diversity of Mniophila and to revise its European species. We describe Mniophila haveli sp. nov. from the Carpathians and Balkans, M. wroblewskiiWańkowicz, 1880 from Central Europe and the Balkans is restored as a valid species, and M. bosnica Apfelbeck, 1914 is newly recognized as a Dinaric endemic. We reveal an exceedingly large distribution range for M. muscorum (Koch, 1803), which is unusual for a flightless beetle.
Racial Disparities in Pulse Oximetry, in COVID-19 and ICU Settings
Authors: Reep Carmen A.T. , Fleuren Lucas M. , Heunks Leo , Wils Evert-Jan ,   on behalf of the National COVID Cohort Collaborative Consortium
Published: August 2024

OBJECTIVES (BACKGROUND):

This study aimed to assess the impact of race on pulse oximetry reliability, taking into account Spo
2 ranges, COVID-19 diagnosis, and ICU admission.

DESIGN:

Retrospective cohort study covering admissions from January 2020 to April 2024.

SETTING:

National COVID Cohort Collaborative (N3C) database, consisting of electronic health records from 80 U.S. institutions.

PATIENTS/SUBJECTS:

Patients were selected from the N3C database based on the availability of data on self-identified race and both pulse oximetry estimated Spo
2 and Sao
2. Subgroups included patients in ICU and non-ICU settings, with or without a diagnosis of COVID-19 disease.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

The agreement between Spo
2 and Sao
2 was assessed across racial groups (American Indian or Alaska Native, Asian, Black, Hispanic or Latino, Pacific Islander, and White). Each patient’s initial Sao
2 measurement was matched with the closest Spo
2 values recorded within the preceding 10-minute time frame. The risk of hidden hypoxemia (Spo
2 ≥ 88% but Sao
2 < 88%) was determined for various Spo
2 ranges, races, and clinical scenarios. We used a generalized logistic mixed-effects model to evaluate the impact of relevant variables, such as COVID-19, ICU admission, age, sex, race, and Spo
2, on the risk of hidden hypoxemia, while accounting for the random effects within each hospital. A total of 80,541 patients were included, consisting of 596 American Indian or Alaska Native, 2,729 Asian, 11,889 Black, 13,154 Hispanic or Latino, 221 Pacific Islander, and 51,952 White individuals. Discrepancies between Spo
2 and Sao
2 were observed across all racial groups, with the most pronounced bias in Black patients. Hidden hypoxemia rates were higher in Black patients across all Spo
2 subgroups, for all clinical scenarios. The odds of hidden hypoxemia were higher for Black and Hispanic or Latino patients and for those with COVID-19 disease.

CONCLUSIONS:

Race significantly impacts pulse oximetry reliability. Not only Black and Hispanic or Latino patients were at higher risk for hidden hypoxemia, but also those admitted with a COVID-19 diagnosis. Future in-depth explorations into the underlying causes and potential solutions are needed.
Association between phthalate exposure and sleep quality in pregnant women: Results from the Korean Children’s Environmental Health Study with repeated assessment of exposure
Authors: Lamichhane Dirga Kumar , Ha Eunhee , Bakian Amanda V. , Hong Yun-Chul , Lee Dong-Wook , Park Myung-Sook , Song Sanghwan , Kim Suejin , Park Hyunju , Kim Woo Jin , Bae Jisuk , Kim Hwan-Cheol ,   Ko-CHENS group
Published: August 2024

Background:

Evidence linking environmental toxicants to sleep quality is growing; however, these associations during pregnancy remain unclear. We examined the associations of repeated measures of urinary phthalates in early and late pregnancy with multiple markers of sleep quality among pregnant women.

Methods:

The study population included 2324 pregnant women from the Korean Children’s Environmental Health Study. We analyzed spot urine samples collected at two time points during pregnancy for exposure biomarkers of eight phthalate metabolites. We investigated associations between four summary phthalates (all phthalates: ∑Phthalates; di-(2-ethylhexyl) phthalate: ∑DEHP; phthalates from plastic sources: ∑Plastic; and antiandrogenic phthalates: ∑AA) and eight individual phthalates and self-reported sleep measures using generalized ordinal logistic regression and generalized estimating equations models that accounted for repeated exposure measurements. The models were adjusted for age, body mass index, education, gestational age, income, physical activity, smoking, occupation, chronic diseases, depression, and urinary cotinine levels.

Results:

Multiple individual phthalates and summary measures of phthalate mixtures, including ∑Plastic, ∑DEHP, ∑AA, and ∑Phthalates, were associated with lower sleep efficiency. To illustrate, every 1-unit log increase in ∑AA was associated with a reduction of sleep efficiency by 1.37 % (95% confidence interval [CI] = –2.41, –0.32). ∑AA and ∑Phthalates were also associated with shorter sleep duration and longer sleep latency. Associations between summary phthalate measures and sleep efficiency differed by urinary cotinine levels (P for subgroup difference < 0.05).

