bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Intelligence and Machine Learning in Aneurysmal Subarachnoid Hemorrhage: Future Promises, Perils, and Practicalities
Authors: Salman Saif , Gu Qiangqiang , Sharma Rohan , Wei Yujia , Dherin Benoit , Reddy Sanjana , Tawk Rabih , Freeman W David
Published: July 2023

Abstract

Introduction

Aneurysmal subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke with thirty-day mortality as high as 40%. Given the expansion of Machine Learning (ML) and Artificial intelligence (AI) methods in health care, SAH patients desperately need an integrated AI system that detects, segments, and supports clinical decisions based on presentation and severity.

Objectives

This review aims to synthesize the current state of the art of AI and ML tools for the management of SAH patients alongside providing an up-to-date account of future horizons in patient care.

Methods

We performed a systematic review through various databases such as Cochrane Central Register of Controlled Trials, MEDLINE, Scopus, Cochrane Database of Systematic Reviews, and Embase.

Results

A total of 507 articles were identified. Following extensive revision, only 21 articles were relevant. Two studies reported improved mortality prediction using Glasgow Coma Scale and biomarkers such as Neutrophil to Lymphocyte Ratio and glucose. One study reported that ffANN is equal to the SAHIT and VASOGRADE scores. One study reported that metabolic biomarkers Ornithine, Symmetric Dimethylarginine, and Dimethylguanidine Valeric acid were associated with poor outcomes. Nine studies reported improved prediction of complications and reduction in latency until intervention using clinical scores and imaging. Four studies reported accurate prediction of aneurysmal rupture based on size, shape, and CNN. One study reported AI-assisted Robotic Transcranial Doppler as a substitute for clinicians.

Conclusion

AI/ML technologies possess tremendous potential in accelerating SAH systems-of- care. Keeping abreast of developments is vital in advancing timely interventions for critical diseases.
Evidence that intergenerational income mobility is the strongest predictor of drug overdose deaths in U. S. Heartland counties
Authors: Heyman Gene M. , Ryu Ehri , Brownell Hiram
Published: July 2023

In 2017, the Acting U. S. Secretary of Health and Human Services declared the “opioid crisis” a nation-wide health emergency. However, the crisis’s geography was not nation-wide. Many counties and towns had no overdose deaths, whereas others were home to hundreds. According to many influential research reports and news stories, geographic variation in overdose deaths was due to geographic variation in opioid prescription rates and/or geographic variation in socioeconomic factors, such as unemployment. Our goal was to test the degree to which prescription rates and socioeconomic correlates of income inequality predicted overdose deaths in the 1055 U.S. Midwest (“Heartland”) counties over the years 2006 to 2020. We used multilevel regression models to gauge the predictive strength of overdose rates and six socioeconomic measures that are correlated with income inequality. There were significant state-level and county-level differences. Intergenerational income mobility was the strongest predictor of overdose deaths, with regression coefficients that averaged about twice as large as the coefficients for opioid prescription rates. Every year, counties with greater upward intergenerational income mobility had lower overdose death rates. Social capital had the second largest regression coefficients, albeit by a small margin. Counties are the smallest demographic unit for which drug overdose rates are available; the results of this study link growing income inequality and drug overdose deaths at the county level.
Caregivers’ and nurses’ perceptions of the Smart Discharges Program for children with sepsis in Uganda: A descriptive qualitative study
Authors: Behan Justine , Kabajaasi Olive , Derksen Brooklyn , Sendegye George , Kugumikiriza Brenda , Komugisha Clare , Sundararajan Radhika , Jacob Shevin T. , Kenya-Mugisha Nathan , Wiens Matthew O.
Published: July 2023

Sepsis arises when the body’s response to infection results in organ dysfunction. Among children hospitalized with suspected sepsis in low-income country settings, mortality rates following discharge are similar to mortality rates in hospital. The Smart Discharges Program uses a mobile health (mHealth) platform to identify children at high risk of post-discharge mortality to receive enhanced post-discharge care. This study sought to explore the perceptions of the caregivers and nurses of children enrolled into the Smart Discharges Program. We conducted a descriptive qualitative study that used a phenomenological approach. We conducted in-person focus group discussions (FGDs) with 30 caregivers of pediatric patients enrolled in the Smart Discharges Program and individual, semi-structured interviews with eight Smart Discharges Program nurses. The study was carried out at four hospitals in Uganda in 2019.

