Rare Presentation of Stercoral Ulcer Spontaneous Perforation Without Preceding Radiographic Evidence of Colonic Inflammation and Fecal Impaction.

Stercoral ulcers are caused by persistent fecal impaction. A life-threatening consequence of stercoral ulcers is colonic perforation, which is rare. A high index of clinical suspicion should be held for patients with stercoral ulcer, as colonic perforation is a medical emergency, requiring immediate surgical intervention. Here, we report a case of a 45-year-old female admitted with sepsis of unknown picture and subsequently developed stercoral ulcer perforation (SUP), diagnosed intraoperatively, without prior radiographic evidence of colonic inflammation. She was successfully managed with emergency laparotomy and left colectomy with sigmoid colectomy.

Using malnutrition and food insecurity screening to identify broader health-related social needs amongst older adults receiving emergency department care in the Southeastern United States: A cross-sectional study.

Unmet health-related social needs are common amongst older US adults and impact both quality of life and health outcomes. One of the ways that unmet health-related social needs impact health is through malnutrition, an imbalance in a person's intake of energy and/or nutrients. Lack of reliable access to a sufficient quantity of nutritious food is a specific health-related social need that can be assessed rapidly and, when unmet, is a direct risk factor for malnutrition and may be indicative of a broader range of unmet health-related social needs. We conducted a cross-sectional study to characterise malnutrition and food insecurity amongst older adults receiving emergency department (ED) care using brief, validated measures and to assess the burden of a broader range of health-related social needs amongst these patients. Patients were asked about their need for and willingness to receive a range of social services. The study was conducted in an academic ED serving a racially and socioeconomically diverse population in the Southeastern United States. A convenience sample of noncritically ill adults aged 60 years and older was approached between November 2018 and April 2019. Study patients (n = 127) were predominantly non-Hispanic white (67%), community dwelling (91%) and urban residents (66%) with 28% screening positive for malnutrition risk, 16% for food insecurity and 5% for both. Of those at risk for malnutrition, 25 (69%) reported ≥2 unmet health-related social needs and 14 (38%) were receptive to social services. Amongst food insecure patients, 18 (90%) reported additional unmet health-related social needs and 13 (65%) were receptive to receiving social services. In conclusion, a brief set of questions can identify subgroups of older ED patients who are food insecure or at risk for malnutrition. Individuals who screen positive for food insecurity have a high burden of unmet health-related social needs.

Pharmacotherapy and Lung Function Decline in Patients with Chronic Obstructive Pulmonary Disease. A Systematic Review.

Rationale: Whether pharmacological therapy alters decline in FEV1 in chronic obstructive pulmonary disease remains controversial. Because pharmacotherapy improves health status, exacerbation rate, and symptoms, it may be unethical to complete placebo-controlled long-term studies aimed at modifying FEV1 decline.Objectives: We conducted a systematic review of placebo-controlled pharmacological trials lasting ≥1 year to address the question of whether therapy alters FEV1 decline.Methods: A literature search for randomized trials that included repeated spirometry with at least one active and one placebo arm was conducted. Articles were excluded if study duration was <1 year, <3 spirometric measurements, or <100 subjects per arm. Study design was assessed using the Jadad score. To combine studies and find the estimated effect, we used random effects methodology to account for both within-study and between-study variation.Measurements and Main Results: There were 33,051 patients in the analysis (active component, n = 21,941; placebo, n = 11,110 in nine studies). The active treatment arms demonstrated a 5.0 ml/yr reduction (95% confidence interval, 0.8-9.1 ml/yr; P < 0.001) in the rate of FEV1 decline compared with the placebo arms. The relative FEV1 differences between active and placebo arms were within the range of differences reported for health status and for the exacerbation rate in the same studies.Conclusions: In chronic obstructive pulmonary disease, pharmacotherapy ameliorates rate of lung function decline. The relative benefit observed is within the range of those reported for health status and exacerbations in the same studies. Guidelines should be adjusted according to these findings.

