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Purpose: The incidence of visceral leishmaniasis (VL), a global infectious disease, has been on the rise in China's Hebei province. When patients achieve clinical cure, they often do not reach an etiological cure, which may lead to recurrence of the disease. Here, we report a case of visceral leishmaniasis with a negative blood smear and bone marrow cytology. Patients and Methods: A 65-year-old man and bronchoalveolar lavage fluid mNGS. Results: A 65-year-old man developed a chronic fever, anorexia, splenomegaly, and pancytopenia. The blood metagenomic second-generation sequencing (mNGS) revealed Leishmania sequence readings, which led to the diagnosis of VL. After sodium antimony gluconate treatment, the blood smear and bone marrow cytology revealed no Leishmania bodies. However, pancytopenia and respiratory failure did not fully subside, and cardiotoxic damage emerged. The bronchoalveolar lavage fluid (BALF) mNGS was performed to detect the pathogen. Through BALF mNGS, Leishmania sequence was still detectable. Therefore, after the ECG returned to normal, antimony sodium gluconate was administered as a next course of treatment. Conclusion: BALF mNGS may assist in evaluating the therapeutic efficacy of VL with respiratory failure, especially in patients with negative blood and bone marrow cytology.

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Accurate detection of visceral leishmaniasis is essential for clinical diagnosis.It is uncommon to use alveolar lavage fluid mNGS in etiological diagnosis.Patient with negative bone marrow cytology may refer to alveolar lavage fluid mNGS.

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Biorefineries have attracted significant attention from the scientific community and various industrial sectors due to their use of unconventional biomass sources to produce biofuels and other value-added compounds. Various agro-industrial residues can be applied in biorefinery systems, making them economically and environmentally attractive. However, the cost, efficiency, and profitability of the process are directly affected by the choice of biomass, pre-treatments, and desired products. In biorefineries, the simultaneous production of different products during processing is a valuable approach. Chemical, physical, biological, or combined treatments can generate numerous compounds of high commercial interest, such as phenolic compounds. These treatments, in addition to modifying the biomass structure, are essential for the process's viability. Over the years, complex treatments with high costs and environmental impacts have been simplified and improved, becoming more specific in generating high-value resources as secondary outputs to the main process (generally related to the release of sugars from lignocelluloses to produce second-generation ethanol). Innovative methods involving microorganisms and enzymes are the most promising in terms of efficiency and lower environmental impact. Biorefineries enable the use of varied raw materials, such as different agro-industrial residues, allowing for more efficient resource utilization and reducing dependence on non-renewable sources. In addition to producing low-carbon biofuels, biorefineries generate a variety of high-value by-products, such as packaging materials, pharmaceuticals, and nutritional ingredients. This not only increases the profitability of biorefineries but also contributes to a circular economy.

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With the increasing demand for plastics, plastic pollution is growing rapidly. A significant amount of plastic has leaked into the environment, leading to severe environmental issues. Biodegradable plastics are considered promising alternatives to conventional durable plastics, and the environmental impacts of biodegradable plastics have received increasing attention. Poly (butylene adipate-co-terephthalate) (PBAT) is a commercial and cost-competitive biodegradable polymer and has been applied in the packaging and agriculture sectors. The environmental performances of PBAT with second-generation feedstocks from forestry waste have been rarely investigated. Since China is the leading global producer and exporter of PBAT polymer, Chinese cradle-to-gate life cycle inventories of PBAT were compiled in this study. A comparative life cycle assessment (LCA) was conducted to explore the potential for environmental performance of PBAT with second-generation biobased feedstock compared to fossil-derived PBAT and conventional plastics. The results showed that feedstocks contributed to more than 70 % of 18 environmental impact categories of fossil-derived PBAT. In comparison, PBAT with 2nd generation biobased feedstock reduces the environmental loads in 16 impact categories by 15-85 %, and renewable energy substitution has the potential to reduce environmental impacts by 10 %. Biobased PBAT performs better than PVC, PP, HDPE, LDPE, and PET in 16 impact categories by 15-80 %. Biobased PBAT has GWP of 3.72 kg CO2 eq, which is 37 % lower than fossil-derived PBAT (5.89 kg CO2 eq) and 18-32 % lower than conventional plastics. Since feedstock dominates the environmental performance of PBAT, the development of biomanufacturing technologies for biobased polymers and chemicals could significantly improve environmental performance of biodegradable plastics and promote the sustainable development of the plastic industry. Results could serve as the basis for environmental impact and mitigation strategies for biodegradable plastics with biobased feedstocks, as well as the sustainable development of the PBAT industry.

