bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin D supplementation improves the prognosis of patients with colorectal cancer liver metastases
Authors: Rada Miran , Krzywon Lucyna , Kapelanski-Lamoureux Audrey , Kim Diane , Petrillo Stephanie , Lazaris Anthoula , Metrakos Peter
Published: November 2022

Colorectal cancer liver metastasis (CRCLM) is one of the deadliest cancers. CRCLM tumours have two distinct histopathological growth patterns (HGPs) including desmoplastic HGP (DHGP) and replacement HGP (RHGP). The DHGP tumours are angiogenic, while their RHGP counterparts are vessel co-opting. The patients with DHGP tumours have a better response to anti-angiogenic agents and chemotherapy, as well as the prognosis. To determine the influence of vitamin D supplementation in CRCLM, we analyzed the HGPs and the 5-year OS of CRCLM patients (n=106). Interestingly, we found an inverse correlation between vitamin D supplementation and the presence of RHGP tumours in CRCLM patients. Additionally, the 5-year OS of the patients that administered vitamin D was significantly higher. The cancer cells in RHGP lesions are characterized by direct contact with the hepatocytes, and this phenomenon enhances the motility of the cancer cells and facilitates their infiltration through liver parenchyma to co-opt the pre-existing vessels. Significantly, our in vitro data demonstrated the downregulation of motility markers in the co-cultured cancer cells with hepatocytes upon exposure to vitamin D. Altogether, this study highlights the role of vitamin D in CRCLM and provides a rationale to investigate the contribution of vitamin D supplementation to the prognosis of CRCLM patients.
Morning Report Improves Residents’ Diagnostic Competence & Clinical Problem-Solving Ability
Authors: Tariq Muhammad , Vaqar Maham , Abid Shahab , Jafri Wasim
Published: November 2022

Introduction

Morning report (MR) is an educational activity that uses inpatient case-based teaching. Given the rapid changes taking place in medical practice, it is important to assess the residents’ perspective regarding this teaching method.

Objective

To establish the perspective of residents in internal medicine on various aspects of MR and propose a format based on our observations.

Study Design

Observational cross-sectional study.

Place & Duration of Study

Data was collected from groups of residents in the Department of Medicine at the Aga Khan University Hospital, from July 2002 to August 2007.

Methodology

An observational cross-sectional survey on MR was conducted among the residents of the Department of Medicine at Aga Khan University. A 22-item questionnaire was distributed among the residents based on the purpose, format, and contents of the morning report, as well as the most appropriate person to present and conduct it, and how frequently they should be carried out.

Analyses were carried out using the statistical software ‘Statistical Package for Social Sciences’ (SPSS)

Results

92% of residents believed MR to be an effective teaching activity with 65% of them choosing ‘Improvement in clinical problem-solving ability’ as the primary purpose of MR followed by ‘improving presentation skills’ (62%) and ‘conveying medical knowledge to the residents’ (58%). 79 residents (87%) believed that the junior resident should present the case history. 75 residents (83%) thought that faculty on call at time of patient’s admission should conduct MR. Residents wanted to discuss diagnostic work-up (90%) and management (89%) of specific interesting cases (79%) in MR.

Conclusion

MR is an effective educational activity and should be an essential component of any post-graduate residency program within the country and outside.
Nirmatrelvir and the Risk of Post-Acute Sequelae of COVID-19
Authors: Xie Yan , Choi Taeyoung , Al-Aly Ziyad
Published: November 2022

Long Covid – the disease encompassing the post-acute sequelae of SARS-CoV-2 (PASC) —affects millions of people around the world. Prevention of PASC is an urgent public health priority. In this work, we aimed to examine whether treatment with nirmatrelvir in the acute phase of COVID-19 is associated with reduced risk of post-acute sequelae. We used the healthcare databases of the US Department of Veterans Affairs to identify users of the health system who had a SARS-CoV-2 positive test between March 01, 2022 and June 30, 2022, were not hospitalized on the day of the positive test, had at least 1 risk factor for progression to severe COVID-19 illness and survived the first 30 days after SARS-CoV-2 diagnosis. We identify those who were treated with oral nirmatrelvir within 5 days after the positive test (n=9217) and those who received no COVID-19 antiviral or antibody treatment during the acute phase of SARS-CoV-2 infection (control group, n= 47,123). Inverse probability weighted survival models were used to estimate the effect of nirmatrelvir (versus control) on a prespecified panel of 12 post-acute COVID-19 outcomes and reported as hazard ratio (HR) and absolute risk reduction (ARR) in percentage at 90 days. Compared to the control group, treatment with nirmatrelvir was associated with reduced risk of PASC (HR 0.74 95% CI (0.69, 0.81), ARR 2.32 (1.73, 2.91)) including reduced risk of 10 of 12 post-acute sequelae in the cardiovascular system (dysrhythmia and ischemic heart disease), coagulation and hematologic disorders (deep vein thrombosis, and pulmonary embolism), fatigue, liver disease, acute kidney disease, muscle pain, neurocognitive impairment, and shortness of breath. Nirmatrelvir was also associated with reduced risk of post-acute death (HR 0.52 (0.35, 0.77), ARR 0.28 (0.14, 0.41)), and post-acute hospitalization (HR 0.70 (0.61, 0.80), ARR 1.09 (0.72, 1.46)). Nirmatrelvir was associated with reduced risk of PASC in people who were unvaccinated, vaccinated, and boosted, and in people with primary SARS-CoV-2 infection and reinfection. In sum, our results show that in people with SARS-CoV-2 infection who had at least 1 risk factor for progression to severe COVID-19 illness, treatment with nirmatrelvir within 5 days of a positive SARS-CoV-2 test was associated with reduced risk of PASC regardless of vaccination status and history of prior infection. The totality of findings suggests that treatment with nirmatrelvir during the acute phase of COVID-19 reduces the risk of post-acute adverse health outcomes.
Rapid Acquisition and Transmission of Drug Resistance Amongst Beijing LineageMycobacterium tuberculosisin Vietnam
Authors: Silcocks Matthew , Chang Xuling , Thuong Thuong Nguyen Thuy , Qin Youwen , Minh Ha Dang Thi , Khac Thai Phan Vuong , Vijay Srinivasan , Anh Thu Do Dang , Nhung Hoang Ngoc , Lan Nguyen Huu , Quynh Nhu Nguyen Thi , Edwards David , Nath Artika , Pham Kym , Bang Nguyen Duc , Hong Chau Tran Thi , Thwaites Guy , Heemskerk A. Dorothee , Khor Chiea Chuen , Teo Yik Ying , Inouye Michael , Ong Rick Twee-Hee , Caws Maxine , Holt Kathryn E. , Dunstan Sarah J.
Published: November 2022