Adjudication of cardiovascular events in patients with chronic obstructive pulmonary disease: SUMMIT trial.

BACKGROUND: Adjudicated cause-specific mortality has been used in major trials of chronic obstructive pulmonary disease. However, there is less experience with adjudicated major adverse cardiovascular events as a key efficacy outcome in chronic obstructive pulmonary disease trials. The Study to Understand Mortality and Morbidity in chronic obstructive pulmonary disease trial required a Clinical Endpoint Committee to adjudicate the outcomes of modified major adverse cardiovascular events and cause-specific mortality. METHODS AND RESULTS: A six-member Clinical Endpoint Committee reviewed adverse event and serious adverse event reports included in a list of 204 Medical Dictionary for Regulatory Activities terms. Adverse events were triaged by one Clinical Endpoint Committee member, and then reviewed by three reviewers (round 1). If these three disagreed on the adjudication, the event was discussed by the full committee to reach a consensus (round 2). Among 16,485 participants, 48,105 adverse events were reported, among which 3314 were reviewed by the Clinical Endpoint Committee. After triage, 1827 were adjudicated in round 1; 338 required committee consensus in round 2, yielding 450 myocardial infarctions, strokes, unstable anginas or transient ischaemic attacks. Only 20/1627 (1%) non-serious adverse events were adjudicated as cardiovascular events. Only 45/204 Medical Dictionary for Regulatory Activities terms reviewed yielded cardiovascular events. A total of 430 deaths were adjudicated in round 1 and 631 in round 2, yielding 459 cardiovascular deaths. Adjudication of chest pain and sudden death often required additional information from site investigators. Site assessment of cardiovascular death was moderately specific (501/602 = 83%) but not sensitive (256/459 = 56%). CONCLUSION: A Clinical Endpoint Committee is useful for adjudication of major adverse cardiovascular events in chronic obstructive pulmonary disease trials but requires considerable resources and effort by investigators. This process can be streamlined by reviewing only serious adverse events and filtering by selected Medical Dictionary for Regulatory Activities terms.

Leveraging emergency department visits to connect older adults at risk for malnutrition and food insecurity to community resources: design and protocol development for the BRIDGE study.

BACKGROUND: Malnutrition is a complex and costly condition that is common among older adults in the United States (US), with up to half at risk for malnutrition. Malnutrition is associated with several non-medical (i.e., social) factors, including food insecurity. Being at risk for both malnutrition and food insecurity likely identifies a subset of older adults with complex care needs and a high burden of social vulnerability (e.g., difficulty accessing or preparing meals, lack of transportation, and social isolation). US emergency departments (EDs) are a unique and important setting for identifying older patients who may benefit from the provision of health-related social services. This paper describes the protocol development for the Building Resilience and InDependence for Geriatric Patients in the Emergency Department (BRIDGE) study. BRIDGE was designed to assess the feasibility of an ED-based screening process to systematically identify older patients who are at risk for malnutrition and food insecurity and link them to health-related social services to address unmet social needs and support their health and well-being. METHODS: Phase 1 efforts will be formative and focused on identifying screening tools, establishing screening and referral workflows, and conducting initial feasibility testing with a cohort of older patients and ED staff. In phase 2, which includes process and outcome evaluation, the screening and referral process will be piloted in the ED. A partnership will be formed with an Area Agency on Aging (AAA) identified in phase 1, to assess resource needs and identify community-based social services for older ED patients who screen positive for both malnutrition risk and food insecurity. Data on screening, referrals, linkage to community-based social services, and patient-reported quality of life and healthcare utilization will be used to assess feasibility. DISCUSSION: The tools and workflows developed and tested in this study, as well as learnings related to forming and maintaining cross-sector partnerships, may serve as a model for future efforts to utilize EDs as a setting for bridging the gap between healthcare and social services for vulnerable patients.

Reduction in All-Cause Mortality with Fluticasone Furoate/Umeclidinium/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease.

