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Study objective Nonfatal emergency department (ED) visits for opioid overdose are important opportunities to prescribe naloxone and buprenorphine, both of which can prevent future overdose-related mortality. We assessed the rate of this prescribing using national data from August 2019 to April 2021, a period during which US opioid overdose deaths reached record levels. Methods We conducted a retrospective cohort analysis using Symphony Health’s Integrated Dataverse, which includes data from 5,800 hospitals and 70,000 pharmacies. Of ED visits for opioid overdose between August 4, 2019, and April 3, 2021, we calculated the proportion with at least 1 naloxone prescription within 30 days and repeated this analysis for buprenorphine. To contextualize the naloxone prescribing rate, we calculated the proportion of ED visits for anaphylaxis with at least 1 prescription for epinephrine—another life-saving rescue medication—within 30 days. Results Analyses included 148,966 ED visits for opioid overdose. Mean weekly visits increased 23.6% during the period between April 26, 2020 and October 3, 2020 compared with the period between August 4, 2019 to April 25, 2020. Visits declined to prepandemic levels between October 4, 2020 and March 13, 2021, after which visits began to rise. Naloxone and buprenorphine were prescribed within 30 days at 7.4% and 8.5% of the 148,966 visits, respectively. The naloxone prescribing rate (7.4%) was substantially lower than the epinephrine prescribing rate (48.9%) after ED visits for anaphylaxis. Conclusion Between August 4, 2019, and April 3, 2021, naloxone and buprenorphine were only prescribed after 1 in 12 and 1 in 13 ED visits for opioid overdose, respectively. Findings suggest that clinicians are missing critical opportunities to prevent opioid overdose-related mortality.

The authors sought to estimate the prevalence of past-12-month and lifetime cannabis use and cannabis use disorder among U.S. veterans; to describe demographic, substance use disorder, and psychiatric disorder correlates of nonmedical cannabis use and cannabis use disorder; and to explore differences in cannabis use and cannabis use disorder prevalence among veterans in states with and without medical marijuana laws.Participants were 3,119 respondents in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) who identified as U.S. veterans. Weighted prevalences were calculated. Logistic regression analyses tested associations of nonmedical cannabis use and cannabis use disorder with demographic and clinical correlates and examined whether prevalence differed by state legalization status.The prevalences of any past-12-month cannabis use and cannabis use disorder were 7.3% and 1.8%, respectively. Lifetime prevalences were 32.5% and 5.7%, respectively. Past-12-month and lifetime cannabis use disorder prevalence estimates among nonmedical cannabis users were 24.4% and 17.4%, respectively. Sociodemographic correlates of nonmedical cannabis use and use disorder included younger age, male gender, being unmarried, lower income, and residing in a state with medical marijuana laws. Nonmedical cannabis use and use disorder were associated with most psychiatric and substance use disorders examined.Among veterans, the odds of nonmedical cannabis use and use disorder were elevated among vulnerable subgroups, including those with lower income or psychiatric disorders and among survey participants residing in states with medical marijuana laws. The study findings highlight the need for clinical attention (e.g., screening, assessment) and ongoing monitoring among veterans in the context of increasing legalization of cannabis.

The aim of this study was to investigate if the biomarkers myelin basic protein (MBP) and neurofilament-H (NF-H) yielded informative value in forensic diagnostics when examining cadaveric cerebrospinal fluid (CSF) biochemically via an enzyme-linked immunosorbent assay (ELISA) and comparing the corresponding brain tissue in fatal traumatic brain injury (TBI) autopsy cases by immunocytochemistry versus immunohistochemistry. In 21 trauma and 19 control cases, CSF was collected semi-sterile after suboccipital puncture and brain specimens after preparation. The CSF MBP (p = 0.006) and NF-H (p = 0.0002) levels after TBI were significantly higher than those in cardiovascular controls. Immunohistochemical staining against MBP and against NF-H was performed on cortical and subcortical samples from also biochemically investigated cases (5 TBI cases/5 controls). Compared to the controls, the TBI cases showed a visually reduced staining reaction against MBP or repeatedly ruptured neurofilaments against NF-H. Immunocytochemical tests showed MBP-positive phagocytizing macrophages in CSF with a survival time of > 24 h. In addition, numerous TMEM119-positive microglia could be detected with different degrees of staining intensity in the CSF of trauma cases. As a result, we were able to document that elevated levels of MBP and NF-H in the CSF should be considered as usefulneuroinjurybiomarkers of traumatic brain injury.

Background: The role of neuroinflammation has become more evident in the pathogenesis of neurodegenerative diseases. Increased expression of microglial markers is widely reported in Alzheimer’s disease (AD), but much less is known about the role of monocytes in AD pathogenesis. In AD animal models, bone marrow-derived monocytes appear to infiltrate the parenchyma and contribute to the phagocytosis of amyloid-β depositions, but this infiltration has not been established in systematic studies of the human brain postmortem. Objective: In addition to assessing the distribution of different subtypes of microglia by immunostaining for CD68, HLA-DR, CD163, and CD206, we focused on the involvement of C-chemokine receptor type2 (CCR2) positive monocytes during the AD course. Methods: We used formalin-fixed and paraffin-embedded tissue from four vulnerable brain regions (hippocampus, occipital lobe, brainstem, and cerebellum) from neuropathologically characterized AD cases at different Braak stages and age-matched controls. Results: Only singular migrated CCR2-positive cells were found in all brain regions and stages. The brainstem showed the highest number of positive cells overall, followed by the hippocampus. This mechanism of recruitment seems to work less efficiently in the human brain at an advanced age, and the ingress of monocytes obviously takes place in much reduced numbers or not at all. Conclusion: In contrast to studies on animal models, we observed only a quite low level of myeloid monocytes associated with AD pathology. Furthermore, we provide evidence associating early microglial reactions carried out in particular by pro-inflammatory cells with early effects on tangle- and plaque-positive vulnerable brain regions.

Anemia is a common complication of chronic kidney disease, affecting the quality of life of patients. Among various factors, such as iron and erythropoietin deficiency, reduced red blood cell (RBC) lifespan has been implicated in the pathogenesis of anemia. However, mechanistic data on in vivo RBC dysfunction in kidney disease are lacking. Herein, we describe the development of chronic kidney disease-associated anemia in mice with proteinuric kidney disease resulting from either administration of doxorubicin or an inducible podocin deficiency. In both experimental models, anemia manifested at day 10 and progressed at day 30 despite increased circulating erythropoietin levels and erythropoiesis in the bone marrow and spleen. Circulating RBCs in both mouse models displayed altered morphology and diminished osmotic-sensitive deformability together with increased phosphatidylserine externalization on the outer plasma membrane, a hallmark of RBC death. Fluorescence-labelling of RBCs at day 20 of mice with doxorubicin-induced kidney disease revealed premature clearance from the circulation. Metabolomic analyses of RBCs from both mouse models demonstrated temporal changes in redox recycling pathways and Lands’ cycle, a membrane lipid remodeling process. Anemic patients with proteinuric kidney disease had an increased proportion of circulating phosphatidylserine-positive RBCs. Thus, our observations suggest that reduced RBC lifespan, mediated by altered RBC metabolism, reduced RBC deformability, and enhanced cell death contribute to the development of anemia in proteinuric kidney disease.

