The Mediating Effect of Caregiving Relationship Quality on the Association Between Caregiving Stressors and Mental Health Problems Among Older Spousal Caregivers.

Providing care to a spouse can be especially challenging for older adults given their compounding stressors resulting from aging and caregiving. This cross-sectional study examines the relationships between caregiving stressors and caregiver mental health problems and the potential mediator (i.e., caregiving relationship quality) of these associations. A total of 431 Americans (≥65 years) were selected from the National Study of Caregiving. Path analysis shows that care assistance was positively associated with caregiver mental health problems, and this association was mediated by negative relationship quality (Indirect effect = .14, p = .016). Moreover, role overload was positively associated with caregiver mental health problems, which was mediated by negative relationship quality (indirect effect = .13, p = .002). Findings suggest that caregiving stressors can adversely affect mental health by exacerbating negative relationship quality. Interventions that limit negative exchanges and increase compassionate communications between older spousal caregivers and their care-receiving partners are needed.

The acceptability of asking women to delay removal of a long-acting reversible contraceptive to take part in a preconception weight loss programme: a mixed methods study using qualitative and routine data (Plan-it).

BACKGROUND: Having a body mass index (BMI) which is classified as overweight (BMI ≥ 25) or obese (BMI ≥ 30) increases the risk of complications during pregnancy and labour. Weight-management interventions which target excess gestational weight gain during pregnancy have had limited success. Women who use long-acting reversible contraception (LARC) are in contact with services as part of their preparation for conception, creating a potential opportunity to offer a preconception weight-loss intervention. The aims of this mixed methods study were to assess the acceptability and practicability of a weight-loss intervention which asked people to delay LARC removal in order to lose weight before conceiving. METHODS: Routine UK NHS data were analysed to identify pathways from LARC removal to pregnancy. Qualitative surveys and advisory group discussions with service providers and LARC users with experience of being overweight were conducted and analysed thematically. RESULTS: Three hundred fifteen thousand seven hundred fifty-five UK women aged 16-48 years between 2009-2018 had at least one LARC-related event (e.g. insertion, removal) and 1.7% of those events were recorded as related to planning a pregnancy. BMI was included in 62% of women's records, with 54% of those BMI being classified as overweight or obese. Online surveys were completed by 100 healthcare practitioners and 243 LARC users. Stakeholders identified facilitators and barriers associated with the proposed intervention including sensitivities of discussing weight, service-user past experiences, practitioner skills, the setting and ethical implications of the proposed intervention. CONCLUSIONS: Although women and service providers recognised potential benefits, a preconception weight-loss intervention asking people to delay LARC removal posed many barriers, due mainly to the acceptability of such an intervention to women and healthcare practitioners. Weight-loss interventions that target the general population, together with a focus on improving public knowledge of preconception health, may be more acceptable than interventions which solely focus on LARC users. Many of the barriers identified, including communication, understanding and beliefs about weight and risk, appointment systems and the limitations of routine datasets also have relevance for any preconception weight-loss intervention. Work to improve routine datasets and reducing communication barriers to discussing weight are priorities. TRIAL REGISTRATION: ISRCTN14733020 registered 10.05.2019.

Randomised controlled trial and economic evaluation of a targeted cancer awareness intervention for adults living in deprived areas of the UK.

BACKGROUND: Cancer outcomes are poor in socioeconomically deprived communities, with low symptom awareness contributing to prolonged help-seeking and advanced disease. Targeted cancer awareness interventions require evaluation. METHODS: This is a randomised controlled trial involving adults aged 40+ years recruited in community and healthcare settings in deprived areas of South Yorkshire and South-East Wales. INTERVENTION: personalised behavioural advice facilitated by a trained lay advisor. CONTROL: usual care. Follow-up at two weeks and six months post-randomisation. PRIMARY OUTCOME: total cancer symptom recognition score two weeks post-randomisation. RESULTS: Two hundred and thirty-four participants were randomised. The difference in total symptom recognition at two weeks [adjusted mean difference (AMD) 0.6, 95% CI: -0.03, 1.17, p = 0.06] was not statistically significant. Intervention participants reported increased symptom recognition (AMD 0.8, 95% CI: 0.18, 1.37, p = 0.01) and earlier intended presentation (AMD -2.0, 95% CI: -3.02, -0.91, p < 0.001) at six months. "Lesser known" symptom recognition was higher in the intervention arm (2 weeks AMD 0.5, 95% CI: 0.03, 0.97 and six months AMD 0.7, 95% CI: 0.16, 1.17). Implementation cost per participant was £91.34, with no significant between-group differences in healthcare resource use post-intervention. CONCLUSIONS: Improved symptom recognition and earlier anticipated presentation occurred at longer-term follow-up. The ABACus Health Check is a viable low-cost intervention to increase cancer awareness in socioeconomically deprived communities. CLINICAL TRIAL REGISTRATION: ISRCTN16872545.

