Performance of International Classification of Disease-10 codes in detecting emergency department patients with opioid misuse.

BACKGROUND AND AIMS: Accurate case discovery is critical for disease surveillance, resource allocation and research. International Classification of Disease (ICD) diagnosis codes are commonly used for this purpose. We aimed to determine the sensitivity, specificity and positive predictive value (PPV) of ICD-10 codes for opioid misuse case discovery in the emergency department (ED) setting. DESIGN AND SETTING: Retrospective cohort study of ED encounters from January 2018 to December 2020 at an urban academic hospital in the United States. A sample of ED encounters enriched for opioid misuse was developed by oversampling ED encounters with positive urine opiate screens or pre-existing opioid-related diagnosis codes in addition to other opioid misuse risk factors. CASES: A total of 1200 randomly selected encounters were annotated by research staff for the presence of opioid misuse within health record documentation using a 5-point scale for likelihood of opioid misuse and dichotomized into cohorts of opioid misuse and no opioid misuse. MEASUREMENTS: Using manual annotation as ground truth, the sensitivity and specificity of ICD-10 codes entered during the encounter were determined with PPV adjusted for oversampled data. Metrics were also determined by disposition subgroup: discharged home or admitted. FINDINGS: There were 541 encounters annotated as opioid misuse and 617 with no opioid misuse. The majority were males (54.4%), average age was 47 years and 68.5% were discharged directly from the ED. The sensitivity of ICD-10 codes was 0.56 (95% confidence interval [CI], 0.51-0.60), specificity 0.99 (95% CI, 0.97-0.99) and adjusted PPV 0.78 (95% CI, 0.65-0.92). The sensitivity was higher for patients discharged from the ED (0.65; 95% CI, 0.60-0.69) than those admitted (0.31; 95% CI, 0.24-0.39). CONCLUSIONS: International Classification of Disease-10 codes appear to have low sensitivity but high specificity and positive predictive value in detecting opioid misuse among emergency department patients in the United States.

Objective Sleep Duration and All-Cause Mortality Among People With Obstructive Sleep Apnea.

Importance: The association between sleep duration and all-cause mortality remains unclear among people with obstructive sleep apnea (OSA). Objective: To explore whether there is an association between sleep duration and all-cause mortality among people with OSA. Design, Setting, and Participants: This cohort study investigated participants with OSA from the Sleep Heart Health Study (SHHS) in which participants were enrolled between 1995 and 1998 with questionnaires and polysomnography (PSG) assessment and followed up for a median of 11.8 years. SHHS was a multicenter community-based study; 2574 participants with OSA defined by apnea-hypopnea index (AHI) greater than or equal to 15 from SHHS were found; all of them had all-cause mortality data and were included in the study. Data were analyzed from November 2022 to October 2023. Exposures: Participants were divided into 4 groups with objective sleep duration of (1) at least 7 hours, (2) 6 to less than 7 hours, (3) 5 to less than 6 hours, and (4) less than 5 hours, which was determined by total sleep time on PSG at baseline. Main Outcomes and Measures: All-cause mortality was defined as deaths from any cause and its risk was compared among 4 OSA groups using Cox regression models. Results: A total of 2574 participants with OSA were included (1628 [63.2%] men and 946 [36.8%] women; mean [SD] age, 65.4 [10.7] years; 211 [8.2%] Black, 2230 [86.6%] White, 133 [5.2%] other race). Overall, 688 all-cause deaths were observed in participants. Compared with the group sleeping at least 7 hours, the groups sleeping 6 to less than 7 hours (hazard ratio [HR], 1.53 [95% CI, 1.13-2.07]), 5 to less than 6 hours (HR, 1.40 [95% CI, 1.03-1.90]), and less than 5 hours (HR, 1.64 [95% CI, 1.20-2.24]) had significantly higher risks of all-cause mortality independent of AHI. Sensitivity analyses were performed among participants with available data of positive airway pressure treatment during follow-up and the finding was mostly consistent, albeit the HR for the group of 5 to less than 6 hours was not statistically significant. Conclusions and Relevance: In this cohort study of 2574 participants with OSA, those with shorter objective sleep duration had higher risk of all-cause mortality independent of AHI compared with those sleeping at least 7 hours. Further studies would be needed to investigate health benefits of extending sleep length among people with OSA with short sleep duration.