BACKGROUND AND AIMS This study aimed to (1) describe trends in stimulant-alone and stimulant and other substance use overdose deaths from 2012 to 2018 and (2) measure patient and service use characteristics across stimulant-related overdose death profiles. DESIGN Retrospective cohort study of patients who died from stimulant-involved overdose between annual years 2012 and 2018. SETTING United States Veterans Health Administration (VHA). A total of 3631 patients died from stimulant-involved overdose, as identified through the National Death Index. MEASUREMENTS Stimulant-involved overdose deaths were categorized by stimulant type (cocaine or methamphetamine/other) and other substance co-involvement. Cause of death data were linked to patient characteristics, including demographic and treatment use preceding overdose from VHA administrative data. We examined trends over time and compared treatment use factors between the following mutually exclusive overdose profiles: cocaine alone, methamphetamine alone, cocaine + opioid, methamphetamine + opioid, any stimulant + other substance and cocaine + methamphetamine. FINDINGS The rate of overdose death was 3.06 times higher in 2018 than 2012, with increases across all toxicology profiles. Compared with cocaine-involved overdoses, methamphetamine-involved overdoses were less likely in people who were older [adjusted odds ratio (aOR) = 0.22, 95% confidence interval (CI) = 0.06-0.87 aged 65+ versus 18-29] and more likely among those who lived in rural areas (aOR = 2.73, 95% CI = 1.43-5.23). People who died from stimulant + opioid overdoses had lower odds of a stimulant use disorder diagnosis compared with stimulant alone deaths (cocaine: aOR = 0.55, 95% CI = 0.41-0.75, methamphetamine: aOR = 0.44, 95% CI = 0.29-0.68). CONCLUSIONS The rate of deaths among US Veterans from stimulant-related overdose was three times higher in 2018 than 2012. Key differences in characteristics of patients across overdose toxicology profiles, such as geographic location and health-care use, point to distinct treatment needs based on stimulant use type.

The Centers for Disease Control and Prevention’s 2016 Guideline for Prescribing Opioids for Chronic Pain aimed to reduce unsafe opioid prescribing. It is unknown whether the guideline influenced pr...

Background Muscle weakness and exercise intolerance contribute to reduced quality of life (QOL) in Barth syndrome (BTHS). Our group previously found that 12 weeks of resistance exercise training (RET) improved muscle strength, however, did not increase muscle (lean) mass or QOL in n = 3 young adults with BTHS. The overall objective of this pilot study was to examine the safety and effectiveness of RET plus daily protein supplementation (RET + protein) on muscle strength, skeletal muscle mass, exercise tolerance, cardiac function, and QOL in late adolescents/young adults with BTHS. Methods Participants with BTHS (n = 5, age 27 ± 7) performed 12 weeks of supervised RET (60 minutes per session, three sessions/week) and consumed 42 g/day of whey protein. Muscle strength, muscle mass, exercise capacity, cardiac function, and health‐related QOL were assessed pre‐post intervention. Results RET + protein was safe, increased muscle strength and quality of life, and tended to increase lean mass. Conclusions RET + protein appears safe, increases muscle strength and quality of life and tends to increase lean mass. Larger studies are needed to confirm these findings and to fully determine the effects of RET + protein in individuals with BTHS.

Many primary care clinics are resistant to accept new patients taking prescription opioids for chronic pain. It is unclear how much of this practice is specific to individuals who may be perceived to have aberrant opioid use. This study sought to determine whether clinics are more or less willing to accept and prescribe opioids to patients depending on whether their history is more or less suggestive of aberrant opioid use by conducting an audit survey of primary care clinics in 9 states from May to July 2019. Simulated patients taking opioids for chronic pain called each clinic twice, giving one of 2 scenarios for needing a new provider: their previous physician had either (1) retired or (2) stopped prescribing opioids for unspecified reasons. Clinic willingness to continue prescribing opioids and accept the patient for general primary care were assessed. Of 452 clinics responding to both scenarios (904 calls), 193 (43%) said their providers would not prescribe opioids in either scenario, 146 (32%) said their providers might prescribe in both, and 113 (25%) responded differently to each scenario. Clinics responding differently had greater odds (odds ratio = 1.83 confidence interval [1.23-2.76]) of willingness to prescribe when the previous doctor retired than when the doctor had stopped prescribing. These findings suggest that primary care access is limited for patients taking opioids for chronic pain, and differentially further reduced for patients whose histories are suggestive of aberrant use. This denial of care could lead to unintended harms such as worsened pain or conversion to illicit substances.

Zusammenfassung. Hintergrund: Die LEO-Studie 2018 ( Grotlüschen, Buddeberg, Dutz, Heilmann & Stammer, 2019 ) belegt, dass 12,1% der deutschen Bevölkerung im erwerbsfähigen Alter maximal einzelne Sätze lesen und schreiben können und somit als gering literalisiert gelten müssen. Für die Schweiz zeigen Studien, dass eine beachtliche Anzahl von Jugendlichen und Erwachsenen über unzureichende Lesefähigkeiten verfügen. Dieser Beitrag beschäftigt sich mit der Frage, inwiefern sich Zusammenhänge zwischen den lautsprachlichen und den schriftsprachlichen Leistungen bei Menschen mit Illettrismus im Erwachsenenalter zeigen. Methoden: Anhand einer Testbatterie zur Erfassung schriftsprachlicher Kompetenzen und Vorläuferfähigkeiten für den Schriftspracherwerb sowie Interviews zur Lernbiographie wurden in einer Querschnittsstudie mit Erwachsenen Daten von 20 Illettristen und 10 Kontrollproband_innen erhoben und miteinander verglichen. Ergebnisse: Im Gruppenvergleich zeigen sich deutliche Unterschiede zwischen Experimental- und Kontrollgruppe wobei die Kontrollgruppe in den Tests fast durchweg besser abschneidet als die Experimentalgruppe. Diskussion: Insbesondere im Zusammenhang mit der Lernbiographie der Betroffenen ist die Relevanz früher professioneller Unterstützung hervorzuheben. Es lassen sich Hinweise für die schulischen Rahmenbedingungen und die Förderschwerpunkte ableiten.

The aim of the present study was a refined analysis of neuroinflammation including TMEM119 as a useful microglia-specific marker in forensic assessments of traumatic causes of death, e.g., traumatic brain injury (TBI). Human brain tissue samples were obtained from autopsies and divided into cases with lethal TBI (n = 25) and subdivided into three groups according to their trauma survival time and compared with an age-, gender-, and postmortem interval-matched cohort of sudden cardiovascular fatalities as controls (n = 23). Brain tissue samples next to cortex contusions and surrounding white matter as well as samples of the ipsilateral uninjured brain stem and cerebellum were collected and stained immunohistochemically with antibodies against TMEM119, CD206, and CCR2. We could document the highest number of TMEM119-positive cells in acute TBI death with highly significant differences to the control numbers. CCR2-positive monocytes showed a significantly higher cell count in the cortex samples of TBI cases than in the controls with an increasing number of immunopositive cells over time. The number of CD206-positive M2 microglial cells increased survival time-dependent. After 3 days of survival, the cell number increased significantly in all four regions investigated compared with controls. In sum, we validate a specific and robustly expressed as well as fast reacting microglia marker, TMEM119, which distinguishes microglia from resident and infiltrating macrophages and thus offers a great potential for the estimation of the minimum survival time after TBI. Electronic supplementary material The online version of this article (10.1007/s00414-020-02384-z) contains supplementary material, which is available to authorized users.

Intrakranielle Blutungen sind im Säuglingsalter seltene, aber lebensbedrohende Ereignisse. Neben Gefäßmissbildungen, Stoffwechseldefekten sowie Störungen der Blutgerinnung kommen v. a. nichtakzidentielle Traumata, Schütteltrauma in Betracht. Die klinische Diagnostik umfasst hinsichtlich der Blutungsgenese neben Sonographie und MRT als apparatives Verfahren auch eine Fundoskopie sowie laborchemische Analysen, insbesondere der Gerinnungsparameter. Für die Blutgerinnung ist das fettlösliche Vitamin K essenziell: Frühe, klassische und späte Vitamin-K-Mangel-Blutungen werden dabei unterschieden. Um ein gehäuftes Wiederauftreten von Vitamin-K-Mangel-Blutungen bei Neugeborenen und jungen Säuglingen zu verhindern, bedarf es einer hinreichenden Aufklärung der Eltern. Eine Verweigerung der Prophylaxe scheint Folge einer weltanschaulich begründeten Ablehnung der Schulmedizin und ein zunehmendes Phänomen in wohlhabenden Industrieländern zu sein., Intracranial hemorrhages in infants are rare but life-threatening events. Apart from vascular malformations, metabolic disorders and coagulopathies, nonaccidental trauma, in particular shaken baby syndrome must be taken into consideration. Clinical diagnostic tests and procedures to further evaluate the etiology of the hemorrhage include sonography and magnetic resonance imaging (MRI) as imaging procedures as well as fundoscopy and laboratory tests, especially with respect to coagulation parameters. Fat-soluble vitamin K is essential for blood coagulation. A differentiation is made between classical and delayed hemorrhages due to vitamin K deficiency. In order to avoid an increased recurrence of bleeding due to vitamin K deficiency in neonates and young infants, an adequate clarification for the parents is necessary. A refusal of prophylaxis seems to be the result of an ideologically founded rejection of classical medicine and an increasing phenomenon in affluent industrial countries.

