Patient Experience and Attitudes Toward Electronic Intake and Patient-Reported Outcomes Within an Outpatient Whole Health Center.

Background: The use of electronic intake forms within the electronic health record (EHR) is an emerging method for routinely collecting patient-reported outcomes (PRO). However, few studies have evaluated experiences/perspectives toward electronic forms among outpatients receiving care within Integrative Health and Medicine (IHM) clinics. The study purpose was to understand patients' perspectives of electronic intake and PRO forms in the outpatient IHM setting. Methods: Electronic intake (e.g., treatment expectations, medical history, chief complaints, prior experience with integrative modalities) and PRO forms (i.e., Patient Reported Outcome Measurement Information System [PROMIS]-29, Perceived Stress Scale 4, Oswestry Disability Index) were designed in collaboration with clinic leadership and the Information Technology team. Semi-structured interviews were used to gather perspectives of the functionality and acceptability of the forms among outpatients receiving care at the IHM center. Interviews were coded to describe themes regarding perceptions and suggestions for improvement. Results: Qualitative interviews were completed with 10 participants (median age 51 years, 70% female, 30% Black/African American). Participants considered electronic intake and PRO forms as relevant to their health concerns, valuable for conveying important health information to providers, and easy to navigate. Suggested changes to the intake form included adding relevant open-ended questions, save and print functions, and examples and definitions to prompt responses. Conclusion: Participants felt the electronic format was a feasible and acceptable method of collecting patient information and PROs. Future goals are to implement the revised forms in a common EHR to patients receiving care at multiple IHM clinics across the United States.

Updating a diesel engine exhaust job-exposure matrix with published measurement data.

A job-exposure matrix (JEM) is a tool that can estimate diesel engine exhaust (DEE) exposures. JEMs based on expert judgment or measurement data are limited by the information available at the time of development. Over time, more information about hazardous exposures is understood through additional measurements and peer-reviewed publications. This study presents a systematic approach to updating an existing DEE JEM using published data to better reflect current scientific knowledge. The literature was searched for occupational exposure studies that measured DEE as elemental carbon (EC) between January 2010 and May 2022. Four-digit North American Industry Classification System (NAICS) 2002 and National Occupational Classification-Statistics (NOC-S) 2006 codes were assigned to each identified subgroup within the studies. EC exposures were categorized as low (0-10 µg/m3), moderate (10-20 µg/m3), or high (>20 µg/m3). Weighted arithmetic means were calculated for each industry-occupation intersection (IOI) identified in the literature. These means were used to adjust, or retain, the existing exposure level within the JEM cells using a decision tree based on the number of studies, workplace locations, and pooled sample size of the weighted mean. Concordance was measured between the updated JEM (Diesel Exhaust in Canada JEM (DEC-JEM)), the previous (existing) JEM, and the Canadian Job-Exposure Matrix (CANJEM). Thirty-seven studies were identified from the published literature reporting on 53 unique IOIs (20 NAICS and 34 NOC-S codes), including occupations in the mining, construction, and transportation industries. Exposure levels for 66% of identified IOIs increased, most in construction and mining. After the decision tree's results were expanded to the full DEC-JEM, the exposure level of 486 IOIs (12.5% of DEC-JEM) and 286,710 workers (15.8% of DEE-exposed workers) increased. There was a significant correlation between qualitative exposure levels in the updated DEC-JEM and CANJEM (Kendall's τ = 0.364, p < 0.001). This study describes a systematic approach to updating an existing JEM to incorporate new scientific knowledge. The updated DEC-JEM better reflects existing exposure knowledge in several industries, particularly construction. Future analyses include investigating its use as an exposure assessment tool in disease surveillance.

Cost-utility and cost consequence of a telehealth intervention targeting improvement in addictive eating for Australian adults (the TRACE program).