Analysis of Airway Thickening and Serum Cytokines in COPD Patients with Frequent Exacerbations: A Heart of the Matter.

Background: Differences in lung function for Chronic Obstructive Pulmonary Disease (COPD) cause bias in the findings when identifying frequent exacerbator phenotype-related causes. The aim of this study was to determine whether computed tomographic (CT) biomarkers and circulating inflammatory biomarkers were associated with the COPD frequent exacerbator phenotype after eliminating the differences in lung function between a frequent exacerbator (FE) group and a non-frequent exacerbator (NFE) group. Methods: A total of 212 patients with stable COPD were divided into a FE group (n=106) and a NFE group (n=106) according to their exacerbation history. These patients were assessed by spirometry, quantitative CT measurements and blood sample measurements during their stable phase. Univariate and multivariate logistic regression were used to assess the association between airway thickening or serum cytokines and the COPD frequent exacerbator phenotype. Receiver operating characteristic (ROC) curves were calculated for Pi10, WA%, IL-1ß and IL-4 to identify frequent exacerbators. Results: Compared with NFE group, FE group had a greater inner perimeter wall thickness of a 10 mm diameter bronchiole (Pi10), a greater airway wall area percentage (WA%) and higher concentrations of IL-1ß and IL-4 (p<0.001). After adjusting for sex, age, BMI, FEV1%pred and smoking pack-years, Pi10, WA%, IL-ß and IL-4 were independently associated with a frequent exacerbator phenotype (p<0.001). Additionally, there was an increase in the odds ratio of the frequent exacerbator phenotype with increasing Pi10, WA%, IL-4, and IL-1ß (p for trend <0.001). The ROC curve demonstrated that IL-1ß had a significantly larger calculated area under the curve (p < 0.05) than Pi10, WA% and IL-4. Conclusion: Pi10, WA%, IL-4, and IL-1ß were independently associated with the frequent exacerbator phenotype among patients with stable COPD, suggesting that chronic airway and systemic inflammation contribute to the frequent exacerbator phenotype. Trial Registration: This trial was registered in Chinese Clinical Trial Registry (https://www.chictr.org.cn). Its registration number is ChiCTR2000038700, and date of registration is September 29, 2020.

The complete mitochondrial genome of Batocera rubus Linnaeus, 1785 (Coleoptera: Cerambycidae).

Batocera rubus severely impacts on the health of banyan trees. In this study, the whole mitochondrial genome for B. rubus was found to be 16,158 bp with a GC content of 23.9%, including 39.1% A, 37.0% T, 14.8% C, and 9.1% G. This genome contains 13 protein-coding genes, 22 tRNAs, and two rRNAs. Phylogenetic analysis revealed that B. rubus is close to Batocera celebiana. This study provides valuable information that can help improve the classification and phylogeny of B. rubus and facilitate further evolutionary studies.

Mitochondrial cytochrome P450 1B1 is involved in pregnenolone synthesis in human brain cells.

