Stakeholder perceptions of and attitudes towards problematic polypharmacy and prescribing cascades: a qualitative study.

INTRODUCTION: Problematic polypharmacy is the prescribing of five or more medications potentially inappropriately. Unintentional prescribing cascades represent an under-researched aspect of problematic polypharmacy and occur when an adverse drug reaction (ADR) is misinterpreted as a new symptom resulting in the initiation of a new medication. The aim of this study was to elicit key stakeholders' perceptions of and attitudes towards problematic polypharmacy, with a focus on prescribing cascades. METHODS: qualitative one-to-one semi-structured interviews were conducted with predefined key stakeholder groups. Inductive thematic analysis was employed. RESULTS: Thirty-one stakeholders were interviewed: six patients, two carers, seven general practitioners, eight pharmacists, four hospital doctors, two professional organisation representatives and two policymakers. Three main themes were identified: (i) ADRs and prescribing cascades-a necessary evil. Healthcare professionals (HCPs) expressed concern that experiencing an ADR would negatively impact patients' confidence in their doctor. However, patients viewed ADRs pragmatically as an unpredictable risk. (ii) Balancing the risk/benefit tipping point. The complexity of prescribing decisions in the context of polypharmacy made balancing this tipping point challenging. Consequently, HCPs avoided medication changes. (iii) The minefield of medication reconciliation. Stakeholders, including patients and carers, viewed medication reconciliation as a perilous activity due to systemic communication deficits. CONCLUSION: Stakeholders believed that at a certain depth of polypharmacy, the risk that a new symptom is being caused by an existing medication becomes incalculable. Therefore, in the absence of harm, medication changes were avoided. However, medication reconciliation post hospital discharge compelled prescribing decisions and was seen as a high-risk activity by stakeholders.

Varicose Vein Education and Informed coNsent (VVEIN) Study: A Randomized Controlled Pilot Feasibility Study.

BACKGROUND: The primary aim of this study was to assess the feasibility of introducing a digital health education tool (dHET) for varicose vein surgery. METHODS: This randomized, feasibility study allocated 40 patients, into dHET (n = 20) or standard consent (SC) (n = 20) groups. Primary outcomes were related to feasibility. Secondary outcomes were knowledge recall, anxiety, and satisfaction. RESULTS: Recruitment and retention rates were 100% and 97.5%, respectively. Acceptability was also rated high, confirming feasibility. There was also no evidence of a difference between groups for early knowledge recall (14 [12-17] vs. 14 [11-16]; P = 0.72) or delayed (at 2 weeks) knowledge recall (15 [13-16] vs. 15 [13-16]; P = 0.89). The dHET module took significantly longer to complete compared to SC (13 min [12-18] vs. 9 min [8-12]; P < 0.01). However, the control group asked significantly more questions about the intended procedure (P = 0.03). There was no evidence of a difference between groups for patient anxiety or satisfaction. CONCLUSIONS: This trial shows that the addition of a dHET is feasible and noninferior to SC. Digital consent provides a unique opportunity to promote patient education and autonomy for better shared decision making. It also offers better documentation of the consent process.

The correlation between sub-epidermal moisture measurement and other early indicators of pressure ulcer development-A prospective cohort observational study. Part 1. The correlation between sub-epidermal moisture measurement and ultrasound.

The correlation between sub-epidermal moisture (SEM) and other early indicators of pressure ulcer (PU) development is yet to be determined. This three-part series aims to bridge this knowledge gap, through investigating SEM and its correlation with evidence-based technologies and assessments. This article focuses on the correlation between SEM and ultrasound. A prospective cohort observational study was undertaken between February and November 2021. Patients undergoing three surgery types were consecutively enrolled to the study following informed consent. Assessments were performed prior to and following surgery for 3 days at the sacrum, both heels and a control site, using a SEM scanner and high-frequency ultrasound scanner (5-15 MHz). Spearman's rank (rs ) explored the correlation between SEM and ultrasound. A total of 60 participants were included; 50% were male with a mean age of 58 years (±13.46). A statistically significant low to moderately positive correlation was observed between SEM and ultrasound across all anatomical sites (rs range = 0.39-0.54, p < 0.05). The only exception was a correlation between SEM and ultrasound on day 0 at the right heel (rs = 0.23, p = 0.09). These results indicate that SEM and ultrasound agreed in the presence of injury; however, SEM was able to identify abnormalities before ultrasound.

Baseline Assessments of Psychomotor Aptitude Are Associated With the Future Operative Performance of Surgical Trainees: A Prospective Observational Cohort Study.

