bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of in-utero antiretroviral drug exposure on expression of membrane-associated transporters in mouse placenta and fetal brain
Authors: Gilmore Julian C. , Zhang Guijun , Cameron D. William , Serghides Lena , Bendayan Reina
Published: June 2021

Objective:

Although antiretroviral therapy (ART) during pregnancy is effective in limiting vertical HIV transmission, adverse outcomes persist amongst uninfected children exposed to antiretroviral drugs in utero. Membrane-associated drug transporters, metabolic enzymes, and tight junction proteins play important roles in adult antiretroviral drug disposition and toxicity; however, the fetal expression of these proteins in the context of ART, and their impact on in-utero antiretroviral drug distribution remain poorly understood. This study aimed to characterize the role of these proteins in modulating in-utero antiretroviral drug exposure.

Methods:

Pregnant mice were exposed to an ART regimen consisting of lamivudine, abacavir, atazanavir, and ritonavir, at clinically relevant doses. Fetal brain, liver, placenta amniotic fluid, and maternal plasma were collected on gestational day 18.5 and concentration of antiretroviral drugs in fetal tissues was measured by LC/MS/MS, whereas transporter expression was assessed by qPCR.

Results:

Abacavir and lamivudine were detected in fetal brain and amniotic fluid, whereas atazanavir and ritonavir were detected in amniotic fluid only. Robust mRNA expression of key transporters was observed in adult and fetal tissues, and sex differences were identified in the expression of Abcc1 and Slc29a1 in the placenta. Antiretroviral drug exposure was associated with a reduction in relative placental Abcg2, Abcc1, and Slc29a1 expression.

Conclusion:

These findings identify a novel effect of fetal sex and antiretroviral drug treatment on the expression of placental transporters in a mouse model, and characterize the penetration of lamivudine and abacavir into fetal brain, uncovering a potential role of transporters in modulating fetal exposure to antiretroviral drugs.
Accreditation of Simulation Fellowships and Training Programs
Authors: Ahmed Rami A. , Wong Ambrose H. , Musits Andrew N. , Cardell Annemarie , Cassara Michael , Wong Nelson L. , Smith Mary Kay , Bajaj Komal , Meguerdichian Michael , Szyld Demian
Published: June 2021

Summary Statement

As the field of healthcare simulation matures, formal accreditation for simulation fellowships and training programs has become increasingly available and touted as a solution to standardize the education of those specializing in healthcare simulation. Some simulation experts hold opposing views regarding the potential value of simulation fellowship program accreditation. We report on the proceedings of a spirited debate at the 20th International Meeting on Simulation in Healthcare in January 2020. Pro arguments view accreditation as the logical evolution of a maturing profession: improving training quality through standard setting, providing external validation for individual programs, and enhancing the program's return on investment. Con arguments view accreditation as an incompletely formulated construct; burdensome to the “financially strapped” fellowship director, misaligned with simulation fellows' needs and expectations, and confusing to administrators mistakenly equating accreditation with credentialing. In addition, opponents of accreditation postulate that incorporating curricular standards, practice guidelines, and strategies derived and implemented without rigor, supporting evidence and universal consensus is premature. This narrative review of our debate compares and contrasts contemporary perspectives on simulation fellowship program accreditation, concluding with formal recommendations for learners, administrators, sponsors, and accrediting bodies.
Surgical Eligibility Does Not Imply Surgical Equity
Authors: Hester Caitlin A. , Kothari Anai N. , Mason Meredith , Maxwell Jessica , Ikoma Naruhiko , Kim Michael P. , Tzeng Ching-Wei D. , Lee Jeffrey E. , Katz Matthew H. G. , Cao Hop S. Tran
Published: June 2021

Objective:

We sought to characterize differences in pancreatectomy recommendation rates to surgically eligible patients with pancreatic ductal adenocarcinoma of the pancreatic head across age and racial groups.

Background:

Pancreatectomy is not recommended in almost half of otherwise healthy patients with stage I/II pancreatic ductal adenocarcinoma lacking a surgical contraindication. We characterized differences in pancreatectomy recommendation among surgically eligible patients across age and racial groups.

Methods:

Non-Hispanic White (NHW) and Non-Hispanic Black (NHB) patients were identified in the National Cancer Database with clinical stage I/II pancreatic head adenocarcinoma, Charlson Comorbidity Index of 0 to 1, and age 40 to 89 years. Rates of surgery recommendation and overall survival (OS) by age and race were compared. A Pancreatectomy Recommendation Equivalence Point (PREP) was defined as the age at which the rate of not recommending surgery matched the rate of recommending and completing surgery. Marginal standardization was used to identify association of age and race with recommendation. OS was compared using Kaplan–Meier and Cox regression models.

Results:

Among 40,866 patients, 36,133 (88%) were NHW and 4733 (12%) were NHB. For the entire cohort, PREP was 79 years. PREP was 5 years younger in NHB patients than in NHW patients (75 vs 80 years). Adjusted rates of not recommending surgery were significantly higher for NHB than for NHW patients in each age group. After adjusting for surgery recommendation, we found no difference in OS between NHW and NHB patients (hazard ratio 0.98 [95% CI 0.94–1.02]).