Recruitment and retention of participants from socioeconomically deprived communities: lessons from the Awareness and Beliefs About Cancer (ABACus3) Randomised Controlled Trial.

BACKGROUND: Recruitment of research participants poses challenges in socioeconomically deprived areas. The Awareness and Beliefs About Cancer (ABACus) phase 3 Randomised Control Trial recruited adult participants from socioeconomically deprived areas using a combined healthcare/community engagement model. We report the strategies used to successfully recruit and retain our trial participant sample. METHODS: Community and healthcare settings in areas of high socioeconomic deprivation were identified by lay advisors who recruited participants opportunistically or by appointment. Follow-up was done by telephone or post at 2-weeks and 6-months after recruitment, and all participants were offered financial incentives. Qualitative interviews were conducted with lay advisors regarding their experience and reflections. RESULTS: The lay advisors identified and contacted 107 potential recruitment venues across South and West Yorkshire and South East Wales of which 41.1% (n = 42) were opened for recruitment. A total of 234 participants were recruited, with 91% (n = 212) retention at 2-weeks and 85% (n = 199) at 6-months. Community settings yielded 75% (n = 176) of participants. Participants had a mean age of 61.3 years and 63.3% (n = 148) were female, with 66% (n = 154) resident in the most deprived geographical areas. Lay advisors described recruitment as intensive, although engaging participants was easier in community settings. CONCLUSIONS: The ABACus3 trial achieved recruitment and high retention with a population that is often "hard to reach" or entirely missed in health research. Strategies were specifically tailored to engage the venues and adult residents of highly deprived areas. Future studies recruiting adults living in the most deprived areas might benefit from community recruitment and from collaborating with local gatekeepers who are key to engagement. This study adheres to CONSORT guidelines. TRIAL REGISTRATION: Retrospectively registered with ISRCTN ( http://www.isrctn.com/ISRCTN16872545 ) on 12.01.2018.

Using routine referral data for patients with knee and hip pain to improve access to specialist care.

BACKGROUND: Referral letters from primary care contain a large amount of information that could be used to improve the appropriateness of the referral pathway for individuals seeking specialist opinion for knee or hip pain. The primary aim of this study was to evaluate the content of the referral letters to identify information that can independently predict an optimal care pathway. METHODS: Using a prospective longitudinal design, a convenience sample of patients with hip or knee pain were recruited from orthopaedic, specialist general practice and advanced physiotherapy practitioner clinics. Individuals completed a Knee or hip Osteoarthritis Outcome Score at initial consultation and after 6 months. Participant demographics, body mass index, medication and co-morbidity data were extracted from the referral letters. Free text of the referral letters was mapped automatically onto the Unified Medical Language System to identify relevant clinical variables. Treatment outcomes were extracted from the consultation letters. Each outcome was classified as being an optimal or sub-optimal pathway, where an optimal pathway was defined as the one that results in the right treatment at the right time. Logistic regression was used to identify variables that were independently associated with an optimal pathway. RESULTS: A total of 643 participants were recruited, 419 (66.7%) were classified as having an optimal pathway. Variables independently associated with having an optimal care pathway were lower body mass index (OR 1.0, 95% CI 0.9 to 1.0 p = 0.004), named disease or syndromes (OR 1.8, 95% CI 1.1 to 2.8, p = 0.02) and taking pharmacologic substances (OR 1.8, 95% CI 1.0 to 3.3, p = 0.02). Having a single diagnostic procedure was associated with a suboptimal pathway (OR 0.5, 95% CI 0.3 to 0.9 p < 0.001). Neither Knee nor Hip Osteoarthritis Outcome scores were associated with an optimal pathway. Body mass index was found to be a good predictor of patient rated function (coefficient - 0.8, 95% CI -1.1, - 0.4 p < 0.001). CONCLUSION: Over 30% of patients followed sub-optimal care pathway, which represents potential inefficiency and wasted healthcare resource. A core data set including body mass index should be considered as this was a predictor of optimal care and patient rated pain and function.

