Risk Of Medical Conditions Research Articles

The Camden and Islington Viral Hepatitis Identification Tool (CIVHIT): Use of a Clinical Database Case-Finding Tool for Hepatitis B, Hepatitis C and HIV in Primary Care.

Despite the availability of effective treatment and vaccines for hepatitis B virus (HBV) and C virus (HCV), many people are still infected and remain unaware of their infection. The Camden and Islington Viral Hepatitis Identification Tool (CIVHIT), a computer-based search tool, was introduced in 60 general practices (GPs) in April 2014 to support identification, testing and treatment of individuals at high risk for blood-borne viruses (BBVs). CIVHIT searched electronic medical records (EMRs), flagging all those with codes linked to risk factors or medical conditions associated with BBVs. CIVHIT was associated with a 78.5% increase in BBV tests in primary care in both boroughs. This translated to a 55.8% rise in new diagnoses. HBV testing saw the largest increase resulting in twice as many people diagnosed. Only 23.2% of HBV and 14.9% of HCV-positive tests were referred to secondary care. In an index practice, the most common flag was a history of STIs (477/719, 66.3%). Individuals with previous or current drug use and those with a known hepatitis contact were more likely to be offered a test compared to those flagged due to a history of STI. HIV and HBV testing was lower in males following a test offer. There was an increased likelihood of testing for HBV and HCV with increasing age. Additionally, individuals with previous or current drug use and individuals with a known hepatitis contact were more likely to test for HCV compared to individuals flagged due to STI history. CIVHIT shows promise to assist with the elimination of BBVs.

COVID-19 vaccination-induced antibody responses and waning by age and comorbidity status in a large population-based prospective cohort study

BackgroundInformation on the magnitude and duration of antibody levels after COVID-19 vaccination in different groups may be useful for prioritizing of additional vaccinations. MethodsSerum samples were collected every six months in a prospective cohort study among adults in the Netherlands. Geometric mean concentrations (GMCs) of antibodies against the receptor binding domain of the SARS-CoV-2 spike protein were calculated after the primary series, first, and second booster vaccinations. Effects of age (18–59 vs 60–85 years) and medical risk conditions on GMC 2–6 weeks and 21–25 weeks after each vaccination, and on waning during 3–25 weeks after each vaccination, were estimated by linear regression. ResultsWe included 20,640, 15,229 and 8,392 samples collected after primary, first and second booster vaccination, respectively. GMCs at 2–6 and 21–25 weeks after primary series were lower in participants with older age or medical risk conditions. After the first booster, older age was associated with lower GMC at 2–6 weeks and at 21–25 weeks. Waning after the first and second boosters (only 60–85) was not associated with age or medical risk conditions. ConclusionsSince antibody differences by age and medical risk groups have become small with increasing number of doses, other factors such as COVID-19 disease severity rather than antibody levels are useful for prioritization of additional vaccinations.

Association between adverse events after COVID-19 vaccination and anti-SARS-CoV-2 antibody concentrations, the Netherlands, May 2021 to November 2022: a population-based prospective cohort study.

BackgroundNon-severe adverse events (AE) including pain at injection site or fever are common after COVID-19 vaccination.AimTo describe determinants of AE after COVID-19 vaccination and investigate the association between AE and pre- and post-vaccination antibody concentrations.MethodsParticipants of an ongoing prospective cohort study (VASCO) completed a questionnaire on AE within 2 months after vaccination and provided 6 monthly serum samples during May 2021-November 2022. Logistic regression analyses were performed to investigate AE determinants after mRNA vaccination, including pre-vaccination Ig antibody concentrations against the SARS-CoV-2 spike protein receptor binding domain. Multivariable linear regression was performed in SARS-CoV-2-naive participants to assess the association between AE and log-transformed antibody concentrations 3-8 weeks after mRNA vaccination.ResultsWe received 47,947 completed AE questionnaires by 28,032 participants. In 42% and 34% of questionnaires, injection site and systemic AE were reported, respectively. In 2.2% of questionnaires, participants sought medical attention. AE were reported more frequently by women, younger participants (< 60 years), participants with medical risk conditions and Spikevax recipients (vs Comirnaty). Higher pre-vaccination antibody concentrations were associated with higher incidence of systemic AE after the second and third dose, but not with injection site AE or AE for which medical attention was sought. Any AE after the third dose was associated with higher post-vaccination antibody concentrations (geometric mean concentration ratio: 1.38; 95% CI: 1.23-1.54).ConclusionsOur study suggests that high pre-vaccination antibody levels are associated with AE, and experiencing AE may be a marker for higher antibody response to vaccination.

