Cysteamine toxicity presenting with acute encephalopathy and spastic tetraparesis.

Cystinosis is a lysosomal storage disorder usually presenting with renal disease in infancy. As soon as the diagnosis is made, cysteamine (a cystine-depleting medication), is started, significantly improving life expectancy. We describe a young woman taking lifelong cysteamine for nephropathic cystinosis, who became acutely encephalopathic with a spastic tetraparesis secondary to cysteamine toxicity, which was potentially worsened by copper deficiency. On replacing copper and reducing the dose of cysteamine, she made a full neurological recovery. We discuss the case, and review cystinosis and what is known about cysteamine toxicity.

Longitudinal MRI brain studies in live adult zebrafish.

Zebrafish (Danio rerio) has been successfully used for decades in developmental studies and disease modelling. The remarkable uptake of zebrafish as a model system is partly due to its transparency during the early weeks of its development, allowing in vivo imaging of cellular and molecular processes. However, this key advantage wears off when tissues become opaque as the animal reaches juvenile and adult stages, rendering access to tissues for live imaging and longitudinal studies difficult. Here we provide a novel approach to image and assess tissue integrity of adult zebrafish using MRI on live zebrafish suitable for longitudinal studies. We built a 3D-printed life support chamber and designed a protocol-directed sedation regime to recover adult zebrafish after scanning in a 9.4 T MRI scanner. Our life support chamber is cheap and easy to create using 3D printing, allowing other groups to copy our template for quick setup. Additionally, we optimized the delivery of contrast agent to enhance brain signals in order to refine current delivery, usually delivered intravenously in rodents. We show here that immersion in gadolinium was a viable alternative to intraperitoneal injection to reduce T1 relaxation times. This resulted in protocol refinement as per the 3Rs guidelines and improved image contrast in adult zebrafish disease models. In conclusion, we provide here a detailed methodology to allow longitudinal studies of brain tissue integrity of adult zebrafish, combining safe and efficient delivery of contrast agent and live MRI. This technique can be used to bridge the gap between in vivo studies and longitudinal brain analysis in adult zebrafish, and can be applied to the ever-growing number of adult zebrafish models of ageing and neurodegenerative diseases.

Serine-arginine-rich protein kinase-1 inhibition for the treatment of diabetic retinopathy.

Angiogenic VEGF isoforms are upregulated in diabetic retinopathy (DR), driving pathological growth and fluid leakage. Serine-arginine-rich protein kinase-1 (SRPK1) regulates VEGF splicing, and its inhibition blocks angiogenesis. We tested the hypothesis that SRPK1 is activated in diabetes, and an SRPK1 inhibitor (SPHINX31) switches VEGF splicing in DR and prevents increased vascular permeability into the retina. SRPK1 was activated by high glucose (HG), in a PKC-dependent manner, and was blocked by SPHINX31. HG induced release of SRSF1 from the nuclear speckles, which was also SRPK1 dependent, and increased retinal pigment epithelial (RPE) monolayer admittance, which was reversed by SRPK1 inhibition (P < 0.05). Diabetes increased retinal permeability and thickness after 14 days which was blocked by treatment with SPHINX31 eye drops (P < 0.0001). These results show that SRPK1 inhibition, administered as an eye drop, protected the retinal barrier from hyperglycemia-associated loss of integrity in RPE cells in vitro and in diabetic rats in vivo. A clinical trial of another SRPK1 inhibitor has now been initiated in patients with diabetic macular edema.NEW & NOTEWORTHY VEGF-A165b splicing is induced by hyperglycemia through PKC-mediated activation of SRPK1 in RPE cells, increasing their permeability and angiogenic capability. SRPK1 inhibitors can be given as eye drops to reduce retinal permeability and edema in diabetic retinopathy.

Epidemiological and cohort study finds no association between COVID-19 and Guillain-Barré syndrome.

