bluuebunny/crossref_metadata_2025 huggingface dataset:
E082 A review of the development of gangrene in patients with systemic lupus erythematosus: a 44-year follow-up study
Authors: Rua Joana , Isenberg David
Published: April 2023

Background/Aims

Gangrene is a well-recognised complication of diabetes, peripheral arterial disease, frostbite and meningococcal disease amongst other conditions but is rare in patients with systemic lupus erythematosus [SLE]. Most reports describe individual patients and the prevalence in cohorts is very scarce. In 2008, our group reported five patients who had developed digital gangrene and two patients with “near gangrene”. We reviewed all the SLE patients seen in our lupus clinic between January 1978 and June 2022.The main goal was to address the prevalence and identify the possible trigger factors, aiming to find common clinical and serological features. We have also reviewed the acute and long-term management of gangrene in these patients as well as their long-term outcome.

Methods

We reviewed 820 patients with SLE attending the SLE Clinic in our UK tertiary referral center, followed up over 44 years, assessing demographics, clinical and serological features, treatment in the acute phase, outcome and long-term management.

Results

Eight out of 820 patients (0.97%) have developed gangrene. The age of onset of disease ranged from 12 to 26 years (mean 17.5 years, SD 4.609). The first episode of gangrene ranged from between presentation to 27 years after SLE onset, with a mean duration of SLE at the onset of the gangrene of 15.5 years (SD 11.711). All had active SLE at the time of critical peripheral ischaemia and anti-phospholipid (PL) antibodies were present in five out of the eight reported patients. The acute treatment was intravenous (IV) iloprost infusions with antiphospholipid-positive patients being anti-coagulated, most staying on long term anticoagulation therapy. The possible identified triggers (such as infection and cancer) were treated accordingly. Two patients did not respond to the initial treatment and needed further immunosuppression. All of these patients suffered digit loss.

Conclusion

Gangrene is a rare complication of SLE in patients with active disease but potentially able to cause severe damage. Anti-phospholipid antibodies are overrepresented in these patients but infection and cancer are other possible contributors. Anticoagulation therapy, steroids and iloprost are the first line therapy but in non-responders further immunosuppression may be needed to stop the evolution of gangrene.

Disclosure

J. Rua: None. D. Isenberg: Honoraria; Servier, Anges, Astrazeneca, UCB, Eli Lilly.
Magnetic resonance imaging characteristics in patients with psoriatic arthritis and axial manifestations from the MAXIMISE cohort
Authors: Baraliakos Xenofon , Pournara Effie , Coates Laura C , Navarro-Compán Victoria , Blanco Ricardo , O’Brien Eamonn , Schulz Barbara , Landewe Robert
Published: April 2023

Objective

The current analysis of the MAXIMISE trial was conducted to investigate the presence of post-inflammatory and degenerative spinal changes and inflammatory changes in spinal processes identified in baseline MRIs and their potential for predicting differential treatment effects in a cohort of PsA patients with axial manifestations.

Methods

Baseline spinal MRIs from the MAXIMISE trial were re-read to identify additional inflammatory (spinal process), post-inflammatory, and degenerative changes, and investigate the differential treatment effect of these imaging features using logistic regression modelling.

Results

In addition to bone marrow oedema assessed at primary analysis, spinal process inflammation and post-inflammatory changes evaluated by FAt Spondyloarthritis Spine Score were documented in 11.1% and 20.2% patients, respectively. At least one type of degenerative change was noted in 64% patients, with Pfirrmann grade ≥3 (51.1%) being the most common. Combining primary and re-read MRI findings, 67.1% of patients presented with inflammatory or post-inflammatory changes while 21.2% had degenerative changes alone. Although not statistically significant, post-inflammatory changes were associated with a trend for better efficacy outcomes in terms of ASAS20, ASAS40 and BASDAI50 responses; a trend for worse outcomes was observed in the presence of degenerative changes.

Conclusion

The current analysis revealed the occurrence of additional inflammatory and post-inflammatory changes suggestive of axial PsA (axPsA) and a trend for better clinical outcomes for patients treated with secukinumab. These results elucidate the imaging characteristics and improve our current understanding of axPsA thereby supporting the interpretation of future trials.

Trial registration

ClinicalTrials.gov, NCT02721966.
PATIENT DOSIMETRY SURVEY OF PEDIATRIC DIAGNOSTIC AND THERAPEUTIC CARDIAC CATHETERISATION IN JAPAN
Authors: Ishibashi Toru , Takei Yasutaka , Kato Mamoru , Yamashita Yukari , Tsukamoto Atsuko , Matsumoto Kazuma , Sakamoto Hajime , Masuda Takanori , Miyazaki Osamu
Published: April 2023

To propose reference values for air-kerma at the reference point (Ka,r), air-kerma area product (PKA), fluoroscopy time (FT) and number of cine images (CI) for four age groups in Japan, a nationwide questionnaire was posted to 132 pediatric catheterisation of certified facility in Japan, using the conventional post system, to which 43 facilities responded. For diagnostic cardiac angiography, reference values were as follows: Ka,r: 86, 102, 165 and 264 mGy; PKA: 9.3, 9.5, 16 and 34 Gy.cm2; FT: 33, 29, 26 and 30 min and CI: 1904, 1966, 2405 and 1871 images. For therapeutic cardiac angiography, reference values were as follows: Ka,r: 107, 163, 103 and 202 mGy; PKA: 7.5, 18, 7 and 24 Gy.cm2; FT: 56, 52, 42 and 30 min and CI: 3886, 3232, 2212 and 4316 images for less than 1, 1–5, 6–10 and 11–15 y, respectively. To optimal patient exposure from diagnostic and therapeutic cardiac catheterisation, it is therefore necessary to establish reference values for pediatric cardiac catheterisation examinations for four age groups.
Monoclonal antibody: future of malaria control and prevention
Authors: Nema Shrikant , Nitika Nitika
Published: April 2023

