Microbial succession from a subsequent secondary death event following mass mortality.

BACKGROUND: Each death event can be characterized by its associated microbes - a living community of bacteria composed of carcass, soil, and insect-introduced bacterial species - a necrobiome. With the possibility for close succession of these death events, it may be beneficial to characterize how the magnitude of an initial death event may impact the decomposition and necrobiomes of subsequent death events in close proximity. In this paper we hope to characterize the microbial communities associated with a proximate subsequent death event, and distinguish any changes within those communities based on the magnitude of an initial death event and the biomass of preexisting carcass (es) undergoing decomposition. For this experiment, 6 feral swine carcasses in containers were placed in the vicinity of preexisting and ongoing carcass decomposition at sites of three different scales of decomposing carcass biomass. Swab samples were collected from the skin and eye sockets of the container pigs and subjected to 16 s rRNA sequencing and OTU assignment. RESULTS: PERMANOVA analysis of the bacterial taxa showed that there was no significant difference in the bacterial communities based on initial mortality event biomass size, but we did see a change in the bacterial communities over time, and slight differences between the skin and ocular cavity communities. Even without soil input, necrobiome communities can change rapidly. Further characterization of the bacterial necrobiome included utilization of the Random Forest algorithm to identify the most important predictors for time of decomposition. Sample sets were also scanned for notable human and swine-associated pathogens. CONCLUSIONS: The applications from this study are many, ranging from establishing the environmental impacts of mass mortality events to understanding the importance of scavenger, and scavenger microbial community input on decomposition.

Research priorities for childhood chronic conditions: a workshop report.

BACKGROUND: Chronic conditions are the leading cause of mortality, morbidity and disability in children. However, children and caregivers are rarely involved in identifying research priorities, which may limit the value of research in supporting patient-centred practice and policy. OBJECTIVE: To identify priorities of patients, caregivers and health professionals for research in childhood chronic conditions and describe the reason for their choices. SETTING: An Australian paediatric hospital and health consumer organisations. METHODS: Recruited participants (n=73) included patients aged 8 to 14 years with a chronic condition (n=3), parents/caregivers of children aged 0 to 18 years with a chronic condition (n=19), representatives from consumer organisations (n=13) and health professionals including clinicians, researches (n=38) identified and discussed research priorities. Transcripts were thematically analysed. RESULTS: Seventy-eight research questions were identified. Five themes underpinned participants' priorities: maintaining a sense of normality (enabling participation in school, supporting social functioning, promoting understanding and acceptance), empowering self-management and partnership in care (overcoming communication barriers, gaining knowledge and skills, motivation for treatment adherence, making informed decisions, access and understanding of complementary and alternative therapies),strengthening ability to cope (learning to have a positive outlook, preparing for home care management, transitioning to adult services), broadening focus to family (supporting sibling well-being, parental resilience and financial loss, alleviating caregiver burden), and improving quality and scope of health and social care (readdressing variability and inequities, preventing disease complications and treatment side effects, identifying risk factors, improving long-term outcomes, harnessing technology, integrating multidisciplinary services). CONCLUSION: Research priorities identified by children, caregivers and health professionals emphasise a focus on life participation, psychosocial well-being, impact on family and quality of care. These priorities may be used by funding and policy organisations in establishing a paediatric research agenda.

Research priority setting in childhood chronic disease: a systematic review.

