Weight-modification trials in older adults: what should the outcome measure be?

BACKGROUND: Overweight older adults are often counseled to lose weight, even though there is little evidence of excess mortality in that age group. Overweight and underweight may be more associated with health status than with mortality, but few clinical trials of any kind have been based on maximizing years of healthy life (YHL), as opposed to years of life (YOL). OBJECTIVE: This paper examines the relationship of body mass index (BMI) to both YHL and YOL. Results were used to determine whether clinical trials of weight-modification based on improving YHL would be more powerful than studies based on survival. DESIGN: We used data from a cohort of 4,878 non-smoking men and women aged 65–100 at baseline (mean age 73) and followed 7 years. We estimated mean YHL and YOL in four categories of BMI: underweight, normal, overweight, and obese. RESULTS: Subjects averaged 6.3 YOL and 4.6 YHL of a possible 7 years. Both measures were higher for women and whites. For men, none of the BMI groups was significantly different from the normal group on either YOL or YHL. For women, the obese had significantly lower YHL (but not YOL) than the normals, and the underweight had significantly lower YOL and YHL. The overweight group was not significantly different from the normal group on either measure. CONCLUSIONS: Clinical trials of weight loss interventions for obese older women would require fewer participants if YHL rather than YOL was the outcome measure. Interventions for obese men or for the merely overweight are not likely to achieve differences in either YOL or YHL. Evaluations of interventions for the underweight (which would presumably address the causes of their low weight) may be conducted efficiently using either outcome measure

The association between pubertal status and depressive symptoms and diagnoses in adolescent females: A population-based cohort study.

BACKGROUND: There is an association between puberty and depression, but many things remain poorly understood. When assessing puberty in females, most studies combine indicators of breast and pubic hair development which are controlled by different hormonal pathways. The contributions of pubertal timing (age at onset) and pubertal status (stage of development, irrespective of timing) are also poorly understood. We tested the hypothesis that stage of breast development in female adolescents, controlled largely by increased estradiol, would be more strongly associated with depression than pubic hair development which occurs in both males and females, and is controlled by adrenal androgens. We investigated whether this association was independent of pubertal timing. METHODS: ROOTS is an ongoing cohort of 1,238 adolescents (54% female) recruited in Cambridgeshire (UK) at age 14.5, and followed-up at ages 16 and 17.5. Depression was assessed using the Mood and Feelings Questionnaire (MFQ) and clinical interview. Breast and pubic hair development were assessed at 14.5, using Tanner rating scales. RESULTS: For each increase in Tanner breast stage at 14.5, depressive symptoms increased by 1.4 MFQ points (95% CI 0.6 to 2.3), irrespective of age at onset. Pubic hair status was only associated with depressive symptoms before adjustment for breast status, and was not associated with depression in males. The same pattern was observed longitudinally, and for depression diagnoses. LIMITATIONS: We did not directly measure hormone levels, our findings are observational, and the study had a relatively low response rate. CONCLUSIONS: Females at more advanced stages of breast development are at increased risk of depression, even if their age at pubertal onset is not early. Alongside social and psychological factors, hormones controlling breast but not pubic hair development may contribute to increased incidence of female depression during puberty

Large UK retailers' initiatives to reduce consumers' emissions: a systematic assessment

