Team based collaborative care model, facilitated by mHealth enabled and trained nurses, for management of heart failure with reduced ejection fraction in India (TIME-HF): design and rationale of a parallel group, open label, multi-centric cluster randomised controlled trial.

Background: Heart failure (HF) is a debilitating condition associated with enormous public health burden. Management of HF is complex as it requires care-coordination with different cadres of health care providers. We propose to develop a team based collaborative care model (CCM), facilitated by trained nurses, for management of HF with the support of mHealth and evaluate its acceptability and effectiveness in Indian setting. Methods: The proposed study will use mixed-methods research. Formative qualitative research will identify barriers and facilitators for implementing CCM for the management of HF. Subsequently, a cluster randomised controlled trial (RCT) involving 22 centres (tertiary-care hospitals) and more than 1500 HF patients will be conducted to assess the efficacy of the CCM in improving the overall survival as well as days alive and out of hospital (DAOH) at two-years (CTRI/2021/11/037797). The DAOH will be calculated by subtracting days in hospital and days from death until end of study follow-up from the total follow-up time. Poisson regression with a robust variance estimate and an offset term to account for clustering will be employed in the analyses of DAOH. A rate ratio and its 95% confidence interval (CI) will be estimated. The scalability of the proposed intervention model will be assessed through economic analyses (cost-effectiveness) and the acceptability of the intervention at both the provider and patient level will be understood through both qualitative and quantitative process evaluation methods. Potential Impact: The TIME-HF trial will provide evidence on whether a CCM with mHealth support is effective in improving the clinical outcomes of HF with reduced ejection fraction in India. The findings may change the practice of management of HF in low and middle-income countries.

Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL.

T cells expressing CD19-specific chimeric antigen receptors (CD19-CARs) have potent antileukemia activity in pediatric and adult patients with relapsed and/or refractory B-cell acute lymphoblastic leukemia (B-ALL). However, not all patients achieve a complete response (CR), and a significant percentage relapse after CD19-CAR T-cell therapy due to T-cell intrinsic and/or extrinsic mechanisms. Thus, there is a need to evaluate new CD19-CAR T-cell products in patients to improve efficacy. We developed a phase 1/2 clinical study to evaluate an institutional autologous CD19-CAR T-cell product in pediatric patients with relapsed/refractory B-ALL. Here we report the outcome of the phase 1 study participants (n = 12). Treatment was well tolerated, with a low incidence of both cytokine release syndrome (any grade, n = 6) and neurotoxicity (any grade, n = 3). Nine out of 12 patients (75%) achieved a minimal residual disease-negative CR in the bone marrow (BM). High disease burden (≥40% morphologic blasts) before CAR T-cell infusion correlated with increased side effects and lower response rate, but not with CD19-CAR T-cell expansion. After infusion, CD8+ CAR T cells had a proliferative advantage over CD4+ CAR T cells and at peak expansion, had an effector memory phenotype with evidence of antigen-driven differentiation. Patients that proceeded to allogeneic hematopoietic cell transplantation (AlloHCT) had sustained, durable responses. In summary, the initial evaluation of our institutional CD19-CAR T-cell product demonstrates safety and efficacy while highlighting the impact of pre-infusion disease burden on outcomes. This trial was registered at www.clinicaltrials.gov as #NCT03573700.

