bluuebunny/crossref_metadata_2025 huggingface dataset:
Couple therapy with parents: Results from a pragmatic randomized controlled trial testing the Integrative Brief Systemic Intervention (IBSI)
Authors: Darwiche Joëlle , Antonietti Jean‐Philippe , Nunes Cindy Eira , Favez Nicolas , Liekmeier Esther , de Roten Yves
Published: December 2022

This study aimed to compare the effectiveness of the Integrative Brief Systemic Intervention (IBSI), combining therapeutic work on marital and coparenting relationships with brief systemic therapy (BST‐as‐usual) for parent couples. Couples were randomly assigned to the IBSI (n = 51) or BST (n = 50). Both treatments were six‐session interventions and lasted about 6 months. Questionnaires on individual, marital, coparenting and family‐related functioning were completed before and after therapy, and at 6‐month follow‐up. A significant improvement in all areas of functioning was observed after treatment and maintained at follow‐up for both IBSI and BST‐as‐usual treatments. No significant differences in outcomes were found between the treatments. Additionally, women reported more distress overall than men, and this distress was reduced more significantly after therapy. Last, BST‐as‐usual couples requested more additional sessions compared to IBSI couples. This study extends the literature on couple therapy with parents.
Evaluation of molasses on fermentation profiles of wheat straw ensiled with tall fescue in the southwest Tibet
Authors: Dong Dong , Dai Tongtong , Zong Cheng , Yin Xuejing , Bao Yuhong , Shao Tao
Published: December 2022

Two experiments were carried out to determine the optimal proportion of mixed silage made with wheat straw and tall fescue, and further to evaluate the effects of molasses on fermentation quality. In Experiment 1, wheat straw and tall fescue were mixed at proportions of 10:0 (Control), 8:2 (WT20), 6:4 (WT40) and 4:6 (WT60) on fresh weight (FW) basis. Inclusion of tall fescue significantly (p < 0.05) increased lactic acid, water‐soluble carbohydrate contents and ratio of lactic to acetic acid, and significantly (p < 0.05) decreased pH and contents of dry matter, NH3‐N and volatile fatty acids. WT60 had the highest (p < 0.05) lactic acid content, and the lowest (p < 0.05) pH and butyric acid content. In Experiment 2, the mixture of wheat straw and tall fescue (4/6) were treated with 0%, 3%, 4% and 5% molasses on FW basis (defined as control, WTM3, WTM4 and WTM5 respectively). Molasses addition significantly (p < 0.05) increased lactic acid and water‐soluble carbohydrate contents, and significantly (p < 0.05) decreased pH and ammonia‐nitrogen content as compared with control. Acetic acid content slightly (p > 0.05) decreased during ensiling, while trace amounts of propionic and butyric acids were observed. WTM5 had the lowest pH and the highest (p < 0.05) lactic acid, water‐soluble carbohydrate contents and ratio of lactic to acetic acid at end of ensiling. In conclusion, the fermentation quality was maximally improved when the addition rate of molasses was 5% in 40% wheat straw ensiled with 60% tall fescue.
“Teachers think the kids around here, don't really want to learn”: Street‐identified black men and women's attitudes toward teachers and schooling
Authors: Payne Yasser Arafat , Aviles Ann M. , Yates Nefetaria A.
Published: December 2022

This street participatory action research project explored the reflective schooling experiences of street identified Black men and women (ages 18–35) in two small low‐income neighborhoods. Secondary analysis of survey (N = 520) and interview (N = 46) data examined: (1) How are attitudes toward schooling and teachers affected by race, gender and age?; and (2) How do students utilize a street‐identity as a site of resilience inside schools? Overall, street‐identified study participants held positive attitudes toward schooling, but generally performed poorly in schools and had negative experiences with educators. No significance was found as a function of gender and age regarding attitudes toward schooling and attitudes toward teachers. Also, interview results, across gender and age, suggest school‐related structural challenges and poor teacher‐student relationships contributed to severe conflict between students and teachers; and between students. Interviewees argued some Black students internalized a street identity or became disruptive and even engaged in school violence as a protective mechanism to endure hostile schooling environments. Moreover, Street PAR is discussed as a method and intervention to improve student performance and resolve concerns between students and educators.
The impact of rural emptiness on gender relations in postsocialist Albania
Authors: Brooks Sally , Meçe Merita H.
Published: December 2022

This article explores impacts of dramatic levels of outmigration from Puka, a remote region of northern Albania. Since 1991 depopulation, economic decline and state withdrawal have created conditions of what Dzenovska calls rural emptiness. Drawing on focus group discussions with women from eight villages, it explores how conditions of rural emptiness have led to a transformation of gender contracts, with women taking on additional responsibilities. However, these changes have been accommodated within a re‐traditionalised patriarchal system through the devaluation of tasks assigned to women, their increased surveillance by male relatives and erosion of women's social life outside the household.
A preliminary investigation of the impact of artificially carbonated water bathing on canine skin physiological and barrier function
Authors: Iyori Keita , Tamagawa Shinichi , Ide Kaori , Nishifuji Koji
Published: December 2022

Background

The effect of carbon dioxide (CO2)‐rich water bathing on the skin has been studied extensively in humans. However, there have been few studies evaluating the impact of CO2‐rich water bathing on canine skin physiology and barrier functions.

Objectives

To evaluate the impact of artificially carbonated water (ACW) bathing on skin parameters in healthy beagles.