In the interest of climate change mitigation, policy makers, businesses and non-governmental organisations have devised initiatives designed to reduce in-use emissions whilst, at the same time, the number of energy-consuming products in homes, and household energy consumption, is increasing. Retailers are important because they are at the interface between manufacturers of products and consumers and they supply the vast majority of consumer goods in developed countries like the UK, including energy using products. Large retailers have a consistent history of corporate responsibility reporting and have included plans and actions to influence consumer emissions within them. This paper adapts two frameworks to use them for systematically assessing large retailers’ initiatives aimed at reducing consumers’ carbon emissions. The Framework for Strategic Sustainable Development (FSSD) is adapted and used to analyse the strategic scope and coherence of these initiatives in relation to the businesses’ sustainability strategies. The ISM ‘Individual Social Material’ framework is adapted and used to analyse how consumer behaviour change mechanisms are framed by retailers. These frameworks are used to analyse eighteen initiatives designed to reduce consumer emissions from eight of the largest UK retail businesses, identified from publicly available data. The results of the eighteen initiatives analysed show that the vast majority were not well planned nor were they strategically coherent. Secondly, most of these specific initiatives relied solely on providing information to consumers and thus deployed a rather narrow range of consumer behaviour change mechanisms. The research concludes that leaders of retail businesses and policy makers could use the FSSD to ensure processes, and measurements are comprehensive and integrated, in order to increase the materiality and impact of their initiatives to reduce consumer emissions in use. Furthermore, retailers could benefit from exploring different models of behaviour change from the ISM framework in order to access a wider set of tools for transformative system change

Embedding clinical interventions into observational studies

Novel approaches to observational studies and clinical trials could improve the cost-effectiveness and speed of translation of research. Hybrid designs that combine elements of clinical trials with observational registries or cohort studies should be considered as part of a long-term strategy to transform clinical trials and epidemiology, adapting to the opportunities of big data and the challenges of constrained budgets. Important considerations include study aims, timing, breadth and depth of the existing infrastructure that can be leveraged, participant burden, likely participation rate and available sample size in the cohort, required sample size for the trial, and investigator expertise. Community engagement and stakeholder (including study participants) support are essential for these efforts to succeed

Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals

AbstractObjectivesThis study was designed to evaluate the relationship between elevated creatinine levels and cardiovascular events.BackgroundEnd-stage renal disease is associated with high cardiovascular morbidity and mortality. The association of mild to moderate renal insufficiency with cardiovascular outcomes remains unclear.MethodsWe analyzed data from the Cardiovascular Health Study, a prospective population-based study of subjects, aged >65 years, who had a serum creatinine measured at baseline (n = 5,808) and were followed for a median of 7.3 years. Proportional hazards models were used to examine the association of creatinine to all-cause mortality and incident cardiovascular mortality and morbidity. Renal insufficiency was defined as a creatinine level ≥1.5 mg/dl in men or ≥1.3 mg/dl in women.ResultsAn elevated creatinine level was present in 648 (11.2%) participants. Subjects with elevated creatinine had higher overall (76.7 vs. 29.5/1,000 years, p < 0.001) and cardiovascular (35.8 vs. 13.0/1,000 years, p < 0.001) mortality than those with normal creatinine levels. They were more likely to develop cardiovascular disease (54.0 vs. 31.8/1,000 years, p < 0.001), stroke (21.1 vs. 11.9/1,000 years, p < 0.001), congestive heart failure (38.7 vs. 17/1,000 years, p < 0.001), and symptomatic peripheral vascular disease (10.6 vs. 3.5/1,000 years, p < 0.001). After adjusting for cardiovascular risk factors and subclinical disease measures, elevated creatinine remained a significant predictor of all-cause and cardiovascular mortality, total cardiovascular disease (CVD), claudication, and congestive heart failure (CHF). A linear increase in risk was observed with increasing creatinine.ConclusionsElevated creatinine levels are common in older adults and are associated with increased risk of mortality, CVD, and CHF. The increased risk is apparent early in renal disease

Friendships and Family Support Reduce Subsequent Depressive Symptoms in At-Risk Adolescents.

