Beyond mobile apps: a survey of technologies for mental well-being

Mental health problems are on the rise globally and strain national health systems worldwide. Mental disorders are closely associated with fear of stigma, structural barriers such as financial burden, and lack of available services and resources which often prohibit the delivery of frequent clinical advice and monitoring. Technologies for mental well-being exhibit a range of attractive properties, which facilitate the delivery of state-of-the-art clinical monitoring. This review article provides an overview of traditional techniques followed by their technological alternatives, sensing devices, behaviour changing tools, and feedback interfaces. The challenges presented by these technologies are then discussed with data collection, privacy, and battery life being some of the key issues which need to be carefully considered for the successful deployment of mental health toolkits. Finally, the opportunities this growing research area presents are discussed including the use of portable tangible interfaces combining sensing and feedback technologies. Capitalising on the data these ubiquitous devices can record, state of the art machine learning algorithms can lead to the development of robust clinical decision support tools towards diagnosis and improvement of mental well-being delivery in real-time

Estimated number and percentage of US adults with atherosclerotic cardiovascular disease recommended add-on lipid-lowering therapy by the 2018 AHA/ACC multi-society cholesterol guideline

Study objective: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline recommends a maximally-tolerated statin with add-on lipid-lowering therapy, ezetimibe and/or proprotein convertase subtilisin/kexin type 9 (PCSK9) for adults with very-high atherosclerotic cardiovascular disease (ASCVD) risk to achieve a low-density lipoprotein cholesterol (LDL-C) <70 mg/dL. We estimated the percentage of US adults with ASCVD recommended, by the 2018 AHA/ACC cholesterol guideline, and receiving add-on lipid-lowering therapy. Design, setting, and participants: Cross-sectional study including 805 participants from the US National Health and Nutrition Examination Survey (NHANES) 2013–2020 data. NHANES sampling weights were used to obtain estimates for the US adult population. Main measures: Very-high ASCVD risk was defined as either: ≥2 ASCVD events, or one ASCVD event with ≥2 high-risk conditions. Being recommended add-on lipid-lowering therapy was defined as having very-high ASCVD risk and LDL-C ≥ 70 mg/dL, or LDL-C < 70 mg/dL while taking ezetimibe or a PCSK9 inhibitor. Results: An estimated 18.7 (95%CI, 16.0–21.4) million US adults had ASCVD, of whom 81.6 % (95%CI, 76.7 %–86.4 %) had very-high ASCVD risk, and 60.1 % (95%CI, 54.5 %–65.7 %) had very-high ASCVD risk and LDL-C ≥ 70 mg/dL. Overall, 61.4 % (95%CI, 55.8 %–66.9 %) were recommended add-on lipid-lowering therapy and 3.2 % (95 % CI, 1.2 %–5.3 %) were taking it. Smokers, adults with diabetes, hypertension and chronic kidney disease were more likely, while those taking atorvastatin or rosuvastatin were less likely, to be recommended add-on lipid-lowering therapy. Conclusion: The majority of US adults with ASCVD are recommended add-on lipid-lowering therapy by the 2018 AHA/ACC cholesterol guideline but few are receiving it

Sex Differences in the Risk of Coronary Heart Disease Associated With Type 2 Diabetes: A Mendelian Randomization Analysis