Animals

Six healthy beagles with no history of skin disease.

Materials and Methods

Body temperature, skin temperature, transepidermal water loss (TEWL), skin hydration and skin blood flow were evaluated before and after single ACW bathing (37°C, 20 min) with a CO2 concentration of >1000 ppm.

Results

After ACW bathing, skin blood flow significantly increased (p < 0.0001), yet there were no significant changes in body temperature (p = 0.3124), skin temperature (p = 0.4911), TEWL (p = 0.5167) or skin hydration (p = 0.3084). There were no adverse events during the trials.

Conclusions and Clinical Importance

Artificially carbonated water water bathing could potentially increase skin blood flow without affecting skin temperature, body temperature and skin barrier function in dogs, similar to its effects in humans.
In vitro elution of amikacin from four hydrogel preparations: A pilot study
Authors: Hottmann Natasha M. , Raines Katherine , Droog Madeline , Steiner Joerg M. , Thieman Mankin Kelley M.
Published: December 2022

Objective

To determine in vitro elution of amikacin from poloxamer 407 NF, 1% carboxymethylcellulose (CMC), 3% CMC, 5% CMC, and control (sterile water).

Study design

Descriptive in vitro.

Sample population

Triplicate samples from each experimental group.

Methods

Amikacin solution was prepared in poloxamer 407 NF, 1% CMC, 3% CMC, 5% CMC, or sterile water. Then, 1 ml of phosphate‐buffered saline (PBS) was added to each of three aliquots per base and the samples were incubated at 37°C. PBS was removed and replaced at 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours and amikacin concentration was measured.

Results

The highest median concentration of amikacin in the eluent of poloxamer 407 NF, 3% CMC, and 5% CMC was observed at 48 hours: 3300, 3030, and 2190 μg/ml, respectively. The highest median concentration of amikacin in the eluent of 1% CMC and sterile water were observed at 1 hour: 13300 and 15600 μg/ml, respectively. Median eluent concentration of amikacin exceeded 2000 μg/ml (the reported minimum inhibitory concentration [MIC] of certain biofilm‐producing methicillin‐resistant Staphylococcus pseudintermedius) from 24 to 96 hours for poloxamer 407 NF, 24–72 hours for 3% CMC, 48–72 hours for 5% CMC, 1–4 hours for 1% CMC, and 1–4 hours for sterile water.

Conclusion

Amikacin elution from tested substances reached or exceeded target MIC during the 240 hours tested.

Clinical significance

Hydrogel‐amikacin solutions may be useful topical treatment options for some infected wounds. In vivo safety and efficacy should be evaluated.
Maternal allogeneic cancellous bone graft for the treatment of osteitis along the physeal scar of the proximal metatarsus in a foal
Authors: Sauer Fay J. , Verhaar Nicole , Geburek Florian
Published: December 2022

Objective

To describe the treatment and outcome of a foal with a fresh allogenic cancellous bone graft after surgical debridement of a traumatic septic osteitis.

Animal

A neonatal Quarter Horse foal.

Study design

Case report.

Methods

The foal sustained a traumatic laceration exposing the proximal third metatarsal bone. One week after surgical debridement and closure, radiographic signs of septic osteitis were noted along the physeal scar. The lesion was debrided, and antimicrobial therapy was implemented. The infection resolved but left a large defect in the metaphysis and epiphysis. Grafting was indicated to avoid pathologic fractures of the plantar and proximal cortices. Due to a discrepancy between defect size and the bone stock of the foal, an allogeneic cancellous bone graft was harvested from the dam's tuber coxae and used to fill the foal's defect.

Results

No adverse reactions to the graft were noted. After 1 month, the wound had healed. Radiographic examination was consistent with graft incorporation in the bone structure. The foal was sound at a walk and trot when examined at 6, 12, and 21 months. The bone's contour was even and its structure homogeneously radio dense. The surgical site of the mare healed without complications.

Conclusion

Fresh allogenic cancellous bone grafting resulted in the healing of a large traumatic‐septic bone defect in a foal, with an excellent functional and cosmetic outcome. For future use, compatibility testing should be considered prior to allogeneic bone grafting.
Thermodynamic Properties of Vapors
Authors: Leib Erich F.
Published: December 2022

By introducing new properties of state and an ideal system, that is, a perfect vapor, the representation of the thermodynamic properties of vapors is simplified. The field of state reduces to one curve of state which requires in the experimental investigation of vapors only as many measurements as are necessary for the determination of this curve. The equations of state are found more easily, the calculations required to determine the vapor tables are reduced, and a simple formula for the external work is found. An analytic investigation of the equilibrium of a liquid with its vapor shows how the vapor-pressure curve can be found from the equation of state.
Interpretation of Creep Tests on Tubes
Authors: Soderberg C. R.
Published: December 2022

In a companion paper, Professor Norton has presented the results of creep tests on tubes, carried out under Project 10, of the Joint Research Committee on Effect of Temperature on the Properties of Metals. The present paper contains a discussion of the phenomena involved in the light of the accepted theory of yielding, the theoretical basis for the present research program, and the significance of the results thus far obtained.
Measurement of Inertial and Acoustic Waves in a Turbine Chute Rim Seal Cavity
Authors: Bru Revert Anna , Beard Paul F. , Chew John W.
Published: December 2022

