Using Population Reach as a Proxy Metric for Intervention Impact to Prioritize Selection of Obesity Prevention Strategies in Los Angeles County, 2010–2012

Recent federal initiatives have used estimates of population reach as a proxy metric for intervention impact, in part to inform resource allocation and programmatic decisions about competing priorities in the community. However, in spite of its utility, population reach as a singular metric of intervention impact may be insufficient for guiding multifaceted program decisions. A more comprehensive, validated approach to measure or forecast dose may complement reach estimates to inform decision makers about optimal ways to use limited resources.Although federal initiatives in obesity prevention have typically recommended the use of evidence-based community strategies,1 less is known about the level of impact that these strategies can contribute to improving health in the real world. The absence of this type of practice-based information often poses significant challenges to funding agencies and program planners that are tasked with prioritizing and selecting intervention strategies for a city or community. Given that this information is not readily available or regularly reported, recent federal initiatives have begun to request data on intervention impact, using estimates of population reach as a proxy metric for predicting the extent of intervention effectiveness. The Centers for Disease Control and Prevention, for example, recently provided guidance on how to measure and report reach for a range of obesity prevention interventions focused on improving systems and environments in cities and communities across the United States.2 They broadly defined “reach” as the number of unique individuals affected by a program initiative and further refined this concept to include direct reach as the number of unique individuals exposed to the intervention in some way and indirect reach as the number of unique individuals indirectly exposed to the intervention in some way but who are not residents of a targeted community (e.g., visitors).2 To provide more specificity, other agencies and organizations (e.g., the Center for Community Health and Evaluation) have sought to account for the effects of community health interventions by incorporating intervention dose as an additional parameter for consideration in their priority-setting process and program planning.3 In this context, “dose” has been defined as the product of reach (percentage of people exposed to an intervention) and strength (the degree to which people reached by the intervention changed their health behaviors).3 Although dose is a more robust measure of intervention impact, reach is generally easier to estimate and use, given the time constraints and limited availability of relevant data sources to local leaders who must make daily decisions about policy development, program implementation, and operations. It is important to note, however, that the Centers for Disease Control and Prevention and the Center for Community Health and Evaluation differ in their definitions of “reach.” Although the former’s definition distinguishes between direct and indirect number of unique individuals, the latter’s does not, making comparisons of this metric across studies, interventions, places, settings, and times difficult to achieve.Although the aforementioned metrics (reach and dose) can provide meaningful data to inform health and public health decisions,4,5 few strategic planning efforts have incorporated their use in the prioritization process.6 In this article, we describe the effort of the Los Angeles County Department of Public Health (DPH) to systematically incorporate population reach as a proxy metric of intervention impact, using it to guide prioritization of system and environmental change strategies for community implementation (when appropriate). The motivation for writing this article is to inform the efforts of other agencies similarly tasked with addressing the obesity epidemic in their communities but often constrained by limited resources and several competing priorities in their jurisdictions.     

Youth Development Through Mentorship: A Los Angeles School-Based Mentorship Program Among Latino Children

Despite higher risk for school failure, few school-based mentoring (SBM) studies have focused on low-income at-risk Latino children. We describe the development and evaluation of the Youth Empowerment Program (YEP), a sustainable, high-quality, SBM program among urban Latino students. Based on evidence from work in other communities, YEP was created as a partnership between the 4th and 5th grades at a Los Angeles Title I elementary school and university undergraduates. We tested the feasibility of applying a previously validated relationship quality assessment tool in this population. Since 2008, 61 mentor and mentee pairs have participated in YEP, with an average relationship length of 1.5 years. Through 2010, over 95 % of pairs had relationships lasting at least 1 year, while 47 % lasted 2 or more years. Seventy-percent of mentees and 85 % of mentors were female, and an increased trend for early relationship termination was observed among male mentees. Through 2011, relationships lasted under 1 year among 29 % of male mentees compared to 7 % of female mentees (p = 0.15). A previously validated relationship quality assessment tool was easily incorporated into YEP, with relationships exhibiting youth-centeredness, emotional engagement and low dissatisfaction. After 5 years, YEP has become a feasible and sustainable SBM program providing long-term relationships for low-income Latino children. These relationships may improve youth health through fewer risky behaviors and attitude improvements. Future work should focus on supporting male mentors and mentees.     

Effect of Cocaine on Ion Channels and Glutamatergic EPSCs in Noradrenergic Locus Coeruleus Neurons

The locus coeruleus (LC) is an important brainstem area involved in cocaine addiction. However, evidence to elucidate how cocaine modulates the activity of LC neurons remains incomplete. Here, we performed whole recordings in brain slices to evaluate the effects of cocaine on the sodium (Na⁺), potassium (K⁺), calcium (Ca²⁺) channels, and glutamatergic synaptic transmission in the locus coeruleus neurons. Local application of cocaine significantly and reversibly reduced the spontaneous firing rate but did not affect action potential amplitude, rising time, decay time, or half width of noradrenergic locus coeruleus neurons. Moreover, cocaine attenuated the sodium current but did not affect potassium and calcium currents. The N-methyl-d-aspartate receptor mediated excitatory postsynaptic currents were reduced by neuropeptide galanin but not cocaine. All those data demonstrate that cocaine has inhibitory effect on the spontaneous activities and sodium current in locus coeruleus neurons. Therefore, neuromodulation of sodium channel in locus coeruleus neurons may play an important role in drug addiction.     

