Burden of Illness in People with Alzheimer's Disease: A Systematic Review of Epidemiology, Comorbidities and Mortality.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide, and an updated quantification of its impact on morbidity, disability, and mortality is warranted. We conducted a systematic literature review, focusing on the past decade, to characterize AD and assess its impact on affected individuals. METHODS: Searches of Embase, MEDLINE, and the Cochrane Library were conducted on August 7, 2020 and updated on November 10, 2021. Observational studies from any country reporting incidence, prevalence, comorbidities, and/or outcomes related to disability and mortality/life expectancy, in people with mild cognitive impairment (MCI) due to AD, or mild, moderate, or severe AD dementia, were considered relevant. RESULTS: Data were extracted from 88 studies (46 incidence/prevalence; 44 comorbidities; 25 mortality-/disability-related outcomes), mostly from Europe, the USA, and Asia. AD dementia diagnosis was confirmed using biomarkers in only 6 studies. Estimated 5-year mortality in AD was 35%, and comorbidity prevalence estimates varied widely (hypertension: 30.2-73.9%; diabetes: 6.0-24.3%; stroke: 2.7-13.7%). Overall, people with AD dementia were more likely to have cardiovascular disease or diabetes than controls, and 5-year mortality in people with AD dementia was double that in the age- and year-matched general population (115.0 vs 60.6 per 1,000 person-years). CONCLUSIONS: AD is associated with excess morbidity and mortality. Future longitudinal studies of population aging, incorporating biomarker assessment to confirm AD diagnoses, are needed to better characterize the course of MCI due to AD and AD dementia.

Effectiveness of out-patient based acute heart failure care: a pilot randomised controlled trial.

OBJECTIVES: Acute heart failure (AHF) hospitalisation is associated with 10% mortality. Outpatient based management (OPM) of AHF appeared effective in observational studies. We conducted a pilot randomised controlled trial (RCT) comparing OPM with standard inpatient care (IPM). METHODS: We randomised patients with AHF, considered to need IV diuretic treatment for ≥2 days, to IPM or OPM. We recorded all-cause mortality, and the number of days alive and out-of-hospital (DAOH). Quality of life, mental well-being and Hope scores were assessed. Mean NHS cost savings and 95% central range (CR) were calculated from bootstrap analysis. Follow-up: 60 days. RESULTS: Eleven patients were randomised to IPM and 13 to OPM. There was no statistically significant difference in all-cause mortality during the index episode (1/11 vs 0/13) and up to 60 days follow-up (2/11 vs 2/13) [p = .86]. The OPM group accrued more DAOH {47 [36,51] vs 59 [41,60], p = .13}. Two patients randomised to IPM (vs 6 OPM) were readmitted [p = .31]. Hope scores increased more with OPM within 30 days but dropped to lower levels than IPM by 60 days. More out-patients had increased total well-being scores by 60 days (p = .04). OPM was associated with mean cost savings of £2658 (95% CR 460-4857) per patient. CONCLUSIONS: Patients with acute HF randomised to OPM accrued more days alive out of hospital (albeit not statistically significantly in this small pilot study). OPM is favoured by patients and carers and is associated with improved mental well-being and cost savings.

Assessment of Patients Receiving Short-Interval Botulinum Toxin Chemodenervation Treatment for Laryngeal Dystonia and Essential Tremor of the Vocal Tract.