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BACKGROUND: We report the final results of treatment with aripiprazole, blonanserin, and paliperidone from the Japan Useful Medication Program for Schizophrenia (JUMPs), a 104-week naturalistic study. METHODS: JUMPs was an open-label, three-arm, randomized, parallel-group, 104-week study. Patients aged ≥ 20 years with schizophrenia requiring antipsychotic treatment or a switch from previous therapy were enrolled. The primary endpoint was treatment discontinuation rate over 104 weeks. Secondary endpoints included remission rate, Personal and Social Performance (PSP), safety, Positive and Negative Syndrome Scale (PANSS), and quality of life (QOL; EuroQol-5 dimension). RESULTS: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). Treatment discontinuation rates (aripiprazole, 80.5%; blonanserin, 81.2%; paliperidone, 71.4%) were not significantly different (p = 0.2385) among the treatment groups at 104 weeks; comparable outcomes were observed for endpoints, including remission (42.9%, 46.7%, and 45.8%), PANSS, and safety. In the overall cohort, while the improvement in the PSP total score at Week 104 was not significantly different from baseline, a significant improvement (p < 0.05) in QOL and total PANSS scores (including all subscales) was observed at Week 104 compared with baseline. Multivariable analysis identified a shorter disease duration and a higher chlorpromazine-equivalent antipsychotic dosage level (≥ 1000 mg) before switching to monotherapy as predictors of treatment discontinuation. CONCLUSIONS: The 104-week treatment outcomes were comparable between groups; the overall trend of improvement in remission rate, safety, and QOL suggests the importance of continued treatment. CLINICAL TRIAL REGISTRATION: UMIN-Clinical Trials Registry UMIN000007942 (public release date: 14/05/2012).

Asunto(s)

Antipsicóticos , Aripiprazol , Palmitato de Paliperidona , Calidad de Vida , Esquizofrenia , Humanos , Esquizofrenia/tratamiento farmacológico , Antipsicóticos/uso terapéutico , Masculino , Femenino , Adulto , Aripiprazol/uso terapéutico , Palmitato de Paliperidona/uso terapéutico , Palmitato de Paliperidona/administración & dosificación , Persona de Mediana Edad , Piperazinas/uso terapéutico , Piperidinas/uso terapéutico , Resultado del Tratamiento , Inducción de Remisión , Japón , Escalas de Valoración Psiquiátrica , Psicología del Esquizofrénico

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Introduction: Second-Generation Antipsychotics (SGAs) are widely used for treating psychiatric disorders due to their favorable side effect profile compared to First-Generation Antipsychotics (FGAs). However, SGAs are associated with significant metabolic side effects. This study aims to explore the sociodemographic and health differences between individuals using SGAs and those not using them. Methods: A comparative cross-sectional study was conducted with 148 participants, including 102 SGA users and 46 non-users. Data were collected from patients and medical records, encompassing sociodemographic factors and health variables including diabetes mellitus, hypertension, cardiovascular disease, hyperlipidemia, waist circumference, fasting blood glucose, cholesterol, triglycerides, HDL, LDL, and BMI. Statistical analyses included chi-square and Fisher's exact tests to compare the two groups. Results: SGA users had higher rates of overweight and obesity compared to non-users (p = 0.000), with 30.4% overweight and 29.4% obese among SGA users versus 21.7% overweight and 4.3% obese among non-users. A higher prevalence of cardiovascular disease was observed in SGA users (11.8% vs. 2.2%, p = 0.076). Although not statistically significant, trends indicated higher rates of diabetes mellitus and hyperlipidemia in non-users (30.4% vs. 18.6%, p = 0.110 and 7% vs. 0%, p = 0.083, respectively). Conclusion: This study highlights significant differences in BMI and cardiovascular disease prevalence between SGA users and non-users, reinforcing the need for comprehensive metabolic monitoring in patients treated with SGAs. The findings underscore the importance of considering sociodemographic factors in managing the health risks associated with SGA use. Further research with larger sample sizes and longitudinal designs is warranted to better understand these associations and develop targeted interventions.

