bluuebunny/crossref_metadata_2025 huggingface dataset:
Losing Connection
Authors: Altman Molly R. , Mohammed Selina A. , Eagen-Torkko Meghan K. , Kantrowitz-Gordon Ira , Gavin Amelia R.
Published: January 2023

Introduction:

The rapid uptake of telehealth for perinatal care during the coronavirus disease-2019 (COVID-19) pandemic has led to mixed evidence as to its effectiveness, with limited research demonstrating satisfaction and appropriateness for communities at risk for poor birth outcomes. The purpose of this article is to describe the experiences of virtual care during pregnancy and postpartum among a diverse group of pregnant/birthing people in Washington State during the COVID-19 pandemic.

Methods:

We conducted a thematic analysis study exploring experiences of care during the COVID-19 pandemic for 15 pregnant and birthing people in Washington State. This secondary analysis utilized data specific to experiences receiving care via telehealth.

Results:

Three dominant themes were identified: loss of connection and relationships with providers; need for hands-on interactions for reassurance; and virtual care is good for some things but not all—desire for immediate, accessible care when appropriate. The majority of participants felt that it was subpar to in-person care due to a lack of connection and the inability to receive necessary tests and hands-on reassurance.

Discussion/Conclusions:

Our study findings encourage very judicious use of virtual care for communities that are at high risk for birth disparities to avoid impacting relationship building between patient and provider.
Development of risk scores for early and late recurrence of colonic diverticular hemorrhage
Authors: Watanabe Sho , Miyakawa Akihiro , Sato Ayako , Uchida Hitoshi , Uga Misugi , Machida Tomoyo , Matsukawa Naoki , Kurihara Masamichi , Yauchi Tsunehito
Published: January 2023

Objectives

Colonic diverticular hemorrhage (CDH) often recurs. Although several studies have suggested that early rebleeding (ER) and late rebleeding (LR) should be treated independently, and several ER/LR risk factors have been identified, an integrated system for risk evaluation is still lacking. This study aimed to develop risk scores for early and late rebleeding of CDH.

Methods

This two-center, retrospective cohort study included 218 patients between 2008 and 2021. ER and LR risk factors were identified using multivariate analysis, and risk scores were developed using the odds ratios of each risk factor.

Results:

The ER and LR rates were 32.6 and 25.7%, respectively. High heart rate on admission, early endoscopy from the visit, no bowel preparation and no endoscopic treatment were identified as risk factors for ER. On the other hand, LR risk factors included a history of hypertension and diabetes, early endoscopy from the visit, and the use of endoscopic clips. The ER risk score [area under the curve (AUC) = 0.71] was highly sensitive (90.3%) at a cutoff point of 6 and highly specific (98.0%) at a cutoff point of 15. The LR risk score (AUC = 0.70) was highly sensitive (91.1%) at a cutoff point of 2.6 and highly specific (88.3%) at a cutoff point of 7.1.

Conclusions

The ER and LR risk scores were established for the first time, and they can divide CDH patients based on their risk of rebleeding as well as provide clinicians with practical information about the CDH management.
Targeted liver ultrasound performed by an expert is the pivotal imaging examination for low phospholipid-associated cholelithiasis
Authors: Su Shu , Trinh Andrew , Metz Andrew J. , Speer Tony , Simkin Paul , Buchanan Daniel , Boussioutas Alex , Gibson Robert
Published: January 2023

Objectives

Low phospholipid-associatedcholelithiasis (LPAC) is a clinical syndrome that can be associated with variants in the adenosinetriphosphate-binding cassette subfamily B, member 4 (ABCB4) transporter gene, in a proportion of patients. The diagnosis of LPAC is defined by clinical as well as imaging criteria of intrahepatic hyperechoic foci or microlithiasis and biliary sludge on ultrasound. The aim of the study was to assess the role of imaging in investigating patients presenting with clinical features suggesting a diagnosis of LPAC.

Methods

Imaging findings in 51 patients with clinical LPAC were retrospectively reviewed. Most patients had been referred with difficult-to-manage biliary pain postcholecystectomy and some with intrahepatic dilated ducts and stones. The diagnosis of LPAC was made on clinical features.

Results

The patients were young with symptom onset at median age 24 years and were mainly female (75%). Ultrasound was performed by an expert in 48/51 and magnetic resonance cholangiopancreatography (MRCP) in 47/51 patients. Targeted liver ultrasound found small hyperechoic foci with comet tail artifacts or posterior acoustic shadowing typical of LPAC in 30/48 (63%) of examinations. However, ultrasound examinations performed before referral for investigation did not report these findings. Intrahepatic duct dilatation was seen in 26/51 (51%) of cases. MRCP did not reliably detect microlithiasis.

Conclusions

Targeted liver ultrasound performed by an expert aware of the possible diagnosis is the pivotal investigation for patients with clinical features suggesting LPAC. The findings in ultrasound performed before referral suggest LPAC is under-recognized and under-diagnosed.
Long-term effectiveness and safety of ustekinumab in Crohn’s disease: a prospective cohort study
Authors: Thomas Pepijn W.A. , van Caem Mark , West Rachel L. , Russel Maurice G.V.M , Jansen Jeroen M. , Römkens Tessa E.H. , Hoentjen Frank ,   on behalf of the IBDREAM registry
Published: January 2023

Background

Real-world data showed that ustekinumab is an effective treatment for Crohn’s disease for up to 52 weeks. Yet, long-term effectiveness and safety outcomes beyond 52 weeks are limited. This study aimed to evaluate the corticosteroid-free clinical remission for up to 104 weeks. Secondary aims were focused on biochemical disease, dosing adjustments and safety outcomes.

