bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of the oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family kinase inhibitor ritlecitinib over 24 months: integrated analysis of the ALLEGRO phase IIb/III and long-term phase III clinical studies in alopecia areata
Authors: Piliang Melissa , Soung Jennifer , King Brett , Shapiro Jerry , Rudnicka Lidia , Farrant Paul , Magnolo Nina , Piraccini Bianca Maria , Luo Xin , Wolk Robert , Woodworth Deborah , Schaefer Gregor , Lejeune Alexandre
Published: October 2024

Background

The ALLEGRO phase IIa and IIb/III (NCT02974868 and NCT03732807) studies have demonstrated that ritlecitinib is effective and well tolerated in adults and adolescents with alopecia areata (AA) up to 48 weeks.

Objectives

To assess the efficacy of ritlecitinib through month 24 and safety through data cutoff in the ALLEGRO phase IIb/III study and the ongoing long-term open-label phase III ALLEGRO-LT study (NCT04006457).

Methods

Patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss from ALLEGRO IIb/III who rolled over to ALLEGRO-LT after up to 48 weeks were included. Proportions of patients with responses based on clinician-reported Severity of Alopecia Tool (SALT) scores of ≤ 20 and ≤ 10, eyebrow assessment (EBA) and eyelash assessment (ELA), patient global impression of change (PGI-C) and patient satisfaction with hair growth were reported through month 24 for patients who received ritlecitinib 50 mg daily with or without a 200-mg 4-week daily loading dose. Observed and imputed data [last observation carried forward (LOCF)] were reported up to 9 December 2022. Safety was assessed throughout.

Results

At month 12, a SALT score ≤ 20 was achieved by 45.1% and 45.9% (observed) and 40.3% and 41.8% (LOCF) of the 191 and 194 patients who received ritlecitinib 50 mg and ritlecitinib 200 mg/50 mg, respectively. At month 24, these proportions increased to 60.8% and 63.1% (observed) and 46.1% and 50.8% (LOCF), respectively. Patients with abnormal EBA or ELA scores at baseline achieved responses at month 24 [EBA observed: 57.6% (50 mg), 61.0% (200/50 mg); EBA LOCF: 46.8% (50 mg), 50.9% (200/50 mg); ELA observed: 51.2% (50 mg), 62.7% (200/50 mg); ELA LOCF: 43.2% (50 mg), 51.7% (200/50 mg)]. PGI-C response was achieved by patients at month 24 [observed: 70.0% (50 mg), 76.4% (200/50 mg); LOCF: 56.6% (50 mg), 65.5% (200/50 mg)]. Safety profiles for both treatment groups were consistent with the known safety profile of ritlecitinib.

Conclusions

Ritlecitinib has clinically meaningful and sustained efficacy beyond 1 year with a favourable safety and tolerability profile, supporting its long-term use in patients aged ≥ 12 years with AA.

Graphical Abstract
British Association of Dermatologists living guideline for managing people with alopecia areata 2024
Authors: Harries Matthew J , Ascott Anna , Asfour Leila , Farrant Paul , Hale Gordon , Holmes Susan , Johnson Amy , Jolliffe Victoria M L , Kazmi Ahmed , Macbeth Abby E , Messenger Andrew G , Noor Ali , Takwale Anita , Thompson Andrew R , Hashme Maria , Manounah Lina , Mohd Mustapa M Firouz , Constantin Alina M
Published: October 2024

Lay Summary

Alopecia areata (AA) is a long-term condition that can occur in both children and adults. AA can appear as patches of baldness on the scalp. Sometimes, nail growth is also affected. Hair on other parts of the body may also fall out, such as the beard, eyebrows and eyelashes. Total loss of scalp hair is called alopecia totalis (AT). Complete loss of scalp, facial and body hair is called alopecia universalis (AU).

The British Association of Dermatologists gathered a group of experts in managing people of all ages with AA. The group consisted of 11 dermatologists, 1 psychologist, 2 people with AA and a team with expertise in preparing guidelines. This group of experts reviewed relevant studies published until 19 October 2023. Using the evidence, the group produced recommendations using rigorous standards for guideline development.

The guideline development group produced 49 recommendations for management of people with AA. They also made 7 recommendations for future research and suggested 11 audit points for hospitals.

Based on the guideline, the group prepared an updated patient information leaflet. The leaflet is available on the British Association of Dermatologists’ website (https://www.skinhealthinfo.org.uk/condition/alopecia-areata).
Stable multiplex networks: definitions and characterizations
Authors: Ma Ziyu , Parilina Elena
Published: October 2024

Communication and interaction of individuals in the real world cannot be represented by one-layer networks, and in our paper we use multiplex networks capturing the complexity of their interactions. We define players’ utilities taking into account a multilayer structure of the network by specifying different ways of accounting players’ costs. Using two approaches, we obtain stability conditions for special multilplex structures including all-layer complete, all-layer star with unique or different centers, and all-layer unique networks.
Supplementation with probiotics, prebiotics, and synbiotics in patients with chronic functional constipation: a randomized, double-blind, placebo-controlled pilot clinical trial
Authors: Terrén Lora Ana , Penadés Bruno F , López Oliva Sara , Arponen Sari , Okutan Gülşah , Sánchez Niño Guerthy Melissa , San Mauro Martín Ismael
Published: October 2024

Background

Functional constipation includes a set of gastrointestinal symptoms unexplainable by an identifiable underlying physical cause or pathology. The prevalence of this condition is high and there is a need to develop strategies to reduce it. Probiotics, prebiotics, and synbiotics may be an alternative treatment for chronic functional constipation.

