An analysis of complaints about hospital care in the Republic of Ireland.

BACKGROUND: Patients and family members make complaints about their hospital care in order to express their dissatisfaction with the care received and prompt quality improvement. Increasingly, it is being understood that these complaints could serve as important data on how to improve care if analysed using a standardized tool. The use of the Healthcare Complaints Analysis Tool (HCAT) for this purpose has emerged internationally for quality and safety improvement. Previous work has identified hot spots (areas in care where harm occurs frequently) and blind spots (areas in care that are difficult for staff members to observe) from complaints analysis. This study aimed to (i) apply the HCAT to a sample of complaints about hospital care in the Republic of Ireland (RoI) to identify hot spots and blind spots in care and (ii) compare the findings of this analysis to a previously published study on hospital complaints in the UK. METHODS: A sample of complaints was taken from 16 hospitals in the RoI in Quarter 4 of 2019 (n = 641). These complaints were coded using the HCAT to classify complaints by domain, category, severity, stage of care and harm. Chi-squared tests were used to identify hot spots, and logistic regression was used to identify blind spots. The findings of this study were compared to a previously published UK study that used HCAT to identify hot spots and blind spots. RESULTS: Hot spots were identified in Irish hospital complaints while patients were receiving care on the ward, during initial examination and diagnosis, and while they were undergoing operations or procedures. This aligned with hot spots identified in the UK study. Blind spots were found for systemic problems, where patients experience multiple issues across their care. CONCLUSIONS: Hot spots and blind spots for patient harm can be identified in hospital care using the HCAT analysis. These in turn could be used to inform improvement interventions, and direct stakeholders to areas that require urgent attention. This study also highlights the promise of the HCAT for use across different healthcare systems, with similar results emerging from the RoI and the UK.

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.

A systematic review exploring the impact of focal leader behaviours on health care team performance.

AIM: The aim of this study is to understand how the behaviour of focal leaders impacts health care team performance and effectiveness. BACKGROUND: Despite recent shifts towards more collectivistic leadership approaches, hierarchical structures that emphasize the role of an individual focal leader (i.e., the formal appointed leader) are still the norm in health care. Our understanding of the effect of focal leader behaviours on health care team performance remains unclear. EVALUATION: A systematic review was conducted. Five electronic databases were searched using key terms. One thousand forty-seven records were retrieved. Data extraction, quality appraisal and narrative synthesis were conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. KEY ISSUES: Fifty papers met the criteria for inclusion, were reviewed and synthesized under the following categories: task-focused leadership, directive leadership, empowering leadership and relational focused leadership. CONCLUSIONS: Categories are discussed in relation to team performance outcomes, safety specific outcomes, individual-level outcomes and outcomes related to interpersonal dynamics. Emerging themes are explored to examine and reflect on how leadership is enacted in health care, to catalogue best practices and to cascade these leadership practices broadly. IMPLICATIONS FOR NURSING MANAGEMENT: Empowering and relational leadership styles were associated with positive outcomes for nursing team performance. This underscores the importance of training and encouraging nursing leaders to engage in more collaborative leadership behaviours.

Stakeholders' perspectives on models of care in the emergency department and the introduction of health and social care professional teams: A qualitative analysis using World Cafés and interviews.

BACKGROUND: There is some evidence that health and social care professional (HSCP) teams contribute to enhanced patient and process outcomes in increasingly crowded emergency departments (EDs), but the views of service users and providers on this model of care need investigation to optimize implementation. OBJECTIVE: This qualitative study investigated the perspectives of key ED stakeholders about HSCP teams working in the ED. METHODS: Using a participatory design, we conducted World Café focus groups and individual interviews in two Irish hospital sites with 65 participants (purposive sampling) including ED patients and carers/relatives, ED doctors and nurses, HSCPs and pre-hospital staff. Data were thematically analysed using NVivo software. RESULTS: Participants reported that ED-based HSCP teams could improve quality and integration of care and staff experience (Theme 1) and would be appropriate for older adults with complex needs and non-urgent complaints (Theme 2). Concerns were raised about operational and relational barriers to implementation (Theme 3), and changes in processes and culture were considered necessary for HSCPs to work successfully in the ED (Theme 4). In contrast to service providers, service users' concerns centred on the importance of positive communication and relations (Theme 5). CONCLUSIONS: Our study indicates potential acceptability of HSCP teams working in the ED, especially to care for older adults; however, operational and relational aspects, particularly developing interdisciplinary and integrated care, need addressing to ensure successful implementation. Differences in priorities between service users and providers (relational vs operational) highlighted the usefulness of gathering views from multiple stakeholders to understand ED processes.

