Determinants of Depressive Symptoms at 1 Year Following ICU Discharge in Survivors of $ 7 Days of Mechanical Ventilation : Results From the RECOVER Program, a Secondary Analysis of a Prospective Multicenter Cohort Study

Abstract : Background: Moderate to severe depressive symptoms occur in up to one-third of patients at 1 year following ICU discharge, negatively affecting patient outcomes. This study evaluated patient and caregiver factors associated with the development of these symptoms. Methods: This study used the Rehabilitation and Recovery in Patients after Critical Illness and Their Family Caregivers (RECOVER) Program (Phase 1) cohort of 391 patients from 10 medical/surgical university-affiliated ICUs across Canada. We determined the association between patient depressive symptoms (captured by using the Beck Depression Inventory II [BDI-II]), patient characteristics (age, sex, socioeconomic status, Charlson score, and ICU length of stay [LOS]), functional independence measure (FIM) motor subscale score, and caregiver characteristics (Caregiver Assistance Scale and Center for Epidemiologic Studies-Depression Scale) by using linear mixed models at time points 3, 6, and 12 months. Results: BDI-II data were available for 246 patients. Median age at ICU admission was 56 years (interquartile range, 45-65 years), 143 (58%) were male, and median ICU LOS was 19 days (interquartile range, 13-32 days). During the 12-month follow-up, 67 of 246 (27.2%) patients had a BDI-II score ≥ 20, indicating moderate to severe depressive symptoms. Mixed models showed worse depressive symptoms in patients with lower FIM motor subscale scores (1.1 BDI-II points per 10 FIM points), lower income status (by 3.7 BDI-II points; P = .007), and incomplete secondary education (by 3.8 BDI-II points; P = .009); a curvilinear relation with age (P = .001) was also reported, with highest BDI-II at ages 45 to 50 years. No associations were found between patient BDI-II and comorbidities (P = .92), sex (P = .25), ICU LOS (P = .51), or caregiver variables (Caregiver Assistance Scale [P = .28] and Center for Epidemiologic Studies Depression Scale [P = .74]). Conclusions: Increased functional dependence, lower income, and lower education are associated with increased severity of post-ICU depressive symptoms, whereas age has a curvilinear relation with symptom severity. Knowledge of risk factors may inform surveillance and targeted mental health follow-up. Early mobilization and rehabilitation aiming to improve function may serve to modify mood disorders

Comparison of two related lines of tauGFP transgenic mice designed for lineage tracing

Abstract Background The tauGFP reporter fusion protein is produced nearly ubiquitously by the TgTP6.3 transgene in TP6.3 mice and its localisation to microtubules offers some advantages over soluble GFP as a lineage marker. However, TgTP6.3 Tg/Tg homozygotes are not viable and TgTP6.3 Tg/− hemizygotes are smaller than wild-type. TP6.4 mice carry the TgTP6.4 transgene, which was produced with the same construct used to generate TgTP6.3, so we investigated whether TgTP6.4 had any advantages over TgTP6.3. Results Although TgTP6.4 Tg/Tg homozygotes died before weaning, TgTP6.4 Tg/− hemizygotes were viable and fertile and only males were significantly lighter than wild-type. The TgTP6.4 transgene produced the tauGFP fusion protein by the 2-cell stage and it was widely expressed in adults but tauGFP fluorescence was weak or absent in several tissues, including some neural tissues. The TgTP6.4 transgene expression pattern changed over several years of breeding and mosaic transgene expression became increasingly common in all expressing tissues. This mosaicism was used to visualise clonal lineages in the adrenal cortex of TgTP6.4 Tg/− hemizygotes and these were qualitatively and quantitatively comparable to lineages reported previously for other mosaic transgenic mice, X-inactivation mosaics and chimaeras. Mosaicism occurred less frequently in TP6.3 than TP6.4 mice and was only observed in the corneal epithelium and adrenal cortex. Conclusions Mosaic expression makes the TgTP6.4 transgene unsuitable for use as a conventional cell lineage marker but such mosaicism provides a useful system for visualising clonal lineages that arise during development or maintenance of adult tissues. Differences in the occurrence of mosaicism between related transgenic lines, such as that described for lines TP6.3 and TP6.4, might provide a useful system for investigating the mechanism of transgene silencing

Service related needs of older people with dementia: perspectives of service users and their unpaid carers.

