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Post-Acute Sequelae of SARS-CoV-2 infection (PASC), also known as Long-COVID, encompasses a variety of complex and varied outcomes following COVID-19 infection that are still poorly understood. We clustered over 600 million condition diagnoses from 14 million patients available through the National COVID Cohort Collaborative (N3C), generating hundreds of highly detailed clinical phenotypes. Assessing patient clinical trajectories using these clusters allowed us to identify individual conditions and phenotypes strongly increased after acute infection. We found many conditions increased in COVID-19 patients compared to controls, and using a novel method to associate patients with clusters over time, we additionally found phenotypes specific to patient sex, age, wave of infection, and PASC diagnosis status. While many of these results reflect known PASC symptoms, the resolution provided by this unprecedented data scale suggests avenues for improved diagnostics and mechanistic understanding of this multifaceted disease., (© 2024. The Author(s).)

The main sources of lead exposure for children occur in the home environment, yet no low-cost analytical methods exist to screen homes for lead hazards. Previously, an inexpensive (~$20), quantitative lead screening kit was developed in which residents collect soil, paint, and dust samples that are returned to a laboratory for lead analysis using X-ray fluorescence spectroscopy (XRF). This screening kit was initially validated in 2020; it was determined that in situ and ex situ XRF lead measurements on the same samples exhibited strong sensitivity, specificity, and accuracy. As a follow-up to the initial validation, an implementation study and further statistical analyses were conducted. Correlation analysis using the results from nearly 400 screening kits identified an overall lack of correlation between sample types, reinforcing the utility of all eight sample locations. Principal component analysis searched for underlying correlations in sample types and provided evidence that both interior and exterior paint are major sources of lead hazards for Indiana homes. The implementation study compared the results of the government-standard lead inspection and risk assessment (LIRA) and the lead screening kit in 107 Indiana homes. In the United States, the LIRA is a thorough inspection of paint, dust, and soil that is usually state mandated in response to a child's elevated blood level and is used to identify where remediation efforts should be focused. The lead screening kit and LIRA agreed on the presence of lead in 79 of the 107 homes tested (74%). Discrepancies in agreement are likely the result of differences in the sample location and number of samples collected by each method. Overall, these results suggest that the lead screening kit is an acceptable resource that could be used to expand the services health departments provide for lead prevention. Integr Environ Assess Manag 2024;20:1504-1513. © 2024 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)., (© 2024 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).)

Fentanyl test strips (FTS) are lateral flow immunoassays that were originally designed and validated for detecting low concentrations of fentanyl in urine. Some FTS are now being marketed for the harm reduction purpose of testing street drugs for the presence of fentanyl. This manuscript provides a simple protocol to assess whether different brands and lots of fentanyl test strips perform adequately for use in drug checking. The results gathered from this protocol will document problems with particular lots or brands of FTS, help buyers choose from among the array of products, provide feedback to manufacturers to improve their products, and serve as an early warning system for ineffective products., (© 2024. The Author(s).)

Portable near-infrared (NIR) spectrophotometers have emerged as valuable tools for identifying substandard and falsified pharmaceuticals (SFPs). Integration of these devices with chemometric and machine learning models enhances their ability to provide quantitative chemical insights. However, different NIR spectrophotometer models vary in resolution, sensitivity, and responses to environmental factors such as temperature and humidity, necessitating instrument-specific libraries that hinder the wider adoption of NIR technology. This study addresses these challenges and seeks to establish a robust approach to promote the use of NIR technology in post-market pharmaceutical analysis. We developed support vector machine and partial least squares regression models based on binary mixtures of lab-made ciprofloxacin and microcrystalline cellulose, then applied the models to ciprofloxacin dosage forms that were assayed with high performance liquid chromatography (HPLC). A receiver operating characteristic (ROC) analysis was performed to set spectrophotometer independent NIR metrics to evaluate ciprofloxacin dosage forms as "meets standard," "needs HPLC assay," or "fails standard." Over 200 ciprofloxacin tablets representing 50 different brands were evaluated using spectra acquired from three types of NIR spectrophotometer with 85% of the prediction agreeing with HPLC testing. This study shows that non-brand-specific predictive models can be applied across multiple spectrophotometers for rapid screening of the conformity of pharmaceutical active ingredients to regulatory standard., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Background: Fentanyl test strips (FTS) are lateral flow immunoassay strips designed for detection of ng/mL levels of fentanyl in urine. In 2021, the US Centers for Disease Control and the Substance Abuse and Mental Health Administration stated that federal funds could be used for procurement of FTS for harm reduction strategies approved by the government such as drug checking. The market for FTS has expanded rapidly in the US and Canada. However, there is no regulatory oversight by either government to ensure proper function of FTS that are being marketed for drug checking., Main Body: Many brands of FTS have rapidly entered the harm reduction market, creating concerns about the reproducibility and accuracy of their performance from brand to brand and lot to lot. Some examples are provided in this Comment. Similar problems with product quality were observed in the mid 2000's when lateral flow immunoassays for malaria were funded in many countries and again in 2020, when COVID-19 tests were in huge demand. The combination of high demand and low levels of regulation and enforcement led some manufacturers to join the goldrush without adequate field testing or quality assurance. We argue that the harm reduction community urgently needs to set a lot checking program in place. A set of simple protocols for conducting the tests and communicating the results have been developed, and are described in the following Perspectives paper in this issue., Conclusion: In the absence of governmental regulation and enforcement, the harm reduction community should implement a FTS lot checking program. Based on previous experience with the malaria diagnostic lot checking program, this inexpensive effort could identify products that are not suitable for harm reduction applications and provide valuable feedback to manufacturers. Dissemination of the results will help harm reduction organizations to ensure that FTS they use for drug checking are fit for the purpose., (© 2024. The Author(s).)

Post-Acute Sequelae of SARS-CoV-2 infection (PASC), also known as Long-COVID, encompasses a variety of complex and varied outcomes following COVID-19 infection that are still poorly understood. We clustered over 600 million condition diagnoses from 14 million patients available through the National COVID Cohort Collaborative (N3C), generating hundreds of highly detailed clinical phenotypes. Assessing patient clinical trajectories using these clusters allowed us to identify individual conditions and phenotypes strongly increased after acute infection. We found many conditions increased in COVID-19 patients compared to controls, and using a novel method to associate patients with clusters over time, we additionally found phenotypes specific to patient sex, age, wave of infection, and PASC diagnosis status. While many of these results reflect known PASC symptoms, the resolution provided by this unprecedented data scale suggests avenues for improved diagnostics and mechanistic understanding of this multifaceted disease., Competing Interests: Competing Interests The authors declare no competing interests.

Wood is the water conducting tissue of tree stems. Like most angiosperm trees, poplar wood contains water-conducting vessel elements whose functional properties affect water transport and growth rates, as well as susceptibility to embolism and hydraulic failure during water stress and drought. Here we used a unique hybrid poplar pedigree carrying genomically characterized chromosomal insertions and deletions to undertake a systems genomics analysis of vessel traits. We assayed gene expression in wood forming tissues from clonal replicates of genotypes covering dosage quantitative trait loci with insertions and deletions, genotypes with extreme vessel trait phenotypes, and control genotypes. A gene co-expression analysis was used to assign genes to modules, which were then used in integrative analyses to identify modules associated with traits, to identify putative molecular and cellular processes associated with each module, and finally to identify candidate genes using multiple criteria including dosage responsiveness. These analyses identified known processes associated with vessel traits including stress response, abscisic acid and cell wall biosynthesis, and in addition identified previously unexplored processes including cell cycle and protein ubiquitination. We discuss our findings relative to component processes contributing to vessel trait variation including signaling, cell cycle, cell expansion, and cell differentiation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rodriguez-Zaccaro, Lieberman and Groover.)