BACKGROUND: The TRACE (Targeted Research for Addictive and Compulsive Eating) intervention was evaluated in a 3-month randomized controlled trial which demonstrated significant improvement in Yale Food Addiction Scale scores favoring dietitian-led telehealth (active intervention) compared with passive and control groups. This study aimed to determine intervention costs and cost-utility. METHODS: Costs of each intervention (2021$AUD) and incremental net monetary benefit (iNMB; incremental benefit, defined as Quality-Adjusted Life Years (QALY) gained, multiplied by willingness to pay threshold minus incremental cost) were calculated to estimate differences between groups. RESULTS: The active intervention (n = 38) cost $294 (95% UI: $266, $316) per person compared to $47 (95% UI: $40, $54) in the passive intervention (n = 24), and $26 in the control group (n = 37). At a cost-effectiveness threshold of $50 000 per QALY score gained, the active intervention iNMB was -$186 (95% UI: -$1137, $834) and the passive group $127 (95% UI: -$1137, $834). Compared to the control group, estimates indicate a 30% chance of the active intervention, and a 60% chance of the passive intervention being cost effective. CONCLUSION: Although the overall cost of the active intervention was low, this was not considered cost-effective in comparison to the passive intervention, given small QALY score gains. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12621001079831.

Cysteamine dioxygenase (ADO) governs cancer cell mitochondrial redox homeostasis through proline metabolism.

2-Aminoethanethiol dioxygenase (ADO) is a thiol dioxygenase that sulfinylates cysteamine and amino-terminal cysteines in polypeptides. The pathophysiological roles of ADO remain largely unknown. Here, we demonstrate that ADO expression represents a vulnerability in cancer cells, as ADO depletion led to loss of proliferative capacity and survival in cancer cells and reduced xenograft growth. In contrast, generation of the ADO knockout mouse revealed high tolerance for ADO depletion in adult tissues. To understand the mechanism underlying ADO's essentiality in cancer cells, we characterized the cell proteome and metabolome following depletion of ADO. This revealed that ADO depletion leads to toxic levels of polyamines which can be driven by ADO's substrate cysteamine. Polyamine accumulation in turn stimulated expression of proline dehydrogenase (PRODH) which resulted in mitochondrial hyperactivity and ROS production, culminating in cell toxicity. This work identifies ADO as a unique vulnerability in cancer cells, due to its essential role in maintenance of redox homeostasis through restraining polyamine levels and proline catabolism.

Use of Cystourethroscopy to Define the Gross Tumour Volume in Radiation Treatment Planning for Canine Genitourinary Carcinomas.

Radiotherapy (RT) is increasingly utilised for definitive-intent treatment of canine genitourinary carcinomas (CGUC). At our institution, the standard approach is to irradiate tomographically abnormal tissues gross tumour volume (GTV) plus a clinical target volume (CTV) expansion of 2 cm. Cystourethroscopy is often incorporated into the treatment planning workflow, though an optimal approach has yet to be defined. This observational study evaluated cystourethroscopy as a tool for identifying gross lesions that can be targeted with RT. We hypothesised that in most cases, addition of cystourethroscopy would result in a larger GTV than would be drawn with computed tomography (CT) alone. Medical records from 54 dogs diagnosed with CGUC between 2013 and 2023 were reviewed; each had been evaluated before RT using CT and cystourethroscopy. The GTV was initially defined as the tomographically evident disease on a post-contrast sagittal plane CT scan, and then lesions visualised with cystourethroscopy (suspected or confirmed to be tumour) were added. Beyond what was visible on CT, cystourethroscopy extended the GTV by a median of 6.5 cm distally into the urethra (range: 1.5-31.8 cm) and therefore resulted in GTV enlargement in 26 of 54 (48%) cases. Addition of our standard 2 cm CTV expansion to a CT-defined GTV (without use of data from cystourethroscopy) would have underestimated the extent of grossly abnormal tissue in 35% (19/54) of cases. These results suggest that incorporating cystourethroscopy into treatment planning workflows may improve local tumour control by reducing the risk of a geographic miss.

Alterations in cortical and subcortical neuroanatomy and associations with behavior in females with fragile X syndrome.