A chute rim seal cavity has been instrumented with time-resolved and time-averaged pressure transducers as well as a gas concentration measurement system at the Oxford Rotor Facility. The unsteady pressure transducers were unevenly distributed along the circumference generating 15 combinations of angular spacing to conduct a phase analysis. The test operating conditions were modified through different configurations of mainstream flow, a range of rotational speeds and several rates of purge flow to obtain test data in the regimes of rotationally-driven, pressure-driven, and combined ingestion. The rotating unsteady flow structures within the rim seal cavity were studied through a combination of phase analysis of dynamic pressure signals and inspection of the frequency domain. The introduction of mainstream flow (axial and swirled) increased the overall unsteadiness exciting an additional band of lower frequencies. The phase analysis revealed these were associated with acoustic waves, providing the first experimental evidence of the presence and coexistence of inertial and acoustic waves in the rim seal cavity. The interaction of the inertial and acoustic waves strongly depends on the operating conditions, and may be linked to changes in sealing effectiveness.
How to Build Your Mentoring Tree—Insight Gained From a 36-Year Career in Biomedical Engineering
Authors: Grimm Michele J.
Published: December 2022

Mentoring is often viewed as a unidirectional relationship, with the senior, more seasoned individual imparting knowledge, guidance, and experience to more junior individuals. But this structure limits our ability to recognize that the mentoring relationship can bring benefits and opportunities for growth to the mentor as well. On the occasion of receiving the 2022 Robert M. Nerem Education and Mentorship Medal, I have had the opportunity to reflect on the mentoring that I have been lucky enough to participate in—both as mentor and mentee—during my academic career. This paper discusses some of those insights and presents the concept of a mentoring tree—through which we can identify multiple mentors and mentees, each of whom can provide mutual support and insight as we progress through our careers. Each individual who is part of our mentoring tree can play a role at different times and with different challenges within our professional path. This everchanging and growing structure provides continuous mentoring without overtaxing any single relationship.
Associations Among Physical Activity, Adiposity, and Insulin Resistance in Children Exposed In Utero to Maternal Obesity With and Without Gestational Diabetes
Authors: Moore Bethany A. , Callahan Makenzie L. , Martin Samantha L. , Everett Alysha , Garvey W. Timothy , Chandler-Laney Paula
Published: December 2022

Purpose: Investigate whether obesity risk and current weight status are independently associated with physical activity (PA) and whether PA is associated with adiposity and insulin resistance (homeostatic model assessment of insulin resistance) among children with high versus low obesity risk based on in utero exposure to maternal overweight/obesity with gestational diabetes mellitus (GDM; high risk) or without GDM (overweight/obesity; high risk) or maternal normal weight without GDM (low risk). Method: Secondary analysis of data from children born to women with overweight/obesity and GDM, overweight/obesity without GDM, or normal weight without GDM. PA was assessed with accelerometry, percentage of body fat derived from anthropometrics, and homeostatic model assessment of insulin resistance calculated from glucose and insulin. Results: Among 4- to 10-year-old children (N = 163), analyses of covariance showed that children with a current BMI ≥85th percentile had less vigorous PA than those with BMI <85th percentile, but in utero exposure was not an independent predictor of PA. In linear regression modeling, moderate to vigorous PA was inversely associated with percentage of body fat and homeostatic model assessment of insulin resistance independent of age, Tanner stage, and accelerometer wear time, with stronger associations in high-risk groups. Conclusions: Children’s PA is related to current weight status but not underlying risk for obesity but may be especially important to reduce obesity and insulin resistance in high-risk children.
Layer-specific pain relief pathways originating from primary motor cortex
Authors: Gan Zheng , Gangadharan Vijayan , Liu Sheng , Körber Christoph , Tan Linette Liqi , Li Han , Oswald Manfred Josef , Kang Juhyun , Martin-Cortecero Jesus , Männich Deepitha , Groh Alexander , Kuner Thomas , Wieland Sebastian , Kuner Rohini
Published: December 2022

The primary motor cortex (M1) is involved in the control of voluntary movements and is extensively mapped in this capacity. Although the M1 is implicated in modulation of pain, the underlying circuitry and causal underpinnings remain elusive. We unexpectedly unraveled a connection from the M1 to the nucleus accumbens reward circuitry through a M1 layer 6-mediodorsal thalamus pathway, which specifically suppresses negative emotional valence and associated coping behaviors in neuropathic pain. By contrast, layer 5 M1 neurons connect with specific cell populations in zona incerta and periaqueductal gray to suppress sensory hypersensitivity without altering pain affect. Thus, the M1 employs distinct, layer-specific pathways to attune sensory and aversive-emotional components of neuropathic pain, which can be exploited for purposes of pain relief.
Transition metal–free ketene formation from carbon monoxide through isolable ketenyl anions
Authors: Jörges Mike , Krischer Felix , Gessner Viktoria H.
Published: December 2022

The capacity of transition metals to bind and transform carbon monoxide (CO) is critical to its use in many chemical processes as a sustainable, inexpensive C1 building block. By contrast, only few s- and p-block element compounds bind and activate CO, and conversion of CO into useful carbonyl-containing organic compounds in such cases remains elusive. We report that metalated phosphorus ylides provide facile access to ketenyl anions ([RC=C=O]
–
) by phosphine displacement with CO. These anions are very stable and storable reagents with a distinctive electronic structure between that of the prototypical ketene (H
2
C=C=O) and that of ethynol (HC≡C–OH). Nonetheless, the ketenyl anions selectively react with a range of electrophiles at the carbon atom, thus offering high-yielding and versatile access to ketenes and related compounds.
Can peer reviewing preprints catch on?
Authors: Brainard Jeffrey
Published: December 2022

