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Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used for primary staging in prostate cancer (PC), mainly because of its improved accuracy in detecting lymph node metastases compared with conventional imaging. However, the diagnostic benefit of PSMA PET/CT for detecting bone metastases is less well established. This study compares the diagnostic accuracy of 18 F-PSMA PET/CT and 18 F-NaF PET/CT for detecting bone metastases in patients newly diagnosed with PC. Methods: This prospective study included patients with histologically confirmed high-risk PC. All participants were referred from the department of urology to 18 F-NaF PET/CT and underwent 18 F-PSMA PET/CT within 3 weeks. Images were reviewed by 2 nuclear medicine physicians unaware of the results of the other imaging modality. Presence or absence of bone metastases and number of metastatic lesions were recorded. A reference standard was established at the patient level based on agreement between the 2 imaging modalities. In cases of concordance, both modalities were deemed correct. In cases of discordance, additional follow-up scans were performed. Diagnostic performance metrics, including sensitivity, specificity, and accuracy, were calculated. Results: In total, 160 participants were included. Sensitivity, specificity, and accuracy for detecting bone metastases at the patient level were 0.98, 0.99, and 0.99, respectively, for 18 F-PSMA PET/CT, and 0.91, 1.00, and 0.97, respectively, for 18 F-NaF PET/CT. No significant differences were found. The concordance rate of bone metastases between 18 F-NaF and 18 F-PSMA PET/CT at the patient level was observed in 154 patients (96.3%). 18 F-PSMA PET/CT tended to identify more bone metastases per patient than 18 F-NaF PET/CT. Conclusion: Both 18 F-NaF and 18 F-PSMA PET/CT exhibit high diagnostic accuracy for detecting bone metastases in newly diagnosed high-risk PC patients. 18 F-PSMA PET/CT may detect additional metastatic lesions compared with 18 F-NaF PET/CT. Subsequent 18 F-NaF PET/CT may be redundant if no bone metastases are found on 18 F-PSMA PET/CT., (© 2025 by the Society of Nuclear Medicine and Molecular Imaging.)

International commitments advocate large-scale forest restoration as a nature-based solution to climate change mitigation through carbon (C) sequestration. Mounting evidence suggests that mixed compared to monospecific planted forests may sequester more C, exhibit lower susceptibility to climate extremes and offer a broader range of ecosystem services. However, experimental studies comprehensively examining the control of tree diversity on multiple C stocks and fluxes above- and belowground are lacking. To address this gap, we leverage data from the Sardinilla experiment in Panama, the oldest tropical tree diversity experiment, which features a gradient of one-, two-, three- and five-species mixtures of native tree species. Over 16 years, we measured multiple above- and belowground C stocks and fluxes, ranging from tree aboveground C, over leaf litter C production, to soil organic carbon (SOC). We show that tree diversity significantly increased aboveground C stocks and fluxes, with a 57% higher gain in aboveground tree C in five-species mixtures compared to monocultures (35.7 ± 1.8 vs. 22.8 ± 3.4 Mg C ha -1 ) 16 years after planting. In contrast, we observed a net reduction in SOC (on average -11.2 ± 1.1 Mg C ha -1 across diversity levels) and no significant difference in SOC 3 stocks (the predominantly tree-derived, i.e., C 3 plant-derived SOC fraction) between five-species mixtures and monocultures (13.0 ± 0.9 vs. 15.1 ± 1.3 Mg C ha -1 ). Positive tree diversity effects persisted despite repeated climate extremes and strengthened over time for aboveground tree growth. Structural equation models showed that higher tree growth in mixtures enhanced leaf litter and coarse woody debris C fluxes to the soil, resulting in a tightly linked C cycle aboveground. However, we did not observe significant links between above- and belowground C stocks and fluxes. Our study elucidates the mechanisms through which higher tree diversity bolsters the climate mitigation potential of tropical forest restoration. Restoration schemes should prioritize mixed over monospecific planted forests., (Global Change Biology© 2025 The Author(s). Global Change Biology published by John Wiley & Sons Ltd.)

Background: The COVID-19 pandemic introduced complexities that were likely more demanding for some groups, such as children and adolescents, and especially those with pre-existing mental health diagnoses. This study examines long-term patterns of psychiatric healthcare use among this vulnerable group, providing insights into shifts in psychiatric healthcare use during a global health crisis., Methods: We use data from the primary and specialist healthcare registries available from the Norwegian emergency preparedness register for COVID-19 (Beredt C19) to estimate patterns of psychiatric healthcare use. The data spans 2017 to 2022, covering children and adolescents aged 6-19. We identified young people with recent diagnoses of mental health conditions and compared weekly consultation volumes before and during the pandemic for mental health conditions overall and the following diagnostic or symptom categories separately: anxiety/depression and Attention-Deficit Hyperactivity Disorders (ADHD). Analyses were stratified by gender., Results: There was a consistent trend of lower-than-predicted weekly healthcare consultations among young people with pre-existing mental health diagnoses in both primary and specialist healthcare during the pandemic. The reduction was more pronounced in later follow-up periods. The study highlights gender disparities, with boys experiencing more notable declines in healthcare consultations, especially in specialist care. Additionally, the time trends varied across different diagnostic groups. While consultations for anxiety/depression were consistently below the predicted levels, declines in ADHD occurred later in the pandemic. The data suggests an overall decline in healthcare use rather than a shift between sectors., Conclusion: The findings offer insights into healthcare use during pandemic times among children and adolescents with pre-existing mental health diagnoses. The study underscores the importance of continuous monitoring and support for this group, ensuring accessible and responsive healthcare during public health emergencies., Competing Interests: Declarations. Ethics approval and consent to participate: The Regional Ethics Committee for Medical Research South-East Norway approved the current study #267200. For data minimization purposes, we only had access to the data needed from the Beredt C19, not the entire database (data minimization). Data was based on de-identified and routinely collected registry data from the Norwegian population. According to the Norwegian Health Registry Act § 19, The Regional Ethics Committee for Medical Research South-East Norway waived the informed consent requirement. The study was carried out following the ethical standards of the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Patient Reported Outcomes Measurement Information System Fatigue Short-Form (PROMIS-F-SF) is a self-administered, patient reported outcome (PRO) designed to assess fatigue in healthy and clinical populations and for tracking progress during treatment for disorders complicated with fatigue., Methods: Patients in the Mental Health Service Outpatient Clinics and healthy volunteers were invited to complete a survey, which included the Danish translation of the PROMIS-F-SF, the Chalder Fatigue Scale (CFS-11), and measures of depression and anxiety. We conducted a confirmatory factor analysis of the previously suggested single-factor structure of the instrument. We furthermore evaluated the construct validity of the PROMIS-F-SF by means of its relationship with the CFS-11. Finally, we evaluated the utility of the PROMIS-F-SF to identify patient-status by conducting receiver operating characteristic curves., Results: 70 healthy volunteers and 62 patients completed the instruments. The PROMIS-F-SF had a average fit to the previously reported single-factor structure. Cronbach's alpha and McDonald's omega showed good internal reliability (α = 0.96, ωtotal = 0.97). PROMIS-F-SF score was positively correlated with the CFS-11 (r =.76) and it correlated highly with depression (r =.78) and anxiety (r =.74) score. The optimal cut-off point in the ROC-analyses was 15, which yielded a sensitivity of 89% and a specificity of 67% in the prediction of patient status., Conclusions: Level of fatigue among psychiatric outpatients is high in patients with psychiatric illness, compared to levels measured in healthy volunteers. The Danish PROMIS-F-SF shows good psychometric properties in this combined sample of healthy adults and psychiatric patients with non-psychotic disorders and it is recommended as PRO measure for psychiatric populations. Examination of psychometric properties in patient populations with somatic disorder could be a natural next step., Competing Interests: Declarations. Ethics approval and consent to participate: The study was in accordance with local regulations registered with the Danish Data Protection Agency Region Zealand (REG-048-2021). The survey study did not, as per local guidelines and regulations, need approval by the Region Zealand Ethics Committee. Informed consent was taken from participants to participate in the study. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests. The authors has no affiliation to the PROMIS group., (© 2025. The Author(s).)

