bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro efficacy of antibiotic loaded calcium sulfate beads (Stimulan Rapid Cure) against polymicrobial communities and individual bacterial strains derived from diabetic foot infections
Authors: Fletcher Julie , Porter Rob , Boulton Zoe , Brown Laura , Knight Bridget , Romanczuk Lidia , Aiken Sean , Delury Craig , Michell Stephen
Published: May 2022

Introduction. Diabetic foot infection (DFI) is the main reason for diabetes-related hospitalisation and is a major cause of diabetes-related amputation. DFIs are often complicated by ischaemia in the affected limb, the presence of polymicrobial biofilms and increasingly the occurrence of antibiotic resistant bacteria.

Hypothesis/Gap statement. Antibiotic loaded beads could inhibit the growth of polymicrobial DFI communities with differing compositions in vitro.

Aim. This study investigates the in vitro efficacy of antibiotic loaded calcium sulfate beads (Stimulan Rapid Cure, Biocomposites Ltd., UK) against polymicrobial DFI communities and individual bacterial strains derived from DFIs.

Methodology. Debrided tissue obtained from the base of infected diabetic foot ulcers was homogenised and spread over the surface of Columbia blood agar (CBA) and fastidious anaerobe agar (FAA) plates. Calcium sulfate beads containing a combination of vancomycin and gentamicin were then placed on the surface of the agar and following incubation, zones of inhibition (ZOI) were measured. For individual bacterial strains isolated from the infected tissue, calcium sulfate beads containing vancomycin, gentamicin, flucloxacillin or rifampicin and beads containing a combination of vancomycin and gentamicin or flucloxacillin and rifampicin were tested for their ability to inhibit growth.

Results. Calcium sulfate beads loaded with a combination of vancomycin and gentamicin were able to inhibit bacterial growth from all polymicrobial tissue homogenates tested, with ZOI diameters ranging from 15 to 40 mm. In the case of individual bacterial strains, beads containing combinations of vancomycin and gentamicin or flucloxacillin and rifampicin were able to produce ZOI with Gram-positive facultatitive anaerobic strains such as

Staphylococcus aureus

and

Enterococcus faecalis

, Gram-negative facultative anaerobic strains such as

Pseudomonas aeruginosa

and obligate anaerobic strains such as

Finegoldia magna

even where acquired resistance to one of the antibiotics in the combination was evidenced.

Conclusion. The local use of calcium sulfate beads containing a combination of two antibiotics demonstrated high efficacy against polymicrobial DFI communities and individual DFI bacterial strains in in vitro zone of inhibition tests. These results show promise for clinical application, but further research and clinical studies are required.
The lipoprotein DolP affects cell separation in Escherichia coli, but not as an upstream regulator of NlpD
Authors: Boelter Gabriela , Bryant Jack A. , Doherty Hannah , Wotherspoon Peter , Alodaini Dema , Ma Xuyu , Alao Micheal B. , Moynihan Patrick J. , Moradigaravand Danesh , Glinkowska Monika , Knowles Timothy J. , Henderson Ian R. , Banzhaf Manuel
Published: May 2022

Bacterial amidases are essential to split the shared envelope of adjunct daughter cells to allow cell separation. Their activity needs to be precisely controlled to prevent cell lysis. In Escherichia coli, amidase activity is controlled by three regulatory proteins NlpD, EnvC and ActS. However, recent studies linked the outer membrane lipoprotein DolP (formerly YraP) as a potential upstream regulator of NlpD. In this study we explored this link in further detail. To our surprise DolP did not modulate amidase activity in vitro and was unable to interact with NlpD in pull-down and MST (MicroScale Thermophoresis) assays. Next, we excluded the hypothesis that ΔdolP phenocopied ΔnlpD in a range of envelope stresses. However, morphological analysis of double deletion mutants of amidases (AmiA, AmiB AmiC) and amidase regulators with dolP revealed that ΔamiAΔdolP and ΔenvCΔdolP mutants display longer chain length compared to their parental strains indicating a role for DolP in cell division. Overall, we present evidence that DolP does not affect NlpD function in vitro, implying that DolP is not an upstream regulator of NlpD. However, DolP may impact daughter cell separation by interacting directly with AmiA or AmiC, or by a yet undiscovered mechanism.
Comparison of tests done, and Tuberculosis cases detected by Xpert® MTB/RIF and Xpert® MTB/RIF-Ultra in Uganda
Authors: Kakinda Michael , Tugumisirize Didas , Nyombi Abdunoor , Mugisha Marvin , Turyahabwe Stavia , Walusimbi Simon , Matovu Joseph K. B
Published: May 2022

Background

Uganda introduced Xpert® MTB/RIF assay into its TB diagnostic algorithm in January 2012. In July 2018, this assay was replaced with Xpert® MTB/RIF Ultra assay. We set out to compare the tests done and tuberculosis cases detected by Xpert® MTB/RIF and Xpert® MTB/RIF Ultra assay in Uganda.

Methods

This was a before and after study, with the tests done and TB cases detected between Jan-June 2019 when using Xpert® MTB/RIF Ultra assay compared to those done between Jan-June 2018 while using Xpert® MTB/RIF assay. This data was analyzed using Stata version 13, it was summarized into measures of central tendency and the comparison between Xpert® MTB/RIF Ultra and Xpert® MTB/RIF was explored using a two-sided T-test which was considered significant if p <0.05.