Using Lean Six Sigma to improve rates of day of surgery admission in a national thoracic surgery department.

OBJECTIVE: The aim of this study is to improve rates of day of surgery admission (DOSA) for all suitable elective thoracic surgery patients. DESIGN: Lean Six Sigma (LSS) methods were used to enable improvements to both the operational process and the organizational working of the department over a period of 19 months. SETTING: A national thoracic surgery department in a large teaching hospital in Ireland. PARTICIPANTS: Thoracic surgery staff, patients and quality improvement staff at the hospital. INTERVENTION(S): LSS methods were employed to identify and remove the non-value-add in the patient's journey and achieve higher levels of DOSA. A pre-surgery checklist and Thoracic Planning Meeting were introduced to support a multidisciplinary approach to enhanced recovery after surgery (ERAS), reduce rework, improve list efficiency and optimize bed management. MAIN OUTCOME MEASURE(S): To achieve DOSA for all suitable elective thoracic surgery patients in line with the National Key Performance Indicator of 75%. A secondary outcome would be to further decrease overall length of stay by 1 day. RESULTS: Over a 19 month period, DOSA has increased from 10 to 75%. Duplication of preoperative tests reduced from 83 to <2%. Staff and patient surveys show increased satisfaction and improved understanding of ERAS. CONCLUSIONS: Using LSS methods to improve both operational process efficiency and organizational clinical processes led to the successful achievement of increasing rates of DOSA in line with national targets.

Zap it track it: the application of Lean Six Sigma methods to improve the screening system of low-grade mucinous neoplasms of the appendix in an acute hospital setting.

OBJECTIVE: To improve the number of patients receiving annual computed tomography (CT) scan and tumour markers, who are diagnosed with low-grade mucinous neoplasms (LAMN). DESIGN: A pre-/post-intervention design was employed using Lean Six Sigma methods to identify gaps in the screening system and to develop and implement solutions for a more robust, auditable screening programme. SETTING: The patients diagnosed with LAMN of the appendix referred to the acute hospital and are enrolled in the screening service. PARTICIPANTS: Consultant colorectal surgeons, cancer nurse specialist, colorectal medical team and quality improvement staff. INTERVENTIONS: Diagnostic tools identified gaps in the current process. A set of improvements were implemented to standardize the pathway for referral and surveillance of patients, provide information on the condition and treatment and standardize and track information received by patients and their referring hospital. MAIN OUTCOME MEASURE(S): Pre and post-intervention outcome measures were taken for the number of patients who receive an annual CT of thoracic, abdomen and peritoneum and tumour markers and number of patients who receive information and contact details. RESULTS: At baseline, of the 28 patients that met the inclusion criteria only 61% had a correct follow-up. Following the implementation of improvements, 78% of patients had correct follow-up and 90% had received information. CONCLUSIONS: Gaps in the current cancer screening system were identified and improvements implemented a reduced number of patients having an incorrect follow-up. Findings are applicable across all precancerous screening systems irrespective of the type of malignancy. The methods used empowered patients and fostered an interdisciplinary team approach to care.

Do safety briefings improve patient safety in the acute hospital setting? A systematic review.

AIMS: To synthesize current knowledge about the impact of safety briefings as an intervention to improve patient safety. BACKGROUND: Improving safety in health care remains an ongoing challenge. There is a lack of evidence underpinning safety enhancing interventions. DESIGN: Mixed method multi-level synthesis. DATA SOURCES: Four health literature databases were searched (Cinahl, Medline, Scopus and Health Business Elite) from January 2002 - March 2017. REVIEW METHODS: Thomas and Harden approach to mixed method synthesis. RESULTS: Following quality appraisal, 12 studies were included. There was significant heterogeneity in study aims, measures, and outcomes. Findings showed that safety briefings achieved beneficial outcomes and can improve safety culture. Outcomes included improved risk identification, reduced falls, enhanced relationships, increased incident reporting, ability to voice concerns, and reduced length of stay. CONCLUSION: Healthcare leaders should embrace the potential of safety briefings by promoting their effective use whilst allowing for local adaptation.