Prominent ears, also known as prominauris, inflict psychological distress and suffering on both children and adults. Otoplasty has become one of the most common aesthetic operations due to its high prevalence and significant impact on patients. Various surgical techniques for otoplasty have been documented and developed over time. While complications are rare, open and cartilage-resection techniques may result in hemorrhage, hematomas, contour deformities, hypertrophic scarring, and keloid formation. Incisionless otoplasty has been demonstrated in the literature to be an effective method, when correctly indicated, to correct prominauris with a shorter recovery time and reduced morbidity. A thorough preoperative evaluation, awareness of the different techniques, and assessment of their appropriate application minimize potential risks and unpleasant results., Competing Interests: None declared., (Thieme. All rights reserved.)

Follicular lymphoma (FL) is the most common low-grade lymphoma. Despite its indolent nature, FL carries an inherent risk of histological transformation (HT) to a more aggressive lymphoma. Existing biomarkers are insufficient to predict HT, indicating the need for more robust biological predictors. Previously, we used mass spectrometry-based proteomics to identify differentially expressed proteins in diagnostic FLs with and without subsequent HT. This study sought to further investigate identified proteins in transformation of FL, generally acting in important cellular pathways such as (i) apoptosis (BID), (ii) cell cycle (CDC26, CDK6, SRSF1, SRSF2), (iii) GTPase signaling (IQGAP2, MEK1), (iv) cytoskeletal rearrangement and cellular migration (ACTB, CD11a, MMP9, SEPT6), and (v) immune processes (CD81, IgG, MPO, PIK3AP1). We analyzed pre-therapeutic samples from 48 FL patients, either non-transforming FL (nt-FL, n = 30) or subsequently-transforming FL (st-FL, n = 18), the latter with histologically-confirmed transformation after their initial FL diagnosis. Paired high-grade lymphomas (tFL, n = 18) from the time of transformation were also analyzed. We used immunohistochemistry and digital image analysis to quantify protein levels. In all five pathway classes, several proteins were differentially expressed between either the diagnostic nt-FL and st-FL samples, or between the paired st-FL and tFL samples (p < 0.05). Interestingly, we found correlation between expression levels of several proteins, indicating a complex involvement between several pathways. Differential expression of most proteins was also associated with shorter transformation-free survival (p < 0.05). These findings emphasize underlying differences in FL biology predictive of subsequent transformation, highlighting deregulation of important interconnected cellular pathways., Competing Interests: Declarations. Conflict of interest: BH holds shares in Novo Nordisk A/S and Genmab A/S. Novo Nordisk A/S and Genmab A/S had no influence on the study design, analyses and reporting of results. All other authors declare no relevant competing financial interests., (© 2024. The Author(s).)

Objectives: To develop a tool for measuring performance of a coordinated care center against the criteria of an integrated practice unit (IPU) and test it against an established care center in the Military Health System (MHS)., Study Design: Characteristics of 4 patient care coordination models were sorted using the 11 criteria of the IPU., Methods: Subject matter experts evaluated characteristics and criteria for inclusion or exclusion based on the needs of specialty care in the MHS. The consolidated tool was tested using the example of the National Intrepid Center of Excellence (NICoE), which provides coordinated, colocated care for patients with traumatic brain injury, using responses of yes, partial, no, not applicable, or incomplete., Results: The final tool contained 7 IPU criteria subdivided into 18 measures. NICoE was found in 2020 to meet 11 measures fully and 6 partially, with 1 deemed not applicable. In 2023 it met 17 of 18 measures, with the remaining (translation services) available as an enterprise-wide resource. The tool was seen to need improvement in clarification of 3 measures and in 1 criterion that is evaluated differently by patients vs providers., Conclusions: This IPU assessment tool accurately captures both the strengths and weaknesses of a coordinated care facility within the MHS. Iterative refinement of the tool is expected to inform ongoing discussion of the transformation of care in the MHS and the US and to provide a framework by which to measure the care performance of centers wishing to reorganize as IPUs.

The Military Health System (MHS) has historically been at the forefront of innovation in medicine and science, but it has also historically struggled to implement battlefield innovations or civilian technologies for wider domestic use. Artificial intelligence (AI) has emerged as a transformative force in health care with civilian health systems and institutions at the forefront of these innovations. While these tools have the potential to support resolution of military health's most pressing issues, the MHS is behind its civilian counterparts in advancing AI. Adoption of AI could benefit the MHS in such areas as service member and beneficiary access to care; more precise allocation of medical personnel and resources; improved operations of military treatment facilities; early detection of emerging threats to health; and force multiplication of existing telehealth capabilities. This evolving and highly visible technology also presents challenges in the military context above those in the civilian context, such as additional levels of privacy and security, integration with purpose-built secure systems, and additional regulatory obligations. To address these, the MHS should engage in three lines of effort to advance AI: establishing governance, education and training of medical personnel, and engaging in research, development, testing, and piloting of AI applications. This will require dedicated personnel and resources for a substantial initial outlay to be recouped later through more effective administration and care. By leveraging lessons learned from civilian systems, the MHS can design, adopt, and implement AI solutions to improve care for service members in both domestic and operational contexts, and for their beneficiaries., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Systematic reviews and data synthesis of randomised clinical trials play a crucial role in clinical practice, research, and health policy. Trial sequential analysis can be used in systematic reviews to control type I and type II errors, but methodological errors including lack of protocols and transparency are cause for concern. We assessed the reporting of trial sequential analysis., Methods: We searched Medline and the Cochrane Database of Systematic Reviews from 1 January 2018 to 31 December 2021 for systematic reviews and meta-analysis reports that include a trial sequential analysis. Only studies with at least two randomised clinical trials analysed in a forest plot and a trial sequential analysis were included. Two independent investigators assessed the studies. We evaluated protocolisation, reporting, and interpretation of the analyses, including their effect on any GRADE evaluation of imprecision., Results: We included 270 systematic reviews and 274 meta-analysis reports and extracted data from 624 trial sequential analyses. Only 134/270 (50%) systematic reviews planned the trial sequential analysis in the protocol. For analyses on dichotomous outcomes, the proportion of events in the control group was missing in 181/439 (41%), relative risk reduction in 105/439 (24%), alpha in 30/439 (7%), beta in 128/439 (29%), and heterogeneity in 232/439 (53%). For analyses on continuous outcomes, the minimally relevant difference was missing in 125/185 (68%), variance (or standard deviation) in 144/185 (78%), alpha in 23/185 (12%), beta in 63/185 (34%), and heterogeneity in 105/185 (57%). Graphical illustration of the trial sequential analysis was present in 93% of the analyses, however, the Z-curve was wrongly displayed in 135/624 (22%) and 227/624 (36%) did not include futility boundaries. The overall transparency of all 624 analyses was very poor in 236 (38%) and poor in 173 (28%)., Conclusions: The majority of trial sequential analyses are not transparent when preparing or presenting the required parameters, partly due to missing or poorly conducted protocols. This hampers interpretation, reproducibility, and validity., Study Registration: PROSPERO CRD42021273811., (© 2024. The Author(s).)

Introduction: In psychotherapy, having a reliable tracking tool is vital for effective treatment. We have validated the Danish version of the 'Overall Depression Severity and Impairment Scale' (ODSIS), which is used in the Unified Protocol for Emotional Disorders (UP) and other cognitive behavioural therapies. This five-item self-rating scale is expected to correspond closely to the gold-standard Beck Depression Inventory-II (BDI-II), but also to self-rating scales addressing daily functioning and well-being., Methods: Internal consistency is assessed using Cronbach's alpha and McDonald's omega. Criterion validity is explored through Pearson's correlation coefficient with BDI-II, the Work and Social Adjustment Scale (WSAS), the Five-Item World Health Organization Well-Being Index (WHO-5) and scatter plots, and an optimal cut-off score is determined using a receiver operating characteristic curve. The study included 340 respondents: 234 from a recent clinical trial, 56 psychiatric patients from inpatient/outpatient units and 50 healthy volunteers., Results: ODSIS demonstrates strong internal consistency (Cronbach's alpha: 0.887-0.956, McDonald's omega: 0.888-0.957). Correlations with BDI-II, WSAS and WHO-5 highlight its strong criterion validity (BDI-II: 0.847, WSAS: 0.751, WHO-5: 0.771). The optimal cut-off score (> 7.5) for detecting depression shows great sensitivity (0.862) and specificity (0.731)., Conclusion: The Danish version of ODSIS proves to be a reliable instrument for quantification of a combination of depression level and functional impairment from the symptoms. Its high correlation with established BDI-II makes it a brief and handy tool for repeated measurement in clinical and research settings., (© 2024 The Author(s). Clinical Psychology & Psychotherapy published by John Wiley & Sons Ltd.)

