Neonatal Autonomic Regulation as a Predictor of Autism Spectrum Disorder in Very Preterm Infants.

Infants born preterm are at a significantly higher likelihood of having autism spectrum disorder (ASD). Preterm birth and ASD are both associated with neurological differences, notably autonomic nervous system (ANS) dysfunction, pointing to preterm ANS dysfunction as a potential pathway to ASD, particularly in VPT infants. In this study, a subset of very preterm (VPT) infants enrolled in a large, multisite clinical trial were enrolled in this study at birth (N=20). Continuous measures of minute-by-minute thermal gradients, defined by the difference between central and peripheral temperatures, and hour-by-hour abnormal heart rate characteristics (HRCs) were collected from birth-28 days (>40,000 samples/infant). Following NICU discharge, standardized measures of cognition, language, and motor skills were collected at adjusted ages 6, 9, and 12 months. At 12 months, assessments of social communication and early ASD symptoms were administered. Results suggest significant ASD concerns for half of the sample by 12 months of age. Neonatal abnormal HRCs were strongly associated with 12-month ASD symptoms (r=0.81, p<.01), as was birth gestational age (GA), birth weight (BW), and abnormal negative thermal gradients. ANS measures collected in the first month of neonatal life, more than a year prior to the ASD evaluation, were surprisingly strong predictors of ASD. This study highlights complementary ANS measures that describe how ANS dysfunction, likely resulting from an imbalance between the parasympathetic and sympathetic systems, may impact very early regulatory processes for neonates who later develop ASD. This finding offers a promising avenue for researching ANS-related etiological mechanisms and biomarkers of ASD.

Heterogeneity of Mycobacterium tuberculosis Strains Circulating in Panama's Western Region.

Tuberculosis remains a challenge in both rural and urban areas. Although a majority of countries display a higher burden in urban areas compared with rural areas, Panama continues to report the highest mortality rate in Central America. Urban areas, such as Panama City, report a high tuberculosis burden, whereas Panama's western region, including the provinces of Chiriquí, Bocas del Toro (both semiurban) and Ngäbe-Bugle (rural), show a lower burden. We aimed to identify highly transmitted Mycobacterium tuberculosis strains within rural and semiurban settings of Panama's western region during a 3-year period (2017, 2019, 2021). We randomly selected 87 M. tuberculosis isolates from a biobank from Panama's western region and analyzed them using allele-specific oligonucleotide polymerase chain reaction and 24-mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR). Our results show only 11.7% (10/85) of M. tuberculosis strains identified as prevalent A-Beijing, B-Haarlem, or C-LAM Strains. We found a low prevalence of A, B, and C M. tuberculosis strains in both rural and semirural settings compared with isolates collected from the Eastern Colon Province. MIRU-VNTR genotyping revealed a high degree of diversity with no clusters with single loci variation of ≥ 2 loci. These results support the notion that tuberculosis prevalence in the rural and semiurban western region of Panama are not due to previously described highly transmitted strains but is influenced instead by other health determinants, including poor health system access and a lack of systematic transmission chain monitoring. For remote rural and semiurban settings, we recommend allocating resources to reinforce efforts to prevent tuberculosis spread.

Patient-centred outcomes following non-operative treatment or appendicectomy for uncomplicated acute appendicitis in children.

While non-operative treatment has emerged as an alternative to surgery for the treatment of uncomplicated acute appendicitis in children, comparative patient-centred outcomes are not well documented. We investigated these in a feasibility randomised trial. Of 57 randomised participants, data were available for 26. Compared with appendicectomy, children allocated to non-operative treatment reported higher short-term quality of life scores, shorter duration of requiring analgesia, more rapid return to normal activities and shorter parental absence from work. These preliminary data suggest differences exist in recovery profile and quality of life between these treatments that are important to measure in a larger RCT. Trial registration number is ISRCTN15830435.

Separating N2O production and consumption in intact agricultural soil cores at different moisture contents and depths.