The co-design, implementation and evaluation of a serious board game 'PlayDecide patient safety' to educate junior doctors about patient safety and the importance of reporting safety concerns.

BACKGROUND: We believe junior doctors are in a unique position in relation to reporting of incidents and safety culture. They are still in training and are also 'fresh eyes' on the system providing valuable insights into what they perceive as safe and unsafe behaviour. The aim of this study was to co-design and implement an embedded learning intervention - a serious board game - to educate junior doctors about patient safety and the importance of reporting safety concerns, while at the same time shaping a culture of responsiveness from senior medical staff. METHODS: A serious game based on the PlayDecide framework was co-designed and implemented in two large urban acute teaching hospitals. To evaluate the educational value of the game voting on the position statements was recorded at the end of each game by a facilitator who also took notes after the game of key themes that emerged from the discussion. A sample of players were invited on a voluntary basis to take part in semi-structured interviews after playing the game using Flanagan's Critical Incident Technique. A paper-based questionnaire on 'Safety Concerns' was developed and administered to assess pre-and post-playing the game reporting behaviour. Dissemination workshops were held with senior clinicians to promote more inclusive leadership behaviours and responsiveness to junior doctors raising of safety concerns from senior clinicians. RESULTS: The game proved to be a valuable patient safety educational tool and proved effective in encouraging deep discussion on patient safety. There was a significant change in the reporting behaviour of junior doctors in one of the hospitals following the intervention. CONCLUSION: In healthcare, limited exposure to patient safety training and narrow understanding of safety compromise patients lives. The existing healthcare system needs to value the role that junior doctors and others could play in shaping a positive safety culture where reporting of all safety concerns is encouraged. Greater efforts need to be made at hospital level to develop a more pro-active safe and just culture that supports and encourages junior doctors and ultimately all doctors to understand and speak up about safety concerns.

Developing outcome, process and balancing measures for an emergency department longitudinal patient monitoring system using a modified Delphi.

BACKGROUND: Early warning score systems have been widely recommended for use to detect clinical deterioration in patients. The Irish National Emergency Medicine Programme has developed and piloted an emergency department specific early warning score system. The objective of this study was to develop a consensus among frontline healthcare staff, quality and safety staff and health systems researchers regarding evaluation measures for an early warning score system in the Emergency Department. METHODS: Participatory action research including a modified Delphi consensus building technique with frontline hospital staff, quality and safety staff, health systems researchers, local and national emergency medicine stakeholders was the method employed in this study. In Stage One, a workshop was held with the participatory action research team including frontline hospital staff, quality and safety staff and health systems researchers to gather suggestions regarding the evaluation measures. In Stage Two, an electronic modified-Delphi study was undertaken with a panel consisting of the workshop participants, key local and national emergency medicine stakeholders. Descriptive statistics were used to summarise the characteristics of the panellists who completed the questionnaires in each round. The mean Likert rating, standard deviation and 95% bias-corrected bootstrapped confidence interval for each variable was calculated. Bonferroni corrections were applied to take account of multiple testing. Data were analysed using Stata 14.0 SE. RESULTS: Using the Institute for Healthcare Improvement framework, 12 process, outcome and balancing metrics for measuring the effectiveness of an ED-specific early warning score system were developed. CONCLUSION: There are currently no published measures for evaluating the effectiveness of an ED early warning score system. It was possible in this study to develop a suite of evaluation measures using a modified Delphi consensus approach. Using the collective expertise of frontline hospital staff, quality and safety staff and health systems researchers to develop and categorise the initial set of potential measures was an innovative and unique element of this study.

Safety culture in health care teams: A narrative review of the literature.