Background: Dementia is a major cause of disability among older people and constitutes one of the greatest challenges currently facing families, and health and social care services in the developed world. In response to trends in dementia prevalence and the impact the condition has on peoples' lives, dementia care has been placed high on the public and political agenda in the UK. However, despite significant public resources being allocated to combat the impact of the disease, recent evidence indicates that numerous challenges in relation to service provision remain. This study aimed to develop a deeper understanding of the lived experience of people with dementia regarding their service related needs. Method: The study made use of data gathered through individual semi-structured, narrative interviews conducted with persons with experience of dementia and their unpaid carers. Results: Although participants were generally satisfied with the services they received, a number of unmet needs related to service provision were identified. In terms of diagnostic procedures the findings of this study indicate the need for early diagnosis delivered through a comprehensive assessment package. The participants also highlighted the need for well co-ordinated post-diagnostic support, greater continuity of care concerning the personnel involved, and enhanced access to non-pharmacological interventions to support identity and social engagement. Conclusion: This study contributes to a better understanding of service related needs of people with dementia in relation to diagnostic procedures and post-diagnostic support.sch_occ25pub3135pub

Additional file 1: of Comparison of two related lines of tauGFP transgenic mice designed for lineage tracing

Figure S1. Confocal microscope with environmental chamber. (a) The Leica DMIRB/E inverted confocal microscope is shown together with the stage-mounted environmental chamber and some of the equipment required to maintain the correct temperature and gas phase within the chamber. (b) Side view of the environmental chamber with a culture dish on the heated stage. The flow of carbon dioxide from the gas cylinder to the environmental chamber was controlled by an infrared gas monitor to ensure that the gas mixture inside the environmental chamber was maintained at 5% CO2 in air. Embryos were cultured in drops of culture medium under liquid paraffin oil in a WillCo thin glass-bottomed culture dish on the heated stage. Time-lapse images of the embryos were acquired every 15 or 30 min in both fluorescent (FITC) and transmitted light modes for up to 24 h. Abbreviations: EC, environmental chamber; GC, gas cylinder; GM, gas monitor; HS, heated stage; HSC, heated stage controller. Figure S2. Comparison of sizes of E14.5 tauGFP-positive and tauGFP-negative fetuses from two crosses. (a-d) Comparisons of tauGFP-positive and tauGFP-negative fetal sizes using a 2-way analysis of variance (ANOVA) to allow for variation among litters. The graphs show fetal mass (a) and crown-rump length (b) for the TgTP6.4 Tg/− female × TgTP6.4 Tg/− male cross plus fetal mass (c) and crown-rump length (d) for the TgTP6.4 Tg/- female × TgTP6.4 −/− male cross. Each point represents a single fetus and fetuses are arranged by litters. Sexes were not distinguished and only litters with both tauGFP-positive and tauGFP-negative fetuses were included. Numbers of fetuses, means and P-values are shown. (e-h) Differences between within-litter means are shown for fetal mass and crown-rump length for tauGFP-positive and tauGFP-negative fetuses in each cross. P-values are shown for paired t-tests. Abbreviations: GFP-ve, tauGFP-negative; GFP + ve, tauGFP-positive. Figure S3. Relationship between mean stripe width and the percentage of tauGFP-positive cells in TgTP6.4 Tg/− adrenal cortices. (a) The uncorrected mean tauGFP-positive stripe width for 27 TgTP6.4 Tg/− adrenal glands varied widely. It was close to 2% of the adrenal circumference when the percentage of tauGFP-positive cells in the adrenal cortex was low but it was positively correlated with the percentage of tauGFP-positive cells. The Spearman correlation coefficient (rs) is shown. This positive correlation is likely to be because stripes may comprise several adjacent coherent clones of cells and the average number of tauGFP-positive clones per tauGFP-positive stripe will increase with the percentage of tauGFP-positive cells in the adrenal cortex. (b) The corrected mean tauGFP-positive stripe width was not significantly correlated with the percentage of tauGFP-positive cells so allows comparisons among adrenals with different percentages of tauGFP-positive cells. The observed (uncorrected) mean tauGFP-positive stripe number was corrected by dividing it by the correction factor 1/(1-p), where p is the proportion of tauGFP-positive cells around the circumference as explained in the Methods. Figure S4. Age has no effect on percentage of tauGFP-positive cells or corrected stripe number in mosaic adrenal cortices of TgTP6.3 Tg/− and TgTP6.4 Tg/− mice. (a-d) There were no significant differences among age groups for the % tauGFP-positive cells in the adrenal cortex for (a) TgTP6.3 Tg/- females (b) TgTP6.3 Tg/- males (c) TgTP6.4 Tg/- females or (d) TgTP6.4 Tg/- males. Mice were grouped into three or more age groups and analysed by the Kruskal-Wallis test (KW test). (e-h) There were also no significant positive correlations between age and the % tauGFP-positive cells in the adrenal cortex for any of the four groups. Spearman correlation coefficients (rs) are shown. (i-l) There were no significant differences among age groups for the corrected stripe number (tauGFP-positive stripes plus tauGFP-negative stripes) in the adrenal cortex for any sex and genotype combination. Mice were grouped into three or more age groups and analysed by the Kruskal-Wallis test (KW test) or 1-way ANOVA. (m-p) There were also no significant positive correlations between age and the corrected stripe number in the adrenal cortex for any sex and genotype combination. Pearson correlation coefficients (r) and the linear regression lines are shown but no lines differed significantly from horizontal. N = number of adrenal glands; one adrenal gland was analysed per mouse. Table S1. FACS analysis of fetal brains. (PDF 599 kb