Following thematic analysis, three key themes pertaining to the Smart Discharges program were identified: (1) Facilitators and barriers to follow-up care after discharge; (2) Changed behavior following discharge; and (3) Increased involvement of male caregivers. Facilitators included telephone/text message reminders, positive nurse-patient relationship, and the complementary aspects of the program. Resource constraints and negative experiences during post-discharge care seeking were reported as the most prominent barriers to post-discharge follow up. When provided with relevant and well-timed information, caregivers reported increased knowledge about post-discharge care and improvements in their ability to care for their child. Enrolment in the Smart Discharges Program also increased male caregiver involvement, which was reported as improved engagement in care, increased provision of resources and improved communication within the family and with the healthcare system. The Smart Discharges approach is an impactful strategy to improve pediatric post-discharge care, and similar approaches should be considered to improve the hospital to home transition in similar low-income country settings.
Disrupted Limbic-Prefrontal Effective Connectivity in Response to Fearful Faces in Lifetime Depression
Authors: Stolicyn Aleks , Harris Mathew A. , de Nooij Laura , Shen Xueyi , Macfarlane Jennifer A. , Campbell Archie , McNeil Christopher J. , Sandu Anca-Larisa , Murray Alison D. , Waiter Gordon D. , Lawrie Stephen M. , Steele Douglas J. , McIntosh Andrew M. , Romaniuk Liana , Whalley Heather C.
Published: July 2023

Background

Multiple brain imaging studies of negative emotional bias in major depressive disorder (MDD) have used images of fearful facial expressions and focused on the amygdala and the prefrontal cortex. The results have, however, been inconsistent, potentially due to small sample sizes (typicallyN< 50). It remains unclear if any alterations are a characteristic of current depression or of past experience of depression, and whether there are MDD-related changes in effective connectivity between the two brain regions.

Methods

Activations and effective connectivity between the amygdala and dorsolateral prefrontal cortex (DLPFC) in response to fearful face stimuli were studied in a large population-based sample from Generation Scotland. Participants either had no history of MDD (N= 664 in activation analyses,N= 474 in connectivity analyses) or had a diagnosis of MDD during their lifetime (LMDD,N= 290 in activation analyses,N= 214 in connectivity analyses). The within-scanner task involved implicit facial emotion processing of neutral and fearful faces.

Results

Compared to controls, LMDD was associated with increased activations in left amygdala (PFWE= 0.031, kE= 4) and left DLPFC (PFWE= 0.002, kE= 33), increased mean bilateral amygdala activation (β= 0.0715, P= 0.0314), and increased inhibition from left amygdala to left DLPFC, all in response to fearful faces contrasted to baseline. Results did not appear to be attributable to depressive illness severity or antidepressant medication status at scan time.

Limitations

Most studied participants had past rather than current depression, average severity of ongoing depression symptoms was low, and a substantial proportion of participants were receiving medication. The study was not longitudinal and the participants were only assessed a single time.

Conclusions

LMDD is associated with hyperactivity of the amygdala and DLPFC, and with stronger amygdala to DLPFC inhibitory connectivity, all in response to fearful faces, unrelated to depression severity at scan time. These results help reduce inconsistency in past literature and suggest disruption of ‘bottom-up’ limbic-prefrontal effective connectivity in depression.
Association between oral anticoagulant adherence and serious clinical outcomes in patients with atrial fibrillation: A long-term retrospective cohort study
Authors: Safari Abdollah , Helisaz Hamed , Salmasi Shahrzad , Adelakun Adenike , De Vera Mary A. , Andrade Jason G. , Deyell Marc W. , Loewen Peter
Published: July 2023

Background

Patients with atrial fibrillation (AF) are frequently nonadherent to oral anticoagulants (OACs) prescribed for stroke and systemic embolism (SSE) prevention. We quantified the relationship between OAC adherence and AF clinical outcomes using methods not previously applied to this problem.

Methods

Retrospective observational cohort study of incident cases of AF from population-based administrative data over 23 years. The exposure of interest was proportion of days covered (PDC) during 90 days before an event or end of follow-up. Cox proportional hazard models were used to evaluate time to first SSE and the composite of SSE, TIA, or death, and several secondary outcomes.

Results

44,172 patients were included with median follow-up of 6.7 years. For DOACs, each 10% decrease in adherence was associated with a 14% increased hazard of SSE and 5% increased hazard of SSE, TIA, or death. For VKA the corresponding increase in SSE hazard was 3%. Receiving DOAC or VKA was associated with primary outcome hazard reduction across most the PDC spectrum. Differences between VKA and DOAC were statistically significant for all efficacy outcomes and at most adherence levels.

Conclusions

Even small reductions in OAC adherence in patients with AF were associated with significant increases in risk of stroke, with greater magnitudes for DOAC than VKA. DOAC recipients may be more vulnerable than VKA recipients to increased risk of stroke and death even with small reductions in adherence. The worsening efficacy outcomes associated with decreasing adherence occurred without the benefit of major bleeding reduction.
Risk of SARS-CoV-2 infection and hospitalization in individuals with natural, vaccine-induced and hybrid immunity: a retrospective population-based cohort study from Estonia
Authors: Uusküla Anneli , Pisarev Heti , Tisler Anna , Meister Tatjana , Suija Kadri , Huik Kristi , Abroi Aare , Kalda Ruth , Kolde Raivo , Fischer Krista
Published: July 2023