Monoclonal antibodies (mAbs) are extremely specialized proteins that are cloned from B cells and bind to pathogen epitopes. There are currently no known prophylactic immune-based strategies or efficient, widespread treatments to stop the spread of malaria. In order to lower the prevalence of malaria and its associated mortality, we need mAbs that are capable of offering immediate passive protection against the disease. mAbs have become more crucial in the treatment or prevention of several other infectious diseases. Recently, mAb development for malaria prevention and control has greatly evolved and widespread use in public health settings is now a possibility.
Nurse Educators’ Perceptions of Teaching Patient-Centered LGBTQ+ Gender-Affirming Care to Undergraduate Students
Authors: Webb Cibele C. , Zablocki Grace M.
Published: April 2023

Nurse educators are uniquely positioned to equip students with the knowledge, skills, and attitudes to provide LGBTQ+ persons with culturally congruent inclusive care. Using Quality and Safety Education for Nurses’ patient-centered care competency as a framework, this study used a qualitative exploratory-descriptive design to investigate nine undergraduate nurse educators’ perceptions of teaching LGBTQ+ gender-affirming care. Three themes emerged from the interviews denoting challenges: importance of patient-centered care, limited knowledge, and barriers to curricular integration. Incorporating LGBTQ+ topics across the undergraduate nursing curriculum is necessary to support the delivery of person-centered care.
“My Assessments Are Biased!” Measurement and Sociocultural Approaches to Achieve Fairness in Assessment in Medical Education
Authors: Hauer Karen E. , Park Yoon Soo , Bullock Justin L. , Tekian Ara
Published: April 2023

Assessing learners is foundational to their training and developmental growth throughout the medical education continuum. However, growing evidence shows the prevalence and impact of harmful bias in assessments in medical education, accelerating the urgency to identify solutions. Assessment bias presents a critical problem for all stages of learning and the broader educational system. Bias poses significant challenges to learners, disrupts the learning environment, and threatens the pathway and transition of learners into health professionals. While the topic of assessment bias has been examined within the context of measurement literature, limited guidance and solutions exist for learners in medical education, particularly in the clinical environment. This article presents an overview of assessment bias, focusing on clinical learners. A definition of bias and its manifestations in assessments are presented. Consequences of assessment bias are discussed within the contexts of validity and fairness and their impact on learners, patients/caregivers, and the broader field of medicine. Messick’s unified validity framework is used to contextualize assessment bias; in addition, perspectives from sociocultural contexts are incorporated into the discussion to elaborate the nuanced implications in the clinical training environment. Discussions of these topics are conceptualized within the literature and the interventions used to date. The article concludes with practical recommendations to overcome bias and to develop an ideal assessment system. Recommendations address articulating values to guide assessment, designing assessment to foster learning and outcomes, attending to assessment procedures, promoting continuous quality improvement of assessment, and fostering equitable learning and assessment environments.
Patient-, Clinician-, and Institution-level Variation in Inotrope Use for Cardiac Surgery: A Multicenter Observational Analysis
Authors: Mathis Michael R. , Janda Allison M. , Kheterpal Sachin , Schonberger Robert B. , Pagani Francis D. , Engoren Milo C. , Mentz Graciela B. , Shook Douglas C. , Muehlschlegel Jochen D. ,   Multicenter Perioperative Outcomes Group
Published: April 2023

Background

Conflicting evidence exists regarding the risks and benefits of inotropic therapies during cardiac surgery, and the extent of variation in clinical practice remains understudied. Therefore, the authors sought to quantify patient-, anesthesiologist-, and hospital-related contributions to variation in inotrope use.

Methods

In this observational study, nonemergent adult cardiac surgeries using cardiopulmonary bypass were reviewed across a multicenter cohort of academic and community hospitals from 2014 to 2019. Patients who were moribund, receiving mechanical circulatory support, or receiving preoperative or home inotropes were excluded. The primary outcome was an inotrope infusion (epinephrine, dobutamine, milrinone, dopamine) administered for greater than 60 consecutive min intraoperatively or ongoing upon transport from the operating room. Institution-, clinician-, and patient-level variance components were studied.

Results

Among 51,085 cases across 611 attending anesthesiologists and 29 hospitals, 27,033 (52.9%) cases received at least one intraoperative inotrope, including 21,796 (42.7%) epinephrine, 6,360 (12.4%) milrinone, 2,000 (3.9%) dobutamine, and 602 (1.2%) dopamine (non–mutually exclusive). Variation in inotrope use was 22.6% attributable to the institution, 6.8% attributable to the primary attending anesthesiologist, and 70.6% attributable to the patient. The adjusted median odds ratio for the same patient receiving inotropes was 1.73 between 2 randomly selected clinicians and 3.55 between 2 randomly selected institutions. Factors most strongly associated with increased likelihood of inotrope use were institutional medical school affiliation (adjusted odds ratio, 6.2; 95% CI, 1.39 to 27.8), heart failure (adjusted odds ratio, 2.60; 95% CI, 2.46 to 2.76), pulmonary circulation disorder (adjusted odds ratio, 1.72; 95% CI, 1.58 to 1.87), loop diuretic home medication (adjusted odds ratio, 1.55; 95% CI, 1.42 to 1.69), Black race (adjusted odds ratio, 1.49; 95% CI, 1.32 to 1.68), and digoxin home medication (adjusted odds ratio, 1.48; 95% CI, 1.18 to 1.86).