As unreviewed studies proliferate online, researchers are eyeing ways to boost critiques
Mitochondrial augmentation of hematopoietic stem cells in children with single large-scale mitochondrial DNA deletion syndromes
Authors: Jacoby Elad , Bar-Yosef Omer , Gruber Noah , Lahav Einat , Varda-Bloom Nira , Bolkier Yoav , Bar Diana , Blumkin Moriya Ben-Yakir , Barak Sharon , Eisenstein Etzyona , Ahonniska-Assa Jaana , Silberg Tamar , Krasovsky Tal , Bar Orly , Erez Neta , Bielorai Bella , Golan Hana , Dekel Benjamin , Besser Michal J. , Pozner Gat , Khoury Hanan , Jacobs Alan , Campbell John , Herskovitz Eli , Sher Noa , Yivgi-Ohana Natalie , Anikster Yair , Toren Amos
Published: December 2022

Patients with single large-scale mitochondrial DNA (mtDNA) deletion syndromes (SLSMDs) usually present with multisystemic disease, either as Pearson syndrome in early childhood or as Kearns-Sayre syndrome later in life. No disease-modifying therapies exist for SLSMDs. We have developed a method to enrich hematopoietic cells with exogenous mitochondria, and we treated six patients with SLSMDs through a compassionate use program. Autologous CD34
+
hematopoietic cells were augmented with maternally derived healthy mitochondria, a technology termed mitochondrial augmentation therapy (MAT). All patients had substantial multisystemic disease involvement at baseline, including neurologic, endocrine, or renal impairment. We first assessed safety, finding that the procedure was well tolerated and that all study-related severe adverse events were either leukapheresis-related or related to the baseline disorder. After MAT, heteroplasmy decreased in the peripheral blood in four of the six patients. An increase in mtDNA content of peripheral blood cells was measured in all six patients 6 to 12 months after MAT as compared baseline. We noted some clinical improvement in aerobic function, measured in patients 2 and 3 by sit-to-stand or 6-min walk testing, and an increase in the body weight of five of the six patients suffering from very low body weight before treatment. Quality-of-life measurements as per caregiver assessment and physical examination showed improvement in some parameters. Together, this work lays the ground for clinical trials of MAT for the treatment of patients with mtDNA disorders.
Porcine Hemagglutinating Encephalomyelitis Virus Co-Opts Multivesicular-Derived Exosomes for Transmission
Authors: Li Zi , Mu Shaoqian , Tian Yihan , Shi Junchao , Lan Yungang , Guan Jiyu , Zhao Kui , Gao Feng , He Wenqi
Published: December 2022

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a large number of deaths worldwide. Clinical neurological complications have occurred in some cases; however, knowledge of the natural history of coronavirus in the central nervous system (CNS) is thus far limited.
Compendium-Wide Analysis of Pseudomonas aeruginosa Core and Accessory Genes Reveals Transcriptional Patterns across Strains PAO1 and PA14
Authors: Lee Alexandra J. , Doing Georgia , Neff Samuel L. , Reiter Taylor , Hogan Deborah A. , Greene Casey S.
Published: December 2022

Pseudomonas aeruginosa
is a ubiquitous pathogen. There is much diversity among
P. aeruginosa
strains, including two divergent but well-studied strains, PAO1 and PA14.
Ontology of the complex rare-earth elements mineral system
Authors: Babaie Hassan A. , Davarpanah Armita , Elliott W. Crawford
Published: December 2022

The ree-ont ontology formally represents the semantics of the complex interactions in the rare-earth elements (REE) mineral system from a self-organized criticality perspective. This ontology models various primarily heat-driven, melt-led, ore-forming processes that contribute to the formation of the REE-bearing alkaline intrusive bodies and related hydrothermal deposits. It also models the processes that form sediment-hosted concentrations of the REE from the weathering and erosion of the primary REE deposits. The ontology explicitly formalizes the interactions among the members of various magmatic, hydrothermal, basinal, regolith, and supergene subsystems. It represents the principal geodynamic, tectonic, and geological driver, trigger, carrier, conduit, and barrier roles that the components of the REE mineral system recursively play in enriching the REE during the subcritical and critical stages of the evolution of the complex system in and on the surface of the Earth’s crust. ree-ont establishes a logical machine processable basis for understanding the dynamic interactions among various components of the REE mineral system by extending the upper-level Basic Formal Ontology (BFO) and its underlying mid-level Common Core Ontologies (CCO).
Mediterranean spotted fever with multiorgan involvement
Authors: Davis Kimberly , Ahmado Ahmad , Warrell Clare E , Downs Louise O , Furneaux Jenna , Sithamparanathan Karthiga
Published: December 2022

A previously well man in his 50s returned to the UK after a trip to the Mediterranean. The day after returning he developed malaise, fevers, rigors and severe headache. He was hospitalised with sepsis, multiorgan involvement, a maculopapular rash and an eschar on each hip. Serology was positive forRickettsiaspp (spotted fever group) with a rise in titre from 1:64 to 1:1024 eight days later. Blood and tissue PCR were also positive forRickettsiaspp. He had cardiac, pulmonary, renal, ocular and neurological involvement. He completed a 14-day course of doxycycline and recovered well. This is a case of likely Mediterranean spotted fever (MSF) caused byRickettsia conorii,which is endemic to the Mediterranean basin. We highlight the need for awareness and early treatment to prevent severe complications. This case is also the first to describe Purtscher-like retinopathy in the context of likely MSF.
Prolapsing vaginal fibroepithelial polyp
Authors: Leffelman Angela , Valaitis Sandra
Published: December 2022