AIM: Explore the recent literature to examine the factors that affect safety culture within health care teams. BACKGROUND: Health care organisations must understand and improve their safety culture. However, safety culture is a complex phenomenon which interacts with a myriad of factors, making it difficult to define, measure and improve. EVALUATION: A comprehensive search strategy was used to search four major databases. Peer-reviewed which were published in English between 2006 and 2017 and presented research studies related to safety culture in health care teams were included. A narrative analysis was undertaken. KEY ISSUES: Issues relevant to the definition, measurement and improvement of safety culture, the impact of teamwork and communication on safety culture, the role of leaders and accountability are explored. CONCLUSION: The above themes inform our understanding of developing, measuring and sustaining safety culture in health care teams. However, further research is warranted to accurately understand how to measure and improve safety culture. IMPLICATIONS FOR NURSING MANAGEMENT: To support a safety culture, initiatives to facilitate effective communication between nurse practitioners and other health care professionals must be introduced. Nurse managers should adopt leadership strategies that will support nurses' psychological safety and create a just culture.

Calcium mishandling impairs contraction in right ventricular hypertrophy prior to overt heart failure.

Currently, there are no tailored therapies available for the treatment of right ventricular (RV) hypertrophy, and the cellular mechanisms that underlie the disease are poorly understood. We investigated the cellular changes that occur early in the progression of the disease, when RV hypertrophy is evident, but prior to the onset of heart failure. Intracellular Ca2+ ([Ca2+]i) handling was examined in a rat model of monocrotaline (MCT)-induced pulmonary hypertension and subsequent RV hypertrophy. [Ca2+]i and stress production were measured in isolated RV trabeculae under baseline conditions (1-Hz stimulation, 1.5 mM [Ca2+]o, 37 °C), and in response to inotropic interventions (5-Hz stimulation or 1-µM isoproterenol). Under baseline conditions, MCT trabeculae had impaired Ca2+ release in response to stimulation with a 45% delay in the time-to-peak Ca2+, but there was no difference in the amplitude and decay of the Ca2+ transient, or active stress relative to RV trabeculae from normotensive hearts (CON). Increasing stimulation frequency from 1 to 5 Hz increased stress in CON, but not MCT trabeculae. Similarly, ß-adrenergic stimulation with isoproterenol increased Ca2+ transient amplitude and active stress in CON, but not in MCT trabeculae, despite accelerating Ca2+ transient decay in trabeculae from both groups. During isoproterenol treatment, MCT trabeculae showed increased diastolic Ca2+ leak, which may explain the blunted inotropic response to ß-adrenergic stimulation. Confocal imaging of trabeculae fixed following functional measurements showed that myocytes were on average wider, and transverse-tubule organisation was disrupted in MCT which provides a mechanism to explain the observed slower release of Ca2+.

"The era of single disease cowboys is out": evaluating the experiences of students, faculty, and collaborators in an interdisciplinary global health training program.

BACKGROUND: Global Health is an inherently interdisciplinary field but overseas training in global health, particularly among health science institutions, has been an 'individual' or 'individual discipline' experience. Team-based training is an approach to global health education which is increasing in popularity; research on team-training demonstrates that teams are more productive than individuals. In 2015, the Johns Hopkins Center for Global Health (CGH) developed the Global Established Multidisciplinary Sites (GEMS) program, an interdisciplinary training program which was designed to establish a new norm in global health training by bringing interdisciplinary teams of faculty and students together to identify and solve complex global health challenges. This research aims to evaluate the program's first year and contribute to the literature on interdisciplinary team training. We conducted 22 in-depth interviews with students, faculty, and local collaborators from 3 GEMS project sites. Findings were analyzed for themes through a framework approach. RESULTS: The program exposed students, faculty, and collaborators to a wide range of disciplines in global health. Students' desire to learn how other disciplines contribute to global health solutions was an important motivator for joining GEMS; many participants including faculty and collaborators valued exposure to multiple disciplines. Mentorship and communication were a challenge across all teams in part due to members having distinct "disciplinary languages". Balancing disciplinary representation on teams and establishing work plans were also key challenges. CONCLUSIONS: Based on the data the CGH provides four recommendations for institutions developing global health interdisciplinary teams to optimize team functioning and address challenges in mentorship, language, and roles: 1) address interdisciplinary communication early, 2) develop work plans during group formation, 3) meet as a team prior to travel, and 4) establish regular check ins. This article provides first-hand reflections on interdisciplinary team experiences in a global context and provides a pathway for the development of innovative strategies in global health training.