Conclusions:

Findings suggest that higher phthalate exposure may be related to lower sleep efficiency, shorter sleep duration, and prolonged sleep latency during pregnancy.
Unraveling the core and bridge menopausal symptoms of perimenopausal women: a network analysis
Authors: Zhang Tianyu , Wan Yinglu , Geng Li
Published: August 2024

Objective

Perimenopause is the period from the early menopausal transition to 12 months after the final menstrual period. The clustering of menopausal symptoms poses a challenge for perimenopausal management. Core symptoms are targets for interventions that can alleviate other related symptoms. Bridge symptoms are connectors that link related symptom clusters and can improve the effectiveness of interventions. This study aims to construct a network structure of menopausal symptoms and to identify core and bridge symptoms as a reference for future management.

Methods

Two hundred forty-two Chinese perimenopausal women were included in the survey. The structure and associations of the menopausal symptoms assessed by the Greene Climacteric Scale were analyzed using a network analysis. We generated the network structure graph using R software and checked its accuracy and stability.

Results

In the menopausal transition, the most prevalent symptoms were feeling tired or lacking in energy, excitability, and irritability. Sexual dysfunction was common among early postmenopausal women. Irritability (S = 7.16, C = 0.0167, B = 8) was a core symptom of the network. The depressive symptom cluster was a core symptom cluster, most of which have high centrality indices. Excitability (B = 6) was a bridge symptom connecting the anxiety and depressive symptom clusters.

Conclusions

Our study has highlighted the crucial significance of irritability and excitability in perimenopausal management. Overcoming the challenges of perimenopausal management requires the public to ameliorate the prejudice and stigma associated with emotional symptoms.
Screening Preadolescents for Keratoconus Risk Factors in a Low-Resource Setting
Authors: Masiwa Lynett Erita , Moodley Vanessa
Published: August 2024

Background:

Diagnosis of keratoconus (KC) involves the identification of corneal signs, refraction, and corneal imaging. The prevalence of KC ranges between 0.4 per 100,000 and 4,790, depending on geographical location and ethnicity. Diagnosis of KC should occur early for appropriate management with relatively affordable, accessible options to prevent visual impairment in low-income settings.

Method:

Written consent and assent were obtained from subjects before a questionnaire was administered to collate demographics, general and ocular history of subjects, and keratoconus risk factors. A novel scoring system was applied to identify subjects at a higher risk of developing KC and document KC risk factors prevalent in Harare using an informed risk score calculation.

Results:

Thousand one hundred fifty-three subjects aged between 6 and 12 years were seen. The prevalence of KC was found to be 626/100,000 in primary school children resident in Harare. Reduced visual acuity, vernal keratoconjunctivitis, itchy eyes, eye rubbing, and atopy are the most prevalent KC risk factors identified in this community. Informed risk score calculation proved valuable in the screening for KC.

Conclusion:

The prevalence of KC in primary school children in Harare is 626/100,000, which is relatively high. School-aged children stand to benefit from the early screening for KC based on evidence-based practices in the absence of advanced clinical instrumentation.
Clinical Dilemma—Ecthyma Gangrenosum Versus Sweet Syndrome
Authors: Rafique Soomal , Akram Mohammed Sami , Sundareshan Vidya
Published: August 2024

Sweet syndrome is associated with malignancy, drugs, and certain infections; its pathogenesis is not well understood. We report a case of a 30-year-old woman with stage IV breast cancer, who presented with worsening respiratory failure and erythematous skin lesions. Biopsy of the skin lesion was consistent with the Sweet syndrome; however, the culture grew Pseudomonas aeruginosa. The lesions healed without scarring when treated with antibiotics and steroids. This is the first case report of classic Sweet syndrome in association with P. aeruginosa.
Comparable efficacy and safety for bicuspid aortic valve stenosis patients undergoing transcatheter aortic valve replacement with balloon-expandable or self-expanding valves using Wei’s sizing method
Authors: Lee Yung-Tsai , Yin Wei-Hsian , Tsao Tien-Ping , Lee Kuo-Chen , Lin Huan-Chiu , Liu Chun-Ting , Hsiung Ming-Chon , Wei Jeng
Published: August 2024

Background:

The present study aimed to investigate whether proper sizing can improve the procedural and clinical outcomes of transcatheter aortic valve replacement (TAVR) with new-generation self-expanding valves (SEVs) and balloon-expandable valves (BEVs) for treating bicuspid aortic stenosis (BAS).

Methods:

We retrospectively evaluated consecutive patients who underwent TAVR with Sapien 3 valves (Edwards Lifesciences, Irvine, CA) or Evolut R/PRO valves (Medtronic, Minneapolis, MN) for severe BAS from 2017 to 2022. The primary endpoints were device success rate and major adverse cardiac and cerebral events (MACCEs), including mortality, nonfatal myocardial infarction or disabling stroke, transcatheter heart valve failure, or clinically relevant valve thrombosis during follow-up. Our team used a complementary approach of supraannular sizing in addition to the conventional annular sizing method (Wei’s method) to guide the TAVR procedures.

