This needs to be a journey that we're actually on together'-the introduction of integrated care systems for children and young people in England: a qualitative study of the views of local system stakeholders during winter 2021/22.

BACKGROUND: Integrated care has become a central feature of health system reform worldwide. In England, Integrated Care Systems (ICS) are intended to improve integration across public health, the National Health Service (NHS), education and social care. By April 2021, England had been divided into 42 geographical areas, each tasked with developing local ICS provision. However, it was not clear how ICSs would address the specific needs of children and young people (CYP). This study elicited the views of senior professional stakeholders in the first year of the ICS national roll out, to learn how integrated care for CYP was being implemented within the ICSs and future plans for service provision. METHODS: A qualitative analysis of in-depth interviews with stakeholders, including healthcare professionals, NHS managers and local authority leaders (n = 25) selected from a diverse sample of ICSs (n = 7) across England, conducted during winter 2021/22. Reflexive thematic analysis involving a collaborative coding approach was used to analyse interview transcripts. RESULTS: Four themes were identified, indicating challenges and opportunities for ICSs in relation to the health of CYP: 1) Best start in life (a more holistic approach to health afforded by integrated care); 2) Local and national contexts (tensions between local and national settings and priorities); 3) Funding and planning (instituting innovative, long-term plans using limited existing CYP funding streams); 4) Organisational complexities (integrating the work of diverse organisations). CONCLUSIONS: The views of stakeholders, provided at the beginning of the journey towards developing local ICS CYP provision, revealed a common aspiration to change focus from provision of acute, largely adult-orientated services towards one with a broader, population health remit, including prevention and early intervention. This would be delivered by integration of a range of local services, including health, education, housing and social care, to set CYP on a life-long path towards improved health and wellbeing. Yet there was an awareness that change would take place over time within existing national policy and funding frameworks, and would require overcoming organisational barriers through further developing local collaborations and partnerships. As ICSs mature, the experiences of stakeholders should continue to be canvassed to identify practical lessons for successful CYP integrated care.

Thromboembolic Complications After Receipt of Prothrombin Complex Concentrate.

Purpose: Patients presenting with life-threatening bleeding associated with oral anticoagulants (OACs) are challenging with few available treatments. Prothrombin complex concentrate (PCC) is an option for OAC reversal in the setting of life-threatening bleeding with a relatively benign safety profile. Little is known about the risk of developing thromboembolic complications (TEC) in patients receiving PCC who were previously anticoagulated. The aim of this study is to characterize the rate of TEC after receipt of PCC. Methods: All adult patients who received 4-Factor PCC for life-threatening bleeding were retrospectively evaluated over a 2-year time period. Data collected included anticoagulant and indication, bleeding source, PCC dose, INR, and TEC within 14 days of PCC dose, including venous thromboembolism (VTE), acute myocardial infarction, and ischemic stroke. Results: Three hundred thirty-three patients received 383 PCC doses. Of these, 55 (16.5%) patients developed TEC, including VTE, ischemic stroke, and acute myocardial infarction. There was increased rivaroxaban use in patients who developed TEC (25.4% vs 12.2%; P = .011). Additionally, there were more patients who had anticoagulation for a previous TEC in those who developed a new TEC (38.2% vs 23.4%; P = .022). Lastly, there was a higher rate of TEC in those who received >1 dose of PCC (21.8% vs 7.9%; P = .002). Conclusion: PCC administration in the setting of life-threatening bleeding is not benign. Risk of TEC increases in patients who have rivaroxaban reversal, receive a repeat dose of PCC, and have a TEC indication for their anticoagulation and these factors should be further investigated.

Genes and Environment in Multiple Sclerosis project: A platform to investigate multiple sclerosis risk.