Conclusions

Variation in inotrope use during cardiac surgery is attributable to the institution and to the clinician, in addition to the patient. Variation across institutions and clinicians suggests a need for future quantitative and qualitative research to understand variation in inotrope use affecting outcomes and develop evidence-based, patient-centered inotrope therapies.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
True hermaphroditism: A nightmare for an adult
Authors: Vishwakarma Ranjit B. , Gite Venkat A. , Shaw Vivek , Sharma Shashank
Published: April 2023

The disorder of sex development is a rare disorder that usually occurs in early childhood. As adults, those with disorder of sexual development present with gynecomastia, primary amenorrhea, and primary infertility, which often causes great psychological impact. We report a unique case of a male adult hermaphrodite presenting with hematometra and hematosalpinx. Early management including psychiatry counseling, gender reassignment, and surgery is essential. Our patient underwent müllerian tissue removal with phallus reconstruction.
Rating the Rater: A Technique for Minimizing Leniency Bias in Residency Applications
Authors: Seaward James R. , Carter Lillian R. , Nagarkar Purushottam , Zhang Andrew Y.
Published: April 2023

Background:

Each program in the highly competitive match for a surgical residency needs a way to review applicants effectively. Often this task is undertaken by individual faculty members, reviewing an applicant’s file and assigning a score. Despite being asked to rate on a standardized scale, our program found that ratings of the same applicants varied dramatically, with certain faculty consistently scoring higher or lower than others. This is termed leniency bias, or the Hawk-Dove effect, and can affect who is invited to interview depending on which faculty are assigned to review an applicant’s file.

Methods:

A technique to minimize leniency bias was developed and applied to this year’s 222 applicants for our plastic surgery residency. The effect of the technique was evaluated by comparing variance between ratings of the same applicants by different faculty before and after our technique.

Results:

The median variance of ratings of the same applicants reduced from 0.68 before correction to 0.18 after correction, demonstrating better agreement between raters of the applicants’ scores after our technique had been applied. This year, applying our technique affected whether or not 16 applicants (36% of interviewees) were invited for interview, including one applicant who matched to our program but who otherwise would not have been offered an interview.

Conclusions:

We present a simple but effective technique to minimize the leniency bias between raters of residency applicants. Our experience with this technique is presented together with instructions and Excel formulae for other programs to use.
Candida Colonization on the Surface of Contact Lenses in Long-Term Wearers and Boston Type 1 Keratoprosthesis Patients Presenting as White Mulberry-Shaped Deposits
Authors: Orive Bañuelos Ana , Santamaría Carro Alaitz , Feijóo Lera Raquel , Sacristán Egüén Cristina , Andollo Victoriano Noelia , Etxebarria Ecenarro Jaime
Published: April 2023

Purpose:

To report Candida colonies on the surface of the contact lens in long-term contact lens wearers and patients with Boston type 1 keratoprosthesis (KPro I).

Methods:

A retrospective study was performed based on analyzing cultures from bandage contact lenses with small whitish mulberry-shaped deposits on their surface.

Results:

Eight samples (from seven patients) were positive for Candida. Seven of the eight were positive for Candida parapsilosis.

Conclusions:

The whitish deposits on contact lenses are often Candida colonies that colonize the surface but do not cause an active infection in the eye. C. parapsilosis is well-known for colonizing prosthetic devices. We underline the importance of including Candida species in the differential diagnosis of lens deposits, especially in susceptible patients such as keratoprosthesis carriers.
Public access defibrillation: challenges and new solutions
Authors: Folke Fredrik , Shahriari Persia , Hansen Carolina Malta , Gregers Mads Christian Tofte
Published: April 2023

Purpose of review

The purpose of this article is to review the current status of public access defibrillation and the various utility modalities of early defibrillation.

Recent findings

Defibrillation with on-site automated external defibrillators (AEDs) has been the conventional approach for public access defibrillation. This strategy is highly effective in cardiac arrests occurring in close proximity to on-site AEDs; however, only a few cardiac arrests will be covered by this strategy. During the last decades, additional strategies for public access defibrillation have developed, including volunteer responder programmes and drone assisted AED-delivery. These programs have increased chances of early defibrillation within a greater radius, which remains an important factor for survival after out-of-hospital cardiac arrest.