Background: The syndemic nature of gonococcal infections and HIV provides an opportunity to develop a synergistic intervention tool that could address the need for adequate treatment for gonorrhea, screen for HIV infections, and offer pre-exposure prophylaxis (PrEP) for persons who meet the criteria. By leveraging information available on electronic health records, a clinical decision support (CDS) system tool could fulfill this need and improve adherence to Centers for Disease Control and Prevention (CDC) treatment and screening guidelines for gonorrhea, HIV, and PrEP., Objective: The goal of this study was to translate portions of CDC treatment guidelines for gonorrhea and relevant portions of HIV screening and prescribing PrEP that stem from a diagnosis of gonorrhea as an electronic health record-based CDS intervention. We also assessed whether this CDS solution worked in real-world clinic., Methods: We developed 4 tools for this CDS intervention: a form for capturing sexual history information (SmartForm), rule-based alerts (best practice advisory), an enhanced sexually transmitted infection (STI) order set (SmartSet), and a documentation template (SmartText). A mixed methods pre-post design was used to measure the feasibility, use, and usability of the CDS solution. The study period was 12 weeks with a baseline patient sample of 12 weeks immediately prior to the intervention period for comparison. While the entire clinic had access to the CDS solution, we focused on a subset of clinicians who frequently engage in the screening and treatment of STIs within the clinical site under the name "X-Clinic." We measured the use of the CDS solution within the population of patients who had either a confirmed gonococcal infection or an STI-related chief complaint. We conducted 4 midpoint surveys and 3 key informant interviews to quantify perception and impact of the CDS solution and solicit suggestions for potential future enhancements. The findings from qualitative data were determined using a combination of explorative and comparative analysis. Statistical analysis was conducted to compare the differences between patient populations in the baseline and intervention periods., Results: Within the X-Clinic, the CDS alerted clinicians (as a best practice advisory) in one-tenth (348/3451, 10.08%) of clinical encounters. These 348 encounters represented 300 patients; SmartForms were opened for half of these patients (157/300, 52.33%) and was completed for most for them (147/300, 89.81%). STI test orders (SmartSet) were initiated by clinical providers in half of those patients (162/300, 54%). HIV screening was performed during about half of those patient encounters (191/348, 54.89%)., Conclusions: We successfully built and implemented multiple CDC treatment and screening guidelines into a single cohesive CDS solution. The CDS solution was integrated into the clinical workflow and had a high rate of use., (©Saugat Karki, Sarah Shaw, Michael Lieberman, Alejandro Pérez, Jonathan Pincus, Priya Jakhmola, Amrita Tailor, Oyinkansola Bukky Ogunrinde, Danielle Sill, Shane Morgan, Miguel Alvarez, Jonathan Todd, Dawn Smith, Ninad Mishra. Originally published in JMIR Formative Research (https://formative.jmir.org), 15.04.2024.)

Portable NIR spectrometers are effective in detecting authentic pharmaceutical products in intact capsule formulations, which can be used to screen for substandard or falsified versions of those authentic products. However, the chemometric models are trained on libraries of authentic products, and are generally unreliable for detection of quality problems in products from outside their training set, even for products that are nominally the same active pharmaceutical ingredient and same dosage as products in the training set. As part of our research directed at developing better non-brand-specific strategies for pharmaceutical screening, we investigated the impact of capsule composition on NIR modeling. We found that capsule features like gelatin type, color, or thickness, give rise to a similar amount of variance in the NIR spectra as the type of API stored within the capsules. Our results highlight the efficacy of orthogonal projection to latent structures in mitigating the impacts of different types of capsules on the accuracy of NIR chemometric models for classification and regression analysis of lab-made samples. The models showed good performance for classification of field-collected doxycycline capsules as good or bad quality when an NIR-based % w/w metric was used, identifying five samples that were adulterated with talc. However, the % w/w was systematically underestimated, so when evaluating the capsules based on their absolute API content according to the monograph standard, the classification accuracy decreased from 100% to 70%. The underestimation was attributed to an unforeseen variability in the quantities and types of excipients present in the capsules.

Babbling is an important precursor to speech in infancy, and deviations from the typical babbling development can predict later difficulties in speech, language, and communication. This cross-sectional study aimed to investigate babbling and early speech in Swedish extremely premature infants. Samples of babbling were collected from 20 extremely premature infants (EPT group) at the corrected age of 12 months. Data collection was home-based and consisted of an audio-video recording of each infant playing with a parent. Presence of canonical babbling (CB), and three oral stop variables distinctive of typical babbling, and consonant inventory were assessed. The assessment was performed during a standardised observation of babbling. Data from the EPT group were compared to previously collected data of a reference group of 20 10-month-old infants without known medical diagnoses. The results showed that the EPT group had a lower proportion of infants producing CB, and that they used a significantly smaller consonant inventory compared to the reference group. Although not statistically significant, oral stops were less frequently found in the EPT group. The findings of a restricted consonant inventory and low proportion of CB in the EPT group are not surprising considering that the group has been found to be at risk of speech and language delay in toddlerhood. Still, further research is needed to explore whether babbling at 12 months can predict speech and language skills at an older age in extremely premature infants.

The Sandell-Kolthoff (SK) assay is the main analytical method used to monitor population iodine nutrition in low- and middle-income countries. This assay can distinguish between populations that are iodine-deficient (median urinary iodine levels below 100 ppb), iodine-sufficient (median urinary iodine levels between 100 and 300 ppb), and iodine- excessive(median urinary iodine levels above 300 ppb). However, the analysis of urine samples with the SK reaction is technically challenging, partly because urine samples must be rigorously pretreated to remove interferents. In the literature, the only urinary metabolite that has been identified as an interferent is ascorbic acid. In this study, we used the microplate SK method to screen thirty-three of the major organic metabolites present in urine. We identified four previously unknown interferents: citric acid, cysteine, glycolic acid and urobilin. For each interferent, we investigated the following factors: (1) nature of interference-positive or negative, (2) threshold concentration for interference, and (3) possible mechanisms of interference. While this paper does not attempt to provide an exhaustive list of all interferents, knowledge of the main interferents allows for targeted removal., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Shifts in the US drug supply, including the proliferation of synthetic opioids and emergence of xylazine, have contributed to the worsening toll of the overdose epidemic. Drug checking services offer a critical intervention to promote agency among people who use drugs (PWUD) to reduce overdose risk. Current drug checking methods can be enhanced to contribute to supply-level monitoring in the USA, overcoming the selection bias associated with existing supply monitoring efforts and informing public health interventions., Methods: As a group of analytical chemists, public health researchers, evaluators, and harm reductionists, we used a semi-structured guide to facilitate discussion of four different approaches for syringe service programs (SSPs) to offer drug checking services for supply-level monitoring. Using thematic analysis, we identified four key principles that SSPs should consider when implementing drug checking programs., Results: A number of analytical methods exist for drug checking to contribute to supply-level monitoring. While there is likely not a one-size-fits-all approach, SSPs should prioritize methods that can (1) provide immediate utility to PWUD, (2) integrate seamlessly into existing workflows, (3) balance individual- and population-level data needs, and (4) attend to legal concerns for implementation and dissemination., Conclusions: Enhancing drug checking methods for supply-level monitoring has the potential to detect emerging threats in the drug supply and reduce the toll of the worsening overdose epidemic., (© 2024. The Author(s).)