Does the intercept of the heat-stress relation provide an accurate estimate of cardiac activation heat?

KEY POINTS: The heat of activation of cardiac muscle reflects the metabolic cost of restoring ionic homeostasis following a contraction. The accuracy of its measurement depends critically on the abolition of crossbridge cycling. We abolished crossbridge activity in isolated rat ventricular trabeculae by use of blebbistatin, an agent that selectively inhibits myosin II ATPase. We found cardiac activation heat to be muscle length independent and to account for 15-20% of total heat production at body temperature. We conclude that it can be accurately estimated at minimal muscle length. ABSTRACT: Activation heat arises from two sources during the contraction of striated muscle. It reflects the metabolic expenditure associated with Ca2+ pumping by the sarcoplasmic reticular Ca2+ -ATPase and Ca2+ translocation by the Na+ /Ca2+ exchanger coupled to the Na+ ,K+ -ATPase. In cardiac preparations, investigators are constrained in estimating its magnitude by reducing muscle length to the point where macroscopic twitch force vanishes. But this experimental protocol has been criticised since, at zero force, the observed heat may be contaminated by residual crossbridge cycling activity. To eliminate this concern, the putative thermal contribution from crossbridge cycling activity must be abolished, at least at minimal muscle length. We achieved this using blebbistatin, a selective inhibitor of myosin II ATPase. Using a microcalorimeter, we measured the force production and heat output, as functions of muscle length, of isolated rat trabeculae from both ventricles contracting isometrically at 5 Hz and at 37°C. In the presence of blebbistatin (15 µmol l-1 ), active force was zero but heat output remained constant, at all muscle lengths. Activation heat measured in the presence of blebbistatin was not different from that estimated from the intercept of the heat-stress relation in its absence. We thus reached two conclusions. First, activation heat is independent of muscle length. Second, residual crossbridge heat is negligible at zero active force; hence, the intercept of the cardiac heat-force relation provides an estimate of activation heat uncontaminated by crossbridge cycling. Both results resolve long-standing disputes in the literature.

Study protocol for evaluating the implementation and effectiveness of an emergency department longitudinal patient monitoring system using a mixed-methods approach.

BACKGROUND: Early detection of patient deterioration is a key element of patient safety as it allows timely clinical intervention and potential rescue, thus reducing the risks of serious patient safety incidents. Longitudinal patient monitoring systems have been widely recommended for use to detect clinical deterioration. However, there is conflicting evidence on whether they improve patient outcomes. This may in part be related to variation in the rigour with which they are implemented and evaluated. This study aims to evaluate the implementation and effectiveness of a longitudinal patient monitoring system designed for adult patients in the unique environment of the Emergency Department (ED). METHODS: A novel participatory action research (PAR) approach is taken where socio-technical systems (STS) theory and analysis informs the implementation through the improvement methodology of 'Plan Do Study Act' (PDSA) cycles. We hypothesise that conducting an STS analysis of the ED before beginning the PDSA cycles will provide for a much richer understanding of the current situation and possible challenges to implementing the ED-specific longitudinal patient monitoring system. This methodology will enable both a process and an outcome evaluation of implementing the ED-specific longitudinal patient monitoring system. Process evaluations can help distinguish between interventions that have inherent faults and those that are badly executed. DISCUSSION: Over 1.2 million patients attend EDs annually in Ireland; the successful implementation of an ED-specific longitudinal patient monitoring system has the potential to affect the care of a significant number of such patients. To the best of our knowledge, this is the first study combining PAR, STS and multiple PDSA cycles to evaluate the implementation of an ED-specific longitudinal patient monitoring system and to determine (through process and outcome evaluation) whether this system can significantly improve patient outcomes by early detection and appropriate intervention for patients at risk of clinical deterioration.