While there is substantial evidence on excess mortality in the first two years of the COVID-19 pandemic, no study has conducted a cause-specific analysis of excess mortality for the whole period 2020-2022 across multiple countries. We examined cause-specific excess mortality during 2020-2022 in Denmark, Finland, Norway, and Sweden-four countries with similar demographics and welfare provisions, which implemented different pandemic response policies. To this end, we utilized nationwide register-based information on annual cause-specific deaths stratified by age and sex, and applied linear regression models to predict mortality in 2020-2022 based on the reference period 2010-2019. Excess deaths were obtained by contrasting actual and expected deaths. Additional analyses employed standardization to a common population, as well as population adjustments to account for previous deaths. Our results showed that, besides deaths due to COVID-19 (a total of 32,491 during 2020-2022), all countries experienced excess deaths due to cardiovascular diseases (in total 11,610 excess deaths), and under-mortality due to respiratory diseases other than COVID-19 (in total 9878) and dementia (in total 8721). The excess mortality due to cardiovascular diseases was particularly pronounced in Finland and Norway in 2022, and the under-mortality due to dementia was particularly pronounced in Sweden in 2021-2022. In conclusion, while COVID-19 deaths emerge as the most apparent consequence of the pandemic, our findings suggest that mortality has also been influenced by substitutions between different causes of death and over time, as well as indirect consequences of COVID-19 infection and pandemic responses-albeit to different extents in the different countries., (© 2024. The Author(s).)

Follicular lymphoma (FL) exhibits considerable variability in biological features and clinical trajectories across patients. To dissect the diversity of FL, we utilized a Bernoulli mixture model to identify genetic subtypes in 713 pre-treatment tumor tissue samples. Our analysis revealed the existence of five subtypes with unique genetic profiles that correlated with clinicopathological characteristics. The clusters were enriched in specific mutations as follows: CS (CREBBP and STAT6), TT (TNFAIP3 and TP53), GM (GNA13 and MEF2B), Q (quiescent, for low mutation burden), and AR (mutations of mTOR pathway-related genes). The subtype Q was enriched for patients with stage I disease and associated with a lower proliferative history than the other subtypes. The AR subtype was unique in its enrichment for IgM-expressing FL cases and was associated with advanced-stage and more than 4 nodal sites. The existence of subtypes was validated in an independent cohort of 418 samples from the GALLIUM trial. Notably, patients assigned to the TT subtype consistently experienced inferior progression-free survival when treated with immunochemotherapy. Our findings offer insight into core pathways distinctly linked with each FL cluster and are expected to be informative in the era of targeted therapies., (© 2024. The Author(s).)

Background: The Nordic countries represent a unique case study for the COVID-19 pandemic due to socioeconomic and cultural similarities, high-quality comparable administrative register data and notable differences in mitigation policies during the pandemic. We aimed to compare weekly excess mortality in the Nordic countries across the three full pandemic years 2020-2022., Methods: Using data on weekly all-cause mortality from official administrative registers in Denmark, Finland, Norway and Sweden, we employed time series regression models to assess mortality developments within each pandemic year, with the period 2010-2019 used as reference period. We then compared excess mortality across the countries in 2020-2022, taking differences in population size and age- and sex-distribution into account. Results were age- and sex-standardized to the Danish population of 2020. Robustness was examined with a variety of sensitivity analyses., Results: While Sweden experienced excess mortality in 2020 [75 excess deaths per 100 000 population (95% prediction interval 29-122)], Denmark, Finland and Norway experienced excess mortality in 2022 [52 (14-90), 130 (83-177) and 88 (48-128), respectively]. Weekly death data reveal how mortality started to increase in mid-2021 in Denmark, Finland and Norway, and continued above the expected level through 2022., Conclusion: Although the Nordic countries experienced relatively low pandemic excess mortality, the impact and timing of excess mortality differed substantially. These estimates-arguably the most accurate available for any region in capturing pandemic-related excess deaths-may inform future research and policy regarding the complex mortality dynamics in times of a health crisis such as the COVID-19 pandemic., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

This article presents what we believe to be a novel chip-scale 25-45-GHz re-configurable mm-wave remote antenna unit (RAU) for radio over fiber (RoF) distributed antenna systems. The proposed RAU architecture optimizes energy efficiency by operating directly at mm-wave frequencies, and spectral efficiency by selecting re-configurable RF photonic filters topology. Additionally, it achieves frequency agility by rejecting interferes and a small form factor by utilizing the SOI photonics process. Two photonic integrated circuits (PICs) that act as downlink and uplink units are presented while occupying a total area of 12.33 mm 2 . The downlink selects a single channel within the desired frequency range, while the uplink rejects up to four interferes. The building blocks of the proposed architecture are discussed and their design consideration and parameters are shown. Then, a comprehensive system analysis of the proposed RAU architecture including key performance indicators is presented. A scalable 5-channel system is demonstrated each with a 3-dB Bandwidth of 5-GHz. Moreover, this architecture can be continuously tuned and re-configured within a wide frequency range to cover all 5-channels. To the best of the authors' knowledge, this is the first wideband modular and re-configurable mm-wave RAU that covers the entire mm-wave sub-45-GHz band implemented in silicon photonics.

This review summarises the present knowledge of prophylactic progesterone and preterm birth. Preterm birth (less-than 37 weeks) is a leading cause of neonatal mortality and morbidity worldwide. The incidence varies globally but remains low in the Nordic countries (5-6%). Prediction and prevention are complicated due to diverse aetiology, but obstetric history and cervical length can improve prediction. Prophylactic vaginal progesterone initiated between 12 and 24 weeks of gestation is recommended to reduce preterm birth less-than 33-35 weeks in singleton pregnancies with a history of preterm birth or with a short cervix (less-than 25 mm) and can be considered for twin pregnancies with the same risk factors., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Introduction: As a result of the COVID-19 pandemic, telehealth use became widespread, allowing for continued health care while minimizing COVID-19 transmission risk for patients and providers. This rapid scale-up highlighted shortcomings of the current telehealth infrastructure in many health systems. We aimed to identify and address gaps in the United States Military Health System (MHS) response to the COVID-19 pandemic related to the implementation and utilization of telehealth. Methods: We conducted semistructured key informant interviews of MHS stakeholders, including policymakers, program managers, and health care providers. We recruited respondents using purposive and snowball sampling until we reached thematic saturation. Interviews were conducted virtually from December 2022 to March 2023 and coded by deductive thematic analysis using NVivo. Results: We interviewed 28 key informants. Several themes emerged from the interviews and were categorized into four defined areas of obstacles to the effective utilization of telehealth: administrative, technical, organizational, and quality issues. While respondents had positive perceptions of telehealth, issues such as billing, licensure portability, network connectivity and technology, and ability to monitor health outcomes represent major barriers in the current system, preventing the potential for further expansion. Conclusions: While the shift to telehealth during the COVID-19 pandemic demonstrated robust potential within the MHS, it highlighted shortcomings that impair the utility and expansion of telehealth on a level comparable to that of other large health systems. Future focus should be directed toward generating and implementing actionable recommendations that target these identified challenges in the MHS.