Background Increasing naloxone awareness and carrying among individuals who misuse opioid analgesic medications (OAs) could reduce opioid overdose mortality. Methods Self-report surveys were completed by 322 adults receiving residential addiction treatment who misused OAs in the past year. Descriptive analyses and prevalence ratios (using Poisson generalized estimating equations) examined whether illegal opioid (e.g., heroin) initiation was associated with naloxone awareness. Results Among this sample of participants who misused OAs, naloxone awareness was lowest among those who never used illegal opioids (26%) and highest among those who transitioned from OAs to illegal opioid use over time (83%). Naloxone awareness remained higher among participants who had used illegal opioids after adjustment for sociodemographic and substance use characteristics. Those who used OAs before initiating illegal opioids were 2.3-fold (95% CI: 1.5–3.3) more likely to have naloxone awareness than those who had only misused OAs after adjustment. Half of participants who had only used OAs had experienced an overdose, 75% had witnessed an overdose, and 61% were prescribed OAs to treat pain in the past 6 months. Conclusions Implementing overdose education and naloxone distribution programs during addiction treatment could bolster naloxone awareness among people who misuse OAs but who have not used illegal opioids.

BACKGROUND: There has been a reduction in BZD prescribing in the Veterans Affairs (VA) health care system since 2013. It is unknown whether the decline in VA-dispensed BZDs has been offset by Medicare Part D prescriptions. OBJECTIVES: To examine (1) whether, accounting for Part D, declines in BZD prescribing to older Veterans remain; (2) patient characteristics associated with obtaining BZDs outside VA and facility variation in BZD source (VA only, VA and Part D, Part D only). DESIGN: Retrospective cohort study with mixed effects multinomial logistic model examining characteristics associated with BZD source. PATIENTS: A total of 1,746,278 Veterans aged ≥65 enrolled in VA and Part D, 2013–2017. MAIN MEASURES: BZD prescription prevalence and source. KEY RESULTS: From January 2013 to June 2017, the quarterly prevalence of older Veterans with Part D filling BZD prescriptions through the VA declined from 5.2 to 3.1% (p

Treatment with aprotinin, a broad-spectrum serine protease inhibitor with a molecular weight of 6512 Da, was associated with acute kidney injury, which was one of the reasons for withdrawal from the market in 2007. Inhibition of renal serine proteases regulating the epithelial sodium channel ENaC could be a possible mechanism. Herein, we studied the effect of aprotinin in wild-type 129S1/SvImJ mice on sodium handling, tubular function, and integrity under a control and low-salt diet. Mice were studied in metabolic cages, and aprotinin was delivered by subcutaneously implanted sustained release pellets (2 mg/day over 10 days). Mean urinary aprotinin concentration ranged between 642 ± 135 (day 2) and 127 ± 16 (day 8) µg/mL . Aprotinin caused impaired sodium preservation under a low-salt diet while stimulating excessive hyperaldosteronism and unexpectedly, proteolytic activation of ENaC. Aprotinin inhibited proximal tubular function leading to glucosuria and proteinuria. Plasma urea and cystatin C concentration increased significantly under aprotinin treatment. Kidney tissues from aprotinin-treated mice showed accumulation of intracellular aprotinin and expression of the kidney injury molecule 1 (KIM-1). In electron microscopy, electron-dense deposits were observed. There was no evidence for kidney injury in mice treated with a lower aprotinin dose (0.5 mg/day). In conclusion, high doses of aprotinin exert nephrotoxic effects by accumulation in the tubular system of healthy mice, leading to inhibition of proximal tubular function and counterregulatory stimulation of ENaC-mediated sodium transport.

Purpose A provider's ability to translate knowledge about transgender health to affirming patient care is key to addressing disparities. However, standardized patient (SP) programs have little published guidance for gender-affirming care or addressing disparities experienced by transgender and nonbinary patients. Method Between 2018 and 2019, we invited all 208 accredited US and Canadian medical schools to participate in a study to determine how gender minorities are represented in SP encounters. Responding programs (n = 59, response rate = 28%) that represented patients with diverse gender identities were invited to complete semistructured interviews about SP case content, impact, and barriers to this work. Discussions were analyzed using a modified grounded theory method. Results Fifty nine of 208 eligible programs (response rate = 28.3%) completed our survey and 24 completed interviews. More than half of programs used gender minority SPs (n = 35, 59.3%). More than half of the programs also reported portraying gender minority cases (n = 31, 52.5%). Interviewees described how effective SP simulation required purposeful case development, engaging subject matter experts with lived experience, and ensuring psychological safety of gender minority SPs. Barriers included recruitment, fear of disrespecting gender minority communities, and transphobia. Engaging gender minorities throughout case development, training, and implementation of SP encounters was perceived to reduce bias and stereotyping, but respondents unanimously desired guidance on best practices on SP methodology regarding gender identity. Conclusions Many programs have established or are developing SP activities that portray gender minority patients. Effective SP simulation hinges on authenticity, but the decisions around case development and casting vary. Specifically, programs lack consensus about who should portray gender minority patients. This research suggests that input from gender minority communities both to inform best practices at the macro level and in an ongoing advisory capacity at the program level will be essential to teach gender-affirming care.

Chronic pain is associated with mental and physical health difficulties and is prevalent among veterans. Cannabis has been put forth as a treatment for chronic pain, and changes in laws, attitudes, and use patterns have occurred over the past 2 decades. Differences in prevalence of nonmedical cannabis use and cannabis use disorder (CUD) were examined across 2 groups: veterans or nonveterans and those reporting or not reporting recent pain. Data from the National Epidemiologic Survey on Alcohol and Related Conditions-III (2012-2013; n = 36,309) were analyzed using logistic regression. Prevalence differences (PDs) for 3 cannabis outcomes (1) past-year nonmedical cannabis use, (2) frequent (≥3 times a week) nonmedical use, and (3) DSM-5 CUD were estimated for those reporting recent moderate to severe pain (veterans or nonveterans) and veterans reporting or not reporting recent pain. Difference in differences was calculated to investigate PDs on outcomes associated with residence in a state with medical cannabis laws (MCLs). Associations between physical and mental health and cannabis variables were tested. The results indicated that the prevalence of recent pain was greater among veterans (PD = 7.25%, 95% confidence interval (CI) [4.90-9.60]). Among veterans, the prevalence of frequent cannabis use was greater among those with pain (PD = 1.92%, 98% CI [0.21-3.63]), and among veterans residing in a state with MCLs, the prevalence of CUD was greater among those reporting recent pain (PD = 3.88%, 98% CI [0.36-7.39]). Findings failed to support the hypothesis that cannabis use improves mental or physical health for veterans with pain. Providers treating veterans with pain in MCL states should monitor such patients closely for CUD.

The aim of this pilot study was to investigate the diagnostic potential of TMEM119 as a useful microglia-specific marker in combination with immunostainings for phagocytic function and infiltrating capacity of monocytes in cases of lethal monosubstance intoxications by morphine (MOR), methamphetamine (METH), and of ethanol-associated death (ETH) respectively. Human brain tissue samples were obtained from forensic autopsies of cases with single substance abuse (MOR, n = 8; ETH, n = 10; METH, n = 9) and then compared to a cohort of cardiovascular fatalities as controls (n = 9). Brain tissue samples of cortex, white matter, and hippocampus were collected and stained immunohistochemically with antibodies against TMEM119, CD68KiM1P, and CCR2. We could document the lowest density of TMEM119-positive cells in MOR deaths with highly significant differences to the control densities in all three regions investigated. In ETH and METH deaths, the expression of TMEM119 was comparable to cell densities in controls. The results indicate that the immunoreaction in brain tissue is different in these groups depending on the drug type used for abuse.