Neurosteroids, which are steroids synthesized by the nervous system, can exert neuromodulatory and neuroprotective effects via genomic and nongenomic pathways. The neurosteroid and major steroid precursor pregnenolone has therapeutical potential in various diseases, such as psychiatric and pain disorders, and may play important roles in myelination, neuroinflammation, neurotransmission, and neuroplasticity. Although pregnenolone is synthesized by CYP11A1 in peripheral steroidogenic organs, our recent study showed that pregnenolone must be synthesized by another mitochondrial cytochrome P450 (CYP450) enzyme other than CYP11A1 in human glial cells. Therefore, we sought to identify the CYP450 responsible for pregnenolone production in the human brain. Upon screening for CYP450s expressed in the human brain that have mitochondrial localization, we identified three enzyme candidates: CYP27A1, CYP1A1, and CYP1B1. We found that inhibition of CYP27A1 through inhibitors and siRNA knockdown did not negatively affect pregnenolone synthesis in human glial cells. Meanwhile, treatment of human glial cells with CYP1A1/CYP1B1 inhibitors significantly reduced pregnenolone production in the presence of 22(R)-hydroxycholesterol. We performed siRNA knockdown of CYP1A1 or CYP1B1 in human glial cells and found that only CYP1B1 knockdown significantly decreased pregnenolone production. Furthermore, overexpression of mitochondria-targeted CYP1B1 significantly increased pregnenolone production under basal conditions and in the presence of hydroxycholesterols and low-density lipoprotein. Inhibition of CYP1A1 and/or CYP1B1 via inhibitors or siRNA knockdown did not significantly reduce pregnenolone synthesis in human adrenal cortical cells, implying that CYP1B1 is not a major pregnenolone-producing enzyme in the periphery. These data suggest that mitochondrial CYP1B1 is involved in pregnenolone synthesis in human glial cells.

Translocator protein in the rise and fall of central nervous system neurons.

Translocator protein (TSPO), a 18 kDa protein found in the outer mitochondrial membrane, has historically been associated with the transport of cholesterol in highly steroidogenic tissues though it is found in all cells throughout the mammalian body. TSPO has also been associated with molecular transport, oxidative stress, apoptosis, and energy metabolism. TSPO levels are typically low in the central nervous system (CNS), but a significant upregulation is observed in activated microglia during neuroinflammation. However, there are also a few specific regions that have been reported to have higher TSPO levels than the rest of the brain under normal conditions. These include the dentate gyrus of the hippocampus, the olfactory bulb, the subventricular zone, the choroid plexus, and the cerebellum. These areas are also all associated with adult neurogenesis, yet there is no explanation of TSPO's function in these cells. Current studies have investigated the role of TSPO in microglia during neuron degeneration, but TSPO's role in the rest of the neuron lifecycle remains to be elucidated. This review aims to discuss the known functions of TSPO and its potential role in the lifecycle of neurons within the CNS.

The complete mitochondrial genome of Tenebroides mauritanicus Linnaeus, 1758 (Coleoptera: Trogossitidae).

Tenebroides mauritanicus Linnaeus, 1758 (Coleoptera: Trogossitidae) is a storage pest that feeds mainly on soybean and corn. In this study, we sequenced the entire mitochondrial genome of Tenebroides mauritanicus (GenBank accession number: OM161967). The total length of the mitochondrial genome is 15,696 bp, GC content is 29.65%, and the contents of each base is 38.37% A, 18.35% C, 11.30% G and 31.98% T, respectively. The genome encodes 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs) and 2 ribosomal RNA genes (rRNAs). Phylogenetic analysis showed that Tenebroides mauritanicus is clustered with Byturus ochraceus. This study provides a piece of valuable genomic information for the population genetics, phylogeny, and molecular taxonomy of Tenebroides mauritanicus.

Noninvasive electrophysiological imaging identifies 4D uterine peristalsis patterns in subjects with normal menstrual cycles and patients with endometriosis.

Throughout the menstrual cycle, spontaneous mild contractions in the inner layer of the uterine smooth muscle cause uterine peristalsis, which plays a critical role in normal menstruation and fertility. Disruptions in peristalsis patterns may occur in women experiencing subfertility, abnormal uterine bleeding, ovulatory dysfunction, endometriosis, and other disorders. However, current tools to measure uterine peristalsis in humans have limitations that hamper their research or clinical utilities. Here, we describe an electrophysiological imaging system to noninvasively quantify the four-dimensional (4D) electrical activation pattern during human uterine peristalsis with high spatial and temporal resolution and coverage. We longitudinally imaged 4968 uterine peristalses in 17 participants with normal gynecologic anatomy and physiology over 34 hours and 679 peristalses in 5 participants with endometriosis over 12.5 hours throughout the menstrual cycle. Our data provide quantitative evidence that uterine peristalsis changes in frequency, direction, duration, magnitude, and power throughout the menstrual cycle and is disrupted in endometriosis patients. Moreover, our data suggest that disrupted uterine peristalsis contributes to excess retrograde menstruation and infertility in patients with endometriosis and potentially contributes to infertility in this cohort.