Introduction: Previous research has identified low socioeconomic status (SES) as a risk factor for long-term sickness absence (LTSA) and disability pension (DP) following trauma. However, most studies lack information on medical diagnoses, limiting our understanding of the underlying factors. To address this gap, we retrieved information about diagnostic causes for receipt of welfare benefits to explore the role of SES in the transition from post-injury LTSA to permanent DP among the working population in Norway., Materials and Methods: We conducted a population-based cohort study of all Norwegian residents aged 25-59 years registered with a spell of LTSA due to injury commencing in the period 2000-2003. This cohort was followed through 2014 by linking information on receipt of welfare benefits with sociodemographic data from administrative registers. SES was defined as a composite measure of educational attainment and income level. We used flexible parametric survival models to estimate hazard ratios (HR) with 95 % confidence intervals (CI) for all-cause and diagnosis-specific DP according to SES, adjusting for sex, age, marital status, immigrant status and healthcare region of residence., Results: Of 53,937 adults with post-injury LTSA, 9,665 (18 %) transferred to DP during follow-up. The crude risk of DP was highest for LTSA spells due to poisoning and head injuries. Overall, individuals in the lowest SES category had twice the risk of DP compared to those in the highest SES category (HR = 2.25, 95 % CI 2.13-2.38). The difference by SES was greatest for LTSA due to poisoning and smallest for LTSA due to head injuries. A majority (75 %) of DP recipients had a non-injury diagnosis as the primary cause of DP. The socioeconomic gradient was more pronounced for non-injury causes of DP (HR = 2.47, 95 % CI 2.31-2.63) than for injury causes (HR = 1.73, 95 % CI 1.56-1.92) and was especially steep for DP due to musculoskeletal diseases and mental and behavioural disorders., Conclusions: The relationship between SES and DP varied by both the type of injury that caused LTSA and the diagnosis used to grant DP, highlighting the importance of taking diagnostic information into account when investigating long-term consequences of injuries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This review provides a comprehensive overview of the occurrence, fate, treatment and multi-criteria analysis of microplastics (MPs) and organic contaminants (OCs) in biosolids. A meta-analysis was complementarily analysed through the literature to map out the occurrence and fate of MPs and 10 different groups of OCs. The data demonstrate that MPs (54.7% occurrence rate) and linear alkylbenzene sulfonate surfactants (44.2% occurrence rate) account for the highest prevalence of contaminants in biosolids. In turn, dioxin, polychlorinated biphenyls (PCBs) and phosphorus flame retardants (PFRs) have the lowest rates (<0.01%). The occurrence of several OCs (e.g., dioxin, per- and polyfluoroalkyl substances, polycyclic aromatic hydrocarbons, pharmaceutical and personal care products, ultraviolet filters, phosphate flame retardants) in Europe appear at higher rates than in Asia and the Americas. However, MP concentrations in biosolids from Australia are reported to be 10 times higher than in America and Europe, which required more measurement data for in-depth analysis. Amongst the OC groups, brominated flame retardants exhibited exceptional sorption to biosolids with partitioning coefficients (log K d ) higher than 4. To remove these contaminants from biosolids, a wide range of technologies have been developed. Our multicriteria analysis shows that anaerobic digestion is the most mature and practical. Thermal treatment is a viable option; however, it still requires additional improvements in infrastructure, legislation, and public acceptance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Like civilian health systems, the United States Military Health System (MHS) confronts challenges in achieving the aims of reducing cost, and improving quality, access, and safety, but historically has lacked coordinated health services research (HSR) capabilities that enabled knowledge translation and iterative learning from its wealth of data. A military-civilian academic partnership called the Comparative Effectiveness and Provider-Induced Demand Collaboration (EPIC), formed in 2011, demonstrated early proof-of-concept in using the MHS claims database for research focused on drivers of variation in health care. This existing partnership was reorganized in 2015 and its topics expanded to meet the need for HSR in support of emerging priorities and to develop current and HSR capacity within the MHS., Materials and Methods: A Donabedian framework of structure, process, and outcomes was applied to support the project, through a core of principal investigators, researchers, analysts, and administrators. Within this framework, new researchers and student trainees learn foundations of HSR while performing secondary analysis of claims data from the MHS Data Repository (MDR) focusing on Health and Readiness, Pediatrics, Policy, Surgery, Trauma, and Women's Health., Results: Since 2015, the project has trained 25 faculty, staff, and providers; 51 students and residents; 21 research fellows across multiple disciplines; and as of 2022, produced 107 peer-reviewed publications and 130 conference presentations, across all five themes and six cores. Research results have been incorporated into Federal and professional policy guidelines. Major research areas include opioid usage and prescribing, value-based care, and racial disparities. EPIC researchers provide direct support to MHS leaders and enabling expertise to clinical providers., Conclusions: EPIC, through its Donabedian framework and utilization of the MHS Data Repository as a research tool, generates actionable findings and builds capacity for continued HSR across the MHS. Eight years after its reorganization in 2015, EPIC continues to provide a platform for capacity building and knowledge translation., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Telehealth care expanded during the COVID-19 pandemic, although previous studies show racial, gender, and socioeconomic inequalities in its usage. Racial disparities are known to be mitigated in the Military Health System (MHS), whose 9.6 million beneficiaries are universally insured and nationally representative. This study investigated whether known disparities in telehealth usage were mitigated in the MHS. Methods: This study performed a retrospective cross-sectional study of TRICARE telehealth claims data from January 2020 to December 2021. Beneficiaries aged 0 to 64 years were identified with Common Procedural Terminology code modifiers 95, GT, and GQ, which indicated procedures that were delivered through either synchronous or asynchronous telecommunication services. Visits were defined as one encounter per patient per day. Analyses included descriptive statistics of patient demographics, number of telehealth visits, and differences between military-provided and private sector care (PSC). Military rank was used as a proxy for socioeconomic status (SES), generally combining income, education, and occupation type. Results: A total of 917,922 beneficiaries received telehealth visits during the study period: 25% in direct care, 80% in PSC, and 4% in both care settings. The majority of visits were received by females (57%) and associated with a Senior Enlisted rank (66%). The visits by racial category were proportional to the percentage of each category in the population. The lowest number of visits was for those older than 60 years, potentially receiving Medicare instead, and those associated with Junior Enlisted rank, a potential disparity that may also reflect access to leave or smaller family size. Conclusions and Relevance: Within the MHS, telehealth visits were equitable by race, in line with previous findings, but not by gender, SES, or age. Findings by gender are reflected in the greater U.S. population. Further research is needed to assess and address potential disparities associated with Junior Enlisted rank as proxy for low SES.