Due to its protected anatomical location, cerebrospinal fluid (CSF) is a very stable fluid which undergoes comparatively little change in the early post-mortem phase. While many immunohistochemical markers already established for clinical diagnostic issues in tissue samples obtained by biopsy could meanwhile be translated also to post-mortem tissue, no systematic immunocytochemical investigations have generally been conducted on post-mortem body fluids and for CSF specifically, have not been established at all. CSF as the fluid directly surrounding the brain should also be examined to allow a more detailed characterization of processes in the central nervous system. Comparing traumatized tissue and CSF can complete forensic assessment and complement neuropathological evaluation.

The aims of this study were to develop a German Hearing In Noise Test (HINT) using the same methodology as with previous HINT tests; to develop sentence lists for measuring speech reception thresholds (SRTs); and to determine test-retest reliability and norms for measures obtained under headphones.The following steps were followed: develop and record sentences, synthesise masking noise, determine the performance-intensity (PI) function, equalise sentence difficulty in the masking noise. Form sentence lists of equal difficulty. Measure SRTs for normal hearing individuals to determine practice/learning effects, test-retest reliability, and norms.Three groups of adults (median age = 25 years) with average better ear pure-tone averages (PTAs) ≤ 5 dB HL participated.The 12 20-sentence lists were well-matched phonemically and did not differ significantly in difficulty. Test-retest reliability 95% confidence intervals ranged from 1.3 to 2.5 dB. Norms in quiet and in noise exhibited the same pattern as those for other HINT languages. German norms were approximately 2 dB lower than other languages in the noise conditions.The German HINT materials are comparable to those for other languages and are partially consistent with recommendations for construction of multilingual speech tests. They can be used for comparing and pooling research results from the international research community.

Organophosphorus compounds, such as chemical warfare nerve agents and pesticides, are known to cause neurological damage. This study measured nerve agent-related neuropathology and determined whether quantitative T2 MRI could be used as a biomarker of neurodegeneration. Quantitative T2 MRI was performed using a 9.4 T MRI on rats prior to and following soman exposure. T2 images were taken at least 24 h prior, 1 h and 18–24 h after soman exposure. Rats were pre- and post-treated with HI-6 dimethanesulfonate and atropine methyl nitrate. A multicomponent T2 acquisition and analysis was performed. Brains were stained with Fluoro-Jade C to assess neurodegeneration. Rats exposed to soman developed behavioral expression of electrographic seizures. At 18–24 h after soman exposure, significant increases in T2, a possible marker of edema, were found in multiple regions. The largest changes were in the piriform cortex (before: 47.7 ± 1.4 ms; 18–24 h: 82.3 ± 13.4 ms). Fluoro-Jade C staining showed significant neurodegeneration 18–24 h post exposure. The piriform cortex had the strongest correlation between the change in relaxation rate and percent neurodegeneration (r = 0.96, p 2 relaxivity and histopathology supports the use of T2 as a marker of injury.

Objective: To assess mental health symptoms, suicidal ideation/behaviors, and treatment among a nationally representative probability sample of student veterans. Participants: Student veterans enro...

Although most veterans in the Department of Veterans Affairs (VA) health system are treated for posttraumatic stress disorder (PTSD) in the outpatient setting, the VA has approximately 40 residential PTSD treatment facilities across the country for those requiring more intensive care. The symptom profiles of these veterans are poorly understood. Thus, the current study was designed to characterize classes of PTSD symptoms in a national sample of veterans undergoing residential treatment. We analyzed latent classes of PTSD symptoms among 2,452 veterans entering VA PTSD residential treatment in fiscal year 2013. The model with the best fit was a 4-class model comprising a low symptom class, moderate symptom class with high reexperiencing symptoms, a moderate symptom class with high emotional numbing, and a high symptom class. Compared to classes identified in outpatient samples, these classes were similar in type but greater in severity. Classes differed by age, race/ethnicity, trauma type, co-occurring medical conditions, co-occurring psychiatric conditions, and social functioning. Compared to the moderate class with high emotional numbing, those in the moderate class with high reexperiencing symptoms were more likely to be non-White, have greater pain severity, greater sleep problems, and were less likely to be depressed. Our findings suggest that veterans in residential treatment who have more severe PTSD symptoms also experience other medical and psychosocial stressors. A better understanding of symptom profiles may help to create more individualized treatment planning and thus potentially improve care for these veterans. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Context Signature informed consent (SIC) is a part of a Veterans Health Administration ethics initiative for patient education and shared decision making with long-term opioid therapy (LTOT). Historically, patients with cancer-related pain receiving LTOT are exempt from this process. Objectives Our objective is to understand patients' and providers' perspectives on using SIC for LTOT in patients with cancer-related pain. Methods Semistructured interviews with 20 opioid prescribers and 20 patients who were prescribed opioids at two large academically affiliated Veterans Health Administration Medical Centers. We used a combination of deductive and inductive approaches in content analysis to produce emergent themes. Results Potential advantages of SIC are that it can clarify and help patients comprehend LTOT risks and benefits, provide clear upfront boundaries and expectations, and involve the patient in shared decision making. Potential disadvantages of SIC include time delay to treatment, discouragement from recommended opioid use, and impaired trust in the patient-provider relationship. Providers and patients have misconceptions about the definition of SIC. Providers and patients question if SIC for LTOT is really informed consent. Providers and patients advocate for strategies to improve comprehension of SIC content. Providers had divergent perspectives on exemptions from SIC. Oncologists want SIC for LTOT to be tailored for patients with cancer. Conclusion Provider and patient interviews highlight various aspects about the advantages and disadvantages of requiring SIC for LTOT in cancer-related pain. Tailoring SIC for LTOT to be specific to cancer-related concerns and to have an appropriate literacy level are important considerations.

Same-day alcohol and cannabis use is relatively common in adolescents and young adults, constituting a higher-risk behavior relative to single-substance use. However, the association between quantity of alcohol and cannabis use on co-use days is understudied. We examined the association between the quantity of alcohol and same-day cannabis use with a multilevel regression analysis in a sample of youth (16-24 years old) with risky alcohol use. Participants reported one or more days of alcohol and cannabis over the past month (N = 468). Quantity of cannabis use was highest on heavy drinking days [M = 0.91 grams, SD = 0.68] followed by moderate drinking days (M = 0.78 grams, SD = 0.63), and lowest on days without alcohol use (M = 0.74 grams, SD = 0.64, p < 0.001). In multilevel modeling analyses, adjusted for clustering within individuals, greater quantity of drinking on a given day was associated with greater cannabis use (estimate = 0.03, p < 0.001). When using alcohol and cannabis on the same day, greater alcohol use was associated with greater cannabis use. Preventing days of heavy use of multiple substances, particularly among at-risk drinkers, may complement interventions addressing co-use generally to prevent substance-related consequences.

