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Adrianne Kehne,1,2 Steven J Bernstein,1– 3 Jennifer Thomas,1 Mark C Bicket,3,4,* Amy SB Bohnert,2– 4,* Erin Fanning Madden,5,* Victoria D Powell,6,7,* Pooja Lagisetty1– 3 1Division of General Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; 2Center for Clinical Management Research, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA; 3Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA; 4Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA; 5Department of Family Medicine and Public Health Sciences, Wayne State University School of Medicine, Detroit, MI, USA; 6Palliative Care Program, Division of Geriatric and Palliative Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; 7Geriatrics Research, Education, and Clinical Center, LTC Charles S. Kettles VA Medical Center, Ann Arbor, MI, USA*These authors contributed equally to this workCorrespondence: Adrianne Kehne, Division of General Internal Medicine, University of Michigan, 2800 Plymouth Road, Building 16, Floor 4, Ann Arbor, MI, 48109, USA, Tel +1 301 503 3936, Email adkehne@med.umich.eduPurpose: About 5– 8 million US patients take long-term opioid therapy for chronic pain. In the context of policies and guidelines instituted to reduce inappropriate opioid prescribing, abrupt discontinuations in opioid prescriptions have increased and many primary care clinics will not prescribe opioids for new patients, reducing access to care. This may result in uncontrolled pain and other negative outcomes, such as transition to illicit opioids. The objective of this study was to generate policy, intervention, and research recommendations to improve access to care for these patients.Participants and Methods: We conducted a RAND/UCLA Modified Delphi, consisting of workshops, background videos and reading materials, and moderated web-based panel discussions held September 2020–January 2021. The panel consisted of 24 individuals from across Michigan, identified via expert nomination and snowball recruitment, including clinical providers, health science researchers, state-level policymakers and regulators, care coordination experts, patient advocates, payor representatives, and community and public health experts. The panel proposed intervention, policy, and research recommendations, scored the feasibility, impact, and importance of each on a 9-point scale, and ranked all recommendations by implementation priority.Results: The panel produced 11 final recommendations across three themes: reimbursement reform, provider education, and reducing racial inequities in care. The 3 reimbursement-focused recommendations were highest ranked (theme average = 4.2/11), including the two top-ranked recommendations: increasing reimbursement for time needed to treat complex chronic pain (ranked #1/11) and bundling payment for multimodal pain care (#2/11). Four provider education recommendations ranked slightly lower (theme average = 6.2/11) and included clarifying the spectrum of opioid dependence and training providers on multimodal treatments. Four recommendations addressed racial inequities (theme average = 7.2/11), such as standardizing pain management protocols to reduce treatment disparities.Conclusion: Panelists indicated reimbursement should incentivize traditionally lower-paying evidence-based pain care, but multiple strategies may be needed to meaningfully expand access.Keywords: long-term opioid therapy, pain care access, reimbursement models, expert panel