AIM: To address substantial gaps in the literature on neuroanatomical variations in females with fragile X syndrome (FXS). METHOD: Surface-based modeling techniques were applied to the magnetic resonance imaging of 45 females with FXS (mean age = 10 years 9 months, range 6 years-16 years 4 months, SD = 2 years 9 months) and 33 age-matched and developmentally matched females without FXS to elucidate differences in cortical gray matter volume, surface area, and thickness. Gray matter volumes in subcortical regions were examined to ascertain differences in subcortical volume. RESULTS: In females with FXS, cortical volume was greater bilaterally in the occipital pole and smaller in the right postcentral gyrus. Seven regions demonstrated lower surface area in participants with FXS, while cortical thickness was significantly greater over the posterior and medial surfaces in the group with FXS. Subcortical region of interest analyses demonstrated greater volume in the caudate nucleus, globus pallidus, and nucleus accumbens in the group with FXS. Global gray matter volume, pial thickness, and surface area were associated with behavioral outcomes in the group with FXS but not in the comparison group. INTERPRETATION: Females with FXS demonstrated unique cortical and subcortical gray matter anatomy relative to a matched comparison group. These findings may be relevant to the pathogenesis of the FXS behavioral phenotype and provide insights into behavioral interventions targeted to this population.

Airway tryptase levels inform the lack of clinical efficacy of the tryptase inhibitor MTPS9579A in asthma.

BACKGROUND: Tryptase, a mast cell protease, has been identified as a potential therapeutic target in managing patients with refractory asthma. We assessed the efficacy, safety, pharmacokinetics, and pharmacodynamics of MTPS9579A, an anti-tryptase antibody, in a phase 2a randomized trial for patients with uncontrolled asthma and a phase 1c trial to understand activity within the lower respiratory tract. METHODS: Phase 2a patients (n = 134) received 1800 mg MTPS9579A or placebo intravenously every 4 weeks for 48 weeks. The primary endpoint was time to the first composite exacerbation event. Phase 1c patients (n = 27) received one intravenous dose of 300 or 1800 mg MTPS9579A or placebo. Both trials measured MTPS9579A concentrations and effects on tryptase in serum and nasal lining fluid; phase 1c also analyzed bronchial lining fluid. RESULTS: MTPS9579A did not meet the primary endpoint (hazard ratio = 0.90; 95% CI: 0.55-1.47; p = 0.6835); exacerbation rates in the placebo group were low. Serum and nasal MTPS9579A pharmacokinetics and tryptase levels were consistent with data from healthy volunteers. However, in phase 1c patients, compared to nasal levels, MTPS9579A bronchial concentrations were 6.8-fold lower, and bronchial active and total tryptase levels were higher (119-fold and 30-fold, respectively). Pharmacokinetic/pharmacodynamic modeling predicted intravenous doses of 3800 mg every 4 weeks would be necessary to achieve 95% active tryptase inhibition from baseline. CONCLUSIONS: The MTPS9579A dose tested in the phase 2a study was insufficient to inhibit tryptase in bronchial lining fluid, likely contributing to the observed lack of efficacy.

A Comparative Analysis of Oral Health and Self-Rated Health: 'All of Us Research Program' vs. 'Health and Retirement Study'.

Poor oral health can impact overall health. This study assessed the association between dental factors (dentate status and dental utilization) and self-rated health (S-RH) among older adults in two cross-sectional datasets: (1) NIH "All of Us (AoU) Research Program" (May 2018-July 2022 release) and (2) U.S. nationally representative "Health and Retirement Study" (HRS) 2018 wave. Participants aged ≥ 51 years were included in these analyses if (1) from AoU, they had clinical dental and medical data from electronic health records (EHRs) and surveys (n = 5480), and (2) from HRS, they had dental and socio-demographic survey data (n = 14,358). S-RH was dichotomized (fair/poor vs. better) and analyzed with logistic regression. Sample survey weights for HRS and stratification and averaging AoU results used the weighted HRS race-ethnicity and age distribution standardized respective analyses to the U.S. population. Fair/poor S-RH was reported by 32.6% in AoU and 28.6% in HRS. Dentate status information was available from 7.7% of AoU EHRs. In population-standardized analyses, lack of dental service use increased odds of fair/poor S-RH in AoU, OR (95% CI) = 1.28 (1.11-1.48), and in HRS = 1.45 (1.09-1.94), as did having diabetes, less education, and ever being a smoker. Having no natural teeth was not statistically associated with fair/poor S-RH. Lack of dental service was positively associated with fair/poor S-RH in both datasets. More and better oral health information in AoU and HRS are needed.

Quality of Life, Functional Outcomes, and Recurrence After Resection Rectopexy Versus Ventral Mesh Rectopexy for Rectal Prolapse Repair.

