The Myth Of Making Inferences For An Overall Treatment Efficacy With Data From Multiple Comparative Studies Via Meta-analysis

Meta analysis techniques, if applied appropriately, can provide a summary of the totality of evidence regarding an overall difference between a new treatment and a control group using data from multiple comparative clinical studies. The standard meta analysis procedures, however, may not give a meaningful between-group difference summary measure or identify a meaningful patient population of interest, especially when the fixed effect model assumption is not met. Moreover, a single between-group comparison measure without a reference value obtained from patients in the control arm would likely not be informative enough for clinical decision making. In this paper, we propose a simple, robust procedure based on a mixture population concept and provide a clinically meaningful group contrast summary for a well-defined target population. We use the data from a recent meta analysis for evaluating statin therapies with respect to the incidence of fatal stroke events to illustrate the issues associated with the standard meta analysis procedures as well as the advantages of our simple proposal

Prevalence of prediabetes and undiagnosed diabetes in patients with HFpEF and HFrEF and associated clinical outcomes

Purpose: The prevalence and consequences of prediabetic dysglycemia and undiagnosed diabetes is unknown in patients with heart failure (HF) and preserved ejection fraction (HFpEF) and has not been compared to heart failure and reduced ejection fraction (HFrEF). Methods: We examined the prevalence and outcomes associated with normoglycemia, prediabetic dysglycemia and diabetes (diagnosed and undiagnosed) among individuals with a baseline glycated hemoglobin (hemoglobin A1c, HbA1c) measurement stratified by HFrEF or HFpEF in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity programme (CHARM). We studied the primary outcome of HF hospitalization or cardiovascular (CV) death, and all-cause death, and estimated hazard ratios (HR) by use of multivariable Cox regression models. Results: HbA1c was measured at baseline in CHARM patients enrolled in the USA and Canada and was available in 1072/3023 (35%) of patients with HFpEF and 1578/4576 (34%) patients with HFrEF. 18 and 16% had normoglycemia (HbA1c < 6.0), 20 and 22% had prediabetes (HbA1c 6.0–6.4), respectively. Finally among patients with HFpEF 22% had undiagnosed diabetes (HbA1c > 6.4), and 40% had known diabetes (any HbA1c), with corresponding prevalence among HFrEF patients being 26 and 35%. The rates of both clinical outcomes of interest were higher in patients with undiagnosed diabetes and prediabetes, compared to normoglycemic patients, irrespective of HF subtype, and in general higher among HFrEF patients. For the primary composite outcome among HFpEF patients, the HRs were 1.02 (95% CI 0.63–1.65) for prediabetes, HR 1.18 (0.75–1.86) for undiagnosed diabetes and 2.75 (1.83–4.11) for known diabetes, respectively, p value for trend across groups < 0.001. Dysglycemia was also associated with worse outcomes in HFrEF. Conclusions: These findings confirm the remarkably high prevalence of dysglycemia in heart failure irrespective of ejection fraction phenotype, and demonstrate that dysglycemia is associated with a higher risk of adverse clinical outcomes, even before the diagnosis of diabetes and institution of glucose lowering therapy in patients with HFpEF as well as HFrEF

Attentional modulation of crowding

Outside the fovea, the visual system pools features of adjacent stimuli. Left or right of fixation the tilt of an almost horizontal Gabor pattern becomes difficult to classify when horizontal Gabors appear above and below it. Classification is even harder when flankers are to the left and right of the target. With all four flankers present, observers were required both to classify the target’s tilt and perform a spatial frequency task on two of the four flankers. This dual task proved significantly more difficult when attention was directed to the horizontally aligned flankers. We suggest that covert attention to stimuli can increase the weights of their pooled features

The role of brand loyalty and social media in e-commerce interfaces: survey results and implications for user interfaces

This paper explores the role of brand loyalty and social media in e-commerce interfaces. A survey consisting of 118 respondents was contacted to address the questions relating to online shopping and brand loyalty. Link between the frequency of access and time spent on an e-commerce user interface, and brand loyalty, gender and age profile differences, and the role of social media to branding and on-line shopping was analyzed. It was found that online loyalty differs from offline loyalty and loyalty also differed across genders, showing men were more loyal than women when shopping online. Information shared about products on social media by friends and family played an important role in purchase decision making. Website interface and ease of navigation were also key aspects for online shopping. The research concluded with recommendations to create multimodal websites which are more interactive and targeted so customer experience is enhanced and loyalty is achieved through the use of interactivity and social media

Outer-Sphere Contributions to the Electronic Structure of Type Zero Copper Proteins

Bioinorganic canon states that active-site thiolate coordination promotes rapid electron transfer (ET) to and from type 1 copper proteins. In recent work, we have found that copper ET sites in proteins also can be constructed without thiolate ligation (called “type zero” sites). Here we report multifrequency electron paramagnetic resonance (EPR), magnetic circular dichroism (MCD), and nuclear magnetic resonance (NMR) spectroscopic data together with density functional theory (DFT) and spectroscopy-oriented configuration interaction (SORCI) calculations for type zero Pseudomonas aeruginosa azurin variants. Wild-type (type 1) and type zero copper centers experience virtually identical ligand fields. Moreover, O-donor covalency is enhanced in type zero centers relative that in the C112D (type 2) protein. At the same time, N-donor covalency is reduced in a similar fashion to type 1 centers. QM/MM and SORCI calculations show that the electronic structures of type zero and type 2 are intimately linked to the orientation and coordination mode of the carboxylate ligand, which in turn is influenced by outer-sphere hydrogen bonding

Loneliness, coping, suicidal thoughts and self-harm during the COVID-19 pandemic: a repeat cross-sectional UK population survey

Objectives: There has been speculation on the impact of the COVID-19 pandemic and the associated lockdown on suicidal thoughts and self-harm and the factors associated with any change. We aimed to assess the effects and change in effects of risk factors including loneliness and coping, as well as pre-existing mental health conditions on suicidal thoughts and self-harm during the COVID-19 pandemic. Design: This study was a repeated cross-sectional online population-based survey. Participants and measures: Non-probability quota sampling was adopted on the UK adult population and four waves of data were analysed during the pandemic (17 March 2020 to 29 May 2020). Outcomes were suicidal thoughts and self-harm associated with the pandemic while loneliness, coping, pre-existing mental health conditions, employment status and demographics were covariates. We ran binomial regressions to evaluate the adjusted risks of the studied covariates as well as the changes in effects over time. Results: The proportion of individuals who felt lonely increased sharply from 9.8% to 23.9% after the UK lockdown began. Young people (aged 18–24 years), females, students, those who were unemployed and individuals with pre-existing mental health conditions were more likely to report feeling lonely and not coping well. 7.7%–10.0% and 1.9%–2.2% of respondents reported having suicidal thoughts and self-harm associated with the pandemic respectively throughout the period studied. Results from cross-tabulation and adjusted regression analyses showed young adults, coping poorly and with pre-existing mental health conditions were significantly associated with suicidal thoughts and self-harm. Loneliness was significantly associated with suicidal thoughts but not self-harm. Conclusions: The association between suicidality, loneliness and coping was evident in young people during the early stages of the pandemic. Developing effective interventions designed and coproduced to address loneliness and promote coping strategies during prolonged social isolation may promote mental health and help mitigate suicidal thoughts and self-harm associated with the pandemic