An Assessment of Serological Assays for SARS-CoV-2 as Surrogates for Authentic Virus Neutralization.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and has since caused a global pandemic resulting in millions of cases and deaths. Diagnostic tools and serological assays are critical for controlling the outbreak, especially assays designed to quantitate neutralizing antibody levels, considered the best correlate of protection. As vaccines become increasingly available, it is important to identify reliable methods for measuring neutralizing antibody responses that correlate with authentic virus neutralization but can be performed outside biosafety level 3 (BSL3) laboratories. While many neutralizing assays using pseudotyped virus have been developed, there have been few studies comparing the different assays to each other as surrogates for authentic virus neutralization. Here, we characterized three enzyme-linked immunosorbent assays (ELISAs) and three pseudotyped vesicular stomatitis virus (VSV) neutralization assays and assessed their concordance with authentic virus neutralization. The most accurate assays for predicting authentic virus neutralization were luciferase- and secreted embryonic alkaline phosphatase (SEAP)-expressing pseudotyped virus neutralizations, followed by green fluorescent protein (GFP)-expressing pseudotyped virus neutralization, and then the ELISAs. IMPORTANCE The ongoing COVID-19 pandemic is caused by infection with severe acute respiratory syndrome virus 2 (SARS-CoV-2). Prior infection or vaccination can be detected by the presence of antibodies in the blood. Antibodies in the blood are also considered to be protective against future infections from the same virus. The "gold standard" assay for detecting protective antibodies against SARS-CoV-2 is neutralization of authentic SARS-CoV-2 virus. However, this assay can only be performed under highly restrictive biocontainment conditions. We therefore characterized six antibody-detecting assays for their correlation with authentic virus neutralization. The significance of our research is in outlining the advantages and disadvantages of the different assays and identifying the optimal surrogate assay for authentic virus neutralization. This will allow for more accurate assessments of protective immunity against SARS-CoV-2 following infection and vaccination.

Bayesian parameter estimation for automatic annotation of gene functions using observational data and phylogenetic trees.

Gene function annotation is important for a variety of downstream analyses of genetic data. But experimental characterization of function remains costly and slow, making computational prediction an important endeavor. Phylogenetic approaches to prediction have been developed, but implementation of a practical Bayesian framework for parameter estimation remains an outstanding challenge. We have developed a computationally efficient model of evolution of gene annotations using phylogenies based on a Bayesian framework using Markov Chain Monte Carlo for parameter estimation. Unlike previous approaches, our method is able to estimate parameters over many different phylogenetic trees and functions. The resulting parameters agree with biological intuition, such as the increased probability of function change following gene duplication. The method performs well on leave-one-out cross-validation, and we further validated some of the predictions in the experimental scientific literature.

Severe asthma assessment, management and the organisation of care in Australia and New Zealand: expert forum roundtable meetings.

Severe asthma imposes a significant burden on individuals, families and the healthcare system. Treatment is complex, due to disease heterogeneity, comorbidities and complexity in care pathways. New approaches and treatments improve health outcomes for people with severe asthma. However, emerging multidimensional and targeted treatment strategies require a reorganisation of asthma care. Consensus is required on how reorganisation should occur and what areas require further research. The Centre of Excellence in Severe Asthma convened three forums between 2015 and 2018, hosting experts from Australia, New Zealand and the UK. The forums were complemented by a survey of clinicians involved in the management of people with severe asthma. We sought to: (i) identify areas of consensus among experts; (ii) define activities and resources required for the implementation of findings into practice; and (iii) identify specific priority areas for future research. Discussions identified areas of unmet need including assessment and diagnosis of severe asthma, models of care and treatment pathways, add-on treatment approaches and patient perspectives. We recommend development of education and training activities, clinical resources and standards of care documents, increased stakeholder engagement and public awareness campaigns and improved access to infrastructure and funding. Further, we propose specific future research to inform clinical decision-making and develop novel therapies. A concerted effort is required from all stakeholders (including patients, healthcare professionals and organisations and government) to integrate new evidence-based practices into clinical care and to advance research to resolve questions relevant to improving outcomes for people with severe asthma.

Assessment of breath volatile organic compounds in acute cardiorespiratory breathlessness: a protocol describing a prospective real-world observational study.