Whole genome sequencing (WGS) and phenotypic drug susceptibility testing was performed on a collection of 2,542Mycobacterium tuberculosis (Mtb)isolates from tuberculosis (TB) patients recruited in Ho Chi Minh City (HCMC), Vietnam, to investigateMtbdiversity, the prevalence and phylodynamics of drug resistance, andin silicoresistance prediction with sequencing data. Amongst isolates tested phenotypically against first-line drugs, we observed high rates of streptomycin [STR, 37.7% (N=573/1,520)] and isoniazid resistance [INH, 25.7% (N=459/1,786)], and lower rates of resistance to rifampicin [RIF, 4.9% (N=87/1,786)] and ethambutol [EMB, 4.2% (N=75/1,785)]. Resistance to STR and INH was predicted moderately well when applying the TB-Profiler algorithm to WGS data (sensitivities of 0.81 and 0.87 respectively), while resistance to RIF and EMB was predicted relatively poorly (sensitivities of 0.70 and 0.44 respectively). Rates of multidrug-resistance [(MDR, 3.9% (N=69/1,786)], and resistance to a number of second-line drugs [Para-aminosalicylic acid (29.6% N=79/267), Amikacin (15.4% N=41/267) and Moxifloxacin (21.3%), N=57/267], were found to be high within a global context. Comparing rates of drug resistance among lineages, and exploring the dynamics of resistance acquisition through time, suggest the Beijing lineage (lineage 2.2) acquiresde novoresistance mutations at higher rates and suffers no apparent fitness cost acting to impede the transmission of resistance. We infer resistance to INH and STR to have arisen earlier, on average, than resistance to RIF, and to be more widespread across the phylogeny. The high prevalence of ‘background’ INH resistance, combined with high rates of RIF mono-resistance (20.7%, N=18/87) suggests that rapid assays for INH resistance will be valuable in this setting. These tests will allow the detection of INH mono-resistance, and will allow MDR isolates to be distinguished from isolates with RIF mono-resistance.
Real-world effectiveness of nirmatrelvir/ritonavir use for COVID-19: A population-based cohort study in Ontario, Canada
Authors: Schwartz KL , Wang J , Tadrous M , Langford BJ , Daneman N , Leung V , Gomes T , Friedman L , Daley P , Brown KA
Published: November 2022

Background

Our objective was to evaluate the real world effectiveness of nirmatrelvir/ritonavir to prevent severe COVID-19 while Omicron and its subvariants predominate.

Methods

We conducted a population based cohort study in Ontario, Canada including all residents >17 years of age who tested positive for SARS-CoV-2 by PCR between 4 April and 31 August 2022. We compared nirmatrelvir/ritonavir treated patients to unexposed patients and measured the primary outcome of hospitalization or death from COVID-19, and a secondary outcome of death 1-30 days. We used weighted logistic regression to calculate weighted odds ratios (wOR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting (IPTW) to control for confounding.

Results

The final cohort included 177,545 patients with 8,876 (5.0%) exposed and 168,669 (95.0%) unexposed individuals. The groups were well balanced with respect to demographic and clinical characteristics after applying stabilized IPTW. Hospitalization or death within 30 days was lower in the nirmatrelvir/ritonavir treated group compared to unexposed individuals (2.1% vs 3.7%, wOR 0.56; 95%CI, 0.47-0.67). In the secondary analysis, the relative odds of death was also significantly reduced (1.6% vs 3.3%, wOR 0.49; 95%CI, 0.39-0.62). The number needed to treat to prevent one case of severe COVID-19 was 62 (95%CI 43 to 80). Findings were similar across strata of age, DDIs, vaccination status, and comorbidities.

