Catalyzing Collaboration Among Interprofessional Birth Transfer Teams Through Simulation.

INTRODUCTION: Planned home or birth center births sometimes require emergency transfers to a hospital. Poor communication among members of the birth care team during a transfer can lead to unfavorable outcomes for the birthing person and newborn. To improve the quality of birth transfers in Utah, the Utah Women and Newborns Quality Collaborative partnered with the LIFT Simulation Design Lab to develop and pilot an interprofessional birth transfer simulation training. METHODS: We engaged community stakeholders to identify learning objectives and co-design the simulation trainings using principles of participatory design. We conducted 5 simulation trainings featuring birth transfers during a postpartum hemorrhage. The LIFT Lab evaluated the trainings to determine if they were feasible, acceptable, and effective. Measures included a post-training form asking participants to evaluate the quality of the training and a 9-question pre- and post-training survey measuring changes in participants' self-efficacy regarding components of birth transfer. The changes were assessed for significance using a paired t test. RESULTS: A total of 102 participants attended the 5 trainings; all health care provider groups were well represented. Most participants felt the simulations were similar to real situations and would benefit others in their professions. All participants said the trainings were a good use of their time. Following the training, participants had significantly higher levels of self-efficacy regarding their ability to manage birth transfers. DISCUSSION: Birth transfer simulation trainings are an acceptable, feasible, and effective method for training interprofessional birth care teams.

Remotely Delivered Cardiac Rehabilitation Exercise for Coronary Heart Disease: Nonrandomized Feasibility Study.

BACKGROUND: Exercise-based cardiac rehabilitation (CR) is recommended for coronary heart disease (CHD). However, poor uptake of and poor adherence to CR exercise programs have been reported globally. Delivering CR exercise classes remotely may remove some of the barriers associated with traditional hospital- or center-based CR. OBJECTIVE: We have developed a bespoke platform, Eastern Corridor Medical Engineering Centre-Cardiac Rehabilitation (ECME-CR), to support remotely delivered CR exercise. This pilot trial sought to test the ECME-CR platform and examine the efficacy and feasibility of a remote CR exercise program compared to a traditional center-based program. METHODS: In all, 21 participants with CHD were recruited and assigned to either the intervention or control group. Both groups performed the same 8-week exercise program. Participants in the intervention group took part in web-based exercise classes and used the ECME-CR platform during the intervention period, whereas participants in the control group attended in-person classes. Outcomes were assessed at baseline and following the 8-week intervention period. The primary outcome measure was exercise capacity, assessed using a 6-minute walk test (6MWT). Secondary outcomes included measurement of grip strength, self-reported quality of life, heart rate, blood pressure, and body composition. A series of mixed between-within subjects ANOVA were conducted to examine the mean differences in study outcomes between and within groups. Participant adherence to the exercise program was also analyzed. RESULTS: In all, 8 participants (male: n=5; age: mean 69.7, SD 7.2 years; height: mean 163.9, SD 5.4 cm; weight: mean 81.6, SD 14.1 kg) in the intervention group and 9 participants (male: n=9; age: mean 69.8, SD 8.2 years; height: mean 173.8, SD 5.2 cm; weight: mean 94.4, SD 18.0 kg) in the control group completed the exercise program. Although improvements in 6MWT distance were observed from baseline to follow-up in both the intervention (mean 490.1, SD 80.2 m to mean 504.5, SD 93.7 m) and control (mean 510.2, SD 48.3 m to mean 520.6, SD 49.4 m) group, no significant interaction effect (F1,14=.026; P=.87) nor effect for time (F1,14=2.51; P=.14) were observed. No significant effects emerged for any of the other secondary end points (all P>.0275). Adherence to the exercise program was high in both the intervention (14.25/16, 89.1%) and control (14.33/16, 89.6%) group. No adverse events or safety issues were reported in either group during the study. CONCLUSIONS: This pilot trial did not show evidence of significant positive effect for either the remotely delivered or center-based program. The 6MWT may not have been sufficiently sensitive to identify a change in this cohort of participants with stable CHD. This trial does provide evidence that remote CR exercise, supported with digital self-monitoring, is feasible and may be considered for individuals less likely to participate in traditional center-based programs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/31855.

