Database derived from an electronic medical record-based surveillance network of US emergency department patients with acute respiratory illness.

BACKGROUND: For surveillance of episodic illness, the emergency department (ED) represents one of the largest interfaces for generalizable data about segments of the US public experiencing a need for unscheduled care. This protocol manuscript describes the development and operation of a national network linking symptom, clinical, laboratory and disposition data that provides a public database dedicated to the surveillance of acute respiratory infections (ARIs) in EDs. METHODS: The Respiratory Virus Laboratory Emergency Department Network Surveillance (RESP-LENS) network includes 26 academic investigators, from 24 sites, with 91 hospitals, and the Centers for Disease Control and Prevention (CDC) to survey viral infections. All data originate from electronic medical records (EMRs) accessed by structured query language (SQL) coding. Each Tuesday, data are imported into the standard data form for ARI visits that occurred the prior week (termed the index file); outcomes at 30 days and ED volume are also recorded. Up to 325 data fields can be populated for each case. Data are transferred from sites into an encrypted Google Cloud Platform, then programmatically checked for compliance, parsed, and aggregated into a central database housed on a second cloud platform prior to transfer to CDC. RESULTS: As of August, 2023, the network has reported data on over 870,000 ARI cases selected from approximately 5.2 million ED encounters. Post-contracting challenges to network execution have included local shifts in testing policies and platforms, delays in ICD-10 coding to detect ARI cases, and site-level personnel turnover. The network is addressing these challenges and is poised to begin streaming weekly data for dissemination. CONCLUSIONS: The RESP-LENS network provides a weekly updated database that is a public health resource to survey the epidemiology, viral causes, and outcomes of ED patients with acute respiratory infections.

Outcomes of Ultrasound Guided Peripheral Intravenous Catheters Placed in the Emergency Department and Factors Associated with Survival.

Background: Patients with difficult peripheral intravenous (IV) access are common in emergency departments (EDs). Ultrasound-guided peripheral intravenous catheters (USIVs) are frequently used in this population; however, information regarding the effect of patient and IV characteristics on the dwell time (DT) and survival probability (SP) of USIVs is limited. Objective: Our study aimed to evaluate for associations between patient or IV characteristics and the DT and SP of USIVs. Methods: Retrospective analysis was performed on a database from an ED nurse (RN) USIV training program at an urban, academic hospital. Patients over 18 years with an USIV placed during the study period were included. Subject demographics, history, IV characteristics, insertion, and removal times were collected. Data were analyzed using descriptive statistics and univariable and multivariable Cox regression. USIV survival times for variates of interest were estimated using Kaplan-Meier curves for three censoring points. Results: The final analysis cohort was 388 patients. Mean age was 56.6 years, 66.5% were female, mean BMI was 29.9 kg/m2, and 42.5% were obese (BMI ≥30). Median DT was 40.3 hours in admitted patients (N=340). SP for USIVs at 96 hours was 87.8%. A total of 21 of 340 (6.2%) USIVs failed. USIV location conferred a difference on DT in obese patients when dichotomized into upper arm versus antecubital fossa and forearm together (38.6 hours vs 44.6 hours, p=0.03). No factors were associated with a difference in USIV SP. Conclusion: Median USIV DT of 40.3 hours for admitted patients was higher than in previous studies. Only 7% of USIVs in our study failed. Overall, catheters survived longer than expected.

Measurement artifacts in the dithiothreitol (DTT) oxidative potential assay caused by interactions between aqueous metals and phosphate buffer.

Metals in particulate matter (PM) are hypothesized to have enhanced toxicity based on their ability to catalyze reactive oxygen species (ROS) formation. Acellular assays are used to measure the oxidative potential (OP) of PM and its individual components. Many OP assays, including the dithiothreitol (DTT) assay, use a phosphate buffer matrix to simulate biological conditions (pH 7.4 and 37 °C). Prior work from our group observed transition metal precipitation in the DTT assay, consistent with thermodynamic equilibria. In this study, we characterized the effects of metal precipitation on OP measured by the DTT assay. Metal precipitation was affected by aqueous metal concentrations, ionic strength, and phosphate concentrations in ambient PM sampled in Baltimore, MD and a standard PM sample (NIST SRM-1648a, Urban Particulate Matter). Critically, differences in metal precipitation induced differing OP responses of the DTT assay as a function of phosphate concentration in all PM samples analyzed. These results indicate that comparison of DTT assay results obtained at differing phosphate buffer concentrations is highly problematic. Further, these results have implications for other chemical and biological assays that use phosphate buffer for pH control and their use to infer PM toxicity.

