Functional Assessment of Cerebral Capillaries using Single Capillary Reporters in Ultrasound Localization Microscopy.

The brain's microvascular cerebral capillary network plays a vital role in maintaining neuronal health, yet capillary dynamics are still not well understood due to limitations in existing imaging techniques. Here, we present Single Capillary Reporters (SCaRe) for transcranial Ultrasound Localization Microscopy (ULM), a novel approach enabling non-invasive, whole-brain mapping of single capillaries and estimates of their transit-time as a neurovascular biomarker. We accomplish this first through computational Monte Carlo and ultrasound simulations of microbubbles flowing through a fully-connected capillary network. We unveil distinct capillary flow behaviors which informs methodological changes to ULM acquisitions to better capture capillaries in vivo. Subsequently, applying SCaRe-ULM in vivo, we achieve unprecedented visualization of single capillary tracks across brain regions, analysis of layer-specific capillary heterogeneous transit times (CHT), and characterization of whole microbubble trajectories from arterioles to venules. Lastly, we evaluate capillary biomarkers using injected lipopolysaccharide to induce systemic neuroinflammation and track the increase in SCaRe-ULM CHT, demonstrating the capability to detect subtle capillary functional changes. SCaRe-ULM represents a significant advance in studying microvascular dynamics, offering novel avenues for investigating capillary patterns in neurological disorders and potential diagnostic applications.

Dynamic Ultrasound Localization Microscopy Without ECG-Gating.

OBJECTIVE: Dynamic Ultrasound Localization Microscopy (DULM) has first been developed for non-invasive Pulsatility measurements in the rodent brain. DULM relies on the localization and tracking of microbubbles (MBs) injected into the bloodstream, to obtain highly resolved velocity and density cine-loops. Previous DULM techniques required ECG-gating, limiting its application to specific datasets, and increasing acquisition time. The objective of this study is to eliminate the need for ECG-gating in DULM experiments by introducing a motion-matching method for time registration. METHODS: We developed a motion-matching algorithm based on tissue Doppler that leverages the cyclic tissue motion within the brain. Tissue Doppler was estimated for each group of frames in the acquisitions, at multiple locations identified as local maxima in the skin above the skull. Subsequently, each group of frames was time-registered to a reference group by delaying it based on the maximum correlation value between their respective tissue Doppler signals. This synchronization ensured that each group of frames aligned with the brain tissue motion of the reference group, and consequently, with its cardiac cycle. As a result, velocities of MBs could be averaged to retrieve flow velocity variations over time. RESULTS: Initially validated in ECG-gated acquisitions in a rat model (n = 1), the proposed method was successfully applied in a mice model in 2D (n = 3) and in a feline model in 3D (n = 1). Performing time-registration with the proposed motion-matching method or by using ECG-gating leads to similar results. For the first time, dynamic velocity and density cine-loops were extracted without the need for any information on the animal ECG, and complex dynamic markers such as the Pulsatility index were estimated. CONCLUSION: Results suggest that DULM can be performed without external gating, enabling the use of DULM on any ULM dataset where enough MBs are detectable. Time registration by motion-matching represents a significant advancement in DULM techniques, making DULM more accessible by simplifying its experimental complexity.

Bushy-Tailed QACs: The development of multicationic quaternary ammonium compounds with a high degree of alkyl chain substitution.

Quaternary ammonium compounds have served as a first line of protection for human health as surface disinfectants and sanitizers for nearly a century. However, increasing levels of bacterial resistance have spurred the development of novel QAC architectures. In light of the observed reduction in eukaryotic cell toxicity when the alkyl chains on QACs are shorter in nature (≤10C), we prepared 47 QAC architectures that bear multiple short alkyl chains appended to up to three cationic groups, thus rendering them "bushy-tailed" multiQACs. Antibacterial activity was strong (often ~1-4 µM) in a varied set of bushy-tailed architectures, though observed therapeutic indices were not significantly improved over QAC structures bearing fewer and longer alkyl chains.