Recent advances in the use of public access defibrillation show great potential for optimizing early defibrillation. With new technological solutions, AEDs can be transported to the cardiac arrest location reaching OHCAs in both public and private locations. Furthermore, new technological innovations could potentially identify and automatically alert the emergency medical services in nonwitnessed OHCA previously left untreated.
The SERENITY study: online Mindfulness-Based Cancer Recovery (e-MBCR) program for women living with breast and gynecological cancer—protocol for a pilot effectiveness-implementation randomized trial
Authors: Gaignard Marie-Estelle , Stanic Jelena , Bodmer Alexandre , Zaman Khalil , Sarivalasis Apostolos , Labidi-Galy Intidhar , Jermann Francoise , Di Marco Mariagrazia , Ljuslin Michael , Ryser Stephan , Ballabeni Pierluigi , Peters Solange , Dietrich Pierre-Yves , Eicher Manuela , Bondolfi Guido
Published: April 2023

Background:

Mindfulness-Based Interventions (MBIs) have been shown to improve mental and physical health as well as biological processes of patients living with cancer. More research is needed to inform on the determinants that might facilitate or hinder their implementation in hospitals. The primary objective of this study was to explore the feasibility and implementation of an online Mindfulness-Based Cancer Recovery program (e-MBCR) for women with breast and gynecological cancer treated at two academic oncology centers in Switzerland. The secondary objective was to explore the psychological and biological effects of the program.

Methods:

The SERENITY study is a pilot hybrid effectiveness-implementation trial using a randomized waitlist-controlled design, including a mixed methods approach. The intervention groups receive treatment as usual and the e-MBCR program, whereas the control groups are on a wait-list to receive an online Mindfulness-Based Stress Reduction program at the end of the study. Four e-MBCR programs are delivered consecutively, with 12 patients in each group. Participants' attendance to the sessions is the primary outcome. Implementation outcomes of interest are feasibility, acceptability, appropriateness, fidelity, costs, and early sustainability. Implementation determinants will be described, and an exploratory analysis of psychological outcomes and cancer-related biomarkers will be performed at three time points (baseline, postintervention, and 3 months of follow-up).

Discussion:

The results of this study will inform a future large trial and adjustments needed for a real-world implementation of the program. The translational part of this study will contribute to the collective effort to better understand how MBIs affect important cancer-related biomarkers.
Assessment of the Impact of Alternative Fixatives on HER2 Detection in Breast Cancer and Gastric Cancer Tumor Specimens
Authors: Feng Wenqin , Inoue Ryotaku , Kuwata Takeshi , Niikura Naoki , Fujii Satoshi , Kumaki Nobue , Honda Kokichi , Xu Li-An , Goetz Aaron , Gaule Patricia , Cogswell John , Rimm David L. , McGee Robert
Published: April 2023

The type of fixative used for preserving tumor specimens can significantly impact the performance of the immunohistochemistry and in situ hybridization assays used for assessing human epidermal growth factor receptor 2 (HER2) status. This study reports the prevalence of the use of alternative fixatives other than the guideline-recommended 10% neutral buffered formalin (NBF) during HER2 testing in a real-world setting. The effects of alternative fixatives [20% NBF and 10% unbuffered formalin (UBF) fixatives] on HER2 testing of breast cancer (BC) and gastric cancer (GC) cell lines and tissues are also assessed. Overall, 117,636 tumor samples received at a central laboratory from >8000 clinical trial sites across 60 countries were reviewed to determine the prevalence of alternative fixative usage. To investigate the impact of alternative fixatives, 27 cell lines (21 BC and 6 GC) and 76 tumor tissue samples (50 BC and 26 GC) were fixed in 10% NBF, 20% NBF, or 10% UBF, and evaluated for HER2 status by immunohistochemistry and in situ hybridization. Real-world data showed that 9195 (7.8%) tumor samples were preserved using an alternative fixative. In cell lines, overall percentage agreement, negative percentage agreement, and positive percentage agreement among the 3 fixatives were 100%. In tumor tissues, the agreement among 10% NBF, 20% NBF, and 10% UBF ranged between 94.7% and 96.6% for negative percentage agreement and 90.9% for overall percentage agreement compared with a range of 58.3% to 66.7% for positive percentage agreement. These results suggest that alternative fixatives may have the potential to convert HER2 status in tissues from positive to negative.
United States Health Policies on Gender-Affirming Care in 2022
Authors: Chin Madeline G. , LaGuardia Jonnby S. , Morgan Katarina B.J. , Ngo Halena , Moghadam Shahrzad , Huang Kelly X. , Bedar Meiwand , Cronin Brendan J. , Kwan Daniel , Lee Justine C.
Published: April 2023

Background:

Within the United States, access to gender-affirming surgeries covered by health insurance has dramatically increased over the past decade. However, the perpetually changing landscape and inconsistencies of individual state health policies governing private and public insurance coverage present a lack of clarity for reconstructive surgeons and other physicians attempting to provide gender-affirming care. This work systematically reviewed the current U.S. health policies for both private insurance and Medicaid on a state-by-state basis.

Methods:

Individual state health policies in effect as of August 2022 on gender-affirming care were reviewed using the LexisNexis legal database, state legislature publications, and Medicaid manuals. Primary outcomes were categorization of policies as protective, restrictive, or unclear for each state. Secondary outcomes included analyses of demographics covered by current health policies and geographic differences.

Results:

Protective state-level health policies related to gender-affirming care were present in approximately half of the nation for both private insurance (49.0%) and Medicaid (52.9%). Explicitly restrictive policies were found in 5.9% and 17.6% of states for private insurance and Medicaid, respectively. Regionally, the Northeast and West had the highest rates of protective policies, while the Midwest and South had the highest rates of restrictive policies on gender-affirming care.