Effect of Probiotic Use on Antibiotic Administration Among Care Home Residents: A Randomized Clinical Trial.

Importance: Probiotics are frequently used by residents in care homes (residential homes or nursing homes that provide residents with 24-hour support for personal care or nursing care), although the evidence on whether probiotics prevent infections and reduce antibiotic use in these settings is limited. Objective: To determine whether a daily oral probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 compared with placebo reduces antibiotic administration in care home residents. Design, Setting, and Participants: Placebo-controlled randomized clinical trial of 310 care home residents, aged 65 years and older, recruited from 23 care homes in the United Kingdom between December 2016 and May 2018, with last follow-up on October 31, 2018. Interventions: Study participants were randomized to receive a daily capsule containing a probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 (total cell count per capsule, 1.3 × 1010 to 1.6 × 1010) (n = 155), or daily matched placebo (n = 155), for up to 1 year. Main Outcomes and Measures: The primary outcome was cumulative antibiotic administration days for all-cause infections measured from randomization for up to 1 year. Results: Among 310 randomized care home residents (mean age, 85.3 years; 66.8% women), 195 (62.9%) remained alive and completed the trial. Participant diary data (daily data including study product use, antibiotic administration, and signs of infection) were available for 98.7% randomized to the probiotic group and 97.4% randomized to placebo. Care home residents randomized to the probiotic group had a mean of 12.9 cumulative systemic antibiotic administration days (95% CI, 0 to 18.05), and residents randomized to placebo had a mean of 12.0 days (95% CI, 0 to 16.95) (absolute difference, 0.9 days [95% CI, -3.25 to 5.05]; adjusted incidence rate ratio, 1.13 [95% CI, 0.79 to 1.63]; P = .50). A total of 120 care home residents experienced 283 adverse events (150 adverse events in the probiotic group and 133 in the placebo group). Hospitalizations accounted for 94 of the events in probiotic group and 78 events in the placebo group, and deaths accounted for 33 of the events in the probiotic group and 32 of the events in the placebo group. Conclusions and Relevance: Among care home residents in the United Kingdom, a daily dose of a probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 did not significantly reduce antibiotic administration for all-cause infections. These findings do not support the use of probiotics in this setting. Trial Registration: ISRCTN Identifier:16392920.

Computerised Handwriting Speed Test System (CHSTS): Validation of a handwriting assessment for Chinese secondary students.

BACKGROUND/AIM: Handwriting difficulties can be detrimental to students' performance in school tests and even in public examinations. It is crucial for school-based occupational therapists to identify students with handwriting difficulties and support them with appropriate adaptive strategies. The purpose of this study is to validate a computerised assessment - the Computerised Handwriting Speed Test System (CHSTS) of both Chinese and English handwriting for Chinese secondary students and provide an objective reference for extra time allowance in paper-based examinations. METHODS: The internal consistency, test-retest reliability, convergent and discriminant validity of CHSTS were examined using the data from 512 typically developing students and 64 students with special educational needs (SEN) in Hong Kong mainstream secondary schools. RESULTS: Handwriting performance of senior students was better than that of junior students. High internal consistency was shown by over 0.80 Cronbach's α in all measurement items and over 0.90 item-total correlations in temporal domain items. Intra-class correlation indicated good to excellent test-retest reliability of CHSTS (all P < 0.0001). Principal Component Analysis revealed that four components in CHSTS accounted for over 80% of the variance. Handwriting performance was positively associated with manual coordination, automaticity and oculomotor control (all P < 0.05) in linear regression analyses. Students with SEN could be effectively differentiated from typically developing students (over 75% sensitivity and specificity) based on the CHSTS items. CONCLUSION: Validation of CHSTS is the groundwork for identifying students with handwriting difficulties and providing adaptive strategies including fair special examination arrangements for these students.

The IGF-I/IGF-R1 pathway regulates postnatal lung growth and is a nonspecific regulator of alveologenesis in the neonatal rat.