Noninvasive electromyometrial imaging of human uterine maturation during term labor.

Electromyometrial imaging (EMMI) was recently developed to image the three-dimensional (3D) uterine electrical activation during contractions noninvasively and accurately in sheep. Herein we describe the development and application of a human EMMI system to image and evaluate 3D uterine electrical activation patterns at high spatial and temporal resolution during human term labor. We demonstrate the successful integration of the human EMMI system during subjects' clinical visits to generate noninvasively the uterine surface electrical potential maps, electrograms, and activation sequence through an inverse solution using up to 192 electrodes distributed around the abdomen surface. Quantitative indices, including the uterine activation curve, are developed and defined to characterize uterine surface contraction patterns. We thus show that the human EMMI system can provide detailed 3D images and quantification of uterine contractions as well as novel insights into the role of human uterine maturation during labor progression.

Polysaccharides from Enteromorpha prolifera alleviate hypercholesterolemia via modulating the gut microbiota and bile acid metabolism.

Polysaccharides from Enteromorpha prolifera (EP) possess multiple biological activities, while the role of EP in hypercholesterolemia and its relationship with the gut microbiota have not been elucidated. To address this issue, fifty male C57BL/6J mice were randomly subjected to a basal diet and a high-fat and high-cholesterol diet, and 3 treatment groups were fed an HFHC diet supplemented with different dosages of EP (100, 200 and 300 mg kg-1 day-1) for 12 weeks. Here we show that EP intervention lowered serum concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and inhibited hepatic cholesterol deposition. EP intervention also upregulated the gene expression related to the hepatic cholesterol uptake and bile acid synthetic pathway. Apart from that, EP altered the gut microbiota, pre-dominantly increasing microbes associated with bile acid metabolism, such as norank_f_ Muribaculaceae. Moreover, bile acid profile analysis revealed that EP could alter the fecal bile acid profile and reduce fecal conjugated bile acids. Further correlation analysis indicated the negative correlation of Bacteroides, norank_f_ Muribaculaceae and Ileibacterium abundance with the levels of fecal conjugated bile acids and serum TC and LDL-C, while the abundance of Proteobacteria and Lachnoclosteridium showed a positive association with conjugated bile acids and serum TC. To sum up, the above findings revealed that EP may alleviate hypercholesterolemia and regulate cholesterol metabolism in ways that promote a favorable fecal microbiota composition and modulate bile acid metabolism.

Breast microecology improvement using probiotics following needle aspiration in patients with lactational breast abscess: a multi-center randomized double-blind controlled trial.

Although oral probiotics can improve breast microecology and alleviate the inflammatory response, there are no data regarding cases with existing abscesses. We aimed to investigate the effect of Lactobacillus fermentum CECT5716 during needle aspiration in patients with lactational breast abscesses. Patients (aged 20-41 years) with lactational single-cavity breast abscesses (diameter 3-6 cm) from 12 hospitals were randomly assigned to the experimental (n = 51) and control groups (n = 50). Outcome measures included the abscess cure rate on treatment day-5, delactation rate, relieving pain rate, and number of needle aspirations until day-28. The experimental group's 5-day cure rate (43.1%) was significantly higher (p < 0.05). Breastfeeding continuation on day-5 did not differ significantly (experimental group: 88.2%, control group: 96.0%, p = 0.269). In the experimental and control groups, 19.6% and 14.0% of patients experienced moderate to severe pain on day-5, respectively, with no statistically significant differences (p = 0.451). Four patients in each group developed diarrhea, with adverse reaction rates of 7.84% and 8.0%, respectively. No adverse reactions were reported in the infants. L. fermentum can shorten the healing time in patients with lactational breast abscesses.Trial registration This study was registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn ), registration number: ChiCTR2000032682, registration date: 6/May/ 2020; first entry date: 11/May/2020.