Stephanie Slat,1 Avani Yaganti,1 Jennifer Thomas,1 Danielle Helminski,1 Michele Heisler,1– 4 Amy Bohnert,2,4,5 Pooja Lagisetty1,2,4 1Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; 2Center for Clinical Management and Research, Ann Arbor VA Hospital, Ann Arbor, MI, USA; 3Department of Health Behavior & Health Education, University of Michigan School of Public Health, Ann Arbor, MI, USA; 4Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA; 5Departments of Anesthesiology and Psychiatry, University of Michigan, Ann Arbor, MI, USACorrespondence: Stephanie SlatDepartment of Internal Medicine, University of Michigan, NCRC B16-Floor 4, 2800 Plymouth Road, Ann Arbor, MI, 48109, USATel +1 734-755-1574Email stslat@med.umich.eduPurpose: Patients on long-term opioid therapy (LTOT) for pain have difficulty accessing primary care clinicians who are willing to prescribe opioids or provide multimodal pain treatment. Recent treatment guidelines and statewide policies aimed at reducing inappropriate prescribing may exacerbate these access issues, but further research is needed on this issue. This study aimed to understand barriers to primary care access and multimodal treatment for chronic pain from the perspective of multiple stakeholders.Methods: Qualitative, semi-structured phone interviews were conducted with adult patients with chronic pain, primary care clinicians, and clinic office staff in Michigan. Interview questions covered stakeholder experiences with prescription opioids, opioid-related policies, and access to care for chronic pain. Interviews were coded using inductive and deductive methods for thematic analysis.Results: A total of 25 interviews were conducted (15 patients, 7 primary care clinicians, and 3 office staff). Barriers to treatment access were attributed to six themes: (1) reduced clinic willingness to manage prescribed opioids for new patients; (2) lack of time and reimbursement for quality opioid-related care; (3) paucity of multimodal care and coordination between providers; (4) fear of liability and use of new guidelines to justify not prescribing opioids; (5) delayed prescription receipt due to prior authorization and pharmacy issues; and (6) poor availability of effective non-opioid treatments.Conclusion: Issues of policy, logistics, and clinic-level resources converge to disrupt treatment access for patients with chronic pain, as many clinics both do not offer multimodal pain care and are unwilling to prescribe LTOT. The resulting conceptual model can inform the development of policy interventions to help mitigate these access barriers.Keywords: opioid, chronic pain, access, primary care, policy

Abstract The global spread of multidrug-resistant Escherichia coli threatens human, animal, and environmental health. Despite the recognition of water bodies as potential reservoirs, research on antimicrobial resistance (AMR) and antibiotic residues in the Baltic Sea is limited. In this study, we examined the presence of ESBL-producing E. coli in surface water in northeastern Germany. We then conducted phenotypic and genotypic analyses of the strains, which encompassed AMR and heavy metal/metalloid tolerance, biofilm formation, and detailed plasmid examination. In addition, we used solid-phase extraction with ultra-high performance liquid chromatography and mass spectrometry to quantify antibiotic residues. Our analysis identified 30 ESBL-producing E. coli isolates, some of which were associated with clinically relevant high-risk clonal lineages. We detected antibiotic residues in the environmental samples, but the antibiotic concentrations were significantly lower compared to wastewater samples. These results suggest that the Baltic Sea surface water could serve as a reservoir for ESBL-producing E. coli and clinically relevant antibiotics.

Abstract Background Research suggests an association between COVID-19 infection and certain financial hardships in the shorter term and among single-state and privately insured samples. Whether COVID-19 is associated with financial hardship in the longer-term or among socially vulnerable populations is unknown. Therefore, we examined whether COVID-19 was associated with a range of financial hardships 18 months after initial infection among a national cohort of Veterans enrolled in the Veterans Health Administration (VHA)—the largest national integrated health system in the US. We additionally explored the association between Veteran characteristics and financial hardship during the pandemic, irrespective of COVID-19. Methods We conducted a prospective, telephone-based survey. Out of 600 Veterans with COVID-19 from October 2020 through April 2021 who were invited to participate, 194 Veterans with COVID-19 and 194 matched comparators without a history of infection participated. Financial hardship outcomes included overall health-related financial strain, two behavioral financial hardships (e.g., taking less medication than prescribed due to cost), and seven material financial hardships (e.g., using up most or all savings). Weighted generalized estimating equations were used to estimate risk ratios (RR) and 95% confidence intervals (CI) of financial hardship by COVID-19 status, and to assess the relationship between infection and Veteran age, VHA copay status, and comorbidity score, irrespective of COVID-19 status. Results Among 388 respondents, 67% reported at least one type of financial hardship since March 2020, with 21% reporting behavioral hardships and 64% material hardships; 8% reported severe-to-extreme health-related financial strain. Compared with uninfected matched comparators, Veterans with a history of COVID-19 had greater risks of severe-to-extreme health-related financial strain (RR: 4.0, CI: 1.4–11.2), taking less medication due to cost (RR: 2.9, 95% CI: 1.0–8.6), and having a loved one take time off work to care for them (RR: 1.9, CI: 1.1–3.6). Irrespective of COVID-19 status, Veterans aged