Es wurde ein neuer deutscher altersgerechter Sprachaudiometrietest fur Kinder, ausgehend von 26 Nomen, entwickelt, die mit groser Wahrscheinlichkeit Teil des Lexikons von 2‑jahrigen Kindern sind. Als Antwort konnen die Kinder ein Item aus 4 alternativen Bildern oder „nichts gehort“ auswahlen. Zur Normierung und Validierung des Tests wurden Messungen an insgesamt 179 Kindern im Alter zwischen 2;11 und 6;9 Jahren durchgefuhrt. In diesem Testkollektiv hatten 51 Kinder einen Horverlust auf beiden Ohren von bis zu 90 dB. Die normalhorenden Proband*innen wurden dem Alter entsprechend in 3 Gruppen eingeteilt. Fur jede Altersgruppe wurden die Sprachverstandlichkeitsschwelle (SVS) und die Steigung der psychometrischen Funktion des Sprachverstehens bestimmt. Zur Validierung wurde die Ubereinstimmung von Test und Retest an 85 Ohren sowie die Korrelation zwischen dem mittleren Horverlust (PTA) bei 0,5; 1; 2 und 4 kHz und der SVS an 86 Ohren ermittelt. Das Langzeitspektrum der 26 Nomen entspricht dem internationalen Langzeitsprachspektrum und die relative Phonemhaufigkeit der Verteilung der 50 haufigsten deutschen Phoneme. Die SVS bewegte sich im Bereich von 24,6 ± 0,6 dB „sound pressure level“ (SPL) fur die alteste Gruppe (>5,5 Jahre) bis 29,3 ± 1,3 dB SPL fur die jungste Gruppe (

Diagnosing traumatic brain injury (TBI) from body fluids in cases where there are no obvious external signs of impact would be useful for emergency physicians and forensic pathologists alike. None of the previous attempts has so far succeeded in establishing a single biomarker to reliably detect TBI with regards to the sensitivity: specificity ratio in a post mortem setting. This study investigated a combination of body fluid biomarkers (obtained post mortem), which may be a step towards increasing the accuracy of biochemical TBI detection. In this study, serum and cerebrospinal fluid (CSF) samples from 30 acute lethal TBI cases and 70 controls without a TBI-related cause of death were evaluated for the following eight TBI-related biomarkers: brain-derived neurotrophic factor (BDNF), ferritin, glial fibrillary acidic protein (GFAP), interleukin 6 (IL-6), lactate dehydrogenase, neutrophil gelatinase-associated lipocalin (NGAL), neuron-specific enolase and S100 calcium-binding protein B. Correlations among the individual TBI biomarkers were assessed, and a specificity-accentuated threshold value analysis was conducted for all biomarkers. Based on these values, a decision tree modelling approach was performed to assess the most accurate biomarker combination to detect acute lethal TBIs. The results showed that 92.45% of acute lethal TBIs were able to be diagnosed using a combination of IL-6 and GFAP in CSF. The probability of detecting an acute lethal TBI was moderately increased by GFAP alone and considerably increased by the remaining biomarkers. BDNF and NGAL were almost perfectly correlated (p = 0.002, R2 = 0.944). This study provides evidence that acute lethal TBIs can be detected to a high degree of statistical accuracy using forensic biochemistry. The high inter-individual correlations of biomarkers may help to estimate the CSF concentration of an unknown biomarker, using extrapolation techniques.

BACKGROUND Recent national data are lacking on the prevalence, safety, and prescribers of opioid prescriptions dispensed to children and young adults aged 0 to 21 years. METHODS We identified opioid prescriptions dispensed to children and young adults in 2019 in the IQVIA Longitudinal Prescription Database, which captures 92% of US pharmacies. We calculated the proportion of all US children and young adults with ≥1 dispensed opioid prescription in 2019. We calculated performance on 6 metrics of high-risk prescribing and the proportion of prescriptions written by each specialty. Of all prescriptions and those classified as high risk by ≥1 metric, we calculated the proportion written by high-volume prescribers with prescription counts at the ≥95th percentile. RESULTS Analyses included 4 027 701 prescriptions. In 2019, 3.5% of US children and young adults had ≥1 dispensed opioid prescription. Of prescriptions for opioid-naive patients, 41.8% and 3.8% exceeded a 3-day and 7-day supply, respectively. Of prescriptions for young children, 8.4% and 7.7% were for codeine and tramadol. Of prescriptions for adolescents and young adults, 11.5% had daily dosages of ≥50 morphine milligram equivalents; 4.6% had benzodiazepine overlap. Overall, 45.6% of prescriptions were high risk by ≥1 metric. Dentists and surgeons wrote 61.4% of prescriptions. High-volume prescribers wrote 53.3% of prescriptions and 53.1% of high-risk prescriptions. CONCLUSIONS Almost half of pediatric opioid prescriptions are high risk. To reduce high-risk prescribing, initiatives targeting high-volume prescribers may be warranted. However, broad-based initiatives are also needed to address the large share of high-risk prescribing attributable to other prescribers.

Context: Opioid prescribing to cancer patients is declining, but it is unknown whether reductions have been tailored to those at highest risk of opioid-related harms. Objectives: Examine whether declines in opioid dispensing to patients receiving active cancer treatment are sharper in patients with substance use disorder (SUD) or mental health diagnoses. Methods: We used 2008-2018 national, commercial healthcare claims data to examine adjusted and unadjusted trends in opioid dispensing (receipt of ≥1 fill; average daily dosage; receipt of high-dose opioids; receipt of concurrent opioids and benzodiazepines) to patients ages ≥18 receiving treatment for one of four cancer types (breast; colorectal; head and neck; sarcoma; N=324,789 patients). To compare declines across subgroups with varying risk of opioid-related harms, we stratified by SUD and mental health diagnosis. To address potential confounding, we estimated subgroup-specific trends using generalized estimating equations, adjusting for covariates. Results: Across groups, rate of ≥1 opioid fill per quarter fell 32.5% (95% CI: 31.8%-33.2%) from 2008 to 2018; daily dose among those receiving opioids fell 37.6% (95% CI: 36.7%-38.6%). In most cases, these declines were not sharper in subgroups at greater risk of opioid-related harms. For example, patients with opioid use disorder experienced the smallest declines in dispensing frequency, and there was no evidence that declines were sharper in patients with mental health diagnoses. Conclusion: Sharp declines in opioid prescribing during the drug overdose crisis have affected a wide range of patients undergoing cancer treatment and may not have been sufficiently tailored to patient characteristics. Research on implications for opioid-related harms and pain management is needed.

IMPORTANCE: Opioid-related mortality and national prescribing guidelines have led to tapering of doses among patients prescribed long-term opioid therapy for chronic pain. There is limited information about risks related to tapering, including overdose and mental health crisis. OBJECTIVE: To assess whether there are associations between opioid dose tapering and rates of overdose and mental health crisis among patients prescribed stable, long-term, higher-dose opioids. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using deidentified medical and pharmacy claims and enrollment data from the OptumLabs Data Warehouse from 2008 to 2019. Adults in the US prescribed stable higher doses (mean ≥50 morphine milligram equivalents/d) of opioids for a 12-month baseline period with at least 2 months of follow-up were eligible for inclusion. EXPOSURES: Opioid tapering, defined as at least 15% relative reduction in mean daily dose during any of 6 overlapping 60-day windows within a 7-month follow-up period. Maximum monthly dose reduction velocity was computed during the same period. MAIN OUTCOMES AND MEASURES: Emergency or hospital encounters for (1) drug overdose or withdrawal and (2) mental health crisis (depression, anxiety, suicide attempt) during up to 12 months of follow-up. Discrete time negative binomial regression models estimated adjusted incidence rate ratios (aIRRs) of outcomes as a function of tapering (vs no tapering) and dose reduction velocity. RESULTS: The final cohort included 113 618 patients after 203 920 stable baseline periods. Among the patients who underwent dose tapering, 54.3% were women (vs 53.2% among those who did not undergo dose tapering), the mean age was 57.7 years (vs 58.3 years), and 38.8% were commercially insured (vs 41.9%). Posttapering patient periods were associated with an adjusted incidence rate of 9.3 overdose events per 100 person-years compared with 5.5 events per 100 person-years in nontapered periods (adjusted incidence rate difference, 3.8 per 100 person-years [95% CI, 3.0-4.6]; aIRR, 1.68 [95% CI, 1.53-1.85]). Tapering was associated with an adjusted incidence rate of 7.6 mental health crisis events per 100 person-years compared with 3.3 events per 100 person-years among nontapered periods (adjusted incidence rate difference, 4.3 per 100 person-years [95% CI, 3.2-5.3]; aIRR, 2.28 [95% CI, 1.96-2.65]). Increasing maximum monthly dose reduction velocity by 10% was associated with an aIRR of 1.09 for overdose (95% CI, 1.07-1.11) and of 1.18 for mental health crisis (95% CI, 1.14-1.21). CONCLUSIONS AND RELEVANCE: Among patients prescribed stable, long-term, higher-dose opioid therapy, tapering events were significantly associated with increased risk of overdose and mental health crisis. Although these findings raise questions about potential harms of tapering, interpretation is limited by the observational study design.