Serious health-related suffering experienced by children with disability and their families living in Bangladesh: A scoping review.

BACKGROUND: In 2020, the International Association for Hospice and Palliative Care redefined palliative care to incorporate the concept of serious health-related suffering. An estimated 21 million children globally live with conditions which would benefit from a palliative approach to relieve suffering. Bangladesh is a lower-middle income country with isolated provision of palliative care. AIM: To synthesise existing evidence describing serious health-related suffering of children with disability and their families living in Bangladesh and the intersection between this suffering, palliative care and rehabilitation. DESIGN: Scoping review methodology. DATA SOURCES: A search strategy related to serious health-related suffering and childhood disability was applied to online databases and grey literature. English language studies (1990-2021) were included. Papers pertaining to serious health-related suffering of typically developing children and those over eighteen years were excluded. Data which addressed the three domains of serious health-related suffering (physical, social and emotional/spiritual) were extracted. Palliative care interventions were assessed with a pre-existing checklist. RESULTS: Forty-six studies were included, representing ten different methodologies. Sample sizes ranged from 11 to 2582 participants, with 87% of studies including children with cerebral palsy. Serious health-related suffering was described in 100% of the studies, only 14 of the studies described specific interventions to mitigate suffering. Convergence between palliative care and rehabilitation approaches was evident. CONCLUSION: Findings document the extensive nature and burden of serious childhood health-related suffering that may be remediated by a palliative approach. They highlight the urgent need to prioritise service development and research in this area.

The role of phone-based triage nurses in supporting older adults with multimorbidity to digitally self-manage - Findings from the ProACT proof-of-concept study.

Background: Achieving patient-centred care necessitates supporting individuals to have more involvement in the self-management of their care. Digital health technologies are widely recognised as a solution to empower more effective self-management. However, given the complexity of multiple chronic condition (multimorbidity) management, coupled with changes that occur as part of the normal ageing process, human support alongside digital self-management is often necessary for older people with multimorbidity (PwM) to sustain successful self-management. Methods: The aim of the study was to explore the role played by a clinical, nurse-led telephone triage service in responding to alerts generated by older adults using a digital health platform, ProACT, to self-manage multiple chronic conditions over a period of 1 year. Semi-structured interviews with participants with multimorbidity were carried out across four time points during the trial, while interviews and focus groups were conducted with triage nurses at the end of the trial. Thematic analysis was conducted on the resulting transcripts. Results: Themes found in the data include the work of triage nurses; the benefits of triage support; tensions such as anxiety due to patient monitoring; and the relationship between triage nurses and participants. Discussion: This work contributes to an understanding of how older adults with multimorbidity and triage nurses collaborate in multiple chronic disease self-management. Findings are discussed within the context of Hudon et al.'s patient-centred care framework and indicate that patient-centred care was achieved, with both PwM and triage participants reporting positive experiences, relationships and several benefits of the triage support alongside digital self-management.

Measurement of Heart Rate Using the Withings ScanWatch Device During Free-living Activities: Validation Study.