Developing a novel algorithm for comparing cluster patterns in networks on journal articles during and after COVID-19: Bibliometric analysis.

BACKGROUND: Cluster analysis is vital in bibliometrics for deciphering large sets of academic data. However, no prior research has employed a cluster-pattern algorithm to assess the similarities and differences between 2 clusters in networks. The study goals are 2-fold: to create a cluster-pattern comparison algorithm tailored for bibliometric analysis and to apply this algorithm in presenting clusters of countries, institutes, departments, authors (CIDA), and keywords on journal articles during and after COVID-19. METHODS: We analyzed 9499 and 5943 articles from the Journal of Medicine (Baltimore) during and after COVID-19 in 2020 to 2021 and 2022 to 2023, sourced from the Web of Science (WoS) Core Collection. Follower-leading clustering algorithm (FLCA) was compared to other 8 counterparts in cluster validation and effectiveness and a cluster-pattern-comparison algorithm (CPCA) was developed using the similarity coefficient, collaborative maps, and thematic maps to evaluate CIDA cluster patterns. The similarity coefficients were categorized as identical, similar, dissimilar, or different for values above 0.7, between 0.5 and 0.7, between 0.3 and 0.5, and below 0.3, respectively. RESULTS: Both stages displayed similar trends in annual publications and average citations, although these trends are decreasing. The peak publication year was 2020. Similarity coefficients of cluster patterns in these 2 stages for CIDA entities and keywords were 0.73, 0.35, 0.80, 0.02, and 0.83, respectively, suggesting the existence of identical patterns (>0.70) in countries, departments, and keywords plus, but dissimilar (<0.5) and different patterns (<0.3) found in institutes and 1st and corresponding authors, during and after COVID-19. CONCLUSIONS: This research effectively created and utilized CPCA to analyze cluster patterns in bibliometrics. It underscores notable identical patterns in country-/department-/keyword based clusters, but dissimilar and different in institute-/author- based clusters, between these 2 stages during and after COVID-19, offering a framework for future bibliographic studies to compare cluster patterns beyond just the CIDA entities, as demonstrated in this study.

Identifying China's distinctive academic fields among the top 2% of influential scientists: A bibliometric analysis using Rasch KIDMAP.

BACKGROUND: Leading scientists worldwide are recognized by their placement in the top 2% based on their career-spanning contributions, as categorized by the Science-Metrix classification. However, there has been little focus on the unique scientific fields and subfields that separate countries. Although the KIDMAP in the Rasch model has been utilized to depict student performance, its application in identifying distinctive academic areas remains unexplored. Our study uses this model to pinpoint unique research domains specific to countries based on the top 2% author data. METHODS: We sourced our data from Elsevier career-long author database updated until the end of 2022. This encompassed 168 countries, 22 scientific domains, and 174 subdomains in 2021 and 2022 (with a total of 194,983 and 204,643 researchers, respectively). Our approach was threefold: identifying unique fields, subfields, and researchers. Visualizations included scatter plots, KIDMAP, and the Impact Bam Plot (IBP). China distinctive research areas were identified using the Rasch KIDMAP. RESULTS: Key insights include the following: The US prevailing dominance in scientific domains in both 2021 and 2022. China distinct contribution in the "Enabling & Strategic Technologies" domain. China notable emphasis on the "Complementary & Alternative Medicine" subfield in 2022. Dr Phillip Low from the Mayo Clinic (US) emerged as a leading figure in the General & Internal Medicine research domain. CONCLUSIONS: Despite trailing the US in global research achievements, China showcased pronounced expertise in specific scientific areas, such as the "Complementary & Alternative Medicine" subfield in 2022, when compared to China other subfields based on the level of academic performance (-3.09 logits). Future research could benefit from incorporating KIDMAP visuals to gauge other countries' strengths in various research sectors, expanding beyond the China-centric focus in this study.