Importance: The gold-standard treatment for laryngeal dystonia (LD) and essential tremor of the vocal tract (ETVT) is botulinum toxin (BoNT) chemodenervation. Although safe and effective, it is not curative, and periodic injections are required. Some medical insurance companies only cover injections at a 3-month interval, though some patients benefit from injections more frequently. Objective: To determine the proportion and characteristics of patients who receive BoNT chemodenervation treatment in intervals shorter than 90 days. Design, Setting, and Participants: This retrospective cohort study across 3 quaternary care neurolaryngology specialty practices in Washington and California recruited patients who underwent at least 4 consecutive laryngeal BoNT injections for LD and/or ETVT in the past 5 years. Data were collected from March through June 2022 and analyzed from June through December 2022. Exposure: Laryngeal BoNT treatment. Main Outcomes and Measures: Biodemographic and clinical variables, injection characteristics, evolution during the 3 interinjection intervals, and lifetime laryngeal BoNT treatment data were collected from patient medical records. Logistic regression was used to assess association to the short-interval outcome, defined as an average injection interval shorter than 90 days. Results: Of 255 patients included from the 3 institutions, 189 (74.1%) were female, and the mean (SD) age was 62.7 (14.3) years. The predominant diagnosis was adductor LD (n = 199 [78.0%]), followed by adductor dystonic voice tremor (n = 26 [10.2%]) and ETVT (n = 13 [5.1%]). Seventy patients (27.5%) received short-interval injections (<90 days). The short-interval group was younger than the long-interval group (≥90 days), with a mean (SD) age of 58.6 (15.5) years and 64.2 (13.5) years, respectively, and a mean difference of -5.7 years (95% CI, -9.6 to -1.8 years). There were no patient-related differences between the short- and long-interval groups in terms of sex, employment status, or diagnosis. Conclusions and Relevance: This cohort study demonstrated that while insurance companies often mandate a 3-month or greater interval for BoNT chemodenervation financial coverage, there is a considerable subset of patients with LD and ETVT who receive short-interval treatment to optimize their vocal function. Short-interval chemodenervation injections demonstrate a similar adverse effect profile and do not appear to predispose to resistance through antibody formation.

Assessment of Laryngeal Sensory Function using a Tactile Aesthesiometer in Healthy Adults.

INTRODUCTION: Laryngeal sensory function in healthy adults was assessed through the delivery of tactile stimuli using Cheung-Bearelly monofilaments. METHODS: 37 healthy adults were recruited with 340 tactile stimuli analyzed. Four calibrated tactile stimuli were delivered to three laryngeal sites: false vocal fold (FVF), aryepiglottic fold (AEF), and lateral pyriform sinus (LPS). Primary outcome was the elicitation of laryngeal adductor reflex (LAR). Secondary outcomes were gag, patient-reported laryngeal sensation (PRLS), and perceptual strength. Analysis was performed with mixed effects logistic regression modeling. RESULTS: Positive LAR was observed in 35.7%, 70.2%, and 91.2% of stimuli at LPS, AEF, and FVF respectively. LAR rates were significantly associated with laryngopharyngeal subsite (p < 0.001), tactile force (p = 0.001), age (p = 0.022) and sex (p = 0.022). LAR, gag, PRLS, and perceptual strength significantly increased as a more medial laryngeal subsite was stimulated and as stimulus force increased. Each of the ten years of age increase was associated with 19% reduction in odds of LAR (aOR = 0.81, 95% CI [0.68, 0.97]; p = 0.022). Male gender was associated with a 55% reduction in odds of LAR (aOR = 0.45, 95% CI [0.23, 0.89]; p = 0.022). CONCLUSION: LAR elicitation capability decreases in the male gender, aging, and a more lateral subsite. This study provides insight into the pathophysiology of hypo- and hyper-sensitive laryngeal disorders and is paramount to making accurate diagnostic assessments and finding novel treatment options for various laryngological disorders. Laryngoscope, 133:2525-2532, 2023.

Ending the Energy-Poverty Nexus: An Ethical Imperative for Just Transitions.

Arguments for a just transition are integral to debates about climate change and the drive to create a carbon-neutral economy. There are currently two broad approaches rooted in ethics and justice for framing just energy transitions. The first can be described as internal to the transition and emphasizes the anticipation, assessment, and redressing of harms created by the transition itself and the inclusion in transition governance of groups or communities potentially harmed by its disruptions. In this article, we propose a second approach to ethics and justice in an energy transition, which we describe as systemic or societal in scope. This approach complements attention to the proximate dynamics and impacts of the transition process with a focus on the distant societal and economic outcomes the transition brings into being and how they compare to conditions prior to the transition. It poses the question: do the transformative social, economic, and technological changes wrought by energy systems create more just societies and economies, or do they instead reinforce or recreate long-standing injustices and inequalities? We illustrate this approach with an assessment of one of the most significant existing forms of energy injustice: the energy-poverty nexus. We argue that the energy-poverty nexus reflects configurations of socio-energy systems that create complex, extractive feedbacks between energy insecurity and economic insecurity and, over time, reinforce or exacerbate poverty. We further argue that just energy transitions should work to disentangle these configurations and re-design them so as to create generative rather than extractive feedbacks, thus ending the energy-poverty nexus and creating long-term outcomes that are more just, equitable, and fair.