Abstract Background Grapevine Pinot gris virus (GPGV) infects grapevines worldwide and causes symptoms such as chlorotic mottling and deformations on leaves, stunted shoots and short panicles, or none of these symptoms if it appears as latent infection. So far, the consequences of GPGV infections for winegrowers are difficult to assess since important information such as plant performance at different GPGV infection levels and symptom expression are not fully clarified. Methods In order to investigate the course of GPGV spread, annual visual evaluations and ELISA tests were conducted over 3–4 consecutive years in four GPGV-infected vineyards in southern Germany: GEM, HEC, NIM, and REI. The program PATCHY was used to analyze spatial disease patterns. Sanger sequencing was used to determine virus isolates in vines at different GPGV infection levels, to test their respective influence on symptom expression. Yield and GrapeScan (FTIR) analyses were conducted to test the impact of different GPGV infection levels and isolates on fruit quantity and quality. Results GPGV infections significantly increased in all four vineyards (GEM 22–32%, HEC 50–99%, NIM 83–90%, REI 56–76%) with significant spreading patterns across and along rows. Specific symptom progression patterns were not observed. According to our results, the virus isolate has an influence on whether symptoms develop during a GPGV infection. While yield analyses revealed that yield losses only occur in symptomatic vines and range from 13 to 96% depending on the severity of symptoms, latent infections have no impact on grape production. No relevant effects of GPGV infections on must quality were observed. Conclusions Secondary spread of GPGV was observed in all vineyards monitored, indicating vector-borne transmission that is likely to be accelerated by human viticultural management. GPGV should be further monitored to prevent the accumulation of detrimental symptomatic isolates. The results of this study can be used to assess the risk of GPGV to viticulture and should be considered when developing management strategies against the virus.

Abstract Traumatic brain injury (TBI) is a ubiquitous, common sequela of accidents with an annual prevalence of several million cases worldwide. In forensic pathology, structural proteins of the cellular compartments of the CNS in serum and cerebrospinal fluid (CSF) have been predominantly used so far as markers of an acute trauma reaction for the biochemical assessment of neuropathological changes after TBI. The analysis of endogenous metabolites offers an innovative approach that has not yet been considered widely in the assessment of causes and circumstances of death, for example after TBI. The present study, therefore, addresses the question whether the detection of metabolites by liquid-chromatography-mass spectrometry (LC/MS) analysis in post mortem CSF is suitable to identify TBI and to distinguish it from acute cardiovascular control fatalities (CVF). Metabolite analysis of 60 CSF samples collected during autopsies was performed using high resolution (HR)-LC/MS. Subsequent statistical and graphical evaluation as well as the calculation of a TBI/CVF quotient yielded promising results: numerous metabolites were identified that showed significant concentration differences in the post mortem CSF for lethal acute TBI (survival times up to 90 min) compared to CVF. For the first time, this forensic study provides an evaluation of a new generation of biomarkers for diagnosing TBI in the differentiation to other causes of death, here CVF, as surrogate markers for the post mortem assessment of complex neuropathological processes in the CNS (“neuroforensomics”).

Abstract Background Chronic pain affects over 100 million Americans, with a disproportionately high number being Veterans. Chronic pain is often difficult to treat and responds variably to medications, with many providing minimal relief or having adverse side effects that preclude use. Cannabidiol (CBD) has emerged as a potential treatment for chronic pain, yet research in this area remains limited, with few studies examining CBD’s analgesic potential. Because Veterans have a high need for improved pain care, we designed a clinical trial to investigate CBD’s effectiveness in managing chronic pain symptoms among Veterans. We aim to determine whether CBD oral solution compared to placebo study medication is associated with greater improvement in the Patient Global Impression of Change (PGIC). Methods We designed a randomized, double-blind, placebo-controlled, pragmatic clinical trial with 468 participants. Participants will be randomly assigned in a 1:1 ratio to receive either placebo or a CBD oral solution over a 4-week period. The trial is remote via a smartphone app and by shipping study materials, including study medication, to participants. We will compare the difference in PGIC between the CBD and placebo group after four weeks and impacts on secondary outcomes (e.g., pain severity, pain interference, anxiety, suicide ideation, and sleep disturbance). Discussion Once complete, this trial will be among the largest to date investigating the efficacy of CBD for chronic pain. Findings from this clinical trial will contribute to a greater knowledge of CBD’s analgesic potential and guide further research. Given the relative availability of CBD, our findings will help elucidate the potential of an accessible option for helping to manage chronic pain among Veterans. Trial registration This protocol is registered at clinicaltrials.gov under study number NCT06213233.

