Accuracy of the electronic health record's problem list in describing multimorbidity in patients with heart failure in the emergency department.

Patients with heart failure (HF) often suffer from multimorbidity. Rapid assessment of multimorbidity is important for minimizing the risk of harmful drug-disease and drug-drug interactions. We assessed the accuracy of using the electronic health record (EHR) problem list to identify comorbid conditions among patients with chronic HF in the emergency department (ED). A retrospective chart review study was performed on a random sample of 200 patients age ≥65 years with a diagnosis of HF presenting to an academic ED in 2019. We assessed participant chronic conditions using: (1) structured chart review (gold standard) and (2) an EHR-based algorithm using the problem list. Chronic conditions were classified into 37 disease domains using the Agency for Healthcare Research Quality's Elixhauser Comorbidity Software. For each disease domain, we report the sensitivity, specificity, positive predictive value, and negative predictive of using an EHR-based algorithm. We calculated the intra-class correlation coefficient (ICC) to assess overall agreement on Elixhauser domain count between chart review and problem list. Patients with HF had a mean of 5.4 chronic conditions (SD 2.1) in the chart review and a mean of 4.1 chronic conditions (SD 2.1) in the EHR-based problem list. The five most prevalent domains were uncomplicated hypertension (90%), obesity (42%), chronic pulmonary disease (38%), deficiency anemias (33%), and diabetes with chronic complications (30.5%). The positive predictive value and negative predictive value of using the EHR-based problem list was greater than 90% for 24/37 and 32/37 disease domains, respectively. The EHR-based problem list correctly identified 3.7 domains per patient and misclassified 2.0 domains per patient. Overall, the ICC in comparing Elixhauser domain count was 0.77 (95% CI: 0.71-0.82). The EHR-based problem list captures multimorbidity with moderate-to-good accuracy in patient with HF in the ED.

Brief Educational Video plus Telecare to Enhance Recovery for Older Emergency Department Patients with Acute Musculoskeletal Pain: an update to the study protocol for a randomized controlled trial.

BACKGROUND: This update describes changes to the Brief Educational Tool to Enhance Recovery (BETTER) trial in response to the COVID-19 pandemic. METHODS/DESIGN: The original protocol was published in Trials. Due to the COVID-19 pandemic, the BETTER trial converted to remote recruitment in April 2020. All recruitment, consent, enrollment, and randomization now occur by phone within 24 h of the acute care visit. Other changes to the original protocol include an expansion of inclusion criteria and addition of new recruitment sites. To increase recruitment numbers, eligibility criteria were expanded to include individuals with chronic pain, non-daily opioid use within 2 weeks of enrollment, presenting musculoskeletal pain (MSP) symptoms for more than 1 week, hospitalization in past 30 days, and not the first time seeking medical treatment for presenting MSP pain. In addition, recruitment sites were expanded to other emergency departments and an orthopedic urgent care clinic. CONCLUSIONS: Recruiting from an orthopedic urgent care clinic and transitioning to remote operations not only allowed for continued participant enrollment during the pandemic but also resulted in some favorable outcomes, including operational efficiencies, increased enrollment, and broader generalizability. TRIAL REGISTRATION: ClinicalTrials.gov NCT04118595 . Registered on October 8, 2019.

Quantifying fatal and non-fatal drowning in children under five in Aotearoa, New Zealand.