Methods

This multicentre prospective cohort study enrolled Crohn’s disease patients who started ustekinumab between May 2016 and September 2019. Participants had scheduled outpatient visits at week 0, 13, 26, 52 and 104. Data on clinical disease [Harvey Bradshaw Index (HBI) = 4 points = remission], biochemical disease (faecal calprotectin = 200 µg/g or C-reactive protein = 10 mg/l = remission), dose adjustments and adverse drug reactions (ADRs) were recorded.

Results

We included 101 Crohn’s disease patients. In all patients, the proportion of patients in corticosteroid-free clinical remission was 35 and 36% at week 52 and 104. Of patients achieving corticosteroid-free remission at week 52, more than half maintained corticosteroid-free remission throughout week 104. Biochemical remission rates were 25 and 30% at week 52 and 104, respectively. In the first year of treatment, 33% required their first dose escalation, and 15% in the second year. Overall, 7% of patients discontinued ustekinumab due to ADRs. Ustekinumab persistency rates were 68% at week 52 and 59% at week 104.

Conclusion

Ustekinumab is an effective and well-tolerated treatment for Crohn’s disease. More than half of all patients continued ustekinumab treatment after 104 weeks whereas one-third achieved corticosteroid-free remission.
Impact of improved upper endoscopy quality on detection of gastric precancerous lesions
Authors: Manfredi Guido , Pedaci Marianna , Iiritano Elena , Alicante Saverio , Romeo Samanta , Bertè Roberto , Londoni Claudio , Menozzi Fernanda , Brambilla Gianfranco , Pezzilli Raffaele , Zullo Angelo , Buscarini Elisabetta
Published: January 2023

Objective

Intestinal metaplasia (IM) is the point of no return in gastric carcinogenesis, and patients with extensive (antrum plus corpus) IM are at high risk of developing gastric cancer. We evaluated the impact of improved gastroscopy quality on the detection of gastric IM in an Italian area at high risk for gastric cancer.

Methods

Data of consecutive patients with gastric biopsies according to the updated Sydney System observed in 2013, 2016 and 2019 resulting in IM diagnosis were retrieved. In the first period, endoscopy was performed with standard white light instruments. In the second period, preendoscopic gastric preparation was administered, and the examinations lasting at least 7 min with standard endoscopes were performed. In the third period, the latter procedure was followed, with virtual chromoendoscopy equipped instruments. The prevalence of IM in any gastric site and that of extensive IM were compared among the three periods.

Results

Data of 3485 patients were available. The detection of IM in at least one gastric site increased from 29.9 to 33.6% and 34.5% (95% CI, 32.1–36.8) in the first, second and third period, respectively. The difference was statistically significant between the first and last (P = 0.02; OR, 1.24; 95% CI, 1.04–1.48) period. When considering extensive IM, the detection increased from 4.28 to 6.1% and 5.44%, although the difference failed to reach statistical significance (P = 0.076).

Conclusion

Our data showed that implementation of a quality protocol increased the probability to detect IM in the stomach, allowing us to select patients deserving stricter follow-up.
The Determining Factors for Outcome of Pediatric Intensive Care Admitted Children After Stem Cell Transplantation
Authors: Öztürk Musa , Botan Edin , Gün Emrah , Baskin Avniye Kübra , İslamoğlu Candan , Erkol Gül Hatice , Havan Merve , Çakmak Fatih Hasan , Haskoloğlu Şule , İleri Talia , İnce Elif , Doğu Figen , Ertem Mehmet , İkinciogullari Aydan , Kendirli Tanil
Published: January 2023

Introduction:

Requiring pediatric intensive care unit (PICU) admission relates to high mortality and morbidity in patients who received hematopoietic stem cell transplantation (HSCT). In this study, we aimed to evaluate the indications for PICU admission, treatments, and the determining risk factors for morbidity and mortality in patients who had allogeneic HSCT from various donors.

Materials and Methods:

In this retrospective study, we enrolled to patients who required the PICU after receiving allogeneic HSCT at our Pediatric Bone Marrow Transplantation Unit between 2005 and 2020. We evaluated to indication to PICU admission, applications, mortality rate, and the determining factors to outcomes.

Results:

Thirty-three (7%) patients had 47 PICU admissions and 471 patients underwent bone marrow transplantation during 16-year study period. Also, 14 repeated episodes were registered in 9 different patients. The median age of PICU admitted patients was 4 (0.3 to 18) years and 29 (62%) were male. The main reasons for PICU admission were a respiratory failure, sepsis, and neurological event in 20, 8, and 7 patients, respectively. The average length of PICU stay was 14.5 (1 to 80) days, 14 (43%) of patients survived and the mortality rate was 57%. Multiple organ failure (P=0.001), need for respiratory support (P=0.007), inotrope agents (P=0.001), and renal replacement therapy (P=0.013) were found as significant risk factors for mortality.