A large proportion of the world’s population has some form of immunity against SARS-CoV- 2, through either infection (‘natural’), vaccination or both (‘hybrid’). This retrospective cohort study used data on SARS-CoV-2, vaccination, and hospitalization from national health system from February 2020 to June 2022 and Cox regression modelling to compare those with natural immunity to those with no (Cohort1, n=92917), hybrid (Cohort2, n=46813), and vaccine (Cohort3, n=252414) immunity. In Cohort 1, those with natural immunity were at lower risk for infection during the Delta (aHR 0.17, 95%CI 0.15-0.18) and higher risk (aHR 1.24, 95%CI 1.18-1.32) during the Omicron period than those with no immunity. Natural immunity conferred substantial protection against COVID-19-hospitalization. Cohort 2 - in comparison to natural immunity hybrid immunity offered strong protection during the Delta (aHR 0.61, 95%CI 0.46-0.80) but not the Omicron (aHR 1.05, 95%CI 0.93-1.1) period. COVID-19-hospitalization was extremely rare among individuals with hybrid immunity. In Cohort 3, individuals with vaccine-induced immunity were at higher risk than those with natural immunity for infection (Delta aHR 4.90, 95%CI 4.48-5.36; Omicron 1.13, 95%CI 1.06-1.21) and hospitalization (Delta aHR 7.19, 95%CI 4.02-12.84). These results show that risk of infection and severe COVID-19 are driven by personal immunity history and the variant of SARS-CoV-2 causing infection.
Identification of Multi-repeat Sequences using Genome Mining Approaches for Developing Highly Sensitive Molecular Diagnostic Assay for the Detection ofChlamydia trachomatis
Authors: Shiluli Clement , Kamath Shwetha , Kanoi Bernard N. , Kimani Rachael , Maina Michael , Waweru Harrison , Kamita Moses , Ndirangu Ibrahim , Abkallo Hussein M. , Oduor Bernard , Pamme Nicole , Dupaty Joshua , Klapperich Catherine M. , Lolabattu Srinivasa Raju , Gitaka Jesse
Published: July 2023

1.

Chlamydia trachomatis (C. trachomatis)is a common sexually transmitted infection (STI). In 2019, the World Health Organization reported about 131 million infections. The majority of infected patients are asymptomatic with cases remaining undetected. It is likely that missedC. trachomatisinfections contribute to preventable adverse health outcomes in women and children. Consequently, there is an urgent need of developing efficient diagnostic methods. In this study, genome-mining approaches to identify identical multi-repeat sequences (IMRS) distributed throughout theC. trachomatisgenome were used to design a primer pair that would target regions in the genome. Genomic DNA was 10-fold serially diluted (100pg/μL to 1×10-3pg/μL) and used as DNA template for PCR reactions. The gold standard PCR using 16S rRNA primers was also run as a comparative test, and products were resolved on agarose gel. The novel assay,C. trachomatisIMRS-PCR, had an analytical sensitivity of 9.5 fg/μL, representing better sensitivity compared with 16S rRNA PCR (4.31 pg/μL). Our experimental data demonstrate the successful development of lateral flow and isothermal assays for detectingC. trachomatisDNA with potential use in field settings. There is a potential to implement this concept in miniaturized, isothermal, microfluidic platforms, and laboratory-on-a-chip diagnostic devices for reliable point-of-care testing.
A data-driven framework for clinical decision support applied to pneumonia management
Authors: Free Robert C. , Lozano Rojas Daniel , Richardson Matthew , Skeemer Julie , Small Leanne , Haldar Pranabashis , Woltmann Gerrit
Published: July 2023

Despite their long history, it can still be difficult to embed clinical decision support into existing health information systems, particularly if they utilise machine learning and artificial intelligence models. Moreover, when such tools are made available to healthcare workers, it is important that the users can understand and visualise the reasons for the decision support predictions. Plausibility can be hard to achieve for complex pathways and models and perceived ’black-box’ functionality often leads to a lack of trust. Here, we describe and evaluate a data-driven framework which moderates some of these issues and demonstrate its applicability to the in-hospital management of community acquired pneumonia, an acute respiratory disease which is a leading cause of in-hospital mortality world-wide. We use the framework to develop and test a clinical decision support tool based on local guideline aligned management of the disease and show how it could be used to effectively prioritise patients using retrospective analysis. Furthermore, we show how this tool can be embedded into a prototype clinical system for disease management by integrating metrics and visualisations for assisting decision makers examining complex patient journeys, risk scores and predictions from embedded machine learning and artificial intelligence models. Our results show the potential of this approach for developing, testing and evaluating workflow based clinical decision support tools which include complex models and embedding them into clinical systems.
The in-frame p.Lys254del-CAPN3 deletion is not sufficient to cause late-onset camptocormia in dominantly inherited calpainopathy
Authors: Valls Andrea , Gutiérrez-Gutiérrez Gerardo , Martínez Agustín , Ruiz-Roldán Cristina , Camaño Pilar , López de Munain Adolfo , Sáenz Amets
Published: July 2023

Introduction/Aims

Limb-girdle muscular dystrophy R1 (LGMDR1) calpain 3-related is one of the most common forms of LGMD. It is typically recessively inherited and associated with progressive weakness of proximal limb-girdle muscles. Recently, several families with an autosomal dominant inheritance transmission pattern have been reported (LGMDD4). Camptocormia is a common clinical feature in these patients. In these families, different mutations inCAPN3have been identified, including in-frame deletions and missense mutations. In particular, two patients presenting with camptocormia carried the p.Lys254del missense mutation without a second identified mutation inCAPN3.