BACKGROUND: Wrist-worn devices that incorporate photoplethysmography (PPG) sensing represent an exciting means of measuring heart rate (HR). A number of studies have evaluated the accuracy of HR measurements produced by these devices in controlled laboratory environments. However, it is also important to establish the accuracy of measurements produced by these devices outside the laboratory, in real-world, consumer use conditions. OBJECTIVE: This study sought to examine the accuracy of HR measurements produced by the Withings ScanWatch during free-living activities. METHODS: A sample of convenience of 7 participants volunteered (3 male and 4 female; mean age 64, SD 10 years; mean height 164, SD 4 cm; mean weight 77, SD 16 kg) to take part in this real-world validation study. Participants were instructed to wear the ScanWatch for a 12-hour period on their nondominant wrist as they went about their day-to-day activities. A Polar H10 heart rate sensor was used as the criterion measure of HR. Participants used a study diary to document activities undertaken during the 12-hour study period. These activities were classified according to the 11 following domains: desk work, eat or drink, exercise, gardening, household activities, self-care, shopping, sitting, sleep, travel, and walking. Validity was assessed using the Bland-Altman analysis, concordance correlation coefficient (CCC), and mean absolute percentage error (MAPE). RESULTS: Across all activity domains, the ScanWatch measured HR with MAPE values <10%, except for the shopping activity domain (MAPE=10.8%). The activity domains that were more sedentary in nature (eg, desk work, eat or drink, and sitting) produced the most accurate HR measurements with a small mean bias and MAPE values <5%. Moderate to strong correlations (CCC=0.526-0.783) were observed between devices for all activity domains, except during the walking activity domain, which demonstrated a weak correlation (CCC=0.164) between devices. CONCLUSIONS: The results of this study show that the ScanWatch measures HR with a degree of accuracy that is acceptable for general consumer use; however, it would not be suitable in circumstances where more accurate measurements of HR are required, such as in health care or in clinical trials. Overall, the ScanWatch was less accurate at measuring HR during ambulatory activities (eg, walking, gardening, and household activities) compared to more sedentary activities (eg, desk work, eat or drink, and sitting). Further larger-scale studies examining this device in different populations and during different activities are required.

Investigating the needs and concerns of older adults with multimorbidity and their healthcare professionals for conceivable digital psychotherapeutic interventions.

Multimorbidity, defined as the concurrent experience of more than one chronic health condition in an individual, affects ∼65% of people over 65 and 85% of those over 85 years old with 30% of those also experiencing mental health concerns. This can lead to reduced quality of life and functioning as well as poorer outcomes in terms of condition management, adherence to treatment, and ultimately disease prognosis and progression. Digital health interventions offer a viable means of condition self-management, as well as psychological support, particularly for those who may have difficulty accessing in-person services. To best meet the needs of older adults with multimorbidity, deeper insights are needed into their specific concerns and issues around condition management, particularly with regard to distress in relation to managing one's condition. The present study aimed to explore this using one-to-one qualitative interviews and focus groups with people with chronic health conditions and healthcare professionals. Participants were 11 older adults with multimorbidity (4 males; mean age: M = 72.7 years) and 14 healthcare professionals including five clinical nurse specialists, four pharmacists, two general practitioners, one occupational therapist, one speech and language therapist and one dietician. Thematic analysis was used to identify key themes, which included: patient feelings of anxiety or worry leading to an unwillingness to access essential information; the various mental health challenges faced by those with multimorbidity; the importance of personal values in providing motivation; and the importance of social support. Findings are discussed in relation to the potential development of transdiagnostically applicable digital interventions for the management of distress in those with multimorbidity.

Efficacy of a Digital Acceptance and Commitment Therapy Intervention for the Improvement of Self-management Behaviors and Psychological Flexibility in Adults With Cardiac Disease: Protocol for a Single Case Experimental Design.

BACKGROUND: Research indicates that the management of distress levels in those with cardiac disease is not only important for improving quality of life and functioning but also critical for condition management; adherence to treatment; and, ultimately, disease prognosis and progression. Acceptance and commitment therapy (ACT) has consistently demonstrated positive long-term outcomes across a wide array of conditions, including chronic illness. However, most empirical investigations conducted to date have also involved in-person therapy, which can be difficult to access, particularly for those dealing with the demands of chronic disease. OBJECTIVE: The objective of our research is to evaluate a digital ACT intervention for improving self-management behaviors and distress levels in those with cardiac conditions. METHODS: The digital ACT intervention will be delivered via a digital health self-management platform over 6 sessions. This will involve a randomized, multiple baseline, single case experimental design with approximately 3 to 15 adults with cardiac disease. The independent variable for each participant will be the pre-post intervention phase. The dependent variables will be a daily self-report measure of psychological flexibility as well as objective measures of condition self-management (eg, blood pressure readings) and engagement with the app (eg, completing guided mindfulness). One-to-one qualitative interviews will also be conducted to further examine participants' experiences with using the intervention and what factors contribute to or impede successful outcomes. RESULTS: Participant recruitment and data collection began in October 2021, and it is projected that the study findings will be available for dissemination by spring 2022. CONCLUSIONS: The findings will be discussed in terms of how a digital ACT intervention can best meet the needs of cardiac patients. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/33783.