OBJECTIVE: To evaluate research priority setting approaches in childhood chronic diseases and to describe the priorities of stakeholders including patients, caregivers/families and health professionals. DESIGN: We conducted a systematic review of MEDLINE, Embase, PsycINFO and CINAHL from inception to 16 October 2016. Studies that elicited stakeholder priorities for paediatric chronic disease research were eligible for inclusion. Data on the prioritisation process were extracted using an appraisal checklist. Generated priorities were collated into common topic areas. RESULTS: We identified 83 studies (n=15 722). Twenty (24%) studies involved parents/caregivers and four (5%) children. The top three health areas were cancer (11%), neurology (8%) and endocrine/metabolism (8%). Priority topic areas were treatment (78%), disease trajectory (48%), quality of life/psychosocial impact (48%), disease onset/prevention (43%), knowledge/self-management (33%), prevalence (30%), diagnostic methods (28%), access to healthcare (25%) and transition to adulthood (12%). The methods included workshops, Delphi techniques, surveys and focus groups/interviews. Specific methods for collecting and prioritising research topics were described in only 60% of studies. Most reviewed studies were conducted in high-income nations. CONCLUSIONS: Research priority setting activities in paediatric chronic disease cover many discipline areas and have elicited a broad range of topics. However, child/caregiver involvement is uncommon, and the methods often lack clarity. A systematic and explicit process that involves patients and families in partnership may help to inform a more patient and family-relevant research agenda in paediatric chronic disease.

The effect of baseline characteristics on clinical efficacy of liraglutide in patients treated with high-dose insulin.

In patients requiring high-dose insulin treatment, a randomized, double-blind, placebo-controlled study showed that liraglutide improved glycaemic control and treatment satisfaction while promoting weight loss. We performed a post hoc analysis to evaluate if patients' baseline characteristics impact the efficacy of liraglutide, and which outcomes correlate with treatment satisfaction. We used regression analysis to model the change in HbA1c and weight, with treatment assignment and baseline characteristics [HbA1c, age, body mass index (BMI), total daily dose (TDD) of insulin, duration of insulin treatment, and type of insulin regimen] as independent variables. Improvement in HbA1c was best predicted by treatment with liraglutide, followed by higher baseline HbA1c, BMI and age. Changes in weight were only associated with liraglutide treatment, independent of all baseline characteristics. Improvement in HbA1c was the only significant predictor of improvement in treatment satisfaction, while weight loss, change in TDD of insulin and rate of hypoglycaemia did not influence treatment satisfaction. In patients treated with high-dose insulin, liraglutide significantly improved glycaemic control and led to weight loss regardless of patients' baseline characteristics. Improvement in HbA1c was the most important predictor of patients' treatment satisfaction.

Effect of Adding Liraglutide vs Placebo to a High-Dose lnsulin Regimen in Patients With Type 2 Diabetes: A Randomized Clinical Trial.

IMPORTANCE: An increasing number of patients with type 2 diabetes are treated with high doses of insulin. Such treatment is associated with weight gain, hypoglycemia, and high treatment burden. OBJECTIVE: To assess the effectiveness and safety of adding a glucagon-like peptide 1 receptor agonist to the treatment regimen of patients with type 2 diabetes requiring therapy with high-dose insulin. DESIGN, SETTING, AND PARTICIPANTS: This clinical trial was a double-blind, placebo-controlled, randomized (1:1) study with 6 months of follow-up, conducted from August 13, 2012, to February 9, 2015, at ambulatory clinics at the University of Texas Southwestern Medical Center and Parkland Hospital. Participants were 71 patients with uncontrolled type 2 diabetes (glycated hemoglobin level, 7.5%-11.0%) using more than 1.5 U/kg/d of insulin. INTERVENTIONS: Subcutaneous injection of liraglutide (1.8 mg/d) or matching placebo for 6 months. MAIN OUTCOMES AND MEASURES: The primary outcome was the change in glycated hemoglobin level. Secondary outcomes were changes in weight, hypoglycemia rate, insulin dosage, and quality-of-life measures. RESULTS: Among 71 patients, 45 (63%) were female. The mean (SD) age of patients was 54.2 (7.4) years, with a mean (SD) type 2 diabetes duration of 17.9 (8.4) years and a mean (SD) total daily dose of insulin of 247.0 (95.1) U. Ninety-three percent (66 of 71) of participants completed all scheduled visits. The glycated hemoglobin level improved from a mean (SD) of 9.0% (1.2%) to 7.9% (1.1%) in the liraglutide group (P < .001) and remained unchanged (8.9%) in the placebo group, with an estimated treatment difference of 0.9% (95% CI, -1.5 to -0.4) (P = .002). Weight decreased from a mean (SD) of 114.6 (21.4) kg to 113.6 (20.8) kg in the liraglutide group vs a mean (SD) increase from 116.1 (26.6) kg to 117.2 (27.2) kg in the placebo group, with a treatment difference of -2.3 kg (95% CI, -4.3 to -0.4 kg) (P = .02). The total daily dose of insulin decreased 11.5% (95% CI, -21.8% to -1.1%) in the liraglutide group (P = .20). The hypoglycemia rate was higher in the first month after initiation of liraglutide compared with placebo (2.30 vs 0.91 events per person-month, P = .01), while the overall hypoglycemia rate over the entire follow-up was similar between groups (P = .11). Glycemia control perception, satisfaction with insulin treatment, and willingness to continue insulin use improved more in the liraglutide group. CONCLUSIONS AND RELEVANCE: Liraglutide added to high-dose insulin therapy improved glycemic control, decreased body weight, and enhanced treatment satisfaction in this difficult-to-treat patient population with high-dose insulin requirements. Further studies are warranted to confirm these findings and evaluate the long-term risk and benefit of this treatment option. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01505673.