Abstract Background To improve patient outcomes and provider team practice, the California Perinatal Quality Care Collaborative (CPQCC) created the Simulating Success quality improvement program to assist hospitals in implementing a neonatal resuscitation training curriculum. This study aimed to examine the costs associated with the design and implementation of the Simulating Success program. Methods From 2017–2020, a total of 14 sites participated in the Simulating Success program and 4 of them systematically collected resource utilization data. Using a micro-costing approach, we examined costs for the design and implementation of the program occurring at CPQCC and the 4 study sites. Data collection forms were used to track personnel time, equipment/supplies, space use, and travel (including transportation, food, and lodging). Cost analysis was conducted from the healthcare sector perspective. Costs incurred by CPQCC were allocated to participant sites and then combined with site-specific costs to estimate the mean cost per site, along with its 95% confidence interval (CI). Cost estimates were inflation-adjusted to 2022 U.S. dollars. Results Designing and implementing the Simulating Success program cost $228,148.36 at CPQCC, with personnel cost accounting for the largest share (92.2%), followed by program-related travel (6.1%), equipment/supplies (1.5%), and space use (0.2%). Allocating these costs across participant sites and accounting for site-specific resource utilizations resulted in a mean cost of $39,210.69 per participant site (95% CI: $34,094.52-$44,326.86). In sensitivity analysis varying several study assumptions (e.g., number of participant sites, exclusion of design costs, and useful life span of manikins), the mean cost per site changed from $35,645.22 to $39,935.73. At all four sites, monthly cost of other neonatal resuscitation training was lower during the program implementation period (mean = $1,112.52 per site) than pre-implementation period (mean = $2,504.01 per site). In the 3 months after the Simulating Success program ended, monthly cost of neonatal resuscitation training was also lower than the pre-implementation period at two of the four sites. Conclusions Establishing a multi-site neonatal in situ simulation program requires investment of sufficient resources. However, such programs may have financial and non-financial benefits in the long run by offsetting the need for other neonatal resuscitation training and improving practice.

BackgroundInformation about the effectiveness of oral antivirals in preventing short- and long-term COVID-19-related outcomes in the setting of Omicron variant transmission and COVID-19 vaccination is limited.ObjectiveTo measure the effectiveness of nirmatrelvir-ritonavir and molnupiravir for outpatient treatment of COVID-19.DesignThree retrospective target trial emulation studies comparing matched cohorts of nirmatrelvir-ritonavir versus no treatment, molnupiravir versus no treatment, and nirmatrelvir-ritonavir versus molnupiravir.SettingVeterans Health Administration (VHA).ParticipantsNonhospitalized veterans in VHA care who were at risk for severe COVID-19 and tested positive for SARS-CoV-2 during January through July 2022.InterventionNirmatrelvir-ritonavir or molnupiravir pharmacotherapy.MeasurementsIncidence of any hospitalization or all-cause mortality at 30 days and from 31 to 180 days.ResultsEighty-seven percent of participants were male; the median age was 66 years, and 18% were unvaccinated. Compared with matched untreated control participants, those treated with nirmatrelvir-ritonavir (n = 9607) had lower 30-day risk for hospitalization (22.07 vs. 30.32 per 1000 participants; risk difference [RD], -8.25 [95% CI, -12.27 to -4.23] per 1000 participants) and death (1.25 vs. 5.47 per 1000 participants; RD, -4.22 [CI, -5.45 to -3.00] per 1000 participants). Among persons alive at day 31, reductions were seen in 31- to 180-day incidence of death (hazard ratio, 0.66 [CI, 0.49 to 0.89]) but not hospitalization (subhazard ratio, 0.90 [CI, 0.79 to 1.02]). Molnupiravir-treated participants (n = 3504) had lower 30-day and 31- to 180-day risks for death (3.14 vs. 13.56 per 1000 participants at 30 days; RD, -10.42 [CI, -13.49 to -7.35] per 1000 participants; hazard ratio at 31 to 180 days, 0.67 [CI, 0.48 to 0.95]) but not hospitalization. A difference in 30-day or 31- to 180-day risk for hospitalization or death was not observed between matched nirmatrelvir- or molnupiravir-treated participants.LimitationThe date of COVID-19 symptom onset for most veterans was unknown.ConclusionNirmatrelvir-ritonavir was effective in reducing 30-day hospitalization and death. Molnupiravir was associated with a benefit for 30-day mortality but not hospitalization. Further reductions in mortality from 31 to 180 days were observed with both antivirals.Primary funding sourceU.S. Department of Veterans Affairs.