Conclusions:

PREP of NHB patients was 5 years younger than NHW patients, and in every age group, the rate of not recommending pancreatectomy was higher in NHB patients. Age and race disparities in treatment recommendations may contribute to shorter longevity of NHB patients.
Clinical and Microbiological Outcomes Associated With Use of Platelet-Rich Plasma in Chronic Venous Leg Uclers
Authors: Pires Bruna Maiara Ferreira Barreto , Baptista de Oliveira Beatriz Guitton Renaud , Bokehi Luciana Castilho , Luiz Ronir Raggio , Carvalho Bernadete Teixeira Ferreira , Santana Rosimere Ferreira , Alfradique de Souza Priscilla , Renato de Paula Geraldo , Teixeira Lenise Arneiro
Published: June 2021

PURPOSE:

To evaluate the susceptibility profiles of Staphylococcus aureus and Pseudomonas aeruginosa strains identified in chronic venous ulcers treated with platelet-rich plasma (PRP) and petrolatum gauze or petrolatum gauze alone and to quantitatively evaluate the bacterial load and biofilm-forming capacities of the detected S. aureus and P. aeruginosa strains.

DESIGN:

Randomized controlled trial.

SUBJECTS AND SETTING:

The convenience sample included 36 participants; 18 were allocated to the PRP combined with the petrolatum gauze group, and 18 were allocated to the control group, which was treated with petrolatum gauze alone.

METHODS:

Thirty-six patients presenting with chronic venous ulcers were consecutively randomized to the PRP group (n = 18) or the petrolatum gauze control group (n = 18). We followed participants for 3 months during treatment and collected swab cultures from their wounds during weeks 1, 6, and 12 or until the wounds healed. The samples were analyzed using mass spectrometry. Antimicrobial susceptibility tests were performed using disk diffusion.

RESULTS:

P. aeruginosa was identified in 39 (39%) of 100 samples, and S. aureus was detected in only 10 (10%) samples collected over the study period. At the end of the 12-week treatment period, the wound infections reduced in both the PRP (P = .0078) and control groups (P = .01). The microorganisms were susceptible to most of the tested antimicrobials. The PRP did not increase the bacterial load in the wounds. All S. aureus strains identified showed biofilm-forming capacities and were classified as weak biofilm producers. All P. aeruginosa strains produced biofilm, with 17 strains being classified as weak, 14 as moderate, and 8 as strong biofilm producers.

CONCLUSIONS:

The PRP plus petrolatum gauze did not increase bacteriological growth or the microbial load in chronic venous ulcers compared with petrolatum gauze alone and could be a considered as an advanced treatment option for these types of chronic wounds.
Development and Implementation of a Simple Wound Care Guideline for Minor Skin Lesions
Authors: Bates Alexandra Nicole , Ercolano Elizabeth
Published: June 2021

PURPOSE:

The purpose of this quality improvement project was to use the best available evidence and expert opinion to develop and implement a simple inpatient nursing care guideline (“The Guideline”) for patients with minor skin lesions, including candidiasis, skin tears, incontinence-associated dermatitis, and stage 1 and stage 2 pressure injuries that would not require a WOC nurse consultation.

PARTICIPANTS AND SETTING:

The Guideline was developed for nurses working on inpatient adult acute care units in a large community hospital in southwest Minnesota.

APPROACH:

The Guideline was validated for its clarity and appropriateness by internal and external hospital-based wound care nurses and implemented through in-person rounding on the nursing units and distribution of badge cards and required completing an online education module. Surveys and wound documentation audits were conducted to measure changes in knowledge and skin care pre- and postimplementation of The Guideline.

OUTCOMES:

We conducted wound documentation audits of approximately 491 records that assessed whether patients received appropriate treatment and found an improvement from 45% (104 of 231) to 80% (209 of 260). Nurses' self-rating of their knowledge about which dressings and topical treatment to use improved from 18% (16 of 89) agreement to 57% (55 of 96). Nurses' self-rating of their knowledge about when to change dressings and reapply topical treatments improved from 27% (24 of 89) agreement to 65% (62 of 96).

IMPLICATIONS FOR PRACTICE:

Although there is evidence for a variety of dressings or products to treat wounds, this quality improvement project demonstrated increased adherence with providing appropriate care when fewer treatment options were recommended to nursing staff through our structured guideline. The Guideline continues to be used at the project site and is now being implemented at affiliate hospitals.
GWAS meta-analysis and gene expression data link reproductive tract development, immune response and cellular proliferation/apoptosis with cervical cancer and clarify overlap with other cervical phenotypes
Authors: Koel Mariann , Võsa Urmo , Lepamets Maarja , Läll Kristi , Pujol-Gualdo Natàlia , Laivuori Hannele , Lemmelä Susanna , Daly Mark ,   Estonian Biobank Research Team,   FinnGen, Palta Priit , Mägi Reedik , Laisk Triin
Published: June 2021

