The effectiveness of smoking cessation, physical activity/diet and alcohol reduction interventions delivered by mobile phones for the prevention of non-communicable diseases: A systematic review of randomised controlled trials.

BACKGROUND: We conducted a systematic review to assess the effectiveness of smoking cessation, physical activity (PA), diet, and alcohol reduction interventions delivered by mobile technology to prevent non-communicable diseases (NCDs). METHODS: We searched for randomised controlled trials (RCTs) of mobile-based NCD prevention interventions using MEDLINE, EMBASE, Global Health, CINAHL (Jan 1990-Jan 2016). Two authors extracted data. FINDINGS: 71 trials were included: smoking cessation (n = 18); PA (n = 15), diet (n = 3), PA and diet (n = 25); PA, diet, and smoking cessation (n = 2); and harmful alcohol consumption (n = 8). 4 trials had low risk of bias. The effect of SMS-based smoking cessation support on biochemically verified continuous abstinence was pooled relative risk [RR] 2.19 [95% CI 1.80-2.68], I2 = 0%) and on verified 7 day point prevalence of smoking cessation was pooled RR 1.51 [95% CI 1.06-2.15], I2 = 0%, with no reported adverse events. There was no difference in peak oxygen intake at 3 months in a trial of an SMS-based PA intervention. The effect of SMS-based diet and PA interventions on: incidence of diabetes was pooled RR 0.67 [95% CI 0.49, 0.90], I2 = 0.0%; end-point weight was pooled MD -0.99Kg [95% CI -3.63, 1.64] I2 = 29.4%; % change in weight was pooled MD -3.1 [95%CI -4.86- -1.3] I2 0.3%; and on triglyceride levels was pooled MD -0.19 mmol/L [95% CI -0.29, -0.08], I2 = 0.0%. The results of other pooled analyses of the effect of SMS-based diet and PA interventions were heterogenous (I2 59-90%). The effects of alcohol reduction interventions were inconclusive. CONCLUSIONS: Smoking cessation support delivered by SMS increases quitting rates. Trials of PA interventions reporting outcomes ≥3 months showed no benefits. There were at best modest benefits of diet and PA interventions. The effects of the most promising SMS-based smoking, diet and PA interventions on morbidity and mortality in high-risk groups should be established in adequately powered RCTs.

Chronic exposure to insufficient sleep alters processes of pain habituation and sensitization.

Chronic pain conditions are highly comorbid with insufficient sleep. While the mechanistic relationships between the 2 are not understood, chronic insufficient sleep may be 1 pathway through which central pain-modulatory circuits deteriorate, thereby contributing to chronic pain vulnerability over time. To test this hypothesis, an in-laboratory model of 3 weeks of restricted sleep with limited recovery (5 nights of 4-hour sleep per night followed by 2 nights of 8-hour sleep per night) was compared with 3 weeks of 8-hour sleep per night (control protocol). Seventeen healthy adults participated, with 14 completing both 3-week protocols. Measures of spontaneous pain, heat-pain thresholds, cold-pain tolerance (measuring habituation to cold over several weeks), and temporal summation of pain (examining the slope of pain ratings during cold water immersion) were assessed at multiple points during each protocol. Compared with the control protocol, participants in the sleep-restriction protocol experienced mild increases in spontaneous pain (P < 0.05). Heat-pain thresholds decreased after the first week of sleep restriction (P < 0.05) but normalized with longer exposure to sleep restriction. By contrast, chronic exposure to restricted sleep was associated with decreased habituation to, and increased temporal summation in response to cold pain (both P < 0.05), although only in the past 2 weeks of the sleep-restriction protocol. These changes may reflect abnormalities in central pain-modulatory processes. Limited recovery sleep did not completely resolve these alterations in pain-modulatory processes, indicating that more extensive recovery sleep is required. Results suggest that exposure to chronic insufficient sleep may increase vulnerability to chronic pain by altering processes of pain habituation and sensitization.

Repeating patterns of sleep restriction and recovery: Do we get used to it?