Exploring COVID-19 Vaccine Attitudes among Racially and Ethnically Minoritized Communities: Community Partners' and Residents' Perspectives.

COVID-19 has disproportionately affected Black, Indigenous, and People of Color (BIPOC) communities, yet rates of COVID-19 vaccination remain low among these groups. A qualitative study was undertaken to better understand the factors contributing to low vaccine acceptance among these communities. Seventeen focus groups were conducted in English and Spanish from 8/21 to 9/22, with representatives from five critical community sectors: (1) public health departments (n = 1); (2) Federally Qualified Health Centers (n = 2); (3) community-based organizations (n = 1); (4) faith-based organizations (n = 2); and (5) BIPOC residents in six high-risk, underserved communities in metropolitan Houston (n = 11), for a total of 79 participants, comprising 22 community partners and 57 community residents. A social-ecological model and anti-racism framework were adopted to guide data analysis using thematic analysis and constant comparison, which yielded five key themes: (1) legacy of structural racism: distrust and threat; (2) media misinformation: mass and social; (3) listening and adapting to community needs; (4) evolving attitudes towards vaccination; and (5) understanding alternative health belief systems. Although structural racism was a key driver of vaccine uptake, a notable finding indicated community residents' vaccine attitudes can be changed once they are confident of the protective benefits of vaccination. Study recommendations include adopting an explicitly anti-racist lens to: (1) listen to community members' needs and concerns, acknowledge their justified institutional distrust concerning vaccines, and learn community members' healthcare priorities to inform initiatives built on local data; (2) address misinformation via culturally informed, consistent messaging tailored to communal concerns and delivered by trusted local leaders through multimodal community forums; (3) take vaccines to where people live through pop-up clinics, churches, and community centers for distribution via trusted community members, with educational campaigns tailored to the needs of distinct communities; (4) establish vaccine equity task forces to continue developing sustainable policies, structures, programs and practices to address the structural issues driving vaccine and health inequities within BIPOC communities; and (5) continue investing in an effective infrastructure for healthcare education and delivery, essential for competently responding to the ongoing healthcare and other emergency crises that impact BIPOC communities to achieve racial justice and health equity in the US. Findings underscore the crucial need to provide culturally tailored health education and vaccination initiatives, focused on cultural humility, bidirectionality, and mutual respect to support vaccine re-evaluation.

Does Vitamin D Provide Added Benefit to Antihypertensive Therapy in Reducing Left Ventricular Hypertrophy Determined by Cardiac Magnetic Resonance?

BACKGROUND: Left ventricular hypertrophy (LVH) and vitamin D deficiency have been linked to hypertension (HTN) and cardiovascular disease, particularly in African Americans (AAs). Our objective was to determine if the addition of vitamin D to antihypertensive therapy would lead to greater regression of LV mass index (LVMI) as determined by cardiac magnetic resonance (CMR) after 1 year in vitamin D deficient AA patients with uncontrolled HTN and LVH. METHODS: This study was a randomized, double-blind, placebo-controlled, single-center study. AA patients with HTN (systolic blood pressure [BP] >160 mm Hg), increased LVMI, and vitamin D deficiency (<20 ng/ml) were randomized. All patients received antihypertensive therapy combined with biweekly 50,000 IU vitamin D3 (vitamin D group, n = 55) or placebo (placebo group, n = 58). RESULTS: At 1 year, there were no statistical differences between the vitamin D and placebo groups in LVMI (-14.1 ± 14.6 vs. -16.9 ± 13.1 g/m2; P = 0.34) or systolic BP (-25.6 ± 32.1 vs. -25.7 ± 25.6 mm Hg; P = 0.99) reduction, respectively. Serum vitamin D levels increased significantly in the vitamin D group compared with placebo (12.7 ± 2.0 vs. 1.8 ± 8.2 ng/ml; P < 0.001). CONCLUSIONS: In this high-risk cohort of AAs we did not find an association between vitamin D supplementation and differential regression of LVMI or reduction in systolic BP. However, our study suffered from a small sample size with low statistical power precluding a definitive conclusion on the therapeutic benefit of vitamin D in such patients. CLINICAL TRIALS REGISTRATION: Trial Number NCT01360476. Full trial protocol is available from corresponding author.