Results:

We recruited a total of 75 consecutive patients, of whom 43 (57%) were treated with BEVs from October 2017 to June 2021, and 32 (43%) were treated with SEVs from July 2021 to December 2022. Device success was similar between the BEV and SEV groups (93% vs 94%; p > 0.99), and no cases of annular rupture occurred in either group. Similar rates of moderate-to-severe paravalvular leak were observed in the BEV and SEV groups (5% vs 6%, p > 0.99). At a median follow-up of 464 days, the MACCE rates were comparable between the two groups. In multivariate analysis, the presence of previous percutaneous coronary interventions (hazard ratio: 5.43; p = 0.039) and New York Heart Association functional class III/IV heart failure at 30 days of follow-up after TAVR (hazard ratio: 9.90; p = 0.037) were independently associated with long-term MACCEs.

Conclusion:

Our results demonstrated comparable efficacy and safety for BAS patients undergoing TAVR using either BEVs or SEVs when using Wei’s sizing method.
Endoscopic Shelf Acetabuloplasty Combined With Hip Arthroscopic Labral Repair, Cam Osteoplasty, and Capsular Plication Enables Elite Athletes With Acetabular Dysplasia to Return to Sport: A Case Series
Authors: Shimizu Kenta , Murata Yoichi , Tsukamoto Manabu , Yamanaka Yoshiaki , Quinn Patrick , Sakai Akinori , Uchida Soshi
Published: August 2024

Objective:

To investigate clinical outcomes and return to sport timeline for athletes with acetabular dysplasia after endoscopic shelf acetabuloplasty (ESA).

Design:

A retrospective review.

Setting:

Wakamatsu Hospital of the University of Occupational and Environmental Health, Japan between 2012 and 2019.

Patients:

Fifteen elite athletes (median age: 20 years) of 253 patients undergoing ESA, arthroscopic labral repair/reconstruction, cam osteochondroplasty, and capsular plication. The mean follow-up period was 27.8 months after surgery.

Main Outcome Measures:

Patient-reported outcome scales (PROSs), including the modified Harris Hip Score, Nonarthritic Hip Score, International Hip Outcome Tool 12, Hip Outcome Score-Sports, and Vail Hip Score.

Results:

After ESA, all 15 elite athletes were able to return to sport effectively and compete at a preoperative level. The mean time between the operation and the first practice was 6.5 months, while the mean time between the ESA procedure and the first game was 9.6 months. Approximately 27.8 months after surgery, PROS outcomes improved significantly with no hips requiring emergency revision surgery at the final follow-up. At a mean of 47.1 months after surgery, 7 athletes decided to retire from their sport. Up to 71.1 months after surgery, the additional 8 patients continued to compete in their sport at an elite level.

Conclusions:

ESA enables elite athletes with acetabular dysplasia to return to competition at a mean of 9.6 months postsurgery. The ESA procedure is an effective and promising method of treating elite athletes with acetabular dysplasia.

Level of Evidence:

IV.
Quantification of high-density lipoprotein particle number by proton nuclear magnetic resonance: don’t believe the numbers
Authors: Vaisar Tomas , Heinecke Jay
Published: August 2024

Purpose of review

Proton nuclear magnetic resonance (NMR) can rapidly assess lipoprotein concentrations and sizes in biological samples. It may be especially useful for quantifying high-density lipoprotein (HDL), which exhibits diverse particle sizes and concentrations. We provide a critical review of the strengths and limitations of NMR for quantifying HDL subclasses.

Recent findings

Recent studies using NMR have shed light on HDL's role in various disorders, ranging from residual cardiovascular risk to host susceptibility to infection. However, accurately quantifying HDL particle number, size, and concentration (HDL-P) remains a challenge. Discrepancies exist between NMR and other methods such as gel electrophoresis, ion mobility analysis and size-exclusion chromatography in estimating the abundance of HDL species and the ratio of apolipoprotein A-I (APOA1) to HDL particles.

NMR is a low-cost method for quantifying HDL-P that is readily applicable to clinical and translational studies. However, inconsistencies between the results of NMR quantification of HDL-P and other independent methods hinder the interpretation of NMR results. Because proton NMR apparently fails to accurately quantify the sizes and concentrations of HDL, the relevance of such studies to HDL biology poses challenges. This limits our understanding of pathophysiological implications of HDL-P as determined by NMR, particularly in determining cardiovascular disease (CVD) risk.
Beta-blockers and calcium channel blockers
Authors: Sturdivant Tyler , Allen-Thomas Katrina , Allen-Tew Kristin
Published: August 2024

Nurses must know the difference between beta-blockers and calcium channel blockers, including understanding their mechanisms, indications, adverse reactions, and interactions, and how to monitor patient needs to promote patient care.
Longitudinal Transition of Symptom Cluster Profiles Among Community-Dwelling Older Adults With Heart Failure
Authors: Wang Zequan , Redeker Nancy S. , Walsh Stephen , Jeon Sangchoon , Kim Kyounghae , Conley Samantha , Tocchi Christine , Chyun Deborah
Published: August 2024

Background

Older adults with heart failure experience clustered symptoms. However, little is known about how symptom clusters transition over time.

Objectives

This study aimed to (a) identify the longitudinal transition of symptom cluster profiles over 8 years and (b) examine the associations between demographic and clinical factors and the transition between symptom cluster profiles over time.