Imaging versus Intervention in Managing Small Unruptured Intracranial Aneurysms: A Cost-Effectiveness Analysis.

OBJECTIVE: Current guidelines recommend active surveillance with serial magnetic resonance angiography (MRA) for management of small, asymptomatic unruptured anterior circulation aneurysms (UIAs). We sought to determine the cost-effectiveness of active surveillance compared to immediate surgery. METHODS: We developed a Markov cost-effectiveness model simulating patients with small (<7 mm) UIAs managed by active surveillance via MRA, immediate surgery, or watchful waiting. Inputs for the model were abstracted from the literature and used to construct a comprehensive model following persons from diagnosis to death. Outcomes were quality-adjusted life-years (QALYs), lifetime medical costs (2015 USD), and incremental cost-effectiveness ratios (ICERs). Cost-effectiveness, deterministic, and probabilistic sensitivity analyses were performed. RESULTS: Immediate surgical treatment was the most cost-effective management strategy for small UIAs with ICER of USD 45,772 relative to active surveillance. Sensitivity analysis demonstrated immediate surgery was the preferred strategy, if rupture rate was >0.1%/year and if the diagnosis age was <70 years, while active surveillance was preferred if surgical complication risk was >11%. Probabilistic sensitivity analysis demonstrated that at a willingness-to-pay of USD 100,000/QALY, immediate surgical treatment was the most cost-effective strategy in 64% of iterations. CONCLUSION: Immediate surgical treatment is a cost-effective strategy for initial management of small UIAs in patients <70 years of age. While more costly than MRA, surgical treatment increased QALY. The cost-effectiveness of immediate surgery is highly sensitive to diagnosis age, rupture rate, and surgical complication risk. Though there are a wide range of rupture rates and complications associated with treatment, this analysis supports the treatment of small, unruptured anterior circulation intracranial aneurysms in patients <70 years of age.

Professional agency vs consumer directed care workers: Outcomes in managed care.

Direct care workers are a major part of the long-term services and supports (LTSS) needed to address the health of individuals and accounted for $112 billion in United States spending in 2015. Direct care workers are hired within professional agency models (PAMs) or consumer-directed models (CDMs) where workers (including family) are contracted by the individual to obtain services. We sought to identify differences in cost and utilisation outcomes between PAM and CDM participants. Data were obtained from the University of Pittsburgh Medical Center (UPMC) Insurance Services Division from the participants enrolled in UPMC Community HealthChoices in Pennsylvania during 2018. A retrospective, observational cohort study design was performed using claims data. Utilisation outcomes were assessed using multivariate logistic regression and cost outcomes by linear regression. The 3,232 participants met the inclusion criteria. Of these, 69% (N = 2,217) were in a PAM, 23% (N = 752) were in a CDM, and 8% (N = 263) used a combination of services. PAM groups were older (mean 62.4 years vs 54.1 years), more likely to be women (69.0% vs 62.8%), and had more healthcare needs. Hospital utilisation was the same among groups. However, total cost was lower in CDM groups due to differences in LTSS costs between CDM and PAM services. Among dually eligible Medicare and Medicaid beneficiaries receiving LTSS, there are significant differences in age, gender, race and health needs. While hospital utilisation was not different between groups, CDM groups had lower total costs of care compared to PAM. These findings have implications for families, policymakers and insurers in helping to govern community LTSS while supporting member autonomy.

Assessment with clinical data of a coupled bio-hemodynamics numerical model to predict leukocyte adhesion in coronary arteries.