Although uncommon, vaginal fibroepithelial polyps can present as prolapsing vaginal tissue, causing discomfort and anxiety. Surgical excision of the polyps can provide a minimally invasive solution. In this case, we describe a nulliparous female in late adolescence who presented for evaluation of tissue protruding through the vagina. On exam, a 5×4 cm fibroepithelial polyp was extending from the distal posterior vagina on a broad stalk. Successful transperineal surgical excision was performed. Fibroepithelial polyps, although uncommon, can be a cause for prolapsing vaginal tissue and should be part of the differential diagnosis, especially in patients who have no risk factors for pelvic organ prolapse. They can be excised vaginally, alleviating symptoms and distress. Because they sometimes recur, continued surveillance with gynaecological exams is recommended.
Digital solution for detection of undiagnosed diabetes using machine learning-based retinal image analysis
Authors: Zee Benny , Lee Jack , Lai Maria , Chee Peter , Rafferty James , Thomas Rebecca , Owens David
Published: December 2022

Introduction

Undiagnosed diabetes is a global health issue. Previous studies have estimated that about 24.1%–75.1% of all diabetes cases are undiagnosed, leading to more diabetic complications and inducing huge healthcare costs. Many current methods for diabetes diagnosis rely on metabolic indices and are subject to considerable variability. In contrast, a digital approach based on retinal image represents a stable marker of overall glycemic status.

Research design and methods

Our study involves 2221 subjects for developing a classification model, with 945 subjects with diabetes and 1276 controls. The training data included 70% and the testing data 30% of the subjects. All subjects had their retinal images taken using a non-mydriatic fundus camera. Two separate data sets were used for external validation. The Hong Kong testing data contain 734 controls without diabetes and 660 subjects with diabetes, and the UK testing data have 1682 subjects with diabetes.

Results

The 10-fold cross-validation using the support vector machine approach has a sensitivity of 92% and a specificity of 96.2%. The separate testing data from Hong Kong provided a sensitivity of 99.5% and a specificity of 91.1%. For the UK testing data, the sensitivity is 98.0%. The accuracy of the Caucasian retinal images is comparable with that of the Asian data. It implies that the digital method can be applied globally. Those with diabetes complications in both Hong Kong and UK data have a higher probability of risk of diabetes compared with diabetes subjects without complications.

Conclusions

A digital machine learning-based method to estimate the risk of diabetes based on retinal images has been developed and validated using both Asian and Caucasian data. Retinal image analysis is a fast, convenient, and non-invasive technique for community health applications. In addition, it is an ideal solution for undiagnosed diabetes prescreening.
Progressive resistance training in young people with Prader-Willi syndrome: protocol for a randomised trial (PRESTO)
Authors: Shields Nora , Bennell Kim L , Southby Alesha , Rice Lauren J , Markovic Tania , Bigby Christine , Prendergast Luke , Watts Jennifer J , Schofield Cara , Loughnan Georgina , Franklin Janet , Levitt David , Chikani Viral , McCallum Zoe , Blair Susan , Proietto Joseph , Taylor Nicholas F
Published: December 2022

Introduction

Preliminary evidence suggests that progressive resistance training may be beneficial for people with Prader-Willi Syndrome (PWS), a rare genetic condition that results in muscle weakness and low muscle tone.To establish whether community-based progressive resistance training is effective in improving the muscle strength of people with PWS; to determine cost-effectiveness; and, to complete a process evaluation assessing intervention fidelity, exploring mechanisms of impact, understanding participant experiences and identifying contextual factors affecting implementation.

Methods and analysis

A multisite, randomised controlled trial will be completed. Sixty participants with PWS will be randomised to receive either progressive resistance training (experimental) or non-progressive exercise (placebo control). Participants will be aged 13 to 60 years, be able to follow simple instructions in English and have no contraindications to performing progressive resistance training. The experimental group will complete progressive resistance training two times weekly for 24 weeks supervised by an exercise professional at a community gym. The control group will receive all aspects of the intervention except progressive overload. Outcomes will be assessed at week 25 (primary endpoint) and week 52 by a blinded assessor. The primary outcome is muscle strength assessed using one repetition maximum for upper limb and lower limb. Secondary outcomes are muscle mass, functional strength, physical activity, community participation, health-related quality of life and behaviour. Health economic analysis will evaluate cost-effectiveness. Process evaluation will assess safety and intervention fidelity, investigate mechanism of impact, explore participant experiences and identify contextual factors affecting implementation. Data collection commenced in February 2020 and will conclude in September 2023.

Ethics and dissemination

Ethical approval was obtained from The Royal Children’s Hospital Human Research Ethics Committee (HREC/50874/RCHM-2019) under the National Mutual Acceptance initiative. Research governance approvals were obtained from five clinical sites. Results will be disseminated through published manuscripts, conference presentations, public seminars and practical resources for stakeholder groups.