Interpretation

Nirmatrelvir/ritonavir was associated with significantly reduced risk of hospitalization and death from COVID-19 in this observational study, supporting ongoing use of this therapeutic to treat patients with mild COVID-19 at risk for severe disease.
Understanding Knowledge, Attitudes and Practices on Ebola Virus Disease: A Multi-Site Mixed Methods Survey on Preparedness in Rwanda
Authors: Karuhije Janvier , Nkeshimana Menelas , Zakham Fathiah , Hewins Benjamin , Rutayisire Justin , Martinez Gustavo S. , Kelvin David , Ndishimye Pacifique
Published: November 2022

The overall goal of this survey was to understand the Ebola Virus Disease (EVD) - related knowledge, attitudes, and practices (KAP) at individual, inter-personal, institutional, and societal levels in Rwanda. This cross-sectional mixed-methods survey was conducted in five selected districts: Rusizi, Karongi, Rubavu, Burera and Gasabo. Quantitative data was collected from 1,010 participants using a structured questionnaire and Kobo Collect. Qualitative data was collected from 98 participants through Key Informant Interviews and Focus Group Discussions using a semi structured interview guide. Among the 1,010 surveyed respondents, 56% were male, 70.3% were married, and 50% had primary education. An important finding was the high level of Ebola awareness and knowledge in all the five districts, with 99.6% reporting having previously heard of Ebola, which indicates previous awareness-raising efforts were successful. More than 54% of respondents indicated that Ebola is caused by a virus which originates from wild animal animals (42.1%). Furthermore, fever (85%), bleeding (87.7), and vomiting (40.2%) were cited as the primary signs and symptoms for Ebola. Most of the respondents were knowledgeable regarding prevention measures for Ebola. Despite this, 80% of the survey respondents had not received formal training or health education on Ebola. The majority of respondents (78.2%) reported having a positive attitude towards EVD survivors. Many respondents (90%) believe that the country is at risk of an EVD outbreak and about 87.8% think that they are personally at risk of contracting Ebola. Most respondents reported adopting habits that included avoiding physical contact with the patients and reducing unnecessary movements/travel throughout the Ebola-affected regions. At the community level, participants state that they participate in the sharing of Ebola-related information and reporting suspected cases to relevant authorities. Additionally, many participants know the necessary emergency contact number (114) for assistance and reporting of EVD-related information. Most respondents (97.2%) believed that it is important to be vaccinated to prevent Ebola, and around 93.3% are ready/willing to be vaccinated once the EVD vaccine is available. While the radio is the preferred source for Ebola-related information, the most trusted sources are the ministry of health and governmental institutions, such as the Rwanda Biomedical Centre. Our results show that there was high EVD-related knowledge and awareness among the general population in Rwanda. However, for strong public health awareness, preparedness, and protection, there is a need to implement public sensitization programmes that address EVD-related misconceptions and discriminatory attitudes toward EVD patients.
WITHDRAWN: Application of diagnostic network optimization in Kenya and Nepal to design integrated, sustainable and efficient bacteriology and antimicrobial resistance surveillance networks
Authors: Brunetti Marie , Singh Amit , Chebore Sheilla , Gyenwali Deepak , Malou Nada , Ferreyra Cecilia , Gompo Tulsi Ram , Acharya Jyoti , Rijal Nisha , Githii Susan , Wesangula Evelyn , Albert Heidi
Published: November 2022

Withdrawal Statement

The authors have withdrawn this manuscript as it contains data that did not have the proper permissions to be publicly distributed. Therefore, the authors do not wish this work to be cited as a reference for the project. Please refer to the published version under DOI: 10.1371/journal.pgph.0002247. If you have any questions, please contact the corresponding author.
Conversational AI facilitates mental health assessments and is associated with improved recovery rates
Authors: Rollwage Max , Juchems Keno , Habicht Johanna , Carrington Ben , Hauser Tobias , Harper Ross
Published: November 2022

Mental health services across the globe are overburdened due to increased patient need for psychological therapies and a shortage of qualified mental health practitioners. This is unlikely to change in the short- to-medium term. Digital support is urgently needed to facilitate access to mental healthcare whilst creating efficiencies in service delivery. In this paper, we evaluate the use of a conversational artificial intelligence (AI) solution (Limbic Access) to assist both patients and mental health practitioners around referral, triage, and clinical assessment of mild-to-moderate adult mental illness. Assessing this solution in the context of England’s NHS Improving Access to Psychological Therapies (IAPT) services, we demonstrate that deploying such an AI solution is associated with improved recovery rates. We find that those IAPT services that introduced the conversational AI solution improved their recovery rates, while comparable IAPT services across the country reported deteriorating recovery rates during the same time period. Further, we provide an economic analysis indicating that the usage of this AI tool can be highly cost-effective relative to other methods of improving recovery rates. Together, these results highlight the potential of AI solutions to support mental health services in the delivery of quality care in the context of worsening workforce supply and system overburdening.