An introduction to the Emergency Department Adult Clinical Escalation protocol: ED-ACE.

PURPOSE OF THE STUDY: This study demonstrates how a participatory action research approach was used to address the challenge of the early and effective detection of the deteriorating patient in the ED setting. The approach enabled a systematic approach to patient monitoring and escalation of care to be developed to address the wide-ranging spectrum of undifferentiated presentations and the phases of ED care from triage to patient admission. This paper presents a longitudinal patient monitoring system, which aims to provide monitoring and escalation of care, where necessary, of adult patients from triage to admission to hospital in a manner that is feasible in the unique ED environment. METHODS: An action research approach was taken to designing a longitudinal patient monitoring system appropriate for the ED. While the first draft protocol for post-triage monitoring and escalation was designed by a core research group, six clinical sites were included in iterative cycles of planning, action, reviewing and further planning. Reasons for refining the system at each site were collated and the protocol was adjusted accordingly before commencing the process at the next site. RESULTS: The ED Adult Clinical Escalation longitudinal patient monitoring system (ED-ACE) evolved through iterative cycles of design and testing to include: (1) a monitoring chart for adult patients; (2) a standardised approach to the monitoring and reassessment of patients after triage until they are assessed by a clinician; (3) the ISBAR (I=Identify, S=Situation, B=Background, A=Assessment, R=Recommendation) tool for interprofessional communication relating to clinical escalation; (4) a template for prescribing a patient-specific monitoring plan to be used by treating clinicians to guide patient monitoring from the time the patient is assessed until when they leave the ED and (5) a protocol for clinical escalation prompted by single physiological triggers and clinical concern. CONCLUSIONS: This tool offers a link in the 'Chain of Prevention' between the Manchester Triage System and ward-based early warning scores taking account of the importance of standardisation, while being sufficiently adaptable for the unique working environment and patient population in the ED.

Impaired ADP channeling to mitochondria and elevated reactive oxygen species in hypertensive hearts.

Systemic hypertension initially promotes a compensatory cardiac hypertrophy, yet it progresses to heart failure (HF), and energetic deficits appear to be central to this failure. However, the transfer of energy between the mitochondria and the myofibrils is not often considered as part of the energetic equation. We compared hearts from old spontaneously hypertensive rats (SHRs) and normotensive Wistar controls. SHR hearts showed a 35% depression in mitochondrial function, yet produced at least double the amount of reactive oxygen species (ROS) in all respiration states in left ventricular (LV) homogenates. To test the connectivity between mitochondria and myofibrils, respiration was further tested in situ with LV permeabilized fibers by addition of multiple substrates and ATP, which requires hydrolysis to mediate oxidative phosphorylation. By trapping ADP using a pyruvate kinase enzyme system, we tested ADP channeling towards mitochondria, and this suppressed respiration and elevated ROS production more in the SHR fibers. The ADP-trapped state was also less relieved on creatine addition, likely reflecting the 30% depression in total CK activity in the SHR heart fibers. Confocal imaging identified a 34% longer distance between the centers of myofibril to mitochondria in the SHR hearts, which increases transverse metabolite diffusion distances (e.g., for ATP, ADP, and creatine phosphate). We propose that impaired connectivity between mitochondria and myofibrils may contribute to elevated ROS production. Impaired energy exchange could be the result of ultrastructural changes that occur with hypertrophy in this model of hypertension.

Positive Inotropic Effect of Prostaglandin F2α in Rat Ventricular Trabeculae.

Prostaglandins are ubiquitous signaling molecules in the body that produce autocrine/paracrine effects on target cells in response to mechanical or chemical signals. In the heart, long-term exposure to prostaglandin (PG) F2α has been linked to the development of hypertrophy; however, there is no consensus on the acute effect of PGF2α. Our aim was to determine the response to exogenous PGF2α in isolated trabeculae from rat hearts. PGF2α (1 µM) increased both the Ca transients and the isometric stress in trabeculae, reaching steady state after 10-15 minutes, without altering the time course of Ca transient decay. The precursor of PGF2α, arachidonic acid, also stimulated a similar response. The positive inotropic effect of PGF2α was mediated through a protein kinase C signaling pathway that involved activation of the sarcolemmal Na/H exchanger. We also found that the slow force response to stretch was attenuated in the presence of PGF2α and by addition of indomethacin, a blocker of prostaglandin synthesis. In conclusion, PGF2α was positively inotropic when acutely applied to trabeculae and contributed to the increased Ca transients during the slow force response to stretch. Together, these data suggest that PGF2α is important in maintaining homeostasis during volume loading in healthy hearts.