OBJECTIVE: Observational studies have demonstrated that type 2 diabetes is a stronger risk factor for coronary heart disease (CHD) in women compared with men. However, it is not clear whether this reflects a sex differential in the causal effect of diabetes on CHD risk or results from sex-specific residual confounding. RESEARCH DESIGN AND METHODS: Using 270 single nucleotide polymorphisms (SNPs) for type 2 diabetes identified in a type 2 diabetes genome-wide association study, we performed a sex-stratified Mendelian randomization (MR) study of type 2 diabetes and CHD using individual participant data in UK Biobank (251,420 women and 212,049 men). Weighted median, MR-Egger, MR-pleiotropy residual sum and outlier, and radial MR from summary-level analyses were used for pleiotropy assessment. RESULTS: MR analyses showed that genetic risk of type 2 diabetes increased the odds of CHD for women (odds ratio 1.13 [95% CI 1.08–1.18] per 1-log unit increase in odds of type 2 diabetes) and men (1.21 [1.17–1.26] per 1-log unit increase in odds of type 2 diabetes). Sensitivity analyses showed some evidence of directional pleiotropy; however, results were similar after correction for outlier SNPs. CONCLUSIONS: This MR analysis supports a causal effect of genetic liability to type 2 diabetes on risk of CHD that is not stronger for women than men. Assuming a lack of bias, these findings suggest that the prevention and management of type 2 diabetes for CHD risk reduction is of equal priority in both sexes

Stimulation of Na⁺/H⁺ Exchanger Isoform 1 Promotes Microglial Migration

Regulation of microglial migration is not well understood. In this study, we proposed that Na+/H+ exchanger isoform 1 (NHE-1) is important in microglial migration. NHE-1 protein was co-localized with cytoskeletal protein ezrin in lamellipodia of microglia and maintained its more alkaline intracellular pH (pHi). Chemoattractant bradykinin (BK) stimulated microglial migration by increasing lamellipodial area and protrusion rate, but reducing lamellipodial persistence time. Interestingly, blocking NHE-1 activity with its potent inhibitor HOE 642 not only acidified microglia, abolished the BK-triggered dynamic changes of lamellipodia, but also reduced microglial motility and microchemotaxis in response to BK. In addition, NHE-1 activation resulted in intracellular Na+ loading as well as intracellular Ca2+ elevation mediated by stimulating reverse mode operation of Na+/Ca2+ exchange (NCXrev). Taken together, our study shows that NHE-1 protein is abundantly expressed in microglial lamellipodia and maintains alkaline pHi in response to BK stimulation. In addition, NHE-1 and NCXrev play a concerted role in BK-induced microglial migration via Na+ and Ca2+ signaling. © 2013 Shi et al

Acute Treatment Effects on GFR in Randomized Clinical Trials of Kidney Disease Progression

Background Acute changes in GFR can occur after initiation of interventions targeting progression of CKD. These acute changes complicate the interpretation of long-term treatment effects. Methods To assess the magnitude and consistency of acute effects in randomized clinical trials and explore factors that might affect them, we performed a meta-analysis of 53 randomized clinical trials for CKD progression, enrolling 56,413 participants with at least one estimated GFR measurement by 6 months after randomization. We defined acute treatment effects as the mean difference in GFR slope from baseline to 3 months between randomized groups. We performed univariable and multivariable metaregression to assess the effect of intervention type, disease state, baseline GFR, and albuminuria on the magnitude of acute effects. Results The mean acute effect across all studies was 20.21 ml/min per 1.73 m2 (95% confidence interval, 20.63 to 0.22) over 3 months, with substantial heterogeneity across interventions (95% coverage interval across studies, 22.50 to 12.08 ml/min per 1.73 m2). We observed negative average acute effects in renin angiotensin system blockade, BP lowering, and sodium-glucose cotransporter 2 inhibitor trials, and positive acute effects in trials of immunosuppressive agents. Larger negative acute effects were observed in trials with a higher mean baseline GFR. Conclusion The magnitude and consistency of acute GFR effects vary across different interventions, and are larger at higher baseline GFR. Understanding the nature and magnitude of acute effects can help inform the optimal design of randomized clinical trials evaluating disease progression in CKD

The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) Study: Trial Design and Baseline Characteristics