Results

One hundred and twelve (112) GeneXpert sites out of a possible 239 were included in the study. 128,476 (M: 1147.11, SD: 842.88) tests were performed with Xpert® MTB/RIF Ultra assay, with 9693 drug-susceptible TB (DS-TB) cases detected (M: 86.54, SD: 62.12) and 144 (M: 1.28, SD: 3.42) Rifampicin Resistant TB cases (RR-TB). Whilst 107, 890 (M: 963.30, SD: 842.88) tests were performed with Xpert® MTB/RIF assay between, 8807 (M: 78.63, SD: 53.29) DS-TB cases were detected, and 147 (M: 1.31, SD: 2.39) RR-TB cases. The Number Need to Test (NNT) to get one TB case was 12 for Xpert® MTB/RIF and 13 for Xpert ®MTB/RIF Ultra. On comparing the two assays in terms of test performance (p=0.75) and case detection both susceptible TB (p=0.31) and RR-TB (p=0.95) were not found statistically significant.

Conclusions

This study found no significant difference in test performance and overall detection of DS-TB and RR-TB when using Xpert® MTB/RIF Ultra and Xpert® MTB/RIF assays. The health systems approach should be used to elucidate all the probable potential of Xpert® MTB/RIF Ultra.
Japanese Encephalitis emergence in Australia: the potential population at risk
Authors: Yakob Laith , Hu Wenbiao , Frentiu Francesca D. , Gyawali Narayan , Hugo Leon E. , Johnson Brian , Lau Colleen , Kanamori Luis Furuya , Magalhaes Ricardo Soares , Devine Gregor
Published: May 2022

In Australia, Japanese Encephalitis virus circulated in tropical north Queensland between 1995 and 2005. In 2022, a dramatic range expansion across the southern states resulted in 24 confirmed human cases and three deaths. We discuss the outbreak drivers and estimate the potential size of the human population at risk.
Recent advances in efficacy of corticosteroids as adjunct therapy for the treatment of community-acquired pneumonia in children: a systematic review and meta-analysis
Authors: Mukanhaire Lydia , Wang Junyan , Zong Xiaoyu , Zhang Lingjian , Zhou Xiaohui , Gong Jian
Published: May 2022

It has been recently shown that the adjunct use of corticosteroids in the treatment of community-acquired pneumonia shorten the time taken to reach clinical stability (time to clinical stability) in patients with community-acquired pneumonia (CAP). Considering the hyperglycemic effects of corticosteroids, there are concerns about the efficacy and safety of this therapy for children with CAP. Our objective is to evaluate the influence of recent advances in adjunct corticosteroid use and/or aerosolized antibiotic administration on admission to hospital with our main outcome being duration of fever and hospital stay, and additional outcomes as the time to clinical stability therapeutic efficacy, C-reactive protein and defervescence at 24, 48, and 72 hours after starting treatment in a well-defined cohort of children with community-acquired pneumonia. Therapeutic efficacy is defined as the rate of achieving clinical recovery with no fever, improvement or disappearance of cough, and improved or normal laboratory values. Five academic literature databases will be searched using Boolean keyword searches. Articles eligible for inclusion are those that present original research with the study topic as CAP, the study was designed as a randomized controlled trial (RCT) or clinical trial (CT) or an observational study with controls. The review will result in a narrative synthesis that summarizes the effectiveness of corticosteroid use in children.
Aggressive Antipyretics in CNS Malaria: Study Protocol of a Randomized-Controlled Trial Assessing Antipyretic Efficacy and Parasite Clearance Effects (Malaria FEVER Study)
Authors: Chilombe Moses , McDermott Michael , Seydel Karl B. , Mathews Manoj , Mwenechanya Musaku , Birbeck Gretchen L.
Published: May 2022

Background

Despite ongoing eradication efforts, malaria remains a major public health challenge in Africa where annually, ~250,000 children with malaria experience a neurologic injury with subsequent neurodisability. Evidence indicates that among children with CNS malaria, a higher temperature during the acute illness is a risk factor for post-infectious neurologic sequelae. As such, aggressive antipyretic therapy may be warranted, at least among children with complicated malaria who are at substantial risk of brain injury. Previous clinical trials conducted primarily in children with uncomplicated malaria and using only a single antipyretic medication have shown limited benefits in terms of fever reduction; however, no studies to date have examined malaria fever management using dual therapies. In this clinical trial of aggressive antipyretic therapy, children hospitalized with CNS malaria will be randomized to usual care (acetaminophen every 6 hours for a temperature ≥ 38.5°C) vs. prophylactic acetaminophen and ibuprofen every 6 hours for 72 hours. This proof-of-concept study will determine whether aggressive antipyretic therapy results in a lower mean maximum temperature relative to usual care.

Methods

We will enroll 284 participants from three settings at Queen Elizabeth Central Hospital in Blantyre, Malawi; at the University Teaching Hospitals Children’s Hospital in Lusaka, Zambia and at Chipata Central Hospital, Chipata, Zambia. Parents or guardians must provide written informed consent. Eligible participants are 2-11 years with evidence of P. falciparum malaria infection by peripheral blood smear or rapid diagnostic test with CNS symptoms associated with malaria. Eligible children will receive treatment allocation as determined by randomization and will be assigned to treatment groups with 1:1 allocation using blocked randomization.