Background: Soil constitutes a major source of childhood lead exposure, disproportionately affecting communities of color. Mulching offers a low-cost interim control., Objectives: A community-academic partnership was established for lead poisoning prevention, with a three-fold aim: (1) control soil lead hazards by applying mulch, (2) identify home lead hazards with screening kits, and (3) connect residents to resources to address lead hazards., Methods: Student volunteers canvassed neighborhoods one month prior to the annual event. They requested consent for mulching, distributed lead screening kits, and screened residents for grant eligibility. Soil samples were collected from each home before mulching. According to principles of community-based participatory research, materials and plans were iterative, guided and adjusted by neighborhood association feedback, and detailed reports about home lead results were shared with each participating resident. Composite neighborhood data and survey results were shared with volunteers and community partners., Results: The project was evaluated in the third (41 homes) and fourth (48 homes) years of implementation. Before mulching, the median soil lead level was over 400 ppm, and after mulching, it was less than 20 ppm. Lead screening kits identified widespread lead hazards in paint, soil, and dust, but not water. Challenges remain in (a) increasing child blood lead testing and (b) increasing submissions for city grant funding for lead abatement. Evaluation surveys indicate a sense of ownership in the project among community partners and high levels of engagement among students., Conclusions: Community-academic partnerships are an effective tool for lead poisoning prevention, generating evidence for public health action.

Background: Fentanyl test strips (FTS) are a commonly deployed tool in drug checking, used to test for the presence of fentanyl in street drug samples prior to consumption. Previous reports indicate that in addition to fentanyl, FTS can also detect fentanyl analogs like acetyl fentanyl and butyryl fentanyl, with conflicting reports on their ability to detect fentanyl analogs like Carfentanil and furanyl fentanyl. Yet with hundreds of known fentanyl analogs, there has been no large-scale study rationalizing FTS reactivity to different fentanyl analogs., Methods: In this study, 251 synthetic opioids-including 214 fentanyl analogs-were screened on two brands of fentanyl test strips to (1) assess the differences in the ability of two brands of fentanyl test strips to detect fentanyl-related compounds and (2) determine which moieties in fentanyl analog chemical structures are most crucial for FTS detection. Two FTS brands were assessed in this study: BTNX Rapid Response and WHPM DanceSafe., Results: Of 251 screened compounds assessed, 121 compounds were detectable at or below 20,000 ng/mL by both BTNX and DanceSafe FTS, 50 were not detectable by either brand, and 80 were detectable by one brand but not the other (n = 52 BTNX, n = 28 DanceSafe). A structural analysis of fentanyl analogs screened revealed that in general, bulky modifications to the phenethyl moiety inhibit detection by BTNX FTS while bulky modifications to the carbonyl moiety inhibit detection by DanceSafe FTS., Conclusions: The different "blind spots" are caused by different haptens used to elicit the antibodies for these different strips. By utilizing both brands of FTS in routine drug checking, users could increase the chances of detecting fentanyl analogs in the "blind spot" of one brand., (© 2023. The Author(s).)

Background: There is limited evidence that the diabetes in-person consult in hospitalized patients can be replaced by a virtual consult. During COVID-19 pandemic, the diabetes in-person consult service at the University of Miami and Miami Veterans Affairs Healthcare System transitioned to a virtual model. The aim of this study was to assess the impact of telemedicine on glycemic control after this transition., Methods: We retrospectively analyzed glucose metrics from in-person consults (In-person) during January 16 to March 14, 2020 and virtual consults during March 15 to May 14, 2020. Data from virtual consults were analyzed by separating patients infected with COVID-19, who were seen only virtually (Virtual-COVID-19-Pos), and patients who were not infected (Virtual-COVID-19-Neg), or by combining the two groups (Virtual-All)., Results: Patient-day-weighted blood glucose was not significantly different between In-person, Virtual-All, and Virtual-COVID-19-Neg, but Virtual-COVID-19-Pos had significantly higher mean ± SD blood glucose (mg/dL) compared with others (206.7 ± 49.6 In-person, 214.6 ± 56.2 Virtual-All, 206.5 ± 57.2 Virtual-COVID-19-Neg, 229.7 ± 51.6 Virtual-COVID-19-Pos; P = .015). A significantly less percentage of patients in this group also achieved a mean ± SD glucose target of 140 to 180 mg/dL (23.8 ± 22.5 In-person, 21.5 ± 20.5 Virtual-All, 25.3 ± 20.8 Virtual-COVID-19-Neg, and 14.4±18.1 Virtual-COVID-19-Pos, P = .024), but there was no significant difference between In-person, Virtual-All, and Virtual-COVID-19-Neg. The occurrence of hypoglycemia was not significantly different among groups., Conclusions: In-person and virtual consults delivered by a diabetes team at an academic institution were not associated with significant differences in glycemic control. These real-world data suggest that telemedicine could be used for in-patient diabetes management, although additional studies are needed to better assess clinical outcomes and safety., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

An LC-MS/MS method for the analysis of 53 benzodiazepines, including various designer benzodiazepines, was developed. The developed method was applied to a total of 79 illicit street drug samples collected in Chicago, IL. Of these samples, 68 (84%) had detectable amounts of at least one benzodiazepine. Further, of the 53 benzodiazepines included in the developed method just 14 were measured in samples. Clonazolam, a potent designer benzodiazepine and derivative of clonazepam, was the most frequently measured benzodiazepine in 63% of samples and was measured in the highest concentrations. Other benzodiazepines measured in more than 10% of samples included clonazepam, alprazolam, flualprazolam, and oxazepam. Mixtures of benzodiazepines were frequently measured in samples, with just 24% of samples containing just one benzodiazepine. To determine the response of benzodiazepines on a rapid, point-of-use drug checking tool, all 53 benzodiazepine standards were screened on a lateral flow immunoassay benzodiazepine test strip. Sixty eight percent of standards gave a positive BTS response at a concentration of 20 μg/mL, demonstrating BTS have response to a wide variety of benzodiazepines, including many designer benzodiazepines. A comparison of this data to previous data reported for the same samples demonstrated all samples containing a benzodiazepine also had an opioid present, with fentanyl being present in 94% of benzodiazepine samples. These results highlight high rates of polysubstance drug presence in Chicago, IL illicit drug samples, posing an increased risk of drug overdoses in people who use drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