Osteoimmune-modulating and BMP-2-eluting anodised 3D printed titanium for accelerated bone regeneration.

3D printing of titanium (Ti) metal has potential to transform the field of personalised orthopaedics and dental implants. However, the impacts of controlled surface topographical features of 3D printed Ti implants on their interactions with the cellular microenvironment and incorporation of biological growth factors, which are critical in guiding the integration of implants with bone, are not well studied. In the present study, we explore the role of surface topological features of 3D printed Ti implants using an anodised titania nanotube (TiNT) surface layer in guiding their immune cell interaction and ability to deliver bioactive form of growth factors. TiNT layers with precisely controlled pore diameter (between 21and 130 nm) were anodically grown on 3D printed Ti surfaces to impart a nano-micro rough topology. Immune biomarker profiles at gene and protein levels show that anodised 3D Ti surfaces with smaller pores resulted in classical activation of macrophages (M1-like), while larger pores (i.e., >100 nm) promoted alternate activation of macrophages (M2-like). The in vitro bone mineralisation studies using the conditioned media from the immunomodulatory studies elucidate a clear impact of pore diameter on bone mineralisation. The tubular structure of TiNTs was utilised as a container to incorporate recombinant human bone morphogenetic protein-2 (BMP-2) in the presence of various sugar and polymeric cryoprotectants. Sucrose offered the most sustainable release of preserved BMP-2 from TiNTs. Downstream effects of released BMP-2 on macrophages as well as bone mineralisation were assessed showing bioactivity retention of the released rhBMP-2. Overall, the TiNT surface topography in combination with controlled, sustained, and local release of bioactive growth factors can potentially enhance the osseointegration outcomes of custom 3D printed Ti implants in the clinic.

Differences in Opioid-Related Deaths in the Appalachian Region in 2018-2021 by State and Rural-Urban County Classification.

Introduction The rapid increase in opioid-related deaths since the early 2000s is a major US public health concern. This crisis has transitioned from pharmaceuticals to illicit synthetic opioids and street mixtures. This epidemic has significantly impacted the Appalachian region. This study investigated opioid-related death rates among the Appalachian states, focusing on death rates among urban, suburban, and rural counties. Methods Opioid-related death data from 2018-2021 for the 13 states that make up the Appalachian region were collected using the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database. Opioid analgesic overdose deaths were defined using ICD-10 codes X40-X44, X60-X64, and Y10-Y14, where an opioid analgesic was also coded (T40.2-T40.4). US census data was used to calculate opioid-related death rates by population. Counties were classified as urban, suburban, and rural using the 2013 Rural-Urban Continuum Codes from the US Department of Agriculture. The data were descriptively broken down and reported as either percentages or means. Results Of the opioid-related deaths between 2018 and 2021, 498 counties were identified in the 13 Appalachian states as having reported at least 10 opioid-related deaths per year. Among these counties, 337 (67.7%) were classified as urban/metropolitan, 138 (27.7%) as suburban, and 23 (4.62%) as rural. Overall, mean opioid-related deaths by populations per 1000 among all counties were 0.24 in 2018, 0.24 in 2019, 0.33 in 2020, and 0.38 in 2021. For urban/metropolitan counties, opioid-related deaths per 1000 gradually increased from 0.23 in 2018 to 0.35 in 2021. For suburban counties, the mean opioid-related deaths per 1000 increased from 0.25 in 2018 to 0.43 in 2021. For rural counties, the mean opioid-related deaths per 1000 increased from 0.43 in 2018 to 0.62 in 2021. Conclusion Opioid-related deaths, on average and by population, have risen steadily in the Appalachian region from 2018-2021 across all geographic areas (urban/metropolitan, suburban, rural). Rural counties consistently showed the highest opioid-related deaths per population compared to urban/metropolitan and suburban areas. Addressing social determinants of health such as income level, education level, healthcare access, and community-based interventions is crucial in combating this issue. Community and health system interventions must be implemented to combat the disproportionately high rate of opioid prescribing in the Appalachian region.