Discussion

The clinical trial proposed here seeks to challenge the practice paradigm of limited fever treatment based upon hyperpyrexia by evaluating the fever-reduction efficacy of more aggressive antipyretic use involving two antipyretics and prophylactic administration while also taking advantage of a relatively new method for quantifying total parasite burden (HRP2 quantification) to further characterize malaria severity and elucidate the impact of antipyretics on parasite sequestration and clearance. If aggressive antipyretic therapy is shown to safely reduce the maximum temperature during CNS malaria, a clinical trial evaluating the neuroprotective effects of temperature reduction in CNS malaria is warranted.

Trial registration

This trial is registered withClinicalTrial.gov(NCT03399318) and with the Pan African Clinical Trials Registry (PACTR201804003255157)
A blueprint for biobanking in everyday clinical practice in psychiatry: The Munich Mental Health Biobank
Authors: Kalman JL , Burkhardt G , Adorjan K , Barton BB , De Jonge S , Eser-Valeri D , Falter-Wagner CM , Heilbronner U , Jobst A , Keeser D , Koenig C , Koller G , Koutsouleris N , Kurz C , Landgraf D , Merz K , Musil R , Nelson AM , Padberg F , Papiol S , Pogarell O , Perneczky R , Raabe F , Reinhard MA , Richter A , Rüther T , Simon MS , Schmitt A , Slapakova L , Scheel N , Schüle C , Wagner E , Wichert SP , Zill P , Falkai P , Schulze TG , Schulte EC
Published: May 2022

Translational research on complex, multifactorial mental health disorders, such as bipolar disorder, major depressive disorder, schizophrenia, and substance use disorders requires databases with large-scale, harmonized, and integrated real-world and research data.

The Munich Mental Health Biobank (MMHB) is a mental health-specific biobank that was established in 2019 to collect, store, connect, and supply such high-quality phenotypic data and biospecimens from patients and study participants, including healthy controls, recruited at the Department of Psychiatry and Psychotherapy and the Institute of Psychiatric Phenomics and Genomics, University Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany. Participants are asked to complete a questionnaire that assesses sociodemographic and cross-diagnostic clinical information, provide blood samples, and grant access to their existing medical records. The generated data and biosamples are available to both academic and industry researchers. In the current manuscript, we outline the workflow and infrastructure of the MMHB, describe the clinical characteristics and representativeness of the sample collected so far, and reveal future plans for expansion and application.

As of October 31, 2021, the MMHB contains a continuously growing set of data from 578 patients and 104 healthy controls (46.37% female; median age, 38.31 years). The five most common mental health diagnoses in the MMHB are recurrent depressive disorder (38.78%; ICD-10: F33), alcohol-related disorders (19.88%; ICD-10: F10), schizophrenia (19.69%; ICD-10: F20), depressive episode (15.94%; ICD-10: F32), and personality disorders (13.78%; ICD-10: F60). Compared with the average patient treated at the recruiting hospitals, MMHB participants have significantly more mental health-related contacts, less severe symptoms, and a higher level of functioning. The distribution of diagnoses is also markedly different in MMHB participants compared with individuals who did not participate in the biobank.

After establishing the necessary infrastructure and initiating recruitment, the major tasks for the next phase of the MMHB project are to improve the pace of participant enrollment, diversify the sociodemographic and diagnostic characteristics of the sample, and improve the utilization of real-world data generated in routine clinical practice.
Testing the Triple Network Model of Psychopathology in a Transdiagnostic Neurodevelopmental Cohort
Authors: Jones Jonathan S. ,   The CALM Team, Leyland-Craggs Amelia , Astle Duncan E.
Published: May 2022

Background

The triple network model of psychopathology posits that altered connectivity between the Salience (SN), Central Executive (CEN), and Default Mode Networks (DMN) may underlie neurodevelopmental conditions. However, this has yet to be tested in a transdiagnostic sample of youth.

Methods

We investigated triple network connectivity in a sample of 175 children (60 girls) that represent a heterogeneous population who are experiencing neurodevelopmental difficulties in cognition and behavior, and 60 comparison children (33 girls) without such difficulties. Hyperactivity/impulsivity and inattention were assessed by parent-report and resting-state functional Magnetic Resonance Imaging data were acquired. Functional connectivity was calculated between independent network components and regions of interest. We then examined whether connectivity between the SN, CEN and DMN was dimensionally related to hyperactivity/impulsivity and inattention, whilst controlling for age, gender, and motion.

Results

Hyperactivity/impulsivity was associated with decreased segregation between the SN, CEN, and DMN in at-risk children, whereas it was associated with increased segregation of the CEN and DMN in comparison children. We replicated these effects in networks and regions derived from an adult parcellation of brain function and when using increasingly stringent exclusion criteria for in-scanner motion.

Conclusions

Triple network connectivity characterizes transdiagnostic neurodevelopmental difficulties with hyperactivity/impulsivity. This may arise from delayed network segregation, difficulties sustaining CEN activity to regulate behavior, and/or a heightened developmental mismatch between neural systems implicated in cognitive control relative to those implicated in reward/affect processing.
Association of socioeconomic status with arterial stiffness in older African American and White Adults: The ARIC Study Cohort
Authors: Spikes T.A. , Alam A.B. , Lewis T.T. , Windham B.G. , Kucharska-Newton A. , Alonso A.
Published: May 2022

Background

The contributions of traditional CVD risk factors do not fully explain the racial and socioeconomic disparities in arterial stiffness. The extent to which the association of socioeconomic status (SES) with subclinical CVD is different for older African American and White adults is unclear.