The Genes and Environment in Multiple Sclerosis project establishes a platform to investigate the events leading to multiple sclerosis (MS) in at-risk individuals. It has recruited 2,632 first-degree relatives from across the USA. Using an integrated genetic and environmental risk score, we identified subjects with twice the MS risk when compared to the average family member, and we report an initial incidence rate in these subjects that is 30 times greater than that of sporadic MS. We discuss the feasibility of large-scale studies of asymptomatic at-risk subjects that leverage modern tools of subject recruitment to execute collaborative projects.

Clinical Experience With Pharmacological Venous Thromboembolism Prophylaxis in the Underweight and Critically Ill.

BACKGROUND: The optimal regimen for pharmacological prophylaxis of venous thromboembolism (VTE) in underweight, critically ill patients is unknown. OBJECTIVE: To describe prescribing patterns for VTE prophylaxis in underweight (≤50 kg or body mass index ≤18.5 kg/m(2)), critically ill patients and identify the prevalence of VTE and bleeding. METHODS: This was a retrospective cohort study that included patients who received standard- or reduced-dose VTE prophylaxis for ≥48 hours. RESULTS: A total of 295 individuals were included in the study. The majority of underweight patients in this study (79.7%) received unfractionated heparin, 5000 units 3 times daily. No statistically significant difference in the prevalence of clinically relevant VTEs between the reduced- and standard-dose groups was observed (4.4% vs 5.6%, P = 1.00), but a higher proportion of bleeding events was identified within the standard-dose group (6.7% vs 11.2%, P = 0.4). CONCLUSIONS: Empirical dose reductions of VTE prophylaxis are infrequently used in underweight, critically ill patients. Further studies need to be conducted that assess the safety and efficacy of reduced-dose VTE prophylactic regimens in this population to determine if acceptable efficacy can be achieved, with lower risks of bleeding.

Total triage model in general practice: a systematic review of the opportunities and challenges.

BACKGROUND: Total triage (TT) has the potential to achieve more equitable access to primary care, to improve the overall quality of care, and enhance health outcomes. TT has gained increasing attention from the public, policymakers, and academics. AIM: To examine relevant scientific literature regarding the implementation of TT, the reported opportunities and challenges for patients and staff, and implications for practice. METHOD: Medline, Embase, CINAHL, and Scopus were searched for articles and grey literature between 2013 and February 2023. Included documents described the implementation of TT during in-hours general practice and provided perspectives from patients/staff. Patients and stakeholders were involved throughout each stage of the review process. Findings were synthesised using a framework approach. RESULTS: In total, 23 documents were included at full-text screening. Analysis highlights a range of TT approaches, sometimes conflating remote and TT systems. TT was seen to both increase and reduce workload. Consistently, patient and staff views worsened with TT use. TT can increase barriers to care access with potential to exacerbate inverse care laws across the UK. Critical knowledge gaps included patient co-production in TT systems and the role of reception teams to adapt systems to meet patients' needs. CONCLUSION: TT can influence patient access, safety, and equity. The approach may also generate profoundly different working styles for general practice. This review adds to current debates surrounding patient access and TT, and consequences for staff/patients. The findings can be used to aid practices when navigating the new GP contract and the implementation of new TT approaches.

A realist evaluation of a multi-component program with disengaged students.

Periods spent in the absence of education, employment, or training (NEET) are associated with adverse psychological wellbeing, social marginalisation, and premature mortality. Implementing effective programs to re-engage young people who are classified, or are at risk of becoming NEET, is of importance to these individuals, family, and society. We conducted a realist evaluation to understand how, and under which circumstances a multi-component program may impact the engagement, behavioural, and psychosocial outcomes of disengaged students at risk of becoming NEET. During the early project phase, a narrative review of the literature and key stakeholder discussions were conducted to develop our initial program theories regarding how the program was expected to achieve its outcomes. Participant observations, video footage, and forty-two interviews were then conducted with teachers and students to form context-mechanism-outcome configurations and to refine these theories. Overall, refined program theories relating to positions of authority, the power of collective experience, exploration of possible life directions, constructivist pedagogies and active learning, and the endorsement of an ethic of caring and strengths-based orientation were developed. Collectively, our findings provide a detailed understanding of the architecture of programs that may benefit disengaged students and help inform the design of future programs aimed at reducing disaffection.