Real-time dynamic single-molecule protein sequencing on an integrated semiconductor device.

Studies of the proteome would benefit greatly from methods to directly sequence and digitally quantify proteins and detect posttranslational modifications with single-molecule sensitivity. Here, we demonstrate single-molecule protein sequencing using a dynamic approach in which single peptides are probed in real time by a mixture of dye-labeled N-terminal amino acid recognizers and simultaneously cleaved by aminopeptidases. We annotate amino acids and identify the peptide sequence by measuring fluorescence intensity, lifetime, and binding kinetics on an integrated semiconductor chip. Our results demonstrate the kinetic principles that allow recognizers to identify multiple amino acids in an information-rich manner that enables discrimination of single amino acid substitutions and posttranslational modifications. With further development, we anticipate that this approach will offer a sensitive, scalable, and accessible platform for single-molecule proteomic studies and applications.

A Detroit Student-Run Free Clinic's Management of Select Chronic Diseases.

AIM: The Cass Clinic is a student-run free clinic in Detroit, Michigan that treats chronic diseases including hypertension (HTN), diabetes mellitus (DM), and obesity. Our study aims to quantify the effectiveness of our clinic in managing chronic diseases. SUBJECT AND METHODS: This study assessed selected health outcomes for 137 patients who visited our clinic between September 1, 2017 and August 31, 2018 based on initial and most recent surrogate markers including manual blood pressure, hemoglobin A1c (HbA1c), and body mass index (BMI) recorded in the clinic's medical record system dating back to 2012. RESULTS: Patients were divided into two groups: occasionally seen patients (OSP) and frequently seen patients (FSP). FSP with HTN had systolic blood pressure (SBP) decreased by an average of 14.1 mmHg and diastolic blood pressure (DBP) decreased by 9.8 mmHg, which were statistically associated with the number of clinic visits. Additionally, all patients treated at Cass Clinic saw a decrease in their HbA1c and BMI. HbA1c in OSP decreased by 0.50%. HbA1c in the FSP decreased by 1.7%. Patients with at least two recorded BMIs (n=73) saw a decrease of 0.13 kg/m2. CONCLUSION: The data from our analysis support that a student-run free clinic model like Cass Clinic provides long-term value for patients who frequently utilize the clinic. These clinics also act as an important resource for the community by making positive strides toward better health in multiple measurable outcomes, including HTN and DM management.

Characterization of Pyrrolidinyl-hexahydro-pyranopiperazines as a Novel Kappa Opioid Receptor Agonist Scaffold.

The kappa agonist structure-activity relationship around the novel, pyrrolidinyl substituted pyranopiperazine scaffold was developed. More specifically, the dichloroPhenylAcetamide-Pyrrolidinyl-PyranoPiperazine (PAPPP) core A was the focus of our work. The modulation of kappa receptor potency/G-protein activation and arrestin recruitment with respect to changes of the piperazine R group in A was demonstrated. Reduced ß2-arrestin recruitment and differential G-protein bias were observed for select analogues. To better understand the subtlety in receptor signaling, analogues were profiled as the resolved enantiomers. To determine in vivo target engagement, a subset of compounds was tested in mice for stimulation of serum prolactin, a neuroendocrine biomarker of KOR-agonist effects. Additional in vivo characterization included measurement of potential unwanted effects of kappa receptor activation such as sedation. These studies demonstrate a novel kappa receptor agonist scaffold with potential for G-protein signaling bias to probe in vivo pharmacology.