Methods and Results

Cross-section associations of individual SES [education and income] with carotid femoral pulse wave velocity (cfPWV), a subclinical marker of arterial stiffness, and modification of this relationship by race were examined among 3,342 participants of the Atherosclerosis Risk in Communities (ARIC) Study (age=75±4.9 years, 64% female, 23% African American, free of CVD in 2011-2013) using multivariable linear regression. Post-graduate education compared to less than high school, was associated with lower cfPWV (less stiffness) in African Americans (β = −1.28 m/s; 95% CI, −1.97, −0.59), but not in Whites (β = −0.69 m/s; 95% CI, −1.39, 0.01). Income ≥$50K as compared to <$25K, was associated with lower cfPWV both in African Americans (β = −0.82 m/s; 95% CI, −1.42, −0.22) and Whites (β = −0.76 m/s; 95% CI, −1.19, −0.32). However, interaction of race with individual measures of SES on cfPWV in African American and White adults were not statistically significant (p-value for interaction >0.05).

Conclusions

Higher SES was cross-sectionally associated with lower arterial stiffness in this cohort; the data did not support differences by race. Prospective studies of SES and cfPWV among a racially socioeconomically diverse cohort merit further study.
Novel method for estimating right atrial pressure with point-of-care ultrasound (POCUS)
Authors: Istrail Larry , Kiernan Joseph , Stepanova Maria
Published: May 2022

Current noninvasive estimation of right atrial pressure (RAP) by either bedside jugular venous pressure (JVP) exam or inferior vena cava (IVC) measurement during a formal echocardiogram offer imprecise estimates of actual RAP. We enrolled 41 patients in a prospective, blinded study to validate a novel point-of-care ultrasound method to estimate RAP. Two subjects were excluded and 39 were included in the final analysis. The ultrasound estimate of RAP (RAPU) was compared to the RAP measurement during right heart catheterization (RAPi) both as measured and corrected for the mid-AP diameter. The correlation coefficient between RAPi and corrected RAPU measurements was +0.72, regression R2 0.52, bias −0.60 mmHg (95% confidence interval [CI], −1.60 to +0.39 mmHg) with the limits of agreement −5.56 to +7.24 mmHg, and 3 mmHg accuracy of 26 (67%). Similarly, for the uncorrected RAPU measurement, the correlation coefficient was +0.75, regression R2 0.56, bias −0.49 mmHg (95% CI, −1.42 to +0.43 mmHg) with the limits of agreement −5.56 to +7.24 mmHg, and 3 mmHg accuracy of 29 (74%). This simple bedside evaluation of right atrial depth and the right jugular vein correlates with actual right atrial pressure better than traditional IVC parameters, and can accurately estimate RAP within 3mmHg in most patients.
Precision Digital Intervention for Depression Based on Social Rhythm Principles Adds Significantly to Outpatient Treatment
Authors: Frank Ellen , Wallace Meredith , Matthews Mark J. , Kendrick Jeremy , Leach Jeremy , Moore Tara , Aranovich Gabriel , Choudhury Tanzeem , Shah Nirav R. , Framroze Zeenia , Posey Greg , Burgess Samuel , Kupfer David J.
Published: May 2022

We conducted a 16-week randomized controlled trial in psychiatric outpatients with a lifetime diagnosis of a mood and/or anxiety disorder to measure the impact of a first of its kind precision digital intervention based on social rhythm regulation principles (Cue). The full intent to treat (ITT) sample consisted of 133 individuals, aged 18 to 65. The primary sample of interest were individuals with moderately severe to severe depression at study entry (baseline PHQ-8 score greater than or equal to 15; N=28).

Cue is a novel digital intervention platform that capitalizes on the smartphone’s ability to continuously monitor depression relevant behavior patterns and use each patient’s behavioral data to provide timely, personalized micro interventions, making this the first example of a digital precision intervention that we are aware of. Participants were randomly allocated to receive Cue plus care as usual or digital monitoring only plus care as usual.

Within the depressed and full ITT samples, we fit a mixed effects model to test for group differences in the slope of depressive symptoms over 16 weeks. To account for the nonlinear trajectory with more flexibility, we also fit a mixed effects model considering week as a categorical variable and used the resulting estimates to test the group difference in PHQ change from baseline to 16 weeks.

In the depressed at entry sample, we found evidence for benefit of Cue. The large group difference in the slope of PHQ-8 (Cohen’s d= -0.72) indicated a meaningfully more rapid rate of improvement in the intervention group than in the control group. The Cue group also demonstrated significantly greater improvement in PHQ-8 from baseline to 16 weeks (p=0.009). In the full sample, the group difference in the slope of PHQ-8 was negligible (Cohen’s d=-0.10); however, the Cue group again demonstrated significantly greater improvement from baseline to 16 weeks (p=0.040).

We are encouraged by the size of the intervention effect in those who were acutely ill at baseline and by the finding that across all participants, 80% of whom were receiving pharmacotherapy, we observed significant benefit of Cue at 16 weeks of treatment. These findings suggest that a social rhythm focused digital intervention platform may represent a useful and accessible adjunct to antidepressant treatment.