The multi-factorial modes of action of urease in the pathogenesis of incontinence associated dermatitis.

Background: Incontinence Associated Dermatitis (IAD) is a type of skin inflammation caused by chronic exposure to urine and/or faeces. Current treatment strategies involve creating a barrier between the skin and urine/faeces rather than targeting specific irritants. Urease expressing pathogens catalyse the conversion of urea, present in urine, into ammonia. The accumulation of ammonia causes an elevation in skin pH which is believed to activate faecal enzymes which damage skin, and opportunistic pathogens, which lead to secondary infections. Objectives: To develop a better, multi-factorial model of IAD pathogenesis, including the effect of urease-expressing bacteria on skin, mechanism of damage of urease and urease-triggered activity of faecal enzymes and secondary pathogens. To study the effect of urease inhibition on preventing IAD skin damage. Methods: Five separate studies were made using ex vivo porcine skin and in vivo human skin models. Measurements of the change in skin barrier function were made using skin impedance, trans-epidermal water loss (TEWL), stratum corneum moisture and pH. Skin was exposed to artificial urine, inoculated with various microbes, enzymes and chemicals to examine the influence of: 1) urease-positive Proteus mirabilis 2) ammonia, 3) combination of P. mirabilis and a faecal enzyme, trypsin, 4) combination of P. mirabilis and opportunistic pathogens, Candida albicans and Staphylococcus aureus, 5) inhibition of urease using acetohydroxamic acid (AHA) on barrier function. Results: The urease-mediated production of ammonia had two principal effects: it elevated skin pH and caused inflammation, leading to significant breakdown in skin (stratum corneum) barrier function. Urease was found to further increase the activity of faecal enzymes and opportunistic pathogens, due to elevated skin pH. The urease inhibitor, AHA, was shown to have significantly reduced damage to skin barrier function, measured as its electrical resistance. Conclusions: Targeted therapeutic strategies should be developed to prevent the manifestation of IAD, rather than creating a generic barrier between skin and urine/faeces. Urease has been identified as a crucial component in the manifestation of IAD, due to its role in the production of ammonia. Urease inhibition provides a promising therapeutic target to halt the progression of IAD.

GP workforce sustainability to maximise effective and equitable patient care: a realist review of what works, for whom and in what circumstances?

BACKGROUND: UK general practice has been described as being in crisis. A shortage and exodus of GPs is an urgent and challenging problem, attracting significant media attention, widespread public debate, and policy action. AIM: Our review aims to examine which aspects of the healthcare system affect GP workforce sustainability, how, why, and for whom. METHOD: A realist review is an interpretive, theory-driven approach to evidence synthesis, that brings together data from quantitative, qualitative, mixed methods research, and the wider grey literature (e.g., policy documentation). Using this data allows us to examine a diverse range of evidence with a clear focus on understanding factors which support (or hinder) GP workforce sustainability, how these are shaped by contexts, and the mechanisms that underpin them. We identify important individual and system-level contexts that may be amenable to change. RESULTS: We present our emerging findings in the form of a programme theory which explores human connection with patients, colleagues, and across organisations, gaining intellectual enrichment and learning systems comprising socially-situated knowledge. Relational continuity is key across these, supporting GP workforce sustainability. Challenges include standardisation, alienation and professional loneliness, inflexible organisation, and restrictive technologies. CONCLUSION: Our research generates new knowledge about the interdependencies between contexts, mechanisms, and outcomes. The findings can inform strategies and interventions intended to support, facilitate, and assist the GP workforce in delivering equitable and effective patient care. We identify critical gaps in knowledge and prioritise the expectations for scope and nature of future GP work and retention strategies.

Non-Antibiotic Approaches to Infection that Preserve the Microbiome in Critically Ill Patients.

