Childhood Obesity Task Forces Established by State Legislatures, 2001-2010

Introduction - States and communities are considering policy and environmental strategies, including enacting legislation, to reduce and prevent childhood obesity. One legislative approach has been to create task forces to understand key issues and develop a course of action. The goal of this study was to describe state-level, childhood obesity task forces in the United States created by legislation from 2001 through 2010. Methods - We used the Center for Disease Control and Prevention\u27s Division of Nutrition, Physical Activity, and Obesity database to identify state-level childhood obesity task forces created through legislation from 2001 through 2010. Results - We identified 21 states that had enacted legislation creating childhood obesity task forces of which 6 has created more than one task force. Most task forces were charged with both gathering and reviewing information and making recommendations for obesity-prevention actions in the state. Most legislation required that task forces include representation from the state legislature, state agencies, community organizations, and community members. Conclusion - Evaluation of the effectiveness of obesity-prevention task forces and the primary components that contribute to their success may help to determine the advantages of the use of such strategies in obesity prevention

Cost‐effectiveness of real‐world administration of tobacco pharmacotherapy in the United States Veterans Health Administration

Background and aimsCost‐effectiveness studies in randomized clinical trials have shown that tobacco cessation pharmacotherapy is among the most cost‐effective of health‐care interventions. Clinical trial eligibility criteria and treatment protocols may not be followed in actual practice. This study aimed to determine whether tobacco cessation pharmacotherapy is cost‐effective in real‐world settings.DesignA retrospective analysis of costs and outcomes.SettingHospitals and clinics of the US Veterans Health Administration, USA.ParticipantsA total of 589 862 US veterans who screened positive for tobacco use in 2011.Intervention and comparatorTobacco users who initiated smoking cessation pharmacotherapy in the 6 months after screening were compared with those who did not use pharmacotherapy in this period. Pharmacotherapy included nicotine replacement therapy, bupropion (if prescribed at 300 mg per day or specifically for tobacco cessation) or varenicline.MeasuresEffectiveness was determined from responses to a subsequent tobacco screening conducted between 7 and 18 months after the treatment observation period. Cost of medications and prescribing health‐care encounters was determined for the period between initial and follow‐up tobacco use screening. Multivariate fixed‐effects regression was used to assess the effect of initial treatment status on cost and outcome while controlling for differences in case‐mix with propensity weighting to adjust for confounding by indication.FindingsThirteen per cent of participants received tobacco cessation pharmacotherapy within 6 months of initial screening. After an average of an additional 218.1 days’ follow‐up, those who initially received pharmacotherapy incurred $143.79 in additional treatment cost and had a 3.1$4705 per quit. The upper limit of the 99.9% confidence region was $5600 per quit. Without propensity adjustment, the cost‐effectiveness ratio was$7144 per quit, with the upper limit of the 99.9% confidence region $9500/quit.ConclusionsTobacco cessation pharmacotherapy provided by the US Veterans Health Administration in 2011/12 was cost‐effective in this real‐world setting, with an incremental cost‐effectiveness ratio of$4705 per quit.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150598/1/add14621_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150598/2/add14621.pd

Microsomal prostaglandin E2 synthase-1 is induced by conditional expression of RET/PTC in thyroid PCCL3 cells through the activation of the MEK-ERK pathway

RET/PTC rearrangements are believed to be tumor-initiating events in papillary thyroid carcinomas. We identified microsomal prostaglandin E2 synthase-1 (mPGES-1) as a RET/PTC-inducible gene through subtraction hybridization cloning and expression profiling with custom microarrays. The inducible prostaglandin E2 (PGE2) biosynthetic enzymes cyclooxygenase-2 (COX-2) and mPGES-1 are up-regulated in many cancers. COX-2 is overexpressed in thyroid malignancies compared with benign nodules and normal thyroid tissues. Eicosanoids may promote tumorigenesis through effects on tumor cell growth, immune surveillance, and angiogenesis. Conditional RET/PTC1 or RET/PTC3 expression in PCCL3 thyroid cells markedly induced mPGES-1 and COX-2. PGE2 was the principal prostanoid and up-regulated (by approximately 60-fold), whereas hydroxyeicosatetraenoic acid metabolites were decreased, consistent with shunting of prostanoid biosynthesis toward PGE2 by coactivation of the two enzymes. RET/PTC activated mPGES-1 gene transcription. Based on experiments with kinase inhibitors, with PCCL3 cell lines with doxycycline-inducible expression of RET/PTC mutants with substitutions of critical tyrosine residues in the kinase domain, and lines with inducible expression of activated mutants of H-RAS and MEK1, RET/PTC was found to regulate mPGES-1 through Shc-RAS-MEK-ERK. These data show a direct relationship between activation of a tyrosine kinase receptor oncogene and regulation of PGE2 biosynthesis. As enzymes involved in prostanoid biosynthesis can be targeted with pharmacological inhibitors, these findings may have therapeutic implications