Depotentiation of intact rat cardiac muscle unmasks an Epac-dependent increase in myofilament Ca(2+) sensitivity.

Recently, a family of guanine nucleotide exchange factors have been identified in many cell types as important effectors of cyclic adenosine 3',5'-monophospahte (cAMP) signalling that is independent of protein kinase A (PKA). In the heart, investigation of exchange protein directly activated by cAMP (Epac) has yielded conflicting results. Since cAMP is an important regulator of cardiac contractility, this study aimed to examine whether Epac activation modulates excitation-contraction coupling in ventricular preparations from rat hearts. The study used 8-(4-chlorophenylthio)-2'-O-methyladenosine-3', 5'-cyclic monophosphate (cpTOME), an analogue of cAMP that activates Epac, but not PKA. In isolated myocytes, cpTOME increased Ca(2+) spark frequency from about 7 to 32/100 µm(3)/s (n = 10), P = 0.05 with a reduction in the peak amplitude of the sparks. Simultaneous measurements of intracellular Ca(2+) and isometric force in multicellular trabeculae (n = 7, 1.5 mmol/L [Ca(2+)]o) revealed no effect of Epac activation on either the amplitude of Ca(2+) transients (Control 0.7 ± 0.1 vs cpTOME 0.7 ± 0.1; 340/380 fura-2 ratio, P = 0.35) or on peak stress (Control 24 ± 5 mN/mm(2) vs cpTOME 23 ± 5 mN/mm(2), P = 0.20). However, an effect of Epac in trabeculae was unmasked by lowering extracellular [Ca(2+)]o. In these depotentiated trabeculae, activation of the Epac pathway increased myofilament Ca(2+) sensitivity, an effect that was blocked by addition of KN-93, a Ca(2+)/calmodulin-dependent protein kinase II (CaMK-II) inhibitor. This study suggests that Epac activation may be a useful therapeutic target to increase the strength of contraction during low inotropic states.

The Falls In Care Home study: a feasibility randomized controlled trial of the use of a risk assessment and decision support tool to prevent falls in care homes.

OBJECTIVE: To explore the feasibility of implementing and evaluating the Guide to Action Care Home fall prevention intervention. DESIGN: Two-centre, cluster feasibility randomized controlled trial and process evaluation. SETTING: Purposive sample of six diverse old age/learning disability, long stay care homes in Nottinghamshire, UK. SUBJECTS: Residents aged over 50 years, who had fallen at least once in the past year, not bed-bound, hoist-dependent or terminally ill. INTERVENTIONS: Intervention homes (n = 3) received Guide to Action Care Home fall prevention intervention training and support. Control homes (n = 3) received usual care. OUTCOMES: Recruitment, attrition, baseline and six-month outcome completion, contamination and intervention fidelity, compliance, tolerability, acceptance and impact. RESULTS: A total of 81 of 145 (56%) care homes expressed participatory interest. Six of 22 letter respondent homes (27%) participated. The expected resident recruitment target was achieved by 76% (52/68). Ten (19%) residents did not complete follow-up (seven died, three moved). In intervention homes 36/114 (32%) staff attended training. Two of three (75%) care homes received protocol compliant training. Staff valued the training, but advised greater management involvement to improve intervention implementation. Fall risks were assessed, actioned and recorded in care records. Of 115 recorded falls, 533/570 (93%) of details were complete. Six-month resident fall rates were 1.9 and 4.0 per year for intervention and control homes, respectively. CONCLUSIONS: The Guide to Action Care Home is implementable under trial conditions. Recruitment and follow-up rates indicate that a definitive trial can be completed. Falls (primary outcome) can be ascertained reliably from care records.