Food Insecurity and Psychological Distress Amongst Parenting Women in Treatment for Opioid Use: Identifying Barriers to Nutritional Equity and Implications for Future Intervention Research.

PURPOSE: To describe the prevalence of food insecurity among pregnant and parenting women with opioid use disorder (OUD), its association with psychosocial health, and their experience with the Special Supplemental Nutrition Program for Women Infant Child (WIC) program. DESIGN: This cross-sectional study collected survey data through REDCAP. SETTING: The study was conducted at a single, urban, opioid treatment program. SUBJECTS: A total of 91 female participants (≥18 years of age and receiving OUD treatment services) were approached about the study and all consented. MEASURES: Measures included: US Household Short Form Food Security Survey, Patient Health Questionnaire 4(PHQ4), Perceived Stress Scale (PSS), and a demographics and food behavior survey. ANALYSIS: Descriptive analyses (frequency, means) described data and Chi-Square, Fischer's exact, t-tests were used to compare data between food security groups. RESULTS: Participants were on average 34 years old, Caucasian (68%), and non-Hispanic (87%). Most reported low (32%) to very low (33%) food security. Pearson correlation analyses indicate a strong positive linear relationship between Food Security Score and PHQ4 Total (P = .0002), PHQ4 Depression (P = .0003), PHQ4 Anxiety (P = .0009), and PSS Total (P < .0001). Only 38% felt the foods available in WIC supported their breastfeeding. Limitations include a single site and recall bias. CONCLUSIONS: Significant nutritional inequity in families affected by maternal substance use exists, with potential for adverse maternal and child development related implications.

Double BAC and Triple BAC: A Systematic Analysis of the Disinfectant Properties of Multicationic Derivatives of Benzalkonium Chloride (BAC).

Over the past decades, the shortcomings of established quaternary ammonium disinfectants have become increasingly clear. Although benzalkonium chloride (BAC) has enjoyed nearly a century of significantly protecting human health through surgical preparation, home use, and industrial applications, increasing levels of bacterial resistance have rendered it decreasingly effective. In light of more recent efforts that have informed us that multicationic amphiphilic disinfectants show both higher activity as well as diminished susceptibility to resistance, we embarked on the preparation of 27 multicationic QACs in an attempt to clearly document structure-activity relationships of next-generation BAC structures. Select biscationic BAC derivatives demonstrate single-digit micromolar activity against all seven bacteria tested and MIC values of 2- to 32-fold better than BAC. Particularly notable is the improvement against the more concerning bacteria like Acinetobacter baumannii and Pseudomonas aeruginosa, which pose a modern threat to legacy disinfectants like BAC. With simple synthetic paths, consistently high yields (averaging ∼80 %), and strong biological activity, potent structures with clear SAR trends and strong therapeutic indices have been established.

Recommendations and guidelines for the diagnosis and management of Coronavirus Disease-19 (COVID-19) associated bacterial and fungal infections in Taiwan.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

COVID-19 associated mold infections: Review of COVID-19 associated pulmonary aspergillosis and mucormycosis.

COVID-19-associated mold infection (CAMI) is defined as development of mold infections in COVID-19 patients. Co-pathogenesis of viral and fungal infections include the disruption of tissue barrier following SARS CoV-2 infection with the damage in the alveolar space, respiratory epithelium and endothelium injury and overwhelming inflammation and immune dysregulation during severe COVID-19. Other predisposing risk factors permissive to fungal infections during COVID-19 include the administration of immune modulators such as corticosteroids and IL-6 antagonist. COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) is increasingly reported during the COVID-19 pandemic. CAPA usually developed within the first month of COVID infection, and CAM frequently arose 10-15 days post diagnosis of COVID-19. Diagnosis is challenging and often indistinguishable during the cytokine storm in COVID-19, and several diagnostic criteria have been proposed. Development of CAPA and CAM is associated with a high mortality despiteappropriate anti-mold therapy. Both isavuconazole and amphotericin B can be used for treatment of CAPA and CAM; voriconazole is the primary agent for CAPA and posaconazole is an alternative for CAM. Aggressive surgery is recommended for CAM to improve patient survival. A high index of suspicion and timely and appropriate treatment is crucial to improve patient outcome.

