Cognitive and brain function in adults with Type 1 diabetes mellitus : is there evidence of accelerated ageing?

The physical complications of Type 1 diabetes mellitus (T1DM) have been understood as an accelerated ageing process (Morley, 2008). Do people with T1DM also experience accelerated cognitive and brain ageing? Using findings from research of the normal cognitive and brain ageing process and conceptualized in theories of the functional brain changes in cognitive ageing, a combination of cognitive testing and functional magnetic resonance imaging (fMRI) techniques were used to evaluate evidence of accelerated cognitive and brain ageing in middle-aged adults with T1DM. The first part of this thesis comprises a cognitive study of 94 adults (≥ 45 years of age) with long duration (≥ 10 years) of T1DM. Participants completed cognitive assessment and questionnaires on general mood and feelings about living with diabetes. Findings highlighted the importance of microvascular disease (specifically retinopathy) as an independent predictor of cognitive function. The incidence and predictors of mild cognitive impairment (MCI) were then explored. Results indicate a higher percentage of the group met criteria for MCI than expected based on incidence rates in the general population, providing initial evidence of accelerated cognitive ageing. Psychological factors were explored next. The relationship between the measures of well-being, diabetes health, and cognitive function highlighted the need for attention to patient’s psychological well-being in diabetes care. Finally, a subgroup of 30 participants between the ages of 45 and 65 who differed on severity of retinopathy were selected to take part in an fMRI study. Blood oxygen level dependent (BOLD) activity was evaluated while participants were engaged in cognitive tasks and during rest. The findings provided evidence that the pattern of BOLD activation and functional connectivity for those with high severity of retinopathy are similar to patterns found in adults over the age of 65. In line with the theories of cognitive ageing, functional brain changes appear to maintain a level of cognitive function. Evidence of accelerated brain ageing in this primarily middle-aged group, emphasizes the importance of treatments and regimens to prevent or minimize microvascular complications.

Identification and assessment of intimate partner violence in nurse home visitation

Aims and objectives: To develop strategies for the identification and assessment of intimate partner violence in a nurse home visitation programme. Background: Nurse home visitation programmes have been identified as an intervention for preventing child abuse and neglect. Recently, there is an increased focus on the role these programmes have in addressing intimate partner violence. Given the unique context of the home environment, strategies for assessments are required that maintain the therapeutic alliance and minimise client attrition. Design: A qualitative case study. Methods: A total of four Nurse–Family Partnership agencies were engaged in this study. Purposeful samples of nurses (n = 32), pregnant or parenting mothers who had self-disclosed experiences of abuse (n = 26) and supervisors (n = 5) participated in this study. A total of 10 focus groups were completed with nurses: 42 interviews with clients and 10 interviews with supervisors. The principles of conventional content analysis guided data analysis. Data were categorised using the practice–problem–needs analysis model for integrating qualitative findings in the development of nursing interventions. Results: Multiple opportunities to ask about intimate partner violence are valued. The use of structured screening tools at enrolment does not promote disclosure or in-depth exploration of women\u27s experiences of abuse. Women are more likely to discuss experiences of violence when nurses initiate nonstructured discussions focused on parenting, safety or healthy relationships. Nurses require knowledge and skills to initiate indicator-based assessments when exposure to abuse is suspected as well as strategies for responding to client-initiated disclosures. Conclusion: A tailored approach to intimate partner violence assessment in home visiting is required. Relevance to clinical practice: Multiple opportunities for exploring women\u27s experiences of violence are required. A clinical pathway outlining a three-pronged approach to identification and assessment was developed

The utility of single nucleotide DNA variations as predictors of postoperative pain