Conclusions:

Allogeneic HSCT recipients need PICU admission because of its related different life-threatening complications. But there is a good chance of survival with quality PICU care and different advanced organ support methods.
Prolonged Bleeding After Dental Extraction Due to Decreased Serum Level of Von Willebrand Factor Caused by Untreated Profound Hypothyroidism
Authors: Dagdeviren Cakir Aydilek , Yildirmak Zeynep Yildiz , Eren Simge , Özdemir Ebru Misirli , Özdemir Mustafa , Uçar Ahmet
Published: January 2023

Background:

Delayed diagnosis of hypothyroidism may result in atypical presentations. Here, we report a case with decreased serum level and activity of von Willebrand factor due to untreated profound hypothyroidism

Observation:

A 9-year-old girl, presented with prolonged gingival bleeding after dental extraction. Clinical findings of the case were consistent with hypothyroidism, and the laboratory workup results revealed decreased serum level and activity of von Willebrand factor associated with profound hypothyroidism. Restoration of euthyroidism normalized the coagulation parameters.

Conclusion:

Delayed diagnosis of hypothyroidism may lead to atypical presentations such as bleeding diathesis. Profound hypothyroidism should be considered in the differential diagnosis of acquired von Willebrand disease to avoid undue treatment.
Factors Associated With Sun Protection Behaviors Among Childhood Cancer Survivors
Authors: Fluehr Melissa , Kwok Gary , Stapleton Jerod L. , Masterson Margaret , Devine Katie A.
Published: January 2023

Background:

Childhood cancer survivors (CCS) are at increased risk of developing skin cancer. Engaging in sun-protective behaviors may ameliorate that risk, but prior work shows that survivors engage in suboptimal levels of sun-protective behaviors. Guided by the Health Belief Model (HBM), this study evaluated factors associated with sun-protective behavior among CCS.

Methods:

This is a secondary analysis of a survey study of 94 adult survivors of childhood cancer recruited from a long-term follow-up clinic. Participants reported their sun protection habits, skin type/sensitivity, barriers to sun protection, and perceived severity and susceptibility of getting skin cancer. Descriptive statistics were used to describe the prevalence of sun protection behaviors and hierarchical linear regression was used to evaluate predictors of sun protection behavior following the HBM.

Results:

On average, CCS engaged in moderate levels of sun-protective behaviors (M=2.53; SD=0.59). Hierarchical linear regression indicated that fair skin type (P=0.02) and higher perceived susceptibility relative to noncancer survivors (P=0.02) were associated with increased sun protection behaviors. Perceived barriers to sun protection were marginally significant (P=0.09), whereas other constructs from the HBM did not contribute significantly to the model.

Conclusions:

Although CCS are at increased risk of developing skin cancer, they engage in suboptimal levels of sun protection behaviors. Findings suggest that interventions to educate survivors about their unique risk of skin cancer and effective prevention behaviors are needed.
Immune Checkpoint Inhibitors in Solid Organ Transplant Recipients With Advanced Skin Cancers—Emerging Strategies for Clinical Management
Authors: Ferrándiz-Pulido Carla , Leiter Ulrike , Harwood Catherine , Proby Charlotte M. , Guthoff Martina , Scheel Christina H. , Westhoff Timm H. , Bouwes Bavinck Jan Nico , Meyer Thomas , Nägeli Mirjam C. , del Marmol Veronique , Lebbé Celeste , Geusau Alexandra
Published: January 2023

Use of immune checkpoint inhibitors (ICIs) in solid organ transplant recipients (SOTRs) with advanced skin cancers presents a significant clinical management dilemma. SOTRs and other immunosuppressed patients have been routinely excluded from ICI clinical trials with good reason: immune checkpoints play an important role in self- and allograft-tolerance and risk of acute allograft rejection reported in retrospective studies affects 10% to 65% of cases. These reports also confirm that cutaneous squamous cell carcinoma and melanoma respond to ICI therapy, although response rates are generally lower than those observed in immunocompetent populations. Prospective trials are now of critical importance in further establishing ICI efficacy and safety. However, based on current knowledge, we recommend that ICIs should be offered to kidney transplant recipients with advanced cutaneous squamous cell carcinoma, melanoma, or Merkel cell carcinoma if surgery and/or radiotherapy have failed. For kidney transplant recipients, this should be first line ahead of chemotherapy and targeted therapies. In SOTRs, the use of ICIs should be carefully considered with the benefits of ICIs versus risks of allograft rejection weighed up on a case-by-case basis as part of shared decision-making with patients. In all cases, parallel management of immunosuppression may be key to ICI responsiveness. We recommend maintaining immunosuppression before ICI initiation with a dual immunosuppressive regimen combining mammalian target of rapamycin inhibitors and either corticosteroids or calcineurin inhibitors. Such modification of immunosuppression must be considered in the context of allograft risk (both rejection and also its subsequent treatment) and risk of tumor progression. Ultimately, a multidisciplinary approach should underpin all clinical decision-making in this challenging scenario.
Predictors of Driving Cessation in Older Adults
Authors: Wood Isabella , Bhojak Tejal , Jia Yichen , Jacobsen Erin , Snitz Beth E. , Chang Chung-Chou H. , Ganguli Mary
Published: January 2023

Background:

Changes in physical health and cognition during aging can result in some older adults to stop driving. In this population-based longitudinal study, we describe potential predictors of driving cessation in older adults.