BACKGROUND: Early life stress (ELS) consists of child family adversities (CFA: negative experiences that happened within the family environment) and/or peer bullying. ELS plays an important role in the development of adolescent depressive symptoms and clinical disorders. Identifying factors that may reduce depressive symptoms in adolescents with ELS may have important public mental health implications. METHODS: We used structural equation modelling and examined the impact of adolescent friendships and/or family support at age 14 on depressive symptoms at age 17 in adolescents exposed to ELS before age 11. To this end, we used structural equation modelling in a community sample of 771 adolescents (322 boys and 477 girls) from a 3 year longitudinal study. Significant paths in the model were followed-up to test whether social support mediated or moderated the association between ELS and depressive symptoms at age 17. RESULTS: We found that adolescent social support in adolescence is negatively associated with subsequent depressive symptoms in boys and girls exposed to ELS. Specifically, we found evidence for two mediational pathways: In the first pathway family support mediated the link between CFA and depressive symptoms at age 17. Specifically, CFA was negatively associated with adolescent family support at age 14, which in turn was negatively associated with depressive symptoms at age 17. In the second pathway we found that adolescent friendships mediated the path between peer bullying and depressive symptoms. Specifically, relational bullying was negatively associated with adolescent friendships at age 14, which in turn were negatively associated with depressive symptoms at age 17. In contrast, we did not find a moderating effect of friendships and family support on the association between CFA and depressive symptoms. CONCLUSIONS: Friendships and/or family support in adolescence mediate the relationship between ELS and late adolescent depressive symptoms in boys and girls. Therefore, enhancing affiliate relationships and positive family environments may benefit the mental health of vulnerable youth that have experienced CFA and/or primary school bullying.AlvH was supported by a Rubicon Fellowship from the Netherlands Organization for Scientific Research. IMG was supported by a Wellcome Trust programme grant, and grants from the NIHR Collaboration for Leadership in Applied Health Research, and Care (CLAHRC) for Cambridgeshire and Peterborough; IMG, AlvH, and JLG were supported through a grant from Kidscompany UK; PBJ was supported by Wellcome Trust grants, and National Institute for Health Research grant; RAK is supported by a Wellcome grant; JLG reports grants from ESRC, grants from MRC, grants, and personal fees from Royal College of Speech, and Language therapists.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.015371

Stroke Ready: a multi-level program that combines implementation science and community-based participatory research approaches to increase acute stroke treatment: protocol for a stepped wedge trial

Abstract Background Post-stroke disability is common, costly, and projected to increase. Acute stroke treatments can substantially reduce post-stroke disability, but few patients take advantage of these cost-effective treatments. Practical, cost-efficient, and sustainable interventions to address underutilized acute stroke treatments are currently lacking. In this context, we present the Stroke Ready project, a stepped wedge design, multi-level intervention that combines implementation science and community-based participatory research approaches to increase acute stroke treatments in the predominately African American community of Flint, Michigan, USA. Methods Guided by the Tailored Implementation of Chronic Disease (TICD) framework, we begin with optimization of acute stroke care in emergency departments, with particular attention given to our safety-net hospital partners. Then, we move to a community-wide, multi-faceted, stroke preparedness intervention, with workshops led by peer educators, over 2 years. Measures of engagement of the safety-net hospital and the feasibility and sustainability of the implementation strategy as well as community intervention reach, dose delivered, and satisfaction will be collected. The primary outcome is acute stroke treatment rates, which includes both intravenous tissue plasminogen activator, and endovascular treatment. The co-secondary outcomes are intravenous tissue plasminogen activator treatment rates and the proportion of stroke patients who arrive by ambulance. Discussion If successful, Stroke Ready will increase acute stroke treatment rates through emergency department and community level interventions. The stepped wedge design and process evaluation will provide insight into how Stroke Ready works and where it might work best. By exploring the relative effectiveness of the emergency department optimization and the community intervention, we will inform hospitals and communities as they determine how best to use their resources to optimize acute stroke care. Trial registration ClinicalTrials.gov Trial Identifier NCT03645590 .https://deepblue.lib.umich.edu/bitstream/2027.42/148211/1/13012_2019_Article_869.pd