Despite its prevalence in modern society, little is known about the long-term impact of restricting sleep during the week and 'catching up' on weekends. This common sleep pattern was experimentally modeled with three weeks of 5 nights of sleep restricted to 4h followed by two nights of 8-h recovery sleep. In an intra-individual design, 14 healthy adults completed both the sleep restriction and an 8-h control condition, and the subjective impact and the effects on physiological markers of stress (cortisol, the inflammatory marker IL-6, glucocorticoid receptor sensitivity) were assessed. Sleep restriction was not perceived to be subjectively stressful and some degree of resilience or resistance to the effects of sleep restriction was observed in subjective domains. In contrast, physiological stress response systems remain activated with repeated exposures to sleep restriction and limited recovery opportunity. Morning IL-6 expression in monocytes was significantly increased during week 2 and 3 of sleep restriction, and remained increased after recovery sleep in week 2 (p<0.05) and week 3 (p<0.09). Serum cortisol showed a significantly dysregulated 24h-rhythm during weeks 1, 2, and 3 of sleep restriction, with elevated morning cortisol, and decreased cortisol in the second half of the night. Glucocorticoid sensitivity of monocytes was increased, rather than decreased, during the sleep restriction and sleep recovery portion of each week. These results suggest a disrupted interplay between the hypothalamic-pituitary-adrenal and inflammatory systems in the context of repeated exposure to sleep restriction and recovery. The observed dissociation between subjective and physiological responses may help explain why many individuals continue with the behavior pattern of restricting and recovering sleep over long time periods, despite a cumulative deleterious physiological effect.

Global dietary quality, undernutrition and non-communicable disease: a longitudinal modelling study.

OBJECTIVES: To determine the relationship between global dietary energy availability and dietary quality, and nutrition-related health outcomes. DESIGN: A worldwide longitudinal modelling study using country-level data. Data on total dietary energy availability and dietary energy from 10 distinct food groups (as a proxy for dietary quality) were obtained from the FAO Food Balance Sheets database. Indicators of development were abstracted from the World Bank's World Development Indicators database. Data on nutrition and health outcomes were taken from the WHO mortality database and major cross-country analyses. We investigated associations of energy availability from food groups and health and nutrition outcomes in the combined data set using mixed effects models, while adjusting for measures of development. POPULATION: 124 countries over the period 1980-2009. MAIN OUTCOME MEASURES: Prevalence of stunting in children under 5 years and mortality rate from ischaemic heart disease (IHD) in adults aged 55+ years. RESULTS: From 1980 to 2009, global dietary energy availability increased, and rates of child stunting and adult IHD mortality declined. After adjustment for measures of development, increased total dietary energy availability was significantly associated with reduced stunting rates (-0.84% per 100 kcal increase in energy, 95% CI -0.97 to -0.72) and non-significantly associated with increased IHD mortality rates (by 4.2 deaths per 100,000/100 kcal increase, 95% CI -1.85 to 10.2). Further analysis demonstrated that the changing availability of energy from food groups (particularly fruit, vegetables, starchy roots, meat, dairy and sugar) was important in explaining the associations with health outcomes. CONCLUSIONS: Our study has demonstrated that by combining large, publicly available data sets, important patterns underlying trends in diet-related health can be uncovered. These associations remain even after accounting for measures of development over a 30-year period. Further work and joined-up multisectoral thinking will be required to translate these patterns into policies that can improve nutrition and health outcomes globally.

Sleep characteristics as predictor variables of stress systems markers in insomnia disorder.

This study investigates the extent to which sleep characteristics serve as predictor variables for inflammatory, hypothalamic-pituitary-adrenal and autonomic systems markers. Twenty-nine participants with a diagnosis of insomnia disorder based on the Diagnostic Statistical Manual of Mental Disorders, Fifth Edition (age 25.3 ± 1.6 years, insomnia duration 6.6 ± 0.8 years) and 19 healthy control sleepers (age 25.4 ± 1.4 years) underwent a 2-week at-home evaluation keeping a sleep diary and wearing an actigraph, followed by a visit to the Research Center to measure blood pressure, and collect blood and urine samples. The actigraphy- and diary-based variables of sleep duration, sleep-onset latency, wake after sleep onset and sleep fragmentation/number of night-time awakenings were averaged and entered as dependent variables in regression analyses. Composite scores were calculated for the autonomic (blood pressure, norepinephrine), inflammatory (monocyte counts, interleukin-6, C-reactive protein) and hypothalamic-pituitary-adrenal systems (cortisol), and used as predictor variables in regression models. Compared with controls, individuals with insomnia had a shorter sleep duration (P < 0.05), and a higher hypothalamic-pituitary-adrenal and inflammatory composite score (P < 0.05). The higher inflammatory score was mainly due to higher circulating monocytes (P < 0.05), rather than differences in interleukin-6 or C-reactive protein. In persistent insomnia disorder, cortisol is upregulated and associated with actigraphy- and diary-based wake after sleep onset, suggesting that wake after sleep onset may serve as a marker to identify individuals at increased risks for disorders associated with a hyperactive hypothalamic-pituitary-adrenal system. The absence of autonomic and pro-inflammatory changes (interleukin-6, C-reactive protein), despite a substantial decrease in actigraphic sleep duration, may relate to a higher resilience to the adverse biological consequences of insomnia in this young age group.