Conclusions:

State-level health policies on gender-affirming care vary significantly across the United States with regional associations. Clarity in the current and evolving state-specific health policies governing gender-affirming care is essential for surgeons and physicians caring for transgender and gender-diverse individuals.
Neurobrucellosis
Authors: Soares Cristiane N. , da Silva Marcus Tulius T. , Lima Marco Antonio
Published: April 2023

Purpose of review

Brucellosis is one of the most common zoonosis worldwide, affecting 500 000 people, annually. Neurobrucellosis incidence is approximately 4%, and it is almost always heterogeneous. As there are no typical clinical features, its diagnosis is frequently misdiagnosing by other infections.

Recent findings

Neurobrucellosis picture includes meningitis, meningoencephalitis, encephalitis, cranial neuropathies, intracranial hypertension, sinus thrombosis, hemorrhages radiculitis, peripheral neuropathy, myelitis, and psychiatric manifestations. The diagnosis should be based on symptoms and signs suggestive of neurobrucellosis, not explained by other neurological disease, cerebrospinal fluid analysis, a positive Brucella serology or culture, and a response to specific antibiotics, with a significant improvement of cerebrospinal fluid parameters.

Neurobrucellosis can be insidious, and despite its global distribution, it is still unrecognized and frequently goes unreported. The understanding of the current epidemiology is necessary for eradication of the disease in humans, as well as the disease control in animals and prevention based on occupational hygiene and food hygiene.
Viral meningitis and encephalitis: an update
Authors: Gundamraj Vaishnavi , Hasbun Rodrigo
Published: April 2023

Purpose of review

The most common infectious etiologies of meningitis and encephalitis are viruses. In this review, we will discuss current epidemiology, prevention, diagnosis, and treatment of the most common causes of viral meningitis and encephalitis worldwide.

Recent findings

Viral meningitis and encephalitis are increasingly diagnosed as molecular diagnostic techniques and serologies have become more readily available worldwide but recent progress in novel antiviral therapies remains limited. Emerging and re-emerging viruses that have caused endemic or worldwide outbreaks or epidemics are arboviruses (e.g., West Nile virus, Japanese encephalitis, Tick borne encephalitis, Dengue, Zika, Toscana), enteroviruses (e.g., Enterovirus 71, Enterovirus D68), Parechoviruses, respiratory viruses [e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, metapneumoviruses, measles, mumps], and herpes viruses [e.g., herpes simplex virus (HSV) type 1 (HSV-1), HSV-2, human herpes (HV) 6, varicella zoster virus (VZV)]. Future efforts should concentrate in increasing availability for those viruses with effective vaccination [e.g., Japanese encephalitis, Tick borne encephalitis, varicella zoster viruses, SARS-CoV-2, influenza], prompt initiation of those with encephalitis with treatable viruses (e.g., HSV-1, VZV), increasing the diagnostic yield by using novel techniques such as metagenomic sequencing and avoiding unnecessary antibiotics in those with viral meningitis or encephalitis.

We review the current epidemiology, clinical presentation, diagnosis, and treatment of the common causative agents of viral meningitis and encephalitis worldwide.
Disease-Modifying Antirheumatic Drug Use and Its Effect on Long-term Opioid Use in Patients With Rheumatoid Arthritis
Authors: Sood Akhil , Kuo Yong-Fang , Westra Jordan , Raji Mukaila A.
Published: April 2023

Background/Objectives

The prevalence of chronic pain is high in patients with rheumatoid arthritis (RA), increasing the risk for opioid use. The objective of this study was to assess disease-modifying antirheumatic drug (DMARD) use and its effect on long-term opioid use in patients with RA.

Methods

This cohort study included Medicare beneficiaries with diagnosis of RA who received at least 30-day consecutive prescription of opioids in 2017 (n = 23,608). The patients were grouped into non-DMARD and DMARD users, who were further subdivided into regimens set forth by the American College of Rheumatology. The outcome measured was long-term opioid use in 2018 defined as at least 90-day consecutive prescription of opioids. Dose and duration of opioid use were also assessed. A multivariable model identifying factors associated with non-DMARD use was also performed.

Results

Compared with non-DMARD users, the odds of long-term opioid use were significantly lower among DMARD users (odds ratio, 0.89; 95% confidence interval, 0.83–0.95). All regimens except non–tumor necrosis factor biologic + methotrexate were associated with lower odds of long-term opioid use relative to non-DMARD users. The mean total morphine milligram equivalent, morphine milligram equivalent per day, and total days of opioid use were lower among DMARD users compared with non-DMARD users. Older age, male sex, Black race, psychiatric and medical comorbidities, and not being seen by a rheumatologist were significantly associated with non-DMARD use.

Conclusion

Disease-modifying antirheumatic drug use was associated with lower odds of long-term opioid use among RA patients with baseline opioid prescription. Factors associated with non-DMARD use represent a window of opportunity for intervention to improve pain-related quality of life in patients living with RA.
Streptomyces phytophilus sp. nov., an endophytic actinobacterium with biosynthesis potential as an antibiotic producer
Authors: Kaewkla Onuma , Suriyachadkun Chanwit , Franco Christopher Milton Mathew
Published: April 2023

An endophytic actinobacterium, strain PIP175T, was isolated from the root sample of a native apricot tree (Pittosporum angustifolium) growing on the Bedford Park campus of Flinders University, Adelaide, South Australia. This strain is a Gram stain-positive, aerobic actinobacterium with well-developed substrate mycelia. Aerial mycelia rarely produce spores and the spore chain is spiral. Strain PIP175T showed the highest 16S rRNA gene sequence similarity to