Agricultural soils are a major source of the potent greenhouse gas and ozone depleting substance, N2O. To implement management practices that minimize microbial N2O production and maximize its consumption (i.e., complete denitrification), we must understand the interplay between simultaneously occurring biological and physical processes, especially how this changes with soil depth. Meaningfully disentangling of these processes is challenging and typical N2O flux measurement techniques provide little insight into subsurface mechanisms. In addition, denitrification studies are often conducted on sieved soil in altered O2 environments which relate poorly to in situ field conditions. Here, we developed a novel incubation system with headspaces both above and below the soil cores and field-relevant O2 concentrations to better represent in situ conditions. We incubated intact sandy clay loam textured agricultural topsoil (0-10 cm) and subsoil (50-60 cm) cores for 3-4 days at 50% and 70% water-filled pore space, respectively. 15N-N2O pool dilution and an SF6 tracer were injected below the cores to determine the relative diffusivity and the net N2O emission and gross N2O emission and consumption fluxes. The relationship between calculated fluxes from the below and above soil core headspaces confirmed that the system performed well. Relative diffusivity did not vary with depth, likely due to the preservation of preferential flow pathways in the intact cores. Gross N2O emission and uptake also did not differ with depth but were higher in the drier cores, contrary to expectation. We speculate this was due to aerobic denitrification being the primary N2O consuming process and simultaneously occurring denitrification and nitrification both producing N2O in the drier cores. We provide further evidence of substantial N2O consumption in drier soil but without net negative N2O emissions. The results from this study are important for the future application of the 15N-N2O pool dilution method and N budgeting and modelling, as required for improving management to minimize N2O losses.

A randomized, feasibility trial of an exercise and nutrition-based rehabilitation programme (ENeRgy) in people with cancer.

BACKGROUND: Despite rehabilitation being increasingly advocated for people living with incurable cancer, there is limited evidence supporting efficacy or component parts. The progressive decline in function and nutritional in this population would support an approach that targets these factors. This trial aimed to assess the feasibility of an exercise and nutrition based rehabilitation programme in people with incurable cancer. METHODS: We randomized community dwelling adults with incurable cancer to either a personalized exercise and nutrition based programme (experimental arm) or standard care (control arm) for 8 weeks. Endpoints included feasibility, quality of life, physical activity (step count), and body weight. Qualitative and health economic analyses were also included. RESULTS: Forty-five patients were recruited (23 experimental arm, 22 control arm). There were 26 men (58%), and the median age was 78 years (IQR 69-84). At baseline, the median BMI was 26 kg/m2 (IQR: 22-29), and median weight loss in the previous 6 months was 5% (IQR: -12% to 0%). Adherence to the experimental arm was >80% in 16/21 (76%) patients. There was no statistically significant difference in the following between trial arms: step count - median % change from baseline to endpoint, per trial arm (experimental -18.5% [IQR: -61 to 65], control 5% [IQR: -32 to 50], P = 0.548); weight - median % change from baseline to endpoint, per trial arm (experimental 1%[IQR: -3 to 3], control -0.5% [IQR: -3 to 1], P = 0.184); overall quality of life - median % change from baseline to endpoint, per trial arm (experimental 0% [IQR: -20 to 19], control 0% [IQR: -23 to 33], P = 0.846). Qualitative findings observed themes of capability, opportunity, and motivation amongst patients in the experimental arm. The mean incremental cost of the experimental arm versus control was £-319.51 [CI -7593.53 to 6581.91], suggesting the experimental arm was less costly. CONCLUSIONS: An exercise and nutritional rehabilitation intervention is feasible and has potential benefits for people with incurable cancer. A larger trial is now warranted to test the efficacy of this approach.

Developing an intervention to optimise the outcome of cardiac surgery in people with diabetes: the OCTOPuS pilot study.