Precipitation of aqueous transition metals in particulate matter during the dithiothreitol (DTT) oxidative potential assay.

Transition metals in particulate matter (PM) are hypothesized to have enhanced toxicity based on their oxidative potential (OP). The acellular dithiothreitol (DTT) assay is widely used to measure the OP of PM and its chemical components. In our prior study, we showed that the DTT assay (pH 7.4, 0.1 M phosphate buffer, 37 °C) provides favorable thermodynamic conditions for precipitation of multiple metals present in PM. This study utilizes multiple techniques to characterize the precipitation of aqueous metals present at low concentrations in the DTT assay. Metal precipitation was identified using laser particle light scattering analysis, direct chemical measurement of aqueous metal removal, and microscopic imaging. Experiments were run with aqueous metals from individual metal salts and a well-characterized urban PM standard (NIST SRM-1648a, Urban Particulate Matter). Our results demonstrated rapid precipitation of metals in the DTT assay. Metal precipitation was independent of DTT but dependent on metal concentration. Metal removal in the chemically complex urban PM samples exceeded the thermodynamic predictions and removal seen in single metal salt experiments, suggesting co-precipitation and/or adsorption may have occurred. These results have broad implications for other acellular assays that study PM metals using phosphate buffer, and subsequently, the PM toxicity inferred from these assays.

Kappa Opioid Receptor Antagonists as Potential Therapeutics for Mood and Substance Use Disorders.

The kappa opioid receptor (KOR) and its primary cognate ligands, the dynorphin peptides, are involved in diverse physiological processes. Disruptions to the KOR/dynorphin system have been found to likely play a role in multiple neuropsychological disorders, and hence KOR has emerged as a potential therapeutic target. Targeting KOR is complicated by close homology to the mu and delta opioid receptors (MOR and DOR), and many KOR ligands have at least moderate affinity to MOR and/or DOR. Animal models utilizing primarily very long-lasting selective KOR antagonists (>3 weeks following a single dose) have demonstrated that KOR antagonism attenuates certain anxiety-like and depression-like behaviors and blocks stress- and cue-induced reinstatement to drug seeking. Recently, relatively selective KOR antagonists with medication-like pharmacokinetic and pharmacodynamic properties and durations of action have been developed. One of these, JNJ-67953964 (also referred to as CERC-501, LY2456302, OpraKappa or Aticaprant) has been studied in humans, and shown to be safe, relatively KOR selective, and able to substantially attenuate binding of a KOR PET tracer to CNS localized KOR for greater than 24 h. While animal studies have indicated that compounds of this structural class are capable of normalizing withdrawal signs in animal models of cocaine and alcohol dependence and reducing cocaine and alcohol intake/seeking, additional studies are needed to determine the value of these second generation KOR antagonists in treating mood disorders and substance use disorders in humans.

Cancer Incidence and Mortality Among Fighter Aviators in the United States Air Force.

OBJECTIVE: This study sought to clarify cancer risk in fighter aviators. METHODS: US Air Force officers who served between 1970 and 2004 were followed through 2018 for incidence and mortality of 10 cancers: colon and rectum; pancreas; melanoma skin; prostate; testis; urinary bladder; kidney and renal pelvis; brain and other nervous system; thyroid; and non-Hodgkin lymphoma. Fighter aviators were compared with other officers and the general US population. RESULTS: Compared with other officers, male fighter aviators had greater adjusted odds of developing testis, melanoma skin, and prostate cancers; mortality odds were similar for all cancers. When compared with the US population, male fighter aviators were more likely to develop and die from melanoma skin cancer, prostate cancer, and non-Hodgkin lymphoma. CONCLUSIONS: Military fighter aviation may be associated with slightly increased risk of certain cancers.

Video-assisted self-reflection of resuscitations for resident education and improvement of leadership skills: A pilot study.