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Antipsicóticos , Síndrome Metabólico , Humanos , Estudios Transversales , Masculino , Femenino , Antipsicóticos/efectos adversos , Antipsicóticos/administración & dosificación , Arabia Saudita/epidemiología , Síndrome Metabólico/epidemiología , Síndrome Metabólico/inducido químicamente , Persona de Mediana Edad , Adulto , Trastornos Mentales/epidemiología , Trastornos Mentales/tratamiento farmacológico , Prevalencia , Obesidad/epidemiología , Obesidad/inducido químicamente , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/inducido químicamente , Sobrepeso/epidemiología , Sobrepeso/inducido químicamente

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Background: Adenocarcinoma with positive echinoderm microtubule-associated protein-like 4 gene and anaplastic lymphoma kinase (EML4-ALK) gene fusion accounts for 3-7% of lung cancer cases and can be targeted with ALK tyrosine kinase inhibitors (TKIs). Second-generation TKIs are the standard of care for targeted populations, especially those with central nervous system (CNS) metastasis. However, most patients eventually experience disease progression because of drug resistance caused by multiple mechanisms, predominantly secondary mutations. Case description: We present a female advanced non-small cell lung cancer (NSCLC) case with positive EML4-ALK gene fusion, in which disease progression occurred in only 3 months after first-line treatment with alectinib. Two secondary mutations were detected by next-generation sequencing; one was V1180L located in exon 23, and the other was E803Q located in exon 14, which was a novel mutation that had never been reported. Ensartinib and ceritinib were administered as second-line and third-line treatments. However, the response to these TKIs was poor, and her overall survival was only 7 months. Conclusion: The secondary mutation E803Q located in exon 14 seems resistant to most second-generation ALK-TKIs. If there is an opportunity, the efficacy of the third-generation ALK-TKI loratinib should be tested.

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MOTIVATION: Structural variants (SVs) play an important role in genetic research and precision medicine. As existing SV detection methods usually contain a substantial number of false positive calls, approaches to filter the detection results are needed. RESULT: We developed a novel deep learning-based SV filtering tool, CSV-Filter, for both short and long reads. CSV-Filter uses a novel multi-level grayscale image encoding method based on CIGAR strings of the alignment results and employs image augmentation techniques to improve SV feature extraction. CSV-Filter also utilizes self-supervised learning networks for transfer as classification models, and employs mixed-precision operations to accelerate training. The experiments showed that the integration of CSV-Filter with popular SV detection tools could considerably reduce false positive SVs for short and long reads, while maintaining true positive SVs almost unchanged. Compared with DeepSVFilter, a SV filtering tool for short reads, CSV-Filter could recognize more false positive calls and support long reads as an additional feature. AVAILABILITY AND IMPLEMENTATION: https://github.com/xzyschumacher/CSV-Filter.

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Introduction: This study investigates the Health-Led Growth Hypothesis (HLGH) within OECD countries, examining how health expenditures influence economic growth and the role of different health financing systems in this relationship. Methods: Utilizing a comprehensive analysis spanning 2000 to 2019 across 38 OECD countries, advanced econometric methodologies were employed. Both second-generation panel data estimators (Dynamic CCEMG, CS-ARDL, AMG) and first-generation models (Panel ARDL with PMG, FMOLS, DOLS) were utilized to test the hypothesis. Results: The findings confirm the positive impact of health expenditures on economic growth, supporting the HLGH. Significant disparities were observed in the ability of health expenditures to stimulate economic growth across different health financing systems, including the Bismarck, Beveridge, Private Health Insurance, and System in Transition models. Discussion: This study enriches the ongoing academic dialog by providing an exhaustive analysis of the relationship between health expenditures and economic growth. It offers valuable insights for policymakers on how to optimize health investments to enhance economic development, considering the varying effects of different health financing frameworks.

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Desarrollo Económico , Gastos en Salud , Financiación de la Atención de la Salud , Modelos Econométricos , Organización para la Cooperación y el Desarrollo Económico , Humanos , Gastos en Salud/estadística & datos numéricos

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The management of chronic myeloid leukemia in the chronic phase (CML-CP) has witnessed significant advancements since the identification of a common chromosomal translocation anomaly involving chromosomes 9 and 22, which results in the formation of the Philadelphia chromosome driven by the BCR-ABL1 fusion protein. This discovery paved the way for the development of tyrosine kinase inhibitors (TKIs) that target the adenosine triphosphate (ATP) binding site of ABL1 through the BCR-ABL-1 fusion protein. Following the approval of Imatinib by the Food and Drug Administration (FDA) as the first TKI for CML treatment in 2001, the median overall survival (OS) for chronic phase CML (CML-CP) has significantly improved, approaching that of the general population. However, achieving this milestone crucially depends on reaching certain treatment response milestones. Since the introduction of imatinib, five additional TKIs have been approved for CML-CP treatment. Despite the availability of these treatments, many patients may experience treatment failure and require multiple lines of therapy due to factors such as the emergence of resistance, such as mutations in the ATP binding site of ABL, or intolerance to therapy. This review will primarily focus on exploring treatment options for patients who fail second-generation TKI therapy due to true resistance.