(https://clinicaltrials.gov/ct2/show/NCT03152864?term=ellen+frank&draw=2&rank=3)
Antibody responses to known and unknown SARS-CoV-2 infections after mRNA vaccine booster
Authors: Demonbreun Alexis R. , Sancilio Amelia , Vaught Lauren A. , Reiser Nina L. , Pesce Lorenzo , Sode Eoin P. , Mustanski Brian , D’Aquila Richard , McNally Elizabeth M. , McDade Thomas W.
Published: May 2022

We followed a fully-vaccinated (two mRNA vaccine doses) community cohort (n=41) without prior COVID-19 diagnosis from September 2021 through March 2022 through the Omicron wave following a booster mRNA vaccination. 19.5% of participants reported a known SARS-CoV-2 infection during the Omicron wave, which was confirmed by anti-nucleocapsid IgG. An additional 36.5% also developed anti-nucleocapsid IgG after the boost, consistent with unknown, asymptomatic SARS-CoV-2 infection during this period. Infection defined by anti-nucleocapsid IgG, whether known to participant or not, increased anti-spike IgG levels, relative to those lacking anti-nucleocapsid IgG, at 120 days post-booster.
Functional genomics in primary T cells and monocytes identifies mechanisms by which genetic susceptibility loci influence systemic sclerosis risk
Authors: González-Serna David , Shi Chenfu , Kerick Martin , Hankinson Jenny , Ding James , McGovern Amanda , Tutino Mauro , Martin Gonzalo Villanueva , Ortego-Centeno Norberto , Luis Callejas José , Martin Javier , Orozco Gisela
Published: May 2022

Objectives

Systemic sclerosis (SSc) is a complex autoimmune disease with a strong genetic component. However, most of the genes associated to the disease are still unknown because associated variants affect mostly non-coding intergenic elements of the genome. The challenge now is to use functional genomics to translate the genetic findings into a better understanding of the disease.

Methods

Promoter capture Hi-C and RNA sequencing experiments were performed in CD4+T cells and CD14+monocytes samples from 10 SSc patients and 5 healthy controls to link SSc-associated variants with their target genes, followed by differential expression and differential interaction analyses between cell types.

Results

We linked SSc-associated loci to 39 new potential target genes and confirm 7 previously known genes. We highlight novel causal genes, such asCXCR5as the most probable candidate gene for theDDX6locus. Some previously known SSc associated genes such asIRF8, STAT4, orCD247interestingly showed cell type specific interactions. We also identified 15 potential drug targets already in use in other similar immune-mediated diseases that could be repurposed for SSc treatment. Furthermore, we observed that interactions are directly correlated with the expression of important genes implicated in cell type specific pathways and find evidence that chromatin conformation is associated with genotype.

Conclusions

Our study reveals potential causal genes for SSc-associated loci, some of them acting in a cell type specific manner, suggesting novel biological mechanisms that might mediate SSc pathogenesis.
Interactions between Perceived Stress and Microbial-Host Immune Components in Pregnancy
Authors: Bernabé Beatriz Peñalver , Maki Pauline M. , Cunningham Janet L. , Eisenlohr-Moul Tory , Tussing-Humphreys Lisa , Carroll Ian M. , Meltzer-Brody Samantha , Gilbert Jack A. , Kimmel Mary
Published: May 2022

Background

Higher stress during pregnancy associates with negative outcomes and elevated inflammation. The gut microbiota reflects the environment, lifestyle, and the perinatal period. The gut microbiota, alongside host immune responses, has the potential to aid in identifying when stress is excessive.

Methods

Two U.S. cohorts, of 84 pregnant individuals, composed of urban women of color and suburban white women, completed the Perceived Stress Scale-10 (PSS-10) and provided fecal and blood samples at two time points. Confirmatory Factor Analysis assessed the robustness of a two-factor PSS-10 (Emotional Distress and Self-Efficacy) in the two cohorts. Gut microbiota composition was measured by 16S rRNA amplicon sequencing and the immune system activity was assessed with a panel of 21 T-cell related cytokines and chemokines.

Results

Emotional Distress levels were higher in the suburban compared to the urban cohort, but levels of Self-Efficacy were similar. Emotional Distress and Self-Efficacy levels were associated with distinct taxonomical signatures and the gut microbiota data improved the prediction of Self-Efficacy levels compared with models based on socio-demographic characteristics alone. Integration of self-reported symptoms, microbial and immune information revealed a possible mediation effect of Bacteroides uniformis between the immune system (through CXCL11) and Self-Efficacy.

Conclusions

The study identified links between distinct taxonomical and immunological signatures with perceived stress. The data is congruent with a model where gut microbiome and immune factors may modulate neural plasticity resulting in increased Self-Efficacy during pregnancy. The predictive value of these peripheral markers merit further study.
Behavioral Effects in Disorders of Consciousness Following Transcranial Direct Current Stimulation: A Systematic Review and Individual Patient Data Meta-analysis of Randomized Clinical Trials
Authors: Xu Zeyu , Zheng Ruizhe , Xia Tiantong , Qi Zengxin , Zang Di , Wang Zhe , Wu Xuehai
Published: May 2022

Background

In patients with Disorders of Consciousness (DoC), transcranial direct current stimulation (tDCS) was a promising intervention for it. However, uncertainties remain about the treatment effect and the optimal treatment strategy of the tDCS in the DoC.

Objective

In this meta-analysis of individual patient data (IPD), we assess whether utilizing tDCS as a treatment in DoC could improve patients’ behavioral performance and whether patient characteristics or tDCS protocol could modify the treatment effect.

Methods

We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials through April 7, 2022, using the terms “persistent vegetative state,” “minimally conscious state,” “disorder of consciousness,” or “unresponsive wakefulness syndrome,” and “transcranial direct current stimulation” to identify Randomized Controlled Trials (RCTs) in English-language publication. Studies were eligible for inclusion if they reported pre- and post-tDCS Coma Recovery Scale-Revised (CRS-R) scores. From the included studies, any patients who had incomplete data were excluded. We performed a meta-analysis to assess the treatment effect of the tDCS compared with sham control. Additionally, a subgroup analysis was performed to determine whether patients’ baseline characteristics could modify the treatment effect and the optimal tDCS protocol.