INTRODUCTION: One of the most challenging aspects of Emergency Medicine (EM) residency is mastering the leadership skills required during a resuscitation. Use of resuscitation video recording for debriefing is gaining popularity in graduate medical education. However, there are limited studies of how video technology can be used to improve leadership skills in the emergency department. We aim to evaluate the utility of video-assisted self-reflection, compared with self-reflection alone, in the setting of resuscitation leadership. METHODS: This was a prospective, randomized, controlled pilot study conducted in 2018 at an urban level 1 trauma center with a three-year EM residency program. The trial included postgraduate year (PGY) 2 and 3 residents (n = 10). Each resident acted as an individual team leader for a live real-time resuscitation in the emergency department. The authors classified a patient as a resuscitation if there was an immediate life- or limb-threatening disease process or an abnormal vital sign with an indication of hypoperfusion. Each resident was recorded as the team leader twice. Both control and intervention groups produced written self-reflection after their first recording. The intervention group viewed their resuscitation recording while completing the written reflection. After their reflection, all participants were recorded for a second resuscitation. Two faculty experts, blinded to the study, scored each video using the Concise Assessment of Leader Management (CALM) scale to measure the leadership skills of the resident team leader. RESULTS: Five PGY­3 and five PGY­2 residents participated. The weighted kappa between the two experts was 0.45 (CI 0.34-0.56, p < 0.0001). The median gain score in the control group was -1.5 (IQR) versus 0.5 in the intervention group (IQR). DISCUSSION: Video-assisted self-reflection showed positive gain score trends in leadership evaluation for residents during a resuscitation compared with the non-video assisted control group. This tool would be beneficial to implement in EM residency.

Randomized Controlled Trial of a Novel Silicone Device for the Packing of Cutaneous Abscesses in the Emergency Department: A Pilot Study.

OBJECTIVE: Traditional treatment of abscesses in the emergency department includes packing with gauze; however, this can add pain and discomfort to the procedure and frequently involves a follow-up visit for packing removal. Alternatives to gauze packing have been proposed, but they may have disadvantages in the context of emergency care. The objective of this pilot study was to investigate the use of a novel silicone packing device - the Derma-Stent. METHODS: This was a randomized controlled pilot study of 50 patients from two urban emergency departments with uncomplicated superficial abscesses. The primary outcome was the likelihood of self-removal of packing gauze versus the silicone device. Secondary outcome measures included subjective clinician and patient metrics, such as pain and ease of use. RESULTS: Patients identified with simple cutaneous abscesses were randomized to intervention (packing with the novel silicone device, n=25) or standard care (gauze packing, n=25). Mean age was 36 years, 54% were female, and 96% identified as African American. Although it took longer to place, the silicone device (19.0 vs 15.3 minutes, p=0.03), pain scores were significantly lower (4.3/10 vs 7.1/10, p=0.008) and ease of use reported by physicians better in the silicone-device group (4.8/5 vs 4.0/5, p=0.002). A high unknown rate in the gauze-packing group limits discussion of the likelihood of self-removal; however, the silicone device was more likely to remain in place (60%) versus the gauze packing at 3 days (24%, p=0.01). CONCLUSION: This pilot randomized controlled trial compared the treatment of packing cutaneous abscesses with gauze versus using the silicone device. Limitations in the data prevent discussion on likelihood of self-removal. However, the silicone device was more likely to remain in place at day 3 follow-up and was equally effective to gauze packing in abscess reduction while also improving patient-reported pain scores. It did take longer to place the silicone device; however, physicians reported better ease of use and removal. This pilot study is encouraging for additional larger-scale trials that are required to further assess the utility of this device in the emergency department.

Nalmefene, a mu opioid receptor antagonist/kappa opioid receptor partial agonist, potentiates cocaine motivation but not intake with extended access self-administration in adult male mice.