Methods

To compare the efficacy of dietary supplementation on symptoms of patients who suffer from chronic functional constipation. An exploratory, randomized, double-blind, placebo-controlled pilot clinical trial was conducted with 74 patients diagnosed with chronic functional constipation who were divided into four treatment groups—Group A: probiotics; Group B: prebiotics; Group C: synbiotics; Group D: placebo. Each patient was treated for 8 weeks. At the beginning and end of treatment, data were collected by administering questionnaires and scales, including the Bristol stool scale, on gastrointestinal symptoms, bowel movements, and sociodemographic and anthropometric characteristics.

Results

Stool frequency increased in all four study groups, and greatest difference was observed in the synbiotics group (2.8 ± 1.3 vs. 5.9 ± 2.6; P < 0.001). Stool consistency improved only in the active treatment groups. Based on the evaluation of gastrointestinal symptoms, participants treated with prebiotics, probiotics and synbiotics showed the greatest improvement in abdominal pain (8.28 ± 2.63 vs. 6.56 ± 2.62; P = 0.009), gastroesophageal reflux (4.60 ± 2.66 vs. 3.45 ± 2.42; P = 0.039) and constipation symptoms (13.00 ± 3.97 vs. 8.71 ± 3.35; P = 0.003), respectively. As for quality of life, the main changes were observed in physical health domains, with a placebo effect.

Conclusions

The present study provides evidence supporting the efficacy of dietary supplementation with probiotics, prebiotics, and synbiotics in patients with chronic functional constipation after 8 weeks of treatment.
Safety culture in focus: review of patient safety culture survey results in Primary Health Care Corporation Qatar
Authors: AlAbdulmalik Reem , Khattabi Nawal , Francis Reena , Manoharan Divya , Al-Ali Amal , Abdulmalik Mariam
Published: October 2024

Background

Patient safety is a crucial aspect of every health care organization and understanding the safety culture is essential for improving patient health outcomes. Evaluating the patient safety culture enables the health care organizations to gain insights into how their internal system’s structure and processes impact the patient’s overall well-being. In this paper, the Hospital Survey On Patient Safety (HSOPS) that is adopted from Agency for Healthcare Research and Quality (AHRQ) was used to examine the patient safety culture in the Primary Health Care Corporation in Qatar (PHCC), allowing for a better understanding of areas of strength and areas that require improvements.

Objectives

The aim of this study is to identify factors that contribute to a positive patient safety culture within PHCC Qatar utilizing the AHRQ HSOPS. Additionally, the study explores the barriers to enhancing the culture through qualitative data and evaluate its impact on health outcomes and care quality.

Method

The study aimed at comparing the organization’s safety culture in 2021 and its improvement in 2023. The survey was disseminated into 28 primary health centers with different sizes and patient volumes. The survey was sent electronically to all PHCC staff, allowing for better convenience and higher response rate.

Results

The results of this survey revealed numerous areas of strength, including teamwork across departments, error reporting, management support, communication error, non-punitive response to errors and staffing. On the other side, survey composites such as continuous learning and teamwork within department were identified as areas for improvement.

Conclusion

By allowing for better insights into the culture of safety and identifying areas of strength and weaknesses, PHCC can make informed decisions and implement effective interventions. This will support in enhancing the health and wellbeing of Qatar’s population that aligns with the national health strategies, which improves the overall health care in the region.
Rickettsia rickettsii subsp californica subsp nov, the Etiologic Agent of Pacific Coast Tick Fever
Authors: Paddock Christopher D , Karpathy Sandor E , Henry Asa , Ryle Luke , Hecht Joy A , Hacker Jill K , Padgett Kerry A , Kjemtrup Anne M , Bullock Hannah , Lane Robert S , Ladner Jason T
Published: October 2024

The etiologic agent of Pacific Coast tick fever, a moderately severe tickborne illness that resembles Rocky Mountain spotted fever (RMSF), was first isolated in 1966 from specimens of Dermacentor occidentalis (the Pacific Coast tick) obtained in California. For several decades, this bacterium was identified ambiguously as the unclassified spotted fever group Rickettsia species 364-D, Rickettsia 364, or Rickettsia philipii. However, none of these epithets satisfied criteria of formal bacterial nomenclature. Data developed from mouse serotyping studies performed >45 years ago, and multilocus sequence typing several decades later, indicated that this bacterium was similar to, but distinct from, isolates of Rickettsia rickettsii, the etiological agent of RMSF. We applied an integrative taxonomic approach, combining phenotypic, ecological, and clinical data with whole-genome sequencing of 11 contemporary isolates of this pathogen to identify it as a distinct subspecies of R. rickettsii, and propose the name Rickettsia rickettsii subsp californica subsp nov.
Associations between tripartite dimensions of internalizing symptoms and transition readiness in a sample of emerging adults with and without chronic physical health conditions
Authors: Macaulay Taylor , Buscemi Joanna , Tran Susan , Miller Steven A , Greenley Rachel Neff
Published: October 2024

Objective

Theoretical models note psychosocial functioning as a key influence on transition readiness skills (TRS) among emerging adults (EA), but little is known about the relative importance of unique vs. shared anxiety and depressive dimensions, operationalized according to Clark and Watson’s (1991) tripartite model, in contributing to TRS. Moreover, although development of TRS is important for all EA, few studies have examined whether the strength of relationships between internalizing symptoms and TRS vary between EA with and without chronic physical health conditions (CHC). Given the links between suboptimal TRS and adverse health outcomes, additional research is needed. This study examined individual and additive associations between three internalizing symptom dimensions (anxious arousal, anhedonic depression, and general distress) and TRS, as well as the moderating role of CHC status.