Reports of Guillain-Barré syndrome (GBS) have emerged during the Coronavirus disease 2019 (COVID-19) pandemic. This epidemiological and cohort study sought to investigate any causative association between COVID-19 infection and GBS. The epidemiology of GBS cases reported to the UK National Immunoglobulin Database was studied from 2016 to 2019 and compared to cases reported during the COVID-19 pandemic. Data were stratified by hospital trust and region, with numbers of reported cases per month. UK population data for COVID-19 infection were collated from UK public health bodies. In parallel, but separately, members of the British Peripheral Nerve Society prospectively reported incident cases of GBS during the pandemic at their hospitals to a central register. The clinical features, investigation findings and outcomes of COVID-19 (definite or probable) and non-COVID-19 associated GBS cases in this cohort were compared. The incidence of GBS treated in UK hospitals from 2016 to 2019 was 1.65-1.88 per 100 000 individuals per year. GBS incidence fell between March and May 2020 compared to the same months of 2016-19. GBS and COVID-19 incidences during the pandemic also varied between regions and did not correlate with one another (r = 0.06, 95% confidence interval: -0.56 to 0.63, P = 0.86). In the independent cohort study, 47 GBS cases were reported (COVID-19 status: 13 definite, 12 probable, 22 non-COVID-19). There were no significant differences in the pattern of weakness, time to nadir, neurophysiology, CSF findings or outcome between these groups. Intubation was more frequent in the COVID-19 affected cohort (7/13, 54% versus 5/22, 23% in COVID-19-negative) attributed to COVID-19 pulmonary involvement. Although it is not possible to entirely rule out the possibility of a link, this study finds no epidemiological or phenotypic clues of SARS-CoV-2 being causative of GBS. GBS incidence has fallen during the pandemic, which may be the influence of lockdown measures reducing transmission of GBS inducing pathogens such as Campylobacter jejuni and respiratory viruses.

Non-invasive measurement of retinal permeability in a diabetic rat model.

OBJECTIVE: The gold standard for measuring blood-retinal barrier permeability is the Evans blue assay. However, this technique has limitations in vivo, including non-specific tissue binding and toxicity. This study describes a non-toxic, high-throughput, and cost-effective alternative technique that minimizes animal usage. METHODS: Sodium fluorescein fundus angiography was performed in non-diabetic and diabetic Brown Norway rats on days 0, 7, 14, 21, and 28. Sodium fluorescein intensity in the retinal interstitium and a main retinal vessel were measured over time. The intensity gradients were used to quantify retinal vascular permeability. Post-study eyes were fixed, dissected, and stained (isolectin B4) to measure required parameters for permeability quantification including total vessel length per retinal volume, radius, and thickness. RESULTS: In the non-diabetic cohort retinal permeability remained constant over the 28-day study period. However, in the diabetic cohort there was a significant and progressive increase in retinal permeability from days 14-28 (P < .01, P < .001, P < .0001). CONCLUSIONS: This novel imaging methodology in combination with mathematical quantification allows retinal permeability to be non-invasively and accurately measured at multiple time points in the same animal. In addition, this technique is a non-toxic, rapid, sensitive, and cost-effective alternative to the Evans blue assay.

Disseminating Evidence-Based Interventions in Small, Low-Wage Worksites: A Randomized Controlled Trial in King County, Washington (2014-2017).

Objectives. To determine whether (1) participating in HealthLinks, and (2) adding wellness committees to HealthLinks increases worksites' evidence-based intervention (EBI) implementation.Methods. We developed HealthLinks to disseminate EBIs to small, low-wage worksites. From 2014 to 2017, we conducted a site-randomized trial in King County, Washington, with 68 small worksites (20-200 employees). We assigned worksites to 1 of 3 arms: HealthLinks, HealthLinks plus wellness committee (HealthLinks+), or delayed control. At baseline, 15 months, and 24 months, we assessed worksites' EBI implementation on a 0% to 100% scale and employees' perceived support for their health behaviors.Results. Postintervention EBI scores in both intervention arms (HealthLinks and HealthLinks+) were significantly higher than in the control arm at 15 months (51%, 51%, and 23%, respectively) and at 24 months (33%, 37%, and 24%, respectively; P < .001). Employees in the intervention arms perceived greater support for their health at 15 and 24 months than did employees in control worksites.Conclusions. HealthLinks is an effective strategy for disseminating EBIs to small worksites in low-wage industries.Public Health Implications. Future research should focus on scaling up HealthLinks, improving EBI maintenance, and measuring impact of these on health behavior.