Numerical simulations of coupled hemodynamics and leukocyte transport and adhesion inside coronary arteries have been performed. Realistic artery geometries have been obtained for a set of four patients from intravascular ultrasound and angiography images. The numerical model computes unsteady three-dimensional blood hemodynamics and leukocyte concentration in the blood. Wall-shear stress dependent leukocyte adhesion is also computed through agent-based modeling rules, fully coupled to the hemodynamics and leukocyte transport. Numerical results have a good correlation with clinical data. Regions where high adhesion is predicted by the simulations coincide to a good approximation with artery segments presenting plaque increase, as documented by clinical data from baseline and six-month follow-up exam of the same artery. In addition, it is observed that the artery geometry and, in particular, the tortuosity of the centerline are a primary factor in determining the spatial distribution of wall-shear stress, and of the resulting leukocyte adhesion patterns. Although further work is required to overcome the limitations of the present model and ultimately quantify plaque growth in the simulations, these results are encouraging towards establishing a predictive methodology for atherosclerosis progress.

The socioeconomic cost of chronic rhinosinusitis study.

INTRODUCTION: Chronic rhinosinusitis (CRS) is highly prevalent, affecting 11% of the population. Studies evaluating the socio-economic impact of CRS are mostly limited to the US population. Currently there is no study that has evaluated the socio-economic costs of CRS in the UK. METHODS: A case-control study of patients with CRS and healthy controls was conducted to investigate the wider socio-economic impact of the disease. Data on demographic and socioeconomic characteristics, out-of-pocket expenditure (OOPE), health resource utilisation, productivity losses and health-related quality of life (HRQoL) via the EQ-5D and SNOT-22 instruments, were collected from questionnaires. RESULTS: A total of 139 CRS participants and 67 control participants completed the questionnaires. The average total OOPE per patient extrapolated to a 12-month period was £304.84. Other important findings include significantly higher reported primary care interactions (4.14 vs. 1.16) as well as secondary care interactions (2.61 vs 0.4) in CRS group as compared to controls over three-months. The average total missed workdays was estimated to be 18.7 per patient per year. The estimated incremental healthcare cost of CRS per year is £16.8 billion or £2.8 billion per million inhabitants. Factors predictive of a higher OOPE include higher household occupancy and income and these accounted for only 9.7% of the total variance in total OOPEs. Other socioeconomic, demographic and HRQoL variables were not found to be predictive factors of OOPE. CONCLUSIONS: This study showed that CRS has a significant wider economic burden beyond the immediate direct healthcare costs. CRS participants had a high level of healthcare service use, OOPE and productivity loss. Results from this study will add to the existing limited data both for the UK and abroad and emphasises the need for effective treatments for these patients to reduce the disease impact.

Impact of Healthcare Delivery System Type on Clinical, Utilization, and Cost Outcomes of Patient-Centered Medical Homes: a Systematic Review.

BACKGROUND: As healthcare reimbursement shifts from being volume to value-focused, new delivery models aim to coordinate care and improve quality. The patient-centered medical home (PCMH) model is one such model that aims to deliver coordinated, accessible healthcare to improve outcomes and decrease costs. It is unclear how the types of delivery systems in which PCMHs operate differentially impact outcomes. We aim to describe economic, utilization, quality, clinical, and patient satisfaction outcomes resulting from PCMH interventions operating within integrated delivery and finance systems (IDFS), government systems including Veterans Administration, and non-integrated delivery systems. METHODS: We searched PubMed, the Cochrane Library, and Embase from 2004 to 2017. Observational studies and clinical trials occurring within the USA that met PCMH criteria (as defined by the Agency for Healthcare Research and Quality), addressed ambulatory adults, and reported utilization, economic, clinical, processes and quality of care, or patient satisfaction outcomes. RESULTS: Sixty-four studies were included. Twenty-four percent were within IDFS, 29% were within government systems, and 47% were within non-IDFS. IDFS studies reported decreased emergency department use, primary care use, and cost relative to other systems after PCMH implementation. Government systems reported increased primary care use relative to other systems after PCMH implementation. Clinical outcomes, processes and quality of care, and patient satisfaction were assessed heterogeneously or infrequently. DISCUSSION: Published articles assessing PCMH interventions generally report improved outcomes related to utilization and cost. IDFS and government systems exhibit different outcomes relative to non-integrated systems, demonstrating that different health systems and populations may be particularly sensitive to PCMH interventions. Both the definition of PCMH interventions and outcomes measured are heterogeneous, limiting the ability to perform direct comparisons or meta-analysis.

Assessing the effectiveness of a naturally occurring population-level physical activity intervention for children.