Trial registration number

ACTRN12620000416998; Australian and New Zealand Clinical Trial Registry.
Anti-corruption in global health systems: using key informant interviews to explore anti-corruption, accountability and transparency in international health organisations
Authors: Gorodensky Ariel , Bowra Andrea , Saeed Gul , Kohler Jillian
Published: December 2022

Objectives

Corruption undermines the quality of healthcare and leads to inequitable access to essential health products. WHO, Global Fund, United Nations Development Programme (UNDP) and World Bank are engaged in anti-corruption in health sectors globally. Throughout the COVID-19 pandemic, weakened health systems and overlooked regulatory processes have increased corruption risks. The objective of this study is thus to explore the strengths and weaknesses of these organisations’ anti-corruption mechanisms and their trajectories since the pandemic began.

Design, setting and participants

25 semistructured key informant interviews with a total of 27 participants were conducted via Zoom between April and July 2021 with informants from WHO, World Bank, Global Fund and UNDP, other non-governmental organisations involved in anti-corruption and academic institutions. Key informant selection was guided by purposive and snowball sampling. Detailed interview notes were qualitatively coded by three researchers. Data analysis followed an inductive-deductive hybrid thematic analysis framework.

Results

The findings demonstrate that WHO, World Bank, Global Fund and UNDP have shifted from criminalisation/punitive approaches to anti-corruption to preventative ones and that anti-corruption initiatives are strong when they are well funded, explicitly address corruption and are complemented by strong monitoring and evaluation mechanisms. Weaknesses in the organisations’ approaches to anti-corruption include one-size-fits-all approaches, lack of political will to address corruption and zero-tolerance policies for corruption. The COVID-19 pandemic has highlighted the necessity of improving anti-corruption by promoting strong accountability and transparency in health systems.

Conclusions

Results from this study highlight the strengths, weaknesses and recent trajectories of anti-corruption in the Global Fund, World Bank, UNDP and WHO. This study underscores the importance of implementing strong and robust anti-corruption mechanisms specifically geared towards corruption prevention that remain resilient even in times of emergency.
Correlation between the ratio of physician consultation fees to hourly minimum wage and consultation length: a cross-sectional study of nine countries
Authors: Kim Ju-Ryoung , Byun Se-Jin , Son Dae-Soon , Kim Hyun Ah
Published: December 2022

Objectives

Current healthcare reimbursement system is criticised for not adequately compensating physicians’ cognitive services. This study was performed to examine primary care physicians’ consultation fees in nine countries, relative to the national hourly minimum wage and to examine the correlations of the physician consultation fee with consultation length and other healthcare indices.

Design and outcome measures

Nine reference countries for which healthcare statistics are publicly available and outpatient consultation is compensated by fee-for-service payment were selected. A representative consultation fee was chosen to calculate the ratio of the consultation fee to the hourly minimum wage. The primary outcome was the correlation between the consultation fee/hourly minimum wage ratio and consultation length. In addition, the consultation fees were compared with fees for haemoglobin A1c tests and brain imaging. Pearson’s method was primarily used for correlation analysis.

Results

The mean representative consultation fee/hourly minimum wage ratio was 4.02 (median, 2.7; range, 0.80–10.36). The mean consultation length was 12.9 min (median, 14.7 min; range, 5–21.1 min). A significant correlation (r=0.79) was found between consultation length and the consultation fee/hourly minimum wage ratio. The ratio of consultation fee to hourly minimum wage was moderately negatively correlated with the annual number of physician visits, number of consultations per doctor and length of hospital stay. The brain CT fee/consultation fee ratio was moderately positively correlated with the number of CT units per 1 million population. In Japan and Korea, where the brain CT/consultation fee ratio was highest, the number of CT examinations per population was also highest.

Conclusions

The relationship of consultation fees to each country’s hourly minimum wage varied in nine reference countries; however, it was strongly correlated with consultation length. The imbalance in compensation for cognitive services might drive increased use of imaging tests in some countries.
Comanagement with rheumatology and prescription biologics filled during pregnancy in women with rheumatic diseases: a retrospective analysis of US administrative claims data
Authors: Shridharmurthy Divya , Lapane Kate L , Baek Jonggyu , Nunes Anthony , Kay Jonathan , Liu Shao-Hsien
Published: December 2022

Objectives

To evaluate comanagement with rheumatology and biological prescriptions filled during pregnancy among women with axial spondyloarthritis (axSpA), rheumatoid arthritis (RA) or psoriatic arthritis (PsA) and to examine factors associated with receiving comanagement with rheumatology during pregnancy.

Design

A retrospective analysis of US claims data.

Setting

Commercially insured enrollees using data from the 2013–2018 IBM MarketScan Commercial Claims and Encounters Database.

Participants

We identified 4131 pregnant women aged ≤55 years from the 2013–2018 IBM MarketScan Commercial Claims and Encounters Database with an International Classification of Disease, 9th Revision/10th Revision codes for RA, axSpA or PsA, with continuous enrolment at ≥3 months before the date of the last menstrual period (LMP) (index date) and throughout pregnancy.

Primary outcomes

Filled biologics (prescriptions and infusions) claims were categorised by 90 days before the LMP and trimester, as were primary care, obstetrician and rheumatological claims.