Multifocal Osteonecrosis in Spinal Cord Injury

Dear Editors, Necrosis of the bone marrow and trabecular portion as a result of limited blood flow is known as osteonecrosis (ON) [1]. Several causes have been proposed for the development of ON, including vascular occlusions, ischemia, intravascular coagulation in interosseous tissue, increased intracortical pressure, mechanical stress, precursor cell death, and suppression of angiogenesis. There are multiple risk factors and medical condition associated with ON, including infections, hematological and coagulation problems, connective tissue illnesses, kidney diseases, excessive alcohol and tobacco use, and the use of corticosteroids and cytotoxic drugs [2]. Multifocal osteonecrosis, defined as the presence of osteonecrosis in three or more bone sites, is a rare entity representing less than 3% of osteonecrosis patients [3]. Due to its potent anti-inflammatory properties, methyl prednisolone (MP), one of the most extensively used corticosteroids, has been used for a long time in the acute phase of spinal cord injury and brain edema due to its strong anti-inflammatory properties [4]. Although studies have reported cases of multifocal osteonecrosis (MFON) brought on by corticosteroid medication, this link has never been examined in a patient with a spinal cord injury. This letter aims to highlight MFON that occurred in a patient who underwent acute spinal cord injury and high-dose steroid therapy.

Cis-lunar and surface missions: Health risks and potential surgical conditions

The next goal of human space exploration is to return to the Moon to stay, and to establish a new, more advanced space station in lunar orbit: the ‘Lunar Gateway’. The authors aim to contribute to this goal through undertaking an ongoing comprehensive survey of relevant published scientific literature to seek information regarding the risk of medical conditions that might require operative or non-operative surgical solutions during long-duration spaceflight. The intended outcome is to create a roadmap for future mission planning. To date, we have identified more than 50 such potential surgical conditions. Based on disease severity and mission duration, these can be classified into: (Category 1) Time-critical conditions requiring immediate surgery; (Category 2) Urgent surgical conditions requiring minor temporising surgical intervention or conservative care (these patients can return to Earth for definitive treatment); or (Category 3) Non-urgent, as these conditions do not require immediate surgical intervention, and definitive treatment can be delayed. The proposed Lunar Gateway will be an international collaboration. Reaching Gateway is anticipated to take around three days. Gateway will operate in microgravity conditions, and include a communications lab (ground support from Earth is still available with minimal signal delay), a scientific lab, and a habitat for astronauts. Transfers to and from the lunar surface will allow astronauts to undertake extra-vehicular activities (EVA). Habitation on Gateway will present similar physiological and psychological challenges as experienced on the International Space Station (ISS), with the addition of a slightly increased communications lag. The Moon is only within Earth's magnetosphere for approximately 25 % of the time, which will increase space radiation exposure compared to the ISS. Gravitational conditions will range from microgravity on Gateway to ⅙ of the Earth's gravity on the lunar surface. Considering the duration and distance necessary in order to undertake a lunar mission, time-critical surgical interventions (Category 1) will likely be necessary, such as treating a bowel perforation, or fixation for musculoskeletal trauma. For urgent conditions (Category 2), antibiotic treatment of responsive appendicitis, drainage of uncomplicated cholecystitis, or other conservative measures might be acceptable as a temporising measure. If a return to Earth is possible within three days, delayed surgery can be undertaken if the conservative measures are unsuccessful, or the condition recurs. In the case of non-urgent procedures that can be delayed (Category 3), planned evacuation to Earth is expected to be available, for example, if a malignancy develops or is detected. Anticipating the medical and surgical challenges a lunar mission presents, and subsequent adequate planning and preparation for possible surgical emergencies, will help ensure mission success. Creating a system for triaging of surgical cases will be paramount in order to guide appropriate management.