OBJECTIVES: The aim of the study was to assess the impact of a recreation access pass on grade 5 children's physical activity (PA) levels. STUDY DESIGN: This is a pre-post evaluation of a population-level community-based intervention. METHODS: All grade 5 students in (London, Ontario, Canada) were invited to participate in the [ACT-i-Pass] program (G5AP) in May 2014. A total of 643 children completed surveys, that included Physical Activity Questionnaire for Children (PAQ-C), at baseline (October 2014) and 6-month follow-up (April 2015). Difference in the means t-test compared PAQ-C scores between baseline and follow-up for the sample and subgroups. Multiple regression analysis tested associations between change in PAQ-C scores and intrapersonal-, interpersonal-, and physical environment-level variables. RESULTS: PA increased significantly from baseline to 6-month follow-up. Girls, visible minorities, immigrants, and children with low parental support experienced significant increases in PA. Regression found girls benefitted from the G5AP significantly more than boys, and lower parental support is related to increases in PA. CONCLUSION: The findings indicate that collaboratively developed, community-based interventions can significantly increase children's PA levels, particularly among subgroups with traditionally lower PA. The pre-post evaluation of this community-based intervention provides useful evidence for developing policies and programs aimed at making population-level improvements in children's PA levels.

scRNA-seq assessment of the human lung, spleen, and esophagus tissue stability after cold preservation.

BACKGROUND: The Human Cell Atlas is a large international collaborative effort to map all cell types of the human body. Single-cell RNA sequencing can generate high-quality data for the delivery of such an atlas. However, delays between fresh sample collection and processing may lead to poor data and difficulties in experimental design. RESULTS: This study assesses the effect of cold storage on fresh healthy spleen, esophagus, and lung from ≥ 5 donors over 72 h. We collect 240,000 high-quality single-cell transcriptomes with detailed cell type annotations and whole genome sequences of donors, enabling future eQTL studies. Our data provide a valuable resource for the study of these 3 organs and will allow cross-organ comparison of cell types. We see little effect of cold ischemic time on cell yield, total number of reads per cell, and other quality control metrics in any of the tissues within the first 24 h. However, we observe a decrease in the proportions of lung T cells at 72 h, higher percentage of mitochondrial reads, and increased contamination by background ambient RNA reads in the 72-h samples in the spleen, which is cell type specific. CONCLUSIONS: In conclusion, we present robust protocols for tissue preservation for up to 24 h prior to scRNA-seq analysis. This greatly facilitates the logistics of sample collection for Human Cell Atlas or clinical studies since it increases the time frames for sample processing.

Multidose Botulinum Toxin A for Intralaryngeal Injection: A Cost Analysis.

OBJECTIVES: Botulinum toxin A (BtxA) injection is the mainstay treatment for laryngeal dystonias. BtxA product labeling states that reconstituted toxin should be used within 4 hours on a single patient despite several studies that have demonstrated multidose BtxA to be safe and effective. Many insurance carriers mandate the use of an outside pharmacy which necessitates a single-use approach. This study compares the cost savings of multidose BtxA for laryngeal dystonia compared to single-use. STUDY DESIGN: This is a retrospective review and projected cost savings analysis. METHODS: Records and billing information were reviewed for patients receiving BtxA for intralaryngeal injection at a single laryngology division in 2015. Inclusion criteria included CPT 64617 or J0585; exclusion criteria included CPT 64616. The price of BtxA 100 unit vial for calculation was $670. RESULTS: A total of 142 patients were seen for intralaryngeal BtxA injection resulting in 337 visits over 1 year. The average BtxA dose per visit was 2.86 units with an average of 3.06 procedure visits per year. The calculated cost of BtxA treatment using a single vial approach was found to be $2,050 per patient per year. If billed instead for $7/unit with 5 units wastage charge per visit, the yearly per patient charge is $168. Single vial-use of BtxA injection thus represents a 1,118% price increase versus multidose use. When estimated for yearly prevalence of spasmodic dysphonia, multidose BtxA use would save almost $100 million annually. CONCLUSIONS: Multidose botulinum toxin A application utilizing per unit billing is significantly less expensive than per single-use vial billing and would save the health-care system significant amount of money without any sacrifice in safety or effectiveness.

