The Same IκBα Mutation in Two Related Individuals Leads to Completely Different Clinical Syndromes

Both innate and adaptive immune responses are dependent on activation of nuclear factor κB (NF-κB), induced upon binding of pathogen-associated molecular patterns to Toll-like receptors (TLRs). In murine models, defects in NF-κB pathway are often lethal and viable knockout mice have severe immune defects. Similarly, defects in the human NF-κB pathway described to date lead to severe clinical disease. Here, we describe a patient with a hyper immunoglobulin M–like immunodeficiency syndrome and ectodermal dysplasia. Monocytes did not produce interleukin 12p40 upon stimulation with various TLR stimuli and nuclear translocation of NF-κB was impaired. T cell receptor–mediated proliferation was also impaired. A heterozygous mutation was found at serine 32 in IκBα. Interestingly, his father has the same mutation but displays complex mosaicism. He does not display features of ectodermal dysplasia and did not suffer from serious infections with the exception of a relapsing Salmonella typhimurium infection. His monocyte function was impaired, whereas T cell function was relatively normal. Consistent with this, his T cells almost exclusively displayed the wild-type allele, whereas both alleles were present in his monocytes. We propose that the T and B cell compartment of the mosaic father arose as a result of selection of wild-type cells and that this underlies the widely different clinical phenotype

Acceptability of a nurse-led, person-centred, anticipatory care planning intervention for older people at risk of functional decline: A qualitative study

Background As the population of older adults increases, the complexity of care required to support those who choose to remain in the community amplifies. Anticipatory Care Planning (ACP), through earlier identification of healthcare needs, is evidenced to improve quality of life, decrease aggressive interventions, and prolong life. With patient acceptability of growing importance in the design, implementation, and evaluation of healthcare interventions, this study reports on the acceptability of a primary care based ACP intervention on the island of Ireland. Methods As part of the evaluation of a feasibility cluster randomized controlled trial (cRCT) testing an ACP intervention for older people at risk of functional decline, intervention participants [n = 34] were interviewed in their homes at 10-week follow-up to determine acceptability. The intervention consisted of home visits by specifically trained registered nurses who assessed participants’ health, discussed their health goals and plans, and devised an anticipatory care plan in collaboration with participants’ GPs and adjunct clinical pharmacist. Thematic analysis was employed to analyze interview data. The feasibility cRCT involved eight general practitioner (GP) practices as cluster sites, stratified by jurisdiction, four in Northern Ireland (NI) (two intervention, two control), and four in the Republic of Ireland (ROI) (two intervention, two control). Participants were assessed for risk of functional decline. A total of 34 patients received the intervention and 31 received usual care. Findings Thematic analysis resulted in five main themes: timing of intervention, understanding of ACP, personality &amp; individual differences, loneliness &amp; social isolation, and views on healthcare provision. These map across the Four Factor Model of Acceptability (‘4FMA’), a newly developed conceptual framework comprising four components: intervention factors, personal factors, social support factors, and healthcare provision factors. Conclusion Acceptability of this primary care based ACP intervention was high, with nurses’ home visits, GP anchorage, multidisciplinary working, personalized approach, and active listening regarded as beneficial. Appropriate timing, and patient health education emerged as vital. </jats:sec

Acceptability of a nurse-led, person-centred, anticipatory care planning intervention for older people at risk of functional decline: A qualitative study

BACKGROUND: As the population of older adults increases, the complexity of care required to support those who choose to remain in the community amplifies. Anticipatory Care Planning (ACP), through earlier identification of healthcare needs, is evidenced to improve quality of life, decrease aggressive interventions, and prolong life. With patient acceptability of growing importance in the design, implementation, and evaluation of healthcare interventions, this study reports on the acceptability of a primary care based ACP intervention on the island of Ireland. METHODS: As part of the evaluation of a feasibility cluster randomized controlled trial (cRCT) testing an ACP intervention for older people at risk of functional decline, intervention participants [n = 34] were interviewed in their homes at 10-week follow-up to determine acceptability. The intervention consisted of home visits by specifically trained registered nurses who assessed participants’ health, discussed their health goals and plans, and devised an anticipatory care plan in collaboration with participants’ GPs and adjunct clinical pharmacist. Thematic analysis was employed to analyze interview data. The feasibility cRCT involved eight general practitioner (GP) practices as cluster sites, stratified by jurisdiction, four in Northern Ireland (NI) (two intervention, two control), and four in the Republic of Ireland (ROI) (two intervention, two control). Participants were assessed for risk of functional decline. A total of 34 patients received the intervention and 31 received usual care. FINDINGS: Thematic analysis resulted in five main themes: timing of intervention, understanding of ACP, personality & individual differences, loneliness & social isolation, and views on healthcare provision. These map across the Four Factor Model of Acceptability (‘4FMA’), a newly developed conceptual framework comprising four components: intervention factors, personal factors, social support factors, and healthcare provision factors. CONCLUSION: Acceptability of this primary care based ACP intervention was high, with nurses’ home visits, GP anchorage, multidisciplinary working, personalized approach, and active listening regarded as beneficial. Appropriate timing, and patient health education emerged as vital

Successful implementation of a trans-jurisdictional, primary care, anticipatory care planning intervention for older adults at risk of functional decline: interviews with key health professionals