Introduction: Despite optimal current care, up to 30% of individuals suffering from immunoglobulin A nephropathy (IgAN) will develop kidney failure requiring dialysis or kidney transplantation. The Therapeutic Evaluation of STeroids in IgA Nephropathy Global (TESTING) study was designed to assess the benefits and risks of steroids in people with IgAN. We report the trial design as well as the baseline characteristics of study participants. Methods: It is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized trial of individuals with kidney biopsy-confirmed IgAN, proteinuria ≥1 g/day, and an estimated GFR of 20-120 mL/min/1.73 m2, following at least 3 months of standard of care including maximum labelled (or tolerated) dose of renin-angiotensin system blockade. The original study design randomized participants 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/day, maximum 48 mg/day) for 2 months, with subsequent weaning by 8 mg/day/month over 6-8 months, or matching placebo. The intervention was modified in 2016 (due to an excess of serious infection) to low-dose methylprednisolone (0.4 mg/kg/day, maximum 32 mg/day) for 2 months, followed by weaning by 4 mg/day/month over 6-9 months, or matching placebo. Participants recruited after 2016 also received prophylaxis against Pneumocystis jirovecii pneumonia during the first 12 weeks of treatment. Results: The study recruitment period extended from May 2012 to November 2019. By the time the excess of serious infections was observed, 262 participants had been randomized to the original full-dose treatment algorithm, and an interim analysis was reported in 2016. Subsequently, 241 additional participants were randomized to a revised low-dose protocol, for a total of 503 participants from China (373), India (78), Canada (24), Australia (18), and Malaysia (10). The mean age of randomized participants was 38, 39% were female, mean eGFR at randomization was 62.7 mL/min/1.73 m2, and mean 24-h urine protein 2.54 g. The primary endpoint is a composite of 40% eGFR decline from baseline or kidney failure (dialysis, transplantation, or death due to kidney disease), and participants will be followed until the primary outcome has been observed in at least 160 randomized participants. Analyses will also be made across predefined subgroups. Effects on eGFR slope and albuminuria will also be assessed overall, as well as by the steroid dosing regimen. Conclusions: The TESTING study (combined full and low dose) will define the benefits of corticosteroid use on major kidney outcomes, as well as the risks of therapy, and provide data on the relative effects of different doses, in individuals with high-risk IgAN

The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) Study: Trial Design and Baseline Characteristics

INTRODUCTION: Despite optimal current care, up to 30% of individuals suffering from immunoglobulin A nephropathy (IgAN) will develop kidney failure requiring dialysis or kidney transplantation. The Therapeutic Evaluation of STeroids in IgA Nephropathy Global (TESTING) study was designed to assess the benefits and risks of steroids in people with IgAN. We report the trial design as well as the baseline characteristics of study participants. METHODS: It is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized trial of individuals with kidney biopsy-confirmed IgAN, proteinuria ≥1 g/day, and an estimated GFR of 20-120 mL/min/1.73 m2, following at least 3 months of standard of care including maximum labelled (or tolerated) dose of renin-angiotensin system blockade. The original study design randomized participants 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/day, maximum 48 mg/day) for 2 months, with subsequent weaning by 8 mg/day/month over 6-8 months, or matching placebo. The intervention was modified in 2016 (due to an excess of serious infection) to low-dose methylprednisolone (0.4 mg/kg/day, maximum 32 mg/day) for 2 months, followed by weaning by 4 mg/day/month over 6-9 months, or matching placebo. Participants recruited after 2016 also received prophylaxis against Pneumocystis jirovecii pneumonia during the first 12 weeks of treatment. RESULTS: The study recruitment period extended from May 2012 to November 2019. By the time the excess of serious infections was observed, 262 participants had been randomized to the original full-dose treatment algorithm, and an interim analysis was reported in 2016. Subsequently, 241 additional participants were randomized to a revised low-dose protocol, for a total of 503 participants from China (373), India (78), Canada (24), Australia (18), and Malaysia (10). The mean age of randomized participants was 38, 39% were female, mean eGFR at randomization was 62.7 mL/min/1.73 m2, and mean 24-h urine protein 2.54 g. The primary endpoint is a composite of 40% eGFR decline from baseline or kidney failure (dialysis, transplantation, or death due to kidney disease), and participants will be followed until the primary outcome has been observed in at least 160 randomized participants. Analyses will also be made across predefined subgroups. Effects on eGFR slope and albuminuria will also be assessed overall, as well as by the steroid dosing regimen. CONCLUSIONS: The TESTING study (combined full and low dose) will define the benefits of corticosteroid use on major kidney outcomes, as well as the risks of therapy, and provide data on the relative effects of different doses, in individuals with high-risk IgAN