Socioeconomic position and depression in South African adults with long-term health conditions: a longitudinal study of causal pathways.

AIMS: There is convincing evidence that lower socioeconomic position is associated with increased risk of mental disorders. However, the mechanisms involved are not well understood. This study aims to elucidate the causal pathways between socioeconomic position and depression symptoms in South African adults. Two possible causal theories are examined: social causation, which suggests that poor socioeconomic conditions cause mental ill health; and social drift, which suggests that those with poor mental health are more likely to drift into poor socioeconomic circumstances. METHODS: The study used longitudinal and cross-sectional observational data on 3904 adults, from a randomised trial carried out in 38 primary health care clinics between 2011 and 2012. Structural equation models and counterfactual mediation analyses were used to examine causal pathways in two directions. First, we examined social causation pathways, with language (a proxy for racial or ethnic category) being treated as an exposure, while education, unemployment, income and depression were treated as sequential mediators and outcomes. Second, social drift was explored with depression treated as a potential influence on health-related quality of life, job loss and, finally, income. RESULTS: The results suggest that the effects of language on depression at baseline, and on changes in depression during follow-up, were mediated through education and income but not through unemployment. Adverse effects of unemployment and job loss on depression appeared to be mostly mediated through income. The effect of depression on decreasing income appeared to be mediated by job loss. CONCLUSIONS: These results suggest that both social causation and social selection processes operate concurrently. This raises the possibility that people could get trapped in a vicious cycle in which poor socioeconomic conditions lead to depression, which, in turn, can cause further damage to their economic prospects. This study also suggests that modifiable factors such as income, employment and treatable depression are suitable targets for intervention in the short to medium term, while in the longer term reducing inequalities in education will be necessary to address the deeply entrenched inequalities in South Africa.

The association between alcohol outlet accessibility and adverse birth outcomes: A retrospective cohort study.

BACKGROUND: Alcohol outlet accessibility is positively associated with alcohol consumption, although this relationship has not been thoroughly examined in pregnant women. The present study examines the relationship between proximity and density of alcohol outlets and risk for low birth weight (LBW: <2,500 grams) and preterm birth (PTB: <37 weeks gestational age), and is the first Canadian study to investigate this association. METHODS: Maternal accessibility to alcohol outlets was specified using a gravity-type measure of accessibility, which provides the amount of accessibility that a given household has to liquor stores within 30-minutes of their home. All singleton newborns without congenital anomalies that were born between February 2009 and February 2014 at London Health Sciences Centre in London, Ontario, were included in this cohort. RESULTS: The sample consisted of 25,734 live births, of which 5.8% were LBW and 7.6% were PTB. Only 2.0% of women reported alcohol use during pregnancy. Alcohol outlet gravity was positively correlated with the percentage of mothers living in poverty (rs = 0.33, p < 0.001) and in single-parent families (rs = 0.39, p < 0.001), and who self-identify as visible minorities (rs = 0.45, p < 0.001). Alcohol outlet gravity increased the odds that mothers drank alcohol during pregnancy (OR 1.05; 95% CI: 1.02, 1.07), although the association was weak. Furthermore, alcohol outlet gravity did not increase the likelihood of a LBW or PTB infant. CONCLUSIONS: Women with high accessibility to alcohol outlets are more likely to consume alcohol during pregnancy, but greater alcohol outlet accessibility does not translate into poor birth outcomes.

The urgent need for a harmonized severity scoring system for acute allergic reactions.

The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three-grade-based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice.

Rampant polyphyly in the Arracacia clade (Apiaceae) and an assessment of the phylogenetic utility of 20 noncoding plastid loci.