OBJECTIVE: To quantify unintentional drowning trends and risk factors for children under five years of age in Aotearoa, New Zealand. METHODS: A population-based analyses of fatal and non-fatal (hospitalisations and Accident Compensation Corporation [ACC] claims) unintentional drowning of children 0-4 years of age between 2005 and 2019 was conducted using DrownBase™ data. Analyses comprises calculation of linear temporal trends, crude drowning rates per 100,000 and relative risk (95% confidence interval) and ratios of fatal to non-fatal drowning. RESULTS: 557 incidents (16.0% fatal) were recorded. Fatalities declined (y=-0.0769x+2.5678;R2=0.01509), while hospitalisations increased (y=0.1418x+9.1093;R2=0.0979). Males were overrepresented. One year-olds recorded the highest rates (fatal=4.39/100,000) and (non-fatal=2.14/100,000). 'Other' ethnicity (8.77/100,000) and Maori (2.49/100,000) children recorded the highest fatal drowning rates. Home pools were the leading fatal location, while domestic environments attracted the highest hospitalisation rate. For every one fatal drowning there were 6.9 hospitalisations and 74.7 ACC claims. CONCLUSIONS: Drowning among young children represents a preventable cause of injury-related harm. While fatalities are declining, non-fatal drowning is increasing. Implications for public health: Strategies to prevent drowning among young children are well understood, particularly restricting water access and active adult supervision. Further investment in effective prevention strategies for young children will deliver significant social, economic and health system savings.

Reliability of the longitudinal experts all data (LEAD) methodology for determining the presence of elder mistreatment.

Developing reliable screening tools to identify elder mistreatment requires an accurate and reproducible reference standard. This study sought to investigate the reliability of the Longitudinal, Experts, All Data (LEAD) methodology as a reference standard in confirming presence of elder mistreatment. We analyzed data from a large, emergency department-based study that used a LEAD panel to determine the reference standard. For this study, a second, blinded LEAD panel reviewed clinical material for 40 patients. For each panel, five content experts voted on whether elder mistreatment was present. We found moderate agreement between the two LEAD panels in determining presence of elder mistreatment: 85% agreement; k = 0.58; 95% Confidence Interval 0.28-0.87. Individual raters for both LEAD panels reported being mostly certain or certain >90% of votes. Efforts to further characterize and improve the reliability of the LEAD methodology in this context are warranted.

Research priorities for elder abuse screening and intervention: A Geriatric Emergency Care Applied Research (GEAR) network scoping review and consensus statement.

The Geriatric Emergency Care Applied Research (GEAR) Network (1) conducted a scoping review of the current literature on the identification of and interventions to address elder abuse among patients receiving care in emergency departments and (2) used this review to prioritize research questions for knowledge development. Two questions guided the scoping review: What is the effect of universal emergency department screening compared to targeted screening or usual practice on cases of elder abuse identified, safety outcomes, and health care utilization?; and What is the safety, health, legal, and psychosocial impact of emergency department-based interventions vs. usual care for patients experiencing elder abuse? We searched five article databases. Additional material was located through reference lists of identified publications, PsychInfo, and Google Scholar. The results were discussed in a consensus conference; and stakeholders voted to prioritize research questions. No studies were identified that directly addressed the first question regarding assessment strategies, but four instruments used for elder abuse screening in the emergency department were identified. For the second question, we located six articles on interventions for elder abuse in the emergency department; however, none directly addressed the question of comparative effectiveness. Based on these findings, GEAR participants identified five questions as priorities for future research - two related to screening, two related to intervention, and one encompassed both. In sum, research to identify best practices for elder abuse assessment and intervention in emergency departments is still needed. Although there are practical and ethical challenges, rigorous experimental studies are needed.

Another gender data gap: female drowning in Aotearoa, New Zealand.

INTRODUCTION: A gender gap is present in drowning research and prevention interventions, resulting in an inequitable focus on males. This study aimed to address the gender data gap, exploring female drowning in Aotearoa, New Zealand. METHODS: National data on female fatal and non-fatal drowning requiring hospitalisation between 2003 and 2019 were sourced from DrownBase, Water Safety New Zealand's drowning database. Univariate and χ2 analyses were conducted for fatal and hospitalisation data. Crude rates were calculated and used to explore temporal trends and RR by age groups and ethnicity for fatal and non-fatal drowning. Ratios for drowning-related hospitalisations and Accident Compensation Corporation (ACC) claims to drowning deaths were also calculated. RESULTS: From 2003 to 2019, a total of 1087 female drowning fatalities and non-fatal (76.0%) drowning incidents requiring hospitalisation occurred. Linear trends indicate hospitalisations increased (y=0.0766x+1.4271; R2=0.4438), while fatal drowning decreased (y=-0.0101x+0.7671; R2=0.1011). The highest fatal (1.60) and non-fatal (8.22) drowning rates were seen among children aged 0-4 years. For every one female drowning fatality, there are 3.46 hospital admissions and 675.55 ACC claims. DISCUSSION: Female drowning represents a significant burden on the health system and the community in New Zealand. Further investment in interventions targeting females about their own risky behaviours around water (not only children in their care) is suggested, including interventions focused on hazardous conditions and alcohol consumption. CONCLUSION: For decades, the focus of drowning prevention among adolescents and adults has been on males. However, efforts must be broadened to prevent any further increase in drowning-related incidents among females in Aotearoa, New Zealand.