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BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative condition leading to memory loss, cognitive impairment, and neuropsychiatric symptoms. Second-generation antipsychotics (SGAs) are commonly used to manage these neuropsychiatric symptoms, but their safety profile in patients with AD requires further investigation. OBJECTIVE: The objective was to evaluate the safety of SGAs in patients with AD by analyzing adverse drug reactions (ADRs) using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: This study conducted a comprehensive analysis of FAERS data from 2014 to 2023, focusing on ADRs in patients with AD treated with SGAs such as risperidone, quetiapine, olanzapine, clozapine, and aripiprazole. Descriptive, disproportionality, time, and dose analysis were performed using the Bayesian confidence propagation neural network, Weibull, and physiologically based pharmacokinetic model. RESULTS: Out of 1289 patients with AD treated with SGAs, the most common ADRs involved the nervous system, gastrointestinal system, and cardiac disorders. Disproportionality analysis identified significant positive signals in cardiac, renal, and vascular systems. Quetiapine, risperidone, and olanzapine showed more positive signals compared with clozapine and aripiprazole. Time analysis indicated that cardiovascular ADRs occurred randomly, whereas renal ADRs increased with prolonged use. Dose analysis suggested that small doses of SGAs did not elevate the risk of multiple cardiac, renal, or vascular ADRs. CONCLUSION AND RELEVANCE: The study underscores the importance of monitoring for ADRs, particularly in the cardiac and renal systems, when using SGAs in patients with AD. Future research incorporating more comprehensive clinical data is warranted to support safe and rational drug utilization.

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BACKGROUND: Lignocellulose is a renewable and sustainable resource used to produce second-generation biofuel ethanol to cope with the resource and energy crisis. Furfural is the most toxic inhibitor of Saccharomyces cerevisiae cells produced during lignocellulose treatment, and can reduce the ability of S. cerevisiae to utilize lignocellulose, resulting in low bioethanol yield. In this study, multiple rounds of progressive ionizing radiation was combined with adaptive laboratory evolution to improve the furfural tolerance of S. cerevisiae and increase the yield of ethanol. RESULTS: In this study, the strategy of multiple rounds of progressive X-ray radiation combined with adaptive laboratory evolution significantly improved the furfural tolerance of brewing yeast. After four rounds of experiments, four mutant strains resistant to high concentrations of furfural were obtained (SCF-R1, SCF-R2, SCF-R3, and SCF-R4), with furfural tolerance concentrations of 4.0, 4.2, 4.4, and 4.5 g/L, respectively. Among them, the mutant strain SCF-R4 obtained in the fourth round of radiation had a cellular malondialdehyde content of 49.11 nmol/mg after 3 h of furfural stress, a weakening trend in mitochondrial membrane potential collapse, a decrease in accumulated reactive oxygen species, and a cell death rate of 12.60%, showing better cell membrane integrity, stable mitochondrial function, and an improved ability to limit reactive oxygen species production compared to the other mutant strains and the wild-type strain. In a fermentation medium containing 3.5 g/L furfural, the growth lag phase of the SCF-R4 mutant strain was shortened, and its growth ability significantly improved. After 96 h of fermentation, the ethanol production of the mutant strain SCF-R4 was 1.86 times that of the wild-type, indicating that with an increase in the number of irradiation rounds, the furfural tolerance of the mutant strain SCF-R4 was effectively enhanced. In addition, through genome-transcriptome analysis, potential sites related to furfural detoxification were identified, including GAL7, MAE1, PDC6, HXT1, AUS1, and TPK3. CONCLUSIONS: These results indicate that multiple rounds of progressive X-ray radiation combined with adaptive laboratory evolution is an effective mutagenic strategy for obtaining furfural-tolerant mutants and that it has the potential to tap genes related to the furfural detoxification mechanism.