Results

The prevalence of axSpA, RA and PsA was 0.7%, 0.2% and 0.04% among reproductive age women. The average maternal age was 32.7 years (SD 5.7). During pregnancy, 9.1% of those with axSpA (n=2,410) and 56.4% of those with RA/PsA (n=1,721) had a rheumatological claim. Biologics claims were less common among those with axSpA (90 days before LMP: 1.6%, during pregnancy: 1.1%) than those with RA/PsA (90 days before LMP: 11.9%, during pregnancy: 6.9%). Medications during pregnancy included corticosteroids (axSpA: 0.3%, RA/PsA: 2.2%), non-biological disease-modifying antirheumatic drugs (axSpA: 0.2%, RA/PsA: 1.7%), non-steroidal anti-inflammatory drugs (axSpA: 0.2%, RA/PsA: 1.3%) and opioids (axSpA: 0.2%, RA/PsA: 0.6%). Established rheumatological care and biologics claims during the 90 days before LMP showed good prediction accuracy for receiving comanagement with rheumatology during pregnancy (axSpA: area under the receiver operator curve (AUC) 0.73, RA/PsA: AUC 0.70).

Conclusion

Comanagement with rheumatology during pregnancy occurs infrequently, especially for women with axSpA. Biologics claims during pregnancy may not align with published guidelines. Future research is warranted to improve comanagement with rheumatology during pregnancy.
Symptom descriptors and patterns in lumbar radicular pain caused by disc herniation: a 1-year longitudinal cohort study
Authors: Hasvik Eivind , Haugen Anne Julsrud , Grøvle Lars
Published: December 2022

Objective

The objective of the present study was to explore the diversity, quality, severity and distribution of symptoms in patients with radicular pain and a lumbar disc herniation.

Design

Longitudinal cohort study.

Setting

Hospital-based back clinic.

Participants

Ninety patients referred to secondary healthcare with (a) low back-related leg pain, (b) age between 18 and 65 years and (c) MRI confirmed lumbar disc herniation at a relevant side and level.

Outcome measures

Neuropathic pain symptoms were assessed using the Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) and the painDETECT Questionnaire. In a subsample classified with neuropathic pain, in-depth interviews were performed, and symptomatic areas were drawn on standardised body charts.

Results

At baseline, the most frequently used painDETECT symptom descriptor was numbness sensation, reported by 94%, followed by sudden pain attacks and tingling or prickling. The mean (SD) SF-MPQ-2 score (0–10) for aching pain was 5.9 (2.8); numbness 4.3 (3.3); tingling 4.0 (3.4); burning 2.6 (3.1); pain caused by light touch 1.5 (2.6). Leg pain was rated as extremely bothersome by 73%, numbness and tingling by 38%, weakness by 24% and back pain by 17%. In the subsample (n=52), deep-lying pain and non-painful abnormal sensations were frequent, at 71% and 85%. Drawings demonstrated substantial overlap between symptoms from compromised L5 and the S1 nerve roots. Painful and non-painful symptoms improved at approximately the same rate. At the 1-year follow-up, 45% (14/31) of patients who had received disc surgery, and 34% (18/53) of those who had received conservative treatment reported no bothersome back pain, leg pain, numbness/tingling or weakness.

Conclusion

Patients reported several highly bothersome symptoms, but not all are described as painful. The overall symptom profile of lumbar disc-related radicular pain differs from other neuropathic pain conditions with limited allodynia and thermal hyperalgesia. Symptomatic areas for the L5 and S1 nerve roots have a large overlap.
Evidence-based guidelines for hypertension and diabetes in sub-Saharan Africa: a scoping review
Authors: Nagavci Blin , Nyirenda John L Z , Balugaba Bonny E , Osuret Jimmy , Meerpohl Joerg J , Grummich Kathrin , Kobusingye Olive , Toews Ingrid
Published: December 2022

Objective

The Collaboration for Evidence-Based Healthcare and Public Health in sub-Saharan Africa (CEBHA+), a research network, aims to build capacities for evidence-based healthcare. Hypertension (HTN) and diabetes mellitus (DM) are two priority areas of the network, both are major causes of burden of disease in this region. This review aimed to: (1) identify existing evidence-based guidelines for HTN and DM, (2) map their recommendations and (3) assess their quality.

Setting

Sub-Saharan Africa.

Design

Scoping review.

Methods

Systematic searches for evidence-based guidelines, developed with systematic review of evidence and certainty of evidence assessment, were undertaken in electronic databases and grey literature, and ministries of health of all countries in this region were contacted. Included guidelines were assessed with the Appraisal of Guidelines for research and evaluation II (AGREE-II) tool. Searches were conducted between 7 December 2021 and 14 January 2022. Results are presented descriptively.

Results

66 potentially relevant guidelines were identified, developed in 23, out of 49 sub-Saharan African countries. Of these, only two guidelines (on DM) reported the use of systematic review of evidence and certainty of evidence assessment. Their quality appraisal showed that both have relatively similar scores on domains of AGREE-II, with higher scores on Scope and Purpose and Clarity and Presentation domains, and lower on Stakeholder Involvement, Applicability, Rigour of Development and Editorial independence domains. The overall scores of both guidelines were 50% and 58%, respectively.

Conclusions

Less than half of the countries in sub-Saharan Africa developed and published their own guidelines for HTN or DM. The quality appraisal showed that the two included guidelines scored relatively low in several crucial domains of AGREE-II. Countries in this region could consider adopting or adapting already published high-quality recommendations, in order to facilitate a more efficient and faster development of much needed trustworthy evidence-based guidance.
Registry-based cohort study of alpha-1 antitrypsin deficiency prevalence, incidence and mortality in Denmark 2000–2018
Authors: Acquavella John , Vágó Emese , Sorensen Henrik Toft , Horváth-Puhó Erzsébet , Hess Gregory P
Published: December 2022

Objective

To estimate the prevalence of diagnosed alpha-1 antitrypsin deficiency (dAATD) in Denmark as of 31 December 2018, and dAATD incidence and mortality from 1 January 2000 to 31 December 2018.

