Well-being in Old Age: A Question of Both Continuity and Change

In this chapter, we are concerned with the well-being of people in old age, living at a residential care home (RCH), and how well-being can be supported in gerontological social work and care at the RCH. Based on empirical data consisting of well-being narratives with elderly residents (average age of 91), a dialogical performance analysis was undertaken about their experiences of well-being at the RCH. The findings of importance are reported through three themes: (1) childhood memories as a source of well-being, (2) family and work as a source of well-being, and (3) opportunities for the well-being of the elderly at the RCH. To be an individual with others is a phenomenon of a personal sense of self and a phenomenon of sociality. Well-being is also found in the individual’s self-renewal. Well-being is about a sense of both individual continuity and change. Well-being is created in social situations with others (including caregivers) in daily interactions and in human contacts at the RCH. This kind of individual self-renewal is about human growth and is a human need regardless of age. Consequently, the human growth in (and despite) old age at RCH should be the main target of gerontological social work and care

The Biology of Retinopathy of Prematurity

Retinopathy of prematurity occurs because the retina of a preterm infant at birth is incompletely vascularized, and if the postnatal environment does not match the in utero environment that supported retinal development, the vessels and neural retina will not grow normally. Risk factors determined from many clinical studies and animal studies fall into 2 categories: prenatal factors and postnatal factors

Evaluation of the Retinopathy of Prematurity Activity Scale (ROP-ActS) in a randomised controlled trial aiming for prevention of severe ROP : A substudy of the Mega Donna Mega trial

Objective The current grading of retinopathy of prematurity (ROP) does not sufficiently discriminate disease severity for evaluation of trial interventions. The published ROP Activity Scales (original: ROP-ActS and modified: mROP-ActS), describing increasing severity of ROP, versus the categorical variables severe ROP, stage, zone and plus disease were evaluated as discriminators of the effect of an ROP preventive treatment. Methods and analysis The Mega Donna Mega trial investigated ROP in infants born <28-week gestational age (GA), randomised to arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation or no supplementation. Of 207 infants, 86% with finalised ROP screening were included in this substudy. ROP-ActS versus standard variables were evaluated using Fisher’s non-parametric permutation test, multivariable logistic and linear regression and marginal fractional response models. Results The AA:DHA group (n=84) and the control group (n=93) were well balanced. The maximum ROP-ActS measurement was numerically but not significantly lower in the AA:DHA group (mean: 4.0 (95% CI 2.9 to 5.0)) versus the control group (mean: 5.3 (95% CI 4.1 to 6.4)), p=0.11. In infants with any ROP, the corresponding scale measurements were 6.8 (95% CI 5.4 to 8.2) and 8.7 (95% CI 7.5 to 10.0), p=0.039. Longitudinal profiles of the scale were visually distinguished for the categories of sex and GA for the intervention versus control. Conclusions The preventive effect of AA:DHA supplementation versus no supplementation was better discriminated by the trial’s primary outcome, severe ROP, than by ROP-ActS. The sensitivity and the linear qualities of ROP-ActS require further validations on large data sets and perhaps modifications. Trial registration number NCT03201588

Immune priming using DC- and T cell-targeting gene therapy sensitizes both treated and distant B16 tumors to checkpoint inhibition

Immune checkpoint inhibitors have revolutionized the treatment of metastatic melanoma, but most tumors show resistance. Resistance is connected to a non-T cell inflamed phenotype partially caused by a lack of functional dendritic cells (DCs) that are crucial for T cell priming. Herein, we investigated whether the adenoviral gene vehicle mLOAd703 carrying both DC- and T cell-activating genes can lead to inflammation in a B16-CD46 model and thereby overcome resistance to checkpoint inhibition therapy. B16-CD46 cells were injected subcutaneously in one or both flanks of immuno-competent C57BL/6J mice. mLOAd703 treatments were given intratumorally alone or in combination with intraperitoneal checkpoint inhibition therapy (anti-PD-1, anti-PD-L1, or anti-TIM-3). Tumor, lymph node, spleen, and serum samples were analyzed for the presence of immune cells and cytokines/chemokines. B16-CD46 tumors were non-inflamed and resistant to checkpoint blockade. In contrast, mLOAd703 treatment led to infiltration of the tumor by CD8(+) T cells, natural killer (NK) cells, and CD103(+) DCs, accompanied by a systemic increase of pro-inflammatory cytokines interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin-27 (IL-27). This response was even more pronounced after combining the virus with checkpoint therapy, in particular with anti-PD-L1 and anti-TIM-3, leading to further reduced tumor growth in injected lesions. Moreover, anti-PD-L1 combination also facilitated abscopal responses in non-injected lesions

Low Birth Weight Is a Risk Factor for Severe Retinopathy of Prematurity Depending on Gestational Age