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Within the circular bioeconomy the production of optically pure LA from 2nd generation feedstocks would be ideal but it is very challenging. In this paper genetically engineered Escherichia coli strains were created to resolve racemic LA solutions synthesised and produced from the fermentation of organic waste or ensiled grass. Refining LA racemic mixtures into either a D- or L-LA was achieved by cells being able to consume one LA isomer as a sole carbon and energy source while not being able to consume the other. A D-LA refining strain JSP0005 was grown on fermented source-sorted organic household waste and different grass silage leachates, which are 2nd generation feedstocks containing up to 33 g/L lactic acid racemate. In all growth experiments, L-LA was completely removed leaving D-LA as the only LA stereoisomer, i.e. resulting in optically pure D-LA, which also increased by as much as 248.6 % from its starting concentration, corresponding to 38 g/L. The strains resulting from this study are a promising first step towards a microbial based LA biorefining process.

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Escherichia coli , Fermentación , Ácido Láctico , Escherichia coli/metabolismo , Ácido Láctico/metabolismo , Ácido Láctico/biosíntesis

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Suicidal behaviour is defined as taking actions with the intention of killing oneself and thinking of performing these actions. Suicide is a serious public health problem with complex biological, social and psychological risk factors and a multidimensional clinical appearance, occurring all over the world and ranking among the leading causes of death. In this study, psychological approaches explaining suicide were evaluated under the headings of first-generation and second-generation suicide theories, the different aspects of these theories were put forward, and previously published studies and recent evidence were reviewed. A literature review on the theoretical foundations of suicide is presented. First-generation suicide theories were developed before the 2000s and second-generation suicide theories were developed after the 2000s. While Psychodynamic Theory, Social Learning Theory, Hopelessness Theory, Shneidman's Suicide Theory and Escape Theory are included under the title of first-generation suicide theories, Interpersonal Psychological Suicide Theory, Three Stage Suicide Theory, Complementary Motivational-Demotivational Theory and Variable Predisposition Theory are examined as second-generation suicide theories. The approaches of the theories provide important evidence in understanding suicidal behaviour and recognising various risk factors in the transition from suicidal ideation to suicidal action. Controlling the risk factors may contribute both in terms of preventive community mental health and in the development of health policies.

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BACKGROUND: Second-generation antipsychotics (SGAs) are commonly used to treat schizophrenia (SCZ), but SGAs may differ in the severity of side effects. Long-term studies are lacking, and previous observational studies have limitations, such as failure to account for confounding factors and short follow-up durations. AIMS: To compare the long-term anthropometric and metabolic side effects of seven SGAs in a Chinese population, using a within-subject approach to reduce the risk of confounding. METHOD: We collected longitudinal data of SGA prescriptions, concomitant medications, fasting blood glucose (BG), lipid profiles, and BMI in a cohort of 767 patients with SCZ, with follow-up lasting up to 18.7 years (median ∼6.2 years). A total of 192,152 prescription records were retrieved, with 27,723 metabolic measures analysed. Linear mixed models were used to estimate the effects of SGA on BG, lipid profiles and BMI. Besides studying the effects of SGA medications (as binary predictors), we also investigated the effects of SGA dosage on metabolic profiles. RESULTS: Considering SGA medications as binary predictors, clozapine and olanzapine were associated with the most substantial worsening of lipid profiles and BMI. A significant increase in BG was observed with clozapine only. Amisulpride, paliperidone and quetiapine were associated with worsened lipid profiles and increased BMI. Conversely, aripiprazole was associated with significant improvement in lipid profiles but a small increase in BMI. When SGA dosage was considered, the model showed consistent results overall. At the minimum effective dose, clozapine was associated with the most severe metabolic side effects, followed by olanzapine. Risperidone and aripiprazole showed the least metabolic side effects, with aripiprazole being significantly associated with lower lipids. CONCLUSIONS: This study clarified the long-term and dose-dependent effects of different SGAs on anthropometric and metabolic parameters in Chinese SCZ patients. Our findings may inform clinicians and SCZ patients of SGA choices.

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Antipsicóticos , Olanzapina , Esquizofrenia , Humanos , Antipsicóticos/efectos adversos , Antipsicóticos/administración & dosificación , Esquizofrenia/tratamiento farmacológico , Femenino , Masculino , Adulto , China , Olanzapina/efectos adversos , Olanzapina/administración & dosificación , Persona de Mediana Edad , Índice de Masa Corporal , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Estudios Longitudinales , Clozapina/efectos adversos , Clozapina/administración & dosificación , Fumarato de Quetiapina/efectos adversos , Fumarato de Quetiapina/administración & dosificación , Risperidona/efectos adversos , Risperidona/administración & dosificación , Estudios de Seguimiento , Adulto Joven , Relación Dosis-Respuesta a Droga , Aripiprazol/administración & dosificación , Aripiprazol/efectos adversos , Aripiprazol/farmacología , Lípidos/sangre , Pueblos del Este de Asia