Improving the science and evidence base of disaster response: a policy research study.

BACKGROUND: In order to elicit the knowledge, experience, and attitudes of individuals involved in disaster response with regard to evidence-based best practices, Evidence Aid and its institutional partners, Georgetown University and the Uniformed Services University of the Health Sciences, carried out a Policy Delphi study in 2015-2016. METHODS: Purposive and snowball methods were used to select study participants. The Delphi study comprised two rounds of iterative questions, with the questionnaires completed online. In addition, participants at the Evidence Aid conference in November 2016 discussed the findings in focus groups. Excel was used to analyze the quantitative data and Glaser and Strauss (1967) to analyze the qualitative data. RESULTS: Thirty-six participants responded to the first round of the study, 165 responded to the second round, and 30 participated in the focus group discussions. The salient findings include 1) ensuring that all key stakeholders are engaged in planning for and responding to disasters in a collaborative, coordinated manner-including local community members; 2) using, insofar as possible, evidence-based responses; 3) increasing and strengthening research to ensure that such data are available; and 4) addressing ethical, legal and social issues throughout the planning, immediate response, and post-disaster periods. CONCLUSIONS: Recent humanitarian disasters, due to natural and man-made hazards or a combination of the two, reinforce the need for more effective, efficient, humane responses at the local, national and international levels. This study has yielded findings that can be used to strengthen planning and response by taking into account, where possible, evidence based on research that has been carried out with the engagement of community members and with support by key stakeholders. The most effective means of facilitating the development and implementation of consistent, coordinated policies and practices might be for the United Nations Office for Disaster Risk Reduction to take the lead in engaging key organizations in the required discussions and collaborations.

Quantitative comparison of taxa and taxon concepts in the diatom genus Fragilariopsis: a case study on using slide scanning, multiexpert image annotation, and image analysis in taxonomy1.

Semiautomated methods for microscopic image acquisition, image analysis, and taxonomic identification have repeatedly received attention in diatom analysis. Less well studied is the question whether and how such methods might prove useful for clarifying the delimitation of species that are difficult to separate for human taxonomists. To try to answer this question, three very similar Fragilariopsis species endemic to the Southern Ocean were targeted in this study: F. obliquecostata, F. ritscheri, and F. sublinearis. A set of 501 extended focus depth specimen images were obtained using a standardized, semiautomated microscopic procedure. Twelve diatomists independently identified these specimen images in order to reconcile taxonomic opinions and agree upon a taxonomic gold standard. Using image analyses, we then extracted morphometric features representing taxonomic characters of the target taxa. The discriminating ability of individual morphometric features was tested visually and statistically, and multivariate classification experiments were performed to test the agreement of the quantitatively defined taxa assignments with expert consensus opinion. Beyond an updated differential diagnosis of the studied taxa, our study also shows that automated imaging and image analysis procedures for diatoms are coming close to reaching a broad applicability for routine use.

Nonsteroidal anti-inflammatory drugs for pain in women with endometriosis.