Methods

Among our patients, we identified two LGMDR1 families as carriers of the p.Lys254del mutation by DNA sequencing, both in homozygous and compound heterozygous states and clinically analyzed the family members carrying this mutation.

Results

Interestingly, these patients did not present the myopathic characteristics described in the so-called dominant patients. No camptocormia or any other severe clinical symptoms were observed.

Discussion

Accordingly, we conclude that the p.Lys254del mutationper secannot be solely responsible for the camptocormia observed in dominant patients. Other additional undisclosed factors might regulate the phenotype associated to a dominant inheritance pattern inCAPN3mutation carriers.
Multi-omics analysis in primary T cells elucidates mechanisms behind disease associated genetic loci
Authors: Shi Chenfu , Zhao Danyun , Rossi Stefano , Frantzeskos Antonios , Ding James , Ferrazzano Carlo , Wynn Charlotte , Hum Ryan , Richards Ellie , Gupta Muskan , Yap Chuan Fu , Plant Darren , Grencis Richard , Martin Paul , Adamson Antony , Eyre Stephen , Bowes John , Barton Anne , Ho Pauline , Rattray Magnus , Orozco Gisela
Published: July 2023

In this study, we present the most extensive dataset of chromatin conformation data with matching gene expression and chromatin accessibility from primary T cells to date. We use this data to enhance our understanding of the different mechanisms by which GWAS variants impact gene regulation and revealing how natural genetic variation alter chromatin accessibility and structure in primary cells at an unprecedented scale. Capitalizing on this vast dataset, we refine the mapping of GWAS loci to implicated regulatory elements, such as CTCF binding sites and other enhancer elements, aiding gene assignment. Importantly, we uncoverBCL2L11as the probable causal gene within the RA locus rs13396472, despite the GWAS variants’ intronic positioning relative toACOXLand we identify mechanisms involvingSESN3dysregulation in the RA locus rs4409785. Given these genes’ significant role in T cell development and maturation, our work is vital for deepening our comprehension of autoimmune disease pathogenesis and suggesting potential treatment targets.
Subset scanning for multi-trait analysis using GWAS summary statistics
Authors: Cao Rui , Olawsky Evan , McFowland Edward , Marcotte Erin , Spector Logan , Yang Tianzhong
Published: July 2023

Multi-trait analysis has been shown to have greater statistical power than single-trait analysis. Most of the existing multi-trait analysis methods only work with a limited number of traits and usually prioritize high statistical power over identifying relevant traits, which heavily rely on domain knowledge. To handle diseases and traits with obscure etiology, we developed TraitScan, a powerful and fast algorithm that agnostically searches and tests a subset of traits from a moderate or large number of traits (e.g., dozens to thousands) based on either individual-level or summary-level genetic data. We evaluated TraitScan using extensive simulations and found that it outperformed existing methods in terms of both testing power and trait selection when sparsity was low or modest. We then applied it to search for traits associated with Ewing Sarcoma, a rare bone tumor with peak onset in adolescence, among 706 traits in UK Biobank. Our analysis revealed a few promising traits worthy of further investigation, highlighting the use of TraitScan for more effective multi-trait analysis as biobanks emerge. Our algorithm is implemented in an R package ‘TraitScan’ available athttps://github.com/RuiCao34/TraitScan.
The role of Patient and Public Involvement (PPI) in pre-clinical spinal cord research: an interview study
Authors: Carroll Pádraig , Dervan Adrian , McCarthy Ciarán , Woods Ian , Beirne Cliff , Harte Geoff , O’Flynn Dónal , O’Connor Cian , McGuire Tara , Leahy Liam M. , Gonzalez Javier Gutierrez , Stasiewicz Martyna , Maughan Jack , Quinlan John , Smith Éimear , Moriarty Frank , O’Brien Fergal J. , Flood Michelle
Published: July 2023

Background

Patient and public involvement in research (PPI) has many benefits including increasing relevance and impact. While using PPI in clinical research is now an established practice, the involvement of patients and the public in pre-clinical research, which takes place in a laboratory setting, has been less frequently described and presents specific challenges. This study aimed to explore the perspectives of seriously injured rugby players’ who live with a spinal cord injury on PPI in pre-clinical research.

Methods

Semi-structured interviews were conducted via telephone with 11 male seriously injured rugby players living with spinal cord injury on the island of Ireland. A purposive sampling approach was used to identify participants. Selected individuals were invited to take part via gatekeeper in a charitable organisation that supports seriously injured rugby players. Interviews were transcribed verbatim and analysed thematically.

Findings

Six themes were identified during analysis: ‘limited knowledge of PPI’, ‘connecting pre-clinical research with the day-to-day realities of spinal cord injury’, ‘making pre-clinical research accessible for non-scientific audiences’, ‘barriers to involvement include disinterest, accessibility issues, and fear of losing hope if results are negative’, ‘personal contact and dialogue facilitate PPI’, and ‘collaborating on dissemination builds trust in research.’