Overview of Radar-Based Gait Parameter Estimation Techniques for Fall Risk Assessment.

Current methods for fall risk assessment rely on Quantitative Gait Analysis (QGA) using costly optical tracking systems, which are often only available at specialized laboratories that may not be easily accessible to rural communities. Radar placed in a home or assisted living facility can acquire continuous ambulatory recordings over extended durations of a subject's natural gait and activity. Thus, radar-based QGA has the potential to capture day-to-day variations in gait, is time efficient and removes the burden for the subject to come to a clinic, providing a more realistic picture of older adults' mobility. Although there has been research on gait-related health monitoring, most of this work focuses on classification-based methods, while only a few consider gait parameter estimation. On the one hand, metrics that are accurately and easily computable from radar data have not been demonstrated to have an established correlation with fall risk or other medical conditions; on the other hand, the accuracy of radar-based estimates of gait parameters that are well-accepted by the medical community as indicators of fall risk have not been adequately validated. This paper provides an overview of emerging radar-based techniques for gait parameter estimation, especially with emphasis on those relevant to fall risk. A pilot study that compares the accuracy of estimating gait parameters from different radar data representations - in particular, the micro-Doppler signature and skeletal point estimates - is conducted based on validation against an 8-camera, marker-based optical tracking system. The results of pilot study are discussed to assess the current state-of-the-art in radar-based QGA and potential directions for future research that can improve radar-based gait parameter estimation accuracy.

Association between positive blood culture and clinical outcomes among children treated for sepsis in the emergency department

ObjectiveAmong children treated for sepsis in a pediatric emergency department (ED), compare clinical features and outcomes between those with blood cultures positive versus negative for a bacterial pathogen. DesignSingle-center retrospective cohort study. SettingPediatric emergency department (ED) at a quaternary pediatric care center. PatientsChildren aged 0–18 years treated for sepsis defined by the Children's Hospital Association's Improving Pediatric Sepsis Outcomes (IPSO) definition. InterventionsNone. Measurements and main resultsWe analyzed 1307 patients treated for sepsis during the study period, of which 117 (9.0%) had blood cultures positive for a bacterial pathogen. Of children with blood culture positive sepsis, 62 (53.0%) had organ dysfunction compared to 514 (43.2%) with culture negative sepsis (adjusted odds ratio 1.56, 95% confidence interval (CI) 1.04–2.34, adjusting for age, high risk medical conditions, and time to antibiotics). Children with blood culture positive sepsis had a larger base deficit, −4 vs −1 (p < 0.01), and higher procalcitonin, 3.84 vs 0.56 ng/mL (p < 0.01). ConclusionsChildren meeting the IPSO Sepsis definition with blood culture positive for a bacterial pathogen have higher rates of organ dysfunction than those who are culture negative, although our 9% rate of blood culture positivity is lower than previously cited literature from the pediatric intensive care unit.

Primary Care Management Pathways to Reduce Wait Times in Hematology: Monoclonal Gammopathy of Undetermined Significance