Results

We identified 145 papers, eight trials (including 181 patients) were finally included in the analysis, and one individual data were excluded because of incompletion. Our meta-analysis demonstrated a mean difference change in the CRS-R score of 0.89 (95% CI, 0.17-1.61) between tDCS and sham-control, favoring tDCS. The subgroup analysis showed that patients who were male or in minimally conscious state (MCS) were associated with a greater improvement in CRS-R score and that adopting 5 or more sessions of tDCS protocol might have a better treatment effect than just one session.

Conclusion

tDCS can improve the behavioral performance of DoC patients. However, heterogeneity existed within the patients’ baseline condition and the stimulation protocol. There should be more exploration of the optimal tDCS protocol and the most beneficial patient group based on the mechanism of tDCS in the future.
Association of sleep abnormalities in older adults with risk of developing Parkinson’s disease
Authors: Otaiku Abidemi I.
Published: May 2022

Background

Parkinson’s disease (PD) is associated with abnormalities of sleep macro- and microstructure as measured using polysomnography (PSG). Whether sleep abnormalities precede the development of PD is unknown. This study investigated the association between PSG measured sleep abnormalities in older adults and the risk of developing PD.

Methods

2,770 men aged 67 years or older from the ancillary sleep study of the Osteoporotic Fractures in Men Study (MrOS), a population-based cohort from the USA, who were free from PD at baseline (December 2003 – March 2005) and in whom there was PSG data available, were included in this analysis. Incident PD was based on a clinical diagnosis from a medical professional. Multivariable logistic regression was used to estimate odds ratios (OR) for incident PD by quartiles of PSG measures.

Findings

During a median follow-up of 10.1 years, 70 (2.5%) cases of incident PD were identified. Longer total sleep time, lower rapid eye movement sleep (REM) percentage, a lower α/θ ratio during non-REM sleep and higher minimum oxygen saturations during REM sleep, were independently associated with an increased risk of developing PD during follow-up. Conversely, a higher awakening index was independently associated with a decreased risk of developing PD. The OR for the highest risk quartiles compared to the lowest risk quartiles, ranged from 2.3 to 4.0 (P < 0.05). The associations remained significant when incident PD cases occurring within the first two years of follow-up were excluded from the analyses.

Conclusions

Macro- and microstructural sleep abnormalities precede the development of PD by several years and can identify individuals at high risk of developing PD in the future. Future studies are needed to determine whether sleep abnormalities represent preclinical markers of PD or causal risk factors.
Implementing a data infrastructure for precision oncology projects leveraging REDCap
Authors: Vesteghem Charles , Dahl Simon Christian , Brøndum Rasmus Froberg , Sønderkær Mads , Bødker Julie Støve , Schmitz Alexander , Weischenfeldt Joachim , Pedersen Inge Søkilde , Sommer Mia , Rytter Anne Stoffersen , Nielsen Marlene Maria , Ladekarl Morten , Severinsen Marianne Tang , Dybkær Karen , Grønbæk Kirsten , El-Galaly Tarec , Roug Anne Stidsholt , Bøgsted Martin
Published: May 2022

Objectives

To facilitate clinical implementation and research in precision oncology, notably the pairing of patients, variants and treatments to identify candidates for clinical trials, we have built a data infrastructure to 1) capture and store data, 2) reduce manual tasks for clinical and genomic data collection and management, 3) combine data for quality controls, reporting and findability.

Infrastructure

The infrastructure uses REDCap repositories to capture and store data. The structure of these repositories is customized for each project. Additionally, a cross-project web platform was developed using software development best practices and state-of-the-art web technologies to circumvent REDCap’s limitations and integrate other third-party resources. Using REDCap’s application programming interfaces, this platform allowed validation of data across multiple repositories, easy import of data from external sources, generation of overviews of included patients and available data, combination of genomic and clinical data to generate tumour board reports and the findability of data. Its design was driven by data stewardship best practices.

Usage

Across four precision medicine projects, the infrastructure has been used to collect data for 1921 patients, including 453 genomic data files. The custom-built web platform made it possible to import, validate, and present data in a comprehensive manner. This included building tumour board reports for clinicians, combining clinical and genomic data, and search functionalities for researchers.

Discussion

REDCap allowed us to capitalize on the numerous data capture and management features developed in this solution. Designing a cross-project platform guarantees long-term relevance where developments can be mutualised across projects and allowed us to make the overall solution more compliant with the FAIR (Findable, Accessible, Interoperable, Reusable) data principles. Further developments should be considered, notably automatic retrieval of data from electronic health records to limit the number of manual tasks.