Genome-wide association studies (GWAS) have successfully identified associations for cervical cancer, but the underlying mechanisms of cervical biology and pathology remain uncharacterised. Our GWAS meta-analyses fill this gap, as we characterise the genetic architecture of cervical phenotypes, including up to 9,229 cases and 490,304 controls for cervical cancer from diverse ancestries. We prioritisePAX8/PAX8-AS1,LINC00339,CDC42,CLPTM1L,HLA-DRB1, andGSDMBas the most likely candidate genes for cervical cancer signals, providing insights into cervical cancer pathogenesis and supporting the involvement of reproductive tract development, immune response, and cellular proliferation/apoptosis. We construct a GRS that associates with cervical cancer (HR=3.7 for top 5% vs lowest 5%), and with other HPV- and immune-system related diagnoses in a PheWAS analysis. Our results propose valuable leads for further functional studies and the presented GRS offers an additional opportunity for risk stratification together with conventional screening strategies.
Seroconversion panels demonstrate anti-SARS-CoV-2 antibody development after administration of the mRNA-1273 vaccine
Authors: Belda Francisco , Mora Oscar , Lopez-Martinez Monica , Torres Nerea , Vivanco Ana , Christie Rebecca , Crowley Michael
Published: June 2021

Seroconversion panels are an important tool for investigating antibody responses in acute and chronic phases of disease and development of serological assays for viral diseases including COVID-19. Globally it is anticipated that vaccines against SARS-CoV-2 will facilitate control of the current pandemic. The two COVID-19 seroconversion panels analyzed in this study were obtained from consenting donors with samples collected before vaccination with the mRNA-1273 vaccine (Moderna) and after the first and second doses of the vaccine. Panel samples were tested for antibodies to SARS-CoV-2 (IgG). Individual subjects with a positive response for anti-SARS-CoV2 IgG in their pre-vaccination samples showed a significantly enhanced response to the first vaccination. In older subjects, weaker immunological responses to the first injection were observed, which were overcome by the second injection. All subjects in the study were positive for anti-SARS-CoV-2 IgG after the second dose of vaccine.
A randomized crossover trial of short versus conventional pulse width DBS in Parkinson’s Disease
Authors: Petry-Schmelzer Jan Niklas , Schwarz Lisa M , Jergas Hannah , Reker Paul , Steffen Julia K. , Dafsari Haidar S. , Baldermann Juan Carlos , Fink Gereon R. , Visser-Vandewalle Veerle , Dembek Till A. , Barbe Michael T.
Published: June 2021

Background

Subthalamic nucleus deep brain stimulation is a well-established treatment for patients with Parkinson’s disease. Previous acute challenge studies suggested that short pulse widths might increase the therapeutic window while maintaining motor symptom control.

Objectives

To investigate in patients with Parkinson’s disease and nucleus subthalamicus deep brain stimulation (STN-DBS) whether short pulse width stimulation with 30µs maintains equal motor control as conventional 60µs stimulation over a period of 4 weeks.

Methods

In this monocentric, double-blinded, randomized crossover trial, 30 patients with Parkinson’s disease and STN-DBS were enrolled and assigned to 4 weeks of stimulation with 30µs and 4 weeks of stimulation with 60µs in randomized order (German Clinical Trials Register No. DRKS00017528). The primary outcome was the difference in motor symptom control as assessed by a motor diary. Secondary outcomes included energy consumption measures, non-motor effects, side-effects, and quality of life.

Results

A total of 24 patients were included in the final analysis. There was no difference in motor symptom control between the two treatment conditions. Concerning secondary outcomes there was no difference in energy consumption, non-motor symptoms, side-effects, or quality of life. On the individual level, patients preferring 30µs tended to be more dyskinetic in the 60µs setting, whereas patients preferring 60µs experienced more off-time in the 30µs setting.

Conclusions

Short pulse width settings (30µs) provide equal motor symptom control as conventional (60µs) stimulation without significant differences in energy consumption. Future studies are warranted to evaluate a potential benefit of short pulse width settings in patients with pronounced dyskinesia.
Risk of dementia after hospitalization due to traumatic brain injury: a longitudinal, population-based study
Authors: Raj Rahul , Kaprio Jaakko , Jousilahti Pekka , Korja Miikka , Siironen Jari
Published: June 2021

Objective

Traumatic brain injury (TBI) is considered a potential modifiable dementia risk factor. We aimed to determine whether TBI actually increases the risk of dementia when adjusting for other relevant dementia risk factors.

Methods

National prospective longitudinal cohort study that included 32,385 participants aged 25–64 during 1992–2012. Of these, 288 suffered from a major TBI (diagnosis of traumatic intracranial hemorrhage and hospital length of stay (LOS) ≥3 days) and 406 from a minor TBI (concussion diagnosis and hospital LOS ≤1 day). Dementia was defined as any first hospital contact with a diagnosis of dementia; first use of an anti-dementia drug; and dementia as an underlying or contributing cause of death. Follow-up until the end of 2017 yielded a total of 1,010 incident dementia cases.

Results

After adjusting for age and sex, hospitalization due to major TBI (hazard ratio [HR] 1.51, 95% CI 1.03–2.22), but not minor TBI, increased the risk of dementia. After additional adjustment for educational status, smoking status, alcohol consumption, physical activity, and hypertension, the association between major TBI and dementia weakened (HR 1.30, 95% CI 0.86–1.97). The risk factors most strongly attenuating the association between major TBI and dementia were alcohol consumption and physical activity.