Conclusion

People affected by spinal cord injury in this study desire further involvement in pre-clinical spinal cord injury research through dialogue and contact with researchers. Sharing experiences of spinal cord injury can form the basis of PPI for pre-clinical spinal cord injury research.
Several Mathematical Aspects on Daily Number of COVID-19 Infection Cases in Eight Southeast Asian Places
Authors: Chow C.L. , Cheng C.H. , Chow W.K.
Published: July 2023

The number of daily confirmed infected cases is a key parameter to determine emergency management actions to take. The mathematical characteristics of the daily infection number should be explored for working out appropriate control scheme. Several mathematical aspects on the daily number of infected cases will be discussed in 8 Southeastern Asian places using the confirmed daily infection numbers available in public websites. Phase space diagrams of plotting the daily infection rate estimated numerically against daily infection number on those tests are presented first. Modeling parameters including the Farr’s Law are also discussed. A parameter is proposed to describe the extent of infection by estimating the transient daily infection number divided by the time.
icognition: a smartphone-based cognitive screening battery
Authors: Denissen Stijn , Van Laethem Delphine , Baijot Johan , Costers Lars , Descamps Annabel , Van Remoortel Ann , Van Merhaegen-Wieleman Annick , D’hooghe Marie B , D’Haeseleer Miguel , Smeets Dirk , Sima Diana Maria , Van Schependom Jeroen , Nagels Guy
Published: July 2023

Background

Telemedicine is feasible and well-accepted by people with multiple sclerosis (MS).

Objective

The aim of this study is to validate a smartphone-based cognitive screening battery, icognition, to faster signal cognitive deterioration.

Methods

icognitionconsists of three tests (Symbol Test, Dot Test and visual Backwards Digit Span (vBDS)) that are equivalents of validated paper-pencil tests. These are the Symbol Digit Modalities Test (SDMT), the 10/36 Spatial Recall Test (SPART) and the auditory Backwards Digit Span (aBDS), respectively. To establish the validity of icognition, 101 people with MS and 82 healthy subjects completed all tests. 21 healthy subjects repeated testing 2 to 3 weeks later.

Results

All tests in icognitioncorrelate well with their paper-pencil equivalent (Symbol Test: r=.63, p<.001; Dot Test: r=.31, p=0.002; vBDS: r=.71, p<.001), negatively correlate with the Expanded Disability Status Scale (EDSS: Symbol Test: rho=-.27, p=.01; Dot Test: rho=-.29, p=.006; vBDS: rho=- .23, p=.027) and show high test-retest reliability (Symbol Test: r=.81, p<.001; Dot Test: r=.75, p<.001; vBDS: r=.84, p<.001). Test performance was not significantly different between people with MS and healthy subjects for all cognitive tests, both in icognitionand their paper-pencil equivalents.

Conclusion

icognitionis a valid and reliable tool to remotely screen for cognitive functioning in persons with MS.
Admissions for eating disorders and other mental health diagnoses during the COVID-19 pandemic
Authors: Jones Sydney C. , Jacobs Megan , Latour Emile , Marshall Rebecca , Noelck Michelle , Foster Byron A.
Published: July 2023

Objective

To examine how hospital admissions for mental health and eating disorders changed at the beginning of the COVID-19 pandemic and with the return to fully in-person school with increased vaccine availability.

Methods

Data from a tertiary care children’s hospital were examined for admissions to the hospital from March 2018 through March 2022, including children 6-20 years old admitted with ICD-10 codes for mental health and eating disorders. Interrupted time series (ITS) analyses were used to examine for changes at specific time points.

Results

In the time between March 2018 through March 2022, 851 admissions met inclusion criteria for eating disorders and 1,505 admissions for other mental health diagnoses. In the first year of the pandemic, the ITS analysis showed a significant increase in admissions per month for eating disorders with a slope of 1.2 (95% CI: 0.2, 2.2) and for other mental health diagnoses, a slope of 1.9 (95% CI: 1.1, 2.7). In a longer-term ITS analysis, return to fully in-person school was associated with a subsequent decrease in admissions over time at -1.0 per month (95% CI: - 2.1, 0.1). For other mental health diagnoses, return to school was associated with an initial drop and then an increase in admissions over time, slope of 2.2 (95% CI: -0.5, 3.8).

Conclusion

The COVID-19 pandemic had an initial impact on admissions for eating disorders and other mental health that attenuated over time. We note differences in the association of return to school on eating disorders compared with other mental health diagnoses.
Infection, inflammation and post-stroke cognitive impairment
Authors: Milosevich Elise , Demeyere Nele , Pendlebury Sarah T.
Published: July 2023

Background

Infection and inflammation are risk factors for dementia in population-based cohorts, however studies in stroke are scarce. We determined the prevalence of stroke-associated infection and routinely measured inflammatory biomarkers during hospitalization for stroke, and their associations with global and domain-specific cognition acutely and at 6-months.

Methods

A prospective stroke cohort completed the Oxford Cognitive Screen ≤2 weeks and at 6 months. Global post-stroke cognitive impairment (PSCI) was defined as proportion of domains impaired and domain-specific impairment was binarized as present/absent. Infection, inflammatory markers (C-reactive protein-CRP, white cell count-WCC, and neutrophil/lymphocyte ratio-NLR), and systemic inflammatory response syndrome-SIRS, were ascertained throughout admission through linkage to electronic patient records-EPRs supplemented by hand-searches. Associations of infection, inflammatory markers, and SIRS, with acute and 6-month global and domain-specific cognitive impairment were analyzed using multivariable regression adjusting for demographic/vascular factors and stroke severity.