OBJECTIVE: This study sought to investigate the association between validated psychomotor ability tests and future in-theater and simulated operative performance. BACKGROUND: Assessments of visuospatial ability, perceptual ability, and manual dexterity correlate with simulated operative performance. Data showing the predictive value of such assessments in relation to future performance in the workplace is lacking. METHODS: Core surgical residents in Ireland recruited from 2016 to 2019 participated in assessments of baseline perceptual, visuospatial, and psychomotor ability; Pictorial Surface Orientation (PicSOr) testing, digital visuospatial ability testing, and manual dexterity testing. Operative performance was prospectively assessed using the in-theater Supervised Structured Assessment of Operative Performance (SSAOP) tool, and simulation-based Operative Surgical Skill (OSS) assessments performed over a 2-year core training period. SSAOP assessments were scored using a 15-point checklist and a global 5-point operative performance score. OSS assessments were scored using procedure-specific checklists. Univariate correlations and multiple linear regression analyses were used to explore the association between fundamental ability measures and operative performance. RESULTS: A total of 242 residents completed baseline psychomotor ability assessments. Aggregated fundamental ability scores were associated with performance in submitted workplace-based SSAOP assessments using the Total Checklist score ( P =0.002) and Overall Performance scores ( P =0.002), independent of operative experience, and undergraduate centile scores. Aggregated ability scores were also positively associated with simulation-based OSS assessment scores on multivariable analysis ( P =0.03). CONCLUSION: This study indicates that visuospatial, psychomotor, and perceptual ability testing scores are associated with the future operative performance of surgical residents.

Exploring the Multidimensional Relationship Between Medication Beliefs and Adherence to Medications Among Older Adults Living With Multimorbidity Using Polynomial Regression: An Observational Cohort Study.

BACKGROUND: People living with multimorbidity may hold complex beliefs about medicines, potentially influencing adherence. Polynomial regression offers a novel approach to examining the multidimensional relationship between medication beliefs and adherence, overcoming limitations associated with difference scores. PURPOSE: To explore the multidimensional relationship between medication beliefs and adherence among people living with multimorbidity. METHODS: Secondary analysis was conducted using observational data from a cohort of older adults living with ≥2 chronic conditions, recruited from 15 family practices in Ireland in 2010 (n = 812) and followed up in 2012 (n = 515). Medication beliefs were measured with the Beliefs about Medicines Questionnaire-Specific. Adherence was assessed with the medication possession ratio using prescription data from the national primary care reimbursement service. Polynomial regression was used to explore the best-fitting multidimensional models for the relationship between (i) beliefs and adherence at baseline, and (ii) beliefs at baseline and adherence at follow-up. RESULTS: Confirmatory polynomial regression rejected the difference-score model, and exploratory polynomial regression indicated quadratic models for both analyses. Reciprocal effects were present in both analyses (slope [Analysis 1]: ß = 0.08, p = .007; slope [Analysis 2]: ß = 0.07, p = .044), indicating that adherence was higher when necessity beliefs were high and concern beliefs were low. Nonreciprocal effects were also present in both analyses (slope [Analysis 1]: ß = 0.05, p = .006; slope [Analysis 2]: ß = 0.04, p = .043), indicating that adherence was higher when both necessity and concern beliefs were high. CONCLUSIONS: Among people living with multimorbidity, there is evidence that the relationship between medication beliefs and adherence is multidimensional. Attempts to support adherence should consider the combined role of necessity and concern beliefs.

When people live with multiple ongoing health conditions, they might have complex beliefs about their prescribed medicines. These beliefs could relate to the perceived necessity of medicines (necessity beliefs) and perceived concerns about medicines (concern beliefs). This study aimed to explore how necessity and concern beliefs, in combination, relate to the extent to which people living with multiple ongoing conditions take their medicines as prescribed. The study analyzed an existing dataset that included 812 older adults recruited via family practice settings in Ireland in 2010. Of these, 515 people were followed up again in 2012. All participants were living with at least two ongoing health conditions. Participants self-reported their medication-related necessity and concern beliefs by completing a questionnaire. Their level of medication taking was calculated using pharmacy records. The results showed that having a combination of high necessity beliefs and low concern beliefs was related to higher levels of medication taking than having a combination of low necessity beliefs and high concern beliefs. Having a combination of high necessity beliefs and high concern beliefs was related to higher levels of medication taking than having a combination of low necessity beliefs and low concern beliefs. Attempts to support patients to take their medicines should consider the combined role of their necessity and concern beliefs on behavior.