Continuation of all-trans retinoic acid despite the development of scrotal ulcerations in a black male.

Acute promyelocytic leukemia, an aggressive subtype of acute myeloid leukemia, is characterized by the t(15;17) translocation. Standard induction chemotherapy consists of (ATRA) in combination with anthracycline-based chemotherapy with or without the addition of cytarabine. Rare and serious side effects of ATRA have been reported including painful lip and scrotal ulcerations. Of 20 previous reports of genital ulceration, 17 patients had ATRA discontinued and corticosteroids initiated; however, the corticosteroid regimens and duration of therapy were not well described. Herein we present the first known case of a Black male with ATRA-associated scrotal ulcerations who was successfully managed with corticosteroids without cessation of all-trans retinoic acid. We report this case to highlight its rarity and to note that ATRA can be continued in combination with corticosteroids throughout induction.

Fewer adults add salt at the table after initiation of a national salt campaign in the UK: a repeated cross-sectional analysis.

In 2003, the UK Food Standards Agency and the Department of Health began attempts to reduce national salt intakes via reformulation of processed foods and a consumer awareness campaign on the negative impacts of salt on health. The present study uses large nationally representative samples of households in England to assess whether discretionary salt use was affected by the national salt reduction campaign. Large cross-sectional datasets from the Health Survey for England were used to analyse trends in adults adding salt at the table between 1997 and 2007. Since 1997, there has been a steady decline in salt use at the table. Ordinal logistic regression analysis controlling for age, sex, total household income, region, ethnicity and background trends revealed that the reduction in salt use was significantly greater after the campaign (OR 0·58; 95% CI 0·54, 0·63). Women (OR 0·71; 95% CI 0·68, 0·74), non-white ethnic groups (OR 0·69; 95% CI 0·62, 0·77), high-income households (OR 0·75; 95% CI 0·69, 0·82), middle-income households (OR 0·79; 95% CI 0·75, 0·84) and households in central (OR 0·90; 95% CI 0·84, 0·98) or the south of England (OR 0·82; 95% CI 0·77, 0·88) were less likely to add salt at the table. The results extend previous evidence of a beneficial response to the salt campaign by demonstrating the effect on salt use at the table. Future programmatic and research efforts may benefit from targeting specific population groups and improving the evidence base for evaluating the impact of the campaign.

Fosfomycin enhances the active transport of tobramycin in Pseudomonas aeruginosa.

Elevated levels of mucins present in bronchiectatic airways predispose patients to bacterial infections and reduce the effectiveness of antibiotic therapies by directly inactivating antibiotics. Consequently, new antibiotics that are not inhibited by mucins are needed to treat chronic respiratory infections caused by Pseudomonas aeruginosa and Staphylococcus aureus. In these studies, we demonstrate that fosfomycin synergistically enhances the activity of tobramycin in the presence of mucin. The bactericidal killing of a novel 4:1 (wt/wt) combination of fosfomycin-tobramycin (FTI) is superior (>9 log(10) CFU/ml) relative to its individual components fosfomycin and tobramycin. Additionally, FTI has a mutation frequency resulting in an antibiotic resistance >3 log(10) lower than for fosfomycin and 4 log(10) lower than for tobramycin for P. aeruginosa. Mechanistic studies revealed that chemical adducts are not formed, suggesting that the beneficial effects of the combination are not due to molecular modification of the components. FTI displayed time-kill kinetics similar to tobramycin and killed in a concentration-dependent fashion. The bactericidal effect resulted from inhibition of protein biosynthesis rather than cell wall biosynthesis. Studies using radiolabeled antibiotics demonstrated that tobramycin uptake was energy dependent and that fosfomycin enhanced the uptake of tobramycin in P. aeruginosa in a dose-dependent manner. Lastly, mutants resistant to fosfomycin and tobramycin were auxotrophic for specific carbohydrates and amino acids, suggesting that the resistance arises from mutations in specific active transport mechanisms. Overall, these data demonstrate that fosfomycin enhances the uptake of tobramycin, resulting in increased inhibition of protein synthesis and ultimately bacterial killing.