Streptomyces aculeolatus

DSM 41644T (99.4 %). Other closely related phylogenetic representatives include

Streptomyces synnematoformans

DSM 41902T (98.3 %),

Streptomyces albospinus

NBRC 13846T (97.6 %),

Streptomyces cacaoi

subsp.

cacaoi

NRRL B-1220T (97.5 %) and

Streptomyces ruber

NBRC 14600T (97.4 %). The major cellular fatty acid of this strain was iso-C16 : 0 and the major menaquinone was MK-9(H6). The whole-cell sugar contained galactose, glucose and mannose. Chemotaxonomic data confirmed that strain PIP175T belonged to the genus

Streptomyces

. Digital DNA–DNA hybridization, average nucleotide identity based on blast and OrthoANIu results between strain PIP175T and

S. aculeolatus

DSM 41644T were 60.0, 94.1 and 94.9 %, respectively. Genotypic and phenotypic data and genome analysis results allowed the differentiation of strain PIP175T from its closest species with validly published names. Strain PIP175T showed good activity against methicillin-resistant

Staphylococcus aureus

03120385. Genome mining of strain PIP175T revealed biosynthetic genes encoding proteins relating to antibiotic production, plant growth promotion and biodegradation enzymes. The name proposed for the new species is Streptomyces phytophilus sp. nov. The type strain is PIP175T (=DSM 103379T=TBRC 6026T).
Improving Model Transferability for Clinical Note Section Classification Models Using Continued Pretraining
Authors: Zhou Weipeng , Yetisgen Meliha , Afshar Majid , Gao Yanjun , Savova Guergana , Miller Timothy A.
Published: April 2023

Objective

The classification of clinical note sections is a critical step before doing more fine-grained natural language processing tasks such as social determinants of health extraction and temporal information extraction. Often, clinical note section classification models that achieve high accuracy for one institution experience a large drop of accuracy when transferred to another institution. The objective of this study is to develop methods that classify clinical note sections under the SOAP (“Subjective”, “Object”, “Assessment” and “Plan”) framework with improved transferability.

Materials and methods

We trained the baseline models by fine-tuning BERT-based models, and enhanced their transferability with continued pretraining, including domain adaptive pretraining (DAPT) and task adaptive pretraining (TAPT). We added out-of-domain annotated samples during fine-tuning and observed model performance over a varying number of annotated sample size. Finally, we quantified the impact of continued pretraining in equivalence of the number of in-domain annotated samples added.

Results

We found continued pretraining improved models only when combined with in-domain annotated samples, improving the F1 score from 0.756 to 0.808, averaged across three datasets. This improvement was equivalent to adding 50.2 in-domain annotated samples.

Discussion

Although considered a straightforward task when performing in-domain, section classification is still a considerably difficult task when performing cross-domain, even using highly sophisticated neural network-based methods.

Conclusion

Continued pretraining improved model transferability for cross-domain clinical note section classification in the presence of a small amount of in-domain labeled samples.
The influence of highly effective modulator therapies on the sputum proteome in cystic fibrosis
Authors: Maher Rosemary E , Barry Peter J , Emmott Edward , Jones Andrew M , Lin Lijing , McNamara Paul S , Smith Jaclyn A , Lord Robert W
Published: April 2023

Background

There have been dramatic clinical improvements in cystic fibrosis (CF) patients commenced on the cystic fibrosis conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (ETI). Sputum proteomics is a powerful research technique capable of identifying important airway disease mechanisms. Using this technique, we evaluated how ETI changes the sputum proteome in people with CF.

Methods

Sputum samples from 21 CF subjects pre- and post-ETI, 6 CF controls ineligible for ETI, and 15 healthy controls were analysed by liquid chromatography mass spectrometry.

Results

Post-ETI, mean FEV1% increased by 13.7% (SD 7.9). Principal component and hierarchical clustering analysis revealed that the post-ETI proteome shifted to an intermediate state that was distinct from pre-ETI and healthy controls, even for those achieving normal lung function. Functional analysis showed incomplete resolution of neutrophilic inflammation. The CF control sputum proteome did not alter. At the protein-level many more proteins increased in abundance than decreased following ETI therapy (80 vs 30; adjusted p value <0.05), including many that have anti-inflammatory properties. Of those proteins that reduced in abundance many were pro-inflammatory neutrophil-derived proteins. Several important respiratory proteases were unchanged.

Conclusions

Sputum proteomics can provide insights into CF lung disease mechanisms and how they are modified by therapeutic intervention, in this case ETI. This study identifies imbalances in pro- and anti-inflammatory proteins in sputum that partially resolve with ETI even in those achieving normal spirometry values. This post-ETI intermediate state could contribute to ongoing airway damage and therefore its relevance to clinical outcomes needs to be established.
Estimating overdiagnosis in giant cell arteritis diagnostic pathways using genetic data: genetic association study
Authors: Chatzigeorgiou Charikleia , Barrett Jennifer H , Martin Javier ,   UK GCA Consortium, Morgan Ann W , Mackie Sarah L
Published: April 2023

Objectives

Prompt diagnosis of giant cell arteritis (GCA) is important to avert visual loss. False-negative temporal artery biopsy (TAB) can occur. Without vascular imaging, GCA may be overdiagnosed in TAB-negative cases, but it is unclear how often this occurs. An unbiased test is a way to address an imperfect reference standard. We used the known Human Leukocyte Antigen (HLA) region genetic association of TAB-positive GCA to estimate the extent of overdiagnosis before widespread adoption of temporal artery ultrasound as a first-line test.