Conclusion

The proposed infrastructure allowed our precision oncology projects to gain efficiency in data collection and increase data quality by reducing manual work, and it gave a straightforward and customized access to data for researchers and clinicians.
Mental-health before and during the COVID-19 pandemic in adults with neurodevelopmental disorders
Authors: Shakeshaft Amy , Blakey Rachel , Kwong Alex S.F. , Riglin Lucy , Smith George Davey , Stergiakouli Evie , Tilling Kate , Thapar Anita
Published: May 2022

The COVID-19 pandemic negatively impacted mental health globally. Individuals with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), are at elevated risk of mental health difficulties. Therefore, we investigated the impact of the pandemic on anxiety, depression and mental wellbeing in adults with NDDs using longitudinal data from the Avon Longitudinal Study of Parents and Children study (n=3,058). Mental health data were collected pre-pandemic (age 21-25) and at three timepoints during the pandemic (ages 27-28) using the Short Mood and Feelings Questionnaire, Generalised Anxiety Disorder Assessment-7, and Warwick Edinburgh Mental Wellbeing Scale. ADHD and ASD were defined using validated cut-points of the Strengths and Difficulties Questionnaire and Autism Spectrum Quotient, self-reported at age 25. We used multi-level mixed-effects models to investigate changes in mental health in those with ADHD and ASD compared to those without. Prevalences of depression, anxiety and poor mental wellbeing were higher at all timepoints (pre-pandemic and during pandemic) in those with ADHD and ASD compared to those without. Anxiety increased to a greater extent in those with ADHD (β=0.8 [0.2,1.4], p=0.01) and ASD (β=1.2 [-0.1,2.5], p=0.07), while depression symptoms decreased, particularly in females with ASD (β=-3.1 [-4.6,-1.5], p=0.0001). On average, mental wellbeing decreased in all, but to a lesser extent in those with ADHD (β=1.3 [0.2,2.5], p=0.03) and females with ASD (β=3.0 [0.2,5.9], p=0.04). To conclude, anxiety disproportionately increased in adults with NDDs during the pandemic, however, the related lockdowns may have provided a protective environment for depressive symptoms in the same individuals.
Use of antihypertensive drugs and breast cancer risk: a two-sample Mendelian randomization study
Authors: Zheng Guoqiao , Chattopadhyay Subhayan , Sundquist Jan , Sundquist Kristina , Ji Jianguang
Published: May 2022

Background

Observational studies regarding the correlation between the use of antihypertensive medication and the risk of breast cancer (BC) reported inconsistent findings. We performed a two-sample Mendelian randomization using instrumental variables to proxy changes in gene expressions of antihypertensive medication targets to interrogate this.

Methods

We assessed the association between single-nucleotide polymorphisms (SNPs) and drug targetable gene expression with expression quantitative trait loci in blood. Further, we investigated association between the SNPs and BC risk with genome-wide association study summary statistics. We then confirmed the hits from Mendelian randomization with tissue-specific analyses along with additional sensitivity assessments (horizontal pleiotropy, colocalization, multiple tissue enrichment etc.).

Results

The overall BC risk was decreased 16% with one standard deviation (SD) increase of SLC12A2 gene expression in blood (odds ratio, 0.86, 95% confidential interval, 0.78-0.94). This signal was further confirmed in estrogen receptor positive (ER+) BC (0.85, 0.78-0.94). In addition, one SD increase in expression of PDE1B in blood was associated with 7% increased risk of ER+ BC (1.07, 1.03-1.11). We detected no evidence of horizontal pleiotropy for these associations and the probability of the causal variants being shared between the gene expression and BC risk was 81.5%, 40.5% and 66.8%, respectively. We failed to observe any significant association between other targeted genes and BC risk.

Conclusions

Use of antihypertensive medications that target SLC12A2 and PDE1B is associated with increased and decreased BC risk, respectively.

Funding

This work was supported by the Swedish Research Council [2018-02400 to K.S., 2020-01175 to J.S., 2021-01187 to J.J.], Cancerfonden [2017 CAN2017/340 to J.J.], Crafoordska Stiftelsen [to J.J.], MAS Cancer [to J.J.], ALF funding from Region Skåne [to J.J. and K.S.]. The funding body was not involved in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Health Economic Analysis of the Integrated Cognitive Assessment Tool to Aid Dementia Diagnosis in the United Kingdom
Authors: Shore Judith , Kalafatis Chris , Modarres Mohammad Hadi , Khaligh-Razavi Seyed-Mahdi
Published: May 2022

Objectives

The aim of this study was to develop a comprehensive economic evaluation of the Integrated Cognitive Assessment (ICA) tool compared with standard cognitive tests when used for dementia screening in primary care and for initial patient triage in memory clinics.

Methods

ICA was compared with standard of care comprising a mixture of cognitive assessment tools over a lifetime horizon and employing the UK health and social care perspective. The model combined a decision tree to capture the initial outcomes of the cognitive testing with a Markov structure that estimated long-term outcomes of people with dementia. Quality of life outcomes were quantified using quality-adjusted life years (QALYs). Both costs and QALYs were discounted at 3.5% per annum and cost-effectiveness was assessed using a threshold of £20,000 per QALY gained.

Results

ICA dominated standard cognitive assessment tools in both the primary care and memory clinic settings. Introduction of the ICA tool was estimated to result in a lifetime cost saving of approximately £147 and £283 per person in primary care and memory clinics, respectively. QALY gains associated with early diagnosis were modest (0.0019 in primary care and 0.0035 in memory clinic). The net monetary benefit of ICA introduction was estimated at £184 in the primary care and £368 in the memory clinic settings.

Conclusions

Introduction of ICA as a tool to screen primary care patients for dementia and perform initial triage in memory clinics could be cost saving to the UK public health and social care payer.
The impact of side effect framing on COVID-19 booster vaccine intentions in an Australian sample
Authors: Barnes K. , Faasse K. , Colagiuri B.
Published: May 2022

Objective

To evaluate the effect of presenting positively attribute-framed side effect information on COVID-19 booster vaccine intention relative to standard negatively-framed wording and a no-intervention control.