No effect of carotenoid supplementation on phytohemagglutinin response or body condition of nestling house wrens.

Carotenoids are an essential and often limiting resource in animals and play important roles in immune system function. In birds, the period shortly after hatching is an energetically demanding stage characterized by rapid growth in body size and organ systems, including the immune system. Availability of carotenoids for the growing nestlings may be of particular importance and potentially limiting at this stage of development. We tested the hypothesis that the availability of carotenoids for the embryo in the egg and in the diet of nestlings limits the condition and immune responses of nestling house wrens (Troglodytes aedon Vieillot 1809), a species with melanin-based plumage pigments. In one experiment, nestlings within females' second broods were randomly assigned to receive either a control or a lutein supplement (2008); in a second experiment, females, before their first broods, were either induced to lay additional eggs or not induced, and nestlings within both kinds of broods were supplemented as in the first experiment (2009). There were no significant effects of lutein supplementation on nestling condition or phytohemagglutinin response. There was a significant effect of lutein supplementation on nestling mass in 2008, but the difference was opposite to that predicted. Moreover, even when breeding females were stressed by inducing them to lay supernumerary eggs, lutein supplementation of nestlings had no effect on the size or condition of nestlings hatching from these eggs. These results suggest that maternally derived lutein in the egg and that provided in the diet of nestlings are not limiting to normal development and to the components of the immune system involved in the phytohemagglutinin response of nestling house wrens.

Validation of the Individualized Numeric Rating Scale (INRS): a pain assessment tool for nonverbal children with intellectual disability.

Clinical observations suggest that nonverbal children with severe intellectual disability exhibit pain in a wide variety yet uniquely individual ways. Here, we investigate the feasibility and describe the initial psychometrics properties of the Individualized Numeric Rating Scale (INRS), a personalized pain assessment tool for nonverbal children with intellectual disability based on the parent's knowledge of the child. Parents of 50 nonverbal children with severe intellectual disability scheduled for surgery were able to complete the task of describing then rank ordering their child's usual and pain indicators. The parent, bedside nurse and research assistant (RA) triad then simultaneously yet independently scored the patient's post-operative pain using the INRS for a maximum of two sets of pre/post paired observations. A total of 170 triad assessments were completed before (n=85) and after (n=85) an intervention to manage the child's pain. INRS inter-rater agreement between the parents and research nurse was high (ICC 0.82-0.87) across all ratings. Parent and bedside nurse agreement (ICC 0.65-0.74) and bedside nurse and research nurse agreement (ICC 0.74-0.80) also suggest good reliability. A moderate to strong correlation (0.63-0.73) between INRS ratings and NCCPC-PV total scores provides evidence of convergent validity. These results provide preliminary data that the INRS is a valid and reliable tool for assessing pain in nonverbal children with severe intellectual disability in an acute care setting.

Antibacterial activities of a fosfomycin/tobramycin combination: a novel inhaled antibiotic for bronchiectasis.