BACKGROUND: Cardiothoracic surgical outcomes are poorer in people with diabetes compared with those without diabetes. There are two important uncertainties in the management of people with diabetes undergoing major surgery: (1) how to improve diabetes management in the weeks leading up to an elective procedure and (2) whether that improved management leads to improved postoperative outcomes. The aim of this study was to develop and pilot a specialist diabetes team-led intervention to improve surgical outcomes in people with diabetes. DESIGN: Open pilot feasibility study SETTING: Diabetes and cardiothoracic surgery departments, University Hospital Southampton NHS Foundation Trust PARTICIPANTS: Seventeen people with diabetes undergoing cardiothoracic surgery INTERVENTION: Following two rapid literature reviews, a prototype intervention was developed based on a previously used nurse-led outpatient intervention and tested. PRIMARY OUTCOME: Feasibility and acceptability of delivering the intervention SECONDARY OUTCOMES: Biomedical data were collected at baseline and prior to surgery. We assessed how the intervention was used. In depth qualitative interviews with participants and healthcare professionals were used to explore perceptions and experiences of the intervention and how it might be improved. RESULTS: Thirteen of the 17 people recruited completed the study and underwent cardiothoracic surgery. All components of the OCTOPuS intervention were used, but not all parts were used for all participants. Minor changes were made to the intervention as a result of feedback from the participants and healthcare professionals. Median (IQR) HbA1c was 10 mmol/mol (3, 13) lower prior to surgery than at baseline. CONCLUSION: This study has shown that it is possible to develop a clinical pathway to improve diabetes management prior to admission. The clinical and cost-effectiveness of this intervention will now be tested in a multicentre randomised controlled trial in cardiothoracic centres across the UK. TRIAL REGISTRATION: ISRCTN; ISRCTN10170306 . Registered 10 May 2018.

The Optimising Cardiac Surgery ouTcOmes in People with diabeteS (OCTOPuS) randomised controlled trial to evaluate an outpatient pre-cardiac surgery diabetes management intervention: a study protocol.

INTRODUCTION: Cardiothoracic surgical outcomes are poorer in people with diabetes compared with those without diabetes. There are two important uncertainties in the management of people with diabetes undergoing major surgery: (1) how to improve diabetes management in the weeks leading up to an elective procedure and (2) whether that improved management leads to better postoperative outcomes. We previously demonstrated the feasibility of delivering the Optimising Cardiac Surgery ouTcOmes in People with diabeteS (OCTOPuS) intervention, an outpatient intervention delivered by diabetes healthcare professionals for people with suboptimally managed diabetes over 8-12 weeks before elective cardiac surgery. The present study will assess the clinical and cost-effectiveness of the intervention in cardiothoracic centres across the UK. METHODS AND ANALYSIS: A multicentre, parallel group, single-blinded 1:1 individually randomised trial comparing time from surgery until clinically fit for discharge in adults with suboptimally managed type 1 diabetes or type 2 diabetes undergoing elective surgery between the OCTOPuS intervention and usual care (primary endpoint). Secondary endpoints will include actual time from surgery to discharge from hospital; days alive and either out of hospital or judged as clinically fit for discharge; mortality; time on intensive therapy unit (ITU)/ventilator; infections; acute myocardial infarction; change in weight; effect on postoperative renal function and incidence of acute kidney injury; change in HbA1c; frequency and severity of self-reported hypoglycaemia; operations permanently cancelled for suboptimal glycaemic levels; cost-effectiveness; psychosocial questionnaires. The target sample size will be 426 recruited across approximately 15 sites. The primary analysis will be conducted on an intention-to-treat population. A two-sided p value of 0.05 or less will be used to declare statistical significance for all analyses and results will be presented with 95% CIs. ETHICS AND DISSEMINATION: The trial was approved by the South Central-Hampshire A Research Ethics Committee (20/SC/0271). Results will be disseminated through conferences, scientific journals, newsletters, magazines and social media. TRIAL REGISTRATION NUMBER: ISRCTN10170306.

Conservative treatment for uncomplicated appendicitis in children: the CONTRACT feasibility study, including feasibility RCT.