Method

One hundred twenty-six EA completed an online survey measuring TRS and internalizing symptoms. The sample was 70.6% women, 39.7% of minoritized racial identity, and 21.2% Hispanic ethnicity. The mean participant age was 21.23 years.

Results

In two of three regression models, anhedonic depression alone was significantly related to TRS. CHC moderated the relationship between internalizing and TRS in only two of nine models. In both cases, internalizing symptoms were negatively associated with TRS for those without CHCs, but not for those with CHCs.

Conclusions

Assessment of anhedonic depression may be particularly useful in identifying youth at risk for suboptimal TRS regardless of CHC status. Moreover, interventions such as behavioral activation to improve TRS skill attainment warrant additional investigation.
FINE CULM1 Encoding a TEOSINTE BRANCHED1-like TCP Transcription Factor Negatively Regulates Axillary Meristem Formation in Rice
Authors: Tanaka Wakana , Ohyama Ami , Toriba Taiyo , Tominaga Rumi , Hirano Hiro-Yuki
Published: October 2024

Shoot branching is a critical determinant of plant architecture and a key factor affecting crop yield. The shoot branching involves two main processes: axillary meristem formation and subsequent bud outgrowth. While considerable progress has been made in elucidating the genetic mechanisms underlying the latter process, our understanding of the former process remains limited. Rice FINE CULM1 (FC1), which is an ortholog of teosinte branched1 in maize (Zea mays) and BRANCHED1/2 in Arabidopsis (Arabidopsis thaliana), is known to act in the latter process by repressing bud outgrowth. In this study, we found that FC1 also plays a role in the former process, i.e. axillary meristem formation, in rice. This study was triggered by our unexpected observation that fc1 mutation suppresses the loss of axillary meristems in the loss-of-function mutant of the rice WUSCHEL gene TILLERS ABSENT1 (TAB1). In tab1 fc1, unlike in tab1, both stem cells and undifferentiated cells were maintained during axillary meristem formation, similar to the wild type. Morphological analysis showed that axillary meristem formation was accelerated in fc1, compared to the wild type. Consistent with this, cell proliferation was more active in the region containing stem cells and undifferentiated cells during axillary meristem formation in fc1 than in the wild type. Taken altogether, these findings suggest that FC1 negatively regulates axillary meristem formation by mildly repressing cell proliferation during this process.
RNA sequencing uncovers key players of cartilage calcification: potential implications for osteoarthritis pathogenesis
Authors: Bernabei Ilaria , Faure Elodie , Wegrzyn Julien , Bertheaume Nicolas , Falgayrac Guillaume , Hugle Thomas , Nasi Sonia , Busso Nathalie
Published: October 2024

Objective

OA is a joint disease linked with pathologic cartilage calcification, caused by the deposition of calcium-containing crystals by chondrocytes. Despite its clinical significance, the precise mechanisms driving calcification remain elusive. This study aimed to identify crucial players in cartilage calcification, offering insights for future targeted interventions against OA.

Methods

Primary murine chondrocytes were stimulated with secondary calciprotein particles (CPP2) or left untreated (NT) for 6 h. Calcification was assessed by alizarin red staining. RNA was analysed by Bulk RNA sequencing. Differentially expressed (DE) genes were identified [cutoff: abs(LogFC)>1 and adjusted P-value < 0.05], and top 50 DE genes were cross-referenced with human OA datasets from previous studies (i.e. healthy vs. OA cartilage, or undamaged vs. damaged cartilage). RNA from NT and CPP2-stimulated primary human OA chondrocytes were used to validate genes by qPCR.

Results

CPP2 induced crystal formation by chondrocytes and significantly modulated 1466 genes. Out of the top 50 DE genes in CPP2, 27 were confirmed in published OA cartilage datasets. Of those genes, some are described in calcification and/or OA (Errfi1, Ngf, Inhba, Col9a1). Two additional ones (Rcan1, Tnfrsf12a) appear novel and interesting in the context of calcification and OA. We validated modulation of these six genes in calcifying human chondrocytes from five patients. Ultimately, we unveiled two distinct gene families modulated by CPP2: the first comprised cytoskeletal genes (Actb, Tpm1, Cfl1, Tagln2, Lmna), while the second encompassed extracellular matrix genes (Fmod, Sparc, Col9a1, Cnmd).

Conclusion

CPP2 modulates genes in chondrocytes that could represent new targets for therapeutic interventions in OA.
Neurosurgical Procedures in Patients Requiring Extracorporeal Membrane Oxygenation
Authors: Lee Ryan , Helmy Samantha , Cardona Jeronimo , Zhao David , Rector Raymond , Rabin Joseph , Mazzeffi Michael , Cho Sung-Min , Parikh Gunjan , Morris Nicholas A. , Khan Imad
Published: October 2024

OBJECTIVES:

Extracorporeal membrane oxygenation (ECMO) is often withheld in patients with significant neurologic injury or recent neurosurgical intervention due to perceived futility. Studies of neurosurgical interventions before or during ECMO are limited to case reports or single-center series, limiting generalizability, and outcomes in this population are unknown. We therefore sought to report the outcomes of ECMO patients with acute neurosurgical interventions at four high-volume ECMO and comprehensive stroke centers.