Establishing consensus for the assessment of chronic pain in children and young people with cerebral palsy: a Delphi study.

PURPOSE: Inconsistent and inadequate pain assessment practices in cerebral palsy (CP) have resulted from a lack of standardisation of pain assessment, limited use of appropriate tools and failure to integrate disability and biopsychosocial models. To assist with improving consistency, this study aimed to establish consensus from key stakeholders regarding domains considered essential for measuring chronic pain in children and young people with CP. METHOD: A modified electronic Delphi study was conducted on 83 stakeholders, including clinicians, researchers, people with CP and parents of children with CP. Participants rated 18 domains sourced from existing literature as either "core", "recommended", "exploratory" or "not required". RESULTS: After two rounds of surveys, 12 domains were considered core: pain location, pain frequency, pain intensity, changeable factors, impact on emotional wellbeing, impact on participation, pain communication, influence on quality of life, physical impacts, sleep, pain duration and pain expression. CONCLUSION: These domains reflect the complexity of pain in a heterogeneous population where medical comorbidities are common and communication and intellectual limitations impact significantly on the ability of many to self-report. The domains will be utilised to build a framework of pain assessment specific to children and young people with CP guided by the biopsychosocial model.Implications for rehabilitationChronic pain is under-identified and poorly assessed in the cerebral palsy (CP) population.The perspectives of clinicians, researchers and consumers are vital for developing a framework for chronic pain assessment in CP.Consensus of key stakeholders found 12 domains considered essential to incorporate into a chronic pain assessment model in CP.

A Digital Platform to Support Self-management of Multiple Chronic Conditions (ProACT): Findings in Relation to Engagement During a One-Year Proof-of-Concept Trial.

BACKGROUND: Populations globally are ageing, resulting in higher incidence rates of chronic diseases. Digital health platforms, designed to support those with chronic conditions to self-manage at home, offer a promising solution to help people monitor their conditions and lifestyle, maintain good health, and reduce unscheduled clinical visits. However, despite high prevalence rates of multimorbidity or multiple chronic conditions, most platforms tend to focus on a single disease. A further challenge is that despite the importance of users actively engaging with such systems, little research has explored engagement. OBJECTIVE: The objectives of this study are to design and develop a digital health platform, ProACT, for facilitating older adults self-managing multimorbidity, with support from their care network, and evaluate end user engagement and experiences with this platform through a 12-month trial. METHODS: The ProACT digital health platform is presented in this paper. The platform was evaluated in a year-long proof-of-concept action research trial with 120 older persons with multimorbidity in Ireland and Belgium. Alongside the technology, participants had access to a clinical triage service responding to symptom alerts and a technical helpdesk. Interactions with the platform during the trial were logged to determine engagement. Semistructured interviews were conducted with participants and analyzed using inductive thematic analysis, whereas usability and user burden were examined using validated questionnaires. RESULTS: This paper presents the ProACT platform and its components, along with findings on engagement with the platform and its usability. Of the 120 participants who participated, 24 (20%) withdrew before the end of the study, whereas 3 (2.5%) died. The remaining 93 participants actively used the platform until the end of the trial, on average, taking 2 or 3 health readings daily over the course of the trial in Ireland and Belgium, respectively. The participants reported ProACT to be usable and of low burden. Findings from interviews revealed that participants experienced multiple benefits as a result of using ProACT, including improved self-management, health, and well-being and support from the triage service. For those who withdrew, barriers to engagement were poor health and frustration when technology, in particular sensing devices, did not work as expected. CONCLUSIONS: This is the first study to present findings from a longitudinal study of older adults using digital health technology to self-manage multimorbidity. Our findings show that older adults sustained engagement with the technology and found it usable. Potential reasons for these results include a strong focus on user-centered design and engagement throughout the project lifecycle, resulting in a platform that meets user needs, as well as the integration of behavior change techniques and personal analytics into the platform. The provision of triage and technical support services alongside the platform during the trial were also important facilitators of engagement. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/22125.