Author summary

In this paper, we evaluate the use of a conversational artificial intelligence solution (Limbic Access) to assist both patients and mental health practitioners around referral, triage, and clinical assessment of mild-to-moderate adult mental illness. Assessing this solution in the context of England’s NHS mental health services, we demonstrate that deploying such an AI solution is associated with improved recovery rates. We find that those services that introduced the conversational AI solution improved their recovery rates, while comparable mental health services across the country reported declining recovery rates during the same time period. Further, we provide an economic analysis indicating that the usage of this AI tool can be highly cost-effective relative to other methods of improving recovery rates. Together, these results highlight the potential of AI solutions to support mental health services in the delivery of quality care in the context of reduced workforce supply and an overburdened system.
Multi-omics endotype of preterm infants with bronchopulmonary dysplasia and pulmonary hypertension
Authors: Siddaiah Roopa , Oji-Mmuo Christiana , Aluquin Vincent , Kawasawa Yuka Imamura , Donnelly Ann , Rousselle Dustin , Fuentes Nathalie , Austin Eric D. , Silveyra Patricia
Published: November 2022

Rationale

Pulmonary hypertension associated with bronchopulmonary dysplasia is a severe complication of preterm birth resulting in high mortality of up to 50% within the first 2 years of life. There is a direct relationship between bronchopulmonary dysplasia severity and incidence of associated pulmonary hypertension. However, it is challenging to clinically characterize severe bronchopulmonary dysplasia with and without pulmonary hypertension and there is need for better understanding of the two entities.

Objectives

To identify markers to help understand biological processes and endotype characterization of infants with pulmonary hypertension associated with bronchopulmonary dysplasia in tracheal aspirates.

Methods

We conducted multi-omic analysis of tracheal aspirates via miRNA PCR arrays, RNA sequencing and mass spectrometry proteomics in preterm infants with severe bronchopulmonary dysplasia with (n=21) and without (n=25) pulmonary hypertension.

Results

Our study analysis revealed 12 miRNAs (hsa-miR-29a, has-miR-542-3p, has-miR-624, has-miR-183, hsa-miR-501-3p, hsa-miR-101, hsa-miR-3131, hsa-miR-3683, hsa-miR-3193, hsa-miR-3672, hsa-miR-3128, and hsa-miR-1287); 6 transcripts (IL6, RPL35P5, HSD3B7, RNA5SP215, OR2A1-AS1, and RNVU1-19), and 5 proteins (CAPS, AAT, KRT5, SFTPB, and LGALS3BP) with significant differential expression in preterm infants with severe lung disease with pulmonary hypertension when compared to infants with severe lung disease but no pulmonary hypertension. Pathway analysis of the integrated multi-omic expression signatures revealed NFkB, VEGF, SERPINA1, IL6 and ERK12 as target molecules for miRNAs, and angiogenesis and hyperoxia stress as recurrent pathways of individual markers.

Conclusion

Our multi-omic analysis of tracheal aspirates revealed a comprehensive thumbprint of miRNAs, mRNAs and proteins that could help endotype infants with severe lung disease and pulmonary hypertension.
Citizen involvement in research on technological innovations for health, care or well-being: a scoping review
Authors: van Leersum Catharina M. , Jaschinski Christina , Bults Marloes , van der Zwart Johan
Published: November 2022

Citizen science can be a powerful approach to foster the successful implementation of technological innovations in health, care or well-being. Involving experience experts as co-researchers or co-designers of technological innovations facilitates mutual learning, community building, and empowerment. By utilizing the expert knowledge of the intended users, innovations have a better chance to get adopted and solve complex health-related problems. As citizen science is still a relatively new practice for health and well-being, little is known about effective methods and guidelines for successful collaboration. This scoping review aims to provide insight in 1) the levels of citizen involvement in current research on technological innovations for health, care or well-being, 2) the used participatory methodologies, and 3) lesson’s learned by the researchers.

The search was performed in SCOPUS in January 2021 and included peer-reviewed journal and conference papers published between 2016 and 2020. The final selection (N=83) was limited to empirical studies that had a clear focus on technological innovations for health, care or well-being and involved citizens at the level of collaboration or higher. Our results show a growing interest in citizens science as an inclusive research approach. Citizens are predominantly involved in the design phase of innovations and less in the preparation, data-analyses or reporting phase. Eight records had citizens in the lead in one of the research phases.

Researcher use different terms to describe their methodological approach including participatory design, co-design, community based participatory research, co-creation, public and patient involvement, partcipatory action research, user-centered design and citizen science. Our selection of cases shows that succesfull citizen science projects develope a structural and longtidutinal partnership with their collaborators, use a situated and adaptive research approach, and have researchers that are willing to give-up tradional power dynamics and engage in a mutual learning experience.
Co-production of an online research and resource platform for improving the health of young people - The HYPE Project
Authors: Gunasinghe Cerisse , Bergou Nicol , MacCrimmon Shirlee , Rhead Rebecca , Woodhead Charlotte , Jones Nielsen Jessica D. , Hatch Stephani L
Published: November 2022

Mental health conditions tend to go unrecognised and untreated in adolescence, and therefore it is crucial to improve the health and social outcomes for these individuals through age and culturally appropriate interventions. This paper aims firstly to describe the development and implementation of the HYPE project platform (a research and resource platform co-designed and co-produced with young people). The second aim is to describe the characteristics of participants who engaged with the platform and an embedded pilot online survey.

A mixed methods design (including focus groups and repeated measures surveys) was used to address aims of the HYPE project. Data were analysed using thematic analysis and descriptive statistics to: (1) help improve access to health and social services, (2) guide provision of information of online resources and (3) deliver complementary community-based events/activities to promote mental health and to ultimately prevent mental health issues.