A Comparative Assessment of Non-Laboratory-Based versus Commonly Used Laboratory-Based Cardiovascular Disease Risk Scores in the NHANES III Population

National and international primary CVD risk screening guidelines focus on using total CVD risk scores. Recently, we developed a non-laboratory-based CVD risk score (inputs: age, sex, smoking, diabetes, systolic blood pressure, treatment of hypertension, body-mass index), which can assess risk faster and at lower costs compared to laboratory-based scores (inputs include cholesterol values). We aimed to assess the exchangeability of the non-laboratory-based risk score to four commonly used laboratory-based scores (Framingham CVD [2008, 1991 versions], and Systematic COronary Risk Evaluation [SCORE] for low and high risk settings) in an external validation population.Analyses were based on individual-level, score-specific rankings of risk for adults in the Third National Health and Nutrition Examination Survey (NHANES III) aged 25–74 years, without history of CVD or cancer (n = 5,999). Risk characterization agreement was based on overlap in dichotomous risk characterization (thresholds of 10-year risk >10–20%) and Spearman rank correlation. Risk discrimination was assessed using receiver operator characteristic curve analysis (10-year CVD death outcome). Risk characterization agreement ranged from 91.9–95.7% and 94.2–95.1% with Spearman correlation ranges of 0.957–0.980 and 0.946–0.970 for men and women, respectively. In men, c-statistics for the non-laboratory-based, Framingham (2008, 1991), and SCORE (high, low) functions were 0.782, 0.776, 0.781, 0.785, and 0.785, with p-values for differences relative to the non-laboratory-based score of 0.44, 0.89, 0.68 and 0.65, respectively. In women, the corresponding c-statistics were 0.809, 0.834, 0.821, 0.792, and 0.792, with corresponding p-values of 0.04, 0.34, 0.11 and 0.09, respectively.Every score discriminated risk of CVD death well, and there was high agreement in risk characterization between non-laboratory-based and laboratory-based risk scores, which suggests that the non-laboratory-based score can be a useful proxy for Framingham or SCORE functions in resource-limited settings. Future external validation studies can assess whether the sex-specific risk discrimination results hold in other populations

The risk of angiosarcoma following primary breast cancer

Lymphangiosarcoma of the upper extremity is a rare and aggressive tumour reported to occur following post-mastectomy lymphoedema (Stewart–Treves syndrome). Haemangiosarcoma, a related rare tumour, has occasionally been reported to occur in the breast following irradiation. We conducted a case-control study using the University of Southern California-Cancer Surveillance Program, the population-based cancer registry for Los Angeles County, to evaluate the relationship between invasive female breast cancer and subsequent upper extremity or chest lymphangiosarcoma and haemangiosarcoma together referred to as angiosarcoma. Cases were females diagnosed between 1972 and 1995 with angiosarcoma of the upper extremity (n = 20) or chest (n = 48) who were 25 years of age or older and residing in Los Angeles County when diagnosed. Other sarcomas at the same anatomic sites were also studied. Controls were females diagnosed with cancers other than sarcoma during the same time period (n = 266 444). Cases and controls were then compared with respect to history of a prior invasive epithelial breast cancer. A history of breast cancer increased the risk of upper extremity angiosarcoma by more than 59-fold (odds ratio [OR] = 59.3, 95% confidence interval [95% CI] = 21.9–152.8). A strong increase in risk after breast cancer was also observed for angiosarcoma of the chest and breast (OR = 11.6, 95% CI = 4.3–26.1) and for other sarcomas of the chest and breast (OR = 3.3, 95% CI = 1.1–1.7). © 1999 Cancer Research Campaig