INTRODUCTION Standardized patient (SP) encounters allow medical students to practice physical examination skills and clinical reasoning. SP cases are used for learning and assessment, but recorded encounters can also be valuable curriculum evaluation tools. We aimed to review SP encounters to improve abdominal examination skills and the broader physical examination curriculum. METHODS We reviewed recorded SP encounters of third-year medical students on surgery clerkship rotation. Students examined a cisgender woman presenting with acute right lower abdominal pain. We observed abdominal examinations to determine which maneuvers were attempted and completed correctly. We then used these outcomes to develop targeted clerkship training for the subsequent student cohort. Our intervention targeted abdominal examination gaps by explaining how to integrate abdominal examination findings with a focused history for surgical patients. We evaluated the intervention's impact on abdominal examination skills with third-year medical students in comparison (2021-2022, n = 119) and intervention (2022-2023, n = 132) groups. RESULTS In both the comparison and intervention groups, nearly all students attempted at least 1 general examination maneuver like auscultation, palpation, percussion, or rebound tenderness. Only 40% of students in the comparison group attempted an advanced maneuver like the Rovsing, Psoas, or Obturator sign. After the intervention, 75% of students in the intervention group attempted an advanced maneuver (χ 2 (1, 251) = 31.0, p

OBJECTIVE: Pain is experienced by most patients with cancer and opioids are a cornerstone of management. Our objectives were (1) to identify patterns or trajectories of long-term opioid therapy (LTOT) and their correlates among patients with and without cancer and (2) to assess the association between trajectories and risk for opioid overdose, considering the potential moderating role of cancer. METHODS AND ANALYSIS: We conducted a retrospective cohort study among individuals in the US Veterans Health Administration (VHA) database with incident LTOT with and without cancer (N=44,351; N=285,772, respectively) between 2010-2017. We investigated the relationship between LTOT trajectory and all International Classification of Diseases-9 and 10-defined accidental and intentional opioid-related overdoses. RESULTS: Trajectories of opioid receipt observed in patients without cancer and replicated in patients with cancer were: low-dose/stable trend, low-dose/de-escalating trend, moderate-dose/stable trend, moderate-dose/escalating with quadratic downturn trend, and high-dose/escalating with quadratic downturn trend. Time to first overdose was significantly predicted by higher-dose and escalating trajectories; the two low-dose trajectories conferred similar, lower risk. Conditional hazard ratios (99% CI) for the moderate-dose, moderate-dose/escalating with quadratic downturn and high-dose/escalating with quadratic downturn trends were 1·84 (1·18, 2·85), 2·56 (1·54, 4·25), and 2·41 (1·37, 4·26), respectively. Effects of trajectories on time to overdose did not differ by presence of cancer; inferences were replicated when restricting to patients with stage 3/4 cancer. CONCLUSION: Patients with cancer face opioid overdose risks like patients without cancer. Future studies should seek to expand and address our knowledge about opioid risk in cancer patients. TRIAL REGISTRATION: None.