Background:Prolonged wait times are a worsening barrier to accessing specialist care in Canada and other countries across the globe. The flow of patients between primary care and specialists has been a recognized area for improvement (Liddy et al., 2020; Moir &amp; Barua, 2021). Kingston Health Sciences Centre (KHSC) has aimed to optimize referrals through the implementation of primary care management pathways (PCMPs). PCMPs are diagnostic and/or treatment algorithms, co-developed by local primary care physicians and specialists with input from patients. They are designed to support primary care providers in managing low risk medical conditions in the community while more quickly identifying patients with higher risk conditions to be seen by specialists. A PCMP was implemented in June 2021 for Monoclonal Gammopathy of Undetermined Significance (MGUS) (https://kingstonhsc.ca/refer/hematology). This asymptomatic condition with low levels of monoclonal protein in the blood or urine has an approximately 1% per year risk of transforming to a hematological malignancy such as multiple myeloma (Kyle et al., 2018). The MGUS PCMP outlines diagnostic criteria, management, and monitoring instructions for low-risk MGUS along with patient information. “Red flag” features, such as renal impairment, anemia or significantly increased monoclonal protein levels, are used to highlight those who need urgent referral. The aim of this study is to evaluate the impact of an MGUS PCMP on wait times in Hematology in Kingston, Ontario. Methods:All consecutive outpatient Hematology referrals received at KHSC from January 2021 to December 2022 were reviewed. Monthly outcome measures included the number of new referrals and median wait times for patients seen. Number of MGUS referrals deferred to the PCMP was included as a process measure. Monthly balancing measures included number of re-referrals of PCMP patients, number of deaths without being seen for MGUS, and number of new multiple myeloma diagnoses. To compare 6-month pre-PCMP implementation (January 2021 to June 2021) with 18-month post-PCMP implementation (July 2021 to December 2022), generalized linear regression analysis was conducted. p &amp;lt; 0.05 was considered statistically significant. A survey of primary care providers was distributed through the regional Primary Care Physicians' Council to assess primary care satisfaction with the PCMP. Results: Between January 2021 and December 2022, 4504 Hematology referrals were received, 278 (6%) of which were MGUS referrals. 76 (27%) of MGUS referrals were deferred to the PCMP. There was a significant increase in monthly Hematology referrals from a mean (± standard deviation (SD)) of 163.0 (± 13.9) pre-PCMP to 195.9 (± 27.3) post-PCMP (p&amp;lt;0.0001). There was no significant difference in mean monthly MGUS referrals pre-and post-PCMP (11.7 ± 4.7 versus 11.6 ± 3.5). Hematology's median wait time for those seen fell from a median (interquartile range (IQR)) of 51.3 days (13) pre-PCMP to 28.5 days (11) post-PCMP (p &amp;lt; 0.0001). The MGUS median wait time also fell from a median (IQR) of 40.5 days (59) to 37.0 days (32.5) (p &amp;lt; 0.0001). No significant difference was noted in the balancing measures. Pre-PCMP to post-PCMP, the mean number of deaths without being seen for MGUS (0.17 ± 0.41 versus 0.17 ± 0.38, p=0.36) and mean monthly new multiple myeloma diagnoses (5.17 ± 1.94 versus 5.17 ± 2.50, p = 0.54) remained stable. There were 7/76 (9.2%) re-referrals of patients deferred to the PCMP, with a median (IQR) time to re-referral of 64 days (348). A survey to assess primary care provider satisfaction with the PCMP included a total of 28 respondents; 19/28 (67.9%) reported using PCMPs. On a scale of 0 to 5, where 5 is the highest satisfaction, the median (IQR) overall experience was 4/5 (1.5) and impacts on supporting patient care and changing management were also 4/5 (1). The most common concern, raised by 7/28 respondents (25%), was the downloading of more work to primary care. Conclusion: The MGUS PCMP was associated with reduction in wait times for overall Hematology and MGUS despite an increase in referrals. Limitations of this study include concurrent changes in the program, including staffing and the COVID-19 pandemic. These results suggest that PCMPs may be an effective tool to address Hematology wait times, likely best complemented with other strategies to avoid overburdening primary care providers.

The Multiplexed Opsonophagocytosis Killing Assay (MOPA) in Evaluating Specific Antibody Responses in Patients with Recurrent Infections

