Conducting Virtual Qualitative Interviews with International Key Informants: Insights from a Research Project

There is an increasing need for cross-cultural qualitative studies in an era of globalization. A focus group of five researchers, who were involved in a large international research project, identified effective strategies and challenges associated with five key domains of qualitative research with key informants: identification, recruitment, preparation, conducting the interview, and follow-up. Content analysis revealed nuanced tactics related to effective strategies and challenges associated with each domain. Examples of effective strategies include interview preparation to understand the specific expertise of the interviewee and allowing the informant to offer additional information beyond the questions asked. Challenges included technical difficulties with virtual platforms and scheduling interviews in multiple time zones. These findings provide practical guidelines for researchers conducting virtual interviews with international key informants

Modeling payback from research into the efficacy of left-ventricular assist devices as destination therapy

Objectives: Ongoing developments in design have improved the outlook for left-ventricular assist device (LVAD) implantation as a therapy in end-stage heart failure. Nevertheless, early cost-effectiveness assessments, based on first-generation devices, have not been encouraging. Against this background, we set out (i) to examine the survival benefit that LVADs would need to generate before they could be deemed cost-effective; (ii) to provide insight into the likelihood that this benefit will be achieved; and (iii) from the perspective of a healthcare provider, to assess the value of discovering the actual size of this benefit by means of a Bayesian value of information analysis. Methods: Cost-effectiveness assessments are made from the perspective of the healthcare provider, using current UK norms for the value of a quality-adjusted life-year (QALY). The treatment model is grounded in published analyses of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial of first-generation LVADs, translated into a UK cost setting. The prospects for patient survival with second-generation devices is assessed using Bayesian prior distributions, elicited from a group of leading clinicians in the field. Results: Using established thresholds, cost-effectiveness probabilities under these priors are found to be low (.2 percent) for devices costing as much as £60,000. Sensitivity of the conclusions to both device cost and QALY valuation is examined. Conclusions: In the event that the price of the device in use would reduce to £40,000, the value of the survival information can readily justify investment in further trials

The effect of carbohydrate dose and timing on timed effort and time to exhaustion within a simulated cycle race in male professional cyclists

A key performance limitation affecting professional endurance cycling is carbohydrate storage and utilisation (Pöchmüller, Schwingshack, Colombani & Hoffmann, 2016, Journal of the International Society of Sports Nutrition, 13). Muscle glycogen stores alone are inefficient at maintaining optimal blood glucose levels beyond two hours of exercise; consequently, exogenous CHO is commonly used to counteract this (Jeukendrup, 2011, Journal of Sports Sciences, 21, 91-99). High concentrations of CHO can cause drops in blood glucose, excessive glycogen utilisation and gastrointestinal discomfort (GID) (Jeukendrup, 2011). Therefore, the aim of this study was to determine if frequent, smaller CHO feedings would be preferable to large, bolus CHO feedings on time trial cycling performance. With institutional ethics approval, 5 professional cyclists completed a 4h simulated cycle ride with 3 timed efforts in a randomised, cross-over, double blind design study. Each timed effort occurred in the last 10 min of each hour (TE1, TE2, TE3); participants were asked to cycle with maximum effort for this time. There was also a final effort at the end of the 4th hour to replicate a sprint finish. This was measured as time to exhaustion (TTE). Two interventions were used; a frequent feed (F) where participants drank 20g maltodextrin in 300ml flavoured water solution 3 times per hour and a bolus feed (B) where participants drank 60g maltodextrin solution once per hour. Heart rate, power output, GID, perceived exertion (RPE), blood lactate and blood glucose were recorded before and after TE1, TE2, TE3 and TTE. Wilcoxen signed rank test and Cohen’s D was performed to study differences between interventions and effect sizes.In the F intervention, average watts were significantly higher at TE2 (P<0.05 d=0.75) and TE3 (P<0.05 d=1.21) and the RPE was lower TE1 (P≥0.05 d=1.12), TE2 (P<0.05, d=1.12) and TTE (P≥0.05 d=1.12) compared to B. There was no significant difference between any other variables. The results suggest that despite power output being higher, RPE was lower in the F intervention. Gut absorption of CHO is limited to 1g/h (Jeukendrup, 2011), which may help explain these findings. This is one of the first studies to look at concentration and timing of CHO consumption in endurance cycling. Regular feeds of 20g CHO may be more beneficial on power output and RPE in endurance cycling compared to hourly 60g feeds

The effects of diesel exhaust pollution on floral volatiles and the consequences for honey bee olfaction