Follicular lymphoma (FL) is an indolent lymphoma with a generally favorable prognosis. However, histological transformation (HT) to a more aggressive disease leads to markedly inferior outcomes. This study aims to identify biological differences predictive of HT at the time of initial FL diagnosis. We show differential protein expression between diagnostic lymphoma samples from patients with subsequent HT (subsequently-transforming FL [st-FL]; n = 20) and patients without HT (nontransforming FL [nt-FL]; n = 34) by label-free quantification nano liquid chromatography-tandem mass spectrometry analysis. Protein profiles identified patients with high risk of HT. This was accompanied by disturbances in cellular pathways influencing apoptosis, the cytoskeleton, cell cycle, and immune processes. Comparisons between diagnostic st-FL samples and paired transformed FL (n = 20) samples demonstrated differential protein profiles and disrupted cellular pathways, indicating striking biological differences from the time of diagnosis up to HT. Immunohistochemical analysis of apoptotic proteins, CASP3, MCL1, BAX, BCL-xL, and BCL-rambo, confirmed higher expression levels in st-FL than in nt-FL samples (P < .001, P = .015, P = .003, P = .025, and P = .057, respectively). Moreover, all 5 markers were associated with shorter transformation-free survival (TFS; P < .001, P = .002, P < .001, P = .069, and P = .010, respectively). Notably, combining the expression of these proteins in a risk score revealed increasingly inferior TFS with an increasing number of positive markers. In conclusion, proteomics identified altered protein expression profiles (particularly apoptotic proteins) at the time of FL diagnosis, which predicted later transformation., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Introduction: Eye and vision disorders are estimated to impact 7.08 million people in the United States, including 1.62 million under the age of 40. This study uses the Vision and Eye Health Surveillance System (VEHSS) case definitions to assess the burden of eye and vision disorders in a universally insured, nationally representative population., Materials and Methods: This retrospective, cross-sectional study applied the VEHSS case definitions to TRICARE claims data collected from the Military Health System Data Repository and Defense Enrollment Eligibility Reporting System during 2018. Beneficiaries aged 0-64 years during the fiscal year 2018 were identified with inpatient and outpatient codes matching to the VEHSS diagnostic case definitions, which were organized into 17 categories of eye and vision disorders classified by the ICD-10. Beneficiaries were recorded only once per category but allowed to match to multiple categories. Analyses included descriptive statistics of patient demographics and prevalence of eye disorders., Results: We identified 4,548,897 TRICARE Prime/Plus beneficiaries (54.86% men and 45.14% women), of whom 22.93% were diagnosed with at least one disorder in 2018. Of those with a diagnosis, the majority were men (50.13%), adults (74.91%), and of or sponsored by a senior enlisted rank (57.83%), used as socioeconomic proxy. Disorders of refraction and accommodation were most prevalent, followed by infectious and inflammatory diseases. Potentially preventable and treatable conditions, including amblyopia and strabismus, infectious and inflammatory disease, and diabetic complications, affected up to 22% of those with vision disorders., Conclusions: This study represents the first use of VEHSS measures in a universally insured, socioeconomically diverse population. Identification of potentially treatable or preventable conditions indicates significant opportunity to mitigate the burden of eye and vision disorders in the Military Health System., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: Vestibular disorders affect an estimated 33 million adults and 3.5 million children and adolescents in the United States. Previous research relying on self-reported symptoms versus actual diagnosis has limited the ability to provide prevalence estimates for specific vestibular disorders at the population level. This study seeks to describe the burden of vestibular disorders among children and working-age adult beneficiaries in the Military Health System (MHS)., Materials and Methods: Using the MHS Data Repository (MDR), we conducted a cross-sectional study of all TRICARE Prime and Plus MHS beneficiaries aged 0 to 64 years from fiscal years (FY) 2018 to 2019. Study analyses included descriptive statistics of patient demographics and assessing the prevalence of vestibular disorders in pediatric and working-age adult beneficiaries., Results: Of the 5,541,932 TRICARE Prime/Prime Plus MHS beneficiaries, 52,878 (0.95%) had a diagnosis of vestibular disorder during fiscal years 2018 to 2019, of which 1,359 were pediatric and adolescents (aged 0 to 17 years) and 51,519 were working-age adults (18 to 64 years). Vertigo was the most common diagnosis in both age-group populations (11.46 per 1,000 working-age adults; 0.52 per 1,000 children and adolescents), with benign vertigo being the most prevalent of the three diagnoses and occurring at a seven times higher rate in adults versus pediatric and adolescents., Conclusions: This study demonstrates the effectiveness of using medical claims data to estimate prevalence compared to self-reported survey data and supports prevalence estimates of vestibular disease in <1% of children overall, but indicate much higher prevalence for adolescents., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: During the COVID-19 pandemic, individuals with pre-existing mental health problems may have experienced additional stress, which could worsen symptoms or trigger relapse. Thus, this study aimed to investigate if the number of consultations with general practitioners (GPs) among individuals with a pre-existing common mental health problem during the pandemic differed from pre-pandemic years., Methods: Data on consultations with GPs among 18-65-year-olds registered with common mental health problems in 2017-2021 were retrieved from the Norwegian Control and Payment of Health Reimbursements Database. Based on data from the pre-pandemic years (2017-2019), we predicted the number of consultations per week for depression, anxiety disorder, phobia/obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and eating disorders during the pandemic (March 2020-December 2021) among individuals with pre-existing mental health problems. The forecasted and observed trends in GP consultations per week during the pandemic were stratified by diagnosis, gender, and age groups., Results: The observed number of consultations for anxiety disorder, PTSD, and eating disorders were significantly higher than forecasted during extended periods of the two pandemic years. The differences were largest for PTSD (on average 37% higher in men and 47% higher in women during the pandemic), and for eating disorders among women (on average 87% higher during the pandemic). There were only minor differences between the predicted and observed number of consultations for depression and phobia/OCD., Conclusions: During the pandemic, individuals with a recent history of mental health problems were more likely to seek help for anxiety disorder, PTSD, and eating disorders, as compared to pre-pandemic years., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Opioid misuse is a nationwide issue and is of particular concern with regard to military readiness. The 2017 National Defense Authorization Act charges the Military Health System with greater oversight of opioid use and mitigation of misuse., Methods: We synthesized published articles using secondary analysis of TRICARE claims data, a nationally representative database of 9.6 million beneficiaries. We screened 106 articles for inclusion and identified 17 studies for data abstraction. Framework analysis was conducted, which assessed prescribing practices, patient use, and optimum length of opioid prescriptions after surgery, trauma, and common procedures, as well as factors leading to sustained prescription opioid use., Results: Across the studies, sustained prescription opioid use after surgery was low overall, with <1% of opioid-naïve patients still receiving opioids more than 1 year after spinal surgery or trauma. In opioid-exposed patients who had undergone spine surgery, sustained use was slightly lower than 10%. Higher rates of sustained use were associated with more severe trauma and depression, as well as with prior use and initial opioid prescriptions for low back pain or other undefined conditions. Black patients were more likely to discontinue opioid use than were White patients., Conclusions: Prescribing practices are well correlated with degree of injury or intensity of intervention. Sustained prescription opioid use beyond 1 year is rare and is associated with diagnoses for which opioids are not the standard of care. More efficient coding, increased attention to clinical practice guidelines, and use of tools to predict risk of sustained prescription opioid use are recommended., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)

Background: There is a concern that exposure to psychosocial stressors during the COVID-19 pandemic may have led to a higher incidence of mental disorders. Thus, this study aimed to compare trends in incidence rates of depressive disorder, anxiety disorders, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and eating disorders in primary- and specialist health care before (2015-2019) and during the COVID-19 pandemic (2020-2021)., Methods: We used aggregated population registry data to calculate incidence rates of mental disorders from primary- (The Norwegian Control and Payment of Health Reimbursements Registry (KUHR)) and specialist (The Norwegian Patient Registry (NPR)) health care. The analyses included all Norwegian residents aged 18-65 during the study period. Incident cases were defined as having no previous registration with the same mental disorder in KUHR (from 2006) or NPR (from 2008). We used linear prediction models and mean models to compare incidence rates and test trends before and during the pandemic., Results: During the pandemic, the incidence rates among women were higher or as predicted for OCD in specialist health care and for eating disorders in both primary- and specialist health care. These findings were strongest among women aged 18-24 years. Incidence rates for depression and phobia/OCD among both genders in primary health care and phobic anxiety disorders among both genders in specialist health care were lower or as predicted., Conclusion: The COVID-19 pandemic may have led to more women needing treatment for OCD and eating disorders in the Norwegian population. The decreased incidence rates for some disorders might indicate that some individuals either avoided seeking help or had improved mental health during the pandemic., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: Norway has a high incidence of forearm fractures, however, the incidence rates based on secondary care registers can be underestimated, as some fractures are treated exclusively in primary care. We estimated the proportion of forearm fracture diagnoses registered exclusively in primary care and assessed the agreement between diagnosis for forearm fractures in primary and secondary care., Design: Quality assurance study combining nationwide data from 2008 to 2019 on forearm fractures registered in primary care (Norwegian Control and Payment of Health Reimbursement) and secondary care (the Norwegian Patient Registry)., Setting and Patients: Forearm fracture diagnoses in patients aged ≥20 treated in primary care ( n  = 83,357) were combined with injury diagnoses for in- and outpatients in secondary care ( n  = 3,294,336)., Main Outcome Measures: Proportion of forearm fractures registered exclusively in primary care, and corresponding injury diagnoses for those registered in both primary and secondary care., Results: Of 189,105 forearm fracture registrations in primary and secondary care, 13,948 (7.4%) were registered exclusively in primary care. The proportion ranged from 4.9% to 13.5% on average between counties, but was higher in some municipalities (>30%). Of 66,747 primary care forearm fractures registered with a diagnosis in secondary care, 62% were incident forearm fractures, 28% follow-up controls, and 10% other fractures or non-fracture injuries., Conclusion: An overall small proportion of forearm fractures were registered only in primary care, but it was larger in some areas of Norway. Failing to include fractures exclusively treated in primary care could underestimate the incidence rates in these areas.