Conclusion

There was an association between major TBI and incident dementia. The association was attenuated after adjusting for confounders, especially alcohol consumption and physical activity. Minor TBI was not associated with an increased risk of dementia.
Effectiveness of Face Masks in Blocking the Transmission of SARS-CoV-2: a Preliminary Evaluation of Masks Used by SARS-CoV-2-Infected Individuals
Authors: Mello Vinicius M. , Eller Cristiane M. , Salvio Andreza L. , Nascimento Felipe F. , Figueiredo Camila M. , Silva Emanuelle S. R. F. , Sousa Paulo S. F. , Costa Pamela F. , Paiva Anne A. P. , Mares-Guias Maria A. M. M. , Lemos Elba R. S. , Horta Marco A. P.
Published: June 2021

In 2019, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is transmitted via airborne route, caused a new pandemic namely, “coronavirus disease 2019” (COVID-19). Although it is still debated whether the use of masks can prevent the transmission of SARS-CoV-2, no study has evaluated the virus-blocking efficacy of masks used by patients. We aimed to evaluate this efficacy of masks used by SARS-CoV-2-infected individuals. Data, masks used, and nasopharyngeal swab samples were obtained from these patients. Forty-five paired samples of nasopharyngeal swabs and masks were obtained and processed; the majority of masks were woven. Viral RNAs were amplified using quantitative reverse-transcription polymerase chain reaction and detected only on the inner parts of masks. Median cycle threshold (Ct) values of swabs and masks were 28.41 and 37.95, respectively. Statistically, there was a difference of approximately 10 Ct values between swabs and masks and no significant difference in Ct values among different types of masks. There were statistically significant differences in Ct values between men and women and symptomatic and asymptomatic patients. Our findings suggest the blocking of the transmission of viruses by different types of masks and reinforce the use of masks by both infected and non-infected individuals.
Taiwan on track to end third COVID-19 community outbreak
Authors: Nordling Torbjörn E. M. , Wu Yu-Heng
Published: June 2021

Since the start of the COVID-19 pandemic on December 31st, 2019, with the World Health Organization being notified of pneumonia of unknown cause in Wuhan (China), Taiwan has successfully ended two COVID-19 community outbreaks. For 19 days, the third community outbreak has now been successfully suppressed, putting Taiwan on path to end it too around Aug. 16th based on our forecast using an exponential model. Since May 28th the 7-day average of reported confirmed infected, which peaked at 593, has been falling to 204 on June 16th and the 7-day average of reported suspected and excluded cases increased to above 25 000. Resulting in a decrease in the ratio of the 7-day average of local & unknown confirmed to suspected cases–the identified control variable–to less than one third of its peak value. The later is a hallmark of working contact tracing, which together with testing and isolation of infected are the keys to ending the community outbreak.
Association between preference and e-learning readiness among the Bangladeshi female nursing students in the COVID-19 pandemic: a cross-sectional study
Authors: Kabir Humayun , Tonmon Tajrin Tahrin , Hasan Md. Kamrul , Biswas Lila , Hasnat Chowdhury Md. Abul , Islam Muhammad Didarul , Rahman Mamunur , Mitra Dipak Kumar
Published: June 2021

Background

The COVID-19 pandemic jeopardized the traditional academic learning calendars due to the closing of all educational institutions across the globe. To keep up with the flow of learning, most of the educational institutions shifted toward e-learning. However, the students’ e-learning preference for various subdomains of e-learning readiness did not identify, particularly among the female nursing students’ for a developing country like Bangladesh, where those domains pose serious challenges.

Results

A cross-sectional study was conducted among the female nursing students’ perceived e-learning readiness in subdomains of readiness; availability, technology use, self-confidence, and acceptance. The findings of the study revealed that the prevalence of preference for e-learning was 43.46%. The students did not prefer e-learning compared to ‘prefer group’ has significantly less availability of technology (β = -3.01, 95% CI: -4.46, -1.56), less use of technology (β = - 3.08, 95% CI: -5.11, -1.06), less self-confidence (β = -4.50, 95% CI: -7.02, -1.98), less acceptance (β = -5.96, 95% CI: -7.76, -4.16) and less training need (β = -1.86, 95% CI: -2.67, - 1.06). The age, degree, residence, parents’ highest education, having a single room, having any eye problems were significantly associated with the variation of availability of technology, use of technology, self-confidence, acceptance, and training need of e-learning.

Conclusions

The outcomes of the study could be helpful while developing an effective and productive e-learning infrastructure regarding the preparedness of nursing colleges for the continuation of academia in any adverse circumstances like the COVID-19 pandemic.
More complaints than findings - Long-term pulmonary function in children and adolescents after COVID-19
Authors: Knoke Leona , Schlegtendal Anne , Maier Christoph , Eitner Lynn , Lücke Thomas , Brinkmann Folke
Published: June 2021

Background

The frequency of persistent symptoms after coronavirus disease 2019 (COVID-19) in adults varies from 4.5% to 87%. Pulmonary function can also show long-term impairment in adults: 10% of hospitalised adults had reduced spirometry values, and 24% had decreased diffusion capacity. To date, only preliminary evidence is available on persistent respiratory sequelae in children and adolescents, therefore our objective was to examine the long-term effects of COVID-19 on pulmonary function in this age group.

Methods

Multiple-breath washout, body plethysmography, and diffusion capacity testing were performed after an average of 2.6 months (range 0.4–6.0) following COVID-19 in 73 children and adolescents (age 5–18 years) with different disease severity. Cases were compared to 45 controls with and without infection within six months prior to assessment after exclusion of severe acute respiratory coronavirus-2 infection (SARS-CoV-2).