Methods

We conducted a longitudinal secondary analysis of data from the Health and Retirement Study’s 2008, 2012, and 2016 surveys. We included participants with heart failure in the core data sets and their proxy respondents in the exit data sets. We included demographic and clinical variables as well as six symptoms (fatigue, shortness of breath, pain, swelling, depressive symptoms, dizziness) through physical health interviews. We used latent transition analysis and multinominal regressions to determine longitudinal profiles and explored the association between demographic and clinical factors and membership in symptom cluster profiles.

Results

Among 690 participants, we found four symptom cluster profiles (high burden, low burden, distressing, and respiratory-depressive distress). Participants in the low burden at baseline had the highest probability of transitioning to the respiratory-depressive distress profile. Participants in the respiratory-depressive distress at 4 years had the highest probability of transitioning to the high burden profile. Male sex, Black/African American race, smoking, and comorbidities were associated with the increased odds of transiting from the low symptom burden to the high symptom burden profile.

Discussion

Symptom cluster profile memberships were stable over an 8-year period. However, symptom cluster profiles are changeable and deteriorate over time. Identifying predictive factors enables targeted interventions for those at highest risk.
COVID-19 Pandemic Increases in Nursing-Sensitive Quality Indicators
Authors: Lake Eileen T. , Pascale Angela , Warshawsky Nora E. , Smith Jessica G. , Staiger Douglas , Rogowski Jeannette A.
Published: August 2024

Background

The pandemic profoundly stressed practicing nurses and could have thereby affected trends in nursing-sensitive quality indicators (NSIs), measures that detect changes in patient health status directly affected by nursing care.

Objectives

The aim of the study was to determine if NSIs have worsened in response to the pandemic and then returned to prepandemic levels using data from 2019 through 2022.

Methods

We conducted a cross-sectional descriptive study of annual trends, examining unit data from the National Database of Nursing Quality Indicators (NDNQI) from 2019 through 2022 for five indicators: rates of falls, central line-associated bloodstream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), hospital-acquired pressure injuries (HAPI), and ventilator-associated events (VAE). The NDNQI is the largest repository of nursing quality indicators, which are derived from patient-level events, reported at the nursing unit level, and submitted quarterly by over 2,000 member hospitals. Adult medical-surgical or critical care inpatient nursing units with complete data for the 4 years were included, with samples ranging from 456 to 5,818 nursing units in 2,346 hospitals. Analysis of variance was conducted by comparing the 2019 rates to each subsequent year.

Results

In decreasing order of prevalence, the mean prepandemic rates were 6.58 VAE per 1,000 ventilator days (critical care only), 2.41 HAPI per 1,000 device days, 2.20 falls per 1,000 patient days, 0.96 CAUTI per 1,000 catheter days, and 0.68 CLABSI per 1,000 central line days for medical-surgical and critical care units combined. The rates for all five nurse-sensitive indicators increased significantly beginning in 2020 and have begun to decline but have not returned to baseline by 2022. The maximum rate was observed in 2020 for falls and 2021 for the remaining indicators. These increases to the maximum ranged from a 12% increase in CAUTI to 49% for CLABSI.

Discussion

NSIs increased during the pandemic and are now returning to baseline. The pandemic underscored the importance of nursing practice. The pandemic’s enduring negative effects on the nursing workforce must be addressed to preserve patient safety.
Tumor-infiltrating T-Lymphocyte immunity-related immune tolerance and anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy for advanced hepatocellular carcinoma
Authors: Hu Lingzhen , Wang Zongren , Liao Yang , Jiang Xiaomeng , Lian Huojun , Lin Zhuoying
Published: August 2024

Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma (HCC) whose treatment options are limited. However, the long-term patient response to drugs and the survival outcomes remain a concern. With increasing exploration of the HCC microenvironment, particularly in terms of T lymphocyte immunity, a new era of immunomolecular targeted therapy, based on molecular signaling, has arrived for advanced HCC. In the study of immune tolerance of the intrinsic HCC microenvironment, we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors, such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy, have improved clinical outcomes in some patients with advanced HCC. Furthermore, various combination therapies have been investigated, and HCC types have been categorized into different types based on anti–programmed cell death protein 1 (PD-1)/ligand of programmed cell death protein 1 (PD-L1) treatment. In this paper, we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC. We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy. Thereafter, we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors, anti–T lymphocyte–related signaling pathways in HCC, and other anti-CD8+T cell immune checkpoints. In this way, this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC, in order to provide better individualized treatments for patients with advanced HCC.
Studies on surgical methods for sporadic micromedullary thyroid carcinoma
Authors: Ni Yaqiong , Hou Xiaofeng , Yao Wei , Wang Tao , Liu Qinjiang
Published: August 2024

Background

To observe the changes in serum calcitonin levels after application of different surgical methods for primary medullary thyroid microcarcinoma (MTMC) and explore a more reasonable surgical method.