Natriuretic Peptide Expression and Function in GH3 Somatolactotropes and Feline Somatotrope Pituitary Tumours.

Patients harbouring mutations in genes encoding C-type natriuretic peptide (CNP; NPPC) or its receptor guanylyl cyclase B (GC-B, NPR2) suffer from severe growth phenotypes; loss-of-function mutations cause achondroplasia, whereas gain-of-function mutations cause skeletal overgrowth. Although most of the effects of CNP/GC-B on growth are mediated directly on bone, evidence suggests the natriuretic peptides may also affect anterior pituitary control of growth. Our previous studies described the expression of NPPC and NPR2 in a range of human pituitary tumours, normal human pituitary, and normal fetal human pituitary. However, the natriuretic peptide system in somatotropes has not been extensively explored. Here, we examine the expression and function of the CNP/GC-B system in rat GH3 somatolactotrope cell line and pituitary tumours from a cohort of feline hypersomatotropism (HST; acromegaly) patients. Using multiplex RT-qPCR, all three natriuretic peptides and their receptors were detected in GH3 cells. The expression of Nppc was significantly enhanced following treatment with either 100 nM TRH or 10 µM forskolin, yet only Npr1 expression was sensitive to forskolin stimulation; the effects of forskolin and TRH on Nppc expression were PKA- and MAPK-dependent, respectively. CNP stimulation of GH3 somatolactotropes significantly inhibited Esr1, Insr and Lepr expression, but dramatically enhanced cFos expression at the same time point. Oestrogen treatment significantly enhanced expression of Nppa, Nppc, Npr1, and Npr2 in GH3 somatolactotropes, but inhibited CNP-stimulated cGMP accumulation. Finally, transcripts for all three natriuretic peptides and receptors were expressed in feline pituitary tumours from patients with HST. NPPC expression was negatively correlated with pituitary tumour volume and SSTR5 expression, but positively correlated with D2R and GHR expression. Collectively, these data provide mechanisms that control expression and function of CNP in somatolactotrope cells, and identify putative transcriptional targets for CNP action in somatotropes.

Comparison of the Head and Neck Positions in Ridden Horses Advertised in an Australian Horse Sales Magazine: 2005 Versus 2018.