Results

Of the 19 patients (27.1%) who complained about persistent or newly emerged symptoms since COVID-19, 8 (11.4%) reported respiratory symptoms. Comparing patients with COVID-19 to controls, no significant differences were detected in frequency of abnormal pulmonary function (COVID-19: 12, 16.4%; controls: 12, 27.7%; OR 0.54, 95% CI 0.22–1.34). Only two patients with persistent respiratory symptoms showed abnormal pulmonary function. Multivariate analysis revealed reduced forced vital capacity (p=0.045) in patients with severe infection regardless of SARS-CoV-2 infection.

Discussion

Pulmonary function is rarely impaired in children and adolescents after COVID-19, except of those with severe infection. The discrepancy between persistent respiratory symptoms and normal pulmonary function suggests a different underlying pathology such as dysfunctional breathing.
Deciphering how early life adiposity influences breast cancer risk using Mendelian randomization
Authors: Vabistsevits Marina , Smith George Davey , Sanderson Eleanor , Richardson Tom G , Lloyd-Lewis Bethan , Richmond Rebecca C
Published: June 2021

Studies suggest that adiposity in childhood may reduce the risk of breast cancer in later life. The biological mechanism underlying this effect is unclear but is likely to be independent of body size in adulthood. Using a Mendelian randomization framework, we investigated 18 hypothesised mediators of the protective effect of childhood adiposity on later-life breast cancer, including hormonal, reproductive, physical, and glycaemic traits.

Our results indicate that, while most of the hypothesised mediators are affected by childhood body size, only IGF-1, testosterone, age at menarche and age at menopause influenced breast cancer risk. However, accounting for those traits in multivariable Mendelian randomization showed that the protective effect of childhood body size still remained. This suggests either a direct effect of childhood body size on breast cancer risk or mediation via other pathways not considered.

Our work presents a framework for the systematic exploration of potential biological mediators of disease in Mendelian randomization analysis.
Hospital profiling using Bayesian decision theory
Authors: Hengelbrock Johannes , Rauh Johannes , Cederbaum Jona , Kähler Maximilian , Höhle Michael
Published: June 2021

Background

For evaluating the quality of care provided by hospitals, special interest lies in the identification of performance outliers. We study a setting where the decision to classify hospitals as performance outliers or non-outliers is based on the observed result of a single binary quality indicator.

Methods

We propose to embed the classification of providers into a Bayesian decision theoretical framework which enables the derivation of optimal decision rules with respect to the expected decision consequences. We argue that these consequences depend upon for which pathway to quality improvement the profiling of hospitals takes place. We propose paradigmatic utility functions for the two pathways external reporting and change in care delivery and compare the resulting optimal decision rules with regard to their threshold values, sensitivity and specificity. We further apply them to the area of hip replacement surgeries by analyzing data from the mandatory German hospital profiling program. Based on five quality indicators, we re-evaluate the performance of 1,277 hospitals which treated over 180,000 patients for hip-replacement surgeries during 2017.

Results

Based on the utilities we assigned to the classification decisions, the decision rule for change in care delivery classifies more high-volume providers as outliers compared to the decision rule for external reporting, with consequences for both sensitivity and specificity. The re-evaluation of the five quality indicators illustrates that classification decisions are highly dependent upon the underlying utilities.

Conclusion

Analyzing the classification of hospitals as a decision theoretic problem and considering pathway-specific consequences of decisions can help to derive an appropriate decision rule. Contrasting decision rules with regard to their underlying assumptions about the utilities of classification consequences can be helpful to make implicit assumptions transparent and justifiable.
Technology in Palliative Care (TIP): the identification of digital priorities for palliative care research using a modified Delphi method
Authors: Nwosu Amara Callistus , McGlinchey Tamsin , Sanders Justin , Stanley Sarah , Palfrey Jennifer , Lubbers Patrick , Chapman Laura , Finucane Anne , Mason Stephen
Published: June 2021

Background

Developments in digital health (describing technologies which use computing platforms, connectivity, software, and sensors for health care and related purposes) has the potential to transform the delivery of health and social care to help citizens manage their own health. Currently, we lack consensus about digital health research priorities in palliative care and lack theories about how these technologies might improve care outcomes. Global palliative care need is expected to increase due to the consequences of an ageing population; therefore, it is important for healthcare leaders to identify innovations to ensure that an increasingly frail population have appropriate access to palliative care services. Consequently, it is important to articulate research priorities as the first step to determine how we should allocate finite resources to a field saturated with rapidly developing innovations.

Aims

To identify research priority areas for digital health in palliative care.

Methods

We selected the digital health trends, most relevant to palliative care, from a list of emerging trends reported by the ‘Future Today Institute’. We conducted a modified Delphi process and consensus meeting with palliative care experts to identify research priorities. We used the views of public representatives to gain their perspectives of the agreed priorities.

Results

One hundred and three experts (representing 11 countries) participated in the 1st Delphi round. Fifty-five participated in the 2nd round (53% of 1st round). Eleven experts attended the final consensus meeting. We identified 16 priorities areas, which were summarised into eight themes. These themes were: big data, mobile devices, telehealth and telemedicine, virtual reality, artificial intelligence, the smart home, biotechnology and digital legacy.