Background: Widely published findings from the COVID-19 pandemic show adverse effects on body mass index (BMI) and behavioral health in both adults and children, due to factors such as illness, job loss, and limited opportunity for physical and social activity. This study investigated whether these adverse effects were mitigated in adolescents from military families, who are universally insured with consistent access to healthcare, and who generally have at least one parent who must adhere to physical and mental fitness as a condition of employment., Methods: We conducted a cohort study using two groups of adolescents receiving care in the U.S. Military Health System during the COVID-19 pandemic; one for changes in Body Mass Index (BMI) and the second for changes in behavioral health diagnoses, using TRICARE claims data. Beneficiaries (160,037) ages 13 to 15 years in fiscal years 2017-2018, were followed up during October 2020 to June 2021., Results: Among the BMI cohort, 44.32% of underweight adolescents moved to healthy weight, 28.48% from overweight to obese, and 3.7% from healthy weight to underweight. Prevalence of behavioral disorders showed an overall 29.01% percent increase during the study period, which included in mood (86.75%) and anxiety (86.49%) disorders, suicide ideation (42.69%), and suicide attempts (77.23%). Decreases in percent change were observed in conduct disorders (-15.93%) and ADD/ADHD (-8.61%)., Conclusions: Adolescents in military families experienced adverse health outcomes during the pandemic at approximately the same rates as those in non-military families, suggesting that universal insurance and military culture were not significantly mitigating factors. Obesity and underweight present significant opportunities to intervene in areas such as exercise and food access. Decreased conduct disorders and ADD/ADHD may reflect lower prevalence due to favorable home environment, or lower rates of diagnosis and referral; however, increased rates of anxiety, mood disorders, suicide ideation and attempt are especially concerning. Care should be taken to ensure that adolescents receive consistent opportunity for physical activity and social interaction, and those at risk for suicide should receive active monitoring and appropriate referral to behavioral healthcare providers., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: The COVID-19 pandemic generated a major shift from in-person to telehealth care in efforts to reduce the spread of infection. This study assesses the effects of COVID-19 on the provision of telehealth in the United States Military Health System (MHS), a universally-insured, nationally representative population of beneficiaries who may receive direct care (DC) at military facilities or in the private-sector care (PSC)., Methods: Under a cross-sectional study design, we queried the MHS Data Repository for all telehealth services in the MHS from January 2019 to December 2021, using common procedure terminology code telehealth modifiers GT, GQ, and 95. Analyses were stratified by clinical, provider, and facility characteristics, and comparisons were made between telehealth rates before and during the COVID-19 period using a percent change., Results: Telehealth usage increased by 20-fold in 2020 versus 2019, whereas provider types shifted from predominantly physicians to advanced practice nurses and physician assistants. Patterns of task shifting were different between DC and PSC. Tele-mental health visits showed a 118% change in DC and -20% change in PSC, suggesting recapture of care to military facilities. Decreases in DC telehealth visits for metabolic, endocrine, and musculoskeletal disorders were not compensated by increases in PSC, suggesting care deferred, delivered by another modality, or sought outside the MHS., Conclusion: The increase in telehealth usage and behavioral health is in line with other published studies, whereas the shift in provider types aligns with MHS goals focused on increasing access through telehealth. More research is needed to answer questions of care deferral, which are relevant to national health care discussions., Competing Interests: The authors declare they have no conflicts of interest., (© Thomas Gilder et al., 2023; Published by Mary Ann Liebert, Inc.)

Introduction: Weight gain in pregnancy is expected; however, excessive gestational weight gain and postpartum weight retention (PPWR) can cause long-term changes to a patient's body mass index (BMI) and increase the risk for adverse health outcomes. This phenomenon is understudied in active duty military women, for whom excess weight gain poses challenges to readiness and fitness to serve. This study examines over 30,000 active duty military women with and without preeclampsia to assess changes in BMI postpartum., Materials and Methods: This is a retrospective analysis of claims data for active duty military women, aged 18-40 years, and experiencing pregnancy during fiscal years 2010-2014. Women with eating disorders, high-risk pregnancy conditions other than preeclampsia, scheduled high-risk medical interventions, or a second pregnancy within 18 months were excluded from the analysis. Height and weight were obtained from medical records and used to calculate BMI. Women with and without preeclampsia were categorized into BMI categories according to the Centers for Disease Control and Prevention classification of underweight (BMI < 18.5), normal weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9), or obese (>30.0). Linear regressions adjusted by age and race were performed to assess differences in prepregnancy weight and weight gain, retention, and change at 6 months postpartum., Results: The greatest number of pregnant, active duty service women were found among ages 18-24 years, White race, Army service, junior enlisted rank, married status, and with no mental health diagnosis. Overall, over 50% of women in normal and preeclamptic pregnancies returned to their baseline BMI postpartum. Women in both populations more often gained than lost weight postpartum. Preeclampsia strongly affected weight retention, with 40.77% of overweight women and 5.33% of normal weight women progressing to postpartum obesity, versus 32.95% of overweight women and 2.61% of normal weight women in the main population. Mental health conditions were not associated with significant weight gain or PPWR. Women with cesarean deliveries gained more weight during pregnancy, had more PPWR, and lost more weight from third trimester to 6 months postpartum., Conclusions: Most women remain in their baseline BMI category postpartum, suggesting that prepregnancy weight management is an opportunity to reduce excess PPWR. Other opportunities lie in readiness-focused weight management during prenatal visits and postpartum, especially for patients with preeclampsia and cesarean sections. However, concerns about weight management for readiness must be carefully balanced against the health of the individual service members., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Follicular lymphoma (FL) is a lymphoid neoplasia characterized by an indolent clinical nature. Despite generally favorable prognoses, early progression and histological transformation (HT) to a more aggressive lymphoma histology remain the leading causes of death among FL patients. To provide a basis for possible novel treatment options, we set out to evaluate the expression levels of indoleamine 2,3-dioxygenase 1 (IDO1), an immunoinhibitory checkpoint molecule, in follicular and transformed follicular biopsies. The expression levels of IDO1 were assessed using immunohistochemical staining and digital image analysis in lymphoma biopsies from 33 FL patients without subsequent HT (non-transforming FL, nt-FL) and 20 patients with subsequent HT (subsequently transforming FL, st-FL) as well as in paired high-grade biopsies from the time of HT (transformed FL, tFL). Despite no statistical difference in IDO1 expression levels seen between the groups, all diagnostic and transformed lymphomas exhibited positive expression, indicating its possible role in novel treatment regimens. In addition, IDO1 expression revealed a positive correlation with another immune checkpoint inhibitor, namely programmed death 1 (PD-1). In summary, we report IDO1 expression in all cases of FL and tFL, which provides the grounds for future investigations of anti-IDO1 therapy as a possible treatment for FL patients.

Background: The U.S. Military Health System (MHS) pioneered the use of telehealth in deployed environments in the early 1990s. However, its use in non-deployed environments historically lagged behind that of the Veterans Health Administration (VHA) and comparable large civilian health systems, due to administrative, policy, and other obstacles that slowed or blocked its expansion in the MHS. A report was prepared in December 2016, which summarized past and then-present telehealth initiatives in the MHS; described the obstacles, opportunities, and policy environment; and provided three possible courses of action for expansion of telehealth in deployed and non-deployed settings., Methods: Gray literature, peer-reviewed literature, presentations, and direct input were aggregated under the guidance of subject matter experts., Results: Past and then-current efforts demonstrated significant telehealth capability in use and in development for the MHS, mainly in deployed or operational settings. Policy from 2011 to 2017 demonstrated an environment favorable for MHS expansion, while the review of comparable civilian and veterans' healthcare systems showed significant benefits including increased access and lower cost from use of telehealth in non-deployed settings. The 2017 National Defense Authorization Act charged the Secretary of Defense with promoting telehealth usage for the Department of Defense, including provisions for removing obstacles and reporting progress within 3 years. The MHS has the ability to reduce burdensome interstate licensing and privileging requirements, but still requires an increased level of cybersecurity, compared to civilian systems., Discussion: The benefits of telehealth fit with the MHS Quadruple Aim of improving cost, quality, access, and readiness. Readiness is particularly served by the use of "physician extenders," which allows nurses, physician assistants, medics, and corpsmen to provide hands-on care under remote oversight and to practice at the top of their licenses. Based on this review, three courses of action were recommended: to focus largely on developing telehealth in deployed environments; to maintain focus in deployed environments and increase telehealth development in non-deployed environments to keep pace with the VHA and private sector; or to use lessons learned from military and civilian telehealth initiatives to leapfrog the private sector., Conclusion: This review serves as a snapshot in time of the steps leading to telehealth expansion before 2017, which helped to set the stage for later use of telehealth in behavioral health initiatives and as a response to coronavirus disease 2019. The lessons learned are ongoing and further research is expected to inform additional development of telehealth capability for the MHS., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