The impact of lidocaine plaster prescribing reduction strategies: A comparison of two national health services in Europe.

AIMS: In 2017, two distinct interventions were implemented in Ireland and England to reduce prescribing of lidocaine medicated plasters. In Ireland, restrictions on reimbursement were introduced through implementation of an application system for reimbursement. In England, updated guidance on items which should not be routinely prescribed in primary care, including lidocaine plasters, was published. This study aims to compare how the interventions impacted prescribing of lidocaine plasters in these countries. METHODS: We conducted an interrupted time-series study using general practice data. For Ireland, monthly dispensing data (2015-2019) from the means-tested General Medical Services (GMS) scheme was used. For England, data covered all patients. Outcomes were the rate of dispensings, quantity and costs of lidocaine plasters, and we modelled level and trend changes from the first full month of the policy/guidance change. RESULTS: Ireland had higher rates of lidocaine dispensings compared to England throughout the study period; this was 15.22/1000 population immediately pre-intervention, and there was equivalent to a 97.2% immediate reduction following the intervention. In England, the immediate pre-intervention dispensing rate was 0.36/1000, with an immediate reduction of 0.0251/1000 (a 5.8% decrease), followed by a small but significant decrease in the monthly trend relative to the pre-intervention trend of 0.0057 per month. CONCLUSIONS: Among two different interventions aiming to decrease low-value lidocaine plaster prescribing, there was a substantially larger impact in Ireland of reimbursement restriction compared to issuing guidance in England. However, this is in the context of much higher baseline rates of use in Ireland compared to England.

Vascular Surgery Workforce: Evaluation and Estimation of Future Demand in the United Kingdom.

BACKGROUND: Vascular disease is a common cause of death and disability in our growing elderly population and the demand for vascular procedures is increasing worldwide. Workforce planning is essential to meet future demand and provide safe vascular services. Our aim was to evaluate the current workforce in the United Kingdom and estimate future demand for vascular surgeons. METHODS: From November 2020 to January 2021, we surveyed UK vascular surgeons for information on their work patterns. We estimated current vascular surgery (VS) workforce using the National Vascular Registry (NVR) data and population data from the Office for National Statistics. To estimate future demand, we interrogated Hospital Episode Statistic (HES) data using Hospital Admitted Patient Care Activity (HAPCA) and linear trend analysis. RESULTS: NVR data estimate that currently there are 518 consultant VS in the United Kingdom, or 1 per 128,951 population, lower than international comparisons. HAPCA data (2012-2020) suggests VS Finished Consultant Episodes (FCE), admissions, and waiting lists are growing by approximately 2% per year, and we estimate the workforce will need to grow by more than 50% over the next 10 years to meet this demand and Vascular Society of Great Britain and Ireland recommendation. CONCLUSIONS: The UK has a shortage of vascular surgeons at a time when vascular activity is increasing. The VS workforce, both VS consultant and vascular surgeons in training numbers need to expand to address the ongoing shortage and maintain a safe level of service.

Trikafta Rescues CFTR and Lowers Monocyte P2X7R-induced Inflammasome Activation in Cystic Fibrosis.

Rationale: Cystic fibrosis (CF) is caused by mutations in the CFTR (CF transmembrane conductance regulator) gene and is characterized by sustained inflammation. ATP triggers IL-1ß secretion via P2X7R (P2X7 receptor) and activation of the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome. Objectives: To explore the effect of the CFTR modulator elexacaftor/tezacaftor/ivacaftor (Trikafta) on CFTR expression and the ATP/P2X7R signaling axis in monocytes and on circulating proinflammatory markers. Methods: Inflammatory mediators were detected in blood from 42 patients with CF before and after 3 months of Trikafta therapy. Markers of inflammasome activation and IL-1ß secretion were measured in monocytes before and after stimulation with ATP and LPS, in the presence or absence of the P2X7R inhibitor A438079. Measurements and Main Results: P2X7R is overexpressed in CF monocytes, and receptor inhibition decreased NLRP3 expression, caspase-1 activation, and IL-1ß secretion. In vitro and in vivo, P2X7R expression is regulated by CFTR function and intracellular chloride (Cl-) levels. Trikafta therapy restored CFTR expression yet decreased P2X7R in CF monocytes, resulting in normalized Cl- and potassium efflux, and reduced intracellular calcium levels. CFTR modulator therapy decreased circulating levels of ATP and LPS and reduced inflammasome activation and IL-1ß secretion. Conclusions: P2X7R expression is regulated by intracellular Cl- levels and in CF monocytes promotes inflammasome activation. Trikafta therapy significantly increased CFTR protein expression and reduced ATP/P2X7R-induced inflammasome activation. P2X7R may therefore be a promising target for reducing inflammation in patients with CF who are noneligible for Trikafta or other CFTR modulator therapy.