BACKGROUND: Endometriosis is a common gynaecological condition that affects women and can lead to painful symptoms and infertility. It greatly affects women's quality of life, impacting their careers, everyday activities, sexual and nonsexual relationships and fertility. Nonsteroidal anti-inflammatory drugs (NSAIDs) are most commonly used as first-line treatment for women with pain associated with endometriosis. OBJECTIVES: To assess effects of NSAIDs used for management of pain in women with endometriosis compared with placebo, other NSAIDs, other pain management drugs or no treatment. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials (October 2016), published in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, as well as MEDLINE (January 2008 to October 2016), Embase (date limited from 1 January 2016 to 19 October 2016, as all earlier references are included in CENTRAL output as a result of the Embase project), registers of ongoing trials and the reference lists of relevant publications. We identified no new randomised controlled trials. Unless we identify new evidence in the future, we will not update this review. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) describing use of NSAIDs for management of pain associated with endometriosis in women of all ages. DATA COLLECTION AND ANALYSIS: In the 2009 update of this review, two review authors (CA and SH) independently read and extracted data from each of the included studies. We analysed cross-over trials using the inverse variance method of RevMan to calculate odds ratios for binary outcomes. MAIN RESULTS: We identified no new trials for the 2016 update. This review includes two trials, but we included only one trial, with 24 women, in the analysis.The overall risk of bias was unclear owing to lack of methodological detail. Using the GRADE method, we judged the quality of the evidence to be very low. We downgraded evidence for risk of bias and for imprecision (wide confidence intervals and evidence based on a single small trial).Comparison of NSAIDs (naproxen) versus placebo revealed no evidence of a positive effect on pain relief (odds ratio (OR) 3.27, 95% confidence interval (CI) 0.61 to 17.69; one trial, 24 women; very low-quality evidence) in women with endometriosis. Evidence indicating whether women taking NSAIDs (naproxen) were less likely to require additional analgesia (OR 0.12, 95% CI 0.01 to 1.29; one trial, 24 women; very low-quality evidence) or to experience side effects (OR 0.46, 95% CI 0.09 to 2.47; one trial, 24 women; very low-quality evidence) when compared with placebo was inconclusive.Studies provided no data on quality of life, effects on daily activities, absence from work or school, need for more invasive treatment or participant satisfaction with treatment. AUTHORS' CONCLUSIONS: Owing to lack of high-quality evidence and lack of reporting of outcomes of interest for this review, we can make no judgement as to whether NSAIDs (naproxen) are effective in managing pain caused by endometriosis. No evidence shows whether any individual NSAID is more effective than another. As shown in other Cochrane reviews, women taking NSAIDs must be aware that these drugs may cause unintended effects.

A retrospective review of anesthesia and perioperative care in children with medium-chain acyl-CoA dehydrogenase deficiency.

BACKGROUND: Medium-chain acyl-CoA dehydrogenase deficiency is the most common genetically determined disorder of mitochondrial fatty acid oxidation. Decompensation can result in hypoglycemia, seizures, coma, and death but may be prevented by ensuring glycogen stores do not become depleted. Perioperative care is of interest as surgery, fasting, and infection may all trigger decompensation and the safety of anesthetic agents has been questioned. Current guidelines from the British Inherited Metabolic Disease Group advise on administering fluid containing 10% glucose during the perioperative period. AIM: To review the management of anesthesia and perioperative care for children with medium-chain acyl-CoA dehydrogenase deficiency and determine the frequency and nature of any complications. METHOD: A retrospective review of case notes of children with medium-chain acyl-CoA dehydrogenase deficiency undergoing anesthesia between 1997 and 2014. RESULTS: Fourteen patients underwent 21 episodes of anesthesia. In 20 episodes, the patient received a glucose-containing fluid during their perioperative fast, of which eight received fluid containing 10% dextrose throughout the entire perioperative period. No episodes of hypoglycemia or decompensation occurred, but perioperative hyperglycemia occurred in five episodes. A propofol bolus was administered at induction in 16 episodes and volatile agents were administered for maintenance of anesthesia in all episodes without any observed complications. In one episode, delayed offset of atracurium was reported. CONCLUSIONS: Perioperative metabolic decompensation and hypoglycemia appear to be uncommon in children who are well and receive glucose supplementation. Hyperglycemia may occur as a consequence of surgery and glucose supplementation. Propofol boluses and volatile anesthetic agents were used without any apparent complications. Prolonged action of atracurium was reported in one case, suggesting that nondepolarizing muscle relaxants may have delayed offset in this patient group. We do not recommend any particular approach to anesthesia but would advise administering glucose supplementation according to current guidelines, frequent monitoring of blood glucose perioperatively, and monitoring of neuromuscular blockade.

In vivo physiological recording from the lateral line of juvenile zebrafish.