DESIGN:

Retrospective case series.

SETTING:

Four academic tertiary referral hospitals in the United States.

PATIENTS:

Adults (n = 24) having undergone neurosurgical procedures before or during ECMO.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We retrospectively reviewed adults at four institutions who had undergone neurosurgical procedures immediately before or during ECMO from 2015 to 2023. The primary outcome was survival to hospital discharge. Secondary outcomes included favorable neurologic outcome (Cerebral Performance Category 1 or 2) and neurosurgical complications. Twenty-four of 2957 ECMO patients (0.8%) were included. Primary indications for neurosurgical intervention included traumatic brain (n = 8) or spinal (n = 3) injury, spontaneous intracranial hemorrhage (n = 6), and acute ischemic stroke (n = 5). Procedures included extraventricular drain (EVD) and/or intracranial pressure monitor placement (n = 10), craniectomy/craniotomy (n = 5), endovascular thrombectomy (n = 4), and spinal surgery (n = 3). Fifteen patients (63%) survived to hospital discharge, of whom 12 (80%) were discharged with favorable neurologic outcomes. Survival to discharge was similar for venoarterial and venovenous ECMO patients (8/12 vs. 7/12; p = 0.67) and those who had neurosurgery before vs. during ECMO (8/13 vs. 7/11; p = 0.92). One patient (4%) experienced a neurosurgical complication, a nonlethal tract hemorrhage from EVD placement. Survival to discharge was similar for neurosurgical and nonneurosurgical ECMO patients at participating institutions (63% vs. 57%; p = 0.58).

CONCLUSIONS:

Patients with acute neurologic injury can feasibly undergo neurosurgery during ECMO or can undergo ECMO after recent neurosurgery. Larger studies are needed to fully understand risks for bleeding and other procedure-related complications.
Associations Between Clinical Factors and Postoperative Thrombosis in Pediatric Cardiac Surgery Patients: A Single-Center Retrospective Study
Authors: Chlench Sven , Freudenthal Noa J.
Published: October 2024

IMPORTANCE:

Postoperative thrombosis is a significant complication in pediatric cardiac surgery patients, contributing to morbidity and mortality. Identifying clinical factors associated with thrombosis can improve patient outcomes by guiding early detection and intervention.

OBJECTIVES:

This study aimed to assess factors associated with postoperative thrombosis or thromboembolism in pediatric patients under 12 months old who underwent surgery for congenital heart disease (CHD). Design, Setting, and Participants: This retrospective cohort study analyzed electronic medical records from pediatric patients admitted to the Pediatric Cardiovascular Intensive Care Unit (PCICU) at the German Paediatric Heart Center, Bonn, between March 1, 2020, and March 1, 2021. A total of 197 children under 12 months old who underwent cardiac surgery were included in the analysis.

MAIN OUTCOMES AND MEASURES:

Thrombosis was diagnosed postoperatively using imaging modalities such as ultrasound, echocardiography, and computed tomography. The primary outcome was the incidence of thrombosis and its association with clinical factors such as age, central venous catheter (CVC) duration, CRP levels, and D-dimer levels.

RESULTS:

Among 197 patients, the incidence of thrombosis was 8.63%, predominantly venous (70.6%). Initial associations were observed between thrombosis and younger age, lower body weight, higher hematocrit, cyanosis, longer central venous catheter (CVC) use, and elevated C-reactive protein (CRP) and d-dimer levels. Receiver operating characteristic analysis indicated a higher risk in patients with d-dimer levels above 5.47 mg/L. The stepwise multiregression analysis identified longer CVC duration in situ (β = 0.553; p < 0.001), higher CRP levels (β = 0.217; p = 0.022), and younger age at admission (β = –0.254; p = 0.006) as significant predictors of thrombosis. Decision tree analysis identified CVC use longer than 12.5 days and CRP levels above 118.01 mg/L as the most critical risk factors.

CONCLUSIONS AND RELEVANCE:

Postoperative thrombosis is a notable risk in pediatric CHD patients, particularly in neonates. Prolonged CVC use and elevated CRP levels are critical risk factors. Routine monitoring of D-dimer and CRP levels, along with timely sonographic screening, can aid early thrombosis detection and intervention. Further research is warranted to optimize thrombosis prevention strategies in this population.
Living From Test to Test: A Concept Analysis of CA-125 Preoccupation in Ovarian Cancer Survivorship
Authors: Gormley Maurade , Dunnack Yackel Hayley , Redeker Nancy S.
Published: October 2024

Background:

Ovarian cancer has a high risk of recurrence and is rarely curable. One method for monitoring recurrence is trending Cancer antigen 125 (CA-125) levels. However, treatment based on rising CA-125 levels is controversial, often contributing to anxiety and an excessive focus on test results, described as “CA-125 preoccupation.”

Objective:

To present an analysis on the concept of CA-125 preoccupation.

Methods:

Rodgers’ method of evolutionary concept analysis was used to evaluate the attributes, antecedents, and consequences. PubMed, Medline, PsycINFO, and CINAHL electronic databases were searched.