The complete mitochondrial genome of Priotyrannus closteroides Thomson, 1877 (Coleoptera: Cerambycidae).

Priotyrannus closteroides Thomson, 1877 (Coleoptera: Cerambycidae) is the trunk borer of orange trees. In this study, we sequenced and annotated the whole mitochondrial genome of P. closteroides. The results showed that the length of the complete mitochondrial genome is 15,854 bp with an overall GC content of 32.11%. The genome encodes 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and two ribosomal RNA genes (rRNAs). The relevant phylogenetic tree distinctly showed that P. closteroides is clustered with Dorysthenes paradoxus and Dorysthenes granulosus. This study provides a piece of valuable genomic information for the population genetics, evolution, and classification of P. closteroides.

The complete mitochondrial genome of Chalcophora japonica chinensis Schaufuss, 1879 (Coleoptera: Buprestidae).

Chalcophora japonica chinensis Schaufuss, 1879 (Coleoptera: Buprestidae) is a common pine pest in Chongqing, Fujian, Yunnan, and other in China. The mitochondrial genome of C. japonica is 15,759 bp in size. The genome includes 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and two ribosomal RNA genes (rRNAs). The overall GC content of the mitogenome is 32.0%. The results showed that C. japonica was most related to Chrysochroa fulgidissima, Trachys variolaris, and Agrilus mali. The full mitochondrial genome of C. japonica is now available, allowing researchers to better understand the species' genetic evolution and regulatory strategies.

The neurosteroid pregnenolone is synthesized by a mitochondrial P450 enzyme other than CYP11A1 in human glial cells.

Neurosteroids, modulators of neuronal and glial cell functions, are synthesized in the nervous system from cholesterol. In peripheral steroidogenic tissues, cholesterol is converted to the major steroid precursor pregnenolone by the CYP11A1 enzyme. Although pregnenolone is one of the most abundant neurosteroids in the brain, expression of CYP11A1 is difficult to detect. We found that human glial cells produced pregnenolone, detectable by mass spectrometry and ELISA, despite the absence of observable immunoreactive CYP11A1 protein. Unlike testicular and adrenal cortical cells, pregnenolone production in glial cells was not inhibited by CYP11A1 inhibitors DL-aminoglutethimide and ketoconazole. Furthermore, addition of hydroxycholesterols increased pregnenolone synthesis, suggesting desmolase activity that was not blocked by DL-aminoglutethimide or ketoconazole. We explored three different possibilities for an alternative pathway for glial cell pregnenolone synthesis: (1) regulation by reactive oxygen species, (2) metabolism via a different CYP11A1 isoform, and (3) metabolism via another CYP450 enzyme. First, we found oxidants and antioxidants had no significant effects on pregnenolone synthesis, suggesting it is not regulated by reactive oxygen species. Second, overexpression of CYP11A1 isoform b did not alter synthesis, indicating use of another CYP11A1 isoform is unlikely. Finally, we show nitric oxide and iron chelators deferoxamine and deferiprone significantly inhibited pregnenolone production, indicating involvement of another CYP450 enzyme. Ultimately, knockdown of endoplasmic reticulum cofactor NADPH-cytochrome P450 reductase had no effect, while knockdown of mitochondrial CYP450 cofactor ferredoxin reductase inhibited pregnenolone production. These data suggest that pregnenolone is synthesized by a mitochondrial cytochrome P450 enzyme other than CYP11A1 in human glial cells.

Calorie restriction on normal body weight mice prevents body weight regain on a follow-up high-fat diet by shaping an obesity-resistant-like gut microbiota profile.