A Digital Health Platform for Integrated and Proactive Patient-Centered Multimorbidity Self-management and Care (ProACT): Protocol for an Action Research Proof-of-Concept Trial.

BACKGROUND: Multimorbidity is defined as the presence of two or more chronic diseases and associated comorbidities. There is a need to improve best practices around the provision of well-coordinated, person-centered care for persons with multimorbidities. Present health systems across the European Union (EU) focus on supporting a single-disease framework of care; the primary challenge is to create a patient-centric, integrated care ecosystem to understand and manage multimorbidity. ProACT is a large-scale project funded by the European Commission under the Horizon 2020 programme, that involved the design, development, and evaluation of a digital health platform to improve and advance home-based integrated care, and supported self-management, for older adults (aged ≥65 years) living with multimorbidity. OBJECTIVE: This paper describes the trial implementation protocol of a proof-of-concept digital health platform (ProACT) in 2 EU member states (Ireland and Belgium) to support older persons with multimorbidities self-managing at home, supported by their care network (CN). METHODS: Research was conducted across 2 EU member states, Ireland and Belgium. A 12-month action research trial design, divided into 3 evaluation cycles and lasting 3 months each, with a reflective redesign and development phase of 1 month after cycles 1 and 2 was conducted. Participants were 120 (60/120, 50% in Ireland and 60/120, 50% in Belgium) older persons with multimorbidities diagnosed with two or more of the following chronic conditions: diabetes, chronic obstructive pulmonary disease, chronic heart failure, and cardiovascular diseases. With permission from persons with multimorbidities, members of their CN were invited to participate in the study. Persons with multimorbidities were provided with ProACT technologies (tablet, devices, or sensors) to support them in self-managing their conditions. CN members also received access to an app to remotely support their persons with multimorbidity. Qualitative and quantitative feedback and evaluation data from persons with multimorbidity and CN participants were collected across four time points: baseline (T1), at the end of each 3-month action research cycle (T2 and T3), and in a final posttrial interview (T4). Thematic analysis was used to analyze the qualitative interview data. Quantitative data were analyzed via platform use statistics (to assess engagement) and standardized questionnaires (using descriptive and inferential statistics). This study is approved by the ethics committees of Ireland and Belgium. RESULTS: The trial implementation phase for this 44-month (2016-2019) funded study was April 2018 to June 2019. The trial outcomes are at various stages of publication since 2021. CONCLUSIONS: ProACT aims to co-design and develop a digital intervention with persons with multimorbidities and their CN, incorporating clinical guidelines with the state of the art in human-computer interaction, behavioral science, health psychology, and data analytic methods to deliver a digital health platform to advance self-management of multimorbidity at home, as part of a proactive, integrated model of supported person-centered care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/22125.

Delivering Cardiac Rehabilitation Exercise Virtually Using a Digital Health Platform (ECME-CR): Protocol for a Pilot Trial.