Results:

Antecedents include a diagnosis of ovarian cancer that necessitates CA-125 surveillance, awareness of CA-125 as a tumor marker, and perceived disease status. Attributes include psychosocial symptoms characterized by a fixation with CA-125 levels and symptoms of anxiety, depression, distress, and illness intrusiveness that present in a cyclical pattern. Consequences include urgency to treat rising levels and surveillance and survivorship care preferences.

Conclusions:

CA-125 preoccupation is characterized by psychosocial symptoms that present in a cyclical and dynamic state akin to living “test to test” or feeling suspended in a perpetual cycle of tests, driven by a desire to feel relief or prompt action.

Implications for Practice:

Nurses are poised to influence the patient’s experience through identification of the presence of CA-125 preoccupation and its consequences. Understanding the antecedents and attributes of CA-125 may assist with identifying women who are most at risk.

What is Foundational:

This research presents the first known conceptual definition of CA-125 preoccupation, which may lead to validated survey measures and improved survivorship care.
Ultrasound Therapy as a Treatment for Valvular Aortic Stenosis: A Review
Authors: Kidwai Nermeen , Frishman William H.
Published: October 2024

Calcific aortic stenosis is the most common form of aortic stenosis, and offers a poor prognosis in affected patients. Current treatment methods for aortic stenosis, including open surgical aortic valve repair and transcatheter aortic valve replacement, are invasive, and require the patient to undergo open-heart surgery with cardiopulmonary bypass. Ultrasound therapy offers a potential solution for patients ineligible for traditional surgical treatment. Noninvasive ultrasound therapy allows for decalcification of aortic valves without open sternotomy or cardiopulmonary bypass. This article reviews the use of ultrasound therapy for aortic stenosis, including this newer method of noninvasive ultrasound therapy.
Intrapartum Ultrasound Guidance to Make Safer Any Obstetric Intervention: Fetal Head Rotation, Assisted Vaginal Birth, Breech Delivery of the Second Twin
Authors: Dall’Asta Andrea , Melito Chiara , Ghi Tullio
Published: October 2024

Intrapartum ultrasound (US) is more reliable than clinical assessment in determining parameters of crucial importance to optimize the management of labor including the position and station of the presenting part. Evidence from the literature supports the role of intrapartum US in predicting the outcome of labor in women diagnosed with slow progress during the first and second stage of labor, and randomized data have demonstrated that transabdominal US is far more accurate than digital examination in assessing fetal position before performing an instrumental delivery. Intrapartum US has also been shown to outperform the clinical skills in predicting the outcome and improving the technique of instrumental vaginal delivery. On this basis, some guidelines recommend intrapartum US to ascertain occiput position before performing an instrumental delivery. Manual rotation of occiput posterior position (MROP) and assisted breech delivery of the second twin are other obstetric interventions that can be performed during the second stage of labor with the support of intrapartum US. In this review article we summarize the existing evidence on the role of intrapartum US in assisting different types of obstetric intervention with the aim to improve their safety.
Understanding what it is like to experience pain as you grow up: a poetic meta-ethnography
Authors: Toye Francine , Hannink Erin , Woolverton Amy , Barker Karen L.
Published: October 2024

A recent Lancet Commission raised concerns about the management of child and adolescent pain. We aimed to undertake a comprehensive review of qualitative research to understand children and adolescent pain experiences across contexts. We used the 7 stages of meta-ethnography to synthesise findings. We combined the strengths of arts-based methods, translating themes into poems in a range of languages. We screened 7471 titles, 464 abstracts, and 302 full texts, including 189 reports (177 unique samples) incorporating 5875 young people. Age range across studies was 2 to 38 years, with 93% including those between the age of 11 and 20 years old. Studies spanned 30 years (1993-2023) with 121 (64%) published in the last 10 years. Almost all (93%) were set-in high-income countries. We report 6 themes focusing on transition to adulthood: (1) I want to stay within the safety of home; (2) don't exclude me from my own care; (3) it might hurt but it's for my own good; (4) I rely on others but I want some independence; (5) I am no longer a child but I am not an adult yet; and (6) I wasn't prepared for the transfer to adult health care. Our findings focus on the complex transition into adulthood and the importance of creating a genuine healthcare partnership with young people by acknowledging their perspectives, creating a safe and supportive environment, and preparing them for the transition to adult pain care. Arts-based methods have the potential to make findings from qualitative evidence syntheses accessible and impactful for compassionate health care.
Personalised decision support in the management of patients with musculoskeletal pain in primary physiotherapy care: a cluster randomised controlled trial (the SupportPrim project)
Authors: Granviken Fredrik , Meisingset Ingebrigt , Bach Kerstin , Bones Anita Formo , Simpson Melanie Rae , Hill Jonathan C. , van der Windt Danielle A. , Vasseljen Ottar
Published: October 2024