The negative consequences of Substandard and falsified (SF) medicines are widely documented nowadays and there is still an urgent need to find them in more efficient ways. Several screening tools have been developed for this purpose recently. In this study, three screening tools were used on 292 samples of ciprofloxacin and metronidazole collected in Cameroon. Each sample was then analyzed by HPLC and disintegration tests. Seven additional samples from the nitro-imidazole (secnidazole, ornidazole, tinidazole) and the fluoroquinolone (levofloxacin, ofloxacin, norfloxacin, moxifloxacin) families were analyzed to mimic falsified medicines. Placebo samples that contained only inert excipients were also tested to mimic falsified samples without active pharmaceutical ingredient (API). The three screening tools implemented were: a simplified visual inspection checklist, a low-cost handheld near infrared (NIR) spectrophotometer and paper analytical devices (PADs). Overall, 61.1% of the samples that failed disintegration and assay tests also failed the visual inspection checklist test. For the handheld NIR, one-class classifier models were built to detect the presence of ciprofloxacin and metronidazole, respectively. The APIs were correctly identified in all the samples with sensitivities and specificities of 100%. However, the importance of a representative and up-to-date spectral database was underlined by comparing models built with different calibration set spanning different variability spaces. The PADs were used only on ciprofloxacin samples and detected the API in all samples in which the presence of ciprofloxacin was confirmed by HPLC. However, these PADs were not specific to ciprofloxacin since they reacted like ciprofloxacin to other fluoroquinolone compounds. The advantages and drawbacks of each screening tool were highlighted. They are promising means in the frame of early detection of SF medicines and they can increase the speed of decision about SF medicines in the context of pharmaceutical post-marketing surveillance., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Waffo Tchounga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The opioid epidemic continues to be associated with high numbers of fatalities in the USA and other countries, driven mainly by the inclusion of potent synthetic opioids in street drugs. Drug checking by means of various technologies is being increasingly implemented as a harm reduction strategy to inform users about constituent drugs in their street samples. We assessed how valued drug checking services (DCS) would be for opioid street drug users given the ubiquity of fentanyl and related analogs in the drug supply, the information they would most value from drug checking, and compared expected versus actual constituent drugs in collected samples., Methods: A convenience sample of opioid street drug users (N = 118) was recruited from two syringe service exchange programs in Chicago between 2021 and 2022. We administered brief surveys asking about overdose history, whether fentanyl was their preferred opioid, and interest in DCS. We also collected drug samples and asked participants what drug(s) they expected were in the sample. Provided samples were analyzed using LC-MS technology and the results compared to their expected drugs., Results: Participants reported an average of 4.4 lifetime overdoses (SD = 4.8, range = 0-20) and 1.1 (SD = 1.8, range = 0-10) past-year overdoses. A majority (92.1%) believed they had recently used drugs containing fentanyl whether intentionally or unintentionally. Opinions about the desirability of fentanyl were mixed with 56.1% indicating they did not and 38.0% indicating they did prefer fentanyl over other opioids, mainly heroin. Attitudes toward DCS indicated a general but not uniform receptiveness with a majority indicating interest in DCS though sizeable minorities believed DCS was "too much trouble" (25.2%) or there was "no point" in testing (35.4%). Participants were especially inaccurate identifying common cutting agents and potentiating drugs such as diphenhydramine in their samples (sensitivity = .17)., Conclusions: Results affirmed street drug users remain interested in using DCS to monitor their drugs and such services should be more widely available. Advanced checking technologies that provide information on the relative quantities and the different drugs present in a given sample available at point-of-care, would be most valuable but remain challenging to implement., (© 2023. The Author(s).)

Drug checking services are being utilized worldwide to provide people who use drugs information on the composition and contents of their drugs as a tool for harm reduction and accidental overdose prevention. Existing drug checking services use a variety of techniques including immunoassay strips and spectroscopic techniques like FTIR and Raman. Few services utilize LC-MS based methods for primary or secondary analysis and few methods exist for direct analysis of illicit drugs. To address this, an LC-MS/MS method was developed for 22 illicit drugs and cutting agents using LC-MS/MS with application to 124 illicit drug samples that were collected from Chicago, IL. Samples were also analyzed using fentanyl and benzodiazepine immunoassay test strips. Fentanyl test strips gave a positive result for 86% of samples with only one sample showing a positive result on a benzodiazepine test strip. LC-MS/MS analysis of samples show that opioids were the most commonly quantified in 96% of samples, followed by stimulants at 12% and benzodiazepines at 1%. Fentanyl was measured in 91% of samples, co-occurring with heroin in 58% of opioid-containing samples. A comparison of the gold-standard LC-MS/MS results to fentanyl test strips shows a high level of accuracy for the fentanyl test strips, with just 5% of samples being classified as false negatives and no false positives. These results demonstrate the strengths and benefits of LC-MS/MS when incorporated as a secondary analysis tool for drug checking.

Paper-based analytical devices (PADs) offer a low-cost, user-friendly platform for rapid point-of-use testing. Without scalable fabrication methods, however, few PADs make it out of the academic laboratory and into the hands of end users. Previously, wax printing was considered an ideal PAD fabrication method, but given that wax printers are no longer commercially available, alternatives are needed. Here, we present one such alternative: the air-gap PAD. Air-gap PADs consist of hydrophilic paper test zones, separated by "air gaps" and affixed to a hydrophobic backing with double-sided adhesive. The primary appeal of this design is its compatibility with roll-to-roll equipment for large-scale manufacturing. In this study, we examine design considerations for air-gap PADs, compare the performance of wax-printed and air-gap PADs, and report on a pilot-scale roll-to-roll production run of air-gap PADs in partnership with a commercial test-strip manufacturer. Air-gap devices performed comparably to their wax-printed counterparts in Washburn flow experiments, a paper-based titration, and a 12-lane pharmaceutical screening device. Using roll-to-roll manufacturing, we produced 2700 feet of air-gap PADs for as little as $0.03 per PAD.

Background: The social determinants of health (SDOH) are the conditions in which people are born, grow, work, live, and age. Lack of SDOH training of dental providers on SDOH may result in suboptimal care provided to pediatric dental patients and their families. The purpose of this pilot study is to report the feasibility and acceptability of SDOH screening and referral by pediatric dentistry residents and faculty in the dental clinics of Family Health Centers at NYU Langone (FHC), a Federally Qualified Health Center (FQHC) network in Brooklyn, NY, USA., Methods: Guided by the Implementation Outcomes Framework, 15 pediatric dentists and 40 pediatric dental patient-parent/guardian dyads who visited FHC in 2020-2021 for recall or treatment appointments participated in this study. The a priori feasibility and acceptability criteria for these outcomes were that after completing the Parent Adversity Scale (a validated SDOH screening tool), ≥ 80% of the participating parents/guardians would feel comfortable completing SDOH screening and referral at the dental clinic (acceptable), and ≥ 80% of the participating parents/guardians who endorsed SDOH needs would be successfully referred to an assigned counselor at the Family Support Center (feasible)., Results: The most prevalent SDOH needs endorsed were worried within the past year that food would run out before had money to buy more (45.0%) and would like classes to learn English, read better, or obtain a high school degree (45.0%). Post-intervention, 83.9% of the participating parents/guardians who expressed an SDOH need were successfully referred to an assigned counselor at the Family Support Center for follow-up, and 95.0% of the participating parents/guardians felt comfortable completing the questionnaire at the dental clinic, surpassing the a priori feasibility and acceptability criteria, respectively. Furthermore, while most (80.0%) of the participating dental providers reported being trained in SDOH, only one-third (33.3%) usually or always assess SDOH for their pediatric dental patients, and most (53.8%) felt minimally comfortable discussing challenges faced by pediatric dental patient families and referring patients to resources in the community., Conclusions: This study provides novel evidence of the feasibility and acceptability of SDOH screening and referral by dentists in the pediatric dental clinics of an FQHC network., (© 2023. The Author(s).)

The complex, bis-( N , N -diethyl-4-methyl-4-piperazine-1-carboxamide) tetra-kis(iso-thio-cyanato-κ N )cobalt(II) ( N , N -diethyl-4-methyl-4-piperazine-1-carboxamide = di-ethyl-carbamazine), (C 10 H 22 N 3 O) 2 [Co(NCS) 4 ], is presented. This com-plex is a blue precipitate, insoluble in water but soluble in organic solvents, that is formed from the reaction of diethylcarbamazine citrate, a protonated tertiary amine, with cobalt(II) and thio-cyanate. This reaction, in the form of the Scott test, is a common presumptive test for cocaine hydro-chloride. The known cobalt compound, [K 2 Co(NCS) 4 ]·3H 2 O, has a deep-blue coloration due to the tetra-hedral [Co(NCS) 4 ] 2- that is also present in the ion pair with bulky amines, and is similar to the color of other tetra-hedral cobalt(II) complex ions, such as [CoCl 4 ] 2- . The structure is consistent with a previous proposal that a hydro-phobic ion pair formed between [Co(NCS) 4 ] 2- and two protonated mol-ecules of cocaine is responsible for the blue hydro-phobic products formed by cocaine in the Scott test., (© Oliver et al. 2023.)