Methods:

Age-stratified random population cohort of 1982 adults aged 65 years and older drawn from voter registration lists. Participant characteristics were measured using demographics, physical and self-rated health, sleeping habits, driving status, cognitive screening, modified Center for Epidemiologic Studies-Depression scale, clinical dementia rating, and mini-mental state examination.

Results:

Over 12 years of follow-up, 390 participants stopped driving. These individuals were older, more likely to be women and to have a clinical dementia rating score ≥1, had worse self-reported health, and more symptoms of depression, compared with those who were still driving. In addition, individuals with lower test performance in all cognitive domains, loss of visual acuity and fields, and bilateral hearing loss were more likely to stop driving.

Conclusions:

Age, sex, cognitive impairments, physical health, and depressive symptoms were associated with driving cessation in this cohort. By identifying potential driving cessation predictors, health care providers and families may better recognize these risk factors and begin the driving cessation discussion early.
Genome-wide association study suggests a critical contribution of the adaptive immune system to chronic post-surgical pain
Authors: Parisien Marc , van Reij Roel R.I. , Khoury Samar , Koseli Eda , Karaky Mohamad , van den Hoogen Nynke J. , Peng Garrie , Allegri Massimo , de Gregori Manuela , Chelly Jacques E. , Rakel Barbara A. , Aasvang Eske K. , Kehlet Henrik , Buhre Wolfgang F.F.A. , Bryant Camron D. , Damaj M. Imad , King Irah L. , Mogil Jeffrey S. , Joosten Elbert A.J. , Diatchenko Luda
Published: January 2023

Chronic post-surgical pain affects a large proportion of people undergoing surgery, delaying recovery time and worsening quality of life. Although many environmental variables have been established as risk factors, less is known about genetic risk. To uncover genetic risk factors we performed genome-wide association studies in post-surgical cohorts of five surgery types— hysterectomy, mastectomy, abdominal, hernia, and knee— totaling 1350 individuals. Genetic associations between post-surgical chronic pain levels on a numeric rating scale (NRS) and additive genetic effects at common SNPs were evaluated. We observed genome-wide significant hits in almost all cohorts that displayed significance at the SNP, gene, and pathway levels. The cohorts were then combined via a GWAS meta-analysis framework for further analyses. Using partitioned heritability, we found that loci at genes specifically expressed in the immune system carried enriched heritability, especially genes related to B and T cells. The relevance of B cells in particular was then demonstrated in mouse postoperative pain assays. Taken altogether, our results suggest a role for the adaptive immune system in chronic post-surgical pain.
Association of pre-existing maternal cardiovascular diseases with neurodevelopmental disorders in offspring: a cohort study in Sweden and British Columbia, Canada
Authors: Hossin M. Zakir , de la Cruz Lorena Fernández , McKay Kyla A , Toberlander Tim , Sandström Anna , Razaz Neda
Published: January 2023

Importance

Maternal cardiac disease is associated with impaired placentation and adverse neonatal outcomes, but whether it increases the risk of subsequent neurodevelopmental disorders in offspring remains unknown.

Objective

To assess the associations between pre-existing maternal cardiovascular disease (CVD) and attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID) in offspring.

Design

Population-based cohort study.

Setting

Sweden and British Columbia (BC), Canada.

Participants

Singletons live-born without major malformations between 1990 and 2019. The Swedish Medical Birth Register and the BC Vital Statistics were linked to hospital and physician billing records for identification of exposure and outcomes. All children were followed from age 1 until the outcome, death, emigration, or December 2020.

Exposure

A composite of pre-conception maternal CVDs: cerebrovascular disease, arrhythmia, heart failure, valvular, and congenital heart diseases.

Main Outcomes and Measures

Diagnoses of ADHD, ASD, and ID. The incidence of ADHD, ASD, and ID, comparing offspring of mothers with versus without CVD, was calculated as adjusted hazard ratios (aHRs). These results were compared to models using paternal CVD as negative-control exposure. Fixed-effect meta-analysis was performed to combine the aHRs from Sweden and BC.

Results

We analysed 3,587,257 offspring (48.9% female) – 2,699,675 in Sweden and 887,582 in BC. The meta-analysis suggests that compared with offspring of mothers without CVD, offspring of mothers with CVD had 1.15-fold higher aHRs of ADHD (95% CI: 1.10-1.20) and ASD (95% CI: 1.07-1.22). No association was found between maternal CVD and ID. Stratification by maternal CVD subtypes showed increased hazards of ADHD for maternal heart failure (aHR 1.31; 95% CI: 1.02-1.61), cerebrovascular disease (aHR 1.20; 95% CI: 1.08-1.32), congenital heart disease (aHR 1.18; 95% CI: 1.08-1.27), arrhythmia (aHR 1.13; 95% CI: 1.08-1.19), and valvular heart disease (aHR 1.12; 95% CI: 1.00-1.24). Increased hazards of ASD were observed for maternal cerebrovascular disease (aHR 1.25; 95% CI: 1.04-1.46), congenital heart disease (aHR 1.17; 95% CI: 1.01-1.33), and arrythmia (HR 1.12; 95% CI: 1.01-1.21). Paternal CVDs, except for cerebrovascular disease, did not show associations.