Pilot and main phases of the HYPE project demonstrated the capacity and feasibility for such a platform to reach local, national, and international populations. Analyses demonstrated that the platform was particularly relevant for young females with pre-existing health difficulties. Some of the barriers to involving young people in research and help-seeking are discussed.
Hospitalization forecast to inform COVID-19 pandemic planning and resource allocation using mathematical models
Authors: Wikman-Jorgensen Philip Erick , Ruiz Angel , Giner-Galvañ Vicente , Llenas-García Jara , Seguí-Ripoll José Miguel , Salinas Serrano Jose María , Borrajo Emilio , Ibarra Sánchez José María , García-Sabater José Pedro , Marín-García Juan A
Published: November 2022

Background

The COVID-19 pandemic has put tremendous pressure on hospital resources around the world. Forecasting demand for healthcare services is important generally, but crucial in epidemic contexts, both to facilitate resource planning and to inform situational awareness. There is abundant research on methods for predicting the spread of COVID-19 and even the arrival of COVID-19 patients to hospitals emergency departments. This study builds on that work to propose a hybrid tool, combining a stochastic Markov model and a discrete event simulation model to dynamically predict hospital admissions and total daily occupancy of hospital and ICU beds.

Methods

The model was developed and validated at San Juan de Alicante University Hospital from 10 July 2020 to 10 January 2022 and externally validated at Hospital Vega Baja. An admissions generator was developed using a stochastic Markov model that feeds a discrete event simulation model in R. Positive microbiological SARS-COV-2 results from the health department’s catchment population were stratified by patient age to calculate the probabilities of hospital admission. Admitted patients follow distinct pathways through the hospital, which are simulated by the discrete event simulation model, allowing administrators to estimate the bed occupancy for the next week. The median absolute difference (MAD) between predicted and actual demand was used as a model performance measure.

Results

With respect to the San Juan hospital data, the admissions generator yielded a MAD of 6 admissions/week (interquartile range [IQR] 2-11). The MAD between the tool’s predictions and actual bed occupancy was 20 beds/day (IQR 5-43), or 5% of the hospital beds. The MAD between the intensive care unit (ICU)’s predicted and actual occupancy was 4 beds/day (IQR 2-7), or 25% of the beds. When the model was further evaluated with data from Hospital Vega Baja, the admissions generator showed a MAD of 2.42 admissions/week (IQR 1.02-7.41). The MAD between the tools’ predictions and the actual bed occupancy was 18 beds/day (IQR 19.57-38.89), or 5.1% of the hospital beds. For ICU beds, the MAD was 3 beds/day (IQR 1-5), or 21.4% of the ICU beds.

Conclusion

Predictions of hospital admissions, ward beds, and ICU occupancy for COVID-19 patients were very useful to hospital managers, allowing early planning of hospital resource allocation.
Impact of SARS-CoV-2 infection on disease trajectory in youth with T1D: An EHR-based cohort study from the RECOVER program
Authors: Prahalad Priya , Lorman Vitaly , Wu Qiong , Razzaghi Hanieh , Chen Yong , Pajor Nathan , Case Abigail , Bose-Brill Seuli , Block Jason , Patel Payal B , Rao Suchitra , Mejias Asuncion , Forrest Christopher B. , Bailey L. Charles , Jhaveri Ravi , Thacker Deepika , Christakis Dimitri A. , Lee Grace M.
Published: November 2022

Background

Post-acute sequelae of SARS-Co-V-2 infection (PASC) is associated with worsening diabetes trajectory. It is unknown whether PASC in children with type 1 diabetes (T1D) manifests as worsening diabetes trajectory.

Objective

To explore the association between SARS-CoV-2 infection (COVID-19) and T1D-related healthcare utilization (for diabetic ketoacidosis [DKA] or severe hypoglycemia [SH]) or Hemoglobin (Hb) A1c trajectory.

Methods

We included children <21 years with T1D and ≥1 HbA1c prior to cohort entry, which was defined as COVID-19 (positive diagnostic test or diagnosis code for COVID-19, multisystem inflammatory syndrome in children, or PASC) or a randomly selected negative test for those who were negative throughout the study period (Broad Cohort). A subset with ≥1 HbA1c value from 28-275 days after cohort entry (Narrow Cohort) was included in the trajectory analysis. Propensity score-based matched cohort design followed by weighted Cox regression was used to evaluate the association of COVID-19 with healthcare utilization ≥28 days after cohort entry. Generalized estimating equation models were used to measure change in HbA1c in the Narrow cohort.

Results

From 03/01/2020-06/22/2022, 2,404 and 1,221 youth met entry criteria for the Broad and Narrow cohorts, respectively. The hazard ratio for utilization was (HR 1.45 [95%CI,0.97,2.16]). In the Narrow Cohort, the rate of change (slope) of HbA1c increased 91-180 days after cohort entry for those with COVID-19 (0.138 vs. -0.002, p=0.172). Beyond 180 days, greater declines in HbA1c were observed in the positive cohort (-0.104 vs. 0.008 per month, p=0.024).

Conclusion

While a trend towards worse outcomes following COVID-19 in T1D patients was observed, these findings were not statistically significant. Continued clinical monitoring of youth with T1D following COVID-19 is warranted.

Authorship Statement

Authorship has been determined according to ICMJE recommendations

Disclaimer

The content is solely the responsibility of the authors and does not necessarily represent the official views of the RECOVER Program, the NIH or other funders.