IGF-I, IGF-II, and the IGF-I receptor are widely distributed throughout the neonatal rat lung on days 4, 7, 10, and 14 of life, with a similar abundance at each of these time points. Injection of 20 µg/g of a truncated soluble IGF-I receptor on days 2 and 5 of life, to decoy ligand away from the endogenous IGF-I receptor, reduced lung weight and lung-to-body weight ratio, reduced lung tissue fraction, and impaired alveolar formation, as assessed by secondary crest formation and mean linear intercepts on day 7 of life. Lung procollagen I content and elastin fiber density were also reduced. Injection of 100 µg/day of neutralizing anti-IGF-I, to prevent IGF-I from binding to the IGF-I receptor, on days 3, 4, and 5 of life reduced tissue fraction and elastin fiber density and impaired alveolar formation on day 6 of life. Both interventions reduced total lung cell and secondary crest cell DNA synthesis and small vessel counts per unit area, but these effects were lost after normalization to the reduced tissue fraction. These findings are consistent with a role for IGF-I binding to the IGF-I receptor in postnatal lung growth and on alveologenesis through a nonspecific positive effect on DNA synthesis. Injection of 100 µg/day of neutralizing anti-IGF-II, to prevent IGF-II from binding to the IGF-I receptor, on days 3, 4, and 5 of life had no effect on total lung cell DNA synthesis per unit area on day 6 of life, and a role for IGF-II in postnatal alveologenesis was not further pursued.

Residential Age Segregation: Evidence from a Rapidly Ageing Asian City.

The problem of residential age segregation has been relatively under-studied, since spatial separation of older and younger people tends to be normalized. Prior literature demonstrates that age segregated environments may be socially isolating, especially for older adults, which may have detrimental impacts on their physical and mental health. While there are some studies on residential age segregation in Western contexts, there is scarce literature on age segregation in Asian cities. This mixed methods study examines changing patterns of residential age segregation in Hong Kong, through analyzing a combination of secondary census data and qualitative, in-depth interview data. The findings reveal that the extent of age segregation has remained consistently low from 2006 to 2016, although age segregation appears to be more pronounced between young adults in their early 20s and older adults above 65. Furthermore, in-depth interviews with 26 older people reveal that older people perceive themselves as being socially separated from younger people, especially older people who remain in ageing housing estates in urban districts. The findings add to the growing international literature on generational divides in spatial inequalities, while highlighting the influence of local housing policies on age segregation. The paper concludes by considering the policy implications of the findings, and the practical interventions that might contribute to reducing social isolation experienced by older people.

Acceptability and feasibility of a planned preconception weight loss intervention in women with long-acting reversible contraception: the Plan-it mixed-methods study.

BACKGROUND: Women with overweight (a body mass index of ≥ 25 kg/m2) or obesity (a body mass index of ≥ 30 kg/m2) are at greater risk of experiencing complications during pregnancy and labour than women with a healthy weight. Women who remove their long-acting reversible contraception (i.e. coils or implants) are one of the few groups of people who contact services as part of their preparation for conception, creating an opportunity to offer a weight loss intervention. OBJECTIVES: The objectives were to understand if routine NHS data captured the pathway from long-acting reversible contraception removal to pregnancy and included body mass index; to identify the suitable components of a preconception weight loss intervention; and to engage with key stakeholders to determine the acceptability and feasibility of asking women with overweight/obesity to delay the removal of their long-acting reversible contraception in order to take part in a preconception weight loss intervention. DESIGN: This was a preparatory mixed-methods study, assessing the acceptability and feasibility of a potential intervention, using routine NHS data and purposefully collected qualitative data. PARTICIPANTS: The NHS routine data included all women with a long-acting reversible contraception code. There were three groups of participants in the surveys and interviews: health-care practitioners who remove long-acting reversible contraception; weight management consultants; and women of reproductive age with experience of overweight/obesity and of using long-acting reversible contraception. SETTING: UK-based health-care practitioners recruited at professional meetings; and weight management consultants and contraceptive users recruited via social media. DATA SOURCES: Anonymised routine data from UK sexual health clinics and the Clinical Practice Research Datalink, including the Pregnancy Register; and online surveys and qualitative interviews with stakeholders. RESULTS: The records of 2,632,871 women aged 16-48 years showed that 318,040 had at least one long-acting reversible contraception event, with 62% of records including a body mass index. Given the identified limitations of the routine NHS data sets, it would not be feasible to reliably identify women with overweight/obesity who request a long-acting reversible contraception removal with an intention to become pregnant. Online surveys were completed by 100 health-care practitioners, four weight management consultants and 243 contraceptive users. Ten health-care practitioners and 20 long-acting reversible contraception users completed qualitative interviews. A realist-informed approach generated a hypothesised programme theory. The combination of weight discussions and the delay of long-acting reversible contraception removal was unacceptable as an intervention to contraceptive users for ethical and practical reasons. However, a preconception health intervention incorporating weight loss could be acceptable, and one potential programme is outlined. LIMITATIONS: There was very limited engagement with weight management consultants, and the sample of participating stakeholders may not be representative. CONCLUSIONS: An intervention that asks women to delay long-acting reversible contraception removal to participate in a preconception weight loss intervention would be neither feasible nor acceptable. A preconception health programme, including weight management, would be welcomed but requires risk communication training of health-care practitioners. FUTURE WORK: Work to improve routine data sets, increase awareness of the importance of preconception health and overcome health-care practitioner barriers to discussing weight as part of preconception care is a priority. TRIAL REGISTRATION: This trial is registered as ISRCTN14733020. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 1.