Biomarkers for the early detection of pressure ulcers in the intensive care setting: A comparison between sub-epidermal moisture measurements and interleukin-1α.

Pressure ulcer (PU) prevention in the intensive care unit (ICU) is an important clinical issue as critically unwell patients are at high risk of developing PUs. However, current methods of PU detection are limited, especially for early detection. This study aimed to establish the correlation between Interleukin-1α (IL-1α)/total protein (TP) and sub-epidermal moisture (SEM) measurements in the early identification of PUs in ICU patients. This study employed an observational research design using the STROBE guidelines. Following ethical approval, 53 participants were recruited and sebum was obtained using Sebutape from weight-bearing areas (sacrum, heels and a control site). SEM measurements were taken from the same anatomical sites. Both measures were taken at the same time and participants were followed up for 5 days, or until discharge or death. Correlations between SEM delta measurements, IL-1α, TP and PU incidence and other demographic information were explored using Spearman's correlation for data not normally distributed, and Pearson's R correlation coefficient for normally distributed data. Mean baseline SEM delta measurements indicate abnormal readings for all anatomical sites except the control site, consistent with previous studies. Mean baseline IL-1α/TP readings were higher for the sacrum versus both heels and, on average, readings were higher for the control site versus all other anatomical locations. This is conflicting, given that the control site was non-weight bearing. There were very weak or weak correlations between SEM delta measurements and IL-1α/TP readings. SEM measurements are quick and easy to obtain and results are instant, however Sebutape sampling takes significantly longer and is challenging to conduct among haemodynamically unstable patients. Obtaining SEM measurements is more practical and feasible than Sebutape sampling to assess for the presence of inflammation.

GP-delivered medication review of polypharmacy, deprescribing, and patient priorities in older people with multimorbidity in Irish primary care (SPPiRE Study): A cluster randomised controlled trial.

BACKGROUND: There is a rising prevalence of multimorbidity, particularly in older patients, and a need for evidence-based medicines management interventions for this population. The Supporting Prescribing in Older Adults with Multimorbidity in Irish Primary Care (SPPiRE) trial aimed to investigate the effect of a general practitioner (GP)-delivered, individualised medication review in reducing polypharmacy and potentially inappropriate prescriptions (PIPs) in community-dwelling older patients with multimorbidity in primary care. METHODS AND FINDINGS: We conducted a cluster randomised controlled trial (RCT) set in 51 GP practices throughout the Republic of Ireland. A total of 404 patients, aged ≥65 years with complex multimorbidity, defined as being prescribed ≥15 regular medicines, were recruited from April 2017 and followed up until October 2020. Furthermore, 26 intervention GP practices received access to the SPPiRE website where they completed an educational module and used a template for an individualised patient medication review that identified PIP, opportunities for deprescribing, and patient priorities for care. A total of 25 control GP practices delivered usual care. An independent blinded pharmacist assessed primary outcome measures that were the number of medicines and the proportion of patients with any PIP (from a predefined list of 34 indicators based predominantly on the STOPP/START version 2 criteria). We performed an intention-to-treat analysis using multilevel modelling. Recruited participants had substantial disease and treatment burden at baseline with a mean of 17.37 (standard deviation [SD] 3.50) medicines. At 6-month follow-up, both intervention and control groups had reductions in the numbers of medicines with a small but significantly greater reduction in the intervention group (incidence rate ratio [IRR] 0.95, 95% confidence interval [CI]: 0.899 to 0.999, p = 0.045). There was no significant effect on the odds of having at least 1 PIP in the intervention versus control group (odds ratio [OR] 0.39, 95% CI: 0.140 to 1.064, p = 0.066). Adverse events recorded included mortality, emergency department (ED) presentations, and adverse drug withdrawal events (ADWEs), and there was no evidence of harm. Less than 2% of drug withdrawals in the intervention group led to a reported ADWE. Due to the inability to electronically extract data, primary outcomes were measured at just 2 time points, and this is the main limitation of this work. CONCLUSIONS: The SPPiRE intervention resulted in a small but significant reduction in the number of medicines but no evidence of a clear effect on PIP. This reduction in significant polypharmacy may have more of an impact at a population rather than individual patient level. TRIAL REGISTRATION: ISRCTN Registry ISRCTN12752680.