Funding Source

⍰This research was funded by the National Institutes of Health (NIH) Agreement OT2HL161847-01 as part of the Researching COVID to Enhance Recovery (RECOVER) program of research.
Post-GWAS multiomic functional investigation of theTNIP1locus in Alzheimer’s disease implicates mediation throughGPX3
Authors: Panyard Daniel J. , Reus Lianne M. , Ali Muhammad , Liu Jihua , Deming Yuetiva K. , Lu Qiongshi , Kollmorgen Gwendlyn , Suridjan Ivonne , Wild Norbert , Visser Pieter J. , Bertram Lars , Zetterberg Henrik , Blennow Kaj , Gobom Johan , Western Dan , Sung Yun Ju , Carlsson Cynthia M. , Johnson Sterling C. , Asthana Sanjay , Cruchaga Carlos , Tijms Betty M. , Engelman Corinne D. , Snyder Michael P.
Published: November 2022

The recently reportedTNIP1/GPX3locus from AD GWAS studies was investigated. Using proteomics and other functional omics data, we identified evidence for a functional mechanism linking variants in this locus to decreased CSF GPX3 levels as AD progresses, suggesting a new potential target for intervention.
Caffeine and Sleep in East Tennessee students
Authors: Brahmbhatt Viraj
Published: November 2022

Caffeine is a psychoactive stimulant that works on the central nervous system and is widely consumed for its ability to increase alertness. The well-known effects of caffeine consumption include increasing alertness and focus. In addition, this caffeine consumption is well known for its ability to interrupt sleep. In previous studies investigating the prevalence of caffeine consumption, students indicated that caffeine consumption was a prevalent behavior sought after to improve academic and athletic performance in the college students studied (Mahoney et al., 2019). Current American Academy of Pediatrics guidelines for caffeine consumption of 100 mg/day for those under 18 seem optimistic given the prevalence of caffeine consumption indicated in current literature. Current studies in medical students in the Middle East have indicated high levels of caffeine consumption and lacking sleep as well as elevated anxiety and depression symptoms. This study aims to bridge the gap on caffeine consumption, sleep, and associated behaviors in American students in the East Tennessee area. The method utilized a survey distributed through the REDCap platform. The survey was constructed using the Pittsburgh Sleep Quality Index (PSQI) as well as an original caffeine consumption portion of the survey. An open response section was provided so that respondents may be able to provide specific factors that may have contributed to their loss of sleep or increased caffeine intake. The final sample included 97 responses from high school and college students between the ages of 14 and 45, of which 57 were deemed fully completed and able to be analyzed. Analysis revealed that there was a correlation between decreased sleep and increased caffeine intake. 63.2% of respondents indicated caffeine consumption. For the individuals 18 and under, 75% of respondents indicated caffeine consumption over the healthy guidelines indicated by the American Academy of Pediatrics. Additionally, in the free response section, 27% of respondents indicated that they were unable to sleep due to stress brought on by school or homework, while 15% of respondents indicated that they had been able to get sufficient sleep because of stress. This study offers insight into the higher than recognized caffeine usage within students. Additionally, sleep levels were generally below the recommended guidelines. This data prompts further studies looking into adolescent mental health, associated with the lacking sleep and high caffeine levels, as well as prompts schools to potentially offer additional resources to combat the mental health detriment that may be suffered as a result of lacking sleep and excessive caffeine intake.
Surveillance of COVID-19 vaccine safety among elderly persons aged 65 years and older
Authors: Wong Hui-Lee , Tworkoski Ellen , Zhou Cindy Ke , Hu Mao , Thompson Deborah , Lufkin Bradley , Do Rose , Feinberg Laurie , Chillarige Yoganand , Dimova Rositsa , Lloyd Patricia , MaCurdy Thomas , Forshee Richard A. , Kelman Jeffrey , Shoaibi Azadeh , Anderson Steven A.
Published: November 2022

Background

Monitoring safety outcomes following COVID-19 vaccination is critical for understanding vaccine safety especially when used in key populations such as elderly persons age 65 years and older who can benefit greatly from vaccination. We present new findings from a nationally representative early warning system that may expand the safety knowledge base to further public trust and inform decision making on vaccine safety by government agencies, healthcare providers, interested stakeholders, and the public.

Methods

We evaluated 14 outcomes of interest following COVID-19 vaccination using the US Centers for Medicare & Medicaid Services (CMS) data covering 30,712,101 elderly persons. The CMS data from December 11, 2020 through Jan 15, 2022 included 17,411,342 COVID-19 vaccinees who received a total of 34,639,937 doses. We conducted weekly sequential testing and generated rate ratios (RR) of observed outcome rates compared to historical (or expected) rates prior to COVID-19 vaccination.

Findings

Four outcomes met the threshold for a statistical signal following Pfizer-BioNTech vaccination including pulmonary embolism (PE; RR=1.54), acute myocardial infarction (AMI; RR=1.42), disseminated intravascular coagulation (DIC; RR=1.91), and immune thrombocytopenia (ITP; RR=1.44). After further evaluation, only the RR for PE still met the statistical threshold for a signal; however, the RRs for AMI, DIC, and ITP no longer did. No statistical signals were identified following vaccination with either the Moderna or Janssen vaccines.