With >7000 species the order of rust fungi has a disproportionately large impact on agriculture, horticulture, forestry and foreign ecosystems. The infectious spores are typically dikaryotic, a feature unique to fungi in which two haploid nuclei reside in the same cell. A key example is Phakopsora pachyrhizi, the causal agent of Asian soybean rust disease, one of the world's most economically damaging agricultural diseases. Despite P. pachyrhizi's impact, the exceptional size and complexity of its genome prevented generation of an accurate genome assembly. Here, we sequence three independent P. pachyrhizi genomes and uncover a genome up to 1.25 Gb comprising two haplotypes with a transposable element (TE) content of ~93%. We study the incursion and dominant impact of these TEs on the genome and show how they have a key impact on various processes such as host range adaptation, stress responses and genetic plasticity.

Purpose: Negative perceptions around medications for opioid use disorder (MOUD) amongst the public could deter patients with opioid use disorder (OUD) from engaging with MOUD. Thus, we evaluated whether a brief intervention could improve preferences for MOUD in people who may or may not use opioids. Methods: We employed a pre-post design to assess the effect of a brief educational intervention on preferences for methadone, buprenorphine, naltrexone, and non-medication treatment in an online sample of US adults stratified by race, who may or may not use opioids. Respondents ranked their preferences in OUD treatment before and after watching four one-minute educational videos about treatment options. Changes in treatment preferences were analyzed using Bhapkar’s test and post hoc McNemar’s tests. A binary logistic generalized estimating equation (GEE) assessed factors associated with preference between treatments. Results: The sample had 530 responses. 194 identified as White, 173 Black, 163 Latinx. Treatment preferences changed significantly towards MOUD (p

In this longitudinal observational study, we measured urinary glucose concentration, body composition and volume status (bioimpedance spectroscopy) and plasma renin and aldosterone concentrations in n = 22 kidney transplant recipients (KTRs) initiating on SGLT2I at baseline (BL), and after 1 week and 1, 3, and 6 months. Estimated glomerular filtration rate (eGFR) decreased by −2 mL/min/1.73 m2 (IQR −10–0) after 1 week and remained stable thereafter. Urinary glucose concentration was 10 (3–24) g/g creatinine after 1 week and correlated with eGFR (r2 = 0.273; p = 0.057). SGLT2I did not affect HbA1c, fasting blood glucose, body weight, fat or lean mass. SGLT2I decreased fluid overload dependent on baseline overhydration (OH, r2 = 0.54, p = 0.0003) without occurrence of dehydration. Plasma aldosterone increased at day 7, while plasma renin did not change significantly. In conclusion, SGLT2I corrected fluid overload in patients with elevated overhydration at baseline, while in euvolemic KTRs fluid status remained stable without reduction of body water below the reference range, thus promoting the safety of SGLT2I therapy in patients following kidney transplantation. Glucosuria, together with effects of SGLT2I on blood glucose control and body weight, is attenuated in KTRs dependent on eGFR.

BackgroundConvergence of Klebsiella pneumoniae (KP) pathotypes has been increasingly reported in recent years. These pathogens combine features of both multidrug-resistant and hypervirulent KP. However, clinically used indicators for hypervirulent KP identification, such as hypermucoviscosity, appear to be differentially expressed in convergent KP, potential outbreak clones are difficult to identify. We aimed to fill such knowledge gaps by investigating the temperature dependence of hypermucoviscosity and virulence in a convergent KP strain isolated during a clonal outbreak and belonging to the high-risk sequence type (ST)307.MethodsHypermucoviscosity, biofilm formation, and mortality rates in Galleria mellonella larvae were examined at different temperatures (room temperature, 28°C, 37°C, 40°C and 42°C) and with various phenotypic experiments including electron microscopy. The underlying mechanisms of the phenotypic changes were explored via qPCR analysis to evaluate plasmid copy numbers, and transcriptomics.ResultsOur results show a temperature-dependent switch above 37°C towards a hypermucoviscous phenotype, consistent with increased biofilm formation and in vivo mortality, possibly reflecting a bacterial response to fever-like conditions. Furthermore, we observed an increase in plasmid copy number for a hybrid plasmid harboring carbapenemase and rmpA genes. However, transcriptomic analysis revealed no changes in rmpA expression at higher temperatures, suggesting alternative regulatory pathways.ConclusionThis study not only elucidates the impact of elevated temperatures on hypermucoviscosity and virulence in convergent KP but also sheds light on previously unrecognized aspects of its adaptive behavior, underscoring its resilience to changing environments.