Psychotic disorder induced by a combination of sorafenib and BAY86-9766

The Ras-Raf-mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK cascade is important in the intra-cellular transduction of neurotransmitters, such as dopamine and glutamate. Sorafenib (Nexavar), a multi-kinase inhibitor targeting Raf kinase, vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor, has shown promising results in the treatment of malignancies. BAY86-9766, a novel selective MEK 1/2 inhibitor, is being evaluated in clinical trials as an anticancer drug. We describe herein a hepatocellular carcinoma patient presenting with recurrent psychotic symptoms in the course of the BASIL trial (assessing BAY86-9766 plus sorafenib for the treatment of liver cancer). In this case, VEGFR inhibition caused by sorafenib alone may have contributed to the development of psychosis. A change in ERK activity might also have been involved. However, whether single or combination use of the two drugs is responsible for inducing the psychotic symptoms remains unclear. In summary, the role of the ERK pathway in psychosis is still vague. Further investigation of the ERK activity in patients with psychotic disorders may disclose its role in the pathophysiology of psychosis.     

口颊黏膜在尿道重建中的应用

随着尿道重建技术的不断改进,口颊黏膜替代尿道成形术逐渐成为前尿道缺损修复的最佳选择。本文主要对口颊黏膜的优势特点作一介绍,并阐述口颊黏膜替代尿道成形术在前尿道狭窄和尿道下裂中的临床应用和进展。     

A minimally invasive strategy for Mirizzi syndrome: the combined endoscopic and robotic approach

Background

Mirizzi syndrome (MS) is a rare complication of gallstone disease. Despite the fact that successful laparoscopic treatments have been reported, open surgery remains the gold standard approach for this disease due to technical difficulties involved.

Methods

A minimally invasive strategy combining endoscopic retrograde cholangiopancreatography (ERCP) and robotic surgery for the management of MS was implemented in early 2012. This consisted of a preoperative ERCP for definitive diagnosis and endoscopic stent insertion. Robotic surgical approach was used during operation to facilitate gall bladder removal and suture of defect over common duct. ERCP was repeated postoperatively for stent removal. Patient demographics and treatment outcomes were collected prospectively. A historical cohort of patients with MS who underwent conventional surgery between 1999 and 2011 was identified for comparison of treatment outcomes.

Results

Five patients with MS were managed with this strategy. Robotic subtotal cholecystectomy was successfully performed in all the patients without conversion or morbidity. When compared with a historical cohort of 17 patients who underwent surgery for MS, this group of patients had significantly less conversion and shorter hospital stay though the operation time was longer. It also showed less blood loss and less postoperative complications but these were not statistically significant.

Conclusion

Mirizzi syndrome can be effectively managed with a minimally invasive approach by adopting a robot-assisted surgery together with a planned pre- and postoperative ERCP.     

Evaluation of efficacy,biodistribution and safety of antibiotic-free plasmid encoding somatostatin genes delivered by attenuated Salmonella enterica serovar Choleraesuis

We describe here a balanced-lethal system using an Asd⁺ expression plasmid pVGS/2SS-asd encoding two copies of somatostatin (SS) genes carried by Δasd/Δcrp double mutant Salmonella enterica serovar Choleraesuis (named C501). The advantage of this novel system is the use of asd (aspartate-semialdehyde dehydrogenase) gene as selection marker to replace the antibiotic resistance markers, thus eliminating the industrial cultivation and environmental problems. We then evaluated the efficacy, biodistribution and safety of antibiotic-free plasmid delivered by strains C501. Mice orally immunized with C501 (pVGS/2SS-asd) had significantly higher levels of anti-SS total IgG and IgA antibodies than control mice and demonstrated a bias toward Th2-associated responses (IgG1/IgG2a ratio > 1). Safety evaluation indicated that vaccinated mice displayed no abnormal clinical signs and histological changes. Biodistribution result revealed that the GS/2SS message was detected in several examined tissues with the exception of ovary and brain, but was rapidly cleared from the body (approximately 10 days). Furthermore, the risk of integration of plasmid pVGS/2SS-asd into the host cellular genome was considered to be negligible. These results may have important implications for the use of vaccine strain C501 (pVGS/2SS-asd) in domestic animals and prompt new perspectives on the safety of DNA vaccines delivered by attenuated bacteria.     

Near disappearance of childhood invasive Haemophilus influenzae type b disease in Singapore

Background

Haemophilus influenzae type b (Hib) conjugate vaccines have significantly limited Hib's disease impact in every country where it was introduced. We previously estimated invasive Hib disease incidence in Singapore at ∼4.4 per 100,000 children <5 years (from 1994 to 2003, period 1), but the vaccine was not included in the national childhood immunization schedule until May 2013 (although it was available privately). The current study aims to describe changes in Hib disease incidence and vaccine coverage prior to the introduction of the vaccine.

Methodology

We retrospectively reviewed all invasive Hib cases from January 2004 to December 2012 (period 2) and estimated population-based incidence rates. Vaccine coverage was estimated from vaccine sales for 1994–2003, and from National Immunisation Registry for 2004–2010.

Results

There were 8 cases of invasive Hib disease in period 2, of whom 5 were <5 years. Invasive Hib incidence for period 2 was 0.57 per 100,000 children <5 years, representing an 86.4% reduction compared to period 1 (rate ratio 0.14, 95% confidence interval 0.06–0.26). However, for the later part of period 2 (2008–2012), incidence was 0.2 per 100,000 children <5 years; this represented a 95% reduction from period 1 (rate ratio 0.05, 95% confidence interval 0.01–0.18). Between periods 1 and 2, national Hib vaccine coverage rose from 22% to >80%, with >99% of children receiving combination Hib-containing vaccines.

Conclusions

Childhood invasive Hib disease has nearly disappeared from Singapore, despite the absence of universal mass vaccination. We believe this is likely due to excellent uptake of combination vaccines.