The mu opioid receptor antagonist/kappa opioid receptor (KOR) partial agonist nalmefene (NMF), a close structural analog of naltrexone (NTX), has been shown to reduce cocaine reward in preclinical models. Given the greater KOR potency and improved bioavailability compared to NTX, NMF may be a promising pharmacotherapeutic for cocaine use disorder (CUD). Here we examine the effects of NMF pretreatment on chronic daily extended access (4h) cocaine intravenous self-administration (IVSA) in adult male C57Bl/6J mice. METHODS: separate groups of mice had daily 4h cocaine IVSA sessions (0.25 or 0.5 mg/kg/inf, FR1) for 14 days. Starting on day 8, mice were pretreated with NMF (0, 1, or 10 mg/kg) 30m before each session. A separate group of mice acquired cocaine IVSA [seven days FR1 then four FR3 of 4h daily sessions (0.5 mg/kg/inf)] prior to a single progressive ratio 3 session to examine the effect of 1 mg/kg NMF on cocaine motivation. RESULTS: No significant effect of NMF pretreatment on cocaine intake was observed. Acute pretreatment of 1 mg/kg NMF significantly potentiated cocaine motivation as measured by progressive ratio breakpoint. CONCLUSIONS: NMF did not significantly attenuate cocaine intake and increased motivation for cocaine suggesting that NMF may not be suitable for non-abstinent CUD patients. Further research is needed with KOR selective partial or full agonists to determine their effect on cocaine reinforcement.

Adding a Physical Therapist to the Health Care Team in an HIV Clinic Increases Physical Therapy Referrals and Reduces Opioid Prescriptions Provided for Chronic Musculoskeletal Pain in Patients Living With HIV.

BACKGROUND: Musculoskeletal (MSK) pain is common in people living with HIV (PLWH). Health care providers sometimes prescribe opioids to control pain, which may lead to opioid misuse. An interdisciplinary approach that includes physical therapy has been successful in managing MSK pain in various health care settings. Therefore, we sought to find the impact of recruiting a physical therapist (PT) on the number of opioid prescriptions and physical therapy referrals made by physicians in training to manage MSK pain in PLWH. METHODS: We performed a retrospective chart review of patients seen by Internal Medicine physicians in training in an HIV clinic in Detroit before (2017) and after (2018) recruiting a PT to the health care team and collected demographic and clinical data. We also surveyed the trainees to assess how the PT addition influenced their learning. Institutional review board waiver was obtained. RESULTS: Results showed that of all PLWH seen at the clinic, 28/249 (11%) and 37/178 (21%) had chronic MSK pain in the 2017 and 2018 data sets, respectively. In 2017, all 28 patients with MSK pain were prescribed opioids. This decreased in 2018 after the PT addition (10/37 patients; P < .0001). The number of physical therapy referrals significantly increased after the PT addition (2017: 5/28 patients; 2018: 17/37 patients; P = .03). Trainees felt that the PT helped improve their examination skills and develop a treatment plan for patients. CONCLUSIONS: The addition of a PT encouraged physicians in training to utilize nonopioid management of MSK pain in PLWH and enhanced their learning experience, as perceived by the trainees.

Angiotensin-converting enzyme inhibitors increase anti-fibrotic biomarkers in African Americans with left ventricular hypertrophy.

Angiotensin-converting enzyme inhibitors (ACEi) are part of the indicated treatment in hypertensive African Americans. ACEi have blood pressure-independent effects that may make them preferred for certain patients. We aimed to evaluate the impact of ACEi on anti-fibrotic biomarkers in African American hypertensive patients with left ventricular hypertrophy (LVH). We conducted a post hoc analysis of a randomized controlled trial in which hypertensive African American patients with LVH and vitamin D deficiency were randomized to receive intensive antihypertensive therapy plus vitamin D supplementation or placebo. We selected patients who had detectable lisinopril (lisinopril group) in plasma using liquid-chromatography/mass spectrometry analysis and compared them to subjects who did not (comparison group) at the one-year follow-up. The pro-fibrotic marker type 1 procollagen C-terminal propeptide (PICP) and the anti-fibrotic markers matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinases 1 (TIMP-1), telopeptide of collagen type I (CITP), and N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) peptide were measured. Sixty-six patients were included, and the mean age was 46.2 ± 8 years. No difference was observed in the number and intensity of antihypertensive medications prescribed in each group. Patients with detectable lisinopril had lower blood pressure than those in the comparison group. The anti-fibrotic markers Ac-SDKP, MMP-1, and MMP-1/TIMP-1 ratio were higher in patients with detectable ACEi (all p < .05). In a model adjusted for systolic blood pressure, MMP-1/TIMP-1 (p = .02) and Ac-SDKP (p < .001) levels were associated with lisinopril. We conclude that ACEi increase anti-fibrotic biomarkers in hypertensive African Americans with LVH, suggesting that they may offer added benefit over other agents in such patients.