In critically ill patients, the gut microbiota is subjected to various factors including antimicrobial exposure, modified gastrointestinal transit, nutrition support, as well as infection, which may lead to dysbiosis during the intensive care unit and hospital stay. Dysbiosis occupies an increasingly important role in driving morbidity and perhaps mortality in the critically ill or injured. Given that antibiotics lead to dysbiosis, it is relevant to understand the range of non-antibiotic approaches to infection-including those related to multi-drug-resistant organisms-that may leave the microbiome unimpacted. These strategies most prominently include the elimination of unabsorbed antibiotic agents from the digestive tract, pro-/pre-/synbiotics, fecal microbiota transplant, selective digestive and oropharyngeal decontamination, phage therapy, anti-sense oligonucleotides, structurally nanoengineered antimicrobial peptide polymers, and vitamin C-based lipid nanoparticles for adoptive macrophage transfer. Herein, we review the rationale for these therapies, current data regarding their use in critically ill patients, and the therapeutic potential for strategies that are not yet deployed in human medical care.

Using electrocardiogram electrodes to monitor skin impedance spectroscopic response when skin is subjected to sustained static pressure.

Background: Impedance spectroscopy is a non-invasive technique which can be used to monitor skin barrier function, with potential applications in early-stage pressure ulcer detection. This paper describes how changes in skin impedance, due to mechanical damage of the stratum corneum by tape stripping or applied pressure, can be straightforwardly measured using commercial electrocardiogram electrodes and a relatively low-cost impedance analyser. Two models of pressure injury were studied, an ex vivo porcine and in vivo human skin model. Objectives: Determine whether impedance spectroscopy may have potential utility in measuring the effect on skin of applied pressure on early-stage pressure injury. Methods: Two models were utilized to measure the effect of pressure. Porcine model: 0, 7.5, 15 or 22.5 mmHg of pressure was applied for up to 24 h (N = 4) and monitored at various time intervals. Human Model: 88 mmHg of pressure was applied for four sets of three-minute intervals (N = 13) and post-pressure recovery was monitored for 4 h. For each model, skin impedance was monitored at 0.1 Hz-50 kHz using disposable Ag/AgCl electrodes. The data was analysed using Ordinary One-Way Analysis of Variance. Results: Porcine model: after 24 h, the impedance of pressure-loaded skin was significantly reduced compared to the non-loaded control group (p ≤ 0.0001); this reduction in impedance was proportional to the degree of mechanical loading. Histology images of skin cross-sections provided qualitative evidence that the epidermis was structurally compromised by pressure. Human Model: the response of healthy skin to applied pressure displayed inter-variation. Participants with a significant change in skin impedance (p ≤ 0.01) also demonstrated signs of erythema. Conclusions: This study suggests that using impedance spectroscopy to measure skin (stratum corneum) resistance may have utility in giving early warning of skin pressure injury prior to clinical symptoms, with a good correlation between observed erythema and reduction in skin resistance. Further work should be initiated on patients at risk of pressure injury to improve intervention strategies, including in darker skin tones where early-stage pressure injuries may not be visually distinct.

Expert perspectives for the pharmacist on facilitating and improving the use of albumin in cirrhosis.

PURPOSE: Albumin, the most abundant and arguably most important protein in the human body, plays a unique role in decompensated cirrhosis because its structure and function are quantitatively and qualitatively affected. A literature review was performed to provide insights into albumin use. The manuscript was developed using a multidisciplinary approach; 2 hepatologists, a nephrologist, a hospitalist, and a pharmacist, who are all members of or work closely with the Chronic Liver Disease Foundation, collaborated to write this expert perspective review. SUMMARY: Cirrhosis represents the potential end in the spectrum of all chronic liver diseases. Decompensated cirrhosis, defined by the overt manifestation of liver failure (eg, ascites, hepatic encephalopathy, variceal bleeding), is the inflection point associated with increased mortality. Human serum albumin (HSA) infusion serves an important role in the treatment of advanced liver disease. The benefits of HSA administration in patients with cirrhosis are widely accepted, and its use has been advocated by several professional societies. However, inappropriate HSA use can lead to significant adverse patient events. This paper discusses the rationale for the administration of HSA in the treatment of complications of cirrhosis, analyzes the data on the use of HSA in cirrhosis, and streamlines practical recommendations set forth in published guidance. CONCLUSION: Use of HSA in clinical practice needs to be improved. The objective of this paper is to empower pharmacists to facilitate and improve the use of HSA in patients with cirrhosis at their practice sites.