Conclusions

The identified priorities in this paper represent a wide range of important emerging areas in field of digital health, personalised medicine, and data science. Human-centred design and robust governance systems should be considered in future research. It is important that the risks of using these technologies in palliative care are properly addressed to ensure that these tools are used meaningfully, wisely and safely and do not cause unintentional harm.
Projecting the impact of SARS-CoV-2 variants on the COVID-19 epidemic and social restoration in the United States: a mathematical modelling study
Authors: Li Rui , Li Yan , Zou Zhuoru , Liu Yiming , Li Xinghui , Zhuang Guihua , Shen Mingwang , Zhang Lei
Published: June 2021

Background

The SARS-CoV-2 Alpha variant B.1.1.7 became prevalent in the United States (US). We aimed to evaluate the impact of vaccination scale-up and potential reduction in the vaccination effectiveness on the COVID-19 epidemic and social restoration in the US.

Methods

We extended a published compartmental model and calibrated the model to the latest US COVID-19 data. We estimated the vaccine effectiveness against B.1.1.7 and evaluated the impact of a potential reduction in vaccine effectiveness on future epidemics. We projected the epidemic trends under different levels of social restoration.

Results

We estimated the overall existing vaccine effectiveness against B.1.1.7 to be 88.5% (95%CI: 87.4-89.5%) and vaccination coverage would reach 70% by the end of August, 2021. With this vaccine effectiveness and coverage, we anticipated 498,972 (109,998-885,947) cumulative infections and 15,443 (3,828-27,057) deaths nationwide over the next 12 months, of which 95.0% infections and 93.3% deaths were caused by B.1.1.7. Complete social restoration at 70% vaccination coverage would only slightly increase cumulative infections and deaths to 511,159 (110,578-911,740) and 15,739 (3,841-27,638), respectively. However, if the vaccine effectiveness were reduced to 75%, 50% or 25% due to new SARS-CoV-2 variants, we predicted 667,075 (130,682-1,203,468), 1.7m (0.2-3.2m), 19.0m (5.3-32.7m) new infections and 19,249 (4,281-34,217), 42,265 (5,081-79,448), 426,860 (117,229-736,490) cumulative deaths to occur over the next 12 months. Further, social restoration at a lower vaccination coverage would lead to even greater future outbreaks.

Conclusion

Current COVID-19 vaccines remain effective against the B.1.1.7 variant, and 70% vaccination coverage would be sufficient to restore social activities to a pre-pandemic level. Further reduction in vaccine effectiveness against SARS-CoV-2 variants would result in a potential surge of the epidemic in the future.
Defining the Critical Components of Informed Consent for Genetic Testing: A Delphi Study
Authors: Ormond Kelly E. , Borensztein Maia , Hallquist Miranda L.G. , Buchanan Adam H. , Faucett W. Andrew , Peay Holly L. , Smith Maureen E. , Tricou Eric P. , Uhlmann Wendy R. , Wain Karen E. , Coughlin Curtis R.
Published: June 2021

Purpose

Informed consent for genetic testing has historically happened during pre-test genetic counseling, without specific guidance defining which core concepts are required.

Methods

The Clinical Genome Resource (ClinGen) Consent and Disclosure Recommendations Workgroup (CADRe) used a modified Expert Delphi consensus process to identify the core concepts essential to consent for clinical genetic testing. A literature review identified 77 concepts that are included in informed consent for genetic tests. Twenty five experts (9 medical geneticists, 8 genetic counselors, and 9 bioethicists) completed two rounds of Delphi surveys ranking concepts’ importance to informed consent.

Results

The most highly ranked concepts included: (1) genetic testing is voluntary; (2) why the test is recommended and what does it test for; (3) what results will be returned and to whom; (4) are there other types of potential results; what choices exist; (5) how will prognosis and management be impacted by results; (6) what is the potential family impact; (7) what are the test limitations and next steps; (8) potential risk for genetic discrimination and legal protections.

Conclusion

Defining the core concepts necessary for informed consent for genetic testing provides a foundation for quality patient care across a variety of healthcare providers and clinical indications.
Family functioning but not social capital is associated with better mental health in adolescents affected by violence and displacement by armed conflict in Colombia
Authors: Tamayo-Aguledo William , Acosta-Ortiz Alida , Hamid Aseel , Gómez-García Carolina , García-Durán María Camila , Daccach-González Vanessa , Solmi Francesca , Bell Vaughan
Published: June 2021

Background

The effect of the Colombian armed conflict on the mental health of adolescents is still poorly understood. Given social interventions are most likely to inform policy, we tested whether two potential intervention targets, family functioning and social capital, were associated with mental health in Colombian adolescents, and whether this was moderated by experience of violence and displacement.

Methods

We examined the cross-sectional association between family functioning, cognitive social capital, structural social capital and 12-month prevalence of Composite International Diagnostic Interview (CIDI) diagnosed psychiatric disorder, using data on 12-17-year-old adolescents (N = 1754) from the 2015 National Mental Health Survey of Colombia, a nationally representative epidemiological study. We tested whether associations survived cumulative adjustment for demographic confounders, experience of non-specific violence and harm, and displacement by armed conflict.