INTRODUCTION: Patients presenting with acute undifferentiated breathlessness are commonly encountered in admissions units across the UK. Existing blood biomarkers have clinical utility in distinguishing patients with single organ pathologies but have poor discriminatory power in multifactorial presentations. Evaluation of volatile organic compounds (VOCs) in exhaled breath offers the potential to develop biomarkers of disease states that underpin acute cardiorespiratory breathlessness, owing to their proximity to the cardiorespiratory system. To date, there has been no systematic evaluation of VOC in acute cardiorespiratory breathlessness. The proposed study will seek to use both offline and online VOC technologies to evaluate the predictive value of VOC in identifying common conditions that present with acute cardiorespiratory breathlessness. METHODS AND ANALYSIS: A prospective real-world observational study carried out across three acute admissions units within Leicestershire. Participants with self-reported acute breathlessness, with a confirmed primary diagnosis of either acute heart failure, community-acquired pneumonia and acute exacerbation of asthma or chronic obstructive pulmonary disease will be recruited within 24 hours of admission. Additionally, school-age children admitted with severe asthma will be evaluated. All participants will undergo breath sampling on admission and on recovery following discharge. A range of online technologies including: proton transfer reaction mass spectrometry, gas chromatography ion mobility spectrometry, atmospheric pressure chemical ionisation-mass spectrometry and offline technologies including gas chromatography mass spectroscopy and comprehensive two-dimensional gas chromatography-mass spectrometry will be used for VOC discovery and replication. For offline technologies, a standardised CE-marked breath sampling device (ReCIVA) will be used. All recruited participants will be characterised using existing blood biomarkers including C reactive protein, brain-derived natriuretic peptide, troponin-I and blood eosinophil levels and further evaluated using a range of standardised questionnaires, lung function testing, sputum cell counts and other diagnostic tests pertinent to acute disease. ETHICS AND DISSEMINATION: The National Research Ethics Service Committee East Midlands has approved the study protocol (REC number: 16/LO/1747). Integrated Research Approval System (IRAS) 198921. Findings will be presented at academic conferences and published in peer-reviewed scientific journals. Dissemination will be facilitated via a partnership with the East Midlands Academic Health Sciences Network and via interaction with all UK-funded Medical Research Council and Engineering and Physical Sciences Research Council molecular pathology nodes. TRIAL REGISTRATION NUMBER: NCT03672994.

Best Practices for Dietary Supplement Assessment and Estimation of Total Usual Nutrient Intakes in Population-Level Research and Monitoring.

The use of dietary supplements (DS) is pervasive and can provide substantial amounts of micronutrients to those who use them. Therefore when characterizing dietary intakes, describing the prevalence of inadequacy or excess, or assessing relations between nutrients and health outcomes, it is critical to incorporate DS intakes to improve exposure estimates. Unfortunately, little is known about the best methods to assess DS, and the structure of measurement error in DS reporting. Several characteristics of nutrients from DS are salient to understand when comparing to those in foods. First, DS can be consumed daily or episodically, in bolus form and can deliver discrete and often very high doses of nutrients that are not limited by energy intakes. These characteristics contribute to bimodal distributions and distributions severely skewed to the right. Labels on DS often provide nutrient forms that differ from those found in conventional foods, and underestimate analytically derived values. Finally, the bioavailability of many nutrient-containing DS is not known and it may not be the same as the nutrients in a food matrix. Current methods to estimate usual intakes are not designed specifically to handle DS. Two temporal procedures are described to refer to the order that nutrient intakes are combined relative to usual intake procedures, referred to as a "shrinking" the distribution to remove random error. The "shrink then add" approach is preferable to the "add then shrink" approach when users and nonusers are combined for most research questions. Stratifying by DS before usual intake methods is another defensible option. This review describes how to incorporate nutrient intakes from DS to usual intakes from foods, and describes the available methods and fit-for-purpose of different analytical strategies to address research questions where total usual intakes are of interest at the group level for use in nutrition research and to inform policy decisions. Clinical Trial Registry: NCT03400436.

A risk assessment of Europe's black truffle sector under predicted climate change.

The black truffle (Tuber melanosporum) is a highly revered culinary icon species that grows symbiotically with its host trees across several parts of southern Europe. Where harvested under natural or cultivated conditions, truffles can have a significant socioeconomic impact and may even form a key component of cultural identity. Although some aspects of truffle biology and ecology have been elucidated recently, the role of abiotic, environmental and climatic factors in the production and maturation of their fruitbodies is still largely unknown. Based on 36-year-long, continuous records of Mediterranean truffle yield, we demonstrate that decreased summer precipitation together with increased summer temperatures significantly reduce the fungus' subsequent winter harvest. Using state-of-the-art climate model projections, we predict that a significant decline of 78-100% in southern European truffle production is likely to occur between 2071 and 2100. The additional threats of forecasted heatwaves, forest fires, pest and disease outbreaks are discussed along with socioeconomic and ecological consequences of a warmer and dryer future climate. Our results emphasize the need for unravelling the direct and indirect effects of climate change on Europe's truffle sector and underline the importance of conservation initiatives at local to international scales.

How in silico and QSAR approaches can increase confidence in environmental hazard and risk assessment.

In silico methods are typically underrated in the current risk assessment paradigm, as evidenced by the recent document from the European Chemicals Agency (ECHA) on animal alternatives, in which quantitative structure-activity relationships (QSARs) were practically used only as a last resort. Their primary use is still to provide supporting evidence for read-across strategies or to add credence to experimental results of unknown or limited validity (old studies, studies without good laboratory practices [GLPs], limited information reported, etc.) in hazard assessment, but under the pressure of increasing burdens of testing, industry and regulators alike are at last warming to them. Nevertheless, their true potential for data-gap filling and for resolving sticking points in risk assessment methodology and beyond has yet to be recognized. We postulate that it is possible to go beyond the level of simply increasing confidence to the point of using in silico approaches to accurately predict results that cannot be resolved analytically. For example, under certain conditions it is possible to obtain meaningful results by in silico extrapolation for tests that would be technically impossible to conduct in the laboratory or at least extremely challenging to obtain reliable results. The following and other concepts are explored in this article: the mechanism of action (MechoA) of the substance should be determined, as an aid verifying that the QSAR model is applicable to the substance under review; accurate QSARs should be built with high-quality data that were not only curated but also validated with expert judgment; although a rule of thumb for acute to chronic ratios appears applicable for nonpolar narcotics, it seems unlikely that a "one-value-fits-all" answer exists for other MechoAs; a holistic approach to QSARs can be employed (via reverse engineering) to help validate or invalidate an experimental endpoint value on the basis of multiple experimental studies. Integr Environ Assess Manag 2019;15:40-50. © 2018 SETAC.

The Value of Activated Ion Electron Transfer Dissociation for High-Throughput Top-Down Characterization of Intact Proteins.

High-throughput top-down proteomic experiments directly identify proteoforms in complex mixtures, making high quality tandem mass spectra necessary to deeply characterize proteins with many sources of variation. Collision-based dissociation methods offer expedient data acquisition but often fail to extensively fragment proteoforms for thorough analysis. Electron-driven dissociation methods are a popular alternative approach, especially for precursor ions with high charge density. Combining infrared photoactivation concurrent with electron transfer dissociation (ETD) reactions, i.e., activated ion ETD (AI-ETD), can significantly improve ETD characterization of intact proteins, but benefits of AI-ETD have yet to be quantified in high-throughput top-down proteomics. Here, we report the first application of AI-ETD to LC-MS/MS characterization of intact proteins (<20 kDa), highlighting improved proteoform identification the method offers over higher energy-collisional dissociation (HCD), standard ETD, and ETD followed by supplemental HCD activation (EThcD). We identified 935 proteoforms from 295 proteins from human colorectal cancer cell line HCT116 using AI-ETD compared to 1014 proteoforms, 915 proteoforms, and 871 proteoforms with HCD, ETD, and EThcD, respectively. Importantly, AI-ETD outperformed each of the three other methods in MS/MS success rates and spectral quality metrics (e.g., sequence coverage achieved and proteoform characterization scores). In all, this four-method analysis offers the most extensive comparisons to date and demonstrates that AI-ETD both increases identifications over other ETD methods and improves proteoform characterization via higher sequence coverage, positioning it as a premier method for high-throughput top-down proteomics.

Assessment of litter prevalence of Mycoplasma hyopneumoniae in preweaned piglets utilizing an antemortem tracheobronchial mucus collection technique and a real-time polymerase chain reaction assay.

The swine industry currently lacks validated antemortem methods of detecting baseline herd prevalence of Mycoplasma hyopneumoniae. The focus of our study was to evaluate alternative antemortem detection techniques and to determine baseline litter prevalence in preweaned pig populations utilizing the selected technique and a real-time polymerase chain reaction (qPCR) assay. Preliminary data was analyzed on weaned piglets with evidence of respiratory disease (n = 32). Five sample types (antemortem nasal swab, tracheobronchial mucus, postmortem deep airway swab, bronchoalveolar lavage, and lung tissue) were collected from each pig. Individual samples were tested for M. hyopneumoniae using qPCR. Compared to nasal swabs, tracheobronchial mucus demonstrated higher test sensitivity (P < 0.0001). Tracheobronchial mucus was collected from apparently healthy preweaned piglets (n = 1,759; sow farms 1-3) and preweaned piglets exhibiting signs of respiratory disease (n = 32; sow farm 4), ranging in age from 12 to 25 days. Samples from sow farms 1-3 were pooled into 2 groups of 5 per litter (n = 360 pools from 180 litters), and qPCR was utilized to analyze each pool. A qPCR-positive result, threshold cycle <37, from either pool designated the litter positive for M. hyopneumoniae. Two out of 180 litters revealed a positive result (1.1%). Individual qPCR assays were run on the samples collected from sow farm 4. Five out of 30 samples revealed a positive result (16.7%). Tracheobronchial mucus collection in combination with qPCR is a sensitive antemortem sampling technique that can be used to estimate the prevalence of M. hyopneumoniae in preweaned pigs, thus providing insight into the infection dynamics across the entire farrow-to-finish process.

Why US adults use dietary supplements.

BACKGROUND: Dietary supplements are used by more than half of adults, although to our knowledge, the reasons motivating use have not been previously examined in US adults using nationally representative data. The purpose of this analysis was to examine motivations for dietary supplement use, characterize the types of products used for the most commonly reported motivations, and to examine the role of physicians and health care practitioners in guiding choices about dietary supplements. METHODS: Data from adults (≥20 years; n = 11 956) were examined in the 2007-2010 National Health and Nutrition Examination Survey, a nationally representative, cross-sectional, population-based survey. RESULTS: The most commonly reported reasons for using supplements were to "improve" (45%) or "maintain" (33%) overall health. Women used calcium products for "bone health" (36%), whereas men were more likely to report supplement use for "heart health or to lower cholesterol" (18%). Older adults (≥60 years) were more likely than younger individuals to report motivations related to site-specific reasons like heart, bone and joint, and eye health. Only 23% of products were used based on recommendations of a health care provider. Multivitamin-mineral products were the most frequently reported type of supplement taken, followed by calcium and ω-3 or fish oil supplements. Supplement users are more likely to report very good or excellent health, have health insurance, use alcohol moderately, eschew cigarette smoking, and exercise more frequently than nonusers. CONCLUSIONS: Supplement users reported motivations related to overall health more commonly than for supplementing nutrients from food intakes. Use of supplements was related to more favorable health and lifestyle choices. Less than a quarter of supplements used by adults were recommended by a physician or health care provider.

Economic analysis of FDG-PET-guided management of the neck after primary chemoradiotherapy for node-positive head and neck squamous cell carcinoma.

BACKGROUND: The aim of this economic analysis was to model different strategies using pre-treatment nodal stage or nodal response assessment with CT or positron emission tomography (PET)/CT to determine the need for neck dissection. METHODS: A cost-minimization analysis was developed on the basis of probability data from a prospective study of PET-guided management of the neck in patients achieving a complete response at the primary site. Costs were derived from our institution's activity-based clinical costing system. The effect of uncertainty was tested with sensitivity and scenario analyses including nationally representative cost data. RESULTS: Strategies incorporating PET had a 7% rate for neck dissection compared with 44% for CT-guided and 90% for planned neck dissection. The cost per patient was A$16,502 for planned neck dissection, A$8014 for CT-guided, and A$2573 for PET-guided. A policy with PET used only for incomplete response on CT was the least-cost strategy (A$2111). Policies incorporating PET remained the most efficient for all sensitivity/scenario analyses. CONCLUSION: The incorporation of PET/CT into nodal response assessment significantly reduced the number of unnecessary neck dissections and generated considerable cost savings in our cohort.

Association of biomarker levels with severity of asbestos-related diseases.

OBJECTIVES: Asbestos-related diseases (ARDs) have increased globally over the decades, causing an economic burden and increased health care costs. It is difficult to predict the risk of development of ARDs and of respiratory disability among workers with a history of asbestos exposure. Blood based biomarkers have been reported as promising tools for the early detection of malignant mesothelioma. This study investigated whether serum soluble mesothelin-related peptide (SMRP) would reflect severity of disablement in compensable ARDs. METHODS: SMRP levels were measured in a cohort of 514 asbestos-exposed subjects. Severity of ARDs was assessed by a Medical Authority comprising four specially qualified respiratory physicians. Severity of ARDs and SMRP levels were compared. RESULTS: Mean (standard deviation) serum SMRP level in the population with compensable ARDs (n = 150) was 0.95 (0.65) nmol/L, and was positively associated with disability assessment (p = 0.01). Mean SMRP level in healthy asbestos-exposed subjects was significantly lower than those with pleural plaques (p < 0.0001) and in subjects with ARDs who received compensation (p < 0.01). CONCLUSION: This study indicates that serum SMRP levels correlate with severity of compensable ARDs. Serum SMRP could potentially be applied to monitor progress of ARDs. Further prospective work is needed to confirm the relationship between SMRP and disability assessment in this population.

Inhibition of genistein glucuronidation by bisphenol A in human and rat liver microsomes.

Genistein is a natural phytoestrogen of the soybean, and bisphenol A (BPA) is a synthetic chemical used in the production of polycarbonate plastics. Both genistein and BPA disrupt the endocrine system in vivo and in vitro. Growing concerns of altered xenobiotic metabolism due to concomitant exposures from soy milk in BPA-laden baby bottles has warranted the investigation of the glucuronidation rate of genistein in the absence and presence (25 µM) of BPA by human liver microsomes (HLM) and rat liver microsomes (RLM). HLM yield V(max) values of 0.93 ± 0.10 nmol · min(-1) · mg(-1) and 0.62 ± 0.05 nmol · min(-1) · mg(-1) in the absence and presence of BPA, respectively. K(m) values for genistein glucuronidation by HLM in the absence and presence of BPA are 15.1 ± 7.9 µM and 21.5 ± 7.7 µM, respectively, resulting in a K(i) value of 58.7 µM for BPA. Significantly reduced V(max) and unchanged K(m) in the presence of BPA in HLM are suggestive of noncompetitive inhibition. In RLM, the presence of BPA resulted in a K(i) of 35.7 µM, an insignificant change in V(max) (2.91 ± 0.26 nmol · min(-1) · mg(-1) and 3.05 ± 0.41 nmol · min(-1) · mg(-1) in the absence and presence of BPA, respectively), and an increase in apparent K(m) (49.4 ± 14 µM with no BPA and 84.0 ± 28 µM with BPA), indicative of competitive inhibition. These findings are significant because they suggest that BPA is capable of inhibiting the glucuronidation of genistein in vitro, and that the type of inhibition is different between HLM and RLM.

Non-invasive assessment of exhaled biomarkers in lung transplantation.