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The Monocled Cobra (Naja kaouthia), a category one medically significant snake from the Elapidae family, inflicts severe envenomation in South and Southeast Asian countries. N. kaouthia is distributed throughout the eastern and northeastern parts of India, Nepal, Bangladesh, Myanmar, Thailand, Vietnam, Malaysia, and southwestern China. Envenomation by N. kaouthia is a medical emergency, and the primary clinical symptoms are neurotoxicity and localized tissue destruction. Unfortunately, data on the actual magnitude of N. kaouthia envenomation is scarce due to poor record keeping, lack of diagnostic kits, and region-wise well-coordinated epidemiological surveys. The present review highlights the diversity in the composition of N. Kaouthia venom (NKV) across various geographical regions, as revealed through biochemical and proteomic analyses. The qualitative and quantitative differences in the toxin isoforms result in differences in lethality and pathophysiological manifestation that may limit the effectiveness of antivenom therapy. Studies on commercial polyvalent antivenom (PAV) effectiveness against distinct NKV samples have revealed varying toxicity and enzymatic activity neutralization. Additionally, the identification of snake venom's poorly immunogenic toxins by mass spectrometry, quantification of venom-specific antibodies, and implications for antivenom therapy against snakebites are highlighted. Future directions involve clinical studies on NK envenomation where the snake is frequently encountered and the correlation of this data with NKV composition in that region. For more efficient and superior hospital management of NK envenomation, research should enhance the current immunization procedure to boost the development of antibodies against less immunogenic venom components of this snake.

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Antivenenos , Venenos Elapídicos , Mordeduras de Serpientes , Animales , Antivenenos/uso terapéutico , Asia Sudoriental/epidemiología , Mordeduras de Serpientes/tratamiento farmacológico , Humanos , Serpientes Venenosas

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The educational outcomes of the descendants of migrants are important indicators of migrants' incorporation into host societies and an indicator of intergenerational social im/mobility. This paper examines this relationship using data from a survey that follows a cohort of young adults, born between 1988 and 1997, who grew up in Switzerland. It looks at the relationship between the educational output of respondents and their parental migratory background, with the theoretical consideration that the family's social capital is a starting point in the descendants' trajectories. The paper is based on secondary data and exploratory cross-sectional quantitative analyses. The results highlight first a correspondence between migrant parents' national origins and their socio-economic status-in other words, an 'ethno-class'. Second, they show differences in educational outcomes between migrants' descendants and native Swiss as well as between the migrants' descendants themselves-which indicates a segmented incorporation process for both the first and the second generation, in confirmation of previous research. Third, results show that parental background and language region of residence are statistically significant in determining the level of education achieved by the migrants' descendants, especially those with a low socio-economic status. Their social mobility is 'limited', and they remain mostly in vocational education. The paper concludes that the Swiss school system still fails to include the most unprivileged and that a glass ceiling remains for them.

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INTRODUCTION: Physostigmine is an effective antidote for antimuscarinic delirium. There is little evidence for its use to reverse delirium following second generation antipsychotic exposure. The purpose of this study is to describe the safety and effectiveness of physostigmine in reversing delirium from second generation antipsychotic exposure. METHODS: This is a retrospective cohort study of all patients reported to a single regional poison center treated with physostigmine following a second generation antipsychotic exposure from January 1, 2000 to April 15, 2021. The poison center electronic medical record was queried to identify cases and for data abstraction. The primary outcome was the positive response rate to physostigmine, as determined by two trained abstractors. Secondary outcomes included physostigmine dosing, and adverse events. RESULTS: Of 147 charts reviewed, 138 individual patients were included, and the response to physostigmine was reported in 128 patients. The most common second-generation antipsychotic exposure was quetiapine (97; 70.3 percent). A positive response to physostigmine was noted in 106/128 (82.8 percent) patients [95 percent confidence interval 68.9-83.6 percent]. Median number of physostigmine doses was 1 (interquartile range 1-3; range 1-9). The median total physostigmine dose received was 2 mg (interquartile range 2-6 mg; range 0.15-30 mg). The positive physostigmine response rate for patients with an antimuscarinic co-ingestion was not significantly different compared to patients with a different co-ingestion or no co-ingestion (25/34 versus 81/94; P = 0.09). Adverse events were reported in four (2.9 percent) patients, including one death. DISCUSSION: A positive response to physostigmine to treat antimuscarinic delirium from second generation antipsychotic exposure was reported in 82.8 percent of patients, which is similar to previous physostