Tuberculosis (TB) is the leading cause of death from infectious disease worldwide, predominantly affecting low- and middle-income countries (LMICs), where resources are limited. As such, countries need to be able to choose the most efficient interventions for their respective setting. Mathematical models can be valuable tools to inform rational policy decisions and improve resource allocation, but are often unavailable or inaccessible for LMICs, particularly in TB. We developed TIME Impact, a user-friendly TB model that enables local capacity building and strengthens country-specific policy discussions to inform support funding applications at the (sub-)national level (e.g. Ministry of Finance) or to international donors (e.g. the Global Fund to Fight AIDS, Tuberculosis and Malaria). TIME Impact is an epidemiological transmission model nested in TIME, a set of TB modelling tools available for free download within the widely-used Spectrum software. The TIME Impact model reflects key aspects of the natural history of TB, with additional structure for HIV/ART, drug resistance, treatment history and age. TIME Impact enables national TB programmes (NTPs) and other TB policymakers to better understand their own TB epidemic, plan their response, apply for funding and evaluate the implementation of the response. The explicit aim of TIME Impact's user-friendly interface is to enable training of local and international TB experts towards independent use. During application of TIME Impact, close involvement of the NTPs and other local partners also builds critical understanding of the modelling methods, assumptions and limitations inherent to modelling. This is essential to generate broad country-level ownership of the modelling data inputs and results. In turn, it stimulates discussions and a review of the current evidence and assumptions, strengthening the decision-making process in general. TIME Impact has been effectively applied in a variety of settings. In South Africa, it informed the first South African HIV and TB Investment Cases and successfully leveraged additional resources from the National Treasury at a time of austerity. In Ghana, a long-term TIME model-centred interaction with the NTP provided new insights into the local epidemiology and guided resource allocation decisions to improve impact.

BACKGROUND:Trials suggest that the use of i.v. hydroxyethyl starch (HES) solutions is associ-ated with increased risk of death and acute kidney injury (AKI) in critically ill patients. It is uncertain whether similar adverse effects occur in surgical patients. METHODS:Systematic review and meta-analysis of trials in which patients were randomly allocated to 6% HES solutions or alternative i.v. fluids in patients undergoing surgery. Ovid Medline, Embase, Cinhal, and Cochrane Database of Systematic Reviews were searched for trials comparing 6% HES with clinically relevant non-starch comparator. The primary end-point was hospital mortality. Secondary endpoints were requirement for renal replacement therapy (RRT) and author-defined AKI. Pre-defined subgroups were cardiac and non-cardiac surgery. RESULTS:Four hundred and fifty-six papers were identified; of which 19 met the inclusion criteria. In total, 1567 patients were included in the analysis. Dichotomous outcomes were expressed as a difference of proportions [risk difference (RD)]. There was no difference in hospital mortality [RD 0.00, 95% confidence interval (CI) -0.02, 0.02], requirement for RRT (RD -0.01, 95% CI -0.04, 0.02), or AKI (RD 0.02, 95% CI -0.02 to 0.06) between compared arms overall or in predefined subgroups. CONCLUSIONS:We did not identify any differences in the incidence of death or AKI in surgical patients receiving 6% HES. Included studies were small with low event rates and low risk of heterogeneity. Narrow CIs suggest that these findings are valid. Given the absence of demonstrable benefit, we are unable to recommend the use of 6% HES solution in surgical patients.

The aim of this study was to evaluate the efficacy of a goal-directed therapy (GDT) protocol designed to augment the oxygen delivery index (DO2I) and to assess the relationship between DO2I measurements and postoperative complications and length of stay.

The aim of this study is to evaluate whether the passive leg raising (PLR) maneuver could be used to predict fluid responsiveness in awake postoperative patients admitted to the ICU. PLR has been demonstrated to be a good indicator of fluid responsiveness even in spontaneously breathing patients, but few data are available in the immediate postoperative period. Nexfin is a new cardiac output monitor that measures and tracks stroke volume (SV) by analyzing the arterial pressure pulse contour noninvasively from a finger probe.

OBJECTIVES:To assess the cumulative costs and consequences of double embryo transfer (DET) or elective single embryo transfer (eSET) in women commencing in vitro fertilisation (IVF) treatment aged 32, 36 and 39 years. DESIGN:Microsimulation model. SETTING:Three assisted reproduction centres in Scotland. SAMPLE:A total of 6153 women undergoing treatment at one of three Scottish IVF clinics, between January 1997 and June 2007. METHODS:A microsimulation model, populated using data inputs derived from a large clinical data set and published literature, was developed to compare the costs and consequences of using eSET or DET over multiple treatment cycles. MAIN OUTCOME MEASURES:Disability-free live births; twin pregnancy rate; women's quality-adjusted life-years (QALYs); health service costs. RESULTS:Not only did DET produce a higher cumulative live birth rate compared with eSET for women of all three ages, but also a higher twin pregnancy rate. Compared with eSET, DET ranged from costing an additional £ 27,356 per extra live birth in women commencing treatment aged 32 years, to costing £ 15,539 per extra live birth in 39-year-old women. DET cost ∼ £ 28,300 and ∼ £ 20,300 per additional QALY in women commencing treatment aged 32 and 39 years, respectively. CONCLUSIONS:Considering the high twin pregnancy rate associated with DET, coupled with uncertainty surrounding QALY gains, eSET is likely to be the preferred option for most women aged ≤ 36 years. The cost-effectiveness of DET improves with age, and may be considered cost-effective in some groups of older women. The decision may best be considered on a case-by-case basis for women aged 37-39 years.

Hospital admission rates attributable to cirrhosis are increasing in the UK. The evidence base for the outcome of critically ill patients with cirrhosis admitted to intensive care (ICU) is currently limited to data from tertiary transplant centres, which report mortality rates of between 45 and 74%. We hypothesised that the disease cohort experienced in secondary care is less severe than that reported in the literature and would subsequently demonstrate lower mortality. We report the prevalence, case mix and outcomes of a dual-centre ICU study in London, UK.

NICOM (Cheetah) is a new non-invasive cardiac output (CO) monitor based on bioreactance. We tested the agreement of NICOM vs LiDCO™ plus in terms of absolute CO values and of the ability to track changes after therapeutic intervention in critically ill patients.

BACKGROUND:Hospital admissions for cirrhosis have been increasing in the United Kingdom, leading to increased pressure on intensive care (ICU) services. Outcome data for patients admitted to ICU are currently limited to transplant centre reports, with mortality rates exceeding 70%. These tertiary reports could fuel a negative bias when patients with cirrhosis are reviewed for ICU admission in secondary care.AIMS:To determine whether disease severity and mortality rates in non-transplant general ICU are less severe than those reported by tertiary datasets.METHODS:A prospective dual-centre non-transplant ICU study. Admissions were screened for cirrhosis and physiological and biochemical data were collected. Disease-specific and critical illness scoring systems were evaluated.RESULTS:Cirrhosis was present in 137/4198 (3.3%) of ICU admissions. ICU and hospital mortality were 38% and 47%, respectively; median age 50 [43-59] years, 68% men, 72% alcoholic cirrhosis, median Child Pugh Score (CPS) 10 [8-11], Model for End-Stage Liver Disease (MELD) 18 [12-24], Acute Physiology and Chronic Health Evaluation II score (APACHE II) 16 [13-22].CONCLUSIONS:Mortality rates and disease staging were notably lower than in the published literature, suggesting that patients have a more favourable outlook than previously considered. Transplant centre data should therefore be interpreted with caution when evaluating the merits of intensive care admission for patients in general secondary care ICUs.