If a woman has overweight or obesity when she is pregnant, then there is a greater risk of health problems for her and her baby. About half of women of childbearing age have overweight or obesity, so we need to find ways of supporting women to lose weight before they become pregnant (described here as 'preconception'). This can be difficult because women do not usually talk to a health-care practitioner (e.g. general practitioners, sexual health doctors, nurses) about becoming pregnant, but one group of women who do are those who need to have a long-acting reversible contraceptive (e.g. a coil or an implant) removed. This study was designed as preparatory work for a potential future study of a preconception weight loss intervention. We wanted to answer three questions: (1) would women with experience of overweight and of using a long-acting reversible contraceptive think that it would be acceptable to ask women to delay having their long-acting reversible contraceptive removed to take part in a weight loss intervention before pregnancy; (2) what did health-care practitioners think about that idea, and would they be happy to ask women to take part; and (3) can NHS information (routine data) tell us how many women might potentially take part in such an intervention? We looked at NHS routine data and the research on preconception weight loss interventions. A total of 100 health-care practitioners and 243 users of long-acting reversible contraceptives completed surveys, and 10 health-care practitioners and 20 users of long-acting reversible contraceptives took part in interviews. We found that routine data could not be used to identify people reliably. Designing a weight loss intervention that needed women to delay the removal of a long-acting reversible contraceptive was not acceptable to women. A population-based preconception weight loss intervention with a positive focus was acceptable, but, for such a programme to be delivered by the NHS, health-care practitioners need more knowledge, skills and confidence in talking about weight with patients.

Post COVID-19 vaccine deaths - Singapore's early experience.

Singapore has been using mRNA vaccines developed by Pfizer-BioNTech and Moderna as part of the nation's COVID vaccination program since 30 December 2020. From 1 February 2021-30 June 2021, a total of 34 deaths that occurred within 72 h of the deceased receiving their COVID-19 vaccination were referred to the Forensic Medicine Division of the Health Sciences Authority of Singapore. Autopsies, histological sampling and ancillary investigations consisting of total tryptase level, Immunoglobulin E (IgE), and C-reactive Protein (CRP), were performed on 29 of these cases. Our study has shown no definite causative relationship between the mRNA vaccination and deaths of individuals who died within 72 h after receiving the vaccination, in particular with regards to anaphylactic reactions, myocarditis and pericarditis, and thrombotic complications. Further studies may consider increasing the incident time frame from 72 h to seven days post-vaccination or longer to include any potential delayed presentation of adverse effects.

Effectiveness of the Strengthening Families Programme in the UK at preventing substance misuse in 10-14 year-olds: a pragmatic randomised controlled trial.

OBJECTIVES: The Strengthening Families Programme 10-14 (SFP10-14) is a USA-developed universal group-based intervention aiming to prevent substance misuse by strengthening protective factors within the family. This study evaluated a proportionate universal implementation of the adapted UK version (SFP10-14UK) which brought together families identified as likely/not likely to experience/present challenges within a group setting. DESIGN: Pragmatic cluster-randomised controlled effectiveness trial, with families as the unit of randomisation and embedded process and economic evaluations. SETTING: The study took place in seven counties of Wales, UK. PARTICIPANTS: 715 families (919 parents/carers, 931 young people) were randomised. INTERVENTIONS: Families randomised to the intervention arm received the SFP10-14 comprising seven weekly sessions. Families in intervention and control arms received existing services as normal. OUTCOME MEASURES: Primary outcomes were the number of occasions young people reported drinking alcohol in the last 30 days; and drunkenness during the same period, dichotomised as 'never' and '1-2 times or more'. Secondary outcomes examined alcohol/tobacco/substance behaviours including: cannabis use; weekly smoking (validated by salivary cotinine measures); age of alcohol initiation; frequency of drinking >5 drinks in a row; frequency of different types of alcoholic drinks; alcohol-related problems. Retention: primary analysis included 746 young people (80.1%) (alcohol consumption) and 732 young people (78.6%) (drunkenness). RESULTS: There was no evidence of statistically significant between-group differences 2 years after randomisation for primary outcomes (young people's alcohol consumption in the last 30 days adjusted OR=1.11, 95% CI 0.72 to 1.71, p=0.646; drunkenness in the last 30 days adjusted OR=1.46, 95% CI 0.83 to 2.55, p=0.185). There were no statistically significant between-group differences for other substance use outcomes, or those relating to well-being/stress, and emotional/behavioural problems. CONCLUSIONS: Previous evidence of effectiveness was not replicated. Findings highlight the importance of evaluating interventions when they are adapted for new settings. TRIAL REGISTRATION NUMBER: ISRCTN63550893.Cite Now.