BACKGROUND: Resection rectopexy and ventral mesh rectopexy are widely accepted surgical options for the treatment of rectal prolapse, however reports on long-term recurrence rates and functional outcomes are lacking. OBJECTIVE: We compared quality of life, long-term functional outcomes and prolapse recurrence after resection rectopexy versus ventral mesh rectopexy. DESIGN: We retrospectively reviewed our prospectively collected rectal prolapse surgery database. SETTINGS: Patients who underwent resection rectopexy or ventral mesh rectopexy at our center between 2009 and 2016 were included. PATIENTS: Two hundred twenty patients were included, of which 208 (94%) female; 85 (39%) underwent resection rectopexy, 135 (61%) ventral mesh rectopexy. MAIN OUTCOMES MEASURE: Prolapse recurrence. RESULTS: The resection rectopexy group was younger (median 52 vs 60 years old, p = 0.02) and had more open procedures (20% vs 9%, p < 0.001). After a median follow-up of 110 (IQR 94 - 146) months for resection rectopexy and 113 (87 - 137) for ventral mesh rectopexy, recurrences occurred in 21 (26%) in the resection rectopexy and 50 (39%) in the ventral mesh rectopexy group (p = 0.041). Median time to recurrence was 44 (18 - 80) months in the resection rectopexy group and 28.5 (11 - 52.5) in the ventral mesh rectopexy group (p = 0.14). There were no differences in the recurrence rate for primary prolapses in resection rectopexy vs ventral mesh rectopexy. Recurrence rate for re-do prolapses was higher in the ventral mesh rectopexy group 63% at 10 years, versus 25% in resection rectopexy group (p = 0.006). Functional outcomes were similar between the two groups. LIMITATIONS: Retrospective review, recall bias. CONCLUSION: Long-term quality of life and functional outcomes after resection rectopexy and ventral mesh rectopexy were comparable. Ventral mesh rectopexy was associated with a higher prolapse recurrence rate after recurrent rectal prolapse repair. See Video Abstract.

An Approximate Bayesian Computation Approach for Embryonic Astrocyte Migration Model Reduction.

During embryonic development of the retina of the eye, astrocytes, a type of glial cell, migrate over the retinal surface and form a dynamic mesh. This mesh then serves as scaffolding for blood vessels to form the retinal vasculature network that supplies oxygen and nutrients to the inner portion of the retina. Astrocyte spreading proceeds in a radially symmetric manner over the retinal surface. Additionally, astrocytes mature from astrocyte precursor cells (APCs) to immature perinatal astrocytes (IPAs) during this embryonic stage. We extend a previously-developed continuum model that describes tension-driven migration and oxygen and growth factor influenced proliferation and differentiation. Comparing numerical simulations to experimental data, we identify model equation components that can be removed via model reduction using approximate Bayesian computation (ABC). Our results verify experimental studies indicating that the choroid oxygen supply plays a negligible role in promoting differentiation of APCs into IPAs and in promoting IPA proliferation, and the hyaloid artery oxygen supply and APC apoptosis play negligible roles in astrocyte spreading and differentiation.

Optimal control of combination immunotherapy for a virtual murine cohort in a glioblastoma-immune dynamics model.

The immune checkpoint inhibitor anti-PD-1, commonly used in cancer immunotherapy, has not been successful as a monotherapy for the highly aggressive brain cancer glioblastoma. However, when used in conjunction with a CC-chemokine receptor-2 (CCR2) antagonist, anti-PD-1 has shown efficacy in preclinical studies. In this paper, we aim to optimize treatment regimens for this combination immunotherapy using optimal control theory. We extend a treatment-free glioblastoma-immune dynamics ODE model to include interventions with anti-PD-1 and the CCR2 antagonist. An optimized regimen increases the survival of an average mouse from 32 days post-tumor implantation without treatment to 111 days with treatment. We scale this approach to a virtual murine cohort to evaluate mortality and quality of life concerns during treatment, and predict survival, tumor recurrence, or death after treatment. A parameter identifiability analysis identifies five parameters suitable for personalizing treatment within the virtual cohort. Sampling from these five practically identifiable parameters for the virtual murine cohort reveals that personalized, optimized regimens enhance survival: 84% of the virtual mice survive to day 100, compared to 60% survival in a previously studied experimental regimen. Subjects with high tumor growth rates and low T cell kill rates are identified as more likely to die during and after treatment due to their compromised immune systems and more aggressive tumors. Notably, the MDSC death rate emerges as a long-term predictor of either disease-free survival or death.