We developed the SupportPrim PT clinical decision support system (CDSS) using the artificial intelligence method case-based reasoning to support personalised musculoskeletal pain management. The aim of this study was to evaluate the effectiveness of the CDSS for patients in physiotherapy practice. A cluster randomised controlled trial was conducted in primary care in Norway. We randomised 44 physiotherapists to (1) use the CDSS alongside usual care or (2) usual care alone. The CDSS provided personalised treatment recommendations based on a case base of 105 patients with positive outcomes. During the trial, the case-based reasoning system did not have an active learning capability; therefore, the case base size remained the same throughout the study. We included 724 patients presenting with neck, shoulder, back, hip, knee, or complex pain (CDSS; n = 358, usual care; n = 366). Primary outcomes were assessed with multilevel logistic regression using self-reported Global Perceived Effect (GPE) and Patient-Specific Functional Scale (PSFS). At 12 weeks, 165/298 (55.4%) patients in the intervention group and 176/321 (54.8%) in the control group reported improvement in GPE (odds ratio, 1.18; confidence interval, 0.50-2.78). For PSFS, 173/290 (59.7%) patients in the intervention group and 218/310 (70.3%) in the control group reported clinically important improvement in function (odds ratio, 0.41; confidence interval, 0.20-0.85). No significant between-group differences were found for GPE. For PSFS, there was a significant difference favouring the control group, but this was less than the prespecified difference of 15%. We identified several study limitations and recommend further investigation into artificial intelligence applications for managing musculoskeletal pain.
A Trauma-Informed Approach for Care of a Postpartum Patient With Provoked-Localized Vulvodynia: A Case Report
Authors: Parr Rebecca E.
Published: October 2024

Introduction:

Vulvodynia is a chronic pelvic pain condition affecting at least 10% of individuals with a vulva. Its complex and multifactorial etiology can be exacerbated by adverse childhood events (ACEs), which intensify pain symptoms and complicate treatment. This case report outlines a comprehensive trauma-informed treatment strategy for addressing persistent vulvodynia in a patient with a history of traumatic ACEs.

Case Description:

This case report describes a 30-year-old female with provoked localized vulvodynia, and a history of multiple ACEs. A trauma-informed plan of care was created which emphasized consent, control, emotional safety, and compassionately listening to avoid re-traumatization. The patient was seen for 15 physical therapy visits over six months. Her pain reduced from 9/10 to 3/10 on the NRPS, exceeding the minimally clinically important difference. The Marinoff dyspareunia scale reduced from 3 to 1. She was able to return to previously painful activities, such as wearing underwear and blue jeans, and unlimited sitting, standing, and walking.

Discussion:

ACEs can adversely affect the pelvic floor and the nervous system. Adopting trauma-informed practices can assist patients in overcoming effects of trauma, and improve communication, plan of care adherence, and overall outcomes. Trauma-informed practice should be standard of care with all patients, as it encourages empowerment, choice, collaboration, and safety.
Taming the hunger hormones
Authors: Butzlaff Alice , Moore Dorothy J.
Published: October 2024

GLP-1 receptor agonists, initially developed to manage type 2 diabetes, are now widely used for weight loss due to their ability to manage hunger. As their use expands rapidly, nurses need to be informed about these drugs and their impact on various health conditions.
Efficacy of Mindfulness Exercises for Primary Osteoporosis Pain and Balance
Authors: Lyu Fang Fei , Ramoo Vimala , Chui Ping Lei , Ng Chong Guan
Published: October 2024

Mindfulness exercise has shown great benefits for patients with osteoporosis. However, there are various types of mindfulness exercises and no studies have compared their efficacy. The aim of this study was to compare the efficacy of mindfulness exercises on pain and balance in patients with primary osteoporosis. Articles published in 10 English and three Chinese language databases from January 1, 2003, to December 31, 2022, were systematically searched. Twenty-two studies (N = 1,603) of five types of mindfulness exercises (Pilates, Ba Duan Jin, Wu Qin Xi, Tai Chi, and Yi Jin Jing) were eligible for this meta-analysis. Evidence from this review indicated that all five of the mindfulness exercises included in this study effectively reduced pain and improved balance for patients with primary osteoporosis. Pilates had the highest value of surface under the cumulative ranking as the best intervention. Future studies could consider developing a standard guideline for mindfulness exercise to be incorporated into osteoporosis rehabilitation.
Minimally Invasive Surgery for the Management of Ovarian Cancer
Authors: Nezhat Farr , Briskin Camille , Lakhi Nisha , Fu Rongwei , Pejovic Tanja
Published: October 2024

OBJECTIVE:

To examine perioperative and survival outcomes of patients with ovarian cancer managed by minimally invasive surgery compared with laparotomy in the context of 1) early-stage epithelial ovarian cancer, 2) primary cytoreduction for advanced disease, and 3) interval debulking after neoadjuvant chemotherapy.

DATA SOURCES:

A literature search was conducted PubMed, MEDLINE and ClinicalTrials.gov, Web of Science, Cochrane Library, and meeting abstract libraries (International Gynecological Cancer Society, Society of Gynecologic Oncology, American Society of Clinical Oncology) from 1994, the year of the first published laparoscopic clinical study in ovarian cancer, to May 2024. Studies that compared minimally invasive surgery with laparotomy for staging of ovarian cancer and reported perioperative or survival outcomes data were included. Single-arm studies, case studies, meeting abstracts, and studies involving borderline tumors, fertility-sparing surgery, or management of recurrent disease were excluded.

METHODS OF STUDY SELECTION:

Three authors independently screened citations for relevance and inclusion and exclusion criteria and assessed the risk of bias of individual studies using the methodologic index for nonrandomized studies criteria for nonrandomized studies.