Conclusion and Relevance

Pre-existing maternal CVD was associated with excess risk of ADHD and ASD in offspring. The associations were broadly robust to genetic confounding, warranting further research to identify the underlying intrauterine mechanisms.
Primary care coding activity related to the use of online consultation systems or remote consulting: an analysis of 53 million peoples’ health records using OpenSAFELY
Authors: Fonseca Martina , MacKenna Brian , Mehrkar Amir ,   The OpenSAFELY Collaborative, Walters Caroline E , Hickman George , Pearson Jonathan , Fisher Louis , Inglesby Peter , Bacon Seb , Davy Simon , Hulme William , Goldacre Ben , Koffman Ofra , Bakhai Minal
Published: January 2023

Background

The pandemic accelerated work by the NHS in England to enable and stimulate use of online consultation systems across all practices, for improved access to primary care.

Objective

We aimed to explore general practice coding activity associated with the use of online consultation systems in terms of trends, COVID-19 effect, variation and quality.

Methods

With the approval of NHS England, OpenSAFELY-TPP and OpenSAFELY-EMIS were used to query and analysein siturecords of electronic health record systems of over 53 million patients in over 6,400 practices, mainly in 2019-2020. SNOMED CT codes relevant to online consultation systems and written online consultations were identified. Coded events were described by volumes, practice coverage, trends pre- and post-COVID-19 and inter-practice and sociodemographic variation.

Results

3,550,762 relevant coding events were found in TPP practices, with code eConsultation detected in 84% of practices. Coding activity related to digital forms of interaction increased rapidly from March 2020 at the onset of the COVID-19 pandemic, though we found large variation in coding instance rates among practices in England. Code instances were more commonly found among females, those aged 18-40, those least deprived or white. eConsultation coded activity was more commonly found recorded among patients with a history of asthma or depression.

Conclusions

We successfully queried general practice coding activity relevant to the use of online consultation systems, showing increased adoption as well as key areas of variation during the COVID-19 pandemic. The work can be expanded to support monitoring of coding quality and underlying activity. In future, large-scale impact evaluation studies can be implemented within the platform, namely looking at resource utilisation and patient outcomes.
Spatiotemporal transmission of SARS-CoV-2 lineages during 2020-2021 in Pernambuco - Brazil
Authors: Machado Lais Ceschini , Dezordi Filipe Zimmer , de Lima Gustavo Barbosa , de Lima Raul Emídio , Silva Lilian Caroliny Amorim , Pereira Leandro de Mattos , da Silva Alexandre Freitas , Neto Antonio Marinho da Silva , Oliveira André Luiz Sá de , Armstrong Anderson da Costa , Pessoa-e-Silva Rômulo , Loyo Rodrigo Moraes , Silva Barbara de Oliveira , de Almeida Anderson Rodrigues , Pitta Maira Galdino da Rocha , Santos Francisco de Assis da Silva , Siqueira Marilda Mendonça , Resende Paola Cristina , Delatorre Edson , Naveca Felipe Gomes , Miyajima Fabio , Gräf Tiago , do Carmo Rodrigo Feliciano , Pereira Michelly Cristiny , Campos Tulio de Lima , Bezerra Matheus Filgueira , Paiva Marcelo Henrique Santos , Wallau Gabriel da Luz
Published: January 2023

In recent years, the SARS-CoV-2 viruses emerged and spread around the world, leaving a large death toll and long-lasting impact on survivors. As of January 2023, Brazil is still among the countries with the highest number of registered deaths. This continental-size and pluralistic country experienced a heterogenous implementation of non-pharmacological and pharmacological interventions which, associated with large socioeconomic differences between the country regions, has led to distinct virus spread dynamics across the country. Here we investigate the spatiotemporal dispersion of emerging SARS-CoV-2 lineages and its dynamics in distinct epidemiological scenarios in the first two years of the pandemics in the Pernambuco state (Northeast Brazil). We generated a total of 1389 new SARS-CoV-2 genomes from June 2020 to August 2021 covering all major regions of the state. This sampling captured the arrival, communitary transmission and the circulation of the B1.1, B.1.1.28 and B.1.1.33 lineages in the first eight months of the pandemics, the emergence of the former variant of interest P.2 and the emergence and fast replacement of all previous variants by the more transmissible variant of concern P.1 (Gamma) lineage. Based on the incidence and lineage spread pattern we observed that there was an East-to-West to inner state pattern of transmission which is in agreement with the transmission of more populous metropolitan areas to medium and small size country-side cities in the state. Such transmission patterns may be partially explained by the main routes of traffic across municipalities in the state. Nevertheless, inter-state traffic was also another important source of lineage introduction and spread into the state. Our results highlight that the fine grained intrastate analysis of lineages and incidence spread can provide actionable insights for planning future non-pharmacological intervention for air-borne transmissible human pathogens.
Prospective Evaluation of a 90-day Mortality Prediction Model: From Silent Pilots to Real Time Deployment in the EHR*
Authors: Rossi Lorenzo A. , Roberts Laura , Zachariah Finly
Published: January 2023