Text Messaging, Telephone, or In-Person Outpatient Visit to the Surgical Clinic: A Randomized Trial.

INTRODUCTION: Routine outpatient follow-up visits for surgical patients are a source of strain on health-care resources and patients. With the COVID-19 pandemic adding a new urgency to finding the safest follow-up arrangement, text message follow-up might prove an acceptable alternative to a phone call or an in-person clinic visit. METHODS: An open-label, three-arm, parallel randomized trial was conducted. The interventions were traditional in-person appointment, a telephone call, or a text message. The primary outcome was the number of postdischarge complications identified. The secondary outcomes were patient satisfaction with follow-up, future preference, default to follow-up, and preference to receiving medical information by text message. RESULTS: Two hundred eight patients underwent randomization: 50 in the in-person group, 80 in the telephone group, and 78 in the text message group. There was no difference in the number of reported complications: 5 (10%) patients in the in-person group, 7 (9%) patients in the text group, and 11 (14%) patients in the telephone group (P = 0.613). The preferred method of follow-up was by telephone (106, 61.6%). The least preferred was the in-person follow-up (15, 8.7%, P = 0.002), which also had the highest default rate (44%). CONCLUSIONS: There was no evidence that text messages and telephone calls are unsafe and ineffective methods of follow-up. Although most patients are happy to receive results by text message, the majority of patients would prefer a telephone follow-up and are less likely to default by this method. Health-care systems should develop telehealth initiatives when planning health-care services in the wake of the COVID-19 pandemic.

The development and validation of a medicines optimisation tool to protect the physical health of people with severe mental illness (OPTIMISE).

BACKGROUND: The life expectancy of people with severe mental illness (SMI) is shorter than those without SMI, with multimorbidity and poorer physical health contributing to health inequality. Screening tools could potentially assist the optimisation of medicines to protect the physical health of people with SMI. The aim of our research was to design and validate a medicines optimisation tool (OPTIMISE) to help clinicians to optimise physical health in people with SMI. METHODS: A review of existing published guidelines, PubMed and Medline was carried out. Literature was examined for medicines optimisation recommendations and also for reference to the management of physical illness in people with mental illness. Potential indicators were grouped according to physiological system. A multidisciplinary team with expertise in mental health and the development of screening tools agreed that 83 indicators should be included in the first draft of OPTIMISE. The Delphi consensus technique was used to develop and validate the contents. A 17-member multidisciplinary panel of experts from the UK and Ireland completed 2 rounds of Delphi consensus, rating their level of agreement to 83 prescribing indicators using a 5-point Likert scale. Indicators were accepted for inclusion in the OPTIMISE tool after achieving a median score of 1 or 2, where 1 indicated strongly agree and 2 indicated agree, and 75th centile value of ≤ 2. Interrater reliability was assessed among 4 clinicians across 20 datasets and the chance corrected level of agreement (kappa) was calculated. The kappa statistic was interpreted as poor if 0.2 or less, fair if 0.21-0.4, moderate if 0.41-0.6, substantial if 0.61-0.8, and good if 0.81-1.0. RESULTS: Consensus was achieved after 2 rounds of Delphi for 62 prescribing indicators where 53 indicators were accepted after round 1 and a further 9 indicators were accepted after round 2. Interrater reliability of OPTIMISE between physicians and pharmacists indicated a substantial level of agreement with a kappa statistic of 0.75. CONCLUSIONS: OPTIMISE is a 62 indicator medicines optimisation tool designed to assist decision making in those treating adults with SMI. It was developed using a Delphi consensus methodology and interrater reliability is substantial. OPTIMISE has the potential to improve medicines optimisation by ensuring preventative medicines are considered when clinically indicated. Further research involving the implementation of OPTIMISE is required to demonstrate its true benefit. TRIAL REGISTRATION: This article does not report the results of a health care intervention on human participants.

Cost-effectiveness of an occupational therapy-led self-management support programme for multimorbidity in primary care.