Methods

Patients diagnosed with GCA between 1990-2014 consented to the UKGCA Consortium study. HLA region variants were jointly imputed from genome-wide genotypic data of cases and controls. Per-allele frequencies across all variants with p<1.0×10−5were compared with population control data to estimate overdiagnosis rates in cases without a positive TAB.

Results

Genetic data from 663 patients diagnosed with GCA were compared with data from 2619 population controls. TAB-negative GCA (n=147) and GCA without a TAB result (n=160) had variant frequencies intermediate between those of TAB-positive GCA and population controls. Making several strong assumptions, we estimated that around two-thirds of TAB-negative cases and around one-third of cases without TAB result may have been overdiagnosed. From these data, TAB sensitivity is estimated at around 88%.

Conclusions

Conservatively assuming 95% specificity, TAB has a negative likelihood ratio of around 0.12. Genotyping alone cannot diagnose GCA at the individual level. Group-level HLA variant genotyping might be used to compare the overall accuracy of different diagnostic pathways or different classification criteria sets.

Key messages

Under certain conditions and assumptions, overdiagnosis can be estimated using genetic data.

The specificity of temporal artery biopsy was estimated as about 88%.

Without vascular imaging, giant cell arteritis may often be overdiagnosed in biopsy-negative patients.
HRSA Population Health Dashboard
Authors: Nguyen Chi
Published: April 2023

Project Purpose

To develop a quality dashboard tool for the Health Resources and Services Administration (HRSA) community health centers to examine health center characteristics associated with performance excellence and predict future healthcare cost.

Background

HRSA is the primary federal agency for improving health care to people who are geographically isolated, economically or medically vulnerable. HRSA-funded health centers are required to upload to Uniform Data System (UDS). HRSA health data is rich; however, their website provides limited meaningful visualization and data-driven analysis.

Method

The project reviewed data from Uniform Data System between 2017 and 2019. The data was cleaned using Excel. Visualization was displayed on Tableau, and the cost prediction modeling was completed using Python Machine Learning libraries. All the findings are available for public view on Weebly-hosted website.

Outcomes

The Tableau dashboard showcases the effectiveness of the preventive intervention and chronic disease management initiatives over the years. This tool focuses on comparison between outcomes in health care programs and cost benefits in all states. The dashboard also uses the most fit Machine Learning model and the most important variables to predict the cost per patient of a health center.

Discussion

The lack of similar performance comparison dashboards by HRSA suggests a need for HRSA Population Health Dashboard to understand the performances of HRSA-funded health centers or regions through times. It shows the ineffectiveness of the current healthcare programs in reducing disease growth and healthcare cost over the course of 3 years.

Next Steps/Opportunities

The final dashboard will be available for public use and will continue to aggregate more real-time data using Application Programming Interface (API) to improve its accuracy of prediction model. The HRSA Population Health Dashboard will be beneficial to management at both HRSA federal- and health center-level to make valuable strategies.
The effectiveness of precision supplements on depression symptoms in a US population
Authors: Julian Cristina , Shen Nan , Molusky Matthew , Hu Lan , Gopu Vishakh , Gorakshakar Anmol , Patridge Eric , Antoine Grant , Connell Janelle , Keiser Hilary , Naidoo Uma , Vuyisich Momchilo , Banavar Guruduth
Published: April 2023

Nutrition plays a pivotal role in depression, but dietary interventions are usually not personalized and do not consider patients’ microbial and human molecular functions. This preliminary study evaluated the effectiveness of precision supplements (PS) on depression symptoms as part of a personalized nutrition subscription plan that accounts for the gene expression activity of the microbiome and the human host. People with depression, 86 taking PS and 45 controls responded to the patient health questionnaire-9 (PHQ-9) at two time points an average of ∼6 months apart. Categorical changes were evaluated using the PHQ-9 score system, and clinically significant categorical differences were observed between the two groups (effect size = 0.48; p <0.001). The difference in differences was calculated using multiple group propensity score weighting adjusting for age, sex, BMI, and physical activity, and the PHQ-9 score decreased by ∼4 points (∼29%) for the intervention group (t0: 13.75+-3.80, t1: 9.78+-6.42) vs Controls (t0: 14.07+-3.64, t1: 13.59 +-6.65). Thus, precision supplement use over ∼6 months significantly reduced depression symptoms, with 69.8% of the individuals in the intervention group improving their category to no/low depression vs. 15.6% in the control group.
Deep resequencing of the 1q22 locus in non-lobar intracerebral hemorrhage
Authors: Parodi Livia , Comeau Mary E , Georgakis Marios K , Mayerhofer Ernst , Chung Jaeyoon , Falcone Guido J , Malik Rainer , Demel Stacie L , Worrall Bradford B , Koch Sebastian , Testai Fernando D , Kittner Steven J , McCauley Jacob L , Hall Christiana E , Mayson Douglas J , Elkind Mitchell SV , James Michael L , Woo Daniel , Rosand Jonathan , Langefeld Carl D , Anderson Christopher D
Published: April 2023

Objective

Genome-wide association studies have identified1q22as a susceptibility locus for cerebral small vessel diseases (CSVDs), including non-lobar intracerebral hemorrhage (ICH) and lacunar stroke. In the present study we performed targeted high-depth sequencing of1q22in ICH cases and controls to further characterize this locus and prioritize potential causal mechanisms, which remain unknown.