BACKGROUND: Although non-operative treatment is known to be effective for the treatment of uncomplicated acute appendicitis in children, randomised trial data comparing important outcomes of non-operative treatment with those of appendicectomy are lacking. OBJECTIVES: The objectives were to ascertain the feasibility of conducting a multicentre randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of a non-operative treatment pathway with appendicectomy for the treatment of uncomplicated acute appendicitis in children. DESIGN: This was a mixed-methods study, which included a feasibility randomised controlled trial, embedded and parallel qualitative and survey studies, a parallel health economic feasibility study and the development of a core outcome set. SETTING: This study was set in three specialist NHS paediatric surgical units in England. PARTICIPANTS: Children (aged 4-15 years) clinically diagnosed with uncomplicated acute appendicitis participated in the feasibility randomised controlled trial. Children, their families, recruiting clinicians and other health-care professionals involved in caring for children with appendicitis took part in the qualitative study. UK specialist paediatric surgeons took part in the survey. Specialist paediatric surgeons, adult general surgeons who treat children, and children and young people who previously had appendicitis, along with their families, took part in the development of the core outcome set. INTERVENTIONS: Participants in the feasibility randomised controlled trial were randomised to a non-operative treatment pathway (broad-spectrum antibiotics and active observation) or appendicectomy. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of eligible patients recruited to the feasibility trial. DATA SOURCES: Data were sourced from NHS case notes, questionnaire responses, transcribed audio-recordings of recruitment discussions and qualitative interviews. RESULTS: Overall, 50% (95% confidence interval 40% to 59%) of 115 eligible patients approached about the trial agreed to participate and were randomised. There was high acceptance of randomisation and good adherence to trial procedures and follow-up (follow-up rates of 89%, 85% and 85% at 6 weeks, 3 months and 6 months, respectively). More participants had perforated appendicitis than had been anticipated. Qualitative work enabled us to communicate about the trial effectively with patients and families, to design and deliver bespoke training to optimise recruitment and to understand how to optimise the design and delivery of a future trial. The health economic study indicated that the main cost drivers are the ward stay cost and the cost of the operation; it has also informed quality-of-life assessment methods for future work. A core outcome set for the treatment of uncomplicated acute appendicitis in children and young people was developed, containing 14 outcomes. There is adequate surgeon interest to justify proceeding to an effectiveness trial, with 51% of those surveyed expressing a willingness to recruit with an unchanged trial protocol. LIMITATIONS: Because the feasibility randomised controlled trial was performed in only three centres, successful recruitment across a larger number of sites cannot be guaranteed. However, the qualitative work has informed a bespoke training package to facilitate this. Although survey results suggest adequate clinician interest to make a larger trial possible, actual participation may differ, and equipoise may have changed over time. CONCLUSIONS: A future effectiveness trial is feasible, following limited additional preparation, to establish appropriate outcome measures and case identification. It is recommended to include a limited package of qualitative work to optimise recruitment, in particular at new centres. FUTURE WORK: Prior to proceeding to an effectiveness trial, there is a need to develop a robust method for distinguishing children with uncomplicated acute appendicitis from those with more advanced appendicitis, and to reach agreement on a primary outcome measure and effect size that is acceptable to all stakeholder groups involved. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15830435. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 10. See the NIHR Journals Library website for further project information.

Appendicitis is usually treated with an operation to remove the appendix. But we have learned, from other research, that some children with appendicitis may not need an operation, and could be treated with antibiotics instead. To find out how these two different treatments compare with one another, we need to do a big study. First, though, we need to see if doing that kind of study would even be possible (or 'feasible'). We carried out a feasibility study that had several parts. First, we did a small study with children who had appendicitis, whereby children were randomly allocated to have either antibiotics or an operation, with an equal chance of having either treatment. Second, we asked parents and health-care staff about why they wanted, or did not want, to take part in that small study. This helped us to understand how to make a bigger future study as acceptable as possible to children, families and surgeons. Third, we asked parents, patients and surgeons what they think are the most important things ­ or 'outcomes' ­ we should look at in future research on children who have appendicitis. From that, we developed a list of outcomes that should be included in our future big study, so we can be certain that the research we do is likely to help parents and surgeons. Overall, we established that a future big study is feasible and we have plenty of information to help us with how to plan it best, so that it has the greatest possible chance of success. We were also guided in all of these steps of the research by a group of parents, children and young people, some of whom had appendicitis and some of whom did not.