Results

Among 255 patients (mean/SD age=73.9/12.6 years, 46.3% female, mean/SD education=12.6/3.7 years, median NIHSS=5, range 0–30), infection was present in 90 (35.3%) patients at mean/SD 4.4/6.9 days post-stroke, most commonly pneumonia (47/90, 52%) and urinary tract infection (39/90, 43%). Admission WCC was elevated in 64 (25.1%, mean/SD=9.5/3.2×109/L), CRP in 105 (41.2%, mean/SD=27.5/50.9 mg/L), NLR in 97 (55.7%, mean/SD=5.5/4.5) and SIRS in 53 (26.6% with 45.2% positive overall during admission). Infection was associated with acute and 6-month PSCI (p<0.05adj) with stronger associations acutely for severe infection (infection+SIRS,p=0.02adj). Acute impairments in language, executive function and attention domains and 6-month impairment in number processing (allp<0.05adj) were associated with infection. No significant relationships were found for any biomarker and cognitive impairment.

Conclusion

Infection and elevations in routinely measured inflammatory biomarkers are common after stroke, however only infection is a risk factor for PSCI, suggesting that the rise in these biomarkers may be non-specific. Infection may present a tractable target for reducing PSCI.
Randomized attention-placebo controlled trial of a digital self-management platform for adult asthma
Authors: Kandola Aaron , Edwards Kyra , Straatman Joris , Dührkoop Bettina , Hein Bettina , Hayes Joseph F
Published: July 2023

Background

Asthma is one of the most common chronic conditions worldwide, with a substantial individual, societal and healthcare burden. Digital apps hold promise as a highly accessible, low-cost method of enhancing self-management in asthma, which is critical to effective asthma control.

Objective

We conducted a fully remote trial to assess the efficacy of juli, a commercially available smartphone self-management platform for asthma.

Methods

We conducted a pragmatic single-blind, randomized controlled trial of juli for asthma management. Our study included participants aged 18 and above with asthma and had an asthma control test (ACT) score of 19 or less (indicating poorly controlled asthma) at the beginning of the trial. Participants were randomized (1:1 ratio) to receive juli for eight weeks or a limited attention-placebo control version of the app. The primary endpoint was the difference in ACT scores after eight weeks. Secondary endpoints included eight-week remission (ACT score greater than 19), minimal clinically important difference (an improvement of three or more points on the ACT), worsening of asthma, and health-related quality of life. The primary analysis included participants using the app for eight weeks (per-protocol), a secondary analysis used modified intention-to-treat.

Results

We randomized 411 participants between May 2021 and April 2023: 152 engaged with the app for eight weeks and were included in the per-protocol analysis, 262 completed the week two outcome assessment and were included in the modified intention-to-treat analysis.

In the per-protocol analysis, the intervention group had a higher mean ACT score (17.93, standard deviation = 4.72) than the control group (16.24, standard deviation = 5.78) by week eight (baseline adjusted β-coefficient 1.91, 95% confidence intervals = 0.31 to 3.51, p=0.020). Participants using juli had greater odds of achieving or exceeding the minimal clinically important difference at eight weeks (adjusted odds ratio = 2.38, 95% confidence intervals = 1.20 to 4.70, p=0.013). There were no between-group differences in the other secondary outcomes at eight weeks. The results from the modified intention-to-treat analysis were similar.

Conclusions

Users of juli had improved asthma symptom control over eight weeks compared with users of a version of the app with limited functionality. These findings suggest that juli is an effective digital self-management platform that could augment existing care pathways for asthma.

Trial Registration

The trial was pre-registered (ISRCTN87679686).
Adoption of policies to improve respectful maternity care in Timor-Leste
Authors: Fernandes Angelina da Costa , Supriyanto Stefanus , Wahyuni Chatarina Umbul , Notobroto Hari Basuki , Gregory Alexandra , Wild Kayli
Published: July 2023

Introduction

There are now well-established global standards for supporting improvement in women’s experience of maternity services, including frameworks for the prevention of mistreatment during childbirth. Given the ongoing reports from Timor-Leste outlining poor quality of care in maternal health services and the low use of health facilities for birth, we aimed to examine the adoption of global respectful maternity care standards in intrapartum care policies in Timor-Leste.

Methods

From May to July 2022, we conducted a desk review of the Timor-Leste National Intrapartum Care Standards and Clinical Protocols for Referral Facilities and Community Health Centres. This was followed by a health-facility audit of policies, guidelines and procedures in three main maternity facilities in the capital, Dili to examine the extent to which the WHO (2016) standards for women’s experiences of care have been adopted.

Results

Despite the availability of global guidelines, key standards to improve women’s experience of care have been omitted from the National Intrapartum Care guidelines in Timor-Leste. There was no mention of avoiding mistreatment of women, needing informed consent for procedures, or strengthening women’s own capability and confidence. In the policy wording, women tended to be distanced from the care ‘procedures’ and their involvement was framed around being told what to do during the birth process. The results of the health facility assessment showed extremely low use of standards that improve women’s experiences of care. Health Facility 1 and 2 met two of the 21 quality measures, while Health Facility 3 met none of them.