Rationale: The IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial demonstrated a significant reduction in all-cause mortality (ACM) risk with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) at risk of future exacerbations. Five hundred seventy-four patients were censored in the original analysis owing to incomplete vital status information.Objectives: Report ACM and impact of stepping down therapy, following collection of additional vital status data.Methods: Patients were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 µg, FF/VI 100/25 µg, or UMEC/VI 62.5/25 µg following a run-in on their COPD therapies. Time to ACM was prespecified. Additional vital status data collection and subsequent analyses were performed post hoc.Measurements and Main Results: We report vital status data for 99.6% of the intention-to-treat population (n = 10,355), documenting 98 (2.36%) deaths on FF/UMEC/VI, 109 (2.64%) on FF/VI, and 66 (3.19%) on UMEC/VI. For FF/UMEC/VI, the hazard ratio for death was 0.72 (95% confidence interval, 0.53-0.99; P = 0.042) versus UMEC/VI and 0.89 (95% confidence interval, 0.67-1.16; P = 0.387) versus FF/VI. Independent adjudication confirmed lower rates of cardiovascular and respiratory death and death associated with the patient's COPD.Conclusions: In this secondary analysis of an efficacy outcome from the IMPACT trial, once-daily single-inhaler FF/UMEC/VI triple therapy reduced the risk of ACM versus UMEC/VI in patients with symptomatic COPD and a history of exacerbations.

Indicators of potential health-related social needs and the association with perceived health and well-being outcomes among community-dwelling medicare beneficiaries.

PURPOSE: Health-related social needs (HRSNs) can make older adults' more vulnerable and impact their health, well-being, and ability to age-in-place. The current study assessed the prevalence of potential HRSNs (pHRSNs) across several domains (e.g., transportation, social isolation) and explored the associations with health and well-being outcomes in a sample of Medicare beneficiaries. METHODS: Cross-sectional analyses were conducted with a representative sample of community-dwelling Medicare beneficiaries (N = 5758) from the 2012 National Health and Aging Trends Study. Binary indicators of pHRSNs were created for five domains: medical and utility financial needs (MUFN), housing, nutrition, social isolation, and transportation. Outcomes were depression/anxiety, self-rated health, meaning/satisfaction, perceived control/adaptability. Variables were weighted, and multivariate regression models assessed associations between pHRSN variables and outcomes, controlling for sociodemographics and health conditions. RESULTS: Of the estimated 32 million community-dwelling beneficiaries, approximately 13.3 million were positive for ≥ 1 pHRSN and 11.4 million for ≥ 2 pHRSNs. The prevalence by domain was 7% for housing, 8% for transportation, 12% for UMFN and nutrition, and 33% for social isolation. Each domain, except for housing, was significantly (p < .05) associated with at least two of the four outcomes, where being positive for a pHRSN was associated with greater depression/anxiety and poorer self-rated general health. CONCLUSIONS: Over 40% of Medicare beneficiaries had ≥ 1 pHRSN indicators, which means they are more vulnerable and that may limit their ability to age-in-place. Given the growing aging population, better measures and methods are needed to identify, monitor, and address HRSNs. For example, leveraging existing community-based services through coordinated care may be an effective strategy to address older adults' HRSNs.

"It's Not Just a Simple Meal. It's So Much More": Interactions Between Meals on Wheels Clients and Drivers.

Background and Objectives: Meals on Wheels (MOW) programs provide home-delivered meals to over 1.5 million older adults; yet, very little is known about the drivers who make meal deliveries possible. Specifically, we do not have clear insight into their interaction with clients or the benefits that they may receive through their service. The objective of this article is to describe the characteristics of MOW drivers, the interactions among drivers and clients, and the benefits of the program to both. Research Design and Method: This qualitative research study reports on interviews with 84 MOW staff (leadership, case managers/client assessors, volunteer coordinators) and drivers at six geographically and operationally distinct programs across the United States. Results: Qualitative analysis of the interviews with MOW staff and drivers revealed the following key themes: (a) clients have multiple vulnerabilities; (b) clients appear to derive social, as well as nutritional benefit from receiving meals; (c) drivers report they provide additional support to their clients beyond delivering the meal; (d) social bonds between drivers and clients were reported to strengthen over time; (e) drivers claim that they, too, derive validation and personal benefit through their meal delivery. Discussion and Implications: This research highlights the significant contributions that meal delivery drivers made in the lives of MOW clients beyond the actual meal itself. This research also spotlights the perceived benefits experienced by the drivers and points to the importance of conducting further research to determine the effects of meal delivery on client and drivers' outcomes, more broadly.