Fate of transition metals in PO4-based in vitro assays: equilibrium modeling and macroscopic studies.

Transition metals are thought to be among the most toxic components in atmospheric particulate matter (PM) due to their role in catalyzing reactive oxygen species (ROS) formation. We show that precipitation of the transition metals Fe(ii), Fe(iii), and Mn(ii) are thermodynamically favored in phosphate-based assays used to measure the oxidative potential (OP) - a surrogate for toxicity - of PM. Fe and Mn precipitation is likely to occur at extremely low metal concentrations (<0.5 µM), levels that are imperceptible to the naked eye. The concentration of each metal (other than Cu) in aqueous PM filter extracts often exceeds the solubility limit in OP assays, indicating favorable thermodynamic conditions for precipitation. Macroscopic experimental results at higher metal concentrations (>100 µM) with visible precipitates provide quasi-validation of the thermodynamic modeling. Oxidation of Fe(ii) to Fe(iii) is likely to be rapid in all in vitro OP assays, transforming Fe to a much less soluble form. Fe precipitates are likely to increase the rate of precipitation of other metals and possibly induce co-precipitation. These results have direct relevance for all PO4-based assays; the implications for studies of PM toxicity are discussed.

Genetic Vulnerability to Opioid Addiction.

Opioid addiction, also referred to as opioid use disorder, continues to be a devastating problem throughout the world. Familial relation and twin studies have revealed opioid addiction, like other addictive diseases, to be profoundly influenced by genetics. Genetics studies of opioid addiction have affirmed the importance of genetics contributors in susceptibility to develop opioid addiction, and also have important implications on treatment for opioid addiction. But the complexity of the interactions of multiple genetic variants across diverse genes, as well as substantial differences in allelic frequencies across populations, thus far limits the predictive value of individual genetics variants.

Stimulant storm - state health department psychostimulant age-adjusted mortality rate correlates with psychostimulant-based Michigan Poison Center case exposures over time.

BACKGROUND: Deaths attributable to psychostimulants with abuse potential have increased in the United States (US) in recent years. Methamphetamine use, in particular, has risen sharply. We evaluated the correlation between amphetamine- and methamphetamine-related case exposures reported to the Michigan Poison Center (MiPC) coinciding with psychostimulant age-adjusted mortality rates from the Michigan Department of Health and Human Services (MDHHS). METHODS: We compared amphetamine and methamphetamine exposures reported to the MiPC from 2012 to 2018, queried from ToxSentry® database, to MDHHS reports on resident death certificates with attributed death due to "overdose, regardless of intent" and related cause of death attributed to psychostimulants with abuse potential. Linear regression assessed goodness-of-fit. Slope with standard error and adjusted R2 were reported. Psychostimulants included methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), dextroamphetamine, levoamphetamine, and methylphenidate. RESULTS: Psychostimulant deaths reported by MDHHS increased from 17 to 165 between 2012 and 2018. The average age-adjusted rate of psychostimulant-involved overdose deaths per 100,000 state residents rose from 0.2 to 1.8. Linear regression of MiPC amphetamine exposure rates with state health department-reported age-adjusted psychostimulant mortality rates yielded a slope of 1.93, SE 0.5, p value 0.035, and adjusted R2 0.55. Linear regression of MiPC methamphetamine exposure rates with state health department-reported age-adjusted psychostimulant mortality rates yielded a slope of 0.78, SE 0.27, p value 0.012, and adjusted R2 0.70 suggesting a strong correlation. CONCLUSION: Psychostimulant use and associated deaths in the US are increasing, representing an evolving public health threat. Michigan demonstrates consistency with national trends and data from the MiPC correlates strongly with state-reported age-adjusted psychostimulant mortality rates. Strengthening collaboration between poison centers and state health departments is critical for detection and mitigation efforts and can thereby inform resource allocation.