CONservative TReatment of Appendicitis in Children: a randomised controlled feasibility Trial (CONTRACT).

OBJECTIVE: To establish the feasibility of a multicentre randomised controlled trial to assess the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy in children with uncomplicated acute appendicitis. DESIGN: Feasibility randomised controlled trial with embedded qualitative study to inform recruiter training to optimise recruitment and the design of a future definitive trial. SETTING: Three specialist paediatric surgery centres in the UK. PATIENTS: Children (aged 4-15 years) with a clinical diagnosis of uncomplicated acute appendicitis. INTERVENTIONS: Appendicectomy or a non-operative treatment pathway (comprising broad-spectrum antibiotics and active observation). MAIN OUTCOME MEASURES: Primary outcome measure was the proportion of eligible patients recruited. Secondary outcomes evaluated adherence to interventions, data collection during follow-up, safety of treatment pathways and clinical course. RESULTS: Fifty per cent of eligible participants (95% CI 40 to 59) approached about the trial agreed to participate and were randomised. Repeated bespoke recruiter training was associated with an increase in recruitment rate over the course of the trial from 38% to 72%. There was high acceptance of randomisation, good patient and surgeon adherence to trial procedures and satisfactory completion of follow-up. Although more participants had perforated appendicitis than had been anticipated, treatment pathways were found to be safe and adverse event profiles acceptable. CONCLUSION: Recruitment to a randomised controlled trial examining the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy for the treatment of uncomplicated acute appendicitis in children is feasible. TRIAL REGISTRATION NUMBER: ISRCTN15830435.

Engaging Community Networks to Improve Depression Services: A Cluster-Randomized Trial of a Community Engagement and Planning Intervention.

This paper explores the effects of a group-randomized controlled trial, Community Partners in Care (CPIC), on the development of interagency networks for collaborative depression care improvement between a community engagement and planning (CEP) intervention and a resources for services (RS) intervention that provided the same content solely via technical assistance to individual programs. Both interventions consisted of a diverse set of service agencies, including health, mental health, substance abuse treatment, social services, and community-trusted organizations such as churches and parks and recreation centers. Participants in the community councils for the CEP intervention reflected a range of agency leaders, staff, and other stakeholders. Network analysis of partnerships among agencies in the CEP versus RS condition, and qualitative analysis of perspectives on interagency network changes from multiple sources, suggested that agencies in the CEP intervention exhibited greater growth in partnership capacity among themselves than did RS agencies. CEP participants also viewed the coalition development intervention both as promoting collaboration in depression services and as a meaningful community capacity building activity. These descriptive results help to identify plausible mechanisms of action for the CPIC interventions and can be used to guide development of future community engagement interventions and evaluations in under-resourced communities.

Edaphic factors and plants influence denitrification in soils from a long-term arable experiment.

Factors influencing production of greenhouse gases nitrous oxide (N2O) and nitrogen (N2) in arable soils include high nitrate, moisture and plants; we investigate how differences in the soil microbiome due to antecedent soil treatment additionally influence denitrification. Microbial communities, denitrification gene abundance and gas production in soils from tilled arable plots with contrasting fertilizer inputs (no N, mineral N, FYM) and regenerated woodland in the long-term Broadbalk field experiment were investigated. Soil was transferred to pots, kept bare or planted with wheat and after 6 weeks, transferred to sealed chambers with or without K15NO3 fertilizer for 4 days; N2O and N2 were measured daily. Concentrations of N2O were higher when fertilizer was added, lower in the presence of plants, whilst N2 increased over time and with plants. Prior soil treatment but not exposure to N-fertiliser or plants during the experiment influenced denitrification gene (nirK, nirS, nosZI, nosZII) relative abundance. Under our experimental conditions, denitrification generated mostly N2; N2O was around 2% of total gaseous N2 + N2O. Prior long-term soil management influenced the soil microbiome and abundance of denitrification genes. The production of N2O was driven by nitrate availability and N2 generation increased in the presence of plants.