This study aims to investigate the spatiotemporal trends and impact of COVID-19 lockdowns to the profile of physiochemical parameters in the influent of wastewater treatment plants (WWTPs) around Brisbane, Australia. One 24-hr composite influent sample was collected from 10 WWTPs and analyzed for a range of physiochemical parameters per week (i.e., chemical oxygen demand (COD), total organic carbon (TOC), total nitrogen (TN), total phosphorus (TP), ammonia, volatile suspended solid (VSS)) and per month (i.e., Ni and Cr) from 2012 to 2020, including the period of COVID-19 lockdowns in the region. The catchments studied were urban, with a mix of domestic and industrial activities contributing towards the contaminant profile. Statistical analysis identified that industrial and commercial land use, as well as population size had a large impact to the parameter loads and profile. Per capita mass loads of Cr in one catchment were 100 times higher than in others from one industrial point source. TP demonstrated a potential monotonic decrease over time due to practical reduction policies that have been implemented for phosphorous content in household detergents, except for one catchment where trade waste from food manufacturing industries contributed to an overall increase of 6.9%/year TP. The COVID-19 lockdown (March-April 2020) posed different impact on different catchments, either decrease (7-61%) or increase (2-40%) of most parameter loads (e.g., COD, TOC, TN, TP, VSS, Ammonia), which was likely driven by catchment characteristics (i.e., the proportion of residential, commercial, and industrial land uses). This study enhances our understanding of spatiotemporal trend of contaminants in the catchments for further effective source control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Racial disparities in health care are a well-documented phenomenon in the USA. Universal insurance has been suggested as a solution to mitigate these disparities. We examined race-based disparities in the Military Health System (MHS) by constructing and analyzing a framework of existing studies that measured disparities between direct care (care provided by military treatment facilities) and private sector care (care provided by civilian health care facilities)., Materials and Methods: We conducted a framework synthesis on 77 manuscripts published in partnership with the Comparative Effectiveness and Provider-Induced Demand Collaboration Project that use MHS electronic health record data to present an overview of racial disparities assessed for multiple treatment interventions in a nationally representative, universally insured population., Results: We identified 32 studies assessing racial disparities in areas of surgery, trauma, opioid prescription and usage, women's health, and others. Racial disparities were mitigated in postoperative complications, trauma care, and cancer screenings but persisted in diabetes readmissions, opioid usage, and minimally invasive women's health procedures., Conclusion: Universal coverage mitigates many, but not all, racial disparities in health care. An examination of a broader range of interventions, a closer look at variation in care provided by civilian facilities, and a look at the quality of care by race provide further opportunities for research., (© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Norway is an elongated country with large variations in climate and duration of winter season. It is also a high-risk country for osteoporotic fractures, in particular hip fractures, which cause high mortality. Although most hip fractures occur indoors, there is a higher incidence of both forearm and hip fractures during wintertime, compared with summertime. In a nationwide longitudinal cohort study, we investigated whether cold ambient (outdoor) temperatures could be an underlying cause of this high incidence and mortality. Hospitalized/outpatient forearm fractures (International Classification of Diseases and Related Health Problems, 10th Revision [ICD-10] code S52) and hospitalized hip fractures (ICD-10 codes S72.0-S72.2) from 2008 to 2018 were retrieved from the Norwegian Patient Registry. Average monthly ambient temperatures (degrees Celsius, °C) from the years 2008 to 2018 were provided by the Norwegian Meteorological Institute and linked to the residential area of each inhabitant. Poisson models were fitted to estimate the association (incidence rate ratios [IRRs], 95% confidence intervals [CIs]) between temperature and monthly incidence of total number of forearm and hip fractures. Flexible parametric survival models (hazard ratios [HR], 95% CI) were used to estimate the association between temperature and post-hip fracture mortality, taking the population mortality into account. Monthly temperature ranged from -20.2°C to 22.0°C, with a median of -2.0°C in winter and 14.4°C in summer. At low temperatures (<0°C) compared to ≥0°C, there was a 53% higher risk of forearm fracture (95% CI, 51%-55%) and 21% higher risk of hip fracture (95% CI, 19%-22%), adjusting for age, gender, calendar year, urbanization, residential region, elevation, and coastal proximity. When taking the population mortality into account, the post-hip fracture mortality in both men (HR 1.08; 95% CI, 1.02-1.13) and women (HR 1.09; 95% CI, 1.04-1.14) was still higher at cold temperatures. There was a higher risk of forearm and hip fractures, and an excess post-hip fracture mortality at cold ambient temperatures. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Objectives: To examine the military-civilian collaborative efforts which addressed the unprecedented challenges of the COVID-19 pandemic, particularly in areas including provision of supplies, patient and provider support, and development and dissemination of new vaccine and drug candidates., Methods: We examined peer reviewed and grey literature from September 2020 to June 2021 to describe the relationship between the U.S. healthcare system and Military Health System (MHS). For analysis, we applied the World Health Organization framework for health systems, which consists of six building blocks., Results: The strongest collaborative efforts occurred in areas of medicine and technology, human resources, and healthcare delivery, most notably in the MHS supplying providers, setting up treatment venues, and participating in development of vaccines and therapeutics. Highlighting that the MHS, with its centralized structure and ability to deploy assets rapidly, is an important contributor to the nation's ability to provide a coordinated, large-scale response to health emergencies., Conclusions: Continuing the relationship between the two health systems is vital to maintaining the nation's capability to meet future health challenges., (© 2022. The Author(s).)

Introduction: The polytrauma clinical triad (PCT), encompassing traumatic brain injury, PTSD, and chronic pain, has been identified as a significant concern in the Military Health System (MHS). Conditions in this triad mutually reinforce one another and can pose a significant challenge to treatment for patients and providers. Polytrauma clinical triad has previously been studied in deployed veterans but remains understudied in the active duty military population. Therefore, this novel study seeks to determine the prevalence of PCT among active duty service members and to identify the subpopulations most at risk for PCT., Materials and Methods: This cross-section study used the MHS Data Repository in order to retrospectively review all administrative claim data for active duty service members within the Army, Navy, Air Force, and Marine Corps from fiscal years 2010 to 2015. Specific ICD-9 codes were extracted that correlated with traumatic brain injury, PTSD, and chronic pain to determine the risk of PCT. We used logistic regression to compare individuals presenting with the PCT conditions to those service members without any of the PCT diagnoses codes., Results: The study identified 2,441,698 active duty service members eligible for inclusion. The prevalence of all three conditions of PCT was 5.99 per 1,000 patients. Patients with PCT were most likely to be 20-29 years old (52.15%), male (89.83%), White (59.07%), married (64.18%), Junior Enlisted (55.27%), and serving in the Army (74.71%)., Conclusion: This study is the first to identify the risk of PCT in the active duty military population. Awareness of the risk and subsequent prompt identification of the triad will enable treatment through an integrated, team approach, which should alleviate potential patient suffering and improve the efficiency of care and readiness of service members., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Several studies have documented an inverse gradient between socioeconomic status (SES) and injury mortality, but the evidence is less consistent for injury morbidity. The aim of this study was to investigate the association between SES and injury severity for acute hospitalizations in a nationwide population-based cohort., Methods: We conducted a registry-based cohort study of all individuals aged 25-64 years residing in Norway by 1st of January 2008. This cohort was followed from 2008 through 2014 using inpatient registrations for acute hospitalizations due to all-cause injuries. We derived two measures of severity: threat-to-life using the International Classification of Disease-based Injury Severity Score (ICISS), and threat of disability using long-term disability weights from the Injury-VIBES project. Robust Poisson regression models, with adjustment for age, sex, marital status, immigrant status, municipality population size and healthcare region of residence, were used to calculate incidence rate ratios (IRRs) by SES measured as an index of education, income, and occupation., Results: We identified 177,663 individuals (7% of the population) hospitalized with at least one acute injury in the observation period. Two percent (n = 4,186) had injuries categorized with high threat-to-life, while one quarter (n = 43,530) had injuries with high threat of disability. The overall adjusted IRR of hospitalization among people with low compared to high SES was 1.57 (95% CI 1.55, 1.60). Comparing low to high SES, injuries with low threat-to-life were associated with an IRR of 1.56 (95% CI 1.54, 1.59), while injuries with high threat-to-life had an IRR of 2.25 (95% CI 2.03, 2.51). Comparing low to high SES, injuries with low, medium, and high threat of disability were associated with IRRs of respectively, 1.15 (95% CI 1.11, 1.19), 1.70 (95% CI 1.66, 1.73) and 1.99 (95% CI 1.92, 2.07)., Discussion: We observed an inverse gradient between SES and injury morbidity, with the steepest gradient for the most severe injuries. This suggests a need for targeted preventive measures to reduce the magnitude and burden of severe injuries for patients with low socioeconomic status., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We have identified a series of novel insulin receptor partial agonists (IRPAs) with a potential to mitigate the risk of hypoglycemia associated with the use of insulin as an antidiabetic treatment. These molecules were designed as dimers of native insulin connected via chemical linkers of variable lengths with optional capping groups at the N-terminals of insulin chains. Depending on the structure, the maximal activation level (%Max) varied in the range of ∼20-70% of native insulin, and EC 50 values remained in sub-nM range. Studies in minipig and dog demonstrated that IRPAs had sufficient efficacy to normalize plasma glucose levels in diabetes, while providing reduction of hypoglycemia risk. IRPAs had a prolonged duration of action, potentially making them suitable for once-daily dosing. Two lead compounds with %Max values of 30 and 40% relative to native insulin were selected for follow up studies in the clinic.