BACKGROUND: Exercise-based cardiac rehabilitation is recognized as a core component of cardiovascular disease management and has been shown to reduce all-cause and cardiovascular mortality and reduce the risk of hospital readmission following a cardiac event. However, despite this, the uptake of and long-term adherence to cardiac rehabilitation exercise is poor. Delivering cardiac rehabilitation exercise virtually (ie, allowing patients to participate from their own homes) may be an alternative approach that could enhance uptake and increase adherence. OBJECTIVE: The aim of this study is to assess the feasibility of delivering a virtual cardiac rehabilitation exercise program supported by the Eastern Corridor Medical Engineering - Cardiac Rehabilitation (ECME-CR) platform. METHODS: A convenience sample (n=20) of participants eligible to participate in community-based cardiac rehabilitation exercise will be recruited. Participants will be randomized to one of two study groups. Both study groups will perform the same exercise program, consisting of twice-weekly sessions of 60 minutes each, over an 8-week intervention period. Participants in the intervention group will partake in virtually delivered cardiac rehabilitation exercise classes in their own home. The virtual exercise classes will be delivered to participants using a videoconferencing platform. Participants in the control group will attend the research center for their cardiac rehabilitation exercise classes. Intervention group participants will receive the ECME-CR digital health platform for monitoring during the class and during the intervention period. Outcomes will be assessed at baseline and following the 8-week intervention period. The primary outcome will be exercise capacity as assessed using the 6-minute walk test. Other outcome measures will include heart rate, blood pressure, weight, percentage body fat, muscle strength, and self-reported quality of life. Semistructured interviews will also be conducted with a subset of participants to explore their experiences of using the digital platform. RESULTS: Participant recruitment and data collection will begin in July 2021, and it is anticipated that the study results will be available for dissemination in spring 2022. CONCLUSIONS: This pilot trial will inform the design of a randomized controlled trial that will assess the clinical effectiveness of the ECME-CR digital health platform. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/31855.

Effect of Miricorilant, a Selective Glucocorticoid Receptor Modulator, on Olanzapine-Associated Weight Gain in Healthy Subjects: A Proof-of-Concept Study.

PURPOSE: Antipsychotic medications, including olanzapine, are associated with substantial weight gain and metabolic disturbances. We sought to determine whether coadministration of miricorilant, a selective glucocorticoid receptor modulator, with olanzapine can ameliorate these effects. METHODS: Sixty-six healthy men were enrolled in a 2-week, randomized, double-blind, placebo-controlled trial. The primary objective was to evaluate changes in body weight after 14 days coadministration of olanzapine (10 mg) + miricorilant (600 mg) compared with olanzapine (10 mg) + placebo. Secondary objectives included evaluating (a) the safety and tolerability of the combination; (b) the effects of the combination on glucose, insulin, insulin resistance, and triglycerides; and (c) the impact of the combination on hepatic enzymes. RESULTS: Subjects administered olanzapine + miricorilant gained less weight than subjects administered olanzapine + placebo (mean weight gain on day 15, 3.91 kg vs 4.98 kg; difference between groups, -1.07 kg; 95% confidence interval, -1.94 to -0.19; P = 0.017]). Compared with the placebo group, coadministration of miricorilant with olanzapine was associated with smaller increases in insulin (difference, -3.74 mIU/L; P = 0.007), homeostatic model assessment of insulin resistance (difference, -0.47; P = 0.007), triglycerides (difference, -0.29 mmol/L; P = 0.057), aspartate aminotransferase (difference, -32.24 IU/L; P = 0.009), and alanine aminotransferase (difference, -49.99 IU/L; P = 0.030). CONCLUSIONS: Miricorilant may provide a promising option for ameliorating the detrimental effects of olanzapine, and investigation of this medication in patients affected by antipsychotic-induced weight gain is warranted. Two phase 2 studies of miricorilant in patients with recent and long-standing antipsychotic-induced weight gain are currently in progress.

Triboelectric Effect Enabled Self-Powered, Point-of-Care Diagnostics: Opportunities for Developing ASSURED and REASSURED Devices.

The use of rapid point-of-care (PoC) diagnostics in conjunction with physiological signal monitoring has seen tremendous progress in their availability and uptake, particularly in low- and middle-income countries (LMICs). However, to truly overcome infrastructural and resource constraints, there is an urgent need for self-powered devices which can enable on-demand and/or continuous monitoring of patients. The past decade has seen the rapid rise of triboelectric nanogenerators (TENGs) as the choice for high-efficiency energy harvesting for developing self-powered systems as well as for use as sensors. This review provides an overview of the current state of the art of such wearable sensors and end-to-end solutions for physiological and biomarker monitoring. We further discuss the current constraints and bottlenecks of these devices and systems and provide an outlook on the development of TENG-enabled PoC/monitoring devices that could eventually meet criteria formulated specifically for use in LMICs.