Objective: To evaluate the impact of low birth weight as a risk factor for retinopathy of prematurity (ROP) that will require treatment in correlation with gestational age at birth (GA). Study design In total, 2941 infants born <32 weeks GA were eligible from five cohorts of preterm infants previously collected for analysis in WINROP (Weight IGF-I Neonatal ROP) from the following locations: Sweden (EXPRESS) (n = 426), North America (n = 1772), Boston (n = 338), Lund (n = 52), and Gothenburg (n = 353). Data regarding GA at birth, birth weight (BW), gender, and need for ROP treatment were retrieved. Birth weight standard deviation scores (BWSDS) were calculated with Swedish as well as Canadian reference models. Small for gestational age (SGA) was defined as BWSDS less than −2.0 SDS using the Swedish reference and as BW below the 10th percentile using the Canadian reference charts. Results: Univariate analysis showed that low GA (p<0.001), low BW (p<0.001), male gender (p<0.05), low BWSDSCanada (p<0.001), and SGACanada (p<0.01) were risk factors for ROP that will require treatment. In multivariable logistic regression analysis, low GA (p<0.0001), male gender (p<0.01 and p<0.05), and an interaction term of BWSDS*GA group (p<0.001), regardless of reference chart, were risk factors. Low BWSDS was less important as a risk factor in infants born at GA <26 weeks compared with infants born at GA ≥26 weeks calculated with both reference charts (BWSDSSweden, OR = 0.80 vs 0.56; and BWSDSCanada, OR = 0.72 vs 0.41). Conclusions: Low BWSDS as a risk factor for vision-threatening ROP is dependent on the infant's degree of immaturity. In more mature infants (GA ≥26 weeks), low BWSDS becomes a major risk factor for developing ROP that will require treatment. These results persist even when calculating BW deficit with different well-established approaches

Insulin-like growth factor 1 has multisystem effects on foetal and preterm infant development.

UNLABELLED: Poor postnatal growth after preterm birth does not match the normal rapid growth in utero and is associated with preterm morbidities. Insulin-like growth factor 1 (IGF-1) axis is the major hormonal mediator of growth in utero, and levels of IGF-1 are often very low after preterm birth. We reviewed the role of IGF-1 in foetal development and the corresponding preterm perinatal period to highlight the potential clinical importance of IGF-1 deficiency in preterm morbidities. CONCLUSION: There is a rationale for clinical trials to evaluate the potential benefits of IGF-1 replacement in very preterm infants.This work was supported by a European Commission FP7 project 305485 PREVENT-ROP grant to all of the authors.This is the final version of the article. It first appeared from Wiley via https://doi.org/10.1111/apa.1335

Randomized Control Trial of Postnatal rhIGF-1/rhIGFBP-3 Replacement in Preterm Infants: Post-hoc Analysis of Its Effect on Brain Injury.

Background: Postnatal insulin-like growth factor-1 (IGF-1) replacement with recombinant human (rh)IGF-1 and IGF binding protein-3 (rhIGF-1/rhIGFBP-3) is being studied as a potential treatment to reduce comorbidities of prematurity. We have recently reported on a phase II, multicenter, randomized, controlled trial comparing postnatal rhIGF-1/rhIGFBP-3 replacement with standard of care (SOC) in extremely preterm infants (NCT01096784). Maximum severity of retinopathy of prematurity was the primary endpoint of the trial and presence of GMH-IVH/PHI one of the pre-specified secondary endpoints. Infants therefore received serial cranial ultrasound scans (CUS) between birth and term age. In this post-hoc analysis we present a detailed analysis of the CUS data of this trial and evaluate the effect of postnatal rhIGF-1/rhIGFBP-3 replacement on the incidence of different kinds of brain injury in extremely preterm infants. Methods: This report is an exploratory post-hoc analysis of a phase II trial in which infants <28 weeks gestational age were randomly allocated to rhIGF-1/rhIGFBP-3 or SOC. Serial cranial ultrasounds were performed between birth and term-equivalent age. Presence of germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH), periventricular hemorrhagic infarction (PHI), post-hemorrhagic ventricular dilatation, and white matter injury (WMI) were scored by two independent masked readers. Results: The analysis included 117 infants; 58 received rhIGF-1/rhIGFBP-3 and 59 received SOC. A trend toward less grade II-III GMH-IVH and PHI was observed in treated infants vs. SOC. A subanalysis of infants without evidence of GMH-IVH at study entry (n = 104) showed reduced progression to GMH-IVH in treated infants (25.0% [13/52] vs. 40.4% [21/52]; not significant). No effects of rhIGF-1/rhIGFBP-3 on WMI were observed. Conclusion: The potential protective effect of rhIGF-1/rhIGFBP-3 on the occurrence of GMH-IVH/PHI appeared most pronounced in infants with no evidence of GMH-IVH at treatment start

Changes in everyday life after discharge from day care rehabilitation

Community-based day care that provides rehabilitation (DCR) targets elderly people with physical disabilities. The goal of these programmes is mainly to improve physical ability in order to enable participants to remain in their ordinary homes. Knowledge of the outcomes of DCR is limited as well as knowledge of what it is that makes a difference for the individual. The aim of this study was to describe what changes in everyday life elderly persons experienced after discharge from a community-based day care rehabilitation centre and to give possible explanations for these changes. Fifteen elderly people were interviewed after that they had been discharged from DCR. A narrative approach was used for analysing the interview data. Four case stories constitute the findings, each of them with unique descriptions of changes in everyday life as well as possible explanations for these changes. The first case story described resumption of daily activities that made the days more eventful and meaningful. The second described how everyday life became an arena for exercising, which create confidence for the future. The third described how an increased sense of certainty and security in the movements led to an increased appetite for life. Finally, the fourth case story described both the stay at the DCR centre and the promise of a new period there as uplifting that made the days easier. Concerning possible explanations for these changes, the findings indicate that it was a combination of several events that together contributed to the changes. Examples were physical training, counselling about how to live in an active and healthy lifestyle, and socialisation with other patients in formal as well as in informal sessions