There is growing evidence of a substantial decline in pollinators within Europe and North America, most likely caused by multiple factors such as diseases, poor nutrition, habitat loss, insecticides, and environmental pollution. Diesel exhaust could be a contributing factor to this decline, since we found that diesel exhaust rapidly degrades floral volatiles, which honey bees require for flower recognition. In this study, we exposed eight of the most common floral volatiles to diesel exhaust in order to investigate whether it can affect volatile mediated plant-pollinator interaction. Exposure to diesel exhaust altered the blend of common flower volatiles significantly: myrcene was considerably reduced, β-ocimene became undetectable, and β-caryophyllene was transformed into its cis-isomer isocaryophyllene. Proboscis extension response (PER) assays showed that the alterations of the blend reduced the ability of honey bees to recognize it. The chemically reactive nitrogen oxides fraction of diesel exhaust gas was identified as capable of causing degradation of floral volatiles

Ocular toxoplasmosis: phenotype differences between toxoplasma IgM positive and IgM negative patients in a large cohort

Purpose: To investigate the differences in demographics and clinical characteristics of patients diagnosed with ocular toxoplasmosis according to their IgM status. Methods: Retrospective case note analysis was carried out on patients who tested positive for serum Toxoplasma gondii-specific IgM antibodies (IgM+) as well as a comparator group who tested negative for serum IgM (IgM-), but positive for serum IgG. Patient demographics and clinical features were compared between the two groups to evaluate for any significant differences. Results: One hundred and six patients were included in the study between March 2011 and June 2018, consisting of 37 in the IgM +group and 69 in the IgM- group. Patients in the IgM +group were significantly older (51.1 vs 34.1 years, p<0.0001), more likely to present with central macular lesions (32% vs 12%, p=0.012), and more likely to develop rhegmatogenous retinal detachment (11% vs 1%, p=0.049). In contrast, patients in the IgM- group were more likely present with pain (20% vs 3%, 0.017) and exhibit more severe inflammation of the anterior chamber and vitreous (p<0.05). Overall, retinal lesions were more likely to be superotemporal (55%) and superonasal (31%). Furthermore, age was associated with larger (p=0.003) and more peripheral lesions (p=0.007). Conclusions: This study demonstrated significant differences in clinical characteristics of ocular toxoplasmosis according to serum IgM status. IgM+ patients were older, less likely to report pain, had lower levels of intraocular inflammation, but were more likely to have macular involvement. We also found age to be correlated with larger and more peripheral lesions

Sample size calculations for cluster randomised controlled trials with a fixed number of clusters

Background\ud Cluster randomised controlled trials (CRCTs) are frequently used in health service evaluation. Assuming an average cluster size, required sample sizes are readily computed for both binary and continuous outcomes, by estimating a design effect or inflation factor. However, where the number of clusters are fixed in advance, but where it is possible to increase the number of individuals within each cluster, as is frequently the case in health service evaluation, sample size formulae have been less well studied. \ud \ud Methods\ud We systematically outline sample size formulae (including required number of randomisation units, detectable difference and power) for CRCTs with a fixed number of clusters, to provide a concise summary for both binary and continuous outcomes. Extensions to the case of unequal cluster sizes are provided. \ud \ud Results\ud For trials with a fixed number of equal sized clusters (k), the trial will be feasible provided the number of clusters is greater than the product of the number of individuals required under individual randomisation ($n_i$) and the estimated intra-cluster correlation ($\rho$). So, a simple rule is that the number of clusters ($\kappa$) will be sufficient provided: \ud \ud $\kappa$ > $n_i$ x $\rho$\ud \ud Where this is not the case, investigators can determine the maximum available power to detect the pre-specified difference, or the minimum detectable difference under the pre-specified value for power. \ud \ud Conclusions\ud Designing a CRCT with a fixed number of clusters might mean that the study will not be feasible, leading to the notion of a minimum detectable difference (or a maximum achievable power), irrespective of how many individuals are included within each cluster. \ud \u

Evidence of methodological bias in hospital standardised mortality ratios: retrospective database study of English hospitals

Objective To assess the validity of case mix adjustment methods used to derive standardised mortality ratios for hospitals, by examining the consistency of relations between risk factors and mortality across hospitals

Vascular endothelial growth factor-D over-expressing tumor cells induce differential effects on uterine vasculature in a mouse model of endometrial cancer