KEY POINTS: Zebrafish provide a unique opportunity to investigate in vivo sensory transduction in mature hair cells. We have developed a method for studying the biophysical properties of mature hair cells from the lateral line of juvenile zebrafish. The method involves application of the anaesthetic benzocaine and intubation to maintain ventilation and oxygenation through the gills. The same approach could be used for in vivo functional studies in other sensory and non-sensory systems from juvenile and adult zebrafish. ABSTRACT: Hair cells are sensory receptors responsible for transducing auditory and vestibular information into electrical signals, which are then transmitted with remarkable precision to afferent neurons. The zebrafish lateral line is emerging as an excellent in vivo model for genetic and physiological analysis of hair cells and neurons. However, research has been limited to larval stages because zebrafish become protected from the time of independent feeding under European law (from 5.2 days post-fertilization (dpf) at 28.5°C). In larval zebrafish, the functional properties of most of hair cells, as well as those of other excitable cells, are still immature. We have developed an experimental protocol to record electrophysiological properties from hair cells of the lateral line in juvenile zebrafish. We found that the anaesthetic benzocaine at 50 mg l(-1) was an effective and safe anaesthetic to use on juvenile zebrafish. Concentrations up to 300 mg l(-1) did not affect the electrical properties or synaptic vesicle release of juvenile hair cells, unlike the commonly used anaesthetic MS-222, which reduces the size of basolateral membrane K(+) currents. Additionally, we implemented a method to maintain gill movement, and as such respiration and blood oxygenation, via the intubation of > 21 dpf zebrafish. The combination of benzocaine and intubation provides an experimental platform to investigate the physiology of mature hair cells from live zebrafish. More generally, this method would allow functional studies involving live imaging and electrophysiology from juvenile and adult zebrafish.

Bisphosphonates for steroid-induced osteoporosis.