OBJECTIVES: To compare the in vitro and in vivo activities of a 4:1 (w/w) fosfomycin/tobramycin combination (FTI) with those of fosfomycin and tobramycin alone against cystic fibrosis (CF) and non-CF bronchiectasis pathogens. METHODS: Clinical isolates of CF Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Stenotrophomonas maltophilia, Burkholderia cepacia complex, Escherichia coli and Klebsiellia spp. were evaluated by MIC, MBC, post-antibiotic effect (PAE), synergy, time-kill, a rat pneumonia model and spontaneous mutation frequency (SMF). RESULTS: FTI showed high activity against E. coli, H. influenzae, S. aureus and Klebsiella spp. For the S. aureus strains, 75% of which were methicillin resistant (MRSA), FTI had a lower MIC(90) than tobramycin. For P. aeruginosa, FTI had a lower MIC(90) than fosfomycin, but tobramycin was more active than either. Synergy studies showed no antagonism between fosfomycin and tobramycin, and 93% of the isolates demonstrated no interaction. FTI was rapidly bactericidal and exhibited concentration-dependent killing in time-kill studies. In the rat pneumonia model, FTI and tobramycin demonstrated bactericidal killing of P. aeruginosa; both were more active than fosfomycin alone. The SMF for S. aureus resistance to FTI was 2-4 log(10) lower than that for tobramycin and 2-7 log(10) lower than that for fosfomycin. For P. aeruginosa, the FTI SMF was 2-3 log(10) lower than that for fosfomycin and 1-2 log(10) lower than that for tobramycin. CONCLUSIONS: FTI is a broad-spectrum antibiotic combination with high activity in vitro and in vivo. These data suggest FTI could be a potential treatment for respiratory infections caused by gram-positive and gram-negative aerobic bacteria.

Anti-leukemic activity of lintuzumab (SGN-33) in preclinical models of acute myeloid leukemia.

Despite therapeutic advances, the long-term survival rates for acute myeloid leukemia (AML) are estimated to be 10% or less, pointing to the need for better treatment options. AML cells express the myeloid marker CD33, making it amenable to CD33-targeted therapy. Thus, the in vitro and in vivo anti-tumor activities of lintuzumab (SGN-33), a humanized monoclonal anti-CD33 antibody undergoing clinical evaluation, were investigated. In vitro assays were used to assess the ability of lintuzumab to mediate effector functions and to decrease the production of growth factors from AML cells. SCID mice models of disseminated AML with the multi-drug resistance (MDR)-negative HL60 and the MDR(+), HEL9217 and TF1-alpha, cell lines were developed and applied to examine the in vivo antitumor activity. In vitro, lintuzumab significantly reduced the production of TNFalpha-induced pro-inflammatory cytokines and chemokines by AML cells. Lintuzumab promoted tumor cell killing through antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) activities against MDR(-) and MDR(+) AML cell lines and primary AML patient samples. At doses from 3 to 30 mg/kg, lintuzumab significantly enhanced survival and reduced tumor burden in vivo, regardless of MDR status. Survival of the mice was dependent upon the activity of resident macrophages and neutrophils. The results suggest that lintuzumab may exert its therapeutic effects by modulating the cytokine milieu in the tumor microenvironment and through effector mediated cell killing. Given that lintuzumab induced meaningful responses in a phase 1 clinical trial, the preclinical antitumor activities defined in this study may underlie its observed therapeutic efficacy in AML patients.

Quaternary structure of the mitochondrial TIM23 complex reveals dynamic association between Tim23p and other subunits.

Tim23p is an essential channel-forming component of the multisubunit TIM23 complex of the mitochondrial inner membrane that mediates protein import. Radiolabeled Tim23p monocysteine mutants were imported in vitro, incorporated into functional TIM23 complexes, and subjected to chemical cross-linking. Three regions of proximity between Tim23p and other subunits of the TIM23 complex were identified: Tim17p and the first transmembrane segment of Tim23p; Tim50p and the C-terminal end of the Tim23p hydrophilic region; and the entire hydrophilic domains of Tim23p molecules. These regions of proximity reversibly change in response to changes in membrane potential across the inner membrane and also when a translocating substrate is trapped in the TIM23 complex. These structural changes reveal that the macromolecular arrangement within the TIM23 complex is dynamic and varies with the physiological state of the mitochondrion.

Psychological, behavioral, and family characteristics of pediatric patients with chronic pain: a 1-year retrospective study and cluster analysis.