Immune reconstitution in children following chemotherapy for acute leukemia.

Although survival rates for pediatric acute lymphoblastic leukemia are now excellent, this is at the expense of prolonged chemotherapy regimens. We report the long-term immune effects in children treated according to the UK Medical Research Council UKALL 2003 protocol. Peripheral blood lymphocyte subsets and immunoglobulin levels were studied in 116 participants, at six time points, during and for 18-month following treatment, with 30-39 patients analyzed at each time point. Total lymphocytes were reduced during maintenance chemotherapy and remained low 18 months following treatment completion. CD4 T cells remained significantly reduced 18 months after treatment, but CD8 cells and natural killer cells recovered to normal values. The fall in naïve B-cell numbers during maintenance was most marked, but numbers recovered rapidly after cessation of treatment. Memory B cells, particularly nonclass-switched memory B cells, remained below normal levels 18 months following treatment. All immunoglobulin subclasses were reduced during treatment compared to normal values, with IgM levels most affected. This study demonstrates that immune reconstitution differs between lymphocyte compartments. Although total B-cell numbers recover rapidly, disruption of memory/naïve balance persists and T-cell compartment persist at 18 months. This highlights the impact of modern chemotherapy regimens on immunity, and thus, infectious susceptibility and response to immunization.

Thirteen-Valent Pneumococcal Conjugate Vaccine in Children With Acute Lymphoblastic Leukemia: Protective Immunity Can Be Achieved on Completion of Treatment.

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) are at increased risk of developing invasive pneumococcal disease. This study describes the immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV13) during and after chemotherapy. METHODS: Children with ALL were allocated to study groups and received a single dose of PCV13: group 1, maintenance chemotherapy; group 2, end of chemotherapy; group 3, 6 months after chemotherapy. A protective vaccine response was defined as at least 10 of 12 serotypes (or >83% of serotypes with data) achieving postvaccination serotype-specific immunoglobulin G ≥0.35 µg/mL and ≥4-fold rise, compared to prevaccination at 1 and 12 months. RESULTS: One hundred eighteen children were recruited. Only 12.8% (5/39; 95% confidence interval [CI], 4.3%-27.4%) of patients vaccinated during maintenance (group 1) achieved a protective response at 1 month postvaccination and none had a protective response at 12 months. For group 2 patients, 59.5% (22/37; 95% CI, 42.1%-75.3%) achieved a response at 1 month and 37.9% (11/29; 95% CI, 20.7%-57.7%) maintained immunity at 12 months. For group 3 patients, 56.8% (21/37; 95% CI, 39.5%-72.9%) achieved a protective response at 1 month and 43.3% (13/30; 95% CI, 25.5%-62.6%) maintained immunity at 12 months. CONCLUSIONS: This study demonstrated that the earliest time point at which protective immunity can be achieved in children with ALL is on completion of chemotherapy. This is earlier than current recommendations and may improve protection during a period when children are most susceptible to infection. CLINICAL TRIALS REGISTRATION: EudraCT 2009-011587-11.

Community Engagement and Planning versus Resources for Services for Implementing Depression Quality Improvement: Exploratory Analysis for Black and Latino Adults.