Cognitive and Social-Emotional Development in Girls With Fragile X Syndrome.

OBJECTIVES: To evaluate the developmental trajectory of key cognitive, social, and emotional features in girls with fragile X syndrome (FXS). METHODS: This longitudinal, parallel cohort study collected data between January 2018 and December 2022. Participants were evaluated 3 times with ∼12-18 months between visits. Participants included 65 girls with FXS, 6 to 16 years, and 52 age- and developmentally-matched girls without FXS. Participants' scores from direct assessment and caregiver report evaluated 3 cognitive domains (verbal abilities, nonverbal abilities, executive function) and 4 social-emotional domains (depression, general anxiety, social behavior, and social anxiety). RESULTS: Participants included 117 girls (mean [M] [SD] age at study entry: FXS M = 10.59 [3.00]; comparison M = 10.45 [2.40])). Omnibus tests showed 4 domains with significant group differences: Verbal (P < .0001, eg, Differential Abilities Scale-II(DAS-II), Picture Vocabulary (-6.25 [1.87])), nonverbal (P < .0001, eg, Kaufman Test of Educational Achievement, Third Edition, Brief Form, Math (-8.56 [2.90])), executive function (P < .0001, eg, NIH Toolbox List Sorting (-6.26 [1.48])), and social anxiety (P < .03, eg, Anxiety, Depression, and Mood Scale (ADAMS) Social Avoidance (1.50 [0.65])). Three domains had significant group by age interaction: Verbal (P < .04, eg, DAS-II, Word Definitions (-1.33 [0.55])), social behavior (P < .01, eg, Social Responsiveness Scale-2 Social Communication (1.57 [0.51])), and social anxiety (P < .01, eg, ADAMS Social Avoidance (0.46 [0.19])). CONCLUSIONS: These findings support the development of early, disorder specific interventions for girls with FXS targeting verbal and nonverbal skills, executive function, social behavior, and social anxiety.

Naltrexone augmented with prazosin for alcohol use disorder: results from a randomized controlled proof-of-concept trial.

AIMS: We conducted a proof-of-concept randomized controlled trial of the mu-opioid receptor antagonist, naltrexone, augmented with the alpha-1 adrenergic receptor antagonist, prazosin, for alcohol use disorder in veterans. We sought a signal that the naltrexone plus prazosin combination regimen would be superior to naltrexone alone. METHODS: Thirty-one actively drinking veterans with alcohol use disorder were randomized 1:1:1:1 to naltrexone plus prazosin (NAL-PRAZ [n = 8]), naltrexone plus placebo (NAL-PLAC [n = 7]), prazosin plus placebo (PRAZ-PLAC [n = 7]), or placebo plus placebo (PLAC-PLAC [n = 9]) for 6 weeks. Prazosin was titrated over 2 weeks to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS. Naltrexone was administered at 50 mg QD. Primary outcomes were the Penn Alcohol Craving Scale (PACS), % drinking days (PDD), and % heavy drinking days (PHDD). RESULTS: In the NAL-PRAZ condition, % reductions from baseline for all three primary outcome measures exceeded 50% and were at least twice as large as % reductions in the NAL-PLAC condition (PACS: 57% vs. 26%; PDD: 51% vs. 22%; PHDD: 69% vs. 15%) and in the other two comparator conditions. Standardized effect sizes between NAL-PRAZ and NAL-PLAC for each primary outcome measure were >0.8. All but one participant assigned to the two prazosin containing conditions achieved the target prazosin dose of 16 mg/day and maintained that dose for the duration of the trial. CONCLUSION: These results suggest that prazosin augmentation of naltrexone enhances naltrexone benefit for alcohol use disorder. These results strengthen rationale for an adequately powered definitive randomized controlled trial.

Global inequities in adverse pregnancy outcomes: what can we do?