Methods

A retrospective analysis of 36 patients with MTMC, 16 in group A and 20 in group B, was performed. In group A, tumors were single and confined to the thyroid lobe, and thyroid lobectomy with isthmusectomy was performed. In group B, tumors were in the isthmus or invaded the thyroid gland, or there were multiple foci in bilateral lobes, and patients with primary foci underwent total thyroidectomy. The median follow-up time was 3.6 years. Clinical and pathological characteristics and changes in serum calcitonin (CTn) and carcinoembryonic antigen levels after the surgery were compared between the 2 groups.

Results

The difference in the biochemical cure rate after surgery was statistically significant between patients with preoperative serum calcitonin levels <150 pg/mL and ≥150 pg/mL (P < 0.01). No significant differences in the biochemical cure rates and serum calcitonin levels were noted at different time points after surgery between group A and group B (P > 0.05). One recurrence and metastasis were observed in each group after surgery.

Conclusions

After performing different surgical methods for the primary foci of MTMC, the changes in serum calcitonin and carcinoembryonic antigen levels are similar. Especially for patients with single foci confined to the thyroid lobe without lateral cervical lymph node metastasis and with serum calcitonin levels <150 pg/mL, the unilateral thyroid lobectomy with isthmectomy can achieve the same therapeutic effect and biochemical cure rate as total thyroidectomy.
Perceptions of telemedicine amongst physical medicine and rehabilitation patients and healthcare providers
Authors: Gilmer Gabrielle , Sowa Gwendolyn
Published: August 2024

Objective

Our purpose was to assess perceptions of telemedicine amongst physical medicine & rehabilitation (PM&R) patients and healthcare providers.

Design

A 28-question online survey was conducted. Patients had to be 18 years or older who used telemedicine for a PM&R visit. Providers had to be a board-certified PM&R provider who has used telemedicine in their practice.

Results

Sixty-eight patients and forty-six providers completed the survey. Patients and providers reported an intention to continue using telemedicine, regardless of insurance coverage/reimbursement. Patients and providers reported circumstances, such as needing a physical examination or a first-time visit, as being preferable for an in-person visit. Patients who were younger or a caretaker were more likely to report being willing to change providers if telemedicine was no longer offered than older or non-caretaker patients. Patients who made less than $30,000 annually or who did not own a car were more likely to report comfortability with telemedicine than patients who made more than $30,000 annually or who owned a car.

Conclusion

Telemedicine will continue as a staple of PM&R healthcare and is a particularly important resource for patients who are younger, caretakers, make less than $30,000 annually, or do not own a car.
A Systematic Review on Conditions Before and After Training of Teamwork Competencies and the Effect on Transfer of Skills to the Clinical Workplace
Authors: Wittig Johannes , Krogh Kristian , Blanchard Erin E. , Xing Kuan , Kushner Jodi , Bichmann Anna , Flin Rhona , Brazil Victoria , Goldhaber-Fiebert Sara N. , Paige John , Lauridsen Kasper G.
Published: August 2024

Summary statement

We conducted a systematic review to assess if any condition before- or after simulation-based training of teamwork competencies for healthcare professionals affects learning or transfer of skills to the clinical environment.

We searched CINAHL, Medline, and Embase for studies published between January 1, 2011, and July 10, 2023. We screened 13,149 abstracts and 335 full texts, of which 5 studies were included. We included primary studies with and without a comparator published in English. We assessed risk of bias using the ROBINS-I tool before narrative synthesis. All studies were observational and reported heterogeneous conditions such as posters, coaching, and leadership support initiatives. Very low certainty evidence suggested that implementing conditions in the clinical environment such as coaching, wider communication of learning objectives, or leadership initiatives could be considered to facilitate the transfer of skill to the clinical environment. Funding: Society for Simulation in Healthcare. Prospero registration: CRD42022320721.
Genetic and antigenic characterization of two diarrhoeic dominant rotavirus A genotypes G3P[12] and G14P[12] circulating in the global equine population
Authors: Uprety Tirth , Soni Shalini , Sreenivasan Chithra , Hause Ben M. , Naveed Ahsan , Ni Shuisong , Graves Amy J. , Morrow Jennifer K. , Meade Nathan , Mellits Kenneth H. , Adam Emma , Kennedy Michael A. , Wang Dan , Li Feng
Published: August 2024

Equine rotavirus species A (ERVA) G3P[12] and G14P[12] are two dominant genotypes that cause foal diarrhoea with a significant economic impact on the global equine industry. ERVA can also serve as a source of novel (equine-like) rotavirus species A (RVA) reassortants with zoonotic potential as those identified previously in 2013–2019 when equine G3-like RVA was responsible for worldwide outbreaks of severe gastroenteritis and hospitalizations in children. One hurdle to ERVA research is that the standard cell culture system optimized for human rotavirus replication is not efficient for isolating ERVA. Here, using an engineered cell line defective in antiviral innate immunity, we showed that both equine G3P[12] and G14P[12] strains can be rapidly isolated from diarrhoeic foals. The genome sequence analysis revealed that both G3P[12] and G14P[12] strains share the identical genotypic constellation except for VP7 and VP6 segments in which G3P[12] possessed VP7 of genotype G3 and VP6 of genotype I6 and G14P[12] had the combination of VP7 of genotype G14 and VP6 of genotype I2. Further characterization demonstrated that two ERVA genotypes have a limited cross-neutralization. The lack of an in vitro broad cross-protection between both genotypes supported the increased recent diarrhoea outbreaks due to equine G14P[12] in foals born to dams immunized with the inactivated monovalent equine G3P[12] vaccine. Finally, using the structural modelling approach, we provided the genetic basis of the antigenic divergence between ERVA G3P[12] and G14P[12] strains. The results of this study will provide a framework for further investigation of infection biology, pathogenesis and cross-protection of equine rotaviruses.
Systematic review and meta-analysis to estimate the burden of non-fatal and fatal overdose among people who inject drugs living in the U.S. and comparator countries: 2010 – 2023
Authors: Shealey Jalissa Y. , Hall Eric W. , Pigott Therese D. , Rosmarin Lexi , Carter Anastasia , Cade Chiquita , Luisi Nicole , Bradley Heather
Published: August 2024