Interpretation

This early warning system is the first to identify temporal associations for PE, AMI, DIC, and ITP following Pfizer-BioNTech vaccination in the elderly. Because an early warning system does not prove that the vaccines cause these outcomes, more robust epidemiologic studies with adjustment for confounding factors, including age and nursing home residency, are underway to further evaluate these signals. FDA strongly believes the potential benefits of COVID-19 vaccination outweigh the potential risks of COVID-19 infection.
Difficult-to-treat rheumatoid arthritis (D2T RA): clinical issues at early stages of disease
Authors: Leon Leticia , Madrid-García Alfredo , Lopez-Viejo Patricia , González-Álvaro Isidoro , Novella-Navarro Marta , Freites Nuñez Dalifer , Rosales Zulema , Fernandez-Gutierrez Benjamin , Abasolo Lydia
Published: November 2022

Objectives

Most studies on difficult-to-treat rheumatoid arthritis (D2T RA) have focused on established RA. Here, we analyze whether disease activity in the early stages of RA could influence progression to a D2T RA under real-life conditions. Other clinical and treatment-related factors were also analyzed.

Methods

A longitudinal multicenter study of RA patients was conducted from 2009 to 2018. Patients were followed up until January 2021. D2T RA was defined based on EULAR criteria (treatment failure, signs suggestive of currently active/progressive disease, and management being perceived as problematic by the rheumatologist and/or patient). The main outcome was disease activity in the early stages. The covariates were sociodemographic, clinical, and treatment-related factors. We ran a multivariable logistic regression analysis to investigate risk factors associated with progression to D2T RA. Weighting techniques were also applied to balance data.

Results

The study population comprised 631 patients and 35 developed D2T RA. At the time of diagnosis, the D2T RA group were younger, with a higher disability, DAS28 score, tender joint count and pain scores. In our final model, DAS28 was not statistically significantly associated with D2T RA. No differences were found between groups for therapy. Disability was independently associated with D2T RA (OR: 1.50; p=0.02).

Conclusions

In this cohort of patients newly diagnosed with RA, our results do not allow us to prove the influence of active disease according to DAS28. However, we did find that patients with elevated initial disability scores are more likely to develop D2T RA regardless of other factors.

What is already known on this topic

Despite T2T and the availability of a range of advanced therapies, D2T RA remains a relevant clinical problem. Evidence for the D2T RA population have focused on established RA. The aim of our study was to analyze whether disease activity at diagnosis could influence progression to D2T RA under real-life conditions.

What this study adds

We did find that patients with elevated initial disability scores are more likely to develop D2T RA regardless of other factors.

How this study might affect research, practice or policy

The implementation of more effective strategies in the early stages of the disease and focused on the most influential factors, including severe disability, may change disease course and prevent D2T RA.
Mental health, blood pressure and the development of hypertension
Authors: Schaare H. Lina , Blöchl Maria , Kumral Deniz , Uhlig Marie , Lemcke Lorenz , Valk Sofie L. , Villringer Arno
Published: November 2022

Hypertension (HTN) has been associated with a greater risk of affective disorders. Paradoxically, several studies have shown the opposite effect in which high blood pressure relates to less depressive symptoms and greater well-being. Here we dissolve this paradox and clarify the relationship between mental health, blood pressure and the development of HTN using the UK Biobank. In adjusted multiple linear regression models, we found that the presence of a HTN diagnosis was associated with impaired mental health (i.e. more depressive symptoms (N = 303,771; β = 0.043; 95% CI [0.039, 0.047]; p<0.001) and lower well-being scores (N = 129,876; β = -0.057; 95% CI [-0.064, - 0.050]; p<0.001)) at baseline, whereas higher systolic blood pressure (SBP) was associated with fewer depressive symptoms (N = 303,771; β = -0.063; 95% CI [-0.067, -0.060]; p<0.001) and higher well-being scores (N = 129,876; β = 0.057; 95% CI [0.051, 0.063]; p<0.001). These effects persisted until follow-up (∼10 years later). To explore a potential link between the mental health-blood pressure association and the development of HTN, we compared participants who were normotensive at baseline and developed HTN until follow-up with those who stayed normotensive. Notably, the adjusted model showed impaired mental health already at baseline in HTN developers (i.e., before HTN diagnosis; depressive symptoms: β = 0.060; 95% CI [0.045, 0.076]; p<0.001; well-being: β = -0.043; 95% CI [-0.068, -0.017]; p<0.001), indicating that people who develop HTN might require higher blood pressure levels for the same mental health outcomes as normotensives. In addition, the negative association between SBP and depressive symptoms at baseline was moderated by HTN development (β = -0.014; 95% CI [-0.026, -0.003]; p=0.015), suggesting that the negative relationship between mental health and blood pressure was accentuated in people developing HTN several years before receiving their HTN diagnosis. We further observed that higher SBP was associated with lower emotion-related brain activity from functional magnetic resonance imaging (fMRI; β = -0.032 95% CI [-0.045, -0.019]; p<0.001). This effect was also moderated by HTN diagnosis, suggesting an impact of SBP and HTN on the central nervous processing of emotions. Possible mechanisms are discussed, including regulatory baroreceptor circuits linking arterial blood pressure to neural processing of emotions. Overall, our results show an interrelation between mental health and blood pressure that may be involved in the development of HTN. In people who develop HTN, this relationship seems to be altered, such that higher blood pressure is required to sustain mental health, potentially offering a novel perspective for developing preventive and therapeutic measures.
Variation inERAP2has opposing effects on severe respiratory infection and autoimmune disease
Authors: Hamilton Fergus , Mentzer Alexander , Parks Tom , Baillie J Kenneth , Davey Smith George , Ghazal Peter , Timpson Nicholas J
Published: November 2022