Assessments of antibody responses to vaccines are essential tools for evaluating humoral immune responses in subjects with suspected inborn errors of immunity (IEI). Low pneumococcal IgG levels following pneumococcal vaccination indicate suboptimal humoral immune function and are often used for diagnosis of IEI. The Multiplexed Opsonophagocytosis Assay (MOPA) measures pneumococcal antibody function (PAF) via killing of pneumococci by serum antibodies in vitro. MOPA may also be useful for clinical diagnosis but has not been studied in patients with suspected IEI. We aimed to compare PAF and Streptococcus pneumoniae IgG levels in patients with recurrent infections. We also evaluated the clinical history and other immune workup results, when available. We collected serum samples from n = 17 patients with a history of recurrent infections undergoing pneumococcal IgG measurements by their primary clinical immunologists. Baseline sera (prior to vaccine challenge) were analyzed for PAF, for the serotypes present in pneumococcal conjugate vaccine (PCV13), and S. pneumoniae 23 serotypes IgG levels using MOPA and a multiplexed bead array assay, respectively. The cohort includes subjects from 2 to 60 years of age, 53% females, 94% Caucasian, and 30% Hispanic. Preliminary results show that 76% patients had protective PAF for 85% or more of the tested serotypes. Of these, 69% patients had received a pneumococcal vaccine in the previous five years as an indication for an underlying high risk medical condition or as part of their immunization schedule. Protective results for serotypes 3, 4, 9V, and 18C were discrepant between IgG levels and PAF in more than 50% of patients. We also found discrepancy between PAF and antibody levels in 35% of patients, showing intact PAF for 5 or more serotypes despite low serotype IgG levels; 83% of whom had no significant sinopulmonary infections in the last year. MOPA analysis between pre and post pneumococcal vaccine administration, in those patients for which it is clinically indicated, is currently in process. This analysis may provide more information regarding the diagnostic performance and predictive value of MOPA in patients with suspected IEI, but preliminary data shows that MOPA might be more reflective of protection than S. pneumonia IgG levels.

Short Message Service Reminder Nudge for Parents and Influenza Vaccination Uptake in Children and Adolescents With Special Risk Medical Conditions

Children with chronic medical conditions are at increased risk of severe influenza. Uptake of influenza vaccination in children and adolescents with these identified special risk medical conditions (SRMCs) is suboptimal. To assess the effectiveness of Flutext-4U, a parent short message service (SMS) reminder nudge intervention, in increasing influenza immunization in children and adolescents with SRMCs. This randomized clinical trial was conducted at a tertiary pediatric hospital in Adelaide, South Australia, from April 15 to September 30, 2021. Children and adolescents aged 6 months to younger than 18 years with SRMCs and a subspecialist outpatient appointment over a 5-month period during the Australian seasonal influenza vaccination season (April-August 2021) were eligible to participate. Follow-up was until September 30, 2021. Participants were randomly assigned (1:1 ratio) to control: clinician nudges (hospital vaccine availability, ease of access, and recommendation from hospital subspecialists) or SMS intervention (control conditions plus an additional SMS reminder nudge to parents), with randomization stratified by age group (<5 years, 5-14 years, or >14 to <18 years). The primary outcome was influenza vaccination, as confirmed by the Australian Immunisation Register. A total of 600 participants (intervention group: 298 [49.7%]; mean [SD] age, 11.5 [4.6] years; 162 female participants [54.4%]; control group: 302 [50.3%]; mean [SD] age, 11.4 [4.7] years; 155 female participants [51.3%]) were included. Influenza vaccination was 38.6% (113 of 293) in the SMS intervention group compared with 26.2% (79 of 302) in the control group (adjusted odds ratio [aOR], 1.79; 95% CI, 1.27-2.55; P = .001). Time to vaccine receipt was significantly lower among SMS participants (adjusted hazard ratio, 1.67; 95% CI, 1.25-2.22; P < .001). For participants randomly assigned by June 15, a significantly greater proportion receiving the SMS intervention were vaccinated during the optimal delivery period April to June 30 (SMS group: 40.0% [76 of 190] vs 25.4% [50 of 197]; aOR, 1.97; 95% CI, 1.28-3.06; P = .002). Results of this randomized clinical trial suggest that an additional SMS reminder nudge for parents delivered in the tertiary care hospital setting to children and adolescents with SMRCs resulted in higher influenza vaccine uptake compared with clinician nudges alone. ANZCTR Identifier: ACTRN12621000463875.