BACKGROUND: It has been hypothesised that increased VEGF-D expression may be an independent prognostic factor for endometrial cancer progression and lymph node metastasis; however, the mechanism by which VEGF-D may promote disease progression in women with endometrial cancer has not been investigated. Our aim was to describe the distribution of lymphatic vessels in mouse uterus and to examine the effect of VEGF-D over-expression on these vessels in a model of endometrial cancer. We hypothesised that VEGF-D over-expression would stimulate growth of new lymphatic vessels into the endometrium, thereby contributing to cancer progression. METHODS: We initially described the distribution of lymphatic vessels (Lyve-1, podoplanin, VEGFR-3) and VEGF-D expression in the mouse uterus during the estrous cycle, early pregnancy and in response to estradiol-17beta and progesterone using immunohistochemistry. We also examined the effects of VEGF-D over-expression on uterine vasculature by inoculating uterine horns in NOD SCID mice with control or VEGF-D-expressing 293EBNA tumor cells. RESULTS: Lymphatic vessels positive for the lymphatic endothelial cell markers Lyve-1, podoplanin and VEGFR-3 profiles were largely restricted to the connective tissue between the myometrial circular and longitudinal muscle layers; very few lymphatic vessel profiles were observed in the endometrium. VEGF-D immunostaining was present in all uterine compartments (epithelium, stroma, myometrium), although expression was generally low. VEGF-D immunoexpression was slightly but significantly higher in estrus relative to diestrus; and in estradiol-17beta treated mice relative to vehicle or progesterone treated mice. The presence of VEGF-D over-expressing tumor cells did not induce endometrial lymphangiogenesis, although changes were observed in existing vessel profiles. For myometrial lymphatic and endometrial blood vessels, the percentage of profiles containing proliferating endothelial cells, and the cross sectional area of vessel profiles were significantly increased in response to VEGF-D in comparison to control tumor cells. In contrast, no significant changes were noted in myometrial blood vessels. In addition, examples of invading cells or tumor emboli were observed in mice receiving VEGF-D expressing 293EBNA cells. CONCLUSIONS: These results illustrate that VEGF-D over-expression has differential effects on the uterine vasculature. These effects may facilitate VEGF-D's ability to promote endometrial cancer metastasis and disease progression

Placental growth factor testing for suspected pre‐eclampsia: a cost‐effectiveness analysis

Objective To calculate the cost‐effectiveness of implementing PlGF testing alongside a clinical management algorithm in maternity services in the UK, compared with current standard care. Design Cost‐effectiveness analysis. Setting Eleven maternity units participating in the PARROT stepped‐wedge cluster‐randomised controlled trial. Population Women presenting with suspected pre‐eclampsia between 20+0 and 36+6 weeks’ gestation. Methods Monte Carlo simulation utilising resource use data and maternal adverse outcomes. Main outcome measures Cost per maternal adverse outcome prevented. Results Clinical care with PlGF testing costs less than current standard practice and resulted in fewer maternal adverse outcomes. There is a total cost‐saving of UK£149 per patient tested, when including the cost of the test. This represents a potential cost‐saving of UK£2,891,196 each year across the NHS in England. Conclusions Clinical care with PlGF testing is associated with the potential for cost‐savings per participant tested when compared with current practice via a reduction in outpatient attendances, and improves maternal outcomes. This economic analysis supports a role for implementation of PlGF testing in antenatal services for the assessment of women with suspected pre‐eclampsia. Tweetable abstract Placental growth factor testing for suspected pre‐eclampsia is cost‐saving and improves maternal outcomes

Global trends in ultraprocessed food and drink product sales and their association with adult body mass index trajectories

This study evaluated global trends in ultraprocessed food and drink (UPFD) volume sales/capita and associations with adult body mass index (BMI) trajectories. Total food/drink volume sales/capita from Euromonitor for 80 countries (2002‐2016) were matched to mean adult BMI from the NCD Risk Factor Collaboration (2002‐2014). Products were classified as UPFD/non‐UPFD according to the NOVA classification system. Mixed models for repeated measures were used to analyse associations between UPFD volume sales/capita and adult BMI trajectories, controlling for confounding factors. The increase in UPF volume sales was highest for South and Southeast Asia (67.3%) and North Africa and the Middle East (57.6%), while for UPD, the increase was highest for South and Southeast Asia (120.0%) and Africa (70.7%). In 2016, baked goods were the biggest contributor to UPF volume sales (13.1%‐44.5%), while carbonated drinks were the biggest contributor to UPD volume sales (40.2%‐86.0%). For every standard deviation increase (51 kg/capita, 2002) in UPD volume sales, mean BMI increased by 0.195 kg/m2 for men (P < .001) and 0.072 kg/m2 for women (P = .003). For every standard deviation (40 kg/capita, 2002) increase in UPF volume sales, mean BMI increased by 0.316 kg/m2 for men (P < .001), while the association was not significant for women. Increases in UPFD volume sales/capita were positively associated with population‐level BMI trajectories