Conclusion

The discourse communicated through policy fundamentally affects how health care issues are framed and how policies are enacted. Given the findings of this study, combined with the widespread documentation of poor quality of care, low satisfaction with maternal health services, and emerging stories of physical and verbal abuse of women during birth, there is a need for a fundamental shift in the culture of care for women in Timor-Leste. This will require an immediate focus on leadership, training and policy-frameworks to stop mistreatment of women in health facilities. It will also require a longer-term focus on addressing the power imbalances that drive disrespect and abuse of women within and across social systems, and understanding how to support relationship-based models of care that inherently foster understanding and compassion.
JOINT APPLICATION OF BRAIN MRI AND GENE EXPRESSION ATLAS TO RECONSTRUCT NMOSD PATHOPHYSIOLOGY
Authors: Cacciaguerra Laura , Storelli Loredana , Pagani Elisabetta , Mesaros Sarlota , Martinelli Vittorio , Moiola Lucia , Radaelli Marta , Ivanovic Jovana , Tamas Olivera , Drulovic Jelena , Filippi Massimo , Rocca Maria A.
Published: July 2023

Objective

Brain lesions in aquaporin-4-antibody-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) occur at areas of high AQP4 expression. However, the pathophysiological cascade requires additional factors such as complement. We sought to investigate the spatial association between brain damage and gene expression in AQP4+NMOSD.

Methods

In this multicenter cross-sectional study, we enrolled 90 patients and 94 age-matched healthy controls who underwent a 3.0/1.5 T brain MRI. In patients, brain damage was assessed through (i) T2-hyperintense lesion probability maps, (ii) white matter (WM) and grey matter (GM) atrophy on 3D T1-weighted sequences, and (iii) WM microstructural abnormalities on diffusion-tensor imaging. The association between imaging maps and the expression of 266 candidate genes in the Allen Human Brain Atlas was obtained and overrepresented biological processes were investigated with a functional-enrichment analysis.

Results

In AQP4+NMOSD, T2-hyperintense lesions were mainly located in the periventricular WM. GM and WM atrophy involved the visual pathway, while WM microstructural abnormalities were represented by a widespread increase of mean diffusivity. The expression of AQP4, C4a and C5 elements of complement resulted associated with all types of brain damage. Complement activation and the regulation and uptake of insulin-like growth factor were the most relevant enriched pathways. Non-specific pathways related to DNA synthesis and repair were associated with brain atrophy.

Interpretation

A joint application of quantitative MRI and gene expression atlas can identify in vivo the key elements of AQP4+NMOSD pathophysiology. This may pave the way to a novel type of imaging analysis helpful in understanding the pathophysiology of antibody-mediated autoimmune disorders.
Medical Students’ Attitudes toward AI in Medicine and their Expectations for Medical Education
Authors: Kimmerle Joachim , Timm Jasmin , Festl-Wietek Teresa , Cress Ulrike , Herrmann-Werner Anne
Published: July 2023

Objectives

Artificial intelligence (AI) is used in a variety of contexts in medicine. This involves the use of algorithms and software that analyze digital information to make diagnoses and suggest adapted therapies. It is unclear, however, what medical students know about AI in medicine, how they evaluate its application, and what they expect from their medical training accordingly. In the study presented here, we aimed at providing answers to these questions.

Methods

In this survey study, we asked medical students about their assessment of AI in medicine and recorded their ideas and suggestions for considering this topic in medical education. Fifty-eight medical students completed the survey.

Results

Almost all participants were aware of the use of AI in medicine and had an adequate understanding of it. They perceived AI in medicine to be reliable, trustworthy, and technically competent, but did not have much faith in it. They considered AI in medicine to be rather intelligent but not anthropomorphic. Participants were interested in the opportunities of AI in the medical context and wanted to learn more about it. They indicated that basic AI knowledge should be taught in medical studies, in particular, knowledge about modes of operation, ethics, areas of application, reliability, and possible risks.

Conclusions

We discuss the implications of these findings for the curricular development in medical education. Medical students need to be equipped with the knowledge and skills to use AI effectively and ethically in their future practice. This includes understanding the limitations and potential biases of AI algorithms by teaching the sensible use of human oversight and continuous monitoring to catch errors in AI algorithms and ensure that final decisions are made by human clinicians.
Service Retention Among Coast Guard Members Seeking Behavioral Healthcare
Authors: Allen John , Vance Mary , Mahlau-Heinert Jerry , Ahluwalia Jaspal , Thomas Dana , Singh Swati , Iskander John
Published: July 2023

Introduction

Behavioral health conditions (BHC) can reduce service member retention. This analysis sought to identify demographic and diagnostic factors among BHC care-seeking Active-Duty United States Coast Guard (ADCG) that were predictive of discharge before completion of obligated service.

Methods

A four-year retrospective cohort study of ADCG personnel was conducted. Five machine-learning (ML) algorithms and logistic regression were applied to data on ADCG who sought outpatient care for BHC in 2016. Covariates examined as possible mediators of early service termination included diagnosis group, gender, rank grouping, and race.