Long-term failure of alveologenesis after an early short-term exposure to a PDGF-receptor antagonist.

Survivors of moderate-to-severe bronchopulmonary dysplasia have impaired alveologenesis lasting at least into early adult life. The mechanisms underlying this long-term effect are unknown. We hypothesized that short-term inhibition of growth factor-mediated early alveolar formation would result in a long-term impairment of subsequent alveologenesis. Neonatal rats were injected daily with the platelet-derived growth factor (PDGF) receptor antagonist, imatinib mesylate, from day 1-7 of life, to inhibit the early alveolar formation occurring by in-growth of secondary crests into precursor saccules. The pups were then allowed to recover for 7, 14, 21, or 58 days. In imatinib-treated pups, DNA synthesis in total lung cells, and specifically in cells of secondary crests, was reduced at day 8 of life, had rebounded on day 14 of life but was then again reduced by day 28 of life. At day 8 of life, imatinib-treated pups had impaired alveologenesis as reflected by a decrease in secondary crests, an increase in alveolar size, and an overall decrease in both estimated alveolar number and generations compared with age-matched controls. No meaningful recovery was observed, even after a 21- or 58-day recovery period. The lungs of imatinib-treated pups had increased fibulin-5 content and an abnormal deposition of elastin. We conclude that reduced signaling through the PDGF pathways, at an early stage of alveologenesis, can result in long-lasting changes in lung architecture. A likely mechanism is through impaired formation of the elastin scaffold required for alveolarization.

Relationships Between Age, Frailty, Length of Care Home Residence and Biomarkers of Immunity and Inflammation in Older Care Home Residents in the United Kingdom.

Aging is associated with changes to the immune system, collectively termed immunosenescence and inflammageing. However, the relationships among age, frailty, and immune parameters in older people resident in care homes are not well described. We assessed immune and inflammatory parameters in 184 United Kingdom care home residents aged over 65 years and how they relate to age, frailty index, and length of care home residence. Linear regression was used to identify the independent contribution of age, frailty, and length of care home residence to the various immune parameters as dependent variables. Participants had a mean age (±SD) of 85.3 ± 7.5 years, had been residing in the care home for a mean (±SD) of 1.9 ± 2.2 years at the time of study commencement, and 40.7% were severely frail. Length of care home residence and frailty index were correlated but age and frailty index and age and length of care home residence were not significantly correlated. All components of the full blood count, apart from total lymphocytes, were within the reference range; 31% of participants had blood lymphocyte numbers below the lower value of the reference range. Among the components of the full blood count, platelet numbers were positively associated with frailty index. Amongst plasma inflammatory markers, C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1ra), soluble E-selectin and interferon gamma-induced protein 10 (IP-10) were positively associated with frailty. Plasma soluble vascular cell adhesion molecule 1 (sVCAM-1), IP-10 and tumor necrosis factor receptor II (TNFRII) were positively associated with age. Plasma monocyte chemoattractant protein 1 was positively associated with length of care home residence. Frailty was an independent predictor of platelet numbers, plasma CRP, IL-1ra, IP-10, and sE-selectin. Age was an independent predictor of activated monocytes and plasma IP-10, TNFRII and sVCAM-1. Length of care home residence was an independent predictor of plasma MCP-1. This study concludes that there are independent links between increased frailty and inflammation and between increased age and inflammation amongst older people resident in care homes in the United Kingdom. Since, inflammation is known to contribute to morbidity and mortality in older people, the causes and consequences of inflammation in this population should be further explored.