BACKGROUND: This is an update of a Cochrane Review first published in 1999. Corticosteroids are widely used in inflammatory conditions as an immunosuppressive agent. Bone loss is a serious side effect of this therapy. Several studies have examined the use of bisphosphonates in the prevention and treatment of glucocorticosteroid-induced osteoporosis (GIOP) and have reported varying magnitudes of effect. OBJECTIVES: To assess the benefits and harms of bisphosphonates for the prevention and treatment of GIOP in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase up to April 2016 and International Pharmaceutical Abstracts (IPA) via OVID up to January 2012 for relevant articles and conference proceedings with no language restrictions. We searched two clinical trial registries for ongoing and recently completed studies (ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal). We also reviewed reference lists of relevant review articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) satisfying the following criteria: 1) prevention or treatment of GIOP; 2) adults taking a mean steroid dose of 5.0 mg/day or more; 3) active treatment including bisphosphonates of any type alone or in combination with calcium or vitamin D; 4) comparator treatment including a control of calcium or vitamin D, or both, alone or with placebo; and 4) reporting relevant outcomes. We excluded trials that included people with transplant-associated steroid use. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials for inclusion, extracted data, performed 'risk of bias' assessment and evaluated the certainty of evidence using the GRADE approach. Major outcomes of interest were the incidence of vertebral and nonvertebral fractures after 12 to 24 months; the change in bone mineral density (BMD) at the lumbar spine and femoral neck after 12 months; serious adverse events; withdrawals due to adverse events; and quality of life. We used standard Cochrane methodological procedures. MAIN RESULTS: We included a total of 27 RCTs with 3075 participants in the review. Pooled analysis for incident vertebral fractures included 12 trials (1343 participants) with high-certainty evidence and low risk of bias. In this analysis 46/597 (or 77 per 1000) people experienced new vertebral fractures in the control group compared with 31/746 (or 44 per 1000; range 27 to 70) in the bisphosphonate group; relative improvement of 43% (9% to 65% better) with bisphosphonates; absolute increased benefit of 2% fewer people sustaining fractures with bisphosphonates (5% fewer to 1% more); number needed to treat for an additional beneficial outcome (NNTB) was 31 (20 to 145) meaning that approximately 31 people would need to be treated with bisphosphonates to prevent new vertebral fractures in one person.Pooled analysis for incident nonvertebral fractures included nine trials with 1245 participants with low-certainty evidence (downgraded for imprecision and serious risk of bias as a patient-reported outcome). In this analysis 30/546 (or 55 per 1000) people experienced new nonvertebral fracture in the control group compared with 29/699 (or 42 per 1000; range 25 to 69) in the bisphosphonate group; relative improvement of 21% with bisphosphonates (33% worse to 53% better); absolute increased benefit of 1% fewer people with fractures with bisphosphonates (4% fewer to 1% more).Pooled analysis on BMD change at the lumbar spine after 12 months included 23 trials with 2042 patients. Eighteen trials with 1665 participants were included in the pooled analysis on BMD at the femoral neck after 12 months. Evidence for both outcomes was moderate-certainty (downgraded for indirectness as a surrogate marker for osteoporosis) with low risk of bias. Overall, the bisphosphonate groups reported stabilisation or increase in BMD, while the control groups showed decreased BMD over the study period. At the lumbar spine, there was an absolute increase in BMD of 3.5% with bisphosphonates (2.90% to 4.10% higher) with a relative improvement of 1.10% with bisphosphonates (0.91% to 1.29%); NNTB 3 (2 to 3). At the femoral neck, the absolute difference in BMD was 2.06% higher in the bisphosphonate group compared to the control group (1.45% to 2.68% higher) with a relative improvement of 1.29% (0.91% to 1.69%); NNTB 5 (4 to 7).Pooled analysis on serious adverse events included 15 trials (1703 participants) with low-certainty evidence (downgraded for imprecision and risk of bias). In this analysis 131/811 (or 162 per 1000) people experienced serious adverse events in the control group compared to 136/892 (or 147 per 1000; range 120 to 181) in the bisphosphonate group; absolute increased harm of 0% more serious adverse events (2% fewer to 2% more); a relative per cent change with 9% improvement (12% worse to 26% better).Pooled analysis for withdrawals due to adverse events included 15 trials (1790 patients) with low-certainty evidence (downgraded for imprecision and risk of bias). In this analysis 63/866 (or 73 per 1000) people withdrew in the control group compared to 76/924 (or 77 per 1000; range 56 to 107) in the bisphosphonate group; an absolute increased harm of 1% more withdrawals with bisphosphonates (95% CI 1% fewer to 3% more); a relative per cent change 6% worse (95% CI 47% worse to 23% better).Quality of life was not assessed in any of the trials. AUTHORS' CONCLUSIONS: There was high-certainty evidence that bisphosphonates are beneficial in reducing the risk of vertebral fractures with data extending to 24 months of use. There was low-certainty evidence that bisphosphonates may make little or no difference in preventing nonvertebral fractures. There was moderate-certainty evidence that bisphosphonates are beneficial in preventing and treating corticosteroid-induced bone loss at both the lumbar spine and femoral neck. Regarding harm, there was low-certainty evidence that bisphosphonates may make little or no difference in the occurrence of serious adverse events or withdrawals due to adverse events. We are cautious in interpreting these data as markers for harm and tolerability due to the potential for bias.Overall, our review supports the use of bisphosphonates to reduce the risk of vertebral fractures and the prevention and treatment of steroid-induced bone loss.

Feasibility of Workplace Health Promotion for Restaurant Workers, Seattle, 2012.

INTRODUCTION: Restaurant workers are a large population at high risk for tobacco use, physical inactivity, and influenza. They are difficult to reach with health care interventions and may be more accessible through workplaces, yet few studies have explored the feasibility of workplace health promotion in this population. This study sought to identify barriers and facilitators to promotion of tobacco cessation, physical activity, and influenza vaccination in restaurants. METHODS: Moderators conducted 7 focus groups, 3 with restaurant owners and managers, 2 with English-speaking workers, and 2 with Spanish-speaking workers. All groups were recorded, and recordings were transcribed and uploaded to qualitative-analysis software. Two researchers coded each transcript independently and analyzed codes and quotations for common themes. RESULTS: Seventy people from the restaurant industry participated. Barriers to workplace health promotion included smoking-break customs, little interest in physical activity outside of work, and misinformation about influenza vaccinations. Facilitators included creating and enforcing equitable break policies and offering free, on-site influenza vaccinations. Spanish-speakers were particularly amenable to vaccination, despite their perceptions of low levels of management support for health promotion overall. Owners required a strong business case to consider investing in long-term prevention for their employees. CONCLUSION: Tobacco cessation and influenza vaccinations are opportunities for health promotion among restaurant workers, whereas physical activity interventions face greater challenges. Promotion of equitable breaks, limited smoking-break policies, and free, on-site influenza vaccinations could improve health for restaurant workers, who often do not have health insurance. Workplace interventions may be particularly important for Hispanic workers who have additional access barriers.