Results

Only 26.4 of every 1,000 members who sought BHC care did not complete their service obligation. Diagnosis group did not predict early service termination, whereas senior enlisted rank was associated with early termination. The ML algorithms best predictive of early discharge from service were bagging classifier and decision tree classifier. Logistic regression performed as well as the two leading algorithms.

Conclusions

Specific ML models can be used to identify personnel groups at risk for early separation, such as senior enlisted personnel. Traditional epidemiologic methods demonstrate value in predicting service member separation.
Effect of household use of multiple micronutrient-fortified bouillon on micronutrient status among women and children in two districts in the Northern Region of Ghana: Protocol for the Condiment Micronutrient Innovation Trial (CoMIT), a community-based randomized controlled trial
Authors: Engle-Stone Reina , Wessells K Ryan , Haskell Marjorie J. , Kumordzie Sika M. , Arnold Charles D. , Davis Jennie N. , Becher Emily R. , Fuseini Ahmed D. , Nyaaba Kania W. , Tan Xiuping (Jenny) , Adams Katherine P. , Lietz Georg , Vosti Stephen A. , Adu-Afarwuah Seth
Published: July 2023

Introduction

Micronutrient deficiencies are prevalent in West Africa, particularly among women of reproductive age (WRA) and young children. Bouillon is a promising food fortification vehicle due to its widespread consumption. This study aims to evaluate the impact of multiple micronutrient-fortified bouillon cubes, compared to control bouillon cubes (fortified with iodine only), on micronutrient status and hemoglobin concentrations among lactating and non-lactating WRA and young children in northern Ghana.

Methods

This randomized, controlled doubly-masked trial will be conducted in the Kumbungu and Tolon districts in the Northern Region of Ghana, where prior data indicate multiple micronutrient deficiencies are common. Participants will be: 1) non-pregnant non-lactating WRA (15-49 y), 2) children 2-5 y, and 3) non-pregnant lactating women 4-18 months postpartum. Eligible participants will be randomly assigned to receive household rations of one of two types of bouillon cubes: 1) a multiple micronutrient-fortified bouillon cube containing vitamin A, folic acid, vitamin B12, iron, zinc, and iodine, or 2) a control cube containing iodine only.

Each participant’s household will receive a ration of bouillon cubes every 2 weeks, and households will be advised to prepare meals as usual, using the study-provided cubes. The trial duration will be 9 months for non-pregnant non-lactating WRA and children, and 3 months for lactating women. The primary outcomes will be changes in biomarkers of micronutrient status and hemoglobin. Secondary outcomes will include change in prevalence of micronutrient deficiency and anemia; dietary intake of bouillon and micronutrients; inflammation, malaria, and morbidity symptoms; and child growth and development.

Discussion

Evidence from this study will inform discussions about bouillon fortification in Ghana and West Africa.
Can a specific biobehavioral based therapeutic education program lead to changes in pain perception and brain plasticity biomarkers in chronic pain patients? A study protocol for a randomized clinical trial
Authors: Di Bonaventura Silvia , Fernández Carnero Josué , Ferrer Peña Raúl
Published: July 2023

Background

Chronic pain conditions are complex multifactorial disorders with physical, psychological, and environmental factors contributing to their onset and persistence. Among these conditions, the role of brain-derived neurotrophic factor (BDNF) and the impact of a specific therapeutic education (TE) on pain management have emerged as important areas of research.

Objective

The aim of this study is to investigate the effects of a specific type of therapeutic education on pain levels and BDNF concentrations.

Methods

In this single-blind, randomized clinical trial, patients will be randomly assigned to one of two groups: one group will receive education with TE and the other group will receive education without TE. Assessments will be made at baseline, mid-treatment, post-intervention, and at one and eight months.

Outcomes

The expected results of this study will shed light on the role of TE in pain management and provide insight into its effects on BDNF levels. The intervention will also provide an opportunity to biochemically measure the plastic changes, thereby improving our understanding of its effects on brain plasticity.

Conclusion

This study aims to determine the applicability of therapeutic education as an effective non-pharmacological intervention for the management of chronic pain. The rigorous scientific methods used ensure that the proposed interventions will be clinically applicable across different health care systems.

Strengths and limitations of this study

The study will use a specifically pain oriented methodological approach that intends to go beyond purely informational pain neuroscience education, aiming for a more useful understanding of pain from patients.

Incorporating the salutogenic model in therapeutic education will bring a health focused perspective to the research, potentially enriching its interpretive framework helping future interventions.

The proposed use of clear and replicable guidelines such as GREET or TIDieR may help in the practical implementation challenge for clinicians, potentially influencing also the study’s reproducibility.

While the study plans to assess psychosocial factors, pain intensity levels, and brain plastic changes due to therapeutic education, this comprehensive approach might pose notable methodological challenges.

Given the emerging field of brain plasticity related to therapeutic education in chronic pain patients, the limited existing research may influence the interpretive depth of the study’s findings.

Protocol version

In this first version of the protocol dated July 2023, we are recruiting the sample, which is planned to be completed in approximately two months (September 2023) in order to start the trial in October 2023.