Biomarkers in exhaled breath condensate (EBC) and fractional exhaled nitric oxide (FeNO) have been widely evaluated in respiratory research as non-invasive methods of sampling the lungs. These methods are particularly attractive in lung transplantation (LTx) as they are simple, repeatable and sensitive. Chronic rejection, manifest by progressive airflow limitation and bronchiolitis obliterans syndrome (BOS), is currently the major limiting factor to long-term survival in LTx. Early detection of BOS and initiation of appropriate treatment could significantly improve survival. Exhaled breath biomarkers could allow early diagnosis of factors associated with chronic rejection. FeNO is elevated in LTx patients with infections and chronic rejection prior to clinical presentation, and several EBC biomarkers and volatile organic compound patterns also show promise in these areas. This review summarizes information on exhaled breath biomarkers in LTx and discusses their potential role in the management of LTx patients.

Dietary supplement use in the United States, 2003-2006.

Dietary supplement use has steadily increased over time since the 1970s; however, no current data exist for the U.S. population. Therefore, the purpose of this analysis was to estimate dietary supplement use using the NHANES 2003-2006, a nationally representative, cross-sectional survey. Dietary supplement use was analyzed for the U.S. population (≥1 y of age) by the DRI age groupings. Supplement use was measured through a questionnaire and was reported by 49% of the U.S. population (44% of males, 53% of females). Multivitamin-multimineral use was the most frequently reported dietary supplement (33%). The majority of people reported taking only 1 dietary supplement and did so on a daily basis. Dietary supplement use was lowest in obese adults and highest among non-Hispanic whites, older adults, and those with more than a high-school education. Between 28 and 30% reported using dietary supplements containing vitamins B-6, B-12, C, A, and E; 18-19% reported using iron, selenium, and chromium; and 26-27% reported using zinc- and magnesium-containing supplements. Botanical supplement use was more common in older than in younger age groups and was lowest in those aged 1-13 y but was reported by ~20% of adults. About one-half of the U.S. population and 70% of adults ≥ 71 y use dietary supplements; one-third use multivitamin-multimineral dietary supplements. Given the widespread use of supplements, data should be included with nutrient intakes from foods to correctly determine total nutrient exposure.

General health care service utilisation: where, when and by whom in a socioeconomically disadvantaged population.

This paper aimed to examine the utilisation of and preferences related to health care services by residents of a disadvantaged area and to identify factors associated with levels of current and future use. Data were collected from face-to-face structured interviews of randomly selected residents of a disadvantaged local government area in 2003-04. Information about respondents' health and socioeconomic status and patterns of use and preferred features of health care was analysed in PASW Statistic 17. Chi-square statistics were used to examine differences in utilisation by sex and simple logistic regression provided sex specific age-adjusted odds ratios about frequent visits. Most respondents (95%) attended a 'usual' general practitioner (GP) service and about two-fifths had obtained other health care in the last 12 months. The median number of visits was four and most providers offered bulk billing (83%). Less common were visits to the dentist (32%), emergency department (14%), specialists (29%) and the hospital (5%). Providers' skills and traits, physical access and bulk billing were key considerations for men and women when choosing a health care provider. Disadvantaged communities want skilled practitioners who reflect their demographic mix and are located at convenient and accessible clinics, which preferably bulk bill. Apart from GP visits, this group appears to make only moderate use of specialists and emergency departments, and little routine use of other primary health services.

Combined horizontal and vertical integration of care: a goal of practice-based commissioning.

Practice-based commissioning (PBC) in the UK is intended to improve both the vertical and horizontal integration of health care, in order to avoid escalating costs and enhance population health. Vertical integration involves patient pathways to treat named medical conditions that transcend organisational boundaries and connect community-based generalists with largely hospital-sited specialists, whereas horizontal integration involves peer-based and cross-sectoral collaboration to improve overall health. Effective mechanisms are now needed to permit ongoing dialogue between the vertical and horizontal dimensions to ensure that medical and nonmedical care are both used to their best advantage. This paper proposes three different models for combining vertical and horizontal integration - each is a hybrid of internationally recognised ideal types of primary care organisation. Leaders of PBC should consider a range of models and apply them in ways that are relevant to the local context. General practitioners, policy makers and others whose job it is to facilitate horizontal and vertical integration must learn to lead such combined approaches to integration if the UK is to avoid the mistakes of the USA in over-medicalising health issues.