Hyperlipidemia is a significant risk factor for atherosclerotic cardiovascular disease. Undertreatment of elevated lipids persists despite existing therapies. Here, we provide an update on monoclonal antibodies, gene silencing therapies, and gene editing techniques for the management of hyperlipidemia. The current era of cutting-edge pharmaceuticals targeting low density lipoprotein cholesterol, PCSK9, lipoprotein (a), angiopoietin-like 3, and apolipoprotein C3 are reviewed. We outline what is known, studies in progress, and futuristic goals. This review of available and upcoming biotechnological lipid therapies is presented for clinicians managing patients with familial hyperlipidemia, statin intolerance, hypertriglyceridemia, or elevated lipoprotein (a) levels.

Global health researchers often discount mutual learning and benefit to address shared health challenges across high and low- and middle-income settings. Drawing from a 30-year partnership called AMPATH that started between Indiana University in the US and Moi University in Kenya, we describe an innovative approach and program for mutual learning and benefit coined 'reciprocal innovation.' Reciprocal innovation harnesses a bidirectional, co-constituted, and iterative exchange of ideas, resources, and innovations to address shared health challenges across diverse global settings. The success of AMPATH in Kenya, particularly in HIV/AIDS and community health, resulted in several innovations being 'brought back' to the US. To promote the bidirectional flow of learning and innovations, the Indiana CTSI reciprocal innovation program hosts annual meetings of multinational researchers and practitioners to identify shared health challenges, supports pilot grants for projects with reciprocal exchange and benefit, and produces educational and training materials for investigators. The transformative power of global health to address systemic health inequities embraces equitable and reciprocal partnerships with mutual benefit across countries and communities of academics, practitioners, and policymakers. Leveraging a long-standing partnership, the Indiana CTSI has built a reciprocal innovation program with promise to redefine global health for shared wellbeing at a global scale.

Background: Iodine is one of the crucial micronutrients needed by the human body, and is vitally important during pregnancy. This study aimed to determine the relationship between the iodine status of pregnant women and their knowledge, and practices regarding iodized salt. All participants were enrolled in the Butajira nutrition, mental health and pregnancy (BUNMAP) cohort, Butajira, Ethiopia in February-May, 2019., Methods: In this cross-sectional study, 152 pregnant women without hypertension or known thyroid disease before or during pregnancy were randomly selected from the BUNMAP mother to child cohort (n = 832). Spot urine samples were collected to estimate the level of urinary iodine concentration (UIC). Salt samples were also collected from their homes. The Sandall-Kolthoff (S-K) method was used to measure the level of iodine in the urine samples, and iodometric titration was used to measure the level of iodine in the salt. Data was entered and cleaned using Epi-info version 3.5.3 and then exported to SPSS version 20 for further analysis. Multivariate logistic regression analysis was performed to identify associations in the collected data., Results: The WHO recommended level of iodine for populations of pregnant women is 150-249 F06Dg/L. The median UIC among pregnant women in this study was 151.2 μg/L [interquartile range (IQR) = 85.5-236.2 F06Dg/L], at the low end of this range. About half (49.65%) of the participants were likely to be iodine deficient. There was a significant association between having a formal job (AOR = 2.56; CI = 1.11-5.96) and iodine sufficiency. Based on a cutoff of >15 ppm (mg/kg), 91.7% (95% CI: 87.2-96.2) of the salts collected from the household had adequate iodine content. The median iodine level of the collected salt samples was 34.9 mg/kg (ppm) (IQR = 24.2-44.6 mg/kg)., Conclusions: The UNICEF 2018 guidelines for adequate iodine nutrition in pregnant women include both a recommended median range of 150-249 μg/L, and an upper limit of 20% on the fraction of the population with UIC below 50 μg/L. Because our study population's median level is 151.2 μg/L and the percentage of pregnant women with urinary iodine concentration of less than 50 μg/L is 9.7% (14/145), the women received adequate iodine nutrition. The availability of adequately iodized salt in households is more than 90%, as recommended by WHO. In light of previous iodine deficiency in this region of Ethiopia, the salt iodization program promotes the health of babies and mothers., Competing Interests: NO authors have competing interests., (Copyright: © 2022 Tadesse et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim: We evaluated the concurrent and predictive validity of questions to parents of 10-month-old children about babbling., Methods: Children with at least one native Swedish-speaking parent were eligible for inclusion in this prospective longitudinal study. The parents were asked three questions about babbling at a routine healthcare visit. If parents reported a lack of canonical babbling (CB), children were assessed by a speech and language pathologist to evaluate the questions' concurrent validity. We then examined whether the babbling questions predicted which children would fail the routine language screening at 2.5/3 years., Results: Fifteen of the 1126 children lacked CB according to the parent responses and the expert assessment confirmed 12 of these cases, providing a concurrent validity of 80%. The sensitivity to predict routine language screening was 8% (95% confidence interval 3-17), and the positive predictive value was 40% (95% confidence interval 20%-65%). However, only six of the children lacking CB at 10 months were among the 71 children who failed later language screening., Conclusion: This study suggests that the babbling questions could be included in the 10-month surveillance at the child health services as valid measures of babbling development, but they cannot predict language screening result at 2.5/3 years., (© 2022 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Near-infrared (NIR) spectroscopy is a promising technique for field identification of substandard and falsified drugs because it is portable, rapid, nondestructive, and can differentiate many formulated pharmaceutical products. Portable NIR spectrometers rely heavily on chemometric analyses based on libraries of NIR spectra from authentic pharmaceutical samples. However, it is difficult to build comprehensive product libraries in many low- and middle-income countries due to the large numbers of manufacturers who supply these markets, frequent unreported changes in materials sourcing and product formulation by the manufacturers, and general lack of cooperation in providing authentic samples. In this work, we show that a simple library of lab-formulated binary mixtures of an active pharmaceutical ingredient (API) with two diluents gave good performance on field screening tasks, such as discriminating substandard and falsified formulations of the API. Six data analysis models, including principal component analysis and support-vector machine classification and regression methods and convolutional neural networks, were trained on binary mixtures of acetaminophen with either lactose or ascorbic acid. While the models all performed strongly in cross-validation (on formulations similar to their training set), they individually showed poor robustness for formulations outside the training set. However, a predictive algorithm based on the six models, trained only on binary samples, accurately predicts whether the correct amount of acetaminophen is present in ternary mixtures, genuine acetaminophen formulations, adulterated acetaminophen formulations, and falsified formulations containing substitute APIs. This data analytics approach may extend the utility of NIR spectrometers for analysis of pharmaceuticals in low-resource settings.

Interventions that increase our sense of belonging can help us confront new challenges.

Purpose/objectives: Self-assessment of clinical competence is an important tool for effective learning and training for some educational programs. The New York University (NYU) Langone Hospital's Advanced Education in General Dentistry (AEGD) Program has had its residents complete self-assessment of clinical competency evaluations for many years. The evaluation is used to understand the residents' perception of their own clinical skill upon beginning the program and to determine the necessary resources to provide to the residents for them to meet program standards. The same evaluation is completed by the residents 6 months later to determine if they perceived advancement in their clinical performance while in the program. Dental education, along with other fields of education was disrupted by the coronavirus disease 2019 (COVID-19) pandemic. The purpose of this study was to examine the impact of COVID-19 on clinical competency self-assessments among the NYU Langone AEGD residents before and during the pandemic., Methods: In this cross-sectional study, data was collected from two AEGD cohorts representing 2019-2020 and 2020-2021 academic years; from July 2019 (n = 196) to January 2020 (n = 189) and July 2020 (n = 202) to January 2021 (n = 184). The self-assessment evaluations were administered via an online residency management platform on the first days of July and January of the academic year. The survey consisted of 48 questions on "clinical skills and performance" as established by CODA standards for postdoctoral general dentistry programs., Results: Survey response rate was 100% for both cohorts. When comparing results, the findings indicate the COVID-19 pandemic had interrupted clinical learning during dental school. However, training through the AEGD program led to improvements in perceived clinical competence by the residents in mid-program evaluation., Conclusion: The self-assessment evaluation can be used as a tool to enhance training as part of the AEGD program's performance improvement plan., (© 2022 American Dental Education Association.)