The Health Equity Leadership & Exchange Network states that "health equity exists when all people, regardless of race, sex, sexual orientation, disability, socioeconomic status, geographic location, or other societal constructs, have fair and just access, opportunity, and resources to achieve their highest potential for health." It is clear from the wide discrepancies in maternal and infant mortalities, by race, ethnicity, location, and social and economic status, that health equity has not been achieved in pregnancy care. Although the most obvious evidence of inequities is in low-resource settings, inequities also exist in high-resource settings. In this presentation, based on the Global Pregnancy Collaboration Workshop, which addressed this issue, the bases for the differences in outcomes were explored. Several different settings in which inequities exist in high- and low-resource settings were reviewed. Apparent causes include social drivers of health, such as low income, inadequate housing, suboptimal access to clean water, structural racism, and growing maternal healthcare deserts globally. In addition, a question is asked whether maternal health inequities will extend to and be partially due to current research practices. Our overview of inequities provides approaches to resolve these inequities, which are relevant to low- and high-resource settings. Based on the evidence, recommendations have been provided to increase health equity in pregnancy care. Unfortunately, some of these inequities are more amenable to resolution than others. Therefore, continued attention to these inequities and innovative thinking and research to seek solutions to these inequities are encouraged.

Dosing and Misuse of Buprenorphine in the New Jersey Department of Corrections.

Opioid use disorder is common in incarcerated persons, and concern about the diversion of buprenorphine is a barrier to treatment. We conducted a retrospective chart review of incarcerated persons in the New Jersey Department of Corrections who received charges for misuse of medication, including buprenorphine, hypothesizing that the prescription of buprenorphine monoproduct, multiple tabs or films of buprenorphine, or higher doses of buprenorphine would be associated with more diversion incidents. Within the dosing range of 2 to 12 mg, there were more incidents of diversion of buprenorphine monoproduct (24.3%) compared with buprenorphine-naloxone (10.7%, p = .004). More incidents of diversion were seen when multiple films or tabs of buprenorphine product were prescribed (21.7%, comparison 12.7%, p = .01). This observation held when considering multiple buprenorphine-naloxone films, but not multiple buprenorphine tablets. No statistically significant association was found for institutional diversion charges related to higher doses of buprenorphine products. These results suggest that, within the dosing range of buprenorphine used in the New Jersey Department of Corrections, misuse charges were not associated with higher doses although were associated with prescribing buprenorphine monoproduct and multiple films of buprenorphine-naloxone.

Stress increases sperm respiration and motility in mice and men.

Semen quality and fertility has declined over the last 50 years, corresponding to ever-increasing environmental stressors. However, the cellular mechanisms involved and their impact on sperm functions remain unknown. In a repeated sampling human cohort study, we identify a significant effect of prior perceived stress to increase sperm motility 2-3 months following stress, timing that expands upon our previous studies revealing significant stress-associated changes in sperm RNA important for fertility. We mechanistically examine this post-stress timing in mice using an in vitro stress model in the epididymal epithelial cells responsible for sperm maturation and find 7282 differentially H3K27me3 bound DNA regions involving genes critical for mitochondrial and metabolic pathways. Further, prior stress exposure significantly changes the composition and size of epithelial cell-secreted extracellular vesicles that when incubated with mouse sperm, increase mitochondrial respiration and sperm motility, adding to our prior work showing impacts on embryo development. Together, these studies identify a time-dependent, translational signaling pathway that communicates stress experience to sperm, ultimately affecting reproductive functions.

implementation of healthy heart ambassador to improve blood pressure control at community health centers in Texas.

BACKGROUND: Hypertension is one of the most prevalent chronic diseases in the United States and can increase a person's risk of stroke and other cardiovascular complications. Yet only 1 in 4 people with high blood pressure in the United States have their blood pressure managed. To improve hypertension control, we supported 9 health centers in Texas with the implementation of the Healthy Heart Ambassador Blood Pressure Self-Monitoring (HHA) Program. METHODS: We provided health center training using the HHA Program Facilitation Training Guide, recorded barriers to implementing the HHA program, and employed strategies to overcome those barriers. RESULTS: There were 68 staff members from the health centers trained to deliver the HHA program. Three health centers successfully implemented all three major components of HHA, three were able to implement two components, two adopted two components, and one withdrew due to insufficient capacity. Capability, technology infrastructure, and motivation were among the barriers most referenced. CONCLUSION: Clinic non-physician team members delivering the HHA program will need training and ongoing technical assistance to overcome implementation barriers.