Process evaluation of a regional public health model to reduce chronic disease through policy and systems changes, Washington State, 2010-2014.

INTRODUCTION: Although the regionalization of public health systems has been well documented in the case of emergency preparedness, there is little literature on the application of regional approaches to other aspects of public health. From 2011 through 2014 the Washington State Department of Health implemented a Community Transformation Grant to support community-level policy and systems changes to decrease chronic disease risk factors and increase access to clinical preventive services. The Department of Health implemented the grant through a regional model, grouping 32 of the state's 35 local health jurisdictions into 5 regions. Our process evaluation identifies the challenges and facilitators to Community Transformation Grant planning and implementation. METHODS: We conducted 34 key informant interviews with people directly involved in the implementation of the Community Transformation Grant. We interviewed state and local partners, including representatives from each region, the Department of Health, external consultants, and regional partners. We collected data from October 2013 through July 2014. RESULTS: Challenges for planning, building, and implementing a regional model for chronic disease prevention included stakeholder buy-in, regional geography, and communication; facilitators included shared regional history and infrastructure, strong leadership, collaborative relationships, shared vision and goals, sufficient funding, and direct technical assistance and training. CONCLUSION: Lessons learned in Washington State provide a foundation for other states interested in using a regional approach to reduce chronic disease risk. Policy and systems changes require adequate time, funding, and staffing. States and funders should work closely with local leaders to address these challenges and facilitators.

Vida PURA: A Cultural Adaptation of Screening and Brief Intervention to Reduce Unhealthy Drinking Among Latino Day Laborers.

BACKGROUND: Brief intervention is known to reduce drinking in primary care; however, because health care access is limited for Latino immigrants, traditional brief interventions are unlikely to reach this population. METHODS: Using Barrera and Castro's framework, our study aims to culturally adapt a screening and brief intervention program to reduce unhealthy alcohol use among Latino day laborers, a particularly vulnerable group of Latino immigrant men. We conducted 18 interviews with Latino day laborers and 13 interviews with mental health and substance use providers that serve Latino immigrant men. Interviews were conducted until saturation of themes was reached. Themes from interviews were used to identify sources of mismatch between traditional screening and brief intervention in our target population. RESULTS: Unhealthy alcohol use was common, culturally accepted, and helped relieve immigration-related stressors. Men had limited knowledge about how to change their behavior. Men preferred to receive information from trusted providers in Spanish. Men faced significant barriers to accessing health and social services but were open to receiving brief interventions in community settings. Findings were used to design Vida PURA, a preliminary adaptation design of brief intervention for Latino day laborers. Key adaptations include brief intervention at a day labor worker center provided by promotores trained to incorporate the social and cultural context of drinking for Latino immigrant men. CONCLUSIONS: Culturally adapted brief intervention may help reduce unhealthy drinking in this underserved population.

Influenza vaccination status and attitudes among restaurant employees.