PurposeAlcohol use among adolescents and emerging adults is an important public health issue requiring prevention approaches. Herein, we describe outcomes from a randomized controlled trial testing the efficacy of group-based social media interventions targeting risky drinking among youth.ProceduresUsing social media advertisements to screen potential participants, we recruited 955 youth (ages 16-24) reporting recent risky drinking. After completing a baseline assessment, participants were randomized to 8-week secret Facebook group conditions: Social Media Intervention + Incentives for engagement, Social Media Intervention only, and attention-placebo control. Electronic coaches trained in motivational interviewing facilitated interaction in intervention groups. Primary outcomes include past 3-month alcohol use and consequences over 3-, 6-, and 12-month follow-ups. Secondary outcomes include other drug use, consequences, and impaired driving. We also measured intervention engagement and acceptability.ResultsThe interventions were well-received, with significantly greater acceptability ratings and engagement in the SMI+I condition relative to other groups. In adjusted analyses, there were no significant differences between interventions and control on alcohol-related outcomes, with all groups showing reductions. Regarding secondary outcomes (70.4% used other drugs), compared to control, the incentivized group reduced other drug use, consequences, and cannabis-impaired driving; the non-incentivized group did not significantly differ from the control condition.ConclusionsAmong this predominantly poly-substance using sample, findings were mixed, with significant effects of the incentivized social media intervention on drug (but not alcohol) outcomes. Future studies are needed to further refine social media-delivered interventions to reduce alcohol and other drug use.Trial registrationClinicalTrials.gov NCT02809586; University of Michigan HUM#00102242.

In this 2-year study, approximately 84 days prior to weaning, 24 calves/year (Angus × Hereford) were randomly assigned to one of two treatments: trace mineral (Cu, Se, and Zn) supplementation following NASEM (2016) recommendations (Control) or trace mineral supplementation above NASEM (2016) recommendations (Super). Calves were individually fed, and trace minerals were provided in 0.5 kg of dry distiller’s grains three times weekly. Body weight (BW), blood, and liver samples were collected on d 0 and at weaning (d 84). Additional BW and blood samples were collected post-weaning on d 85, 87, 88, 91, 95, and 99 during the preconditioning phase. Initial liver concentrations of Se, Cu, and Zn were similar between treatments (p ≥ 0.69). At weaning, a year effect (p < 0.001) and a tendency for treatment × year effect (p = 0.09) were observed for Cu liver concentration. In year 2, but not in year 1, calves assigned to the Super treatment tended to have greater liver Cu concentration than calves assigned to the Control treatment. Except for Cu, a notoriously limited trace mineral in multiple geographical locations, the supplementation of trace minerals above the NASEM (2016) recommendations did not improve the mineral status of calves in this environment.

ABSTRACT: Asian soybean rust, caused by Phakopsora pachyrhizi, is one of the world’s most economically damaging agricultural diseases. Despite P. pachyrhizi’s impact, the exceptional size and complexity of its genome prevented generation of an accurate genome assembly. We simultaneously sequenced three P. pachyrhizi genomes uncovering a genome up to 1.25 Gb comprising two haplotypes with a transposable element (TE) content of ~93%. The proliferation of TEs within the genome occurred in several bursts and correlates with the radiation and speciation of the legumes. We present data of clear de-repression of TEs that mirrors expression of virulence-related candidate effectors. We can see a unique expansion in amino acid metabolism for this fungus. Our data shows that TEs play a dominant role in P. pachyrhizi’s genome and have a key impact on various processes such as host range adaptation, stress responses and genetic plasticity of the genome.