Objective: Racial/ethnic minorities experience disparities in depression1 and there is a paucity of evidence-based interventions to improve depression care access and outcomes. Community Partners in Care (CPIC) is a community-partnered study of depression care quality improvement (QI) in under-resourced, urban communities: Community Engagement and Planning (CEP) for multi-sector coalitions, and Resources for Services (RS) for program technical assistance.2 CEP demonstrated benefits for the overall CPIC study population; effects for Black and Latino sub-populations are unknown. Methods: This sub-analysis examines outcomes for 409 Latino and 488 Black (non-Latino) adults recruited from 90 programs who completed baseline or 6-month follow-up. Regression analyses were used to estimate CEP vs RS intervention effects on primary (Mental Health Related Quality of Life [MHRQL], Patient Health Questionnaire-9 [PHQ-9]) and community-prioritized (mental wellness, physical activity, risk for homelessness) outcomes at 6-months. Results: Baseline characteristics did not differ significantly by intervention in either group. In the adjusted analysis for Black adults, CEP resulted in decreased odds of poor MHRQL (OR: .62, 95% CI=.41-.94, P=.028) with a trend for reducing homelessness risk (OR: .60, .35-1.05, P=.69). For Latino adults, CEP resulted in greater probability of mental wellness (OR: 1.81, 1.05-3.13, P=.034) and a trend for increased physical activity (OR: 1.52, .93-2.49, P=.091). Conclusions: Exploratory analyses of CEP for depression quality improvement suggests significant 6-month benefits in mental health outcomes for Black and Latino participants and trends for improvement in community-prioritized outcomes for both groups. Findings may inform research in multi-sector coalitions to promote equity in depression care.

A Comparative Effectiveness Trial of Depression Collaborative Care: Subanalysis of Comorbid Anxiety.

The purpose of this exploratory subanalysis was to compare the effects of two depression quality improvement approaches on clinical outcomes and service utilization for individuals with comorbid depression/anxiety. This study used data from Community Partners in Care (CPIC), a cluster-randomized comparative effectiveness trial (N = 1,018; depression = 360; comorbid depression/anxiety = 658). Each intervention arm received the same quality improvement materials, plus either technical support (Resources for Services, RS) or support for collaborative implementation planning (Community Engagement and Planning, CEP). For the comorbid depression/anxiety subgroup, the collaborative planning arm was superior at improving mental health-related quality of life and mental wellness, as well as decreasing behavioral hospitalizations and homelessness risk at 6 months. The effects were not significant at 12 months. A collaborative planning process versus technical support for depression quality improvement can have short-term effects on mental wellness and social determinants of health among those with comorbid depression/anxiety.

Improved isotopic model based on 15 N tracing and Rayleigh-type isotope fractionation for simulating differential sources of N2 O emissions in a clay grassland soil.

RATIONALE: Isotopic signatures of N2 O can help distinguish between two sources (fertiliser N or endogenous soil N) of N2 O emissions. The contribution of each source to N2 O emissions after N-application is difficult to determine. Here, isotopologue signatures of emitted N2 O are used in an improved isotopic model based on Rayleigh-type equations. METHODS: The effects of a partial (33% of surface area, treatment 1c) or total (100% of surface area, treatment 3c) dispersal of N and C on gaseous emissions from denitrification were measured in a laboratory incubation system (DENIS) allowing simultaneous measurements of NO, N2 O, N2 and CO2 over a 12-day incubation period. To determine the source of N2 O emissions those results were combined with both the isotope ratio mass spectrometry analysis of the isotopocules of emitted N2 O and those from the 15 N-tracing technique. RESULTS: The spatial dispersal of N and C significantly affected the quantity, but not the timing, of gas fluxes. Cumulative emissions are larger for treatment 3c than treatment 1c. The 15 N-enrichment analysis shows that initially ~70% of the emitted N2 O derived from the applied amendment followed by a constant decrease. The decrease in contribution of the fertiliser N-pool after an initial increase is sooner and larger for treatment 1c. The Rayleigh-type model applied to N2 O isotopocules data (δ15 Nbulk -N2 O values) shows poor agreement with the measurements for the original one-pool model for treatment 1c; the two-pool models gives better results when using a third-order polynomial equation. In contrast, in treatment 3c little difference is observed between the two modelling approaches. CONCLUSIONS: The importance of N2 O emissions from different N-pools in soil for the interpretation of N2 O isotopocules data was demonstrated using a Rayleigh-type model. Earlier statements concerning exponential increase in native soil nitrate pool activity highlighted in previous studies should be replaced with a polynomial increase with dependency on both N-pool sizes.

Comparative Effectiveness of Coalitions Versus Technical Assistance for Depression Quality Improvement in Persons with Multiple Chronic Conditions.