Traumatic brain injury (TBI) affects over 69 million people annually worldwide, and those with pre-existing depression have worse recovery. The molecular mechanisms that may contribute to poor recovery after TBI with co-morbid depression have not been established. TBI and depression have many commonalities including volume changes, myelin disruption, changes in proliferation, and changes in glutamatergic signaling. We used a well-established animal model of depression, the Wistar Kyoto (WKY) rat, to elucidate changes after TBI that may influence the recovery trajectory. We compared the histological and molecular outcomes in the hippocampal dentate gyrus after experimental TBI using the lateral fluid percussion injury (LFPI) in the WKY and the parent Wistar (WIS) strain. We showed that WKY had exaggerated myelin loss after LFPI and baseline deficits in proliferation. In addition, we showed that while after LFPI WIS rats exhibited glutamate receptor subunit changes, namely increased GluN2B, the WKY rats failed to show such injury-related changes. These differential responses to LFPI helped to elucidate the molecular characteristics that influence poor recovery after TBI in those with pre-existing depression and may lead to targets for future therapeutic interventions.

Although there are key differences in shorter-term (days 1–90) and longer-term (days 91–365) risk factors for suicide after discharge from inpatient psychiatry, there are no comparable data on non-fatal suicide attempts. Risk factors for non-fatal attempts in the first 90 days after discharge were compared with those over the remainder of the year to identify temporal changes in risk. Records were extracted from 208,554 male veterans discharged from Veterans Health Administration acute psychiatric inpatient units from 2008 through 2013. Proportional hazard regression models identified correlates of non-fatal attempts for 1–90 days and 91–365 days; adjusted piecewise proportional hazards regression compared risk between these time frames. 5010 (2.4%) veterans made a non-fatal attempt, 1261 (0.60%) on days 1–90 and 3749 (1.78%) on days 91–365. Risk across both time frames was highest among younger veterans ages 18–59, and those hospitalized with a suicide attempt or suicidal ideation. It was lowest among those with a dementia diagnosis. Risk estimates were generally stable over time but increased among those with substance use disorders and decreased among those with sleep disturbance and discharged against medical advice. Estimates of some risk factors for non-fatal attempts change over time in the year after discharge and differ from those that change for suicide. Different preventive approaches may be needed to reduce shorter and longer-term risk for non-fatal attempts and suicide in the year after discharge.

To determine if training residents in a structured communication method elicits specific behaviors in a laboratory model of interaction with vaccine-hesitant parents.Standardized patients portraying vaccine-hesitant parents were used to assess the effectiveness of training in the Announce, Inquire, Mirror, Secure (AIMS) Method for Healthy Conversations. Blinded pediatric residents were pseudorandomized to receive AIMS or control training and underwent pre- and post-training encounters with blinded standardized patients. Encounters were assessed by blinded raters using a novel tool. Participant confidence and standardized patient evaluations of the participants' general communication skills were assessed.Ratings were available for 27 AIMS and 26 control participants. Statistically significant increases in post-training scores (maximum = 30) were detected in AIMS, but not in control, participants (median, 21.3 [IQR, 19.8-24.8] vs 18.8 [IQR, 16.9-20.9]; P .001). Elements (maximum score = 6) with significant increases were Inquire (0.67 [IQR, 0-1.76] vs -0.33 [IQR, -0.67 to 0.33]; P .001); Mirror (1.33 [IQR, 0 to 2] vs -0.33 [IQR, -0.92 to 0]; P .001) and Secure (0.33 [IQR, 0 to 1.67] vs -0.17 [IQR, -0.67 to 0.33]; P = .017). Self-confidence increased equally in both groups. Standardized patients did not detect a difference in communication skills after training and between groups. Internal consistency and inter-rater reliability of the assessment tool were modest.Standardized patients proved useful in studying the effectiveness of structured communication training, but may have been limited in their ability to perceive a difference between groups owing to the predetermined encounter outcome of vaccine refusal. AIMS training should be studied in real-world scenarios to determine if it impacts vaccine acceptance.

OBJECTIVE Risk for suicide is highest in the first 3 months (days 1-90) after discharge from acute psychiatric hospitalization yet remains elevated for the remainder of the year (days 91-365). The purpose of this study was to compare risk factors for suicide in the first 90 days to those over the remainder of the year to identify changes across time frames. METHODS The study included 316,707 male veterans discharged from Veterans Health Administration acute psychiatric inpatient units from 2008 through 2013. Proportional hazard regression models were used to identify predictors of suicide death in the first 90 days and in days 91-365, defined via ICD-10 codes. Adjusted piecewise proportional hazard regression was used to compare risk across time frames. RESULTS Among the 1,037 veterans (

Background and Aims Urinary excretion of the fibrinolytic enzyme plasminogen has been identified as a characteristic feature of nephrotic syndrome (NS) in both human and experimental mouse models. Lack of plasminogen may lead to a hypercoagulable state and thrombosis, and mice with plasminogen deficiency have been shown to suffer from developing spontaneous thrombosis. However, the role of plasminogen in hypercoagulable state and thrombosis in an experimental nephrotic syndrome has not been investigated before. Method We investigated the relationship between plasminogen and a hypercoagulable state in an inducible nephrotic mouse model with conditional podocyte-specific podocin deletion (Nphs2Δipod * Plg+/+, n=12). The Nphs2Δipod mice with constitutive plasminogen knockout were used as negative plasminogen control (Nphs2Δipod * Plg-/-, n=15). All mice received a daily oral doxycycline administration for 2 weeks for NS induction. The last day of doxycycline treatment was set as day 0. Spot urine was collected daily for proteinuria and urinary plasmin activity measurement. Citrate blood was collected from each mouse before induction of NS, 7 days and 21 days after induction, respectively (Nphs2Δipod * Plg+/+ mice, n=4/timepoint; Nphs2Δipod * Plg-/- mice, n=5/timepoint). A global assessment of coagulation (extrinsic coagulation test, EX test) was examined by ClotPro® system. Besides, fibrinolysis was tested by adding tissue plasminogen activator (TPA test). Results According to the EX test, uninduced mice with plasminogen deficiency showed a significantly reduced clotting time (CT, Plg-/- vs. Plg+/+, 42 ± 1s vs. 54 ± 4s, p=0.0213), and decreased clot formation time (CFT, Plg-/- vs. Plg+/+, 82 ± 5s vs. 206 ± 28s p Conclusion The results highlight that loss of plasminogen in the nephrotic state contributes to a hypercoagulable state with shortened clotting time, clot formation time, increased clot firmness, and most strikingly, loss of clot lysis. Changes in nephrotic wild-type mice were similar to mice with constitutive plasminogen deficiency, indicating that loss of plasminogen plays a role in the hypercoagulable state of nephrotic syndrome.