Association between Antimicrobial Consumption and the Prevalence of Nosocomial Carbapenem-Resistant Escherichia coli and Klebsiella pneumoniae in a Tertiary Hospital in Northern Taiwan.

Carbapenem-resistant Enterobacteriales has become a threat in Taiwan. This is the first local study focusing on the association between carbapenem-resistant Enterobacteriales and antimicrobial consumption. From January 2012 to December 2020, data were collected in a tertiary care hospital in Taipei, Taiwan. Antimicrobial consumption was estimated by the defined daily dose/1,000 patient-days. During the same period, the prevalence of carbapenem-resistant Escherichia coli (CREC) and carbapenem-resistant Klebsiella pneumoniae (CRKP) were collected through routine surveillance data. The following retrospective analyses were conducted: 1) analysis of antimicrobial consumption over time, (2) analysis and forecast of CREC and CRKP prevalence over time, and 3) analysis of correlation between antimicrobial consumption and the prevalence of CREC and CRKP. The consumption of piperacillin/tazobactam (ß = 0.615), fluoroquinolones (ß = 0.856), meropenem (ß = 0.819), and doripenem (ß = 0.891) increased during the observation period (P < 0.001), and the consumption of aminoglycosides (ß = -0.852) and imipenem/cilastatin (ß = -0.851) decreased (P < 0.001). The prevalence of CRKP rose over time (ß = 0.522, P = 0.001) and correlated positively with the consumption of fluoroquinolones, levofloxacin, penicillin/ß-lactamase inhibitor, piperacillin/tazobactam, meropenem, and doripenem (P < 0.05). The prevalence of CRKP and CREC both correlated negatively with consumption of aminoglycosides (P < 0.01). The prevalence of CRKP in our hospital increased as the forecast predicted based on an autoregressive integrated moving average model. This study provides alarming messages for members participating in antimicrobial stewardship programs, including the increasing prevalence of CRKP, the increasing consumption of broad-spectrum antibiotics, and the positive correlation between them.

Clinical and molecular characteristics and risk factors for patients acquiring carbapenemase-producing and non-carbapenemase-producing carbapenem-nonsusceptible-Enterobacterales bacteremia.

BACKGROUND/PURPOSE: Carbapenem-nonsusceptible Enterobacterales (CNSE) are a growing global threat. Carbapenemases are often produced by plasmids, which allow rapid transmission. This study aimed to investigate (1) the bacterial type (2) resistant genes (3) antimicrobial susceptibility and (4) risk factors for acquisition of carbapenemase-producing carbapenem-nonsusceptible Enterobacterales (CP-CNSE) and non-carbapenemase-producing carbapenem-nonsusceptible Enterobacterales (non-CP-CNSE) bacteremia. METHODS: There were a total of 113 isolates of Enterobacterales from 2013 to 2018. After excluding nonblood isolates and including only one sample from each patient, 99 isolates were analyzed and the medical charts of these patients were reviewed. Carbapenemase genes, ß-lactamase genes and antimicrobial susceptibility of the isolates were determined. Multilocus sequence typing (MLST) was performed on CP-CNSE isolates. RESULTS: CP-CNSE carried more blaSHV (P = 0.004) and were more resistant to imipenem than non-CP-CNSE (P < 0.001). In the univariate analyses, we found that CP-CNSE bloodstream infection was associated with patient <65 years of age (odds ratio, 3.90; 95% confidence interval [CI], 1.16 to 13.10; P = 0.027), mechanical ventilation at the time of bloodstream infection (BSI) (odds ratio, 3.85; 95% CI, 1.16-12.78; P = 0.028) and exposure to piperacillin/tazobactam (odds ratio, 3.96; 95% CI, 1.09-14.38; P = 0.037). However, on multivariate analyses, no independent predictor for CP-CNSE was identified in this study. CONCLUSION: CP-CNSE carried more blaSHV and were more resistant to imipenem when compared to non-CP-CNSE. No independent predictor for CP-CNSE was identified after multivariate analysis. This is the first study conducted in Taiwan comparing risk factors between CP-CNSE and non-CP-CNSE from both clinical and molecular aspects.