Mechanisms of Action of Liraglutide in Patients With Type 2 Diabetes Treated With High-Dose Insulin.

CONTEXT: The mechanisms of action of incretin mimetics in patients with long-standing type 2 diabetes (T2D) and high insulin requirements have not been studied. OBJECTIVE: To evaluate changes in ß-cell function, glucagon secretion, and fat distribution after addition of liraglutide to high-dose insulin. DESIGN: A single-center, randomized, double-blind, placebo-controlled trial. SETTING: University of Texas Southwestern and Parkland Memorial Hospital clinics. PATIENTS: Seventy-one patients with long-standing (median, 17 years) T2D requiring high-dose insulin treatment (>1.5 U/kg/d; average, 2.2 ± 0.9 U/kg/d). INTERVENTION: Patients were randomized to liraglutide 1.8 mg/d or matching placebo for 6 months. MAIN OUTCOME MEASURES: We measured changes in insulin and glucagon secretion using a 4-hour mixed-meal challenge test. Magnetic resonance-based techniques were used to estimate sc and visceral fat in the abdomen and ectopic fat in the liver and pancreas. RESULTS: Glycosylated hemoglobin improved significantly with liraglutide treatment, with an end-of-trial estimated treatment difference between groups of −0.9% (95% confidence interval, −1.5, −0.4%) (P = .002). Insulin secretion improved in the liraglutide group vs placebo, as measured by the area under the curve of C-peptide (P = .002) and the area under the curves ratio of C-peptide to glucose (P = .003). Insulin sensitivity (Matsuda index) and glucagon secretion did not change significantly between groups. Liver fat and sc fat decreased in the liraglutide group vs placebo (P = .0006 and P = .01, respectively), whereas neither visceral nor pancreatic fat changed significantly. CONCLUSIONS: Treatment with liraglutide significantly improved insulin secretion, even in patients with long-standing T2D requiring high-dose insulin treatment. Liraglutide also decreased liver and sc fat, but it did not alter glucagon secretion.

Intensive therapy in newly diagnosed type 2 diabetes: results of a 6-year randomized trial.

BACKGROUND: This study aimed to assess the efficacy of early intensive diabetes therapy with either insulin plus metformin (INS) or triple oral therapy (TOT) with metformin, glyburide, and pioglitazone on glycemic control and A-cell function. METHODS: Fifty-eight treatment-naive newly diagnosed patients with type 2 diabetes underwent a 3-month lead-in treatment period with insulin and metformin, then were randomized to INS or TOT for 6 years. ß-Cell function was measured using mixed-meal challenge test. ß-Cell function remained stable throughout the 6-year study in both groups, as measured by the C-peptide area under the curve (AUC; P = 0.13), the AUC C-peptide/AUC glucose (P = 0.9), and by the disposition index (P = 0.8). Excellent glycemic control was maintained in both groups (end-of-study hemoglobinA1c, 7.3% [SD, 1.7%] INS vs 6.4% [1.4%] TOT; P = 0.4). There were 8 treatment failures (confirmed hemoglobinA1c, 98%) in INS and 6 in TOT (P = 0.93). The predictors of treatment failure included higher fasting glucose (P = 0.008), fasting C-peptide (P = 0.008), systolic blood pressure (P = 0.004), and lower insulin sensitivity (P = 0.04) at randomization. CONCLUSIONS: Early intensive treatment at the time of type 2 diabetes diagnosis-initial short-term insulin treatment followed by either insulin-based or intensive oral hypoglycemic-based therapy-stabilizes ß-cell function for at least 6 years. Treatment failure was independent of intervention and was associated with worse disease pathology at baseline.

Type 1 diabetes treatment beyond insulin: role of GLP-1 analogs.

OBJECTIVE: To observe the efficacy and safety of glucagonlike peptide-1 (GLP-1) analogs in type 1 diabetes in a real-life medical practice setting. METHODS: We performed a retrospective chart review of patients with type 1 diabetes initiated on a GLP-1 analog and with at least one follow-up visit at more than 4 weeks. RESULTS: We identified 11 patients who were initiated on a GLP-1 analog and had a follow-up visit between 4 and 13 weeks (mean (SD) follow-up 10 ± 3 weeks; age 36.5 ± 16.4 years; duration of diabetes 17.3 ± 9.3 years; all on insulin pump therapy; all started on liraglutide). Seven of these patients had a second follow-up visit at approximately 20 weeks. By 10 weeks, there was a significant decrease in weight (4.2% of total body weight), total daily insulin dose (19.2%, of which 14.0% basal and 24.1% bolus), and mean (SD) insulin units/kg (0.57 [0.17] to 0.48 [0.17] units/kg). Hemoglobin A1c was significantly decreased (7.4 [0.7%] to 7.0 [0.7%], P = 0.02) without an increase in hypoglycemia. These effects were sustained at 20 weeks. Nausea was a common adverse effect and lead to drug discontinuation in 4 of 11 patients. CONCLUSIONS: Patients with long-standing type 1 diabetes can achieve weight loss and improved glycemic control on less insulin without an increase in hypoglycemia when liraglutide is added to insulin therapy.

ß-cell function preservation after 3.5 years of intensive diabetes therapy.

OBJECTIVE: To assess ß-cell function preservation after 3.5 years of intensive therapy with insulin plus metformin (INS group) versus triple oral therapy (TOT group) with metformin, glyburide, and pioglitazone. RESEARCH DESIGN AND METHODS: This was a randomized trial of 58 patients with treatment-naïve newly diagnosed type 2 diabetes. All patients were treated with insulin and metformin for a 3-month lead-in period followed by random assignment to the INS or TOT group. ß-Cell function was assessed using a mixed-meal challenge test at randomization and 6, 12, 18, 30, and 42 months. Analyses were intention to treat and performed with repeated-measures models. RESULTS: Completion rates at 3.5 years were 83% in the insulin group and 72% in the TOT group, with good compliance in both groups (87 ± 20% in the INS group vs. 90 ± 15% in the TOT group). ß-Cell function was preserved at 3.5 years after diagnosis, with no significant change from baseline or difference between the two groups as measured by area under the curve (AUC) of C-peptide (P = 0.14) or the ratio of C-peptide to glucose AUC (P = 0.7). Excellent glycemic control was maintained in both groups (end-of-study HbA(1c) 6.35 ± 0.84% in the INS group vs. 6.59 ± 1.94% in the TOT group). Weight increased in both groups over time (from 102.2 ± 24.9 kg to 106.2 ± 31.7 kg in the INS group and from 100.9 ± 23.0 kg to 110.5 ± 31.8 kg in the TOT group), with no significant difference between groups (P = 0.35). Hypoglycemic events decreased significantly over time (P = 0.01) but did not differ between groups (P = 0.83). CONCLUSIONS: ß-Cell function can be preserved for at least 3.5 years with early and intensive therapy for type 2 diabetes with either insulin plus metformin or triple oral therapy after an initial 3-month insulin-based treatment period.