Spatio-temporal Graph Learning for Epidemic Prediction

The COVID-19 pandemic has posed great challenges to public health services, government agencies, and policymakers, raising huge social conflicts between public health and economic resilience. Policies such as reopening or closure of business activities are formulated based on scientific projections of infection risks obtained from infection dynamics models. Though most parameters in epidemic prediction service models can be set with domain knowledge of COVID-19, a key parameter, namely, human mobility, is often challenging to estimate due to complex spatio-temporal correlations and social contexts under escalating COVID-19 facilities. Moreover, how to integrate the various implicit features to accurately predict infectious cases is still an open issue. To address this challenge, we formulate the problem as a spatio-temporal network representation problem and propose STEP, a Spatio-Temporal Epidemic Prediction framework, to estimate pandemic infection risk of a city by integrating various real-world conditions (e.g., City Risk Index, climate, and medical conditions) into graph-structured data. We also employ a multi-head attention mechanism in representation learning to extract implicit features for a given city. Extensive experiments have been conducted upon the real-world dataset for 51 states (50 states and Washington, D.C.) of the USA. Experimental results show that STEP can yield more accurate pandemic infection risk estimation than baseline methods. Moreover, STEP outperforms other methods in both short-term and long-term prediction.

Medical conditions associated with coffee consumption: Disease-trajectory and comorbidity network analyses of a prospective cohort study in UK Biobank

ABSTRACTBackgroundHabitual coffee consumption has been associated with multiple health benefits. A comprehensive analysis of disease trajectory and comorbidity networks in relation to coffee consumption is, however, currently lacking.ObjectivesWe aimed to comprehensively examine the health outcomes associated with habitual coffee consumption, through clarifying its disease trajectory and comorbidity networks.MethodsBased on the UK Biobank cohort, we included 395,539 individuals with available information on coffee intake collected at recruitment between 2006 and 2010. These individuals were categorized as having low (<1 cup per day), moderate (1–3 cups), and high (≥4 cups) levels of coffee intake, and were followed through 2020 to ascertain 496 medical conditions. Cox regression was used to assess the associations between high-level coffee intake and the risk of medical conditions with a prevalence ≥0.5% in the study population, after adjusting for multiple confounders, using low-level coffee intake as the reference. Disease-trajectory and comorbidity network analyses were then applied to visualize the temporal and nontemporal relationships between the medical conditions that had an inverse association with high-level coffee intake.ResultsDuring a median follow-up of 11.8 years, 31 medical conditions were found to be associated with high-level coffee intake, among which 30 showed an inverse association (HRs ranged from 0.61 to 0.94). The inverse associations were more pronounced for women, compared with men. Disease-trajectory and comorbidity network analyses of these 30 conditions identified 4 major clusters of medical conditions, mainly in the cardiometabolic and gastrointestinal systems, among both men and women; 1 cluster of medical conditions following alcohol-related disorders, primarily among men; as well as a cluster of estrogen-related conditions among women.ConclusionsHabitual coffee consumption was associated with lower risks of many medical conditions, especially those in the cardiometabolic and gastrointestinal systems and those related to alcohol use and estrogen regulation.

COVID-19 Vaccination and Intent for Vaccination of Adults With Reported Medical Conditions

IntroductionIndividuals with certain medical conditions are at substantially increased risk for severe illness from COVID-19. The purpose of this study is to assess COVID-19 vaccination among U.S. adults with reported medical conditions.MethodsData from the National Immunization Survey-Adult COVID Module collected during August 1–September 25, 2021 were analyzed in 2022 to assess COVID-19 vaccination status, intent, vaccine confidence, behavior, and experience among adults with reported medical conditions. Unadjusted and age-adjusted prevalence ratios (PRs and APRs) were generated using logistic regression and predictive marginals.ResultsOverall, COVID-19 vaccination coverage with ≥1 dose was 81.8% among adults with reported medical conditions, and coverage was significantly higher compared with those without such conditions (70.3%) Among adults aged ≥18 years with medical conditions, COVID-19 vaccination coverage was significantly higher among those with a provider recommendation (86.5%) than those without (76.5%). Among all respondents, 9.2% of unvaccinated adults with medical conditions reported they were willing or open to vaccination. Adults who reported high risk medical conditions were more likely to report receiving a provider recommendation, often or always wearing masks during the last 7 days, concerning about getting COVID-19, thinking the vaccine is safe, and believing a COVID-19 vaccine is important for protection from COVID-19 infection than those without such conditions.ConclusionsApproximately 18.0% of those with reported medical conditions were unvaccinated. Receiving a provider recommendation was significantly associated with vaccination, reinforcing that provider recommendation is an important approach to increase vaccination coverage. Ensuring access to vaccine, addressing vaccination barriers, and increasing vaccine confidence can improve vaccination coverage among unvaccinated adults.