Design setting and participants

A representative sample of Australian adults (N=1,204) were randomised to one of six conditions within a factorial design: Framing (Positive; Negative; Control) * Vaccine (Familiar (Pfizer); Unfamiliar (Moderna)).

Intervention

Negative Framing involved presenting the likelihood of experiencing side effects (e.g., heart inflammation is very rare, 1 in every 80,000 will be affected), whereas Positive Framing involved presenting the same information but as the likelihood of not experiencing side effects (e.g., 79,999 in every 80,000 will not be affected).

Primary Outcome

Booster vaccine intention measured pre- and post-intervention.

Results

Positive Framing (M=75.7, SE=0.9, 95% CI[73.9, 77.4]) increased vaccine intention relative to Negative Framing (M=70.7, SE=0.9, 95% CI[68.9, 72.4]) overall (F(1, 1192)=4.68, p=.031, ηp2=.004). Framing interacted with Vaccine and Baseline Intention (F(2, 1192)=6.18, p=.002, ηp2=.01). Positive Framing was superior, or at least equal, to Negative Framing and Control at increasing Booster Intention, irrespective of the participants pre-intervention level of intent. Side effect worry and perceived severity mediated the effect of Positive vs. Negative Framing across vaccines.

Conclusion

Positive framing of side effect information appears superior for increasing vaccine intent relative to the standard negative wording currently used.

Pre-registration

See: aspredicted.org/LDX_2ZL
Epidemiology and determinants of vitamin D deficiency in Eastern Nepal: a community-based, cross-sectional study
Authors: Sherchand O , Baranwal J K , Gelal B
Published: May 2022

Objective

To estimate the prevalence of vitamin D deficiency in the Eastern the part of Nepal and identify the sociodemographic factors associated with it.

Methods

A descriptive cross-sectional study was carried out among 324 participants between the ages of 18 to 65 years from the Sunsari and Morang districts of Nepal. A semi-structured questionnaire helped obtain sociodemographic data followed by anthropometric measurements and blood sampling. 25(OH)D level was measured by Chemiluminescence immunoassay (CLIA) via a fully automated Maglumi 1000 analyzer (SNIBE Co, Ltd, China). Serum 25(OH)D was classified as deficient, insufficient, and sufficient (<20 ng/ml, 20-29 ng/ml, and 30–100 ng/ml respectively). The Chi-square test was used to analyze the sociodemographic variables followed by a post-hoc analysis. Significant variables were subject to multivariate logistic regression.

Result

181(55.9%) of the study population had vitamin D deficiency. There was significant association between vitamin D status and time of maximum sun exposure (Chi-sq = 11.1, p=0.02), duration of sun exposure (Chi-sq = 15.1, p=0.004), type of meat intake (Fischer’s exact test is 16.4, p=0.01), frequency of fish intake (Fischer’s exact test is 19.3, p=0.001), frequency of dairy intake (Chi-sq=11.2, p=0.02). In multivariate regression, consumption of dairy products ≥3/week had lower OR (95% CI) [0.3(0.1-0.8) p:0.02] and weekly fish consumption had lower OR (95% CI) [0.06(0.008-0.6) p: 0.01] for vitamin D deficiency.

Conclusion

The prevalence of vitamin D deficiency was relatively high in eastern Nepal. This highlights the need to create public awareness regarding the importance of bare skin sun exposure and other sources of vitamin D as well as the need to implement food fortification policies by the government.
High prescribing and state-level variation in z-drug use among Medicare patients
Authors: Anderson Kaitlin E. , Basting James L. , Gifeisman Rachel I. , Harris Donovan J. , Rajan Antonica R. , McCall Kenneth L. , Piper Brain J.
Published: May 2022

Background

Z-drugs are nonbenzodiazepine hypnotics used for sleep initiation and maintenance that have been shown to increase the risk of fall-related injuries in patients aged 65 and older. The American Geriatrics Society Beers criteria classifies them as a high-risk medication and strongly recommends avoiding prescribing z-drugs to the elderly due to adverse effects. The objective of this study was to determine the prevalence of Z-drug prescribing among Medicare patients.

Methods

Z-drug prescription data was extracted from the Centers for Medicare and Medicaid Services State Drug Utilization Data (CMS SDUD) for 2018. For all 50 states, the number of prescriptions per 100 Medicare enrollees and days-supply per prescription was determined. The percentage of total prescriptions prescribed by each specialty and the average number of prescriptions prescribed by providers within each specialty was also determined.

Results

Zolpidem was the most prescribed z-drug, making up 95.0% of all z-drug prescriptions. Prescriptions per 100 enrollees were significantly elevated in Utah (28.2) and Arkansas (26.7) and significantly lower in Hawaii (9.3) relative to the national average (17.5). The specialties family medicine (32.1%), internal medicine (31.4%), and psychiatry (11.7%) made up the largest percentages of total prescriptions. The number of prescriptions per provider was significantly elevated for psychiatry relative to other specialties.

Conclusions

Contrary to the Beers criteria, z-drugs are being prescribed to Medicare enrollees over age 65 at high rates. While sleep disturbances in the elderly should not be ignored, alternative therapies must be considered to avoid the serious adverse effects of z-drugs.

Key Points

More than one-half million Medicare patients received z-drug prescriptions in 2018 that were inconsistent with the Beers criteria.

Z-drug prescriptions per 100,000 Medicare patients were significantly elevated in Utah and Arkansas.

Family Medicine had the highest number of prescriptions out of all medical specialties.

Psychiatry had a significantly higher number of prescriptions per provider compared to all other specialties.