The impact of head and neck position (HNP) on horse welfare has received much attention in the scientific literature within the last two decades. Studies have identified physiological and behavioral signs of distress in horses ridden for prolonged time in an HNP with their noseline behind the vertical (BTV), which may compromise their welfare. The objective of this study was to compare potential differences of HNPs shown in horse sales photographs advertised in an Australian horse sales magazine (Horse Deals) from the years 2005 and 2018. In addition, factors potentially impacting HNPs, such as type of tack presented in (e.g., noseband type), riding discipline, and competition experience of the horse, were investigated. The sample population (n = 570) comprised horses ridden with headgear and bit in walk, trot, or canter/gallop, advertised in an Australian horse sales magazine. Issues from April 2005 and October/November 2018 were selected. Head and neck position was categorized as BTV, on the vertical (OV), slightly in front of the vertical (IFV), or extremely in front of the vertical (EIFV; any HNP >30° IFV). Data were analyzed using the chi-squared test and post hoc testing via a multiple regression approach through SPSS and test of proportions via the Z-score calculator for two independent population proportions. Analysis of combined data from years 2005 and 2018 showed 47.0% (n = 570) of the horse sample population were advertised with HNPs BTV. Behind-the-vertical HNP was observed as the predominant HNP (57.8%; n = 268) in the warmblood/eventers/show/performance (WESP) category (P < .0005). In 2005, 53.4% (n = 303) of the sample population were ridden BTV compared with 39.7% (n = 267) in 2018 (P < .001), 12.9% (n = 303) were OV in 2005 compared with 15.0% (n = 267) in 2018 (P > .05), and 10.9% (n = 303) were IFV in 2005 compared with 27.3% (n = 267) in 2018 (P < .0004). These results suggest a positive development with fewer vendors/riders selecting images where the horse's nose was BTV. However, this may be explained by the larger proportion of horses advertised in the WESP category in 2005 (63.0%; n = 303) versus 2018 (28.5%; n = 267), and the WESP category predominantly comprised of dressage, jumper, and eventing horses. In addition, the reduction of HNPs BTV from 53.4% (n = 303) in 2005 to 39.7% (n = 267) in 2018 could be attributed to the observation that in 2018, a larger proportion of horses were listed in categories that do not require the horses to be worked with a flexed HNP referred to as "on-the-bit" (e.g., western, endurance, Australian sStock horses). The HNP BTV remains preferential by a substantial proportion of the horse-owning public when advertising horses for sale, particularly in disciplines where the horse is worked in a flexed HNP or "on-the-bit."

Multicenter Validation of an Emergency Department-Based Screening Tool to Identify Elder Abuse.

STUDY OBJECTIVE: Emergency department (ED) visits provide an important opportunity for elder abuse identification. Our objective was to assess the accuracy of the ED Senior Abuse Identification (ED Senior AID) tool for the identification of elder abuse. METHODS: We conducted a study of the ED Senior AID tool in 3 US EDs. Participants were English-speaking patients 65 years old and older who provided consent or for whom a legally authorized representative provided consent. Research nurses administered the screening tool, which includes a brief mental status assessment, questions about elder abuse, and a physical examination for patients who lack the ability to report abuse or for whom the presence or absence of abuse was uncertain. The reference standard was based on the majority opinion of a longitudinal, expert, all data (LEAD) panel following review and discussion of medical records, clinical social worker notes, and a structured social and behavioral evaluation. For the reference standard, LEAD panel members were blinded to the results of the screening tool. RESULTS: Of 916 enrolled patients, 33 (3.6%) screened positive for elder abuse. The LEAD panel reviewed 125 cases: all 33 with positive screen results and a 10% random sample of negative screen results. Of these, the panel identified 17 cases as positive for elder abuse, including 16 of the 33 cases that screened positive. The ED Senior AID tool had a sensitivity of 94.1% (95% confidence interval [CI] 71.3% to 99.9%) and specificity of 84.3% (95% CI 76.0% to 90.6%). CONCLUSION: This multicenter study found the ED Senior AID tool to have a high sensitivity and specificity as a screening tool for elder abuse, albeit with wide CIs.

Brief educational video plus telecare to enhance recovery for older emergency department patients with acute musculoskeletal pain: study protocol for the BETTER randomized controlled trial.

BACKGROUND: Chronic musculoskeletal pain (MSP) affects more than 40% of adults aged 50 years and older and is the leading cause of disability in the USA. Older adults with chronic MSP are at risk for analgesic-related side effects, long-term opioid use, and functional decline. Recognizing the burden of chronic MSP, reducing the transition from acute to chronic pain is a public health priority. In this paper, we report the protocol for the Brief EducaTional Tool to Enhance Recovery (BETTER) trial. This trial compares two versions of an intervention to usual care for preventing the transition from acute to chronic MSP among older adults in the emergency department (ED). METHODS: Three hundred sixty patients from the ED will be randomized to one of three arms: full intervention (an interactive educational video about pain medications and recovery-promoting behaviors, a telecare phone call from a nurse 48 to 72 h after discharge from the ED, and an electronic communication containing clinical information to the patient's primary care provider); video-only intervention (the interactive educational video but no telecare or primary care provider communication); or usual care. Data collection will occur at baseline and at 1 week and 1, 3, 6, and 12 months after study enrollment. The primary outcome is a composite measure of pain severity and interference. Secondary outcomes include physical function, overall health, opioid use, healthcare utilization, and an assessment of the economic value of the intervention. DISCUSSION: This trial is the first patient-facing ED-based intervention aimed at helping older adults to better manage their MSP and reduce their risk of developing chronic pain. If effective, future studies will examine the effectiveness of implementation strategies. TRIAL REGISTRATION: ClinicalTrials.gov NCT04118595 . Registered on 8 October 2019.