Serum biomarkers and outcomes in patients with moderate COPD: a substudy of the randomised SUMMIT trial.

Rationale: Systemic levels of C reactive protein (CRP), surfactant protein D (SPD), fibrinogen, soluble receptor of activated glycogen end-product (sRAGE) and club cell protein 16 (CC-16) have been associated with chronic obstructive pulmonary disease (COPD) outcomes. However, they require validation in different cohorts. Objectives: Relate systemic levels of those proteins to forced expiratory volume in 1 s (FEV1) decline, exacerbations, hospitalisations and mortality in COPD patients (FEV1 of ≥50 and ≤70% predicted) and heightened cardiovascular risk in a substudy of the Study to Understand Mortality and MorbidITy trial. Methods: Participants were randomised to daily inhalations of placebo, vilanterol 25 µg (VI), fluticasone furoate 100 µg (FF) or their combination (VI 25/FF 100) and followed quarterly until 1000 deaths in the overall 16 485 participants occurred. Biomarker blood samples were available from 1673 patients. The FEV1 decline (mL/year), COPD exacerbations, hospitalisations and death were determined. Associations between biomarker levels and outcomes were adjusted by age and gender. Results: Systemic levels of CC-16, CRP, sRAGE, SPD and fibrinogen did not relate to baseline FEV1, FEV1 decline, exacerbations or hospitalisations. Fibrinogen and CRP were related to mortality over a median follow-up of 2.3 years. Only the CC-16 changed with study therapy (VI, FF and FF/VI, p<0.01) at 3 months. Conclusions: In COPD, systemic levels of CC-16, CRP, sRAGE, SPD and fibrinogen were not associated with FEV1 decline, exacerbations or hospitalisations. These results cast doubts about the clinical usefulness of the systemic levels of these proteins as surrogate markers of these COPD outcomes. The study confirms that CRP and fibrinogen are associated with increased risk of death in patients with COPD. Trial registration number: NCT01313676.

Leveraging Home-Delivered Meal Programs to Address Unmet Needs for At-Risk Older Adults: Preliminary Data.

BACKGROUND: Home-delivered meal programs serve a predominantly homebound older adult population, characterized by multiple chronic conditions, functional limitations, and a variety of complex care needs, both medical and social. DESIGN: A pilot study was designed to test the feasibility of leveraging routine meal-delivery service in two home-delivered meal programs to proactively identify changes in older adult meal recipients' (clients') health, safety, and well-being and address unmet needs. INTERVENTION: Meal delivery personnel (drivers) were trained to use a mobile application to submit electronic alerts when they had a concern or observed a change in a client's condition. Alerts were received by care coordinators, who followed up with clients to offer support and help connect them to health and community services. RESULTS: Over a 12-month period, drivers submitted a total of 429 alerts for 189 clients across two pilot sites. The most frequent alerts were submitted for changes in health (56%), followed by self-care or personal safety (12%) and mobility (11%). On follow-up, a total of 132 referrals were issued, with most referrals for self-care (33%), health (17%), and care management services (17%). Focus groups conducted with drivers indicated that most found the mobile application easy to use and valued change of condition monitoring as an important contribution. CONCLUSION: Findings suggest that this is a feasible approach to address unmet needs for vulnerable older adults and may serve as an early-warning system to prevent further decline and improve quality of life. Efforts are underway to test the protocol across additional home-delivered meal programs. J Am Geriatr Soc 67:1946-1952, 2019.

Sustained participation in community-based physical activity by adolescents with cerebral palsy: a qualitative study.