Study design and setting

We used the Danish National Patient Registry to identify patients with dAATD based on the International Classification of Diseases, 10th Revision (ICD-10) code E88.0A and the Danish Civil Registration System (CRS) for population counts and vital status. We estimated dAATD prevalence, incidence and mortality. We compared mortality among patients with dAATD and an age-matched and sex-matched cohort extracted from the Danish CRS. We conducted a sensitivity analysis to examine whether coding changes during 2000–2018, from a general to a more specific ICD-10 code for AATD, and left truncation affected results appreciably.

Results

The prevalence of dAATD was 12.9 (95% CI 11.9 to 13.8) per 100 000 persons. The age distribution was bimodal, with peaks at ages ≤12 and ≥45 years. The incidence rate per 100 000 person-years was 0.90 (95% CI 0.85 to 0.96), again with a bimodal age distribution. Mortality was higher for patients with dAATD than for the general population (mortality rate ratio (mRR) 4.7, 95% CI 4.1 to 5.3), especially for children (mRR 33.8, 95% CI 6.8 to 167.4). The sensitivity analysis indicated that dAATD prevalence might have been as high as 19.7 per 100 000 persons due to less specific ICD-10 coding for AATD early in the study period or 21.4 per 100 000 persons correcting for left truncation.

Conclusion

Diagnosed AATD was associated with increased mortality, especially for children. The finding for children was based on few deaths and had very wide 95% CIs.
Biallelic frameshift variants inPHLDB1cause mild-type osteogenesis imperfecta with regressive spondylometaphyseal changes
Authors: Tuysuz Beyhan , Uludag Alkaya Dilek , Geyik Filiz , Alaylıoğlu Merve , Kasap Busra , Kurugoğlu Sebuh , Akman Yunus Emre , Vural Mehmet , Bilguvar Kaya
Published: December 2022

Background

Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders characterised by susceptibility to fractures, primarily due to defects in type 1 collagen. The aim of this study is to present a novel OI phenotype and its causative candidate gene.

Methods

Whole-exome sequencing and clinical evaluation were performed in five patients from two unrelated families.PHLDB1mRNA expression in blood and fibroblasts was investigated by real-time PCR, and western blot analysis was further performed on skin fibroblasts.

Results

The common findings among the five affected children were recurrent fractures and/or osteopaenia, platyspondyly, short and bowed long bones, and widened metaphyses. Metaphyseal and vertebral changes regressed after early childhood, and no fractures occurred under bisphosphonate treatment. We identified biallelic NM_001144758.3:c.2392dup and NM_001144758.3:c.2690_2693del pathogenic variants inPHLDB1in the affected patients, respectively, in the families; parents were heterozygous for these variants.PHLDB1encodes pleckstrin homology-like domain family B member-1 (PHLDB1) protein, which has a role in insulin-dependent Akt phosphorylation. Compared with controls, a decrease in the expression levels ofPHLDB1in the blood and skin fibroblast samples was detected. Western blot analysis of cultured fibroblasts further confirmed the loss of PHLDB1.

Conclusion

Two biallelic frameshift variants in the candidate genePHLDB1were identified in independent families with a novel, mild-type, autosomal recessive OI. The demonstration of decreasedPHLDB1mRNA expression levels in blood and fibroblast samples supports the hypothesis thatPHLDB1pathogenic variants are causative for the observed phenotype.
Association between malignancy risk and Janus kinase inhibitors versus tumour necrosis factor inhibitors in Korean patients with rheumatoid arthritis: a nationwide population-based study
Authors: Song Yeo-Jin , Cho Soo-Kyung , You Seung-Hun , Kim Jeong-Yeon , Kim Hyoungyoung , Jung Sun-Young , Sung Yoon-Kyoung
Published: December 2022

Objective

To determine the risk of malignancy in Korean patients with rheumatoid arthritis (RA) receiving Janus kinase inhibitors (JAKis) compared with tumour necrosis factor inhibitors (TNFis).

Methods

A retrospective cohort of patients with RA initiating their first JAKi or TNFi was established using the Korean National Health Insurance database between 2015 and 2019. They were followed up from treatment initiation to the occurrence of malignancy, drug discontinuation, death or until December 2019. Baseline features of the patients were balanced through inverse probability of treatment weighting (IPTW) using a propensity score. A Cox proportional hazard model was established to estimate the HR for malignancy risk in JAKi users compared with TNFi users.

Results

A total of 4929 patients (1064 JAKi-treated and 3865 TNFi-treated patients) were included, and the observation periods were 1288.6 person-years (PYs) for JAKi users and 6823.8 PYs for TNFi users. The incidence rates of overall malignancy were 0.54 per 100 PYs (95% CI 0.26 to 1.14) in JAKi users and 0.85 per 100 PYs (95% CI 0.66 to 1.10) in TNFi users. In IPTW analysis with a balanced sample (4101 JAKi-treated and 5131 TNFi-treated patients), HR was 0.83 (95% CI 0.55 to 1.27) for overall malignancy: 0.77 (95% CI 0.50 to 1.19) for solid malignancy and 2.86 (95% CI 0.41 to 20.00) for haematological malignancy.

Conclusion

Malignancy risk in Korean patients with RA was not increased with JAKi use compared with TNFi use.