Substandard and falsified (SF) pharmaceuticals account for an estimated 10% of the pharmaceutical supply chain in low- and middle-income countries (LMICs), where a lack of regulatory and laboratory resources limits the ability to conduct effective post-market surveillance and allows SF products to penetrate the supply chain. The Distributed Pharmaceutical Analysis Laboratory (DPAL) was established in 2014 to expand testing of pharmaceutical dosage forms sourced from LMICs; DPAL is an alliance of academic institutions throughout the United States and abroad that provides high-quality, validated chemical analysis of pharmaceutical dosage forms sourced from partners in LMICs. Results from analysis are reported to relevant regulatory agencies and are used to inform purchasing decisions made by in-country stakeholders. As the DPAL program has expanded to testing more than 1,000 pharmaceutical dosage forms annually, challenges have surfaced regarding data management and sample tracking. Here, we describe a pilot project between DPAL and ARTiFACTs that applies the blockchain to organize and manage key data generated during the DPAL workflow, including a sample's progress through the workflow, its physical location, provenance of metadata, and lab reputability. Recording time and date stamps with these data will create a permanent and verifiable chain of custody for samples. This secure, distributed ledger will be linked to an easy-to-use dashboard, allowing stakeholders to view results and experimental details for each sample in real time and verify the integrity of DPAL analysis data. Introducing this blockchain-based system as a pilot will allow us to test the technology with real users analyzing real samples. Feedback from users will be recorded and necessary adjustments will be made to the system before the implementation of blockchain across all DPAL sites. Anticipated benefits of implementing the blockchain technology for managing DPAL data include efficient management for routing work, increasing throughput, creating a chain of custody for samples and their data in alignment with the distributed nature of DPAL, and using the analysis results to detect patterns of quality within and across brands of products and develop enhanced sampling techniques and best practices., Competing Interests: One of the authors is employed by a for-profit entity, ARTiFACTS.ai (Artifacts of Research, Inc.), that provides the platform utilized in the pilot described in this article. ARTiFACTS provides a complementary service for the BHTY journal, which allows the authors published in BHTY to link supporting evidence with their manuscripts and receive citations to that evidence. ARTiFACTS intends to apply the learnings from this pilot to determine the viability of developing a commercial solution., (© 2022 The Authors.)

The use of nucleic acid tests (NAT) for sensitive and rapid detection of pathogens relevant to human health has increased due to the ubiquity of nucleic acid amplification techniques such as polymerase chain reaction. The use of such tools for detection of amplified nucleic acid (NA) in field and clinical settings is limited by the need for complex instrumentation and trained users. To address these limitations we developed a rapid, robust, and instrument-free colorimetric detection method for nucleic acids using a visible region dye, Nile Blue (NB). NB is a cationic benzophenoxazine dye with well-known binding interactions with NA and has been used in instrumental methods for DNA quantification. When combined with dsDNA, the color of NB shifts from blue to purple. Images of this color shift are collected and are subjected to image analysis. Observed changes in the red and green colorimetric intensities are linked to the ratio of dsDNA to NB. By titrating solutions of dsDNA against a series of NB concentrations, we found it possible to quantitate dsDNA at concentrations ranging from 10-100 μg mL -1 using a k -means cluster analysis method. This range is comparable to that of NA concentrations quantified using gold-standard UV-Visible spectroscopy and to the concentrations of NA in biological samples after amplification. Unknown concentrations of dsDNA from yeast extracts were correctly identified within ±5 μg mL -1 of true concentration. Preliminary experiments demonstrate use of the developed NB method on paper-based analytical devices. As an instrument-free detection method, NB allows for rapid and robust quantification of dsDNA in field settings.

Mint oil is a key source of natural flavors with wide industrial applications. Two unbalanced polyploid cultivars named Native (Mentha Spicata L) and Scotch (M. × gracilis Sole) are the main producers of spearmint type oil, which is characterized by high levels of the monoterpenes (-)-carvone and (-)-limonene. These cultivars have been the backbone of spearmint oil production for decades, while breeding and improvement remained largely unexplored, in part, due to sterility in cultivated lines. Here we show that sexual breeding at the diploid level can be leveraged to develop new varieties that produce spearmint type oil, along with the improvement of other important traits. Using field trials and GC-FID oil analysis we characterized plant materials from a public germplasm repository and identified a diploid accession that exhibited 89.5% increase in oil yield, compared to the industry standard, and another that produces spearmint type oil. Spearmint-type oil was present at high frequency in a segregating F 2 population (32/160) produced from these two accessions. Field-testing of ten of these F 2 lines showed segregation for oil yield and confirmed the production of spearmint-type oil profiles. Two of these lines combined high yield and spearmint-type oil with acceptable analytic and sensory profiles. These results demonstrate that spearmint-type oil can be produced in a diploid background with high yield potential, providing a simpler genetic system for the development of improved spearmint varieties., (© 2021. The Author(s).)

The sustainability of many crops is hindered by the lack of genomic resources and a poor understanding of natural genetic diversity. Particularly, application of modern breeding requires high-density linkage maps that are integrated into a highly contiguous reference genome. Here, we present a rapid method for deriving haplotypes and developing linkage maps, and its application to Mentha suaveolens, one of the diploid progenitors of cultivated mints. Using sequence-capture via DNA hybridization to target single nucleotide polymorphisms (SNPs), we successfully genotyped ∼5000 SNPs within the genome of >400 individuals derived from a self cross. After stringent quality control, and identification of nonredundant SNPs, 1919 informative SNPs were retained for linkage map construction. The resulting linkage map defined a total genetic space of 942.17 cM divided among 12 linkage groups, ranging from 56.32 to 122.61 cM in length. The linkage map is in good agreement with pseudomolecules from our preliminary genome assembly, proving this resource effective for the correction and validation of the reference genome. We discuss the advantages of this method for the rapid creation of linkage maps., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)

Background: Recent overdose trends are characterized by increased toxicological detection of stimulants with opioids, yet it is unclear whether these substances are mixed prior to consumption or purposefully used simultaneously., Methods: Postmortem toxicology data were collected in Marion County, Indiana, from 45 fatal overdose cases involving heroin, fentanyl, methamphetamine, or cocaine. Substances found by death scene investigators at the scene of the fatal overdose (57 samples) were tested using high-pressure liquid chromatography mass-spectrometry (LC-MS) technology. We compared toxicology and LC-MS results to understand whether substances contributing to overdose were found in combination or separately at the scene of the overdose., Results: Comparing toxicology reports with LC-MS results from substances found at the scene of overdose deaths involving opioids and stimulants reveal that deaths are largely the result of the co-use of opioids and stimulants, rather than use of stimulants combined with opioids., Conclusions: Collecting and testing physical samples from fatal overdose scenes and comparing these to post-mortem toxicology results is a new way to examine polydrug use patterns. This community overdose surveillance method can be used to improve overdose prevention and response efforts., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Gene copy number variation is frequent in plant genomes of various species, but the impact of such gene dosage variation on morphological traits is poorly understood. We used a large population of Populus carrying genomically characterized insertions and deletions across the genome to systematically assay the effect of gene dosage variation on a suite of leaf morphology traits. A systems genetics approach was used to integrate insertion and deletion locations, leaf morphology phenotypes, gene expression, and transcriptional network data, to provide an overview of how gene dosage influences morphology. Dosage-sensitive genomic regions were identified that influenced individual or pleiotropic morphological traits. We also identified cis-expression quantitative trait loci (QTL) within these dosage QTL regions, a subset of which modulated trans-expression QTL as well. Integration of data types within a gene co-expression framework identified co-expressed gene modules that are dosage sensitive, enriched for dosage expression QTL, and associated with morphological traits. Functional description of these modules linked dosage-sensitive morphological variation to specific cellular processes, as well as candidate regulatory genes. Together, these results show that gene dosage variation can influence morphological variation through complex changes in gene expression, and suggest that frequently occurring gene dosage variation has the potential to likewise influence quantitative traits in nature., (Published by Oxford University Press on behalf of American Society of Plant Biologists 2020.)