TABULTATION, INTEGRATION, AND RESULTS:

From a total of 2,777 identified citations, 36 nonrandomized studies were included: 21 early-stage, five primary debulking for advanced stages, seven interval debulking after neoadjuvant chemotherapy, and three with heterogeneous populations. No randomized studies were identified. For early-stage cancer, nine studies found no difference in progression-free survival (risk ratio [RR] 1.05, 95% CI, 1.00–1.10, I
2=34.7%, P=.151), and 12 studies found no difference in overall survival (RR 1.00, 95% CI, 0.98–1.03, I
2=49.7%, P=.025). For primary debulking of advanced disease, rate of optimal debulking (five studies) (RR 1.11, 95% CI, 1.00–1.25, I
2=41.5%, P=.144) slightly favored minimally invasive techniques. For interval debulking, there was no difference in rates of optimal debulking (five studies) (RR 1.03, 95% CI, 0.96–1.11, I
2=54.6%, P<.051) between the two surgical modalities.

CONCLUSION:

The inclusion of observational studies in this analysis with a fair amount of bias warrants caution in the interpretation of the findings. However, minimally invasive surgery may offer some perioperative advantages over laparotomy and may be an acceptable alternative for selected patients. For early-stage disease, there was no difference in survival outcomes between minimally invasive surgery and laparotomy. For those with advanced disease, rates of optimal debulking were similar.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD42022359051.
Diagnostic Safety: Needs Assessment and Informed Curriculum at an Academic Children’s Hospital
Authors: Congdon Morgan , Rasooly Irit R. , Toto Regina L. , Capriola Danielle , Costello Anna , Scarfone Richard J. , Weiss Anna K.
Published: October 2024

Background:

Diagnostic excellence is central to healthcare quality and safety. Prior literature identified a lack of psychological safety and time as barriers to diagnostic reasoning education. We performed a needs assessment to inform the development of diagnostic safety education.

Methods:

To evaluate existing educational programming and identify opportunities for content delivery, surveys were emailed to 155 interprofessional educational leaders and 627 clinicians at our hospital. Educational leaders and learners were invited to participate in focus groups to further explore beliefs, perceptions, and recommendations about diagnostic reasoning. The study team analyzed data using directed content analysis to identify themes.

Results:

Of the 57 education leaders who responded to our survey, only 2 (5%) reported having formal training on diagnostic reasoning in their respective departments. The learner survey had a response rate of 47% (293/627). Learners expressed discomfort discussing diagnostic uncertainty and preferred case-based discussions and bedside learning as avenues for learning about the topic. Focus groups, including 7 educators and 16 learners, identified the following as necessary precursors to effective teaching about diagnostic safety: (1) faculty development, (2) institutional culture change, and (3) improved reporting of missed diagnoses. Participants preferred mandatory sessions integrated into existing educational programs.

Conclusions:

Our needs assessment identified a broad interest in education regarding medical diagnosis and potential barriers to implementation. Respondents highlighted the need to develop communication skills regarding diagnostic errors and uncertainty across professions and care areas. Study findings informed a pilot diagnostic reasoning curriculum for faculty and trainees.
miR-374 family is a key regulator of chronic primary pain onset
Authors: Hernandez Nathaniel P. , Rawls Ashleigh , Chen Jiegen , Zhang Xin , Wang Yaomin , Gao Xianglong , Parisien Marc , Karaky Mohamad , Meloto Carolina Beraldo , Montagna Francesca , Dang Hong , Pan Yue , Zhao Ying , McLean Samuel , Linnstaedt Sarah , Diatchenko Luda , Nackley Andrea G.
Published: October 2024

Introduction:

Chronic primary pain conditions (CPPCs) are linked to catecholamine activation of peripheral adrenergic receptors. Yet, catecholamine-dependent epigenetic mechanisms, such as microRNA (miRNA) regulation of mRNA transcripts, remain largely unknown.

Objectives:

We sought to identify RNA species correlated with case status in 3 pain cohorts, to validate RNAs found to be dysregulated in a mouse model of CPPC onset, and to directly test the role of adrenergic receptors in miRNA regulation. Furthermore, we tested antinociceptive effects of miR-374 overexpression.

Methods:

We used RNA-seq and quantitative reverse transcription polymerase chain reaction to measure RNA expression in 3 pain cohorts. Next, we validated identified RNAs with quantitative reverse transcription polymerase chain reaction in a mouse model of CPPC onset, measuring expression in plasma, peripheral (adipose, muscle, dorsal root ganglia [DRG]), and central (spinal cord) tissues. Then, we stimulated adrenergic receptors in primary adipocyte and DRG cultures to directly test regulation of microRNAs by adrenergic signaling. Furthermore, we used in vitro calcium imaging to measure the antinociceptive effects of miR-374 overexpression.

Results:

We found that one miRNA family, miR-374, was downregulated in the plasma of individuals with temporomandibular disorder, fibromyalgia syndrome, or widespread pain following a motor vehicle collision. miR-374 was also downregulated in plasma, white adipose tissue, and spinal cord from mice with multisite mechanical sensitivity. miR-374 downregulation in plasma and spinal cord was female specific. Norepinephrine stimulation of primary adipocytes, but not DRG, led to decreased miR-374 expression. Furthermore, we identified tissue-specific and sex-specific changes in the expression of predicted miR-374 mRNA targets, including known (HIF1A, NUMB, TGFBR2) and new (ATXN7, CRK-II) pain targets. Finally, we demonstrated that miR-374 overexpression in DRG neurons reduced capsaicin-induced nociceptor activity.

Conclusions:

Downregulation of miR-374 occurs between adrenergic receptor activation and mechanical hypersensitivity, and its adipocyte source implicates adipose signaling in nociception. Further study of miR-374 may inform therapeutic strategies for the millions worldwide who experience CPPCs.
The Status of Liver Margin in Perihilar Cholangiocarcinoma
Authors: Jin Shuo , Lin Ming-Yu , Xiang Can-Hong , Liu Zhi-Peng , Wang Si-Yuan , Jiang Nan , Li Li , Shan Si-Qiao , Zeng Jian-Ping , Yin Hai-Xin , Zhang Tao , Yang Chang-Zhen , Yang Dong-Liang , Zhou Hu , Chen Zhi-Yu , Dong Jia-Hong
Published: October 2024

Objective:

This study aimed to investigate the prevalence and distribution of carcinoma in the liver margin (LM) of resected perihilar cholangiocarcinoma (pCCA) and establish a method for LM examination.

Background:

LM is the largest margin in resected pCCA with undefined status and assessment method.

Methods:

227 pCCA cases underwent major hepatectomy were divided into a discovery cohort (n=101) assessed using serial whole-mount digital large sections (WDLS) combined with small sections, and a control cohort (n=126) assessed using only small sections.

Results:

The LM R1 resection rate was 38.6% (39/101) in the discovery cohort and 5.6% (7/126) in the control cohort. WDLS identified more LM R1 cases compared to the small section in the discovery cohort (38.6% vs. 5.9%, P<0.001). R0 patients in the discovery cohort had better overall survival and recurrence-free survival than those in the control cohort (both P<0.05). Additionally, 95% of carcinoma was found within 20 mm of the proximal ductal margin (DM). A proximal DM distance of<5 mm was an independent risk factor for LM R1 resection. Patients with which are more likely to experience R1 compared to those with ≥ 5 mm (P<0.001).

Conclusions:

Positive LM was the significant cause for R1 resection of pCCA and the utilization of WDLS improved the diagnostic accuracy of LM. An examination methodology was established, highlighting the necessity of examining LM within a 20 mm radius around the proximal DM, especially in patients with a proximal DM of<5 mm.
Starting Physical Activity From Scratch is Never Easy
Authors: Criss Michelle G. , Irwin Kent E. , Wingood Mariana
Published: October 2024

Physical activity is a powerful intervention that addresses physiologic and functional changes stemming from age, pathology, as well as recovery from injury and illness. However, only 9% of older adults complete the recommended amounts and types of physical activity weekly. This article provides a step-by-step process for initiating a physical activity program with individuals who are starting from a baseline of little to no activity. In addition, this article reviews quantifying baseline levels of physical activity, identifying what matters most, determining readiness to perform physical activity, developing goals, creating an action plan, addressing barriers, assessing self-efficacy, and follow-up for challenges.
Dosing Balance Training for Older Adults
Authors: Espy Debbie , Lyon Marissa F.
Published: October 2024

The physical processes that contribute to balance may decline as humans age. In exercise-based balance training, the most effective intervention for improving balance and falls-reduction among older adults, the type of exercise is set first, then intensity, then time. Clinical decision making about type of exercise program is based on examination and assessment of the person, including their goals and contributing impairments. Intensity is poorly reported, but 2 tools to measure and modulate intensity have been developed. Time component recommendations vary: most common are 2 to 3 times per week for 30-45 min for 12 weeks.
Dosing and Specificity of Training to Sustain Maximal Walking Speed in Highly Mobile Older Adults
Authors: Viviers Wendy K. , Jordre Becca D.
Published: October 2024

Compared to their sedentary peers, older track athletes demonstrate a superior ability to negate the normal age-related changes in gait mechanics known to attenuate maximal walking speed performance with age. Sports-specific exercises commonly utilized to affect this end may be appropriately scaled to benefit a wider subset of older adults. Optimal dosing of resistance training to maximize gluteus maximus functional fitness, accompanied by gait reeducation to augment motor patterns facilitating optimal peak trailing leg extension and push-off intensity, create a redundancy in walking capacity likely to prolong functional independence for beneficiaries of this targeted intervention.
Psychotropic Polypharmacy Leading to Reversible Dementia: A Case Report
Authors: Lahiri Durjoy , Seixas-Lima Bruna , Roncero Carlos , Stokes Kathryn , Panda Swayang Sudha , Chertkow Howard
Published: October 2024

Psychotropic polypharmacy presents a diagnostic challenge that may be further complicated by inadequate medication history and underappreciation of the cognitive effects of such polypharmacy. Here we present the case of a 57-year-old man who presented to our memory clinic with progressive cognitive decline and a prior neuropsychological evaluation supporting the diagnosis of a neurodegenerative disorder. He was taking multiple psychotropic medications at the time, but the exact dosages were unclear due to a lack of collateral history. He was also taking prescribed opioids and a combination of buprenorphine and naloxone for pain relief, again with unclear dosages at the time of presentation. Brain imaging and cerebrospinal spinal fluid biomarker testing were negative for Alzheimer pathophysiologic processes. Months later, the patient was taken to the emergency room after an overdose caused by overuse of opioid medications. Once he was taken off all psychoactive medications, the patient’s cognitive impairment completely reversed, and he became independent in activities of daily living. Psychotropic polypharmacy can have a myriad of cognitive manifestations which need to be better recognized by clinicians. Deprescription of such medications should be attempted whenever clinically appropriate.