Bisphosphate nucleotidase 2 (BPNT2), a molecular target of lithium, regulates chondroitin sulfation patterns in the cerebral cortex and hippocampus.

Bisphosphate nucleotidase 2 (BPNT2) is a member of a family of phosphatases that are directly inhibited by lithium, the first-line medication for bipolar disorder. BPNT2 is localized to the Golgi, where it metabolizes the by-products of glycosaminoglycan sulfation reactions. BPNT2-knockout mice exhibit impairments in total-body chondroitin-4-sulfation which lead to abnormal skeletal development (chondrodysplasia). These mice die in the perinatal period, which has previously prevented the investigation of BPNT2 in the adult nervous system. Previous work has demonstrated the importance of chondroitin sulfation in the brain, as chondroitin-4-sulfate is a major component of perineuronal nets (PNNs), a specialized neuronal extracellular matrix which mediates synaptic plasticity and regulates certain behaviors. We hypothesized that the loss of BPNT2 in the nervous system would decrease chondroitin-4-sulfation and PNNs in the brain, which would coincide with behavioral abnormalities. We used Cre-lox breeding to knockout Bpnt2 specifically in the nervous system using Bpnt2 floxed (fl/fl) animals and a Nestin-driven Cre recombinase. These mice are viable into adulthood, and do not display gross physical abnormalities. We identified decreases in total glycosaminoglycan sulfation across selected brain regions, and specifically show decreases in chondroitin-4-sulfation which correspond with increases in chondroitin-6-sulfation. Interestingly, these changes were not correlated with gross alterations in PNNs. We also subjected these mice to a selection of neurobehavioral assessments and did not identify significant behavioral abnormalities. In summary, this work demonstrates that BPNT2, a known target of lithium, is important for glycosaminoglycan sulfation in the brain, suggesting that lithium-mediated inhibition of BPNT2 in the nervous system warrants further investigation.

Sulfation of glycosaminoglycans depends on the catalytic activity of lithium-inhibited phosphatase BPNT2 in vitro.

Golgi-resident bisphosphate nucleotidase 2 (BPNT2) is a member of a family of magnesium-dependent, lithium-inhibited phosphatases that share a three-dimensional structural motif that directly coordinates metal binding to effect phosphate hydrolysis. BPNT2 catalyzes the breakdown of 3'-phosphoadenosine-5'-phosphate, a by-product of glycosaminoglycan (GAG) sulfation. KO of BPNT2 in mice leads to skeletal abnormalities because of impaired GAG sulfation, especially chondroitin-4-sulfation, which is critical for proper extracellular matrix development. Mutations in BPNT2 have also been found to underlie a chondrodysplastic disorder in humans. The precise mechanism by which the loss of BPNT2 impairs sulfation remains unclear. Here, we used mouse embryonic fibroblasts (MEFs) to test the hypothesis that the catalytic activity of BPNT2 is required for GAG sulfation in vitro. We show that a catalytic-dead Bpnt2 construct (D108A) does not rescue impairments in intracellular or secreted sulfated GAGs, including decreased chondroitin-4-sulfate, present in Bpnt2-KO MEFs. We also demonstrate that missense mutations in Bpnt2 adjacent to the catalytic site, which are known to cause chondrodysplasia in humans, recapitulate defects in overall GAG sulfation and chondroitin-4-sulfation in MEF cultures. We further show that treatment of MEFs with lithium (a common psychotropic medication) inhibits GAG sulfation and that this effect depends on the presence of BPNT2. Taken together, this work demonstrates that the catalytic activity of an enzyme potently inhibited by lithium can modulate GAG sulfation and therefore extracellular matrix composition, revealing new insights into lithium pharmacology.