Linking an agency strategic review to increase knowledge management: San Francisco County Human Service Agency.

Led by the agency director, the agency engaged in a Strategic Review, based on a comprehensive assessment of agency performance that identified strategies to improve organizational effectiveness through increased data-informed practice and knowledge management. The Strategic Review gathered information on staff perceptions, perceptions of external stakeholders, changing citywide and neighborhood demographics, policy mandates, and budget and workload issues. The need for the review was based upon multiple, substantial changes not addressed in the 2000 Strategic Plan, including the 2004 merger of the Department of Human Services and the Department of Aging and Adult Services, changes among the executive management team, transitions among key political entities, new policy mandates and changing budget allocations. This case study describes the Strategic Review process and content, summarizing key challenges and lessons related to addressing workload demands, fostering positive staff attitudes, balancing internal and external information needs, and integrating data use and planning processes across the agency.

Transforming data into action: the Sonoma County Human Services Department.

In order to centralize data-based initiatives, the Director of the Department worked with the Board of Supervisors and the executive team to develop a new Planning, Research, and Evaluation (PRE) division. PRE is establishing rules for data-based decision making and consolidating data collection to ensure quality and consistency. It aims to target resources toward visionary, pro-active program planning and implementation, and inform the public about the role of Human Services in creating a healthy, safe and productive environment. PRE staff spent several months studying the job functions of staff, to determine how they use information to inform practice, consulting other counties about their experiences. The PRE team developed Datascript, outlining two agency aims: (a) foster a decision-making environment that values and successfully uses empirical evidence for strategic change, and (b) manage the role and image of the Human Services Department in the external environment. The case study describes action steps developed to achieve each aim.

Quality management as knowledge sharing: experiences of the Napa County Health and Human Services Agency.

Lacking a coordinated effort in utilizing data and tracking program outcomes, one agency developed a Quality Management (QM) division to facilitate and manage more effective data use. To support this process, the agency sought to develop a collective, agency-wide understanding and investment in improving and measuring client outcomes. Similarly, the agency also focused efforts on creating a culture of transparency and accountability, with goals of improving service, increasing agency integrity, meeting regulatory compliance, and engaging in effective risk management. Operationalizing the QM initiative involved developing procedures, systems, and guidelines that would facilitate the generation of reliable and accurate data that could be used to inform program change and decision-making. This case study describes this agency's experience in successfully creating and implementing a QM initiative aimed at engaging in greater knowledge sharing.

Using agency-wide dashboards for data monitoring and data mining: the Solano County Health and Social Services Department.

The Director needed accessible data on critical program areas in order to monitor changes presenting potential negative impacts. The Research, Evaluation and Planning division spearheaded the Dashboard featuring the seven program areas (Employment & Eligibility, Child Welfare Services, Mental Health, Public Health, Older Disabled Adult Services, Substance Abuse, and the Special Investigations Bureau), and three administrative units. Deputy Directors specified several key areas that their divisions were mandated to report or viewed as important for monitoring. The Dashboard enables Directors to communicate internally and externally about program results, strengths and growth areas, as well as track progress in relationship to strategic plan initiatives and intervene in areas needing improvement. Executive team members identify critical areas for improvement and the Assistant Director for Research and Evaluation implements corrective action through the Quality Assurance Committee. Agency lessons relate to the importance of automation, data interpretation, and team members' understanding of the indicators, related practice strategies, and contextual factors.