068 Is MRKH a barrier for regular gynecologic care?

Objective: Evaluate the frequency of visits to the gynecologist of patients with Mayer-Rokitansky-Küster-Hauser (MRKH) and assess the prevalence of risk factors and medical conditions that would benefit from regular gynecologic care.

SARS‐CoV‐2 vaccine clinical efficacy in SOT: What we know and our current gaps

SARS‐CoV‐2 vaccine clinical efficacy in SOT: What we know and our current gaps

Using provider–parent strategies to improve influenza vaccination in children and adolescents with special risk medical conditions: a randomised controlled trial protocol

IntroductionInfluenza immunisation is a highly cost-effective public health intervention. Despite a comprehensive National Immunisation Program, influenza vaccination in children and adolescents with special risk medical conditions (SRMCs) is suboptimal. Flutext-4U...

The miR-4739/DLX3 Axis Modulates Bone Marrow-Derived Mesenchymal Stem Cell (BMSC) Osteogenesis Affecting Osteoporosis Progression.

Osteoporosis is a complex multifactorial disorder linked to various risk factors and medical conditions. Bone marrow-derived mesenchymal stem cell (BMSC) dysfunction potentially plays a critical role in osteoporosis pathogenesis. Herein, the study identified that miR-4739 was upregulated in BMSC cultures harvested from osteoporotic subjects. BMSCs were isolated from normal and osteoporotic bone marrow tissues and identified for their osteogenic differentiation potential. In osteoporotic BMSCs, miR-4739 overexpression significantly inhibited cell viability, osteoblast differentiation, mineralized nodule formation, and heterotopic bone formation, whereas miR-4739 inhibition exerted opposite effects. Through direct binding, miR-4739 inhibited distal-less homeobox 3 (DLX3) expression. In osteoporotic BMSCs, DLX3 knockdown also inhibited BMSC viability and osteogenic differentiation. Moreover, DLX3 knockdown partially attenuated the effects of miR-4739 inhibition upon BMSCs. Altogether, the miR-4739/DLX3 axis modulates the capacity of BMSCs to differentiate into osteoblasts, which potentially plays a role in osteoporosis pathogenesis. The in vivo and clinical functions of the miR-4739/DLX3 axis require further investigation.

Rotavirus Vaccine Safety and Effectiveness in Infants With High-Risk Medical Conditions.

Rotavirus vaccination has 87% to 100% effectiveness against severe rotavirus acute gastroenteritis (AGE) in healthy infants in high-income countries. Little is known whether infants with medical risk conditions (MRCs) are equally protected and if the vaccine is equally well tolerated. We conducted a quasi-experimental prospective multicenter before-after cohort study to assess the vaccine effectiveness (VE) and safety profile of the human rotavirus vaccine (HRV) among MRC infants that required prolonged or frequent postnatal care. The Netherlands has no national rotavirus immunization program, but HRV was implemented in routine care for MRC infants in 13 Dutch hospitals. Participants in the before and after cohort, HRV unvaccinated and vaccinated, respectively, were followed for occurrence of (rotavirus) AGE. VE of at least 1 dose was estimated by using time-to-event analysis for severe rotavirus AGE. Vaccine-related serious adverse event (AEs) after HRV were retrieved systematically from medical charts. Solicited AEs after vaccinations were prospectively collected and compared between vaccination time points with or without HRV. In total, 1482 high-risk infants with MRC were enrolled, including 631 in the before and 851 in the after cohorts; 1302 infants were premature (88.3%), 447 were small for gestational age (30.2%), and 251 had at least 1 congenital disorder (17.0%). VE against severe rotavirus AGE was 30% (95% confidence interval [CI]: -36% to 65%). Overall, the observed number of rotavirus hospitalizations was low and not significantly different between the cohorts (2 and 2, respectively). The rate of vaccine-related serious AE was 0.24 per 100 vaccine doses. The adjusted risk ratio for any AE after HRV vaccination compared with other routine vaccinations was 1.09 (95% CI: 1.05 to 1.12) for concomitant administration and 0.91 (95% CI: 0.81 to 0.99) for single HRV administration. Gastrointestinal AEs were 10% more frequent after HRV. In contrast to previous findings among healthy term infants, in routine use, HRV offered limited protection to vulnerable medical risk infants. HRV is generally well tolerated in this group in single administration, but when coadministered with routine vaccines, it is associated with higher risk of (mostly gastrointestinal) AE. Our study highlights the importance of studying vaccine performance in subgroups of medically vulnerable infants.