Objectives: Genetic variation is an important contributor to postsurgical pain and thereby analgesia requirements. A description of the potential predictive power of genetic variants in pain should instruct improvements in pain management postoperatively. We set out to examine whether a set of genetic variants in pain related genes would show any association with actual pain outcomes in a typical surgical population. Methods: A candidate gene study was carried out in 135 surgical patients with 12 DNA variants (single nucleotide polymorphisms or ‘SNPs’) in known or putative pain pathway genes to detect associations with postoperative pain - measured by a verbal rating score (VRS) and patient-controlled analgesia (PCA) usage rate. Standard PCR based molecular biology approaches were used. Results: At 20-24h after surgery, patients with the 1032G/1032G variant pair for the A1032G variant of the potassium channel KCNJ6 gene had a slightly higher median VRS than those with 1032A/1032A or 1032A/1032G pairs (p=0.04; dominant genetic model). This small difference was most apparent in the orthopaedic surgery patients where the 1032G/1032G pair associated with VRS (median(interquartile range)) of 5(4-6) vs. 3(0.5-4) in 1032A/1032A or 1032A/1032G groups. For PCA, patients with 3435C/3435C or 3435C/3435T pairs for ATPdependent efflux pump gene ABCB1 variant C3435T used PCA at a considerably higher rate of 0.89(0.07-1.66) mg.h-1 compared with just 0.11 (0-0.52) mg.h-1 for the 3435T/3435T pair (p=0.03; dominant model). A significantly higher usage rate was also detected for opioid receptor OPRM1 variant IVS2-691 with usage of 0.77(0.01-1.56) mg.h-1 for the IVS2C/IVS2C or IVS2C/IVS2G group vs. 0.24(0-1.26) mg.h-1 in the IVS2G/IVS2G group (p=0.04; recessive model). Conclusion: While this study has identified some significant statistical associations the potential utility of the studied DNA variants in prediction of postoperative pain and patient-controlled opioid analgesia requirements appears to be quite limited at present

Prostate MR image quality of apparent diffusion coefficient maps versus fractional intracellular volume maps from VERDICT MRI using the PI-QUAL score and a dedicated Likert scale for artefacts

PURPOSE: This study aimed to assess the image quality of apparent diffusion coefficient (ADC) maps derived from conventional diffusion-weighted MRI and fractional intracellular volume maps (FIC) from VERDICT MRI (Vascular, Extracellular, Restricted Diffusion for Cytometry in Tumours) in patients from the INNOVATE trial. The inter-reader agreement was also assessed. METHODS: Two readers analysed both ADC and FIC maps from 57 patients enrolled in the INNOVATE prospective trial. Image quality was assessed using the Prostate Imaging Quality (PI-QUAL) score and a subjective image quality Likert score (Likert-IQ). The image quality of FIC and ADC were compared using a Wilcoxon Signed Ranks test. The inter-reader agreement was assessed with Cohen's kappa. RESULTS: There was no statistically significant difference between the PI-QUAL score for FIC datasets compared to ADC datasets for either reader (p = 0.240 and p = 0.614). Using the Likert-IQ score, FIC image quality was higher compared to ADC (p = 0.021) as assessed by reader-1 but not for reader-2 (p = 0.663). The inter-reader agreement was 'fair' for PI-QUAL scoring of datasets with FIC maps at 0.27 (95% confidence interval; 0.08-0.46) and ADC datasets at 0.39 (95% confidence interval 0.22-0.57). For Likert scoring, the inter-reader agreement was also 'fair' for FIC maps at 0.38 (95% confidence interval; 0.10-0.65) and substantial for ADC maps at 0.62 (95% confidence interval; 0.39-0.86). CONCLUSION: Image quality was comparable for FIC and ADC. The inter-reader agreement was similar when using PIQUAL for both FIC and ADC datasets but higher for ADC maps compared to FIC maps using the image quality Likert score

Effect of Addition of an Intimate Partner Violence Intervention to a Nurse Home Visitation Program on Maternal Quality of Life: A Randomized Clinical Trial

Importance: Intimate partner violence (IPV) is a public health problem with significant adverse consequences for women and children. Past evaluations of a nurse home visitation program for pregnant women and first-time mothers experiencing social and economic disadvantage have not consistently shown reductions in IPV. Objective: To determine the effect on maternal quality of life of a nurse home visitation program augmented by an IPV intervention, compared with the nurse home visitation program alone. Design, Setting, and Participants: Cluster-based, single-blind, randomized clinical trial at 15 sites in 8 US states (May 2011-May 2015) enrolling 492 socially disadvantaged pregnant women (≥16 years) participating in a 2.5-year nurse home visitation program. Interventions: In augmented program sites (n = 229 participants across 7 sites), nurses received intensive IPV education and delivered an IPV intervention that included a clinical pathway to guide assessment and tailor care focused on safety planning, violence awareness, self-efficacy, and referral to social supports. The standard program (n = 263 participants across 8 sites) included limited questions about violence exposure and information for abused women but no standardized IPV training for nurses. Main Outcomes and Measures: The primary outcome was quality of life (WHOQOL-BREF; range, 0-400; higher score indicates better quality of life) obtained through interviews at baseline and every 6 months until 24 months after delivery. From 17 prespecified secondary outcomes, 7 secondary end points are reported, including scores on the Composite Abuse Scale, SPAN (Startle, Physiological Arousal, Anger, and Numbness), Prime-MD Patient Health Questionnaire, TWEAK (Tolerance/Worry About Drinking/Eye-Opener/Amnesia/C[K]ut Down on Drinking), Drug Abuse Severity Test, and the 12-Item Short-Form Health Survey (physical and mental health), version 2. Results: Among 492 participants enrolled (mean age, 20.4 years), 421 (86%) completed the trial. Quality of life improved from baseline to 24 months in both groups (change in WHOQOL-BREF scores from 299.5 [SD, 54.4] to 308.2 [SD, 52.6] in the augmented program group vs from 293.6 [SD, 56.4] to 316.4 [SD, 57.5] in the standard program group). Based on multilevel growth curve analysis, there was no statistically significant difference between groups (modeled score difference, -4.9 [95% CI, -16.5 to 6.7]). There were no statistically significant differences between study groups in any of the secondary participant end points. There were no adverse events recorded in either group. Conclusions and Relevance: Among pregnant women experiencing social and economic disadvantage and preparing to parent for the first time, augmentation of a nurse home visitation program with a comprehensive IPV intervention, compared with the home visitation program alone, did not significantly improve quality of life at 24 months after delivery. These findings do not support the use of this intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT01372098

