Impact of Dementia Behavioral Crises Events on First Responder and Family Systems in Idaho: An Exploratory Study

Enhancing quality of life for people with dementia is identified in Healthy People 2020 as a public health priority. In Idaho, the proportion of individuals diagnosed with Alzheimer’s disease and related dementias (ADRD) is projected to increase by 81 % - 127 % between 2000 and 2025. Policies designed to address needs of this population must be based on an understanding of system wide impacts of disease. The purpose of this exploratory study was to examine the impact of behavioral crises related to dementia on first responders. For the purpose of this study, “first responders” were defined as individuals employed by the Idaho Department of Health and Welfare Mobile Crisis Unit in Regions 1, 3, and 4, Ada County Paramedics/EMS, and social workers employed in health care settings in the Treasure Valley. A mixed methods design was used with information gathered from incident reports from the Ada County Paramedics and focus groups and interviews with key informants. Ada County Paramedics/EMS receives approximately 22,000 calls annually with 924 of calls related to behavioral crisis involving individuals with ADRD. Most calls were from assisted living facilities (n=401), home (n=290), or skilled nursing facilities (n=181). The majority (80%) of calls resulted in transport to a hospital emergency department (ED); none of the calls required use of lights or siren. Annual costs of calls to EMS and ED were estimated to be $457,380 and$905,020, respectively. Themes from key informants included: an increase in number and complexity of calls; lack of appropriate protocols within systems to support individual in crisis or their family or caregiver; and need for training on progression of ADRD and de-escalation strategies

Virtual follow-up care among breast and prostate cancer patients during and beyond the COVID-19 pandemic: association with distress

Background: The purpose of this study was to investigate associations between self-reported distress (anxiety/depression) and satisfaction with and desire for virtual follow-up (VFU) care among cancer patients during and beyond the COVID-19 pandemic. Methods: Breast and prostate cancer patients receiving VFU at an urban cancer centre in Toronto, Canada completed an online survey on their sociodemographic, clinical, and technology, characteristics and experience with and views on VFU. EQ5D-5 L was used to assess distress. Statistical models adjusted for age, gender, education, income and Internet confidence. Results: Of 352 participants, average age was 65 years, 48% were women,79% were within 5 years of treatment completion, 84% had college/university education and 74% were confident Internet users. Nearly, all (98%) had a virtual visit via phone and 22% had a virtual visit via video. The majority of patients (86%) were satisfied with VFU and 70% agreed that they would like VFU options after the COVID-19 pandemic. Participants who reported distress and who were not confident using the Internet for health purposes were significantly less likely to be satisfied with VFU (OR = 0.4; 95% CI: 0.2–0.8 and OR = 0.19; 95% CI: 0.09–0.38, respectively) and were less likely to desire VFU option after the COVID-19 pandemic (OR = 0.49; 95% CI: 0.30–0.82 and OR = 0.41; 95% CI: 0.23–0.70, respectively). Conclusions: The majority of respondents were satisfied with VFU and would like VFU options after the COVID-19 pandemic. Future research should determine how to optimize VFU options for cancer patients who are distressed and who are less confident using virtual care technology

Silac mouse for quantitative proteomics uncovers kindlin-3 as an essential factor for red blood cell function

Stable isotope labeling by amino acids in cell culture (SILAC) has become a versatile tool for quantitative, mass spectrometry (MS)-based proteomics. Here, we completely label mice with a diet containing either the natural or the 13C6-substituted version of lysine. Mice were labeled over four generations with the heavy diet, and development, growth, and behavior were not affected. MS analysis of incorporation levels allowed for the determination of incorporation rates of proteins from blood cells and organs. The F2 generation was completely labeled in all organs tested. SILAC analysis from various organs lacking expression of β1 integrin, β-Parvin, or the integrin tail-binding protein Kindlin-3 confirmed their absence and disclosed a structural defect of the red blood cell membrane skeleton in Kindlin-3-deficient erythrocytes. The SILAC-mouse approach is a versatile tool by which to quantitatively compare proteomes from knockout mice and thereby determine protein functions under complex in vivo conditions

The impact of pregnancy on the pharmacokinetics of antiseizure medications:A systematic review and meta-analysis of data from 674 pregnancies

Objective: Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment outcomes. The aim of this study was to quantify the pregnancy impact on the ASM pharmacokinetics. Methods: A systematic literature search was conducted in PubMed/EMBASE in November 2022 and updated in August 2023 for studies comparing levels of ASM in the same individuals during pregnancy and in the preconception/postpartum period. Alteration ratios between the 3rd trimester and baseline were estimated. We also performed a random-effects meta-analysis calculating between-timepoint differences in mean differences (MDs) and 95% confidence intervals (95%CIs) for dose-adjusted plasma concentrations (C/D ratios). Study quality was assessed using the ClinPK guidelines. Results: A total of 65 studies investigating 15 ASMs in 674 pregnancies were included. The largest differences were reported for lamotrigine, oxcarbazepine and levetiracetam (alteration ratio 0.42, range 0.07–2.45, 0.42, range 0.08–0.82 and 0.52, range 0.04–2.77 respectively): accordingly, C/D levels were lower in the 3rd trimester for lamotrigine, levetiracetam and the main oxcarbazepine metabolite monohydroxycarbazepine (MD = -12.33 × 10−3, 95%CI = -16.08 to −8.58 × 10−3 (μg/mL)/(mg/day), p &lt; 0.001, MD = -7.16 (μg/mL)/(mg/day), 95%CI = -9.96 to −4.36, p &lt; 0.001, and MD = -4.87 (μg/mL)/(mg/day), 95%CI = -9.39 to −0.35, p = 0.035, respectively), but not for oxcarbazepine (MD = 1.16 × 10−3 (μg/mL)/(mg/day), 95%CI = -2.55 to 0.24 × 10−3, p = 0.10). The quality of studies was acceptable with an average rating score of 11.5. Conclusions: Data for lamotrigine, oxcarbazepine (and monohydroxycarbazepine) and levetiracetam demonstrate major changes in pharmacokinetics during pregnancy, suggesting the importance of therapeutic drug monitoring to assist clinicians in optimizing treatment outcomes.</p