Background Alcohol can lead to fatal and nonfatal overdose (OD) through its neurobiological inhibitory effects when used alone or with other drugs. Little research has examined alcohol OD characteristics in the context of concomitant drug use. Methods This study utilized alcohol OD data (defined as alcohol poisoning, passing out, or blacking out) collected in a large residential addiction treatment facility (N = 660). Latent class analysis identified classes of alcohol OD events based on concomitant drug use at the time of OD. We evaluated correlates of alcohol OD classes, including depression, emergency medical services, and hospitalization, using latent class regression. Results Only 20% of alcohol ODs involved alcohol alone. Marijuana was the most commonly used drug during the most recent alcohol OD (43.2%), followed by sedatives (27.9%), cocaine or crack (25.9%), prescription opioids (26.1%), and heroin (20%). The final latent class model included 3 classes: no/low drug involvement (61%), moderate drug involvement (33%), and high drug involvement (6%). Relative to the no/low drug involvement class, participants admitted to the hospital were 6.4‐fold more likely to be in the high drug involvement class (95% CI: 2.4 to 16.6) and 2.9‐fold more likely to be in the moderate drug involvement class (95% CI: 1.2 to 7.2). Participants receiving emergency medical services were more likely to be in the high drug involvement class (aOR: 2.2, 95% CI: 2.2, 1.1 to 4.5) and less likely to be in the moderate drug involvement class (aOR 0.39, 95% CI: 0.2 to 0.96). Conclusions Combining drug classes with alcohol prior to OD was common and associated with a higher likelihood of hospitalization. Overdose prevention efforts should address acute risks of alcohol ingestion with other drugs., This study analyzed alcohol overdose data (i.e. alcohol poisoning, passing out, or blacking out) collected from a residential treatment setting. Only 20% of alcohol overdoses involved alcohol alone. Latent class analysis revealed three alcohol overdose classes: no/low drug involvement (61%), moderate drug involvement (33%), and high drug involvement (6%). Membership in moderate and high drug involvement classes was associated with an increased likelihood of hospitalization. Overdose prevention efforts should address acute risks of alcohol ingestion with other drugs.

BACKGROUND: Any opioid-related hospitalization is an indicator of opioid-related harm and should ideally trigger carefully monitored decreases in opioid prescribing following inpatient stays in many, if not most, cases. However, past studies on opioid prescribing following hospitalizations have largely been limited to overdose related visits. It is unclear whether prescribing is different for other opioid related indications such as opioid dependence and abuse and how that may compare to hospitalizations for overdose. OBJECTIVE: To examine opioid-prescribing patterns before and after opioid-related hospitalizations for all opioid-related indications, not limited to overdose. RESEARCH DESIGN: Retrospective cohort analysis of Veterans Health Administration (VHA) administrative claims from 2011-2014. SUBJECTS: VHA patients who were hospitalized between fiscal years 2011-2014 and had at least one prescription opioid medication filled through the VHA pharmacy prior to their hospitalization. MEASURES: Opioid dispensing trajectories after hospitalization by opioid-related indication (i.e., opioid dependence and/or abuse versus overdose) compared to prescribing patterns for non-opioid-related hospitalizations. RESULTS: Overall, opioid dosage dropped significantly (66% for dependence/abuse, 42% for overdose, and 3% for non-opioid diagnoses, p

Child obesity is a major public health issue with a high disease burden. Although numerous contributing factors have been identified, the family home environment is a central context of influence that requires deeper understanding. The level of organization in the family home environment may influence obesity and obesogenic behaviors, but the literature has suffered from the lack of a strong overarching construct and model to guide this area of research. Family entropy is a conceptual framework that fills this gap by representing the level of organization across the home environment. The current study empirically assesses family entropy using factor analysis in a longitudinal sample of 968 children measured yearly from Grades 3 to 6 as part of the NICHD Study of Early Child Care and Youth Development. Mixed modeling using MPLUS examined the influence of family entropy on child weight both directly and indirectly through weight-related health behaviors (i.e., sleep and physical activity), and considered the moderating role of socioeconomic status (SES). Results suggest that family entropy is comprised of distinct elements of household organization and disorganization, which are moderately related. Household disorganization may be particularly detrimental to child sleeping behavior both concurrently and over time in families of both high and low SES. The study concludes with recommendations for advancing understanding of the home environment by using nuanced measurement strategies, and incorporating support for household organization within child obesity prevention and intervention efforts.

Background Driving under the influence of cannabis (DUIC) is a public health concern among those using medical cannabis. Understanding behaviors contributing to DUIC can inform prevention efforts. We evaluated three past 6-month DUIC behaviors among medical cannabis users with chronic pain. Methods Adults (N = 790) seeking medical cannabis certification or recertification for moderate/severe pain were recruited from February 2014 through June 2015 at Michigan medical cannabis clinics. About half of participants were male (52%) and 81% were White; their Mean age was 45.8 years. Participants completed survey measures of DUIC (driving within 2 h of use, driving while “a little high,” and driving while “very high”) and background factors (demographics, alcohol use, etc.). Unadjusted and adjusted logistic regressions were used to examine correlates of DUIC. Results For the past 6 months, DUIC within 2 h of use was reported by 56.4% of the sample, DUIC while a “little high” was reported by 50.5%, and “very high” was reported by 21.1%. Greater cannabis quantity consumed and binge drinking were generally associated with DUIC behaviors. Higher pain was associated with lower likelihood of DUIC. Findings vary somewhat across DUIC measures. Conclusions The prevalence of DUIC is concerning, with more research needed on how to best measure DUIC. Prevention messaging for DUIC may be enhanced by addressing alcohol co-consumption.

Doxorubicin-induced nephropathy in mice is a model for studying experimental nephrotic syndrome. It corresponds to puromycin aminonucleoside nephrosis in rats. In this model, susceptible 129 S1/SvImJ mice are administered a rapid intravenous injection that can be accomplished via either the lateral tail vein or the retrobulbar sinus. Because doxorubicin is a highly toxic substance, extravasation must be avoided during the administration of the intravenous injection to prevent the development of large necrotizing lesions and exacerbation of the animals’ stress. In the present study, we compared the safety and stress of these two injection routes by using histopathological analyses of the animals’ orbital cavities or tails, respectively. The injection of 14.5 µg/g body weight doxorubicin into the mice’s lateral tail veins ( n = 9) or retrobulbar sinuses ( n = 19) caused no clinically detectable stress or impairment. Histopathologies of the specimens five days after doxorubicin injection revealed inflammatory lesions at the injection sites in both groups. In the orbital sinus specimens from the retrobulbar-injected group, fibrosis was evident 25 days after injection. Moreover, while all of the retrobulbar-injected mice (100%) developed nephrotic syndrome, tail vein-injected mice had a significantly lower response rate (66%, p = 0.047, Fisher’s exact test) and exhibited only attenuated features of nephrotic syndrome. It was therefore concluded that doxorubicin administration via either lateral tail vein or retrobulbar sinus injections led to a similar induction of histopathological changes with no effects on the clinical well-being of the mice. However, retrobulbar sinus injections were more efficient for inducing experimental nephrotic syndrome.

Opioid Use, Overdose, and Suicide This review describes what is known about the links between suicide and overdoses, focusing on pathways involved in opioid use, issues of intent, risk factors, prevention strategies, and unresolved issues.

The original version of this Article contained an error in the spelling of the author Manuela Gago-Dominguez, which was incorrectly given as Manuela G. Dominguez. This has now been corrected in both the PDF and HTML versions of the Article.

Background: Alcohol use disorder (AUD) is a leading preventable cause of morbidity and mortality, but relapse rates are high even with available treatments. Insomnia is a robust predictor of relapse and pilot studies have shown that CBT for insomnia improves insomnia and daytime functioning in adults with AUD and insomnia. The impact of CBT for insomnia on relapse, however, is unclear. This trial will compare telemedicine-delivered CBT for insomnia (CBT-TM) with sleep hygiene education (SHE-TM) on improving insomnia/sleep, daytime symptom, and drinking outcomes in treatment-seeking AUD adults with insomnia. The study will also determine the effects of treatment on sleep mechanisms and their association with clinical outcomes. Methods: This is a single-site randomized controlled trial with planned enrollment of 150 adults meeting criteria for both AUD and chronic insomnia. Eligible participants will be randomized 1:1 to 6 weeks of telemedicine-delivered Cognitive Behavioral Therapy for Insomnia (CBT-TM) or Sleep Hygiene Education (SHE-TM) with clinical assessments conducted at pre-treatment, post- treatment, and at 3-, 6-, and 12-months post-treatment. Overnight polysomnography will be conducted before and after treatment. Primary clinical outcomes will include post-treatment scores on the Insomnia Severity Index and the General Fatigue subscale of the Multidisciplinary Fatigue Inventory, and the percent of days abstinent (PDA) on the interview-administered Time Line Follow Back. EEG delta activity, derived from overnight polysomnography, will be the primary endpoint to assess the sleep homeostasis mechanism. Discussion: This adequately powered randomized controlled trial will provide clinically-relevant information about whether targeting insomnia is effective for improving treatment outcomes among treatment-seeking adults with AUD. Additionally, the study will offer new scientific insights on the impact of an evidence-based non-medication treatment for insomnia on a candidate mechanism of sleep dysfunction in this population - sleep homeostasis.Registration: NCT, NCT # 04457674. Registered 07 July 2020, https://clinicaltrials.gov/ct2/show/NCT04457674?cond=alcohol+use&cntry=US&state=US%3AMI&draw=2&rank=1