Combination of the Probiotics Lacticaseibacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis, BB-12 Has Limited Effect on Biomarkers of Immunity and Inflammation in Older People Resident in Care Homes: Results From the Probiotics to Reduce Infections iN CarE home reSidentS Randomized, Controlled Trial.

Aging is associated with a decline in many components of the immune system (immunosenescence). Probiotics may improve the immune response in older people. The objective was to determine the effect of the combination of two probiotic organisms [Lacticaseibacillus (previously known as Lactobacillus) rhamnosus GG (LGG) and Bifidobacterium animalis subsp. lactis, BB-12 (BB-12)] on a range of immune biomarkers measured in the blood of older people resident in care homes in the UK. In a randomized controlled trial, older people [aged 67-97 (mean 86) years] resident in care homes received the combination of LGG+BB-12 (1.3-1.6 × 109 CFU per day) or placebo for up to 12 months. Full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis, and blood culture responses to immune stimulation were all measured. Response to seasonal influenza vaccination was measured in a subset of participants. Paired samples (i.e., before and after intervention) were available for 30 participants per group. LGG and BB-12 were more likely to be present in feces in the probiotic group and were present at higher numbers. There was no significant effect of the probiotics on components of the full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis by neutrophils and monocytes, and blood culture responses to immune stimulation. There was an indication that the probiotics improved the response to seasonal influenza vaccination with significantly (p = 0.04) higher seroconversion to the A/Michigan/2015 vaccine strain in the probiotic group than in the placebo group (47 vs. 15%).

Small temporal pole encephaloceles: a treatable cause of "lesion negative" temporal lobe epilepsy.

Epilepsy due to encephaloceles of the temporal pole may be an under recognized, treatable cause of refractory temporal lobe epilepsy (TLE). We describe three adult patients initially labeled "lesion negative" TLE. In all, video­electroencephalography (EEG) revealed ictal theta in the left temporal region and positron emission tomography (PET) showed temporal lobe hypometabolism, but neuropsychology revealed preserved verbal memory. Close inspection of structural magnetic resonance imaging (MRI) suggested subtle abnormalities at the tip of the left temporal lobe. High resolution computed tomography (CT) confirmed bony defects in the inner table of the skull. 3T MRI with fine coronal and sagittal slices indicated cerebrospinal fluid (CSF) and brain tissue protruding into the defects. All proceeded to resection of the temporal tip and became seizure free. Patients with "lesion negative" TLE should have careful review of images covering the temporal pole. If encephalocele is suspected, further imaging with high-resolution CT and MRI can be helpful. Temporal polar resection, sparing mesial structures, appears to be curative.

Effects of rho-kinase inhibition on pulmonary hypertension, lung growth, and structure in neonatal rats chronically exposed to hypoxia.

Rho-kinase (ROCK) inhibitors prevent pulmonary hypertension (PHT) in adult rodents, but little is known about their effects on the neonatal lung. Our objective was to examine the effects of ROCK inhibition on chronic hypoxia (CH)-induced PHT and abnormal lung structure in the neonatal rat. Pups were exposed to air or CH from postnatal d 1-14 while receiving Y-27632 (5 or 10 mg x kg(-1) x d(-1)), fasudil (20 mg x kg(-1) x d(-1)), or saline intraperitoneally. Relative to air, CH-exposed pups had increased pulmonary vascular resistance, right ventricular hypertrophy, arterial medial wall thickening, and abnormal distal airway morphology characterized by septal thinning and decreased secondary septation. Treatment with 10 mg/kg Y-27632 or fasudil attenuated the structural and hemodynamic changes of PHT while having no effect on septal thinning or inhibited secondary septation. In addition, Y-27632 (10 mg/kg) and fasudil augmented CH-induced somatic growth restriction. Pulmonary arteries of CH-exposed pups had increased ROCK activity, up-regulated expression of PDGF-BB and increased smooth muscle DNA synthesis, all of which were attenuated by treatment with 10 mg/kg Y-27632. Systemically administered ROCK inhibitors prevented PHT in the CH-exposed neonatal rat but at the cost of inhibited somatic growth. Limiting effects on vascular remodeling likely resulted, in major part, from attenuated vascular PDGF-BB/beta-receptor signaling.

Qualitative process evaluation of the Fostering Changes program for foster carers as part of the Confidence in Care randomized controlled trial.