Significance: Prior research suggests that Community Engagement and Planning (CEP) for coalition support compared with Resources for Services (RS) for program technical assistance to implement depression quality improvement programs improves 6- and 12-month client mental-health related quality of life (MHRQL); however, effects for clients with multiple chronic medical conditions (MCC) are unknown. Objective: To explore effectiveness of CEP vs RS in MCC and non-MCC subgroups. Design: Secondary analyses of a cluster-randomized trial. Setting: 93 health care and community-based programs in two neighborhoods. Participants: Of 4,440 clients screened, 1,322 depressed (Patient Health Questionnaire, PHQ8) provided contact information, 1,246 enrolled and 1,018 (548 with ≥3 MCC) completed baseline, 6- or 12-month surveys. Intervention: CEP or RS for implementing depression quality improvement programs. Outcomes and Analyses: Primary: depression (PHQ9 <10), poor MHRQL (Short Form Health Survey, SF-12<40); Secondary: mental wellness, good physical health, behavioral health hospitalization, chronic homelessness risk, work/workloss days, services use at 6 and 12 months. End-point regressions were used to estimate intervention effects on outcomes for subgroups with ≥3 MCC, non-MCC, and intervention-by-MCC interactions (exploratory). Results: Among MCC clients at 6 months, CEP vs RS lowered likelihoods of depression and poor MHRQL; increased likelihood of mental wellness; reduced work-loss days among employed and likelihoods of ≥4 behavioral-health hospitalization nights and chronic homelessness risk, while increasing faith-based and park community center depression services; and at 12 months, likelihood of good physical health and park community center depression services use (each P<.05). There were no significant interactions or primary outcome effects for non-MCC. Conclusions: CEP was more effective than RS in improving 6-month primary outcomes among depressed MCC clients, without significant interactions.

12-Month Cost Outcomes of Community Engagement Versus Technical Assistance for Depression Quality Improvement: A Partnered, Cluster Randomized, Comparative-Effectiveness Trial.

Objective: To compare community engagement and planning (CEP) for coalition support to implement depression quality improvement (QI) to resources for services (RS) effects on service-use costs over a 12-month period. Design: Matched health and community programs (N=93) were cluster-randomized within communities to CEP or RS. Setting: Two Los Angeles communities. Participants: Adults (N=1,013) with depressive symptoms (Patient Health Questionnaire (PHQ-8) ≥10); 85% African American and Latino. Interventions: CEP and RS to support programs in depression QI. Main Outcome Measures: Intervention training and service-use costs over 12 months. Results: CEP planning and training costs were almost 3 times higher than RS, largely due to greater CEP provider training participation vs RS, with no significant differences in 12-month service-use costs. Conclusions: Compared with RS, CEP had higher planning and training costs with similar service-use costs.

Maintaining Internal Validity in Community Partnered Participatory Research: Experience from the Community Partners in Care Study.

Objective: With internal validity being a central goal of designed experiments, we seek to elucidate how community partnered participatory research (CPPR) impacts the internal validity of public health comparative-effectiveness research. Methods: Community Partners in Care (CPIC), a study comparing a community-coalition intervention to direct technical assistance for disseminating depression care to vulnerable populations, is used to illustrate design choices developed with attention to core CPPR principles. The study-design process is reviewed retrospectively and evaluated based on the resulting covariate balance across intervention arms and on broader peer-review assessments. Contributions of the CPIC Council and the study's design committee are highlighted. Results: CPPR principles contributed to building consensus around the use of randomization, creating a sampling frame, specifying geographic boundaries delimiting the scope of the investigation, grouping similar programs into pairs or other small blocks of units, collaboratively choosing random-number-generator seeds to determine randomized intervention assignments, and addressing logistical constraints in field operations. Study protocols yielded samples that were well-balanced on background characteristics across intervention arms. CPIC has been recognized for scientific merit, has drawn attention from policymakers, and has fueled ongoing research collaborations. Conclusions: Creative and collaborative fulfillment of CPPR principles reinforced the internal validity of CPIC, strengthening the study's scientific rigor by engaging complementary areas of knowledge and expertise among members of the investigative team.