The impact of pregnancy on the pharmacokinetics of antiseizure medications:A systematic review and meta-analysis of data from 674 pregnancies

Objective: Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment outcomes. The aim of this study was to quantify the pregnancy impact on the ASM pharmacokinetics. Methods: A systematic literature search was conducted in PubMed/EMBASE in November 2022 and updated in August 2023 for studies comparing levels of ASM in the same individuals during pregnancy and in the preconception/postpartum period. Alteration ratios between the 3rd trimester and baseline were estimated. We also performed a random-effects meta-analysis calculating between-timepoint differences in mean differences (MDs) and 95% confidence intervals (95%CIs) for dose-adjusted plasma concentrations (C/D ratios). Study quality was assessed using the ClinPK guidelines. Results: A total of 65 studies investigating 15 ASMs in 674 pregnancies were included. The largest differences were reported for lamotrigine, oxcarbazepine and levetiracetam (alteration ratio 0.42, range 0.07–2.45, 0.42, range 0.08–0.82 and 0.52, range 0.04–2.77 respectively): accordingly, C/D levels were lower in the 3rd trimester for lamotrigine, levetiracetam and the main oxcarbazepine metabolite monohydroxycarbazepine (MD = -12.33 × 10−3, 95%CI = -16.08 to −8.58 × 10−3 (μg/mL)/(mg/day), p &lt; 0.001, MD = -7.16 (μg/mL)/(mg/day), 95%CI = -9.96 to −4.36, p &lt; 0.001, and MD = -4.87 (μg/mL)/(mg/day), 95%CI = -9.39 to −0.35, p = 0.035, respectively), but not for oxcarbazepine (MD = 1.16 × 10−3 (μg/mL)/(mg/day), 95%CI = -2.55 to 0.24 × 10−3, p = 0.10). The quality of studies was acceptable with an average rating score of 11.5. Conclusions: Data for lamotrigine, oxcarbazepine (and monohydroxycarbazepine) and levetiracetam demonstrate major changes in pharmacokinetics during pregnancy, suggesting the importance of therapeutic drug monitoring to assist clinicians in optimizing treatment outcomes.</p

Smoking, nicotine and pregnancy 2 (SNAP2) trial: protocol for a randomised controlled trial of an intervention to improve adherence to nicotine replacement therapy during pregnancy

Introduction: Smoking during pregnancy is harmful to unborn babies, infants and women. Nicotine replacement therapy (NRT) is offered as the usual stop-smoking support in the UK. However, this is often used in insufficient doses, intermittently or for too short a time to be effective. This randomised controlled trial (RCT) explores whether a bespoke intervention, delivered in pregnancy, improves adherence to NRT and is effective and cost-effective for promoting smoking cessation. Methods and analysis: A two-arm parallel-group RCT was conducted for pregnant women aged ≥16 years and who smoke ≥1 daily cigarette (pre-pregnancy smoked ≥5) and who agree to use NRT in an attempt to quit. Recruitment is from antenatal care settings and via social media adverts. Participants are randomised using blocked randomisation with varying block sizes, stratified by gestational age (<14 or ≥14 weeks) to receive: (1) usual care (UC) for stop smoking support or (2) UC plus an intervention to increase adherence to NRT, called ‘Baby, Me and NRT’ (BMN), comprising adherence counselling, automated tailored text messages, a leaflet and website. The primary outcome is biochemically validated smoking abstinence at or around childbirth, measured from 36 weeks gestation. Secondary outcomes include NRT adherence, other smoking measures and birth outcomes. Questionnaires collect follow-up data augmented by medical record information. We anticipate quit rates of 10% and 16% in the control and intervention groups, respectively (risk ratio=1.6). By recruiting 1320 participants, the trial should have 90% power (alpha=5%) to detect this intervention effect. An economic analysis will use the Economics of Smoking in Pregnancy model to determine cost-effectiveness. Ethics and dissemination: Ethics approval was granted by Bloomsbury National Health Service’s Research Ethics Committee (21/LO/0123). Written informed consent will be obtained from all participants. Findings will be disseminated to the public, funders, relevant practice/policy representatives, researchers and participants. Trial registration number: ISRCTN16830506. Protocol version: 5.0, 10 Oct 2023

Enhanced methods for unbiased deep sequencing of Lassa and Ebola RNA viruses from clinical and biological samples

We have developed a robust RNA sequencing method for generating complete de novo assemblies with intra-host variant calls of Lassa and Ebola virus genomes in clinical and biological samples. Our method uses targeted RNase H-based digestion to remove contaminating poly(rA) carrier and ribosomal RNA. This depletion step improves both the quality of data and quantity of informative reads in unbiased total RNA sequencing libraries. We have also developed a hybrid-selection protocol to further enrich the viral content of sequencing libraries. These protocols have enabled rapid deep sequencing of both Lassa and Ebola virus and are broadly applicable to other viral genomics studies. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0519-7) contains supplementary material, which is available to authorized users