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.

Diacylglycerol Lipase-Alpha Regulates Hippocampal-Dependent Learning and Memory Processes in Mice.

Diacylglycerol lipase-α (DAGL-α), the principal biosynthetic enzyme of the endogenous cannabinoid 2-arachidonylglycerol (2-AG) on neurons, plays a key role in CB1 receptor-mediated synaptic plasticity and hippocampal neurogenesis, but its contribution to global hippocampal-mediated processes remains unknown. Thus, the present study examines the role that DAGL-α plays on LTP in hippocampus, as well as in hippocampal-dependent spatial learning and memory tasks, and on the production of endocannabinoid and related lipids through the use of complementary pharmacologic and genetic approaches to disrupt this enzyme in male mice. Here we show that DAGL-α gene deletion or pharmacological inhibition disrupts LTP in CA1 of the hippocampus but elicits varying magnitudes of behavioral learning and memory deficits in mice. In particular, DAGL-α-/- mice display profound impairments in the Object Location assay and Morris Water Maze (MWM) acquisition engaging in nonspatial search strategies. In contrast, WT mice administered the DAGL-α inhibitor DO34 show delays in MWM acquisition and reversal learning, but no deficits in expression, extinction, forgetting, or perseveration processes in this task, as well as no impairment in Object Location. The deficits in synaptic plasticity and MWM performance occur in concert with decreased 2-AG and its major lipid metabolite (arachidonic acid), but increases of a 2-AG diacylglycerol precursor in hippocampus, PFC, striatum, and cerebellum. These novel behavioral and electrophysiological results implicate a direct and perhaps selective role of DAGL-α in the integration of new spatial information.SIGNIFICANCE STATEMENT Here we show that genetic deletion or pharmacologic inhibition of diacylglycerol lipase-α (DAGL-α) impairs hippocampal CA1 LTP, differentially disrupts spatial learning and memory performance in Morris water maze (MWM) and Object Location tasks, and alters brain levels of endocannabinoids and related lipids. Whereas DAGL-α-/- mice exhibit profound phenotypic spatial memory deficits, a DAGL inhibitor selectively impairs the integration of new information in MWM acquisition and reversal tasks, but not memory processes of expression, extinction, forgetting, or perseveration, and does not affect performance in the Objection Location task. The findings that constitutive or short-term DAGL-α disruption impairs learning and memory at electrophysiological and selective in vivo levels implicate this enzyme as playing a key role in the integration of new spatial information.

Pituitary Pathology and Gene Expression in Acromegalic Cats.

The prevalence of GH-secreting pituitary tumors in domestic cats (Felis catus) is 10-fold greater than in humans. The predominant inhibitory receptors of GH-secreting pituitary tumors are somatostatin receptors (SSTRs) and D2 dopamine receptor (DRD2). The expression of these receptors is associated with the response to somatostatin analog and dopamine agonist treatment in human patients with acromegaly. The aim of this study was to describe pathological features of pituitaries from domestic cats with acromegaly, pituitary receptor expression, and investigate correlates with clinical data, including pituitary volume, time since diagnosis of diabetes, insulin requirement, and serum IGF1 concentration. Loss of reticulin structure was identified in 15 of 21 pituitaries, of which 10 of 15 exhibited acinar hyperplasia. SSTR1, SSTR2, SSTR5, and DRD2 mRNA were identified in the feline pituitary whereas SSTR3 and SSTR4 were not. Expression of SSTR1, SSTR2, and SSTR5 was greater in acromegalic cats compared with controls. A negative correlation was identified between DRD2 mRNA expression and pituitary volume. The loss of DRD2 expression should be investigated as a mechanism allowing the development of larger pituitary tumors.