BackgroundEfforts to reduce opioid overdose fatalities have resulted in tapering (i.e., reducing or discontinuing) opioid prescriptions despite a limited understanding of patients' experiences.ObjectiveTo explore patients' perspectives on opioid taper experiences to ultimately improve taper processes and outcomes.DesignQualitative study.ParticipantsPatients on long-term opioid therapy for chronic pain who had undergone a reduction of opioid daily prescribed dosage of ≥50% in the past 2 years in two distinct medical systems and regions.ApproachFrom 2019 to 2020, we conducted semi-structured interviews that were audio-recorded, transcribed, systematically coded, and analyzed to summarize the content and identify key themes regarding taper experiences overall and with particular attention to patient-provider relationships and provider communication during tapers.Key resultsParticipants (n=41) had lived with chronic pain for an average of 17.4 years (range, 3-36 years) and described generally adverse experiences with opioid tapers, the initiation of which was not always adequately justified or explained to them. Consequences of tapers ranged from minor to substantial and included withdrawal, mobility issues, emotional distress, exacerbated mental health symptoms, and feelings of social stigmatization for which adequate supports were typically unavailable. Narratives highlighted the consequential role of patient-provider relationships throughout taper experiences, with most participants describing significant interpersonal challenges including poor provider communication and limited patient engagement in decision making. A few participants identified qualities of providers, relationships, and communication that fostered more positive taper experiences and outcomes.ConclusionsFrom patients' perspectives, opioid tapers can produce significant physical, emotional, and social consequences, sometimes reducing trust and engagement in healthcare. Patient-provider relationships and communication influence patients' perceptions of the quality and outcomes of opioid tapers. To improve patients' experiences of opioid tapers, tapering plans should be based on individualized risk-benefit assessments and involve patient-centered approaches and improved provider communication.

In this study, we characterized a Klebsiella pneumoniae strain in a patient with shrapnel hip injury, which resulted in multiple phenotypic changes, including the formation of a small colony variant (SCV) phenotype. Although already described since the 1960s, there is little knowledge about SCV phenotypes in Enterobacteriaceae. The formation of SCVs has been recognized as a bacterial strategy to evade host immune responses and compromise the efficacy of antimicrobial therapies, leading to persistent and recurrent courses of infections. In this case, 14 isolates with different resisto- and morpho-types were distinguished from the patient’s urine and tissue samples. Whole genome sequencing revealed that all isolates were clonally identical belonging to the K. pneumoniae high-risk sequence type 147. Subculturing the SCV colonies consistently resulted in the reappearance of the initial SCV phenotype and three stable normal-sized phenotypes with distinct morphological characteristics. Additionally, an increase in resistance was observed over time in isolates that shared the same colony appearance. Our findings highlight the complexity of bacterial behavior by revealing a case of phenotypic “hyper-splitting” in a K. pneumoniae SCV and its potential clinical significance.

This case-report focuses on a 23-year-old soldier suffering from a fracture-related hip joint infection (FRI) due to extensively drug-resistant Klebsiella pneumoniae and S. epidermidis. The patient underwent multiple septic revision surgeries including the removal of remaining shrapnel accompanied by last-resort antimicrobial therapy with cefiderocol and colistin. Additionally, the surgeries included repeated tissue sampling for microbiological and histopathological analysis. An antibiotic-loaded cemented filler containing cefiderocol was used to improve local antimicrobial therapy. The biopsies prior to and during hip replacement surgery confirmed successful microbe eradication. Hip arthroplasty restored hip joint function and significantly improved patient's quality of life. The utilization of a trabecular metal shell and a meta-diaphyseally anchored cementless hip stem ensured secure implant fixation and early patient mobilisation. An adjusted biofilm active oral antimicrobial therapy after arthroplasty intervention was continued to prevent early periprosthetic joint infection. This case emphasizes the difficulties of managing FRI and multidrug-resistant pathogens. It contributes valuable insight into navigating complex orthopedic cases while ensuring successful hip arthroplasty outcomes. In conclusion, early interdisciplinary collaboration, appropriate antimicrobial therapy along with tailored surgical interventions are crucial for managing such complex cases successfully.