Background

People who inject drugs (PWID) have high risk for overdose, but there are no current estimates of overdose rates in this population. We estimated the rates of non-fatal and fatal overdose among PWID living in the U.S. and comparator countries (Canada, Mexico, United Kingdom, Australia), and ratios of non-fatal to fatal overdose, using literature published 01/01/2010 – 09/29/2023.

Methods

PubMed, PsychInfo, Embase, and ProQuest databases were systematically searched to identify publications reporting prevalence or rates of recent (past 12 months) non- fatal and fatal overdose among PWID. Non-fatal and fatal overdose rates were meta-analyzed using random effects models. Risk of bias was assessed using an adapted quality assessment tool, and heterogeneity was explored using sensitivity analyses.

Results

Our review included 143 records, with 58 contributing unique data to the meta- analysis. Non-fatal and fatal overdose rates among PWID in the U.S. were 32.9 per 100 person- years (PY) (95% CI: 26.4 – 40.9; n=28) and 1.7 per 100 PY (95% CI: 0.9 – 3.2; n=4), respectively. Limiting the analysis to data collected after 2016 yielded a non-fatal rate of 41.0 per 100 PY (95% CI: 32.1 – 52.5; n=16) and a fatal rate of 2.5 per 100 PY (95% CI: 1.4 – 4.3; n=2) in the U.S. An estimated 5% of overdoses among PWID in the U.S. result in death. Among the analyzed countries, Australia had the lowest non-fatal and fatal overdose rates and the largest ratio of non-fatal to fatal overdose.

Conclusion

Findings demonstrate substantial burden of non-fatal and fatal overdose among PWID in the U.S. and comparator countries. Scale-up of interventions that prevent overdose mortality and investments in PWID health research are urgently needed.
Reduced response to SARS-CoV-2 vaccination is associated with impaired immunoglobulin class switch recombination in SLE patients
Authors: Montamat Guillem , Meehan Claire E. , Bradford Hannah F. , Yıldırım Reşit , Guimarães Francisca , Johnson Marina , Goldblatt David , Isenberg David A. , Mauri Claudia
Published: August 2024

Objective

Systemic Lupus Erythematosus (SLE) patients exhibit B-cell abnormalities. Although there are concerns about reduced antibody responses to SARS-CoV-2 vaccines, detailed data on B-cell-specific responses in SLE remain scarce. Understanding the responsiveness to novel vaccine-antigens, and boosters number, is important to avoid unnecessary prolonged isolation of immunocompromised individuals. We assessed humoral and antigen-specific B-cell subset responses, including changes in isotype switching, prior to and after several doses of SARS-CoV-2 vaccines.

Methods

Blood samples were obtained prior to and after SARS-CoV-2 vaccination from cross-sectional and longitudinal cohorts of previously uninfected patients with SLE (n=93). Healthy participants receiving SARS-CoV-2 vaccines were recruited as controls (n=135). We measured serum antibody titres, their neutralizing capacity, and vaccine-specific memory B cells subsets.

Results

Impaired IgG, IgA, and neutralizing responses against the original and various SARS-CoV-2 variants were observed following two doses of vaccine in SLE patients. Follow-up booster doses increased humoral responses compared to baseline, but they remained lower, with poorer neutralisation capacity against most strains, compared to healthy individuals after three or more doses. Analysis of memory B-cells subsets in SLE patients revealed an increase of SARS-CoV-2-specific isotype unswitched IgM+over SARS-CoV-2-specific isotype switched IgG+/IgA+memory B-cells compared to healthy individuals. Culturing healthy naive B-cells with high levels of IFNα, a hallmark of SLE pathogenesis, prevented B-cells from switching to IgG under IgG-polarizing conditions.

Conclusion

SLE patients’ protection against SARS-CoV-2 is overall impaired compared to healthy individuals and is associated with a class switch defect possibly due to chronic exposure of B-cells to IFNα.