Results

Neither structural nor cognitive social capital were associated with better mental health. Better family functioning was associated with reduced risk of poor mental health in an unadjusted analysis (OR 0.90 [0.85 – 0.96]), and after cumulative adjustments for demographic confounders (OR 0.91 [0.86 – 0.97]), non-specific violence and harm (OR 0.91 [0.86 – 0.97]) and social capital variables (OR 0.91 [0.85 – 0.97]). In the final model, each additional point on the family APGAR scale was associated with a 9% reduced odds of any CIDI diagnosed disorder in the last 12 months.

Conclusions

Better family functioning was associated with better mental health outcomes for all adolescents. This effect remained present in those affected by the armed conflict even after accounting for potential confounders.
Early warning signals predict emergence of COVID-19 waves
Authors: O’Brien Duncan A. , Clements Christopher F.
Published: June 2021

Early warning signals (EWSs) aim to predict changes in complex systems from phenomenological signals in time series data. These signals have recently been shown to precede the initial emergence of disease outbreaks, offering hope that policy makers can make predictive rather than reactive management decisions. Here, using daily COVID-19 case data in combination with a novel, sequential analysis, we show that composite EWSs consisting of variance, autocorrelation, and return rate not only pre-empt the initial emergence of COVID-19 in the UK by 14 to 29 days, but also the following wave six months later. We also predict there is a high likelihood of a third wave as of the data available on 9th June 2021. Our work suggests that in highly monitored disease time series such as COVID-19, EWSs offer the opportunity for policy makers to improve the accuracy of time critical decisions based solely upon surveillance data.
Persistently high proportions of Plasmodium-infected Anopheles funestus mosquitoes in two villages in the Kilombero valley, south-eastern Tanzania
Authors: Mapua Salum A. , Hape Emmanuel E. , Kihonda Japhet , Bwanary Hamis , Kifungo Khamis , Kilalangongono Masoud , Kaindoa Emmanuel W. , Ngowo Halfan S. , Okumu Fredros O.
Published: June 2021

Background

In south-eastern Tanzania where insecticide-treated nets have been widely used for more than 20 years, malaria transmission has greatly reduced but remains highly heterogenous over small distances. This study investigated the seasonal prevalence of Plasmodium sporozoite infections in the two main malaria vector species, Anopheles funestus and Anopheles arabiensis for 34 months, starting January 2018 to November 2020.

Methods

Adult mosquitoes were collected using CDC-light traps and Prokopack aspirators inside local houses in Igumbiro and Sululu villages, where earlier surveys had found very high densities of An. funestus. Collected females were sorted by taxa, and the samples examined using ELISA assays for detecting Plasmodium circumsporozoite protein in their salivary glands.

Results

Of 7,859 An. funestus tested, 4.6% (n = 365) were positive for Pf sporozoites in the salivary glands. On the contrary, only 0.4% (n = 9) of the 2,382 An. arabiensis tested were positive. The sporozoite prevalence did not vary significantly between the villages or seasons. Similarly, the proportions of parous females of either species were not significantly different between the two villages (p > 0.05) but was slightly higher in An. funestus (0.50) than in An. arabiensis (0.42). Analysis of the 2020 data determined that An. funestus contributed 97.7% of all malaria transmitted in households in these two villages.

Conclusions

In contexts where individual vector species mediate most of the pathogen transmission, it may be most appropriate to pursue a species-specific approach to better understand the ecology of the dominant vectors and target them with effective interventions to suppress transmission. Despite the widespread use and overall impact of insecticide-treated nets over the past two decades in the two study villages, there is still persistently high Plasmodium infection prevalence in local populations of An. funestus, which now carry ∼97% of all malaria infections and mediates intense year-round transmission. Further reduction in malaria burden in these or other similar settings requires effective targeting of An. funestus.
Conditionality of COVID-19 vaccine acceptance in European countries
Authors: Heyerdahl Leonardo W , Vray Muriel , Lana Benedetta , Tvardik Nastassia , Gobat Nina , Wanat Marta , Tonkin-Crine Sarah , Anthierens Sibyl , Goossens Herman , Giles-Vernick Tamara
Published: June 2021

The COVID-19 vaccine rollout in recent months offers a powerful preventive measure that may help control SARS-CoV-2 transmission. Nevertheless, long-standing public hesitation around vaccines has heightened public health concerns that vaccine coverage may not achieve desired public health impacts.This cross-sectional survey was conducted online in December 2020 among 7000 respondents (aged 18 to 65) in Belgium, France, Germany, Italy, Spain, Sweden, and Ukraine. The survey included open text boxes for fuller explanation of responses. Projected COVID-19 vaccine coverage varied and may not be sufficiently high among certain populations to achieve herd immunity. Overall, 56.9% would accept a COVID-19 vaccine, 19.0% would not, and 24.1% did not know or preferred not to say. By country, between 44% (France) and 66% (Italy) of respondents would accept a COVID-19 vaccine. Respondents expressed conditionality in open responses, voicing concerns about vaccine safety and mistrust of authorities. Public health campaigns must tackle these safety concerns.

Highlights

Mixed-method survey studied expected COVID vaccine uptake in 7 European countries.

Projected COVID vaccine acceptance by country ranged from 44% to 66%.

Explicit COVID vaccine acceptance or rejection was conditional.

Study finds concerns about vaccine safety and authorities’ competence and honesty.