Detecting and monitoring incontinence associated dermatitis: Does impedance spectroscopy have a part to play?

In this review, current understanding of the prevention and treatment of Incontinence Associated Dermatitis (IAD) is discussed. The need for preventative measures which target specific faecal/urinary irritants is highlighted, including the role of urease inhibitors. There is no existing internationally and clinically accepted method to diagnose and categorise the severity of IAD. Diagnosis currently relies on visual inspection; non-invasive techniques to assess skin barrier function could remove subjectiveness, particularly in darker skin tones. Impedance spectroscopy is a non-invasive technique which can be used to monitor skin barrier function, supporting visual assessments. Six studies (2003-2021) which used impedance to assess dermatitis were reviewed; inflamed skin was distinguishable from healthy skin in each case. This suggests that impedance spectroscopy could be useful in diagnosis early-stage IAD, potentially enabling earlier intervention. Finally, the authors present their initial findings on the role of urease in skin breakdown in an in vivo IAD model, using impedance spectroscopy.

Primary care micro-teams: an international systematic review of patient and healthcare professional perspectives.

BACKGROUND: International trends have shifted to creating large general practices. There is an assumption that interdisciplinary teams will increase patient accessibility and provide more cost-effective, efficient services. Micro-teams have been proposed to mitigate for some potential challenges of practice expansion, including continuity of care. AIM: To review available literature and examine how micro-teams are described, and identify opportunities and limitations for patients and practice staff. DESIGN AND SETTING: This was an international systematic review of studies published in English. METHOD: Databases (MEDLINE, EMBASE, CINAHL, Cochrane Library, and Scopus) and grey literature were searched. Studies were included if they provided evidence about implementation of primary care micro-teams. Framework analysis was used to synthesise identified literature. The research team included a public contributor co-applicant. The authors conducted stakeholder discussions with those with and without experience of micro-team implementation. RESULTS: Of the 462 studies identified, 24 documents met the inclusion criteria. Most included empirical data from healthcare professionals, describing micro-team implementation. Results included characteristics of the literature; micro-team description; range of ways micro-teams have been implemented; reported outcomes; and experiences of patients and staff. CONCLUSION: The organisation of primary care has potential impact on the nature and quality of patient care, safety, and outcomes. This review contributes to current debate about care delivery and how this can impact on the experiences and outcomes of patients and staff. This analysis identifies several key opportunities and challenges for future research, policy, and practice.

Improving the Management of Hepatorenal Syndrome-Acute Kidney Injury Using an Updated Guidance and a New Treatment Paradigm.

Cirrhosis, or advanced scarring of the liver, represents the end stage of chronic liver disease and is associated with high morbidity and mortality. Hepatorenal syndrome-acute kidney injury (HRS -AKI), a condition causing functional and progressive kidney failure, is a complication of cirrhosis that contributes to its high mortality rate. In the United States, the standard-of-care treatments for HRS -AKI have historically been suboptimal. Recently, terlipressin became the first drug approved for HRS -AKI in the United States, and the American Association for the Study of Liver Diseases updated its guidance document on HRS diagnosis and management. Clinical practice guidelines and guidance documents have a variable effect on physician behavior owing to a lack of awareness, familiarity, and education. The imple mentation of standardized order sets can improve guidance adherence and the quality of care delivered by encouraging data-driven treatment administration, especially for new therapies. This review seeks to facilitate improvements in the management of HRS -AKI by discussing early HRS -AKI interventions, which will streamline diagnosis and treatment in a practical way for clinical use, and how to incorporate new treatments into patient care to improve survival in this subset of patients. Finally, these recommendations are integrated into a sample order set developed by members of the Chronic Liver Disease Foundation and experts in the management of HRS-AKI.