GRAPHICAL ABSTRACT
Reduced Expression of MTSS1 Increases Sarcomere Number and Improves Contractility in Select Forms of Monogenic DCM
Authors: Kleppe Hannah , Budan Anastasia , Zhang Luke , Majetic Marie , Shenwai Reva , Levinson Alan , Cisne-Thompson Olga , Farshidfar Farshad , Tsui Jonathan , Figarska Sylwia , Hoey Tim , Priest James , Slater Rebecca
Published: August 2024

Background

The I-bar protein MTSS1 is a known modifier of heart failure and contractile phenotypes but its role in modulating contractile dysfunction in genetic forms of Mendelian dilated cardiomyopathy (DCM) is not known.

Methods

The potential role of cardiac MTSS1 in TTN DCM was explored using time-to-event models in longitudinal human datasets. Using induced siRNA and mutant forms of pluripotent stem cell cardiomyocytes (iPSC-CMs) the impact of siRNA knockdown of MTSS upon sarcomere and Cardiomyocyte biology was assessed via quantitative high-content microscopy, and the impact and mechanism of MTSS1 knockdown upon contractility was assessed using engineered heart tissues (EHTs).

Results

Amongst individuals affected with TTN DCM, a variant conferring lower cardiac levels of MTSS1 was associated with significantly improved event-free survival from cardiovascular death or heart transplant (HR 0.29, p=0.0016). Knockdown of MTSS1 by siRNA significantly improved the appearance of iPSC-CM models of TTN (p=2.9e-06), CSRP3 (p=3.1e-14), and RBM20 (p=4.4e-04) DCM as assessed by quantitative microscopy. Correspondingly, siRNA knockdown of MTSS1 increased contractility in EHT models of TTN DCM (p=0.003), CSRP3 DCM (p=0.008), and RBM20 DCM (p<2e-16). Across all genetic backgrounds, knockdown of MTSS1 was observed to increase the number of sarcomeres (p<0.0001), and in co-immunoprecipitation experiments MTSS1 physically interacts with MYO18A a key determinant of early sarcomere formation. Knockdown of MTSS1 resulted in increased transcription of MYH7 (0.29 log2FC, p=2.9e-06) along with other sarcomere genes.

Conclusions

In iPSC-CMs Knockdown of MTSS1 by siRNA increased number of sarcomeres and was observed to increase twitch force in select in vitro models, and may suggest MTSS1 plays a previously unrecognized role in modulating sarcomere production. Human observational and iPSC-CM experimental data supports the hypothesis that reduced expression of MTSS1 may be beneficial in Mendelian DCM caused by TTN, RBM20, and CSRP3.
Investigating chromosomal radiosensitivity in inborn errors of immunity: insights from DNA repair disorders and beyond
Authors: Beyls Elien , Duthoo Evi , Backers Lynn , Claes Karlien ,   RAPID clinicians, De Bruyne Marieke , Pottie Lore , Bordon Victoria , Bonroy Carolien , Tavernier Simon J , Claes Kathleen BM , Vral Anne , Baeyens Ans , Haerynck Filomeen
Published: August 2024

Human inborn errors of immunity (IEI) represent a diverse group of genetic disorders affecting the innate and/or adaptive immune system. Some IEI entities comprise defects in DNA repair factors, resulting in (severe) combined immunodeficiencies, bone marrow failure, predisposition to malignancies, and potentially result in radiosensitivity (RS). While other IEI subcategories such as common variable immunodeficiency (CVID) and immune dysregulation disorders also associate with lymphoproliferative and malignant complications, the occurrence of RS phenotypes in the broader IEI population is not well characterized. Nonetheless, identifying RS in IEI patients through functional testing is crucial to reconsider radiation-related therapeutic protocols and to improve overall patient management. This study aimed to investigate chromosomal RS in a diverse cohort of 107 IEI patients using the G0 cytokinesis-block micronucleus (MN) assay. Our findings indicate significant variability in RS across specific genetic and phenotypical subgroups. Severe RS was detected in all ataxia-telangiectasia (AT) patients, a FANCI deficient and ERCC6L2 deficient patient, but not in any other IEI patient included in this cohort. Age emerged as the single influencing factor for both spontaneous and radiation-induced MN yields, while the manifestation of additional clinical features, including infection susceptibility, immune dysregulation, or malignancies did not associate with increased MN levels. Our extensive analysis of RS in the IEI population underscores the clinical importance of RS assessment in AT patients and supports RS testing in all IEI patients suspected of having a DNA repair disorder associated with radiosensitivity.
What do the Welsh public understand about NHS dental services, what do they think they could look like, and what are their priorities? A qualitative study
Authors: Joseph-Williams Natalie , Sha’aban Abubakar , Mazzaschi Francesca , Cope Anthony
Published: August 2024

NHS General Dental Services in Wales are undergoing reform. To ensure dental services meet the needs of those who use them, we explored what the public think these services could look like and what their priorities for are.

The aim of this study was to consult with the Welsh public to understand their views on NHS dental services to help inform dental reform plans in Wales. Specific objectives were to explore:

What do the public think Welsh NHS dental services could look like?

What do the public understand about dental services and the dental team?

What are their views on skill mix in dentistry?

What are their attitudes towards and needs for oral health self-management?

What are their priorities for dental care services in Wales?