Prognostication in oncology is increasingly difficult due to the rapid evolution of therapies with significant improvement of survival. Accurate prognostication is essential to provide optimal, value-driven end of life care for cancer patients, and can promote goals of care (GOC) conversations with the potential to minimize chemotherapy or ICU utilization in the last weeks of life, and possibly increase hospice admission and length of stay.1There are several recent publications on the application of machine learning for prognostication.2,3

We developed a 90-day mortality prediction model trained with data in the Electronic Health Records (EHR). After a non-interventional pilot stage, we deployed the model in February 2021 in the real-time Electronic Health Record Epic infrastructure of our cancer center. Here we present the model and evaluate its overall performance for the first 7.5 months since the go-live and outline our evaluation process for the next stages.
Awareness and utilization of free maternal healthcare services among women in Mt. Elgon Sub-County, Kenya
Authors: Furechi Oliver
Published: January 2023

Maternal mortality remains a matter of public health concern with over 300,000 women dying while giving birth annually. This has driven policy makers to come up with free maternal healthcare services as policy intervention. The Kenyan Government adopted the free maternal healthcare policy in 2013. The policy exempts maternal services from user fees in all public health facilities. This is aimed at promoting skilled delivery to reduce pregnancy-related mortality. In Mt Elgon sub-county, only 45 percent of women deliver in a health facility, this is below the national average of 61.5 percent.

This paper presents results from a cross-sectional study conducted in January 2021 in Mt Elgon Sub-County among 377 randomly selected women who delivered in the preceding 12 months and 4 FGDs with women of reproductive age. Descriptive statistics were undertaken while Chi-Square test was used for inferential statistics. Andersen behavioral model of health service use was used to examine how womens demographic characteristics and awareness regarding the free maternal health policy has affected utilization of maternal healthcare services. The results indicate that respondents were generally aware that there is a government policy on free maternal health policy. However, gaps still exist in terms of pushing awareness towards universal reach, infrastructure development, health worker patient ratio, timely provision of essential supplies and long distance to health facilities This calls for increased sensitization utilizing community health volunteers and allocation of financial and human resources allocation to the department of health within County Governments.
Call detail record aggregation methodology impacts infectious disease models informed by human mobility
Authors: Gibbs Hamish , Musah Anwar , Seidu Omar , Ampofo William , Asiedu-Bekoe Franklin , Gray Jonathan , Adewole Wole A. , Cheshire James , Marks Michael , Eggo Rosalind M.
Published: January 2023

This paper demonstrates how two different methods used to calculate population-level mobility from Call Detail Records (CDR) produce varying predictions of the spread of epidemics informed by these data. Our findings are based on one CDR dataset describing inter-district movement in Ghana in 2021, produced using two different aggregation methodologies. One methodology, “all pairs,” is designed to retain long distance network connections while the other, “sequential” methodology is designed to accurately reflect the volume of travel between locations. We show how the choice of methodology feeds through models of human mobility to the predictions of a metapopulation SEIR model of disease transmission. We also show that this impact varies depending on the location of pathogen introduction and transmissibility. For central locations or highly transmissible diseases, we do not observe significant differences between aggregation methodologies on the predicted spread of disease. For less transmissible diseases or those introduced into remote locations, we find that the choice of aggregation methodology influences the speed of spatial spread as well as the size of the peak number of infections in individual districts. Our findings can help researchers and users of epidemiological models to understand how methodological choices at the level of model inputs may influence the results of models of infectious disease transmission, as well as the circumstances in which these choices do not alter model predictions.

Author Summary

Predicting the sub-national spread of infectious disease requires accurate measurements of inter-regional travel networks. Often, this information is derived from the patterns of mobile device connections to the cellular network. This travel data is then used as an input to epidemiological models of infection transmission, defining the likelihood that disease is “exported” between regions. In this paper, we use one mobile device dataset collected in Ghana in 2021, aggregated according to two different methodologies which represent different aspects of inter-regional travel. We show how the choice of aggregation methodology leads to different predicted epidemics, and highlight the conditions under which models of infection transmission may be influenced by methodological choices in the aggregation of travel data used to parameterize these models. For example, we show how aggregation methodology changes predicted epidemics for less-transmissible infections and under certain models of human movement. We also highlight areas of relative stability, where aggregation choices do not alter predicted epidemics, such as cases where an infection is highly transmissible or is introduced into a central location.
Access to medicines for the treatment of chronic diseases in Chile: qualitative analysis of perceived patient barriers and facilitators in five regions of the country
Authors: Laborde Carla Castillo , Matute Isabel , Sgombich Ximena , Jofré Daniel
Published: January 2023

Purpose

To know patients’ perceptions of barriers and facilitators in access to medicines in general, and those associated with the treatment of three chronic conditions of high prevalence in Chile: diabetes, dyslipidemia and hypertension. Methods: Ten focus groups of patients with these diseases, diagnosed for at least six months and prescribed medication, were included. These were carried out in five regions of Chile: Arica, in the north, Aysén, in the south, and Valparaíso, Metropolitan, and Maule, in the central zone. The criteria for the formation of groups were region, age, health system (public or private) and socioeconomic level (residence commune). Sessions were recorded, transcribed, and analyzed by categories.