Vaccine communications should address safety anxieties and target specific groups.
Behavioral and psychological symptoms of dementia in different dementia disorders: A large-scale study of 10 000 individuals
Authors: Schwertner Emilia , Pereira Joana B. , Xu Hong , Secnik Juraj , Winblad Bengt , Eriksdotter Maria , Nagga Katarina , Religa Dorota
Published: June 2021

Background

The majority of individuals with dementia will suffer from psychological and behavioral symptoms of dementia (BPSD). There is limited number of studies investigating BPSD in different types of dementia.

Objectives

To characterize BPSD in Alzheimer’s disease (AD), vascular dementia (VaD), mixed (Mixed) dementia, Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD) and unspecified dementia (UNS) in individuals residing in long-term care facilities.

Methods

We included 10,405 individuals with dementia living in long-term care facilities from the Swedish registry for cognitive/dementia disorders (SveDem) and the Swedish BPSD registry. BPSD was assessed with the Neuropsychiatric Inventory - Nursing Home Version (NPI-NH). Multivariate logistic regression models were used to evaluate the associations between dementia diagnoses and different BPSDs.

Results

The most common symptoms were aberrant motor behavior, agitation and irritability. Compared to AD, we found a lower risk of delusions (in FTD, unspecified dementia), hallucinations (in FTD), agitation (VaD, in PDD, unspecified dementia), elation/euphoria (in DLB), anxiety (Mixed, VaD, unspecified dementia), disinhibition (in PDD); irritability (in DLB, FTD, unspecified dementia), aberrant motor behavior (in Mixed, VaD, unspecified dementia), sleep and night-time behavior changes (in unspecified dementia). Higher risk of delusions (in DLB), hallucinations (in DLB, PDD), apathy (VaD, FTD), disinhibition (in FTD) and appetite and eating abnormalities (in FTD) were also found in comparison to AD.

Conclusions

BPSD was common in all types of dementia, with the most common symptoms being aberrant motor behavior, agitation, and irritability. Additionally, presentation of BPSD differ in different dementia types.
Fusion of Fully Integrated Analog Machine Learning Classifier with Electronic Medical Records for Real-time Prediction of Sepsis Onset
Authors: Sadasivuni Sudarsan , Saha Monjoy , Bhatia Neal , Banerjee Imon , Sanyal Arindam
Published: June 2021

The objective of this work is to develop a fusion artificial intelligence (AI) model that combines patient electronic medical record (EMR) and physiological sensor data to accurately predict early risk of sepsis. The fusion AI model has two components - an on-chip AI model that continuously analyzes patient electrocardiogram (ECG) data and a cloud AI model that combines EMR and prediction scores from on-chip AI model to predict fusion sepsis onset score. The on-chip AI model is designed using analog circuits for sepsis prediction with high energy efficiency for integration with resource constrained wearable device. Combination of EMR and sensor physiological data improves prediction performance compared to EMR or physiological data alone, and the late fusion model has an accuracy of 93% in predicting sepsis 4 hours before onset. The key differentiation of this work over existing sepsis prediction literature is the use of single modality patient vital (ECG) and simple demographic information, instead of comprehensive laboratory test results and multiple vital signs. Such simple configuration and high accuracy makes our solution favorable for real-time, at-home use for self-monitoring.
Increased LPS levels coexist with systemic inflammation and result in monocyte activation in severe COVID-19 patients
Authors: Teixeira Paula C , Dorneles Gilson P , Filho Paulo C Santana , Silva Igor M da , Schipper Lucas L , Postiga Isabelle AL , Moreira Neves Carla Andretta , Rodrigues Júnior Luiz Carlos , Peres Alessandra , de Souto Janeusa Trindade , da Fonseca Simone Gonçalves , Eller Sarah , Oliveira Tiago F , Rotta Liane N. , Thompson Claudia , Romão Pedro R T
Published: June 2021

This study aimed to evaluate the link between microbial translocation markers and systemic inflammation at the earliest time-point after hospitalization and at the last 72 h of hospitalization in survivors and non-survivors COVID-19 patients. Sixty-six SARS-CoV-2 RT-PCR+ infected patients and nine non-COVID-19 pneumonia controls were admitted in this study. Blood samples were collected at hospital admission (T1) (Controls and COVID-19+ patients) and 0-72 h before hospital discharge (T2, alive or dead) to analyze systemic cytokines and chemokines, LPS concentrations and soluble CD14 (sCD14) levels. THP-1 human monocytic cell line was incubated with plasma from survivors and non-survivors COVID-19 patients and their phenotype, activation status, TLR4, and chemokine receptors were analyzed by flow cytometry. COVID-19 patients presented higher IL-6, IFN-γ, TNF-α, TGF-β1, CCL2/MCP-1, CCL4/MIP-1β, and CCL5/RANTES levels than controls. Moreover, LPS and sCD14 were higher at hospital admission in SARS-CoV-2-infected patients. Non-survivors COVID-19 patients had increased LPS levels concomitant with higher IL-6, TNF-α, CCL2/MCP-1, and CCL5/RANTES levels at T2. Increased expression of CD16 and CCR5 were identified in THP-1 cells incubated with the plasma of survivor patients obtained at T2. The incubation of THP-1 with T2 plasma of non-survivors COVID-19 leads to higher TLR4, CCR2, CCR5, CCR7, and CD69 expression. In conclusion, increased microbial translocation during hospitalization coexist with the inflammatory condition of SARS-CoV-2 infection and could lead to higher monocyte activation in non-survivors COVID-19 patients.