Evaluation of non-specific effects of human rotavirus vaccination in medical risk infants

BackgroundThe WHO recommends research into non-specific effects of vaccination. For rotavirus vaccines, these have not yet been well established. We studied non-specific effects up to 18 months of age using data from a quasi-experimental before-after study comparing cohorts of rotavirus vaccinated and unvaccinated infants with medical risk conditions. MethodsInfants were enrolled at six weeks of age before and after a stepped-wedge implementation of a hospital-based risk-group rotavirus vaccination program. Other infant vaccinations were administered according to the Dutch National Immunization Program and similar in both cohorts. Non-specific effect outcomes were prospectively collected using monthly questionnaires and included acute hospitalization (excluding for acute gastroenteritis), monthly incidence of acute respiratory illness and eczema. We used time-to-event analysis and negative binomial regression to assess the effect of at least one dose of rotavirus vaccination for each of these outcomes.FindingsThe analysis included 496 rotavirus unvaccinated and 719 vaccinated medical risk infants. In total, 1067 (88%) were premature, 373 (31%) small for gestational age and 201 (17%) had a congenital pathology. The adjusted hazard ratio for first acute hospitalization was 0·91 (95 %CI 0·76;1·16) for rotavirus vaccinated versus unvaccinated infants. Adjusted incidence rate ratio for acute respiratory illness was 1·05 (95 %CI 0·96;1·15) and for eczema 0·89 (95 %CI 0·69;1·15). ConclusionThe results suggest no, or minimal non-specific effects from rotavirus vaccination on acute hospitalization, acute respiratory illness or eczema in medical risk infants.Trial registration: as NTR5361 in the Dutch trial registry, www.trialregister.nl.

Dietary intake of creatine and risk of medical conditions in U.S. older men and women: Data from the 2017-2018 National Health and Nutrition Examination Survey.

We examined dietary intake of creatine in U.S. men and women aged 65 years and over, and evaluated the association between creatine intake and risk of self‐reported medical conditions, and physical functioning/disability variables using data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES). The NHANES 2017–2018 target population included the noninstitutionalized civilian resident population of the United States aged 65 years and over. Detailed dietary intake data from NHANES elderly were obtained by dietary interview component through a 24‐h dietary recall interview, with estimated individual values for total grams of creatine consumed per day for each respondent. A threshold for dietary intake of creatine used to calculate risk between creatine intake and medical conditions was set at 1.00 g/day. The sample population included 1500 participants aged 65 years and older, of which 1221 individuals (627 men and 594 women) provided detailed dietary data via a dietary interview. Creatine intake across all participants was 0.76 ± 0.79 g/day (95% CI from 0.72 to 0.81). As much as 70% of U.S. elderly consume <1.00 g of creatine per day, with about 1 in 5 individuals (19.8%) consume no creatine at all. Elderly with the suboptimal intake of creatine were found to have 2.62 times higher risk of angina pectoris (adjusted OR = 2.62, 95% CI from 1.14 to 6.01, p = .023) and 2.59 times higher risk of liver conditions (adjusted OR = 2.59, 95% CI from 1.23 to 5.48, p = .013), compared with older counterparts who consume ≥1.00 g of creatine per day after controlling for demographic and nutritional variables. The considerable shortage of dietary creatine is associated with an increased risk of heart and liver conditions, which calls for public measures that foster diets rich in creatine‐containing foods, and additional research to investigate the role of creatine in age‐related diseases.