Introduction

ERAP2is an aminopeptidase involved in immunological antigen presentation. Genotype data in human samples from before and after the Black Death, an epidemic due toYersinia pestis, have marked changes in population allele frequency of the common single nucleotide polymorphism (SNP) rs2549794. This SNP in strong linkage disequilibrium with a key splicing SNP inERAP2(rs2248374) and this suggests that variation atERAP2may be relevant for protection from infection. rs2549794 is also associated with Crohn’s disease and findings imply balancing selection between infection and autoimmune disease at this locus. There have been no large-scale prospective case-control studies of variation atERAP2and infection.

Methods

This study aimed to explore the association between variation atERAP2and a) infection, b) autoimmune disease, and c) parental longevity as a proxy for lifespan. Genome Wide Association Studies (GWAS) of these outcomes were identified in contemporary cohorts (UK Biobank, FinnGen, and GenOMICC). Effect estimates were extracted for rs2549794 and rs2248374. Additionally,cisexpression and protein quantitative trait loci (QTLs) forERAP2were used in Mendelian randomisation analyses.

Results

Across all cohorts, the T allele (minor allele frequency of 0.4-0.5) of rs2549794 showed evidence of association with respiratory infection (odds ratio; OR for pneumonia 1.03; 95% CI 1.01-1.05; p = 0.014). Effect estimates were larger in bacterial rather than viral infection and larger for more severe phenotypes (OR for critical care admission with pneumonia 1.08; 95% CI 1.02-1.14, p = 0.008, OR for death from pneumonia 1.07; 95% CI 1.01-1.12; p = 0.014). In contrast, opposing effects were identified for Crohn’s disease (OR 0.86; 95% CI 0.82-0.90, p = 8.6 × 10−9) and type 1 diabetes (OR 0.95; 95% CI 0.90-0.99, p = 0.02). No strong evidence for association was identified for sepsis. Carriage of the T allele was associated with increased age of parental death (beta in Z-scored years across both parents age at death 0.01, 95% CI 0.004-0.017, p = 0.002). Similar results were identified for rs2248374.

In Mendelian randomisation analyses, increasing transcription or protein levels ofERAP2were strongly associated with protection from respiratory infection, with opposing effects identified on Crohn’s disease and type 1 diabetes. Increased expression ofERAP2was associated with reduced parental longevity.

Conclusions

Variation atERAP2is associated with severe respiratory infection in modern societies, with an opposing association with Crohn’s disease and type 1 diabetes. These data support the hypothesis that changes in allele frequencies inERAP2observed at the time of the Black Death reflect protection from infection, and suggest ongoing balancing selection at this locus driven by autoimmune and infectious disease
Charting the Fourth Wave: Geographic, Temporal, Race/Ethnicity, and Demographic Trends in Polysubstance Fentanyl Overdose Deaths in the United States, 2010-2021
Authors: Friedman Joseph , Shover Chelsea
Published: November 2022

Aims

To characterize polysubstance death in the United States during the transition to the fourth wave of the overdose crisis. To characterize co-involved substances in fatal overdose involving synthetic opioids (mainly illicitly manufactured fentanyl analogs) by year, state, and intersectional sociodemographic groups.

Design

Population-based cohort study of national death records.

Setting

United States.

Participants/Cases

People who died from drug overdose in the United States between 2010-2021.

Measurements

Percentage of all fatal overdose involving fentanyls, stimulants, and other drugs. Most commonly co-involved substances in fentanyl overdose by state and year. Percentage of fatal fentanyl overdose co-involving stimulants by state and year. Percentage of fatal fentanyl overdose co-involving stimulants by intersectional region, race/ethnicity, age, and sex.

Findings

The percent of US overdose deaths involving both fentanyl and stimulants concurrently rose nearly 60-fold, from 0.6% (n=235) in 2010 to 32.3% (n=34,424) in 2021. In 2010, fentanyl was most commonly found alongside prescription opioids, benzodiazepines, and alcohol. In the Northeast this shifted to heroin-fentanyl co-involvement in the mid-2010s, and nearly universally to cocaine-fentanyl co-involvement by 2021. Universally in the West, and in the majority of states in the South and Midwest, methamphetamine-fentanyl co-involvement predominated by 2021. The proportion of stimulant involvement in fentanyl-involved overdose deaths rose in virtually every state 2015-2021. Cluster analysis reveals particularly high rates for older Black and African American individuals living in the West.

Conclusions

By 2021 stimulants were the most common drug class found in fentanyl-involved overdoses in every state in the US. The rise of deaths involving cocaine and methamphetamine must be understood in the context of a drug market dominated by illicit fentanyls, which have made polysubstance use more desirable and commonplace. The widespread concurrent use of fentanyl and stimulants, as well as other polysubstance formulations, presents novel health risks and public health challenges. Ongoing nuanced surveillance is needed to track this rapidly shifting phenomenon.