What are the type, direction, and strength of species, community, and ecosystem responses to warming in aquatic mesocosm studies and their dependency on experimental characteristics? A systematic review protocol

Background Mesocosm experiments have become increasingly popular in climate change research as they bridge the gap between small-scale, less realistic, microcosm experiments, and large-scale, more complex, natural systems. Characteristics of aquatic mesocosm designs (e.g., mesocosm volume, study duration, and replication) vary widely, potentially affecting the magnitude and direction of effect sizes measured in experiments. In this global systematic review we aim to identify the type, direction and strength of climate warming effects on aquatic species, communities and ecosystems in mesocosm experiments. Furthermore, we will investigate the context-dependency of the observed effects on several a priori determined effect moderators (ecological and methodological). Our conclusions will provide recommendations for aquatic scientists designing mesocosm experiments, as well as guidelines for interpretation of experimental results by scientists, policy-makers and the general public. Methods We will conduct a systematic search using multiple online databases to gather evidence from the scientific literature on the effects of warming experimentally tested in aquatic mesocosms. Data from relevant studies will be extracted and used in a random effects meta-analysis to estimate the overall effect sizes of warming experiments on species performance, biodiversity and ecosystem functions. Experimental characteristics (e.g., mesocosm size and shape, replication-level, experimental duration and design, biogeographic region, community type, crossed manipulation) will be further analysed using subgroup analyses

Interprofessional education in geriatric medicine: towards best practice. A controlled before-after study of medical and nursing students