OBJECTIVES: There has been a longstanding recognition that adult patients with chronic pain are not a homogenous population and that there are subgroups of patients who report high levels of distress and interpersonal difficulties as well as subgroups of patients who report little distress and high functioning. The purpose of the present study was to attempt to identify similar subgroups in a pediatric chronic pain population. METHODS: The sample consisted of 117 children with chronic pain and their parents who were assessed in a multidisciplinary pain clinic during 2001. Participants completed a set of psychologic self-report questionnaires, as well as demographic and pain characteristic information. A cluster analysis was conducted to identify 3 distinct subgroups of patients to replicate similar studies of adult chronic pain sufferers. RESULTS: Overall, mean scores were within population norms on measures of distress and family functioning, with somatic symptoms at a level of clinical significance. The cluster analysis identified the 3 subgroups that were strikingly similar to those identified in adult chronic pain populations: one with high levels of distress and disability, another with relatively low scores on distress and disability, and a third group that scored in between the other 2 on these measures but with marked low family cohesion. DISCUSSION: The similarity of these subgroups to the adult chronic pain population subgroups as well as implications for future studies are discussed.

Motogenic substrata and chemokinetic growth factors for human skin cells.

Extracellular matrix remodelling and accurate spatio-temporal coordination of growth factor expression are two factors that are believed to regulate mitoses and cell migration in developing and regenerating tissues. The present quantitative videomicroscopical study examined the influence of some of the principal components of extracellular matrix and several growth factors that are known to be expressed in dermal wounds on three important facets of human skin cell behaviour in culture. Keratinocytes, melanocytes and dermal fibroblasts (and myofibroblast controls) exhibited varying degrees of substrate adhesion, division and migration depending on the composition of the culture substrate. Substrates that are recognized components of transitional matrices generally accentuated cell adhesion and proliferation, and were motogenic, when compared with serum-treated control surfaces, whereas components of more stable structures such as basement membrane had less influence. Platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and alpha fibroblastic growth factor (alphaFGF) all promoted cell proliferation and were chemokinetic to dermal fibroblasts, but not keratinocyte growth factor (KGF) or transforming growth factor beta (TGFbeta). PDGF, EGF and KGF, but not TGFbeta or alphaFGF, all enhanced proliferation of dermal keratinocytes. The same growth factors, and in addition KGF, all stimulated motility in keratinocytes, but TGFbeta and alphaFGF again had no effect. Developing a better understanding of the interdependency of factors that control crucial cell behaviour may assist those who are interested in the regulation of histogenesis and also inform the development of rational therapeutic strategies for the management of chronic and poorly healed wounds.

Contact guidance in human dermal fibroblasts is modulated by population pressure.

Morphogenesis is underpinned by orientated cell division, motility and growth. The substratum for migrating cells in vivo comprises either extracellular matrix or the surfaces of adjacent cells and both are believed to inform the dynamic behaviour of adherent cells through contact guidance. Collisions between migrating cells in vitro can induce the phenomena of contact inhibition of locomotion and division, suggesting that their sensitivity to substratum-derived cues may also be influenced by population density. In the present study dermal fibroblasts, which are known to be motile in culture and are fundamental to the organization of the extracellular matrix, were used to examine the influence of population pressure on the ability of substratum topography to induce contact guidance. The findings suggest that sensitivity to substratum-derived morphogenetic guidance cues, as revealed by alignment of cells to microtopography, is modulated by population pressure.

Physical therapy and cognitive-behavioral treatment for complex regional pain syndromes.

Complex regional pain syndromes (CRPS; type 1, reflex sympathetic dystrophy, and type 2, causalgia) involve persistent pain, allodynia, and vasomotor signs. We conducted a prospective, randomized, single-blind trial of physical therapy (PT) and cognitive-behavioral treatment for children and adolescents with CRPS. Children 8 to 17 years of age (n = 28) were randomly assigned to either group A (PT once per week for 6 weeks) or group B (PT 3 times per week for 6 weeks). Both groups received 6 sessions of cognitive-behavioral treatment. Assessments of pain and function were repeated at two follow-up time periods. Outcomes were compared at the three time points through the use of parametric or nonparametric analysis of variance and post hoc tests. All five measures of pain and function improved significantly in both groups after treatment, with sustained benefit evident in the majority of patients at long-term follow-up. Recurrent episodes were reported in 50% of patients, and 10 patients eventually received sympathetic blockade. Most children with CRPS showed reduced pain and improved function with a noninvasive rehabilitative treatment approach. Long-term functional outcomes were also very good.