BACKGROUND: Multimorbidity is a major public health concern. Complex interventions, incorporating individualized care plans, may be appropriate for patients with multimorbidity given their individualized and variable needs. There is a dearth of evidence on the cost-effectiveness of complex multimorbidity interventions. OBJECTIVE: This study examines the cost-effectiveness of a 6-week occupational therapy-led self-management support programme (OPTIMAL) for adults with multimorbidity. METHODS: Economic evaluation, from a healthcare perspective, was conducted alongside a randomized controlled trial of 149 adults with multimorbidity. Intervention was the OPTIMAL programme with a comparison of usual primary care. Incremental costs, quality-adjusted life years (QALYs) gained, and expected cost-effectiveness were estimated at 6 months and uncertainty was explored using cost-effectiveness acceptability curves. RESULTS: The intervention was associated with a mean improvement in QALYs gained of 0.031 per patient (P-value: 0.063; 95% confidence intervals [CIs]: -0.002 to 0.063) and a mean reduction in total costs of €2,548 (P-value: 0.114; 95% CIs: -5,606 to 509) per patient. At cost-effectiveness threshold values of €20,000 and €45,000 per QALY, the probability of the intervention being cost-effective was estimated to be 0.951 and 0.958, respectively. The results remained consistent across all subgroups examined. CONCLUSIONS: This study adds to the limited evidence base on the cost-effectiveness of complex interventions for multimorbidity, and highlights the potential for the OPTIMAL programme to be cost-effective. Further studies are warranted to explore the clinical and cost-effectiveness of complex interventions for the multimorbidity patient population, and for subgroups within it. TRIAL REGISTRATION: Trial number: ISRCTN67235963.

Vascular Surgeon Burnout and Resilience in the United Kingdom: A Report from the Vascular Society Workforce Committee.

BACKGROUND: Occupational burnout is a growing concern in frontline roles such as vascular surgery, and is associated with medical errors and shortened careers. Our aim is to measure burnout, resilience, and associated risk factors among vascular surgeons (VS) in the United Kingdom (UK). METHODS: We carried out an electronic survey of active VS in the UK using validated self-report questionnaires, including the following: Copenhagen Burnout Inventory (CBI), Brief Resilience Scale (BRS), and information on job characteristics, health, and well-being. Univariate regression analysis looked at potential risk factors. RESULTS: One hundred forty-eight VS responded (49% participation rate), and after excluding retirees and nonconsultants, 133 VS practicing in the UK were analyzed. Mean age was 49.9 ± 7.19 years; the majority (83.5%) were male. In total, 81.3% recorded ethnic identity as White. In addition, 93.2% worked full time; 74.8% were contracted above 10 programmed activities and 87.9% worked more than 40 hr/week. On-call was 1 in 6, or above, for 87.4%. Overall, 38.4% of VS had high burnout on the CBI. Resilience was also high, with BRS mean (standard deviation) of 3.6 (0.69) and median (interquartile range) of 3.7 (3-4). Univariate regression analysis found no significant risk factor associated with high burnout or resilience. CONCLUSIONS: VS in the UK have high levels of burnout and work long hours. Resilience levels were also high, which may offer some protection. However, policymakers and our surgical leaders should address contributing factors and excessive working hours and establish measures to identify and support surgeon well-being for optimal surgeon and patient safety.

Impact of assessment and intervention by a health and social care professional team in the emergency department on the quality, safety, and clinical effectiveness of care for older adults: A randomised controlled trial.

BACKGROUND: Older adults frequently attend the emergency department (ED) and experience high rates of adverse events following ED presentation. This randomised controlled trial evaluated the impact of early assessment and intervention by a dedicated team of health and social care professionals (HSCPs) in the ED on the quality, safety, and clinical effectiveness of care of older adults in the ED. METHODS AND FINDINGS: This single-site randomised controlled trial included a sample of 353 patients aged ≥65 years (mean age = 79.6, SD = 7.01; 59.2% female) who presented with lower urgency complaints to the ED a university hospital in the Mid-West region of Ireland, during HSCP operational hours. The intervention consisted of early assessment and intervention carried out by a HSCP team comprising a senior medical social worker, senior occupational therapist, and senior physiotherapist. The primary outcome was ED length of stay. Secondary outcomes included rates of hospital admissions from the ED; hospital length of stay for admitted patients; patient satisfaction with index visit; ED revisits, mortality, nursing home admission, and unscheduled hospital admission at 30-day and 6-month follow-up; and patient functional status and quality of life (at index visit and follow-up). Demographic information included the patient's gender, age, marital status, residential status, mode of arrival to the ED, source of referral, index complaint, triage category, falls, and hospitalisation history. Participants in the intervention group (n = 176) experienced a significantly shorter ED stay than the control group (n = 177) (6.4 versus 12.1 median hours, p < 0.001). Other significant differences (intervention versus control) included lower rates of hospital admissions from the ED (19.3% versus 55.9%, p < 0.001), higher levels of satisfaction with the ED visit (p = 0.008), better function at 30-day (p = 0.01) and 6-month follow-up (p = 0.03), better mobility (p = 0.02 at 30 days), and better self-care (p = 0.03 at 30 days; p = 0.009 at 6 months). No differences at follow-up were observed in terms of ED re-presentation or hospital admission. Study limitations include the inability to blind patients or ED staff to allocation due to the nature of the intervention, and a focus on early assessment and intervention in the ED rather than care integration following discharge. CONCLUSIONS: Early assessment and intervention by a dedicated ED-based HSCP team reduced ED length of stay and the risk of hospital admissions among older adults, as well as improving patient satisfaction. Our findings support the effectiveness of an interdisciplinary model of care for key ED outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03739515; registered on 12 November 2018.

Best Practices: Imaging Strategies for Reduced-Dose Chest CT in the Management of Cystic Fibrosis-Related Lung Disease.

OBJECTIVE. Cystic fibrosis (CF) is a multisystemic life-limiting disorder. The leading cause of morbidity in CF is chronic pulmonary disease. Chest CT is the reference standard for detection of bronchiectasis. Cumulative ionizing radiation limits the use of CT, particularly as treatments improve and life expectancy increases. The purpose of this article is to summarize the evidence on low-dose chest CT and its effect on image quality to determine best practices for imaging in CF. CONCLUSION. Low-dose chest CT is technically feasible, reduces dose, and renders satisfactory image quality. There are few comparison studies of low-dose chest CT and standard chest CT in CF; however, evidence suggests equivalent diagnostic capability. Low-dose chest CT with iterative reconstructive algorithms appears superior to chest radiography and equivalent to standard CT and has potential for early detection of bronchiectasis and infective exacerbations, because clinically significant abnormalities can develop in patients who do not have symptoms. Infection and inflammation remain the primary causes of morbidity requiring early intervention. Research gaps include the benefits of replacing chest radiography with low-dose chest CT in terms of improved diagnostic yield, clinical decision making, and patient outcomes. Longitudinal clinical studies comparing CT with MRI for the monitoring of CF lung disease may better establish the complementary strengths of these imaging modalities.

Characterization of the Inflammatory Response to Severe COVID-19 Illness.

Rationale: Coronavirus disease (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood.Objectives: To define the cytokine profile of COVID-19 and to identify evidence of immunometabolic alterations in those with severe illness.Methods: Levels of IL-1ß, IL-6, IL-8, IL-10, and sTNFR1 (soluble tumor necrosis factor receptor 1) were assessed in plasma from healthy volunteers, hospitalized but stable patients with COVID-19 (COVIDstable patients), patients with COVID-19 requiring ICU admission (COVIDICU patients), and patients with severe community-acquired pneumonia requiring ICU support (CAPICU patients). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of AAT (alpha-1 antitrypsin) to COVID-19 was also evaluated.Measurements and Main Results: IL-1ß, IL-6, IL-8, and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVIDstable patients, and demonstrated higher levels of IL-1ß, IL-6, and sTNFR1 but lower IL-10 than CAPICU patients. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, HIF-1α (hypoxia-inducible factor-1α), and lactate. The production and sialylation of AAT increased in COVID-19, but this antiinflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P < 0.0001). In critically unwell patients with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and mortality, whereas improvement in IL-6:AAT was associated with clinical resolution (P < 0.0001).Conclusions: The COVID-19 cytokinemia is distinct from that of other types of pneumonia, leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population.

Eating behaviour, physical activity, TV exposure and sleeping habits in five year olds: a latent class analysis.