Trends in hydrocodone combination product exposures reported to California Poison Control System (CPCS) following DEA rescheduling.

CONTEXT: On October 6, 2014, the United States Drug Enforcement Administration (DEA) implemented a regulatory change for hydrocodone combination products (HCPs), moving them from Schedule III to II, in an effort to decrease drug overdoses. Existing research suggests this regulatory action reduced HCP prescribing and dispensing; however, there is limited research assessing its possible effects on overdoses and accidental exposures. OBJECTIVE: To analyze the changes in opioid exposures reported to the California Poison Control System (CPCS) before and after DEA rescheduling of HCPs. METHODS: We collected monthly exposure data reported to CPCS from 2012 to 2019 and conducted interrupted time series analyses to assess changes in exposures after rescheduling for HCPs, tramadol, oxycodone, morphine, codeine, fentanyl, and heroin. Additional analyses were done to assess any changes in exposures resulting in severe outcomes (moderate or major health effects). For HCPs, we also conducted logistic regressions to identify characteristics of exposures resulting in severe outcomes before and after rescheduling. RESULTS: Overall monthly opioid exposures reported to CPCS decreased after DEA rescheduling of HCPs. These decreases were significant for HCP, tramadol, and morphine (p < 0.001). Exposures significantly increased for heroin and fentanyl (p < 0.001). There were no significant changes in the share of severe outcomes attributed to HCP exposures after rescheduling. DISCUSSION: The DEA rescheduling of HCPs was associated with a significant decrease in HCP exposures and prescription opioid exposures overall, but was associated with increased fentanyl and heroin exposures. While other initiatives may have contributed to this decrease, our findings suggest that rescheduling may be a useful regulatory strategy to reduce drug exposures. CONCLUSION: DEA rescheduling of HCPs was associated with a significant reduction in prescription opioid exposures, suggesting that rescheduling high-risk drugs may be an effective strategy to improve public health.

Removal of massive subretinal organized blood clot with fragmatome.

The purpose of the study was to describe using fragmatome in removing subretinal organized blood clot in eyes of age-related macular degeneration and massive subretinal hemorrhage. This study was an interventional, consecutive case series. Patients with massive subretinal hemorrhage with total or subtotal retinal detachment from age-related macular degeneration and organized subretinal blood clot were managed by creating large retinectomy. The less organized blood was removed with vitrector. The subretinal organized blood clot was removed by fragmatome. The retina was reattached with perfluorocarbon liquid, and laser was applied at the margin of retinectomy. Silicon oil was infused at the end of surgery. All patients had subretinal blood totally or subtotally removed. The organized blood clot, which was difficult to be removed by vitrector was easily and efficiently removed by fragmatome. Visual acuity improved in all eyes, and retina was well attached under silicon oil. Fragmatome offers a more efficient way in removing organized blood clot, which will much shorten the duration of operation.

Is the rule of halves still relevant today? A cross-sectional analysis of hypertension detection, treatment and control in an urban community.

AIMS: To estimate percentages of patients with undiagnosed hypertension, diagnosed untreated hypertension and diagnosed, treated and uncontrolled hypertension and to identify sociodemographic factors for diagnosed, uncontrolled hypertension and not having a blood pressure (BP) reading recorded. METHODS: Data from 320 094 patients aged 18 to less than 80 years from general practices in inner London was analysed using both last recorded BP (blood pressure) and mean BP. Logistic regression models identified factors associated with uncontrolled hypertension and no recorded BP. RESULTS: Twenty-nine thousand, seven hundred and nineteen (9.3%) patients had a recorded diagnosis of hypertension. On the basis of analysis of the last BP value, 14.2% (n = 4207) were untreated and 46.3% (n = 13 749) had uncontrolled hypertension; 10.0% (n = 28 274) without a prior hypertension diagnosis had undiagnosed hypertension. Corresponding values based on mean BP analysis were 8.9% (n = 2367) untreated, 51.5% (n = 13 734) uncontrolled; 4.1% (n = 11 446) undiagnosed. 17.5% (n = 55 960) had no recorded BP value.Black ethnicity was a predictor of uncontrolled hypertension: compared with the White British population, the adjusted odds ratio (AOR) for the Black African population was 1.39 (95% CI: 1.25-1.53) and for the Black Caribbean was 1.31 (95% CI: 1.19-1.45). The White Other group were most likely to have no record of BP measurement (AOR: 1.52; 95% CI: 1.47-1.57); conversely, unrecorded BP was less likely in the Black African (AOR: 0.79; CI: 0.74-0.83) and Black Caribbean (AOR: 0.71; CI: 0.66-0.76) groups, relative to the White British population. CONCLUSION: In an inner-city, multiethnic population, the 'rule of halves' still broadly applies to the diagnosis and control of hypertension, although only a small proportion were untreated.

Detection in whole blood of autoantibodies for the diagnosis of connective tissue diseases in near patient testing condition.

A novel technology, photonic ring immunoassay (PRI), for detecting 12 autoantibodies simultaneously in whole blood in less than 15 minutes was evaluated by comparing results from 235 clinically diagnosed patients with standard laboratory tests. The overall agreement was greater than 91% for 10 of the 12 assays, with positive percent agreement greater than 89% for 9 of the assays and negative percent agreement greater than 91% for 10 of them. Thus, the clinical sensitivities and specificities were similar for the 2 methods. In addition, 199 normal blood donors were tested on the ANA 12 PRI, yielding specificities greater than 97.5% for all assays. This proof of concept study shows that this new system is suitable for point of care testing for clinically useful autoantibodies, allowing the doctor to have test results in minutes rather than days.

Citrobacter freundii bacteremia: Risk factors of mortality and prevalence of resistance genes.

BACKGROUND/PURPOSE: Multidrug-resistant strains of Citrobacter have emerged, which carry Amp-C ß-lactamase (Amp-C), broad-spectrum ß-lactamase, extended-spectrum ß-lactamase (ESBL), and other resistance mechanisms. These strains are associated with a higher rate of in-hospital mortality. The object of this study is to determine the mortality risk factors, susceptibility pattern to antibiotics, and prevalence of resistance genes in patients with Citrobacter freundii bacteremia. METHODS: From January 2009 to December 2014, blood isolates of C. freundii were collected in MacKay Memorial Hospital, Taipei, Taiwan. PCR technique and sequencing were performed for resistance genes. Pulsed-field gel electrophoresis (PFGE) was done using XbaI restriction enzyme. The clinical characteristics and risk factors for mortality are demonstrated. RESULTS: The 36 blood isolates of C. freundii belonged to 32 different PFGE pulsotypes, and 15 isolates (41.7%) were polymicrobial. The most common source of infection was intra-abdominal origin (61.1%), followed by unknown sources (22.2%), the urinary tract (8.3%), intravascular catheter (5.6%), and soft tissue (2.8%). High degree of antibiotic resistance was noted for cefazolin (100%), cefoxitin (97.2%), and cefuroxime (66.7%). The blaTEM-1 resistance gene was present in 16.7% isolates. 72.2% isolates carried blaAmpC and 5.6% isolates carried ESBL genes (blaSHV-12 or blaCTX-M-15). Multivariate analysis indicated that the independent risk factor for 28-day mortality was carrying the blaTEM-1 resistance gene. CONCLUSION: For patients with C. freundii bacteremia, carrying the blaTEM-1 resistance gene was an independent risk factor for 28-day mortality. Carbapenems, fourth-generation cephalosporins, amikacin, and quinolones are still reliable agents for drug-resistant strains.