Purpose: Short-term physical activity programs may encourage adolescents with cerebral palsy to participate in physical activity but how to sustain their involvement is not well known. This qualitative study aimed to identify facilitators that successfully sustain physical activity participation by adolescents with cerebral palsy.Materials and methods: Adolescents (12-18 years) with cerebral palsy [Gross Motor Function Classification System (GMFCS) levels I-V, without moderate-severe intellectual disability] who participated in regular physical activity were eligible, as well as one parent and an individual who facilitated their physical activity. Data were gathered using semi-structured interviews; verbatim transcripts were analysed using inductive thematic analysis within individuals (n = 15), triads (n = 5), and across participant groups (adolescents, parents and facilitators).Results: Five triads participated (male adolescents, 13-16 years, GMFCS levels I-III). Seven themes emerged: getting started, wanting to succeed, a sense of belonging, the coach is important, endorsement to continue, endorsement to support and being passionate. The themes were synthesized into the Framework for Sustained Participation, which describes the interaction among themes.Conclusions: The Framework for Sustained Participation highlights strategies that may be useful for adolescents, parents, sports facilitators, clinicians and researchers to help ambulatory male adolescents with cerebral palsy continue to participate in physical activity.Implications for rehabilitationSustaining participation in physical activity has the potential to enhance long-term health benefits of young people with cerebral palsy.Key facilitators of sustained physical activity in adolescents with cerebral palsy included tailoring the activity, getting the right coach and the adolescents' desire for health and fitness.The Framework of Sustained Participation may assist clinicians and facilitators who work with young people with cerebral palsy to structure their support in ways that will successfully sustain the adolescents' participation in physical activity.

Home and community-based services coordination for homebound older adults in home-based primary care.

BACKGROUND: Medically complex vulnerable older adults often face social challenges that affect compliance with their medical care plans, and thus require home and community-based services (HCBS). This study describes how non-medical social needs of homebound older adults are assessed and addressed within home-based primary care (HBPC) practices, and to identify barriers to coordinating HCBS for patients. METHODS: An online survey of members of the American Academy of Home Care Medicine (AAHCM) was conducted between March through November 2016 in the United States. A 56-item survey was developed to assess HBPC practice characteristics and how practices identify social needs and coordinate and evaluate HCBS. Data from 101 of the 150 surveys received were included in the analyses. Forty-four percent of respondents were physicians, 24% were nurse practitioners, and 32% were administrators or other HBPC team members. RESULTS: Nearly all practices (98%) assessed patient social needs, with 78% conducting an assessment during the intake visit, and 88% providing ongoing periodic assessments. Seventy-four percent indicated 'most' or 'all' of their patients needed HCBS in the past 12 months. The most common needs were personal care (84%) and medication adherence (40%), and caregiver support (38%). Of the 86% of practices reporting they coordinate HCBS, 91% followed-up with patients, 84% assisted with applications, and 83% made service referrals. Fifty-seven percent reported that coordination was 'difficult.' The most common barriers to coordinating HCBS included cost to patient (65%), and eligibility requirements (63%). Four of the five most frequently reported barriers were associated with practices reporting it was 'difficult' or 'very difficult' to coordinate HCBS (OR from 2.49 to 3.94, p-values < .05). CONCLUSIONS: Despite the barriers to addressing non-medical social needs, most HBPC practices provided some level of coordination of HCBS for their high-need, high-cost homebound patients. More efforts are needed to implement and scale care model partnerships between medical and non-medical service providers within HBPC practices.

Operation and challenges of home-based medical practices in the US: findings from six aggregated case studies.

BACKGROUND: Home-based primary care (HBPC) is a multidisciplinary, ongoing care strategy that can provide cost-effective, in-home treatment to meet the needs of the approximately four million homebound, medically complex seniors in the U.S. Because there is no single model of HBPC that can be adopted across all types of health organizations and U.S. geographic regions, we conducted a six-site HBPC practice assessment to better understand different operation structures, common challenges, and approaches to delivering HBPC. METHODS: Six practices varying in size, care team composition and location agreed to participate. At each site we conducted unstructured interviews with key informants and directly observed practices and procedures in the field and back office. RESULTS: The aggregated case studies revealed important issues focused on team composition, patient characteristics, use of technology and urgent care delivery. Common challenges across the practices included provider retention and unmet community demand for home-based care services. Most practices, regardless of size, faced challenges around using electronic medical records (EMRs) and scheduling systems not designed for use in a mobile practice. Although many practices offered urgent care, practices varied in the methods used to provide care including the use of community paramedics and telehealth technology. CONCLUSIONS: Learnings compiled from these observations can inform other HBPC practices as to potential best practices that can be implemented in an effort to improve efficiency and scalability of HBPC so that seniors with multiple chronic conditions can receive comprehensive primary care services in their homes.

Probiotics in Preventing Acute Upper Respiratory Tract Infections.

Editor's note: This is a summary of a nursing care-related systematic review from the Cochrane Library. For more information, see http://nursingcare.cochrane.org.

Personal and professional challenges confronted by hospital staff following hurricane sandy: a qualitative assessment of management perspectives.

BACKGROUND: Adequate hospital staffing during and after a disaster is critical to meet increased health care demands and to ensure continuity of care and patient safety. However, when a disaster occurs, staff may become both victim and responder, decreasing their ability and willingness to report for work. This qualitative study assessed the personal and professional challenges that affected staff decisions to report to work following a natural disaster and examined the role of management in addressing staff needs and concerns. METHODS: Semi-structured interviews were conducted with individuals who filled key management roles in the United States Department of Veterans Affairs New York Harbor Healthcare System's response to Superstorm Sandy and during the facility's initial recovery phase. All interviews were audio recorded and transcribed. Three major themes were identified: 1) Barriers to reporting ("Barriers"), 2) Facilitators to reporting ("Facilitators"), and 3) Responses to staff needs and concerns ("Responses"). Atlas.ti 7.1.6 software program was used for the management and analysis of the transcripts. RESULTS: Results indicated that staff encountered several barriers that impeded their ability to report to work at mobile vans at the temporarily nonoperational Manhattan campus or at two other VA facilities in Brooklyn and the Bronx in the initial post-Sandy period including transportation problems, personal property damage, and communication issues. In addition, we found evidence of facilitators to reporting as expressed through descriptions of professional duty. Our findings also revealed that management was aware of the challenges that staff was facing and made efforts to reduce barriers and accommodate staff affected by the storm. CONCLUSIONS: During and after a disaster event, hospital staff is often confronted with challenges that affect decisions to report for work and perform effectively under potentially harsh conditions. This study examined barriers and facilitators that hospital staff encountered following a major natural disaster from the management perspective. Insights gained from this study can be used to inform future disaster planning and preparedness efforts, and help ensure that there is adequate staffing to mount an effective response when a disaster occurs, and to recover from its aftermath.

Memory for sequences of events impaired in typical aging.

Typical aging is associated with diminished episodic memory performance. To improve our understanding of the fundamental mechanisms underlying this age-related memory deficit, we previously developed an integrated, cross-species approach to link converging evidence from human and animal research. This novel approach focuses on the ability to remember sequences of events, an important feature of episodic memory. Unlike existing paradigms, this task is nonspatial, nonverbal, and can be used to isolate different cognitive processes that may be differentially affected in aging. Here, we used this task to make a comprehensive comparison of sequence memory performance between younger (18-22 yr) and older adults (62-86 yr). Specifically, participants viewed repeated sequences of six colored, fractal images and indicated whether each item was presented "in sequence" or "out of sequence." Several out of sequence probe trials were used to provide a detailed assessment of sequence memory, including: (i) repeating an item from earlier in the sequence ("Repeats"; e.g., AB A: DEF), (ii) skipping ahead in the sequence ("Skips"; e.g., AB D: DEF), and (iii) inserting an item from a different sequence into the same ordinal position ("Ordinal Transfers"; e.g., AB 3: DEF). We found that older adults performed as well as younger controls when tested on well-known and predictable sequences, but were severely impaired when tested using novel sequences. Importantly, overall sequence memory performance in older adults steadily declined with age, a decline not detected with other measures (RAVLT or BPS-O). We further characterized this deficit by showing that performance of older adults was severely impaired on specific probe trials that required detailed knowledge of the sequence (Skips and Ordinal Transfers), and was associated with a shift in their underlying mnemonic representation of the sequences. Collectively, these findings provide unambiguous evidence that the capacity to remember sequences of events is fundamentally affected by typical aging.