Methods

95,000 base pairs spanning1q22, includingSEMA4A, SLC25A44andPMF1/PMF1-BGLAPwere sequenced in 1,055 spontaneous ICH cases (534 lobar and 521 non-lobar) and 1,078 controls. Firth regression and RIFT analysis were used to analyze common and rare variants, respectively. Chromatin interaction analyses were performed using Hi-C, ChIP-Seq and ChIA-PET databases. Multivariable Mendelian randomization (MVMR) assessed whether alterations in gene-specific expression relative to regionally co-expressed genes at1q22could be causally related to ICH risk.

Results

Common and rare variant analyses prioritized variants inSEMA4A5’-UTR andPMF1intronic regions, overlapping with active promoter and enhancer regions based on ENCODE annotation. Hi-C data analysis determined that1q22is spatially organized in a single chromatin loop and that the genes therein belong to the same Topologically Associating Domain. ChIP-Seq and ChIA-PET data analysis highlighted the presence of long-range interactions between theSEMA4A-promoter andPMF1-enhancer regions prioritized by association testing. MVMR analyses demonstrated thatPMF1overexpression could be causally related to non-lobar ICH risk.

Interpretation

Altered promoter-enhancer interactions leading toPMF1overexpression, potentially dysregulating polyamine catabolism, could explain demonstrated associations with non-lobar ICH risk at1q22, offering a potential new target for prevention of ICH and CSVD.
Risk Factors for Spontaneous Preterm Birth are Mediated through Changes in Cervical Length
Authors: Wolf Hope M. , Latendresse Shawn J. , Strauss Jerome F. , Tarca Adi L. , Romero Roberto , Hassan Sonia S. , Webb Bradley T. , York Timothy P.
Published: April 2023

Although short cervical length in the mid-trimester of pregnancy is a one of the strongest predictors of preterm birth (i.e., parturition before 37 completed weeks), there is limited understanding of how the dynamics of cervical remodeling (i.e., changes in cervical length) leading up to labor and delivery can inform obstetrical risk. In this study, latent growth curve analysis was applied to serial cervical length measurements across pregnancy (median of 6; IQR = 3-8) to quantify characteristics of cervical change in a cohort of 5,111 singleton pregnancies consisting predominantly of Black women. A conditional mediation model including nine common maternal risk factors for spontaneous preterm birth as exogenous predictors accounted for 26.5% of the variability in gestational age at delivery (P< 0.001). This model provides insight into distinct mechanisms by which specific maternal risk factors influence preterm birth. For instance, effects of maternal parity and smoking status were fully mediated through cervical change parameters, whereas the influence of previous preterm birth was only partially explained, suggesting alternative pathways could be involved. This study provides the first account of the intermediary role of cervical dynamics in associations between known maternal risk factors and gestational age at delivery.
Menopausal vasomotor symptoms and subclinical atherosclerotic cardiovascular disease – a population-based study
Authors: Nilsson Sigrid , Qvick Angelika , Henriksson Moa , Sederholm Lawesson Sofia , Spetz Holm Anna-Clara , Leander Karin
Published: April 2023

BACKGROUND

Menopausal vasomotor symptoms (VMS) have been associated with subclinical and manifest atherosclerotic cardiovascular disease (ASCVD) but have not been studied in relation to image-detected coronary atherosclerosis. We assessed the association between VMS and subclinical ASCVD in peri- and postmenopausal women, considering a wide range of cardiovascular related risk factors that could potentially influence the relationship.

METHODS

This cross-sectional population-based study was conducted on a subset of participants from the Swedish CArdioPulmonary BioImage Study (SCAPIS), including women 50-65 years of age. The women underwent comprehensive cardiovascular assessments and completed an extensive questionnaire, which included questions about current and previous menopause-related symptoms. VMS was assessed on a 4-point scale and analyzed in relation to subclinical ASCVD, detected via coronary computed tomography angiography (CCTA), coronary artery calcium score (CACS) and carotid ultrasound using logistic regression analyses.

RESULTS

Of 2995 women included, 14.2% reported previous or on-going severe VMS (n=425), 18.1% moderate VMS (n=543), and 67.7% no or mild VMS (n=2027). Women who had ever experienced severe VMS, but not those with ever moderate VMS, had higher prevalence of CCTA-detected coronary atherosclerosis (34.1 vs 27.8%, p=0.017), but not segmental involvement score (SIS) >3 (4.5 vs 5.1%, p=0.332), CACS>100 (5.8 vs 6.8%, p=0.166) or any carotid plaque (47.6% vs 46.6%, p=249) than women with never or ever mild VMS. Using the same reference, ever severe but not moderate VMS was significantly associated with CCTA-detected coronary atherosclerosis, odds ratio (OR) after multivariable adjustment 1.33, 95% CI 1.02–1.72. This association was only present for durations of severe VMS of more than 5 years (multivariable adjusted OR 1.53 95% CI 1.09-2.14) or when the onset of severe VMS occurred before menopause (multivariable adjusted OR 1.60 95% CI 1.06-2.42). Additional adjustment for menopausal hormone therapy strengthened the associations whereas additional adjustment for physical activity did not. No significant association with SIS>3, CACS>100, nor with any carotid plaque was observed.

CONCLUSIONS

Previous or on-going severe but not moderate VMS were significantly associated with CCTA-detected coronary atherosclerosis, independent of a broad range of cardiovascular risk factors. No corresponding associations was observed for SIS>3, CACS>100 or carotid atherosclerosis.