Germline SAMD9L truncation variants trigger global translational repression.

SAMD9L is an interferon-induced tumor suppressor implicated in a spectrum of multisystem disorders, including risk for myeloid malignancies and immune deficiency. We identified a heterozygous de novo frameshift variant in SAMD9L in an infant with B cell aplasia and clinical autoinflammatory features who died from respiratory failure with chronic rhinovirus infection. Autopsy demonstrated absent bone marrow and peripheral B cells as well as selective loss of Langerhans and Purkinje cells. The frameshift variant led to expression of a truncated protein with interferon treatment. This protein exhibited a gain-of-function phenotype, resulting in interference in global protein synthesis via inhibition of translational elongation. Using a mutational scan, we identified a region within SAMD9L where stop-gain variants trigger a similar translational arrest. SAMD9L variants that globally suppress translation had no effect or increased mRNA transcription. The complex-reported phenotype likely reflects lineage-dominant sensitivities to this translation block. Taken together, our findings indicate that interferon-triggered SAMD9L gain-of-function variants globally suppress translation.

Prioritization and management of calls from older people to GP out-of-hours services.

BACKGROUND: Urgent out-of-hours medical care is necessary to ensure people can remain living at home into older age. However, older people experience multiple barriers to using out-of-hours services including poor awareness about the general practitioner (GP) out-of-hours (GPOOH) service and how to access it. In particular, older people are reluctant users of GPOOH services because they expect either their symptoms will not be taken seriously or they will simply be referred to hospital accident and emergency services. The aim of this study was to examine if this expectation was borne out in the manner of GPOOH service provision. OBJECTIVE: The objective was to establish the urgency categorization and management of calls to GPOOH , for community dwelling older people in Ireland. METHODS: An 8-week sample of 770 calls, for people over 65 years, to a GPOOH service in Ireland, was analysed using Excel and Nvivo software. RESULTS: Urgency categorization of older people shows 40% of calls categorized as urgent. Recognition of the severity of symptoms, prompting calls to the GPOOH service, is also reflected in a quarter of callers receiving a home visit by the GP and referral of a third of calls to emergency services. The findings also show widespread reliance on another person to negotiate the GPOOH system, with a third party making 70% of calls on behalf of the older person seeking care. CONCLUSION: Older people are in urgent need of medical services when they contact GPOOH service, which plays an effective and patient-centred gatekeeping role, particularly directing the oldest old to the appropriate level of care outside GP office hours. The promotion of GPOOH services should be enhanced to ensure older people understand their role in supporting community living.

Improved Immunoprecipitation to Mass Spectrometry Method for the Enrichment of Low-Abundant Protein Targets.

Immunoprecipitation (IP) is commonly used upstream of mass spectrometry (MS) as an enrichment tool for low-abundant protein targets. However, several aspects of the classical IP procedure such as nonspecific protein binding to the isolation matrix, detergents or high salt concentrations in wash and elution buffers, and antibody chain contamination in elution fractions render it incompatible with downstream mass spectrometry analysis. Here, we discuss an improved IP-MS workflow that is designed to minimize sample prep time and these contaminants. The method employs biotinylated antibodies to the targets of interest and streptavidin magnetic beads that exhibit low background binding. In addition, alterations in the elution protocol and subsequent MS sample prep were made to reduce time and antibody leaching in the eluent, minimizing potential ion suppression effects and thereby maximizing detection of multiple target antigens and interacting proteins.

Multiplexed Functional Assessment of Genetic Variants in CARD11.

Genetic testing has increased the number of variants identified in disease genes, but the diagnostic utility is limited by lack of understanding variant function. CARD11 encodes an adaptor protein that expresses dominant-negative and gain-of-function variants associated with distinct immunodeficiencies. Here, we used a "cloning-free" saturation genome editing approach in a diploid cell line to simultaneously score 2,542 variants for decreased or increased function in the region of CARD11 associated with immunodeficiency. We also described an exon-skipping mechanism for CARD11 dominant-negative activity. The classification of reported clinical variants was sensitive (94.6%) and specific (88.9%), which rendered the data immediately useful for interpretation of seven coding and splicing variants implicated in immunodeficiency found in our clinic. This approach is generalizable for variant interpretation in many other clinically actionable genes, in any relevant cell type.