Laparoscopic vs Open approach for transverse colon cancer. A systematic review and meta-analysis of short and long term outcomes

Background: Transverse colon malignancies have been excluded from all randomized controlled trials comparing laparoscopic against open colectomies, potentially due to the advanced laparoscopic skills required for dissecting around the middle colic vessels and the associated morbidity. Concerns have been expressed that the laparospopic approach may compromise the oncological clearance in transverse colon cancer. This study aimed to comprehensively compare the laparoscopic (LPA) to the open (OPA) approach by performing a meta-analysis of long and short term outcomes. Methods: Medline, Embase, Cochrane library, Scopus and Web of Knowledge databases were interrogated. Selected studies were critically appraised and the short-term morbidity and long term oncological outcomes were meta-analyzed. Sensitivity analysis according to the quality of the study, type of procedure (laparoscopic vs laparoscopically assisted) and level of lymphadenectomy was performed. Statistical heterogeneity and publication bias were also investigated. Results: Eleven case control trials (1415 patients) were included in the study. There was no difference between the LPA and the OPA in overall survival [Hazard Ratio (HR)=0.83 (0.56, 1.22); P=0.34], disease free survival (p=0.20), local recurrence (p=0.81) or distant metastases (p=0.24). LPA was found to have longer operative time [Weighted mean difference (WMD)=45.00 (29.48, 60.52);P<0.00001] with earlier establishment of oral intake [WMD=-1.68 (-1.84, -1.53);P<0.00001] and shorter hospital stay [WMD =-2.94 (-4.27, -1.62);P=0.0001]. No difference was found in relation to anastomotic leakage (p=0.39), intra-abdominal abscess (p=0.25), lymph nodes harvested (p=0.17). Conclusions: LPA seems to be safe with equivalent oncological outcomes to OPA and better short term outcomes in selected patient populations. High quality Randomized control trials are required to further investigate the role of laparoscopy in transverse colon cancer

Identification and Characterization of Trimethylamine-N-oxide Uptake and Efflux Transporters

Trimethylamine-N-oxide (TMAO) is a recently identified predictor of cardiovascular and chronic kidney disease. TMAO is primarily generated through gut-microbiome mediated conversion of dietary choline and carnitine to TMA, which is converted to TMAO by hepatic flavin monooxygenase 3 (FMO3) and subsequently undergoes renal elimination. We investigated the role of uptake and efflux drug transporters in TMAO disposition in vitro and in vivo. After screening a large array of uptake transporters, we show organic cation transporter 2 (OCT2) is the key transporter for TMAO cellular uptake. In Oct1/2 knockout mice, we observed increased plasma TMAO levels with reduced renal retention, suggesting the importance of Oct2 in facilitating the uptake of TMAO into renal tubular cells in vivo. Multiple transporters of the ATP-binding cassette (ABC) family, including ABCG2 (BCRP) and ABCB1 (MDR1), were capable of TMAO efflux. In human subjects, clinical, dietary, and pharmacogenetic covariates were evaluated for contribution to TMAO levels in a cohort of dyslipidemic patients (n = 405). Interestingly, genetic variation in ABCG2, but not other transporters, appeared to play a role in modulating TMAO exposure

Impact of Spironolactone on Longitudinal Changes in Health-Related Quality of Life in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial

BACKGROUND: Heart failure (HF) with preserved ejection fraction patients have equally impaired health-related quality of life (HRQL) compared with those with HF with reduced ejection fraction, but limited studies have evaluated the impact of therapies on changes in HRQL. METHODS AND RESULTS: Patients ≥50 years of age, with symptomatic HF and left ventricular ejection fraction ≥45%, were enrolled in Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) and randomized to spironolactone or placebo. Patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ), which was the primary HRQL instrument, and EQ5D visual analog scale at baseline, 4 months, 12 months, and annually thereafter. McMaster Overall Treatment Evaluation was assessed at 4 and 12 months to assess global change scores. Change scores (+SD) were calculated to determine between-group differences, and multivariable repeated-measures models were created to identify other factors associated with change scores. Paired KCCQ data were available for 91.7% of 3445 TOPCAT patients. By 4 months, the mean change in KCCQ was 7.7±16 and mean change in EQ5D visual analog scale was 4.7±16. Adjusted mean changes in KCCQ for the spironolactone group were significantly better than those for the placebo group at 4-month (1.54 better; P=0.002), 12-month (1.35 better; P=0.02), and 36-month (1.86 better; P=0.02) visits. No between-group differences in EQ5D visual analog scale change scores or McMaster Overall Treatment Evaluation were noted. Older age, obesity, current smoking, New York Heart Association class III/IV, and comorbid illnesses were associated with declines in KCCQ scores. Use of spironolactone was an independent predictor of improved KCCQ scores. CONCLUSIONS: In symptomatic HF with preserved ejection fraction patients, use of spironolactone was associated with an improvement in HF-specific HRQL. Several modifiable risk factors were associated with HRQL deterioration. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302