Improving Outcomes in Hepatorenal Syndrome-Acute Kidney Injury With Early Diagnoses and Implementation of Approved Treatment Regimens.

Decompensated cirrhosis, defined by the overt manifestations of liver failure and portal hypertension (eg, ascites, hepatic encephalopathy, variceal bleeding), is the inflection point associated with increased morbidity and mortality in chronic liver disease. Acute kidney injury in the setting of cirrhosis (hepatorenal syndrome-acute kidney injury [HRS-AKI]) is a severe and often fatal complication. The goals of treatment of HRS-AKI are to reverse renal failure and prolong survival in these critically ill patients or perhaps to allow the transplant team to complete the pretransplant evaluation and bridge the patient to transplant. Historically, in the United States, standard-of-care treatments for HRS-AKI were chosen by default despite lack of data, off-label use, and suboptimal results. Terlipressin represents the first drug in the United States indicated for the treatment of HRS-AKI. This review provides an up-to-date overview of HRS-AKI, discusses terlipressin and how to incorporate this new treatment into patient care and streamline society guidelines on HRS diagnosis and treatment in a practical way for clinical use, and concludes with a sample order set that highlights the recommendations discussed throughout the supplement.

"Nothing about us, without us"? A qualitative study of service user involvement in the development of lay-delivered psychological interventions in contexts affected by humanitarian crises.

BACKGROUND: : Service user involvement has become increasingly prioritised within health research, and more recently, within mental health and psychosocial support (MHPSS). However, there is limited exploration of service user involvement in the development of lay-delivered MHPSS psychological interventions. The aim of this research was to investigate how service users have been involved in the development of lay-delivered psychological interventions for populations affected by humanitarian crises. METHODS: : Thirteen semi-structured interviews were conducted with respondents involved in randomized controlled trials (RCTs) of lay-delivered MHPSS psychological interventions, either as principal investigators or as focal points for service user involvement. Thematic data analysis used was used to analyse the data. RESULTS: : There was a common perception that service user involvement is vital to the development of lay-delivered psychological interventions, but there was concern about how that happened in practice. Respondents desired to increase service user involvement, but they either did not know how to do this into practice or felt that they lacked the resources to do so. Recommendations were made for strengthening involvement, such as employing service users onto research teams. However, legal difficulties in compensating service users for their work were raised. CONCLUSION: : Service user involvement was viewed as vital in the development of lay delivered psychological interventions, but remains predominantly tokenistic, partly due to limited guidance, time, and finances. Guidelines could support more meaningful and ethical service user involvement in lay-delivered psychological interventions in areas affected by humanitarian crises.

Community pharmacy and general practice collaborative and integrated working: a realist review protocol.

INTRODUCTION: Increasing collaborative and integrated working between General practice (GP) and Community pharmacy (CP) is a key priority of the UK National Health Service and has been proposed as a solution to reducing health system fragmentation, improving synergies and coordination of care. However, there is limited understanding regarding how and under which circumstances collaborative and integrated working between GP and CP can be achieved in practice and how regulatory, organisational and systemic barriers can be overcome. METHODS AND ANALYSIS: The aim of our review is to understand how, when and why working arrangements between GP and CP can provide the conditions necessary for optimal communication, decision-making, and collaborative and integrated working. A realist review approach will be used to synthesise the evidence to make sense of the complexities inherent in the working relationships between GP and CP. Our review will follow Pawson's five iterative stages: (1) finding existing theories; (2) searching for evidence (our main searches were conducted in April 2022); (3) article selection; (4) data extraction and (5) synthesising evidence and drawing conclusions. We will synthesise evidence from grey literature, qualitative, quantitative and mixed-methods research. The research team will work closely with key stakeholders and include patient and public involvement and engagement throughout the review process to refine the focus of the review and the programme theory. Collectively, our refined programme theory will explain how collaborative and integrated working between GP and CP works (or not), for whom, how and under which circumstances. ETHICS AND DISSEMINATION: Formal ethical approval is not required for this review as it draws on secondary data from published articles and grey literature. Findings will be widely disseminated through: publication in peer-reviewed journals, seminars, international conference presentations, patients' association channels, social media, symposia and user-friendly summaries. PROSPERO REGISTRATION NUMBER: CRD42022314280.