The Arracacia clade (Apiaceae, Apioideae) is a heterogeneous assemblage of 12 genera, comprising 111 known species distributed in high montane temperate and sub-alpine habitats of meso- and South America. Previous studies have indicated that the genera Arracacia, Coulterophytum, and Prionosciadium are polyphyletic, but for the most part relationships among the members of the clade are largely unknown. Initially, cladistic analyses of nrDNA ITS sequences were carried out on 212 accessions (122 taxa), representing 92 species of the Arracacia clade and outgroups from the closely-related páramo genera Cotopaxia, Niphogeton, and Perissocoeleum and members of the Perennial Endemic North American clade and its allies. Using the ITS results to inform sampling of a small subset of taxa, a pilot study examining the phylogenetic utility of 20 noncoding chloroplast loci was subsequently performed to identify those regions most useful at resolving relationships. A cost-benefit analysis determined that five loci (trnQ-5'rps16, trnD-trnT, rpl32-trnL, psbD-trnT, ndhA intron) would maximize resolution and branch support in the clade. Cladistic analyses of four of these loci (trnQ-5'rps16, trnD-trnT, rpl32-trnL, ndhA intron) and the ITS region, separately and combined, revealed that Arracacia, Coaxana, Coulterophytum, Prionosciadium, and Rhodosciadium are each polyphyletic and that Donnellsmithia and Myrrhidendron are each monophyletic. Although most relationships in the Arracacia clade and among the closely-related genera Cotopaxia, Niphogeton, and Perissocoeleum are poorly resolved and supported, ten groups are recognized for future revisionary studies. Polyploidy and rapid species radiation have likely confounded generic circumscriptions and interpretation of relationships.

BSACI guideline for the diagnosis and management of peanut and tree nut allergy.

Peanut nut and tree nut allergy are characterised by IgE mediated reactions to nut proteins. Nut allergy is a global disease. Limited epidemiological data suggest varying prevalence in different geographical areas. Primary nut allergy affects over 2% of children and 0.5% of adults in the UK. Infants with severe eczema and/or egg allergy have a higher risk of peanut allergy. Primary nut allergy presents most commonly in the first five years of life, often after the first known ingestion with typical rapid onset IgE-mediated symptoms. The clinical diagnosis of primary nut allergy can be made by the combination of a typical clinical presentation and evidence of nut specifc IgE shown by a positive skin prick test (SPT) or specific IgE (sIgE) test. Pollen food syndrome is a distinct disorder, usually mild, with oral/pharyngeal symptoms, in the context of hay fever or pollen sensitisation, which can be triggered by nuts. It can usually be distinguish clinically from primary nut allergy. The magnitude of a SPT or sIgE relates to the probability of clinical allergy, but does not relate to clinical severity. SPT of ≥ 8 mm or sIgE ≥ 15 KU/L to peanut is highly predictive of clinical allergy. Cut off values are not available for tree nuts. Test results must be interpreted in the context of the clinical history. Diagnostic food challenges are usually not necessary but may be used to confirm or refute a conflicting history and test result. As nut allergy is likely to be a long-lived disease, nut avoidance advice is the cornerstone of management. Patients should be provided with a comprehensive management plan including avoidance advice, patient specific emergency medication and an emergency treatment plan and training in administration of emergency medication. Regular re-training is required.

Impact on health-related quality of life and costs of managing chronic neuropathic pain in academic pain centres: Results from a one-year prospective observational Canadian study.

BACKGROUND: The management of chronic pain, including neuropathic pain (NeP), is a major public health issue. However, there is a paucity of data evaluating pain management strategies in real-life settings. OBJECTIVE: To inform policy makers about the economic value of managing chronic NeP in academic centres by conducting a subeconomic assessment of a Canadian multicentre cohort study aimed at determining the long-term outcomes of the management of chronic NeP in academic pain centres. Specific questions regarding the economic value of this type of program were answered by a subset of patients to provide further information to policy makers. METHODS: Baseline demographic information and several pain-related measurements were collected at baseline, three, six and 12 months in the main study. A resource use questionnaire aimed at determining NeP-related costs and the EuroQoL-5 Dimension were collected in the subset study from consenting patients. Statistical analyses were conducted to compare outcomes over time and according to responder status. RESULTS: A total of 298 patients were evaluated in the present economic evaluation. The mean (± SD) age of the participants was 53.7±14.0 years, and 56% were female. At intake, the mean duration of NeP was >5 years. Statistically significant improvements in all pain and health-related quality of life outcomes were observed between the baseline and one-year visits. Use decreased over time for many health care resources (eg, visits to the emergency room decreased by one-half), which resulted in overall cost savings. CONCLUSION: The results suggest that increased access to academic pain centres should be facilitated in Canada.