Background: Poly-4-hydroxybutyric acid (P4HB, Phasix™) is a biosynthetic polymer that degrades by hydrolysis that can be woven into a mesh for use in soft tissue reinforcement. Herein, we describe our initial experience performing complex abdominal wall repair (CAWR) utilizing component separation and P4HB mesh as onlay reinforcement., Methods: All patients undergoing CAWR between June 2014 and May 2017 were followed prospectively for postoperative outcomes. Only those patients who underwent components separation with primary repair of the fascial edges followed by onlay of P4HB mesh were included in this study., Results: 105 patients (52 male, 53 female; mean age 59.2 years, range 22-84) met inclusion criteria. Mean BMI was 29.1 (range 16-48); 52% patients had prior attempted hernia repair, most with multiple medical comorbidities (71% of patients with ASA 3 or greater). 30% of cases were not clean at the time of repair (CDC class 2 or greater). Median follow-up was 36 months (range 9-63). Eighteen patients (17%) developed a hernia recurrence ranging from 2 to 36 months postoperatively. Five (5%) patients developed a localized superficial infection treated with antibiotics, three (2.8%) required re-operation for non-healing wounds, and six (6%) patients developed seroma., Conclusions: These data demonstrate a relatively low rate of hernia recurrence, seroma, and other common complications of CAWR in a highly morbid patient population. Importantly, the rate of mesh infection was low and no patients required complete mesh removal, even when placed into a contaminated or infected surgical field.

Background: The opioid epidemic has caused an increase in overdose deaths which can be attributed to fentanyl combined with various illicit substances. Drug checking programs have been started by many harm reduction groups to provide tools for users to determine the composition of their street drugs. Immunoassay fentanyl test strips (FTS) allow users to test drugs for fentanyl by either filling a baggie or cooker with water to dissolve the sample and test. The antibody used in FTS is very selective for fentanyl at high dilutions, a characteristic of the traditional use of urine testing. These street sample preparation methods can lead to mg/mL concentrations of several potential interferents. We tested whether these concentrated samples could cause false positive results on a FTS., Methods: 20 ng/mL Rapid Response FTS were obtained from BTNX Inc. and tested against 4 different pharmaceuticals (diphenhydramine, alprazolam, gabapentin, and naloxone buprenorphine) and 3 illicit stimulants [cocaine HCl, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA)] in concentrations from 20 to 0.2 mg/mL. The FTS testing pad is divided into 2 sections: the control area and the test area. Control and test area signal intensities were quantified by ImageJ from photographs of the test strips and compared to a threshold set by fentanyl at the FTS limit of detection., Results: False positive results indicating the presence of fentanyl were obtained from samples of methamphetamine, MDMA, and diphenhydramine at concentrations at or above 1 mg/mL. Diphenhydramine is a common cutting agent in heroin. The street sample preparation protocols for FTS use suggested by many online resources would produce such concentrations of these materials. Street samples need to be diluted more significantly to avoid interference from potential cutting agents and stimulants., Conclusions: Fentanyl test strips are commercially available, successful at detecting fentanyl to the specified limit of detection and can be a valuable tool for harm reduction efforts. Users should be aware that when drugs and adulterants are in high concentrations, FTS can give a false positive result.

Background: Over 10% of antibiotics in low- and middle-income countries (LMICs) are substandard or falsified. Detection of poor-quality antibiotics via the gold standard method, high-performance liquid chromatography (HPLC), is slow and costly. Paper analytical devices (PADs) and antibiotic paper analytical devices (aPADs) have been developed as an inexpensive way to estimate antibiotic quality in LMICs., Aim: To model the impact of using a rapid screening tools, PADs/aPADs, to improve the quality of amoxicillin used for treatment of childhood pneumonia in Kenya., Methods: We developed an agent-based model, ESTEEM (Examining Screening Technologies with Economic Evaluations for Medicines), to estimate the effectiveness and cost savings of incorporating PADs and aPADs in amoxicillin quality surveillance in Kenya. We compared the current testing scenario (batches of entire samples tested by HPLC) with an expedited HPLC scenario (testing smaller batches at a time), as well as a screening scenario using PADs/aPADs to identify poor-quality amoxicillin followed by confirmatory analysis with HPLC., Results: Scenarios using PADs/aPADs or expedited HPLC yielded greater incremental benefits than the current testing scenario by annually averting 586 (90% uncertainty range (UR) 364-874) and 221 (90% UR 126-332) child pneumonia deaths, respectively. The PADs/aPADs screening scenario identified and removed poor-quality antibiotics faster than the expedited or regular HPLC scenarios, and reduced costs significantly. The PADs/aPADs scenario resulted in an incremental return of $14.9 million annually compared with the reference scenario of only using HPLC., Conclusion: This analysis shows the significant value of PADs/aPADs as a medicine quality screening and testing tool in LMICs with limited resources., Competing Interests: Declaraion of conflicting interests The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.L. is an inventor on a US patent 9354181: Analytical Devices for Detection of Low-quality Pharmaceuticals, issued in 2016. The patent is owned by the University of Notre Dame. As of Nov 12, 2020, the patent is not licensed by any entity. All other authors declare no conflicts of interest.

PRéCIS:: Micropulse cyclophotocoagulation (MPCP) lowered intraocular pressure (IOP) in the short-term but nearly half required additional intervention. Mydriasis was the most common complication (11%); 15% lost ≥3 Snellen lines of acuity; 11% had persistent complications at last follow-up., Purpose: The purpose of this study was to evaluate the efficacy and complications of MPCP in a large series of patients with all stages of glaucoma., Design: Multicenter, retrospective chart review of patients from 3 clinical sites., Participants: One hundred sixty-seven eyes of 143 patients., Methods: MPCP was performed with 2000 mW energy, 31.3% duty cycle and 2 to 4 180-degree applications of 80 seconds duration each per treatment. The procedure was considered a failure if any of the following occurred: additional IOP lowering intervention, <20% IOP reduction from baseline at the last follow-up (with or without medication), or severe complications., Results: Mean age was 71 years, 53% were female, and 53% were Asian. 60% of eyes had POAG, 63% were pseudophakic, 38% had prior glaucoma surgery, and 51% had Snellen visual acuity (VA) of 20/40 or better. Mean follow-up time was 11.9±7.8 months. Mean IOP was 21.9±8.4 mm Hg before intervention, and 17.4±7.2 mm Hg at last follow-up (P<0.0001). There was no change in mean logMAR VA (P=0.0565) but 15% lost ≥3 Snellen lines of VA. The success rate was 36.5% (61/167 eyes) at last follow-up. The probability of survival by Kaplan-Meier analysis was 82%, 71%, and 57% at 3, 6, and 12 months after the procedure, respectively. The reasons for failure were additional intervention in 47%, inadequate IOP reduction in 14%, and severe complication in 1.8%. In a multivariable Cox proportional hazard model, female sex was associated with a 56% decrease in failure rate compared with males (P<0.0001), while a unit increase in baseline IOP corresponded with a 5.7% increase in failure rate (P<0.0001). If repeat MPCP was allowed then success rate increased to 58%. There were no complications in 73% (122/167) but 11% (18/167) had persistent complications at the last follow-up and half of these 18 eyes had decrease in VA of 1 to 6 Snellen lines. Asian race (odds ratio 13.5, P=0.0131) and phakic status (odds ratio 3.1, P=0.0386) were associated with higher odds of developing mydriasis, which was the most common complication., Conclusions: MPCP lowered IOP in the short-term but nearly half required additional IOP lowering intervention. Potential complications should be discussed in detail especially when the procedure is being considered for those with good VA and early stage disease.