Results

The experience of access to medicines is determined by the insurance system, the experience of care with public or private providers, and geographical-administrative difference between capital and other regions. Beneficiaries of public sector, despite their greater socioeconomic vulnerability, perceive greater protection in access: access conditions, delivery reliability and adherence to pharmacological treatment are met. The main problem observed is the financing of treatments not covered by the health system. Policyholders in private sector perceive that they have access to medicines of better quality than those provided free of charge by public sector, but raise fears associated with the inability to afford them and distrust in the process, linked to alliances between laboratories and physicians. Public sector beneficiaries value territorial coverage of primary care, which guarantees access in isolated areas. Regarding the type of provider, public sector shows greater capacity for user loyalty, which is expressed in regular visits and follow-up; unlike discontinuous examinations among private sector beneficiaries.

Conclusions

Different access conditions both at the territorial level and in the health subsystems are evident. It is necessary to make progress in addressing the problem of access to medicines in a comprehensive manner.
The Student Patient Alliance: Development and formative evaluation of an initiative to support collaborations between patient and public involvement contributors and doctoral students
Authors: Simons Gwenda , Birch Rebecca , Stocks Joanne , Insch Elspeth , Rijckborst Rob , Neag Georgiana , McColm Heidi , Romaniuk Leigh , Wright Claire , Phillips Bethan E , Jones Simon W , Pratt Arthur G , Siebert Stefan , Raza Karim , Falahee Marie
Published: January 2023

Background

While the integration of patient and public involvement (PPI) in clinical research is now widespread and recommended as standard practice, meaningful PPI in pre-clinical, discovery science research is more difficult to achieve. One potential way to address this is by integrating PPI into the doctoral training programmes of discovery science postgraduate students. This paper describes the development and formative evaluation of the Student Patient Alliance (SPA), a programme developed at the University of Birmingham that partners PPI contributors with doctoral students.

Methods

Following a successful pilot of the SPA by the Rheumatology Research Group at the University of Birmingham, the scheme was implemented across collaborating Versus Arthritis / MRC centres of excellence at a number of different collaborating centres. Students were partnered with PPI contributors, provided with initial information and guidance, and then encouraged to work together on research and public engagement activities. After six months, students, their PPI partners and the PPI coordinators at each centre completed brief surveys about their participation in the SPA.

Results

Both students and their PPI partners felt that taking part in SPA had a very positive impact. Students reported an increased understanding of PPI and patient priorities and reported improved public engagement and communication skills. Their PPI partners reported a positive impact of the collaboration with the students. They enjoyed learning about the student’s research and contributing to the students ‘personal development. PPI coordinators also highlighted the benefits of the SPA, but noted some challenges they had experienced, such as matching students with PPI partners.

Conclusions

The SPA was valued by students and PPI partners, and it is likely that initiatives of this kind would enhance students’ PPI and public engagement skills and awareness of patients’ experiences on a wider scale. However, appropriate resources are needed at an institutional level to support the implementation of effective programmes of this kind on a larger scale.
Pontine pathology mediates common symptoms of blast-induced chronic mild traumatic brain injury
Authors: Meabon James S. , Schindler Abigail G. , Murray Daniel R. , Colasurdo Elizabeth A. , Sikkema Carl L. , Rodriguez Joshua W. , Omer Mohamed , Cline Marcella M. , Logsdon Aric F. , Cross Donna J. , Richards Todd L. , Meeker Kole D. , Shutes-David Andrew , Yagi Mayumi , Perl Daniel P. , Marshall Desiree A. , Keene C. Dirk , Banks William A. , Thomas Ronald G. , McEvoy Cory , Crabtree Adam , Powell Jake R. , Mihalik Jason P. , Pagulayan Kathleen F. , Raskind Murray A. , Peskind Elaine R. , Cook David G.
Published: January 2023

Understanding how diffuse mild traumatic brain injuries can provoke common and persistent post-concussive symptoms (PCS), such as impaired sleep, is crucial to prevent and treat chronic disability and neurodegeneration. We mapped the spatially-resolved single cell landscape of diffuse mTBI pathology in a mouse model of blast exposure; identifying brainstem injuries predictive of later PCS. Repeated mTBI was necessary to establish chronic microglial activation and phagocytosis of myelin in the pontine reticular formation; where IL33 release by oligodendrocytes predicted microgliopathy. In postmortem brainstem tissues from patients with traumatic brain injury, chronic microglial activation and myelin phagocytosis was evident up to 20 years after diffuse mTBI caused by blast. In living patients with chronic blast mTBI, myelin injury in pontine projections mediated sleep disturbance and other PCS, with a dose dependent effect of mTBI number on sleep disturbance severity. These results support a mechanism for diffuse mTBIs to cause delayed persistent PCS.
Effects of Mitigation and Control Policies in Realistic Epidemic Models Accounting for Household Transmission Dynamics
Authors: Alarid-Escudero Fernando , Andrews Jason , Goldhaber-Fiebert Jeremy D.
Published: January 2023

Background

Compartmental infectious disease (ID) models are often used to evaluate non-pharmaceutical interventions (NPIs) and vaccines. Such models rarely separate within-household and community transmission, potentially introducing biases in situations where multiple transmission routes exist. We formulated an approach that incorporates household structure into ID models, extending the work of House and Keeling.