Correction: Chronic Granulomatous Disease-Associated IBD Resolves and Does Not Adversely Impact Survival Following Allogeneic HCT.

The original version of this article unfortunately contained the missing author, Caridad Martinez. The authors would like to correct the list. We apologize for any inconvenience that this may have caused. The correct author list is shown above.

Mindfulness-based stress reduction improves irritable bowel syndrome (IBS) symptoms via specific aspects of mindfulness.

BACKGROUND: Irritable bowel syndrome (IBS) is a common and often debilitating chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habits. Pharmacological treatments are often ineffective, leading to the development of a variety of behavioral interventions. Mindfulness-based stress reduction (MBSR) is one such program that has shown efficacy in reducing gastrointestinal (GI) symptoms and improving quality of life (QOL). This single-arm intervention study examines the association of clinical outcomes with changes in specific aspects of mindfulness. METHODS: Adults with IBS (53 women, 15 men) participated in an 8-week MBSR class. Primary outcomes of GI symptom severity, quality of life, and GI-specific anxiety, as well as specific aspects of mindfulness using the Five Factor Mindfulness Questionnaire (FFMQ), were assessed at baseline, post-treatment, and 6-month follow-up. KEY RESULTS: Gastrointestinal symptom responder rate was 71%, and there was a significant pre-post treatment change for three of the five FFMQ scales. Regression analysis indicated that change in the Act with Awareness (P = .02) facet of mindfulness was the strongest predictor of GI symptom and QOL improvement. CONCLUSIONS & INFERENCES: Mindfulness-based stress reduction training was associated with robust improvements in GI symptoms and associated problems in participants with IBS. Although significant increases in 3 of the 5 measured facets of mindfulness were found, regression analyses suggest that increases in the ability to retain present moment focus and act with awareness may be particularly important for improving outcomes in individuals with IBS. These results may inform the refinement of mindfulness-based protocols specifically for treatment of IBS.

HLA-Haploidentical Hematopoietic Cell Transplantation for Treatment of Nonmalignant Diseases Using Nonmyeloablative Conditioning and Post-Transplant Cyclophosphamide.

Allogeneic hematopoietic cell transplant (HCT) is often the only curative therapy for patients with nonmalignant diseases; however, many patients do not have an HLA-matched donor. Historically, poor survival has been seen after HLA-haploidentical HCT because of poor immune reconstitution, increased infections, graft-versus-host disease (GVHD), and graft failure. Encouraging results have been reported using a nonmyeloablative T cell-replete HLA-haploidentical transplant approach in patients with hematologic malignancies. Here we report the outcomes of 23 patients with various nonmalignant diseases using a similar approach. Patients received HLA-haploidentical bone marrow (n = 17) or granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (n = 6) grafts after conditioning with cyclophosphamide 50 mg/kg, fludarabine 150 mg/m2, and 2 or 4 Gy total body irradiation. Postgrafting immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, tacrolimus, ± sirolimus. Median patient age at HCT was 10.8 years. Day 100 transplant-related mortality (TRM) was 0%. Two patients died at later time points, 1 from intracranial hemorrhage/disseminated fungal infection in the setting of graft failure and 1 from infection/GVHD. The estimated probabilities of grades II to IV and III to IV acute GVHD at day 100 and 2-year National Institutes of Health consensus chronic GVHD were 78%, 26%, and 42%, respectively. With a median follow-up of 2.5 years, the 2-year overall and event-free rates of survival were 91% and 78%, respectively. These results are encouraging and demonstrate favorable disease-specific lineage engraftment with low TRM in patients with nonmalignant diseases using nonmyeloablative conditioning followed by T cell-replete HLA-haploidentical grafts. However, additional strategies are needed for GVHD prevention to make this a viable treatment approach for patients with nonmalignant diseases.