The Relationship between Therapeutic Alliance and Service User Satisfaction in Mental Health Inpatient Wards and Crisis House Alternatives: A Cross-Sectional Study

Background Poor service user experiences are often reported on mental health inpatient wards. Crisis houses are an alternative, but evidence is limited. This paper investigates therapeutic alliances in acute wards and crisis houses, exploring how far stronger therapeutic alliance may underlie greater client satisfaction in crisis houses. Methods and Findings Mixed methods were used. In the quantitative component, 108 crisis house and 247 acute ward service users responded to measures of satisfaction, therapeutic relationships, informal peer support, recovery and negative events experienced during the admission. Linear regressions were conducted to estimate the association between service setting and measures, and to model the factors associated with satisfaction. Qualitative interviews exploring therapeutic alliances were conducted with service users and staff in each setting and analysed thematically. Results We found that therapeutic alliances, service user satisfaction and informal peer support were greater in crisis houses than on acute wards, whilst self-rated recovery and numbers of negative events were lower. Adjusted multivariable analyses suggest that therapeutic relationships, informal peer support and negative experiences related to staff may be important factors in accounting for greater satisfaction in crisis houses. Qualitative results suggest factors that influence therapeutic alliances include service user perceptions of basic human qualities such as kindness and empathy in staff and, at service level, the extent of loss of liberty and autonomy. Conclusions and Implications We found that service users experience better therapeutic relationships and higher satisfaction in crisis houses compared to acute wards, although we cannot exclude the possibility that differences in service user characteristics contribute to this. This finding provides some support for the expansion of crisis house provision. Further research is needed to investigate why acute ward service users experience a lack of compassion and humanity from ward staff and how this could be changed

An RxLR effector from phytophthora infestans prevents re-localisation of two plant NAC transcription factors from the endoplasmic reticulum to the nucleus

The plant immune system is activated following the perception of exposed, essential and invariant microbial molecules that are recognised as non-self. A major component of plant immunity is the transcriptional induction of genes involved in a wide array of defence responses. In turn, adapted pathogens deliver effector proteins that act either inside or outside plant cells to manipulate host processes, often through their direct action on plant protein targets. To date, few effectors have been shown to directly manipulate transcriptional regulators of plant defence. Moreover, little is known generally about the modes of action of effectors from filamentous (fungal and oomycete) plant pathogens. We describe an effector, called Pi03192, from the late blight pathogen Phytophthora infestans, which interacts with a pair of host transcription factors at the endoplasmic reticulum (ER) inside plant cells. We show that these transcription factors are released from the ER to enter the nucleus, following pathogen perception, and are important in restricting disease. Pi03192 prevents the plant transcription factors from accumulating in the host nucleus, revealing a novel means of enhancing host susceptibility

Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease)

The neuronal ceroid lipofuscinoses are a group of lysosomal storage disorders that comprise the most common, genetically heterogeneous, fatal neurodegenerative disorders of children. They are characterised by childhood onset, visual failure, epileptic seizures, psychomotor retardation and dementia. CLN3 disease, also known as Batten disease, is caused by autosomal recessive mutations in the CLN3 gene, 80–85% of which are a ~1 kb deletion. Currently no treatments exist, and after much suffering, the disease inevitably results in premature death. The aim of this study was to generate a zebrafish model of CLN3 disease using antisense morpholino injection, and characterise the pathological and functional consequences of Cln3 deficiency, thereby providing a tool for future drug discovery. The model was shown to faithfully recapitulate the pathological signs of CLN3 disease, including reduced survival, neuronal loss, retinopathy, axonopathy, loss of motor function, lysosomal storage of subunit c of mitochondrial ATP synthase, and epileptic seizures, albeit with an earlier onset and faster progression than the human disease. Our study provides proof of principle that the advantages of the zebrafish over other model systems can be utilised to further our understanding of the pathogenesis of CLN3 disease and accelerate drug discovery