A comparison of objective and subjective measures of cough in asthma.

BACKGROUND: Cough is widely recognized as a key symptom in the diagnosis and the monitoring of asthma, but little is known about how best to assess cough in asthma. OBJECTIVE: To determine how objective cough rates correlate with subjective measures of cough in asthma. METHODS: We studied 56 subjects, median age 42.0 years (range, 28.5-71), 34 (60.7%) female, with asthma. Subjects performed cough reflex sensitivity testing (concentration of citric acid causing 2 and 5 coughs [C2 and C5]), 24-hour fully ambulatory cough recordings, subjectively scored the severity of their cough (visual analog scales and 0-5 score) and completed a cough-related quality of life questionnaire (Leicester Cough Questionnaire). Ambulatory cough recordings were manually counted and reported in cough seconds per hour (cs/h). RESULTS: The median time spent coughing was 2.6 cs/h (range, 0.0-14.2), with subjects spending more time coughing by day (median, 3.9 cs/h [0.0-18.5]) than by night (median, 0.3 cs/h [0.0-8.7]; P < .001). A weak inverse relationship was seen between day cough rates and log(10)C2 (r = -0.39; P = .03) but not log(10)C5 (r = -0.08; P = .65). Objective time spent coughing was also weak-moderately associated with subjective cough scores and visual analog scales, and most strongly correlated with cough-related quality of life (r = -0.54; P < .001). CONCLUSION: Subjective measures of cough and cough reflex sensitivity are poor surrogates for objective cough frequency in asthma. When designing studies to assess interventions for cough in asthma, we advocate a combination of both objective measures of cough and cough-related quality of life.

Impaired Attention Orienting in Young Children With Fragile X Syndrome.

Fragile X syndrome (FXS) is a genetic disorder caused by a trinucleotide CGG expansion within the FMR1 gene located on the X chromosome. Children with FXS have been shown to be impaired in dynamic visual attention processing. A key component of dynamic processing is orienting-a perceptual ability that requires disengagement and engagement of attention from one stimulus to fixate on a second. Orienting, specifically the disengagement and engagement of attention, has previously not been studied in young children with FXS. Using an eye tracking gap-overlap task, the present study investigated visual disengagement and engagement in young children with FXS, compared to mental age (MA)- and chronological age (CA)-matched typically developing children. On gap trials, the central stimulus elicited fixation, but then disappeared before the peripheral target appeared, imposing a visual gap between stimuli. On overlap trials, the central stimulus elicited fixation, and remained present when the peripheral target appeared, creating visual competition. A gap effect emerges when latencies to shift to the peripheral target are longer in overlap versus gap conditions, reflecting the recruitment of cortical and subcortical disengagement and engagement mechanisms. The gap effect was measured as the latency to orient attention to the peripheral target during gap versus overlap conditions. Both MA and CA groups showed the expected gap effect, where children were slower to orient to peripheral targets on overlap trials than on gap trials. In contrast, in the FXS group, saccadic latencies between gap and overlap trials were not significantly different, indicating no significant gap effect. These findings suggest disrupted attentional engagement patterns in FXS that may be underlying impairments in attention orienting, and suggest potential targets for attention training in this population.