Histological transformation (HT) remains the leading cause of mortality in follicular lymphoma (FL), underlining the need to identify reliable transformation predictors. The hyaluronic acid receptors CD44 and the receptor for hyaluronan mediated motility (RHAMM, also known as HMMR and CD168), have been shown to be involved in the pathogeneses of both solid tumors and hematological malignancies. In an attempt to improve risk stratification, expression of RHAMM and CD44 were evaluated by immunohistochemistry and digital image analysis in pre-therapeutic tumor-tissue biopsies from FL patients, either without (nt-FL, n = 34), or with (st-FL, n = 31) subsequent transformation, and in paired biopsies from the transformed lymphomas (tFL, n = 31). At the time of initial diagnosis, samples from st-FL patients had a higher expression of RHAMM compared with samples from nt-FL patients (p < 0.001). RHAMM expression further increased in tFL samples following transformation (p < 0.001). Evaluation of CD44 expression showed no differences in expression comparing nt-FL, st-FL, and tFL samples. Shorter transformation-free survival was associated with high tumoral and intrafollicular RHAMM expression, as well as with low intrafollicular CD44 expression (p = 0.002, p < 0.001, and p = 0.034, respectively). Our data suggest that high tumor-tissue RHAMM expression predicts the risk of shorter transformation-free survival in FL patients already at initial diagnosis.

Objective: To gain insight into the molecular mechanisms underlying the early stages of vocal fold extracellular matrix (ECM) remodeling after a mid-membranous injury resulting from the use of human amniotic epithelial cells (hAEC), as a novel regenerative medicine cell-based therapy., Methods: Vocal folds of six female, New Zealand White rabbits were bilaterally injured. Three rabbits had immediate bilateral direct injection of 1 × 10 6 hAEC in 100 µl of saline solution (hAEC) and three with 100 µl of saline solution (controls, CTR). Rabbits were euthanized 6 weeks after injury. Proteomic analyses (in-gel trypsin protein digestion, LC-MS/MS, protein identification using Proteome Discoverer and the Uniprot Oryctolagus cuniculus (Rabbit) proteome) and histological analyses were performed., Results: hAEC treatment significantly increased the expression of ECM proteins, elastin microfibril interface-located protein 1 (EMILIN-1) and myocilin that are primarily involved in elastogenesis of blood vessels and granulation tissue. A reactome pathway analysis showed increased activity of the anchoring fibril formation by collagen I and laminin, providing mechanical stability and activation of cell signaling pathways regulating cell function. hAEC increased the abundance of keratin 1 indicating accelerated induction of the differentiation programming of the basal epithelial cells and, thereby, improved barrier function. Lastly, upregulation of Rab GDP dissociation inhibitor indicates that hAEC activate the vesicle endocytic and exocytic pathways, supporting the exosome-mediated activation of cell-matrix and cell-to-cell interactions., Conclusions: This pilot study suggests that injection of hAEC into an injured rabbit vocal fold favorably alters ECM composition creating a microenvironment that accelerates differentiation of regenerated epithelium and promotes stabilization of new blood vessels indicative of accelerated and improved repair., (© 2022. The Author(s).)

Background: A decline of brain serotonin (5-HT) is held responsible for the changes in mood that can be observed in Alzheimer's disease (AD). However, 5-HT'ergic signaling is also suggested to reduce the production of pathogenic amyloid-β (Aβ)., Objective: To investigate the effect of targeted inactivation of tryptophan hydroxylase-2 (Tph2), which is essential for neuronal 5-HT synthesis, on amyloidosis in amyloid precursor protein (APP)swe/presenilin 1 (PS1) ΔE9 transgenic mice., Methods: Triple-transgenic (3xTg) APP/PS1 mice with partial (+/-) or complete Tph2 knockout (-/-) were allowed to survive until 6 months old with APP/PS1, Tph2-/-, and wildtype mice. Survival and weight were recorded. Levels of Aβ42/40/38, soluble APPα (sAβPPα) and sAβPPβ, and cytokines were analyzed by mesoscale, neurotransmitters by mass spectrometry, and gene expression by quantitative PCR. Tph2, microglia, and Aβ were visualized histologically., Results: Tph2 inactivation in APP/PS1 mice significantly reduced viability, without impacting soluble and insoluble Aβ42 and Aβ40 in neocortex and hippocampus, and with only mild changes of soluble Aβ42/Aβ40. However, sAβPPα and sAβPPβ in hippocampus and Aβ38 and Aβ40 in cerebrospinal fluid were reduced. 3xTg-/-mice were devoid of Tph2 immunopositive fibers and 5-HT. Cytokines were unaffected by genotype, as were neocortical TNF, HTR2a and HTR2b mRNA levels in Tph2-/- mice. Microglia clustered around Aβ plaques regardless of genotype., Conclusion: The results suggest that Tph2 inactivation influences AβPP processing, at least in the hippocampus, although levels of Aβ are unchanged. The reduced viability of 3xTg-/-mice could indicate that 5-HT protects against the seizures that can impact the viability of APP/PS1 mice.

Background: Telehealth in the Military Health System (MHS) has long been an important tool for delivering care in deployed settings. However, the scope of nondeployed telehealth usage in the MHS has not previously been published, making full evaluation difficult. This study aims at addressing this gap by assessing trends over time, demographics, provider types, and diagnoses most associated with telehealth usage in the MHS. Methods: Secondary analysis was conducted on health care claims from the MHS Data Repository for all telehealth services provided from fiscal years 2006 to 2018. Telehealth services were identified by using Common Procedural Terminology (CPT) code modifiers GT, GQ, and 95. Patient demographics, provider type, and major diagnostic category were assessed for all telehealth services in both direct (military provided) and purchased (private sector) care. Results: Usage of telehealth services in the MHS rose ∼19-fold, from 2,549 to 48,667 occurrences, from 2006 to 2018. Physicians provided ∼60% of telehealth services overall, and the greatest usage was for mental health diagnoses. Purchased care (PC) showed differences from direct care (DC), including a greater level of expansion, greater inclusion of children and adolescents, and lower usage of telehealth for non-mental health services. Conclusions: Telehealth usage in the MHS has increased substantially from a total 2,549 occurrences in 2006 to 48,667 occurrences in 2018, demonstrating greater acceptance and usage by both DC and PC providers. Future directions include assessing provider types, diagnosis codes, and patient demographics associated with telehealth use, especially in the emerging COVID19 clinical practice environment.

Aims: In order to prevent a major outbreak of COVID-19 disease in Norway, a series of lockdown measures was announced on 12 March 2020. The aim of the present paper was to describe the impact of this lockdown on the treatment of injuries., Methods: We collected hospital data on injury diagnoses from a national emergency preparedness register established during the pandemic. We identified the number of injured patients per day in the period 1 January-30 June 2020, and analysed the change in patient volumes over two three-week periods before and during the lockdown by sex, age, level of care, level of urgency, type of contact and type of injury., Results: Compared to pre-lockdown levels, there was an overall reduction of 43% in injured patients during the first three weeks of lockdown. The decrease in patient contacts did not differ by sex, but was most pronounced among young people. Substantial reductions were observed for both acute and elective treatment and across all levels of care and types of contact, with the exception of indirect patient contacts. The change in patient contacts varied considerably by injury type, with the largest reduction observed for dislocations/sprains/strains. The decrease was much lower for burns/corrosions and poisoning., Conclusions: A substantial reduction in the treatment of injuries was observed during lockdown in Norway. Possible explanations for this finding include an overall decrease in injury risk, a redistribution of hospital resources and a higher threshold for seeking medical attention as a result of the pandemic.

Competing Interests: The authors declare no funding or conflicts of interest.

Many studies have shown a connection between poor oral health and a number of systemic diseases. Recent studies have demonstrated an association between poor oral health and the oral microbiota to carcinogenesis. This review article will focus on studies that link oral dysbiosis, periodontal disease, and specific oral microorganisms to gastrointestinal malignancies. These studies provide some insight and understanding of the role of the oral microbiome in carcinogenesis. Understanding how the oral microbiota is related to carcinogenesis and gastrointestinal malignancies could lead to identifying biomarkers and provides future treatment modalities. More research in this area would be beneficial to the diagnosis and treatment of patients with gastrointestinal malignancies., Competing Interests: Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo.2020.02.03). The series “Global GI Malignancies” was commissioned by the editorial office without any funding or sponsorship. The author has no other conflicts of interest to declare., (2021 Journal of Gastrointestinal Oncology. All rights reserved.)