Introduction There is considerable uncertainty about the reproducibility of the various instruments used to measure dyspnea, their ability to reflect changes in symptoms, whether they accurately reflect the patient's experience and if its evolution is similar between acute heart failure syndrome patients and nonacute heart failure syndrome patients.URGENT was a prospective multicenter trial designed to address these issues.Methods Patients were interviewed within 1 hour of first physician evaluation, in the emergency department or acute care setting, with dyspnea assessed by the patient using both a five-point Likert scale and a 10-point visual analog scale (VAS) in the sitting (60º) and then supine (20º) position if dyspnea had not been considered severe or very severe by the sitting versus decubitus dyspnea measurement.Results Very good agreements were found between the five-point Likert and VAS at baseline (0.891, P <0.0001) and between changes (from baseline to hour 6) in the five-point Likert and in VAS (0.800, P <0.0001) in acute heart failure (AHF) patients.Lower agreements were found when changes from baseline to H6 measured by Likert or VAS were compared with the seven-point comparative Likert (0.512 and 0.500 respectively) in AHF patients.The worse the dyspnea at admission, the greater the amplitude of improvement in the first 6 hours; this relationship is stronger when dyspnea is measured with VAS (Spearman's rho coefficient = 0.672) than with the five-point Likert (0.272) (both P <0.0001) in AHF patients.By the five-point Likert, only nine patients (3% (1% to 5%)) reported an improvement in their dyspnea, 177 (51% (46% to 57%)) had no change, and 159 (46% (41% to 52%)) reported worse dyspnea supine compared with sitting up in AHF patients.The PDA test with VAS was markedly different between AHF and non-AHF patients.Conclusions Both clinical tools five-point Likert and VAS showed very good agreement at baseline and between changes from baseline to tests performed 6 hours later in AHF patients.The PDA test with VAS was markedly different between AHF and non-AHF patients.Dyspnea is improved within 6 hours in more than threequarters of the patients regardless of the tool used to measure the change in dyspnea.The greater the dyspnea at admission, the greater the amplitude of improvement in the first 6 hours. P2

BACKGROUND:There is a perception that the prevalence of infertility is on the rise. This study aimed to determine the current prevalence of infertility in a defined geographical population, ascertain changes in self-reported infertility over time and identify risk factors associated with infertility. METHODS:A postal questionnaire survey of a random population-based sample of women aged 31-50 years was performed in the Grampian region of Scotland. Questions addressed the following areas: pregnancy history, length of time taken to become pregnant each time, whether medical advice had been sought and self-reported exposure to factors associated with infertility. RESULTS:Among 4466 women who responded, 400 (9.0%) [95% CI 8.1, 9.8] had chosen not to have children. Of the remaining 4066 women, 3283 (80.7%) [95% CI 79.5, 82.0] reported no difficulties in having children and the remaining 783 (19.3%) [95% CI 18.1, 20.5] had experienced infertility, defined as having difficulty in becoming pregnant for more than 12 months and/or seeking medical advice. In total 398 (9.8%) [95% CI 8.9, 10.7] women had primary infertility, 285 (7.0%) [95% CI 6.2, 7.8] had secondary infertility, 100 (2.5%) [95% CI 2.0, 2.9] had primary as well as secondary infertility. A total of 342 (68.7%) and 208 (73.0%) women with primary and secondary infertility, respectively, sought medical advice and 202 (59.1%) and 118 (56.7%) women in each group subsequently conceived. History of pelvic surgery, Chlamydial infection, endometriosis, chemotherapy, long-term health problems and obesity were associated with infertility. In comparison with a similar survey of women aged 46-50 from the same geographical area, the prevalence of both primary infertility (>24 months) [70/1081, (6.5%) versus 68/710 (9.6%) P = 0.02] and secondary infertility [29/1081 (2.7%) versus 40/710 (5.6%) P = 0.002] were significantly lower. CONCLUSIONS:Nearly one in five women attempting conception sampled in this study experienced infertility, although over half of them eventually conceived. Fertility problems were associated with endometriosis, Chlamydia trachomatis infection and pelvic surgery, as well as obesity, chemotherapy and some long-term chronic medical conditions. There is no evidence of an increase in the prevalence of infertility in this population over the past 20 years.

Dynamic testing of muscle tissue oxygenation (StO2) with near-infrared spectroscopy and vascular occlusion (VOT) has been used to study pathophysiological states, but there is a paucity of data for standardised techniques in normal subjects. Three-minute VOT is frequently described. We have collected StO2 data for this technique and compared them with a shorter 2-minute test.

We have previously demonstrated that an average of at least two curves is necessary to improve the calibration of the lithium dilution technique of the LiDCO™plus. The precision of the new calibration process is able to detect a least significant change (LSC) of 17% [1]. The primary aim of this study was to evaluate the drift after an initial calibration with two lithium dilution curves. The second aim of the study was to evaluate the relationship between the magnitude of the time to recalibration and the magnitude of the drift.