Systematic review of applications and properties of the NoMAD instrument for assessing implementation outcomes: Study protocol.

Background: Implementation outcomes measures can be used to assess the implementation of complex health and social care interventions, but evidence for the use of these measures, and their psychometric properties, remains limited. The NoMAD ( Normalisation Me asure Development) survey, based on Normalisation Process Theory, was developed to assess, monitor, or measure factors likely to affect normalisation of a new practice from the perspective of participants who are engaged in an implementation process. Since publication in 2015, NoMAD has been translated into several languages and is increasingly being used in health and care research. This systematic review will identify, appraise, and synthesise the existing literature on the use of NoMAD as an implementation outcome measure, focusing on use and application across different studies and settings, and on its properties as a measurement tool. Methods: We will systematically search the bibliographic databases Web of Science, Scopus and PubMed for articles reporting empirical data in peer-reviewed journals. A citation search will also be undertaken in Google Scholar for primary NoMAD publications. Studies will be eligible for inclusion if they: (a) specify using NoMAD as a method and report results from using it, and/or (b) report a translation and/or validation study of NoMAD's measurement properties. Screening of abstracts and full text articles will be done independently by two researchers. Data extraction will be structured to allow collection and descriptive synthesis of data on study characteristics, use of NoMAD, psychometric results, and authors' reflections and recommendations. Conclusions: This review will provide the first synthesis of how NoMAD has been applied in health and care research, and evidence on its properties as an outcome measure since its publication. This will be used to update existing freely accessible guidance for researchers and other users, and disseminated through peer-reviewed publications, and engagement activities with researchers and practitioners.

Background: Implementation outcome measures are survey tools that have been developed to assess the success of implementation of health and social care interventions. Using theory, the NoMAD ( Normalisation Me asure Development) survey was developed to assess implementation processes, by asking structured questions of persons who are involved in a specific implementation. Once measures like NoMAD are used enough over time, and in a range of studies of different kinds of interventions in different settings, we can collate evidence from those studies to decide (1) how useful they are, and (2) how scientifically robust they are for making assessments in research. In this review, we will search the published literature for papers that report data from studies using NoMAD and summarise their characteristics and results to provide recommendations about how useful and scientifically robust NoMAD is at this time. Methods:We will search databases (Web of Science, Scopus and PubMed), and a google search engine for published studies. We will include papers if they have used the NoMAD survey in their research and report results in their paper or have translated it into another language and tested it scientifically. Decisions about whether to include a paper will be made independently by two researchers, compared, and then agreed. A structured form will be used to capture the same information from each paper. We will summarise information on the studies, how they used NoMAD, what scientific evidence they provide about it, and what authors thought about using it. Conclusions: This will be the first review of studies using the NoMAD survey since it was published in 2015. The results will be used to update publicly available guidance for researchers and other users. We will also share our findings directly through engagement activities with researchers and practitioners and will publish them in scientific journals.

A non-invasive measure of bone growth in mammals: Validating urinary CTX-I as a bone resorption marker through long-bone growth velocity in bonobos.

Assessing bone growth trajectories in mammals is crucial for understanding life history dynamics, but the quantification of bone growth in natural settings can be challenging. Bone resorption markers that can be measured in urine, such as C-telopeptide of type I collagen (CTX-I), offer a non-invasive solution to assess bone growth. Although measurement of urinary CTX-I levels has been applied extensively in human studies, its use in other species is so far limited to a few clinical studies. To validate urinary CTX-I as a bone resorption marker under less controlled conditions, we investigated within-individual day-to-day variation, diurnal patterns, and sex and age-specific variation in zoo-housed bonobos (Pan paniscus). We then also correlated urinary CTX-I levels with forearm growth velocity measures. We found a day-to-day variability in urinary CTX-I levels of around 25%, comparable to human variation. Diurnally, CTX-I levels decreased, aligning with observations in humans and other species. Both sexes showed an age-related decline in urinary CTX-I levels, with a steady decrease after the age of 10 years. Additionally, we found a positive correlation between forearm growth velocity and urinary CTX-I levels across age in female, but not in male, bonobos. Our results demonstrate that urinary CTX-I levels are a meaningful measure of bone growth and highlight its potential to examine bone growth trajectories also in wild populations to investigate life history dynamics.