Design

We developed a multi-compartment susceptible-exposed-infectious-recovered-susceptible-vaccinated (MC-SEIRSV) modeling framework, allowing non-exponentially distributed duration in Exposed and Infectious compartments, that tracks within-household and community transmission. We simulated epidemics that varied by community and household transmission rates, waning immunity rate, household size (3 or 5 members), and numbers of Exposed and Infectious compartments (1-3 each). We calibrated otherwise identical models without household structure to the early phase of each parameter combination’s epidemic curve. We compared each model pair in terms of epidemic forecasts and predicted NPI and vaccine impacts on: the timing and magnitude of the epidemic peak and on its total size. Meta-analytic regressions characterized the relationship between household structure inclusion and the size and direction of biases.

Results

Otherwise similar models with and without household structure produced equivalent early epidemic curves. However, forecasts from models without household structure were biased. Without intervention, they were upward-biased on peak size and total epidemic size, with biases also depending on the number of Exposed and Infectious compartments. Model-estimated NPI effects of a 60% reduction in community contacts on peak time and size were systematically overestimated without household structure. Biases were smaller with a 20% reduction NPI. Because vaccination impacted both community and household transmission, their biases were smaller.

Conclusions

ID models without household structure can produce biased outcomes in settings where within-household and community transmission differ.
The genetic architecture of recombination rates is polygenic and differs between the sexes in wild house sparrows (Passer domesticus)
Authors: McAuley John B. , Servin Bertrand , Burnett Hamish A. , Brekke Cathrine , Peters Lucy , Hagen Ingerid J. , Niskanen Alina K. , Ringsby Thor Harald , Husby Arild , Jensen Henrik , Johnston Susan E.
Published: January 2023

Meiotic recombination through chromosomal crossing-over is a fundamental feature of sex and an important driver of genomic diversity. It ensures proper disjunction, allows increased selection responses, and prevents mutation accumulation; however, it is also mutagenic and can break up favourable haplotypes. This cost/benefit dynamic is likely to vary depending on mechanistic and evolutionary contexts, and indeed, recombination rates show huge variation in nature. Identifying the genetic architecture of this variation is key to understanding its causes and consequences. Here, we investigate individual recombination rate variation in wild house sparrows (Passer domesticus). We integrate genomic and pedigree data to identify autosomal crossover counts (ACC) and intra-chromosomal allelic shuffling (r̅intra) in 13,056 gametes. Females had 1.37 times higher ACC, and 1.55 times higherr̅intrathan males. ACC andr̅intrawere heritable in females and males (ACC h2= 0.23 and 0.11;r̅intrah2= 0.12 and 0.14), but cross-sex additive genetic correlations were low (rA= 0.29 and 0.32 for ACC andr̅intra). Conditional bivariate analyses showed that all measures remained heritable after accounting for genetic values in the opposite sex, indicating that sex-specific ACC andr̅intracan evolve somewhat independently. Genome-wide models showed that ACC andr̅intraare polygenic and driven by many small-effect loci, many of which are likely to act intransas global recombination modifiers. Our findings show that recombination rates of females and males can have different evolutionary potential in wild birds, providing a compelling mechanism for the evolution of sexual dimorphism in recombination.
Biohybrid restoration of the hippocampal loop re-establishes the non-seizing state in an in vitro model of limbic seizures
Authors: Caron Davide , Buccelli Stefano , Canal-Alonso Angel , Farsani Javad , Pruzzo Giacomo , Barranco Bernabé Linares , Corchado Juan Manuel , Chiappalone Michela , Panuccio Gabriella
Published: January 2023

Objective

The compromise of the hippocampal loop is a hallmark of mesial temporal lobe epilepsy (MTLE), the most frequent epileptic syndrome in the adult population and the most often refractory to medical therapy. Hippocampal sclerosis is found in >50% of drug-refractory MTLE patients and primarily involves the CA1, consequently disrupting the hippocampal output to the entorhinal cortex (EC). Closed-loop deep brain stimulation (DBS) is the latest frontier to improve drug-refractory MTLE; however, current approaches do not restore the functional connectivity of the hippocampal loop, they are designed by trial-and-error and heavily rely on seizure detection or prediction algorithms. The objective of this study is to evaluate the anti-ictogenic efficacy and robustness of an artificial bridge restoring the dialog between hippocampus and EC.

Approach

In mouse hippocampus-EC slices treated with 4-aminopyridine and in which the Schaffer Collaterals are severed, we established an artificial bridge between hippocampus and EC wherein interictal discharges originating in the CA3 triggered stimulation of the subiculum so to entrain EC networks. Combining quantification of ictal activity with tools from information theory, we addressed the efficacy of the bridge in controlling ictogenesis and in restoring the functional connectivity of the hippocampal loop.

Main results

The bridge significantly decreased or even prevented ictal activity and proved robust to failure; when operating at 100% of its efficiency (i.e., delivering a pulse upon each interictal event), it recovered the functional connectivity of the hippocampal loop to a degree similar to what measured in the intact circuitry. The efficacy and robustness of the bridge stem in mirroring the adaptive properties of the CA3, which acts as biological neuromodulator. Significance. This work is the first stepping stone toward a paradigm shift in the conceptual design of stimulation devices for epilepsy treatment, from function control to functional restoration of the salient brain circuits.