BACKGROUND: Diet, physical activity, sedentary behaviours, and sleep time are considered major contributory factors of the increased prevalence of childhood overweight and obesity. The aims of this study were to (1) identify behavioural clusters of 5 year old children based on lifestyle behaviours, (2) explore potential determinants of class membership, and (3) to determine if class membership was associated with body measure outcomes at 5 years of age. METHODS: Data on eating behaviour, engagement in active play, TV watching, and sleep duration in 1229 5 year old children from the Cork BASELINE birth cohort study was obtained through in-person interviews with parent. Latent class analysis was used to identify behavioural clusters. Potential determinants of cluster membership were investigated using multinomial logistic regression. Associations between the identified classes and cardio metabolic body measures were examined using multivariate logistic and linear regression, with cluster membership used as the independent variable. RESULTS: 51% of children belonged to a normative class, while 28% of children were in a class characterised by high scores on food avoidance scales in combination with low enjoyment of food, and 20% experienced high scores on the food approach scales. Children in both these classes had lower conditional probabilities of engaging in active play for at least 1 hour per day and sleeping for a minimum of 10 h, and higher probability of watching TV for 2 hours or more, compared to the normative class. Low socioeconomic index (SEI) and no breastfeeding at 2 months were found to be associated with membership of the class associated with high scores on the food avoidance scale, while lower maternal education was associated with the class defined by high food approach scores. Children in the class with high scores on the food approach scales had higher fat mass index (FMI), lean mass index (LMI), and waist-to-height ratio (WtHR) compared to the normative class, and were at greater risk of overweight and obesity. CONCLUSION: Findings suggest that eating behaviour appeared to influence overweight and obesity risk to a greater degree than activity levels at 5 years old. Further research of how potentially obesogenic behaviours in early life track over time and influence adiposity and other cardio metabolic outcomes is crucial to inform the timing of interventions.

Incidence of falls among adults with cerebral palsy: a cohort study using primary care data.

AIM: To compare the rate of falls between adults with and without cerebral palsy (CP). METHOD: We used primary care data on 1705 adults with CP and 5115 adults without CP matched for age, sex, and general practice attended. We compared odds of experiencing a fall between adults with and without CP using conditional logistic regression. We compared the rate of falls using a negative binomial model. RESULTS: Participants were 3628 males (53%) and 3192 females (47%) (median age 29y, interquartile range 20-42y) at the start of follow-up. Follow-up was 14 617 person-years for adults with CP and 56 816 person-years for adults without CP. Of adults with CP, 15.3% experienced at least one fall compared to 5.7% of adults without CP. Adults with CP had 3.64 times (95% confidence interval [CI] 2.98-4.45) the odds of experiencing a fall compared to adults without CP. The rate of falls was 30.5 per 1000 person-years and 6.7 per 1000 person-years for adults with and without CP respectively (rate ratio 5.83, 95% CI 4.84-7.02) INTERPRETATION: Adults with CP are more likely to fall, and fall more often, than adults without CP. The causes and consequences of falls in adults with CP need examination. WHAT THIS PAPER ADDS: Twenty adults with CP and 5.3 adults without CP experienced at least one fall per 1000 person-years. Adults with CP experienced 30.5 falls per 1000 person-years compared to 6.7 falls per 1000 person-years among adults without CP. Adults with CP had 3.64 times the odds of experiencing a fall compared to adults without CP. Adults with CP experienced 5.83 times more falls than adults without CP.

Specific Inhibition of the NLRP3 Inflammasome as an Antiinflammatory Strategy in Cystic Fibrosis.

Rationale: Cystic fibrosis (CF) pulmonary disease is characterized by chronic infection with Pseudomonas aeruginosa and sustained neutrophil-dominant inflammation. The lack of effective antiinflammatory therapies for people with CF (PWCF) represents a significant challenge.Objectives: To identify altered immunometabolism in the CF neutrophil and investigate the feasibility of specific inhibition of the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome as a CF antiinflammatory strategy in vivo.Methods: Key markers of increased aerobic glycolysis, known as a Warburg effect, including cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, succinate, HIF-1α (hypoxia-inducible factor-1α), lactate, and the IL-1ß precursor pro-IL-1ß, as well as caspase-1 activity and processing of pro-IL-1ß to IL-1ß by the NLRP3 inflammasome, were measured in neutrophils from blood and airway secretions from healthy control subjects (n = 12), PWCF (n = 16), and PWCF after double-lung transplantation (n = 6). The effects of specific inhibition of NLRP3 on airway inflammation and bacterial clearance in a murine CF model were subsequently assessed in vivo.Measurements and Main Results: CF neutrophils display increased aerobic glycolysis in the systemic circulation. This effect is driven by low-level endotoxemia, unaffected by CFTR (cystic fibrosis transmembrane conductance regulator) modulation, and resolves after transplant. The increased pro-IL-1ß produced is processed to its mature active form in the LPS-rich CF lung by the NLRP3 inflammasome via caspase-1. Specific NLRP3 inhibition in vivo with MCC950 inhibited IL-1ß in the lungs of CF mice (P < 0.0001), resulting in significantly reduced airway inflammation and improved Pseudomonas clearance (P < 0.0001).Conclusions: CF neutrophil immunometabolism is altered in response to inflammation. NLRP3 inflammasome inhibition may have an antiinflammatory and anti-infective role in CF.