Statement of purpose To use longitudinal data collected from youth presenting to an urban emergency department to determine predictors of within-person changes in alcohol and prescription opioid same day use frequency. Methods/Approach Research assistants recruited youth age 14–24 reporting past-six-month substance use into the Flint Youth Injury study from 11/2009–9/2011 (n=599; 349 violently-injured at baseline). Participants self-administered validated measures of alcohol use severity, cannabis use severity, mental health symptoms, social support/influences, and violent injury at baseline and four biannual follow-ups. In addition, participants completed Time Line Follow Back calendars (baseline: 30-days; follow-ups: 90-days) which allowed ascertainment of same day use of alcohol and prescription opioids. We calculated the prevalence of same day alcohol and prescription opioid at each follow-up, and used negative binomial regression with person-level fixed effects to isolate within-person predictor effects on same-day use frequency. Results Between 2.0% (baseline) and 5.7% (18-month follow-up) of youth reported same-day use of alcohol and prescription opioids across follow-ups, with 19.9% reporting same-day use in at least one follow-up. Within-person increases in alcohol use severity, cannabis use severity, and depression and anxiety symptoms all corresponded to increases in same day alcohol and prescription opioid use frequency. Increased exposure to positive peer influences, and decreased exposure to delinquent peers, both coincided with lower same day alcohol and prescription opioid use frequency. Conclusions Same day use of alcohol and prescription opioids is common in this population, and within-person changes are predictable. Interrupting worsening trajectories of substance use severity and mental health symptoms, and enhancing social support and reducing delinquent peer exposures, may reduce same day use frequency. Significance Co-use of alcohol and prescription opioids dramatically increases acute risks (e.g., overdose) associated with each; understanding within-person predictors of same day use may point to catalysts for behavior change.

Statement of purposePreventing opioid misuse and opioid use disorder (OUD) is necessary given the opioid epidemic Prevention programs for adolescents/young adults are needed to alter risk trajectories We developed interventions using telemedicine (synchronous video conference) and a patient portal-like messaging system to address risk factors for opioid misuse/OUD among young Emergency Department (ED) patients Our presentation describes these promising interventions and their feasibility and acceptability Methods/ApproachIn Spring 2020, N = 40 ED patients ages 16–30 who were at risk for opioid misuse/OUD enrolled in a pilot trial involving screening/baseline assessments, motivational interviewing-based remote interventions (baseline telemedicine brief intervention [BI], 1-month of portal messaging), and a 1-month follow-up Before COVID-19, N = 10 enrolled in the ED (in-person cohort: IPC);during COVID-19, N = 30 recent ED patients enrolled via phone recruitment (remote cohort: RC) Feasibility data are presented by cohort;acceptability data are combined ResultsAmong the N=40, the sample had a mean age of 22 9 years Gender was: 70% female, 5% non-conforming, 25% male Race was: 75% White, 15% Black/African American, and 10% other racial identities;17 5% were Hispanic/Latinx Regarding feasibility, eligibility rates were similar (IPC: 17%, RC: 15%);consenting rates differed (IPC: 100%, RC: 56%), likely due to the RC’s telephone approach Portal engagement increased from the IPC (60%) to the RC (93%), possibly due to addressing technical difficulties and IPC user feedback BI and portal satisfaction were high (M = 9 3 on a 1–10 scale and M = 8 5, respectively) Interventions exceeded motivational interviewing fidelity thresholds (adapted for portal messaging) Follow-up rates were high (IPC: 80%, RC: 93%) SignificancePreventing opioid misuse is critical to avoiding escalation of opioid use and overdoses, and emergency department patients are at increased risk This study demonstrates the feasibility and acceptability of these intervention approaches via telemedicine for preventing future injuries

Aim The serine protease prostasin (Prss8) is expressed in the distal tubule and stimulates proteolytic activation of the epithelial sodium channel (ENaC) in co-expression experiments in vitro. The aim of this study was to explore the role of prostasin in proteolytic ENaC activation in the kidney in vivo. Methods We used genetically modified knockin mice carrying a Prss8 mutation abolishing proteolytic activity (Prss8-S238A) or a mutation leading to a zymogen-locked state (Prss8-R44Q). Mice were challenged with low sodium diet and diuretics. Regulation of ENaC activity by Prss8-S238A and Prss8-R44Q was studied in vitro using the Xenopus laevis oocyte expression system. Results Co-expression of murine ENaC with Prss8-wt or Prss8-S238A in oocytes caused maximal proteolytic ENaC activation, whereas ENaC was activated only partially in oocytes co-expressing Prss8-R44Q. This was paralleled by a reduced proteolytic activity at the cell surface of Prss8-R44Q expressing oocytes. Sodium conservation under low sodium diet was preserved in Prss8-S238A and Prss8-R44Q mice but with higher plasma aldosterone concentrations in Prss8-R44Q mice. Treatment with the ENaC inhibitor triamterene over four days was tolerated in Prss8-wt and Prss8-S238A mice, whereas Prss8-R44Q mice developed salt wasting and severe weight loss associated with hyperkalemia and acidosis consistent with impaired ENaC function and renal failure. Conclusion Unlike proteolytically inactive Prss8-S238A, zymogen-locked Prss8-R44Q produces incomplete proteolytic ENaC activation in vitro and causes a severe renal phenotype in mice treated with the ENaC inhibitor triamterene. This indicates that Prss8 plays a role in proteolytic ENaC activation and renal function independent of its proteolytic activity.

The use of reverse shoulder arthroplasty (RSA) to treat complex humerus fractures is increasing, especially in older, osteoporotic patients. Refixation and tuberosity healing are needed to achieve an optimal range of motion (ROM), external rotation, active forward elevation, and patient satisfaction. Proper healing has been reported, however, in only 40–84% of cases. Our study’s aim was to describe a simple, reproducible fixation technique designed to improve tuberosity healing. We included 30 patients with acute proximal humerus fractures undergoing RSA (Global Unite Reverse Fracture, DePuy Synthes, Warsaw, IN, USA) with tuberosity reattachment. The humerus stem was cemented in 24 cases. A standardized suture technique with two fiber tapes was used to reattach tuberosities. Clinical and radiological parameters, which were collected one year post-operatively, included ROM, pain level, Constant scores, subjective shoulder value (SSV), and tuberosity healing. The mean age of the patients was 79.3 years (± 7; range 65–92), and the tuberosity healing rate was 90.0% (27 of 30). Two patients showed migration (one nonunion, one malunion), and another had complete resorption after an initial period of proper healing. Radiolucent lines around the humerus stem occurred in one case, and three patients had scapular notching. The mean SSV was 86% (± 11; range 60–100), the Constant score was 72 (± 10.3; range 48–92), the active forward flexion was 140° (± 14.3; range 115–165), and external rotation was 23° (± 16.5; range 0–50). This reattachment technique, which is simple and reproducible, achieved a higher tuberosity healing rate than previously published rates.

Barth syndrome (BTHS) is a rare, X-linked cardiomyopathy that is characterized by abnormalities in glucose and lipid metabolism, with less known regarding amino acid metabolism. This pilot study characterized whole-body arginine kinetics and found lower arginine rate of appearance into plasma (0.69 ± 0.09 vs. 0.88 ± 0.06 μmol/kgFFM/min, p