Despite considerable global surveillance of antimicrobial resistance (AMR), data on the global emergence of new resistance genotypes in bacteria has not been systematically compiled. We conducted a study of English-language scientific literature (2006-2017) and disease surveillance reports (1994-2017) to identify global events of novel AMR emergence (first clinical reports of unique drug-bacteria resistance combinations). We screened 24,966 abstracts and reports, ultimately identifying 1,773 novel AMR emergence events from 294 articles. Events were reported in 66 countries, with most events in the United States (152), India (129), and China (128). The most common bacteria demonstrating new resistance were Klebsiella pneumoniae (352) and Escherichia coli (218). Resistance was most common against antibiotic drugs imipenem (89 events), ciprofloxacin (85) and ceftazidime (82). We provide an open-access database of emergence events with standardized fields for bacterial species, drugs, location, and date, and we discuss guidelines and caveats for data analysis. This database may be broadly useful for understanding rates and patterns of AMR evolution, identifying global drivers and correlates, and targeting surveillance and interventions., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Mendelsohn E et al.)

Despite considerable global surveillance of antimicrobial resistance (AMR), data on the global emergence of new resistance genotypes in bacteria has not been systematically compiled. We conducted a study of English-language scientific literature (2006-2017) and ProMED-mail disease surveillance reports (1994-2017) to identify global events of novel AMR emergence (first clinical reports of unique drug-bacteria resistance combinations). We screened 24,966 abstracts and reports, ultimately identifying 1,757 novel AMR emergence events from 268 peer-reviewed studies and 26 disease surveillance reports (294 total). Events were reported in 66 countries, with most events in the United States (152), China (128), and India (127). The most common bacteria demonstrating new resistance were Klebsiella pneumoniae (344) and Escherichia coli (218). Resistance was most common against antibiotic drugs imipenem (89 events), ciprofloxacin (84) and ceftazidime (83). We provide an open-access database of emergence events with standardized fields for bacterial species, drugs, location, and date. We discuss the impact of reporting and surveillance bias on database coverage, and we suggest guidelines for data analysis. This database may be broadly useful for understanding rates and patterns of AMR evolution, identifying global drivers and correlates, and targeting surveillance and interventions., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Mendelsohn E et al.)

The distributed pharmaceutical analysis laboratory (DPAL) is a collaboration between 30 academic institutions around the world, whose goal is to determine the quality of medicines collected from partner organizations in low- and middle-income countries (LMICs). Institutions complete system suitability for a high-performance liquid chromatography (HPLC) system using United States Pharmacopeia (USP)-traceable reference standards, and are then approved to analyze batches of samples that are collected in LMICs by covert shoppers. Open Science Framework (OSF) allows DPAL participants access to resources for the program including an HPLC methodology manual, a wiki with HPLC troubleshooting information, detailed checklists and Excel templates for system suitability and sample assay, as well as steps for reporting results. Participants incorporate the DPAL program into their academic curriculum as undergraduate research or via lab activities for analytical chemistry or instrumental analysis courses. Over a thousand samples have been analyzed through DPAL in the last three years, and 168 samples with quality problems have been discovered, including falsified acetaminophen, adulterated amoxicillin-clavulanate and doxycycline, and substandard losartan. These quality problems are reported to the medicine regulatory agencies in the countries of origin and the WHO Rapid Alert System for further action. This real-world program gives students a hands-on opportunity to see the importance of analytical metrics taught in the classroom.

Portable and inexpensive analytical tools are required to monitor pharmaceutical quality in technology limited settings including low- and middle-income countries (LMICs). Whole cell yeast biosensors have the potential to help meet this need. However, most of the readouts for yeast biosensors require expensive equipment or reagents. To overcome this challenge, we have designed a yeast biosensor that produces a unique scent as a readout. This inducible scent biosensor, or "scentsor", does not require the user to administer additional reagents for reporter development and utilizes only the user's nose to be "read". In this Letter, we describe a scentsor that is responsive to the hormone estradiol (E2). The best estimate threshold (BET) for E2 detection with a panel of human volunteers ( n = 49) is 39 nM E2 (15 nM when "non-smellers" are excluded). This concentration of E2 is sensitive enough to detect levels of E2 that would be found in dosage forms. This paper provides evidence that scent has the potential for use in portable yeast biosensors as a readout, particularly for use in LMICs.

As drug overdose deaths across the United States continue to rise, there is increasing interest in field testing of illicit substances. This work discusses a paper-based analytical device (idPAD) that can run a library of 12 colorimetric tests at the same time, each detecting different chemical functional groups and materials found in illicit drugs, distractor substances, and cutting agents. The idPAD requires no electricity, costs less than $2 USD, and requires minimal training to operate. The results of the 12 tests form a color barcode which is "read" by comparison to standard images. The accuracy of the idPAD was assessed using samples of heroin, cocaine HCl, crack, and methamphetamine at concentrations of 25%-100% in a lactose matrix, as well as pure lactose. Based on 840 "reads" by three different users, the idPAD showed 95% sensitivity and 100% specificity for detecting these drugs; the most common error was mistaking cocaine HCl for crack or crack for cocaine HCl. In a second step, samples of heroin, cocaine, and methamphetamine (n = 30) and distractor substances (pharmaceuticals, cutting agents, and other illicit drugs, n = 64) were tested by two readers, yielding a sensitivity of 100% and specificity of 97%. Targeted substances were detected reliably at 55-180 μg/lane, and the idPAD was found to be stable for at least 3 months when stored at room temperature. The library approach used in the idPAD may provide the accuracy and robustness necessary for a presumptive field drug test., (© 2020 American Academy of Forensic Sciences.)

Digital therapeutics is a newly described concept in healthcare which is proposed to change patient behavior and treat medical conditions using a variety of digital technologies. However, the term is rarely defined with criteria that make it distinct from simply digitized versions of traditional therapeutics . Our objective is to describe a more valuable characteristic of digital therapeutics, which is distinct from traditional medicine or therapy: that is, the utilization of artificial intelligence and machine learning systems to monitor and predict individual patient symptom data in an adaptive clinical feedback loop via digital biomarkers to provide a precision medicine approach to healthcare. Artificial intelligence platforms can learn and predict effective interventions for individuals using a multitude of personal variables to provide a customized and more tailored therapy regimen. Digital therapeutics coupled with artificial intelligence and machine learning also allows more effective clinical observations and management at the population level for various health conditions and cohorts. This vital differentiation of digital therapeutics compared to other forms of therapeutics enables a more personalized form of healthcare that actively adapts to patients' individual clinical needs, goals, and lifestyles. Importantly, these characteristics are what needs to be emphasized to patients, physicians, and policy makers to advance the entire field of digital healthcare., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 by S. Karger AG, Basel.)