Abstract Background Aging populations present a challenge to health systems internationally, due to the increasing complexity of care for older adults living with functional decline. This study aimed to elicit expert views of key health professionals on effective and sustainable implementation of a nurse-led, person-centred anticipatory care planning (ACP) intervention for older adults at risk of functional decline in a primary care setting. Methods We examined the feasibility of an ACP intervention in a trans-jurisdictional feasibility cluster randomized controlled trial consisting of home visits by research nurses who assessed participants’ health, discussed their health goals and devised an anticipatory care plan following consultation with participants’ GPs and adjunct clinical pharmacist. As part of the project, we elicited the views and recommendations of experienced key health professionals working with the target population who were recruited using a ‘snowballing technique’ in cooperation with older people health networks in the Republic of Ireland (ROI) and Northern Ireland (NI), United Kingdom [n = 16: 7 ROI, 9 NI]. Following receipt of written information about the intervention and the provision of informed consent, the health professionals were interviewed to determine their expert views on the feasibility of the ACP intervention and recommendations for successful implementation. Data were analyzed using thematic analysis. Results The ACP intervention was perceived to be beneficial for most older patients with multimorbidity. Effective and sustainable implementation was said to be facilitated by accurate and timely patient selection, GP buy-in, use of existing structures within health systems, multidisciplinary and integrated working, ACP nurse training, as well as patient health literacy. Barriers emerged as significant work already undertaken, increasing workload, lack of time, funding and resources, fragmented services, and geographical inequalities. Conclusions The key health professionals perceived the ACP intervention to be highly beneficial to patients, with significant potential to prevent or avoid functional decline and hospital admissions. They suggested that successful implementation of this primary care based, whole-person approach would involve integrated and multi-disciplinary working, GP buy in, patient health education, and ACP nurse training. The findings have potential implications for a full trial, and patient care and health policy. Trial registration Clinicaltrials.gov, ID: NCT03902743. Registered on 4 April 2019. </jats:sec

Successful implementation of a trans-jurisdictional, primary care, anticipatory care planning intervention for older adults at risk of functional decline: interviews with key health professionals

Abstract Background Aging populations present a challenge to health systems internationally, due to the increasing complexity of care for older adults living with functional decline. This study aimed to elicit expert views of key health professionals on effective and sustainable implementation of a nurse-led, person-centred anticipatory care planning (ACP) intervention for older adults at risk of functional decline in a primary care setting. Methods We examined the feasibility of an ACP intervention in a trans-jurisdictional feasibility cluster randomized controlled trial consisting of home visits by research nurses who assessed participants’ health, discussed their health goals and devised an anticipatory care plan following consultation with participants’ GPs and adjunct clinical pharmacist. As part of the project, we elicited the views and recommendations of experienced key health professionals working with the target population who were recruited using a ‘snowballing technique’ in cooperation with older people health networks in the Republic of Ireland (ROI) and Northern Ireland (NI), United Kingdom [n = 16: 7 ROI, 9 NI]. Following receipt of written information about the intervention and the provision of informed consent, the health professionals were interviewed to determine their expert views on the feasibility of the ACP intervention and recommendations for successful implementation. Data were analyzed using thematic analysis. Results The ACP intervention was perceived to be beneficial for most older patients with multimorbidity. Effective and sustainable implementation was said to be facilitated by accurate and timely patient selection, GP buy-in, use of existing structures within health systems, multidisciplinary and integrated working, ACP nurse training, as well as patient health literacy. Barriers emerged as significant work already undertaken, increasing workload, lack of time, funding and resources, fragmented services, and geographical inequalities. Conclusions The key health professionals perceived the ACP intervention to be highly beneficial to patients, with significant potential to prevent or avoid functional decline and hospital admissions. They suggested that successful implementation of this primary care based, whole-person approach would involve integrated and multi-disciplinary working, GP buy in, patient health education, and ACP nurse training. The findings have potential implications for a full trial, and patient care and health policy. Trial registration Clinicaltrials.gov, ID: NCT03902743 . Registered on 4 April 2019

Metal Transfer among Organs Following Short- and Long-Term Exposures Using Autoradiography: Cadmium Bioaccumulation by the Freshwater Prawn <i>Macrobrachium australiense</i>

The uptake, depuration, and organ distribution of the radioisotope ¹⁰⁹Cd were used to explore the internal kinetics of this nonessential metal following accumulation from waterborne cadmium by the freshwater decapod crustacean <i>Macrobrachium australiense</i>. Short- (6 h) and long-term (7 to 14 days) exposures to the radioisotope in solutions of 0.56 μg Cd/L were followed by depuration in metal- and isotope-free water for up to 21 days. The anatomical distribution of the radionuclide was visualized using autoradiography at predefined time points. The gills did not become saturated with cadmium after 14 days of exposure and demonstrated a greater rate of cadmium uptake relative to the hepatopancreas. Cadmium concentrations decreased rapidly during depuration from both gills and hepatopancreas after short exposures but slowly following long-term exposures. This suggests that the duration of cadmium exposure influences the depuration rate for this organism. The study demonstrates the complex behavior of cadmium accumulated by <i>M. australiense</i> and improves our understanding of how exposure duration will influence the internal location and potential toxicity of metals