CONTEXT: Restaurant employees represent a substantial portion of the US workforce, interact closely with the public, and are at risk for contracting influenza, yet their influenza vaccination rates and attitudes are unknown. OBJECTIVE: Assess influenza vaccination rates and attitudes among Seattle restaurant employees, to identify factors that could enhance the success of a restaurant-based vaccination program. DESIGN: In 2012, we invited employees of Seattle restaurants to complete an anonymous paper survey assessing participant demographics, previous influenza vaccination status, and personal attitudes toward influenza vaccination (using a 5-point scale). SETTING: Sit-down, full service restaurants in or near Seattle, Washington, were eligible if they had no previous history of offering worksite influenza vaccinations and had more than 20 employees who were older than 18 years and spoke either English or Spanish. PARTICIPANTS: We invited staff in all restaurant positions (servers, bussers, kitchen staff, chefs, managers, etc) to complete the survey, which was available in English and Spanish. RESULTS: Of 428 restaurant employees surveyed, 26% reported receiving the seasonal influenza vaccine in 2011-2012 (response rate = 74%). Across 8 attitude statements, participants were most likely to agree that the vaccine is not too expensive (89%), and least likely to agree that it is relevant for their age group (25%), or normative at their workplace (13%). Vaccinated participants reported significantly more positive attitudes than unvaccinated participants, and Hispanics reported significantly more positive attitudes than non-Hispanic whites. CONCLUSIONS: Increasing influenza vaccination rates among restaurant employees could protect a substantial portion of the US workforce, and the public, from influenza. Seattle restaurant employees have low vaccination rates against seasonal influenza. Interventions aimed at increasing vaccination among restaurant employees should highlight the vaccine's relevance and effectiveness for working-age adults.

Optimal evidence in difficult settings: improving health interventions and decision making in disasters.

Martin Gerdin and colleagues argue that disaster health interventions and decision-making can benefit from an evidence-based approach Please see later in the article for the Editors' Summary.

TigarB causes mitochondrial dysfunction and neuronal loss in PINK1 deficiency.

OBJECTIVE: Loss of function mutations in PINK1 typically lead to early onset Parkinson disease (PD). Zebrafish (Danio rerio) are emerging as a powerful new vertebrate model to study neurodegenerative diseases. We used a pink1 mutant (pink(-/-) ) zebrafish line with a premature stop mutation (Y431*) in the PINK1 kinase domain to identify molecular mechanisms leading to mitochondrial dysfunction and loss of dopaminergic neurons in PINK1 deficiency. METHODS: The effect of PINK1 deficiency on the number of dopaminergic neurons, mitochondrial function, and morphology was assessed in both zebrafish embryos and adults. Genome-wide gene expression studies were undertaken to identify novel pathogenic mechanisms. Functional experiments were carried out to further investigate the effect of PINK1 deficiency on early neurodevelopmental mechanisms and microglial activation. RESULTS: PINK1 deficiency results in loss of dopaminergic neurons as well as early impairment of mitochondrial function and morphology in Danio rerio. Expression of TigarB, the zebrafish orthologue of the human, TP53-induced glycolysis and apoptosis regulator TIGAR, was markedly increased in pink(-/-) larvae. Antisense-mediated inactivation of TigarB gave rise to complete normalization of mitochondrial function, with resulting rescue of dopaminergic neurons in pink(-/-) larvae. There was also marked microglial activation in pink(-/-) larvae, but depletion of microglia failed to rescue the dopaminergic neuron loss, arguing against microglial activation being a key factor in the pathogenesis. INTERPRETATION: Pink1(-/-) zebrafish are the first vertebrate model of PINK1 deficiency with loss of dopaminergic neurons. Our study also identifies TIGAR as a promising novel target for disease-modifying therapy in PINK1-related PD.

Opportunities for improving cancer prevention at federally qualified health centers.

As the Affordable Care Act unfolds, federally qualified health centers (FQHCs) will likely experience an influx of newly insured, low-income patients at disparate risk for cancer. Cancer-focused organizations are seeking to collaborate with FQHCs and the Primary Care Associations (PCAs) that serve them, to prevent cancer and reduce disparities. To guide this collaboration, we conducted 21 interviews with representatives from PCAs and FQHCs across four western states. We asked about: FQHC priorities, barriers and facilitators to cancer prevention, the PCA-FQHC relationship, and collaboration opportunities for external organizations. FQHC priorities include medical home transformation, electronic health records, and clinical care; prevention efforts must integrate with these. Barriers to cancer prevention include competing priorities, inadequate patient insurance, and lack of reimbursement, while facilitators are the presence of patient navigators and cancer-related performance measures. Collaboration opportunities for external organizations include dissemination of culturally appropriate educational materials and support for patient navigators.