Objectives. To investigate nursing and medical students’ readiness for interprofessional learning before and after implementing geriatric interprofessional education (IPE), based on problem-based learning (PBL) case scenarios. To define the optimal number of geriatric IPE sessions, the size and the ratio of participants from each profession in the learner groups, the outcomes related to the Kirkpatrick four-level typology of learning evaluation, students’ concerns about joint learning and impact of geriatric IPE on these concerns. The study looked at the perception of roles and expertise of the ‘other’ profession in interprofessional teams, and students’ choice of topics for future sessions. Students’ expectations, experience, learning points and the influence on the understanding of IP collaboration, as well as their readiness to participate in such education again were investigated. Design. A controlled before–after study (2014/2015, 2015/2016) with data collected immediately before and after the intervention period. Study includes additional comparison of the results from the intervention with a control group of students. Outcomes were determined with a validated ‘Readiness for Interprofessional Learning’ questionnaire, to which we added questions with free comments, combining quantitative and qualitative research methods. The teaching sessions were facilitated by experienced practitioners/educators, so each group had both, a clinician (either geratology consultant or registrar) and a senior nurse. Participants. 300 medical, 150 nursing students. Setting. Tertiary care university teaching hospital. Results. Analysis of the returned forms in the intervention group had shown that nursing students scored higher on teamwork and collaboration post-IPE (M=40.78, SD=4.05) than pre-IPE (M=34.59, SD=10.36)—statistically significant. On negative professional identity, they scored lower post-IPE (M=7.21, SD=4.2) than pre-IPE (M=8.46, SD=4.1)—statistically significant. The higher score on positive professional identity post-IPE (M=16.43, SD=2.76) than pre-IPE (M=14.32, SD=4.59) was also statistically significant. Likewise, the lower score on roles and responsibilities post-IPE (M=5.41, SD=1.63) than pre-IPE (M=6.84, SD=2.75). Medical students scored higher on teamwork and collaboration post-IPE (M=36.66, SD=5.1) than pre-IPE (M=32.68, SD=7.4)—statistically significant. Higher positive professional identity post-IPE (M=14.3, SD=3.2) than pre-IPE (M=13.1, SD=4.31)—statistically significant. The lower negative professional identity post-IPE (M=7.6, SD=3.17) than pre-IPE (M=8.36, SD=2.91) was not statistically significant. Nor was the post-IPE difference over roles and responsibilities (M=7.4, SD=1.85), pre-IPE (M=7.85, SD=2.1). In the control group, medical students scored higher for teamwork and collaboration post-IPE (M=36.07, SD=3.8) than pre-IPE (M=33.95, SD=3.37)—statistically significant, same for positive professional identity post-IPE (M=13.74, SD=2.64), pre-IPE (M=12.8, SD=2.29), while negative professional identity post-IPE (M=8.48, SD=2.52), pre-IPE (M=9, SD=2.07), and roles and responsibilities post-IPE (M=7.89, SD=1.69), pre-IPE (M=7.91, SD=1.51) shown no statistically significant differences. Student concerns, enhanced understanding of collaboration and readiness for future joint work were addressed, but not understanding of roles. Conclusions. Educators with nursing and medical backgrounds delivered geriatric IPE through case-based PBL. The optimal learner group size was determined. The equal numbers of participants from each profession for successful IPE are not necessary. The IPE delivered by clinicians and senior nurses had an overall positive impact on all participants, but more markedly on nursing students. Surprisingly, it had the same impact on medical students regardless if it was delivered to the mixed groups with nursing students, or to medical students alone. Teaching successfully addressed students’ concerns about joint learning and communication and ethics were most commonly suggested topics for the future

Obstructive sleep apnea in Treacher Collins syndrome

The aim of the present study was to investigate the prevalence of obstructive sleep apnea syndrome (OSAS) among the Norwegian population with Treacher Collins syndrome (TCS). A secondary aim was to establish whether TCS phenotype severity is associated with OSAS severity. A prospective case study design was used. Individuals who were 5 years old and above with a known diagnosis of TCS in Norway were invited to participate in a study. The study included genetic testing, medical and dental examinations and polysomnography. All participants demonstrated disturbed respiration during sleep; 18/19 met the diagnostic criteria for OSAS. Subjectively evaluated snoring was not a reliable predictor of OSAS. We found no significant association between TCS phenotype severity and the severity of OSAS. OSAS is common in TCS, but there is no association with the phenotype severity. Individuals diagnosed with TCS must undergo sleep studies to identify the presence of OSAS

SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study

BACKGROUND: Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood. OBJECTIVES: COVID-19 in patients with antibody deficiency (COV-AD) is a multi-site UK study that aims to determine the immune response to SARS-CoV-2 infection and vaccination in patients with primary or secondary antibody deficiency, a population that suffers from severe and recurrent infection and does not respond well to vaccination. METHODS: Individuals on immunoglobulin replacement therapy or with an IgG less than 4 g/L receiving antibiotic prophylaxis were recruited from April 2021. Serological and cellular responses were determined using ELISA, live-virus neutralisation and interferon gamma release assays. SARS-CoV-2 infection and clearance were determined by PCR from serial nasopharyngeal swabs. RESULTS: A total of 5.6% (n = 320) of the cohort reported prior SARS-CoV-2 infection, but only 0.3% remained PCR positive on study entry. Seropositivity, following two doses of SARS-CoV-2 vaccination, was 54.8% (n = 168) compared with 100% of healthy controls (n = 205). The magnitude of the antibody response and its neutralising capacity were both significantly reduced compared to controls. Participants vaccinated with the Pfizer/BioNTech vaccine were more likely to be seropositive (65.7% vs. 48.0%, p = 0.03) and have higher antibody levels compared with the AstraZeneca vaccine (IgGAM ratio 3.73 vs. 2.39, p = 0.0003). T cell responses post vaccination was demonstrable in 46.2% of participants and were associated with better antibody responses but there was no difference between the two vaccines. Eleven vaccine-breakthrough infections have occurred to date, 10 of them in recipients of the AstraZeneca vaccine. CONCLUSION: SARS-CoV-2 vaccines demonstrate reduced immunogenicity in patients with antibody deficiency with evidence of vaccine breakthrough infection