We used qualitative methods (interviews and focus group style workshops) across two phases between November 2023 and May 2024 to explore the study objectives. Thematic analyses were performed on the data to identify key themes. Forty four participants with diverse backgrounds from all seven local health boards in Wales took part.
Extracting and calibrating population evidence of variant pathogenicity using biobank data
Authors: Bhat Vineel , Yu Tian , Brown Lara , Pejaver Vikas , Lebo Matthew , Harrison Steven , Cassa Christopher A.
Published: August 2024

Advancing genomic medicine relies on our ability to assess the phenotypic impacts of rare germline variants, which remains challenging even in highly sequenced monogenic disease genes. Here, we evaluate the use of population sequencing data from the UK Biobank to identify variants which alter disease risk, focusing on familial hypercholesterolemia (FH), hereditary breast and ovarian cancer syndrome (HBOC), and Lynch syndrome (CRC). We model evidence of pathogenicity from population data at the variant level, and demonstrate that odds ratios generated from population cohort data can significantly separate ClinVar pathogenic and benign variants in FH genes (p = 4.5x10-19), HBOC genes (p = 2.5x10-39), and CRC genes (p = 7.6x10-16). Next, to make use of this information in variant assessment, we calibrate population-based odds ratios (ACMG/AMP PS4) at the gene level, and find that they reach ‘strong’ or ‘very strong’ evidence of pathogenicity in 8 of 11 genes, as well as in aggregate. Among participants with a rare variant in these 8 genes, 4.3% (N = 2,456) have a Variant of Uncertain Significance (VUS) or variant not yet observed in ClinVar with strong population evidence of pathogenicity that could inform variant interpretation for a related disorder. In three genes with functional assays, we combine this population evidence with computational, contextual, and experimental evidence. Notably, 12.4% ofLDLRVUS seen in participants have sufficient evidence to be classified as pathogenic. This method offers a scalable approach to integrate evidence of pathogenicity from population data.

Highlights

Uses population data to identify rare coding variants which increase risk of clinically actionable phenotypes.

Population-based disease odds ratios accurately distinguish ClinVar pathogenic and benign variants.

Calibrates odds ratios at the gene level to identify their strength of evidence for variant classification.

Combines various evidence types to reclassify a substantial fraction of variants of uncertain significance.
Determining Cost-Saving Risk Thresholds for Statin Use
Authors: Gandjour Afschin
Published: August 2024

Background

Statins are widely prescribed to reduce cholesterol levels and decrease the risk of cardiovascular diseases. This study aims to determine cost-saving risk thresholds for statin use in Germany to inform better prescription practices and healthcare policies.

Methods

A decision-analytic approach was employed, using secondary data to compare statin use with no statin use from the perspective of German sickness fund insurees. The analysis focused on cost savings from avoided cardiovascular (CV) events, translating these avoided events into net savings after accounting for treatment costs and potential side effects. The study considered the German adult population insured by sickness funds and used a lifetime horizon for the analysis.

Results

The maximum number needed to treat (NNT) to achieve cost savings over 10 years was found to be 40, leading to a minimum risk threshold for savings of 9.8%. It was estimated that approximately 22% of the adult population in Germany has a 10-year CV risk of ≥9.8%, potentially avoiding between 307,049 and 705,537 CV events over 10 years, with net population savings of approximately €18 billion.

Conclusions

The current official threshold for statin prescription in Germany, set at a 20% 10-year risk, is too stringent. Lowering the threshold to 9.8% could significantly increase the number of patients benefiting from statin therapy, reducing CV events and generating substantial cost savings. These findings suggest that adjustments to prescription guidelines could improve cardiovascular outcomes and economic efficiency within the German healthcare system.
Movement-responsive deep brain stimulation for Parkinson’s Disease using a remotely optimized neural decoder
Authors: Dixon Tanner C. , Strandquist Gabrielle , Zeng Alicia , Fraczek Tomek , Bechtold Raphael , Lawrence Daryl , Ravi Shravanan , Starr Philip A. , Gallant Jack L. , Herron Jeffrey A. , Little Simon J.
Published: August 2024

Deep brain stimulation (DBS) has garnered widespread use as an effective treatment for advanced Parkinson’s Disease (PD). Conventional DBS (cDBS) provides electrical stimulation to the basal ganglia at fixed amplitude and frequency, yet patients’ therapeutic needs are often dynamic with residual symptom fluctuations or side-effects. Adaptive DBS (aDBS) is an emerging technology that modulates stimulation with respect to real-time clinical, physiological, or behavioral states, enabling therapy to dynamically align with patient-specific symptoms. Here, we report a novel aDBS algorithm intended to mitigate movement slowness by delivering targeted stimulation increases during movement using decoded motor signals from the brain. Compared to cDBS and a control algorithm that decreases stimulation during movement, our approach demonstrates enhanced clinical efficacy, with improvements in movement speed, reduced dyskinesia, and better patient-reported therapeutic quality. Furthermore, we demonstrate proof-of-principle of a machine learning pipeline capable of remotely optimizing aDBS parameters in a home setting. This work illustrates the potential of movement-responsive aDBS as a new therapeutic approach and highlights how machine learning assisted programming can simplify optimization to facilitate translational scalability.