Evaluation of Nursing Documentation Completion of Stroke Patients in the Emergency Department: A Pre-Post Analysis Using Flowsheet Templates and Clinical Decision Support.

The primary aim of this performance improvement project was to determine whether the electronic health record implementation of stroke-specific nursing documentation flowsheet templates and clinical decision support alerts improved the nursing documentation of eligible stroke patients in seven stroke-certified emergency departments. Two system enhancements were introduced into the electronic record in an effort to improve nursing documentation: disease-specific documentation flowsheets and clinical decision support alerts. Using a pre-post design, project measures included six stroke management goals as defined by the National Institute of Neurological Disorders and Stroke and three clinical decision support measures based on entry of orders used to trigger documentation reminders for nursing: (1) the National Institutes of Health's Stroke Scale, (2) neurological checks, and (3) dysphagia screening. Data were reviewed 6 months prior (n = 2293) and 6 months following the intervention (n = 2588). Fisher exact test was used for statistical analysis. Statistical significance was found for documentation of five of the six stroke management goals, although effect sizes were small. Customizing flowsheets to meet the needs of nursing workflow showed improvement in the completion of documentation. The effects of the decision support alerts on the completeness of nursing documentation were not statistically significant (likely due to lack of order entry). For example, an order for the National Institutes of Health Stroke Scale was entered only 10.7% of the time, which meant no alert would fire for nursing in the postintervention group. Future work should focus on decision support alerts that trigger reminders for clinicians to place relevant orders for this population.

Investigation of biosecurity risks associated with the feed delivery: A pilot study.

This study explored potential biosecurity issues related to the delivery of feed to commercial farms. A pilot study was conducted to collect information about the day-to-day feed delivery, including biosecurity concerns at the level of the feed truck, the driver, and the farm. In addition, a reusable rubber boot was tested in an effort to increase the proportion of farms at which truck drivers wore clean footwear, and to explore an alternative to the standard plastic disposable boots that may be unsafe in winter conditions. Most farms did well in terms of proper dead-stock management and keeping the farm lane and feed bin areas clean. The provision of reusable rubber boots significantly increased the proportion of deliveries in which the driver wore clean footwear.

Enquête sur les risques pour la biosécurité associés à la livraison des aliments du bétail : étude pilote. Cette étude a exploré les enjeux potentiels de biosécurité reliés à la livraison d'aliments du bétail dans des fermes commerciales. Une étude pilote a été réalisée pour recueillir des renseignements concernant la livraison quotidienne, y compris les préoccupations de biosécurité au niveau du camion de livraison, du conducteur et de la ferme. De plus, une botte réutilisable en caoutchouc a été testée dans un effort visant à accroître la proportion des fermes où les conducteurs de camions portent des chaussures propres et à explorer un remplacement aux bottes jetables en plastique qui peuvent être non sécuritaires dans des conditions hivernales. La plupart des fermes effectuaient une bonne gestion des animaux morts et réalisaient un bon travail au niveau de la propreté des allées et des bacs à aliments. La fourniture de bottes réutilisables en caoutchouc a grandement accru la proportion des livraisons où le conducteur portait des bottes propres.(Traduit par Isabelle Vallières).

Oestrogen therapy for urinary incontinence in post-menopausal women.

BACKGROUND: It is possible that oestrogen deficiency may be an aetiological factor in the development of urinary incontinence in women. This is an update of a Cochrane review first published in 2003 and subsequently updated in 2009. OBJECTIVES: To assess the effects of local and systemic oestrogens used for the treatment of urinary incontinence. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Register of trials (searched 21 June 2012) which includes searches of MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) and handsearching of journals and conference proceedings, and the reference lists of relevant articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that included oestrogens in at least one arm in women with symptomatic or urodynamic diagnoses of stress, urgency or mixed urinary incontinence or other urinary symptoms post-menopause. DATA COLLECTION AND ANALYSIS: Trials were evaluated for risk of bias and appropriateness for inclusion by the review authors. Data were extracted by at least two authors and cross checked. Subgroup analyses were performed by grouping participants under local or systemic administration. Where appropriate, meta-analysis was undertaken. MAIN RESULTS: Thirty-four trials were identified which included approximately 19,676 incontinent women of whom 9599 received oestrogen therapy (1464 involved in trials of local vaginal oestrogen administration). Sample sizes of the studies ranged from 16 to 16,117 women. The trials used varying combinations of type of oestrogen, dose, duration of treatment and length of follow up. Outcome data were not reported consistently and were available for only a minority of outcomes.The combined result of six trials of systemic administration (of oral systemic oestrogens) resulted in worse incontinence than on placebo (risk ratio (RR) 1.32, 95% CI 1.17 to 1.48). This result was heavily weighted by a subgroup of women from the Hendrix trial, which had large numbers of participants and a longer follow up of one year. All of the women had had a hysterectomy and the treatment used was conjugated equine oestrogen. The result for women with an intact uterus where oestrogen and progestogen were combined also showed a statistically significant worsening of incontinence (RR 1.11, 95% CI 1.04 to 1.18).There was some evidence that oestrogens used locally (for example vaginal creams or pessaries) may improve incontinence (RR 0.74, 95% CI 0.64 to 0.86). Overall, there were around one to two fewer voids in 24 hours amongst women treated with local oestrogen, and there was less frequency and urgency. No serious adverse events were reported although some women experienced vaginal spotting, breast tenderness or nausea.Women who were continent and received systemic oestrogen replacement, with or without progestogens, for reasons other than urinary incontinence were more likely to report the development of new urinary incontinence in one large study.One small trial showed that women were more likely to have an improvement in incontinence after pelvic floor muscle training (PFMT) than with local oestrogen therapy (RR 2.30, 95% CI 1.50 to 3.52).The data were too few to address questions about oestrogens compared with or in combination with other treatments, different types of oestrogen or different modes of delivery. AUTHORS' CONCLUSIONS: Urinary incontinence may be improved with the use of local oestrogen treatment. However, there was little evidence from the trials on the period after oestrogen treatment had finished and no information about the long-term effects of this therapy was given. Conversely, systemic hormone replacement therapy using conjugated equine oestrogen may worsen incontinence. There were too few data to reliably address other aspects of oestrogen therapy, such as oestrogen type and dose, and no direct evidence comparing routes of administration. The risk of endometrial and breast cancer after long-term use of systemic oestrogen suggests that treatment should be for limited periods, especially in those women with an intact uterus.

The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments.

BACKGROUND: No treatments are currently available that slow, stop, or reverse disease progression in established multiple sclerosis (MS). The Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) trial tests the safety and feasibility of treatment with a candidate cell-based therapy, and will inform the wider challenge of designing early phase clinical trials to evaluate putative neuroprotective therapies in progressive MS. Illustrated by the MSCIMS trial protocol, we describe a novel methodology based on detailed assessment of the anterior visual pathway as a model of wider disease processes--the "sentinel lesion approach". METHODS/DESIGN: MSCIMS is a phase IIA study of autologous mesenchymal stem cells (MSCs) in secondary progressive MS. A pre-test : post-test design is used with healthy controls providing normative data for inter-session variability. Complementary eligibility criteria and outcomes are used to select participants with disease affecting the anterior visual pathway. RESULTS: Ten participants with MS and eight healthy controls were recruited between October 2008 and March 2009. Mesenchymal stem cells were successfully isolated, expanded and characterised in vitro for all participants in the treatment arm. CONCLUSIONS: In addition to determining the safety and feasibility of the intervention and informing design of future studies to address efficacy, MSCIMS adopts a novel strategy for testing neuroprotective agents in MS--the sentinel lesion approach--serving as proof of principle for its future wider applicability. TRIAL REGISTRATION: ClinicalTrials.gov (NCT00395200).