BACKGROUND: Fostering Changes is an in-service training program for foster carers designed to enhance carer skills, coping strategies and carer-child relationships. The training program has been evaluated in a randomised controlled trial comparing Fostering Changes to usual care. OBJECTIVE: To conduct a qualitative process evaluation drawing on stakeholder perspectives to describe the logic model of Fostering Changes, identify potential mechanisms of impact of the program and enhance understanding of the trial results. PARTICIPANTS AND SETTING: Participants were stakeholders in the Fostering Changes program delivered in Wales, UK including foster carers invited to attend the program (18 attendees, eight non-attendees), two program developers, five trainers, 12 social workers who attended or recruited to the program. METHODS: Total population sampling with qualitative data collection methods. Qualitative data were subject to thematic analysis. RESULTS: A logic model summarising the program resources, activities and anticipated outcomes was generated. Implementation themes were quality of training, setting and group composition. Mechanisms of impact were identified with themes falling into two categories, group process and skills development. Potential barriers to effectiveness included a poor fit between the carer needs and the program in relation to levels of challenge being faced, age-appropriate content and responsiveness. Contextual factors were also relevant, including the existing relationship between foster carers and the agency and the perceived value of training. CONCLUSIONS: Although the group aspects of the program were well received, the program itself did not help foster carers deal with more complex challenges and needed to be more targeted in terms of carers needs and circumstances.

A pragmatic randomised controlled trial of the fostering changes programme.

BACKGROUND: Many looked after young people in Wales are cared for by foster or kinship carers, usually as a consequence of maltreatment or developmentally traumatising experiences within a family context. Confidence in Care is a pragmatic unblinded individually randomised controlled parallel group trial evaluating a training programme to improve foster carer self-efficacy, when compared to usual care. OBJECTIVE: To determine whether group-based training improves foster carer self-efficacy. PARTICIPANTS AND SETTING: Participants are foster carers, currently looking after children aged 2+ years for at least 12 weeks. Carers from households where one or more carer had previously attended the training were not eligible. Sixteen local authorities and three independent fostering providers in Wales took part. METHODS: The primary outcome measure was the Carer Efficacy Questionnaire assessed at 12 months. Secondary outcomes included the Strengths and Difficulties Questionnaire, Quality of Attachment Questionnaire, Carer Defined Problems Scale, Carer Coping Strategies, placement moves. RESULTS: 312 consented foster carers were allocated to FC (n = 204) or usual care (n = 108) group. 65.3 % of FC group participants attended sufficient training sessions (8/12, including sessions three and four). There were no differences in carer-reported self-efficacy at 12 months (adjusted difference in means (95 % CI): -0.19 (-1.38 to 1.00)). Small differences in carer-reported child behaviour difficulties and carer coping strategies over time favoured the intervention but these effects diminished from three to 12 months. No other intervention effects were observed. CONCLUSIONS: Although well-received by participants, training was associated with small and mostly short-term benefit for trial secondary outcomes.

Therapeutic effects of hypercapnia on chronic lung injury and vascular remodeling in neonatal rats.

Permissive hypercapnia, achieved using low tidal volume ventilation, has been an effective protective strategy in patients with acute respiratory distress syndrome. To date, no such protective effect has been demonstrated for the chronic neonatal lung injury, bronchopulmonary dysplasia. The objective of our study was to determine whether evolving chronic neonatal lung injury, using a rat model, is resistant to the beneficial effects of hypercapnia or simply requires a less conservative approach to hypercapnia than that applied clinically to date. Neonatal rats inhaled air or 60% O2 for 14 days with or without 5.5% CO2. Lung parenchymal neutrophil and macrophage numbers were significantly increased by hyperoxia alone, which was associated with interstitial thickening and reduced secondary crest formation. The phagocyte influx, interstitial thickening, and impaired alveolar formation were significantly attenuated by concurrent hypercapnia. Hyperoxic pups that received 5.5% CO2 had a significant increase in alveolar number relative to air-exposed pups. Increased tyrosine nitration, a footprint for peroxynitrite-mediated reactions, arteriolar medial wall thickening, and both reduced small peripheral pulmonary vessel number and VEGF and angiopoietin-1 (Ang-1) expression, which were observed with hyperoxia, was attenuated by concurrent hypercapnia. We conclude that evolving chronic neonatal lung injury in a rat model is responsive to the beneficial effects of hypercapnia. Inhaled 5.5% CO2 provided a significant degree of protection against parenchymal and vascular injury in an animal model of chronic neonatal lung injury likely due, at least in part, to its inhibition of a phagocyte influx.