Fluticasone propionate/salmeterol 250/50 µg versus salmeterol 50 µg after chronic obstructive pulmonary disease exacerbation.

BACKGROUND: Inhaled long-acting beta2 agonists used alone and in combination with an inhaled corticosteroid reduce the risk of exacerbations in patients with stable COPD. However, the relative efficacy of these agents in preventing recurrent exacerbations in those recovering from an initial episode is not known. This study compared the rate of COPD exacerbations over the 26 weeks after an initial exacerbation in patients receiving the combination of fluticasone propionate and salmeterol (FP/SAL) or SAL alone. METHODS: Patients (n = 639) aged ≥40 years were randomized to either twice-daily inhaled FP/SAL 250/50 µg or SAL 50 µg. Primary, and secondary, endpoints were rates of recurrent severe, and moderate/severe, exacerbations of COPD. Lung function, health outcomes and levels of biomarkers of systemic inflammation were also assessed. RESULTS: There was no statistically significant treatment difference in rates of recurrent severe exacerbations (treatment ratio 0.92 [95% CI: 0.58, 1.45]) and moderate/severe exacerbations (0.82 [0.64, 1.06]) between FP/SAL and SAL in the intent-to-treat population. Pre-dose morning FEV1 change from baseline was greater (0.10 L [0.04, 0.16]) with FP/SAL than SAL. No treatment difference was seen for other endpoints including patient-reported health outcomes and biomarker levels for the full cohort. CONCLUSIONS: No significant treatment difference between FP/SAL and SAL was seen in COPD exacerbation recurrence for the complete cohort. Treatment benefit with FP/SAL over SAL (treatment ratio 0.68 [0.47, 0.97]) was seen in patients having FEV1 ≥ 30% and prior exposure to ICS. No unexpected safety issues were identified with either treatment. Patients with the most severe COPD may be more refractory to treatment. TRIAL REGISTRATION: ClinicalTrials.gov (identifier NCT01110200). This study was funded by GlaxoSmithKline (study number ADC113874).

A Sequence of events model of episodic memory shows parallels in rats and humans.

A critical feature of episodic memory is the ability to remember the order of events as they occurred in time, a capacity shared across species including humans, nonhuman primates, and rodents. Accumulating evidence suggests that this capacity depends on a network of structures including the hippocampus and the prefrontal cortex, but their respective contributions remain poorly understood. As addressing this important issue will require converging evidence from complementary investigative techniques, we developed a cross-species, nonspatial sequence memory task suitable for behavioral and neurophysiological studies in rodents and in humans. The task involves the repeated presentation of sequences of items (odors in rats and images in humans) and requires subjects to make a judgment as to whether each item is presented "in sequence" or "out of sequence." To shed light on the cognitive processes and sequence representations supporting performance, different types of "out of sequence" probe trials were used including: (i) repeating an item from earlier in the sequence (Repeats; e.g., ABAD), (ii) skipping ahead in the sequence (Skips; e.g., ABD), and (iii) inserting an item from a different sequence into the same ordinal position (Ordinal Transfers; e.g., A2CD). We found a remarkable similarity in the performance of rats and humans, particularly in the pattern of results across probe trial types. Thus, the results suggest that rats and humans not only remember the sequences of events, but also use similar underlying cognitive processes and mnemonic representations. This strong cross-species correspondence validates this task for use in future basic and clinical interdisciplinary studies aimed at examining the neural mechanisms underlying episodic memory.