The technologies of isolation: apocalypse and self in Kurosawa Kiyoshi's Kairo

In this investigation of the Japanese film Kairo, I contemplate how the horrors present in the film relate to the issue of self, by examining a number of interlocking motifs. These include thematic foci on disease and technology which are more intimately and inwardly focused that the film's conclusion first appears to suggest. The true horror here, I argue, is ontological: centred on the self and its divorcing from the exterior world, especially founded in an increased use of and reliance on communicative technologies. I contend that these concerns are manifested in Kairo by presenting the spread of technology as disease-like, infecting the city and the individuals who are isolated and imprisoned by their urban environment. Finally, I investigate the meanings of the apocalypse, expounding how it may be read as hopeful for the future rather than indicative of failure or doom

Short-term efficacy of physical interventions in osteoarthritic knee pain. A systematic review and meta-analysis of randomised placebo-controlled trials.

BACKGROUND: Treatment efficacy of physical agents in osteoarthritis of the knee (OAK) pain has been largely unknown, and this systematic review was aimed at assessing their short-term efficacies for pain relief. METHODS: Systematic review with meta-analysis of efficacy within 1-4 weeks and at follow up at 1-12 weeks after the end of treatment. RESULTS: 36 randomised placebo-controlled trials (RCTs) were identified with 2434 patients where 1391 patients received active treatment. 33 trials satisfied three or more out of five methodological criteria (Jadad scale). The patient sample had a mean age of 65.1 years and mean baseline pain of 62.9 mm on a 100 mm visual analogue scale (VAS). Within 4 weeks of the commencement of treatment manual acupuncture, static magnets and ultrasound therapies did not offer statistically significant short-term pain relief over placebo. Pulsed electromagnetic fields offered a small reduction in pain of 6.9 mm [95% CI: 2.2 to 11.6] (n = 487). Transcutaneous electrical nerve stimulation (TENS, including interferential currents), electro-acupuncture (EA) and low level laser therapy (LLLT) offered clinically relevant pain relieving effects of 18.8 mm [95% CI: 9.6 to 28.1] (n = 414), 21.9 mm [95% CI: 17.3 to 26.5] (n = 73) and 17.7 mm [95% CI: 8.1 to 27.3] (n = 343) on VAS respectively versus placebo control. In a subgroup analysis of trials with assumed optimal doses, short-term efficacy increased to 22.2 mm [95% CI: 18.1 to 26.3] for TENS, and 24.2 mm [95% CI: 17.3 to 31.3] for LLLT on VAS. Follow-up data up to 12 weeks were sparse, but positive effects seemed to persist for at least 4 weeks after the course of LLLT, EA and TENS treatment was stopped. CONCLUSION: TENS, EA and LLLT administered with optimal doses in an intensive 2-4 week treatment regimen, seem to offer clinically relevant short-term pain relief for OAK

Chemical Genetic Screen for AMPKα2 Substrates Uncovers a Network of Proteins Involved in Mitosis

The energy-sensing AMP-activated protein kinase (AMPK) is activated by low nutrient levels. Functions of AMPK, other than its role in cellular metabolism, are just beginning to emerge. Here we use a chemical genetics screen to identify direct substrates of AMPK in human cells. We find that AMPK phosphorylates 28 previously unidentified substrates, several of which are involved in mitosis and cytokinesis. We identify the residues phosphorylated by AMPK in vivo in several substrates, including protein phosphatase 1 regulatory subunit 12C (PPP1R12C) and p21-activated protein kinase (PAK2). AMPK-induced phosphorylation is necessary for PPP1R12C interaction with 14-3-3 and phosphorylation of myosin regulatory light chain. Both AMPK activity and PPP1R12C phosphorylation are increased in mitotic cells and are important for mitosis completion. These findings suggest that AMPK coordinates nutrient status with mitosis completion, which may be critical for the organism's response to low nutrients during development, or in adult stem and cancer cells.National Institutes of Health (U.S.) (Grant R01-GM068762