Calorie restriction (CR) is one of the most common approaches for obesity treatment, but whether resuming ad libitum feeding after CR in normal-weight mice can affect excessive weight regain remains poorly studied. To address this issue, male C57BL/6 mice were placed in three groups: a control group (n = 10), a group fed normal diet with 30% CR (n = 20); and a group fed a HF diet (n = 30). After four weeks, the CR group was fed either a normal diet (NDCR, n = 10) or a high-fat diet (HFCR, n = 10) for an additional eight weeks. At the end of the experiment, mice in the HF group ranked in the upper and lower thirds for weight gain were designated as obesity-prone (HFOP, n = 10) and obesity-resistant (HFOR, n = 10), respectively. CR delayed weight regain and visceral fat accumulation. Gut microbiota in the HFCR group were more similar to the HFOR group than the HFOP group, mainly due to reversion of the decreased level of Clostridiales induced by CR. Mediation analysis showed that Clostridiales may delay body weight regain by affecting the interconversion of succinate and fumarate. Random forest and structural equation analyses showed Christensenellaceae were the most important biomarker for alleviation of obesity. In conclusion, CR shapes an obesity-resistant-like gut microbiota profile that may attenuate body weight regain.

Association between FADS Gene Expression and Polyunsaturated Fatty Acids in Breast Milk.

Polyunsaturated fatty acid (PUFA) in breast milk provides physiological benefits for offspring and is closely related to endogenous biosynthesis in lactating women. Few studies have addressed the association between fatty acid desaturase (FADS) gene expression patterns and fatty acids in breast milk. This research aimed to explore the differences in PUFA levels among breast milk groups with different levels of FADS gene expression and provide a scientific basis for precision nutrition strategies. A total of 50 healthy women 42-45 days postpartum were included in this study. A basic information questionnaire and breast milk samples were collected. Eight types of PUFA were detected, and RNA was extracted from breast milk. The transcription level of the FADS gene was detected using real-time quantitative PCR. Significant differences in the content of gamma-linolenic acid and eicosatrienoic acid (C20:3n6) were found in breast milk among FADS1 gene transcription groups (p = 0.009, p = 0.042, respectively). No significant differences in PUFA were found among the FADS2 and FADS3 gene expression groups. The results demonstrated that n-6 PUFA was associated with the mRNA expression levels of the FADS1 gene. They are of great significance in developing new methods and diets to optimize infant feeding using breast milk.

Reliability and validity of the Pittsburgh Sleep Quality Index among frontline COVID-19 health care workers using classical test theory and item response theory.

STUDY OBJECTIVES: The applicability of sleep-related scales to frontline medical staff for the COVID-19 pandemic has not been fully proved, so sleep survey results lack credibility and accuracy, creating difficulties for the guidance and treatment of frontline medical staff with sleep disorders, which is not conducive to the prevention and control of COVID-19. This study sought to analyze the reliability and validity of the Pittsburgh Sleep Quality Index (PSQI) among frontline medical staff fighting the COVID-19 pandemic. METHODS: A network questionnaire survey was used to investigate the PSQI among frontline medical staff who fought COVID-19 in Wuhan, China from March 19 to April 15, 2020. Combined with classical test theory and item response theory, the content validity, internal consistency, construct validity, and other aspects of the PSQI were evaluated. RESULTS: According to classical test theory, content validity, criterion validity, and construct validity of the PSQI were good. But the internal consistency was better after the deletion of the "daytime dysfunction" subscale. With regard to item response theory, difficulty, the differential item function, and the Wright map performed well. CONCLUSIONS: The original PSQI showed acceptable applicability in frontline COVID-19 medical staff, and its characteristics moderately improved after the "daytime dysfunction" subscale was removed. CITATION: Wang L, Wu Y-X, Lin Y-Q, et al. Reliability and validity of the Pittsburgh Sleep Quality Index among frontline COVID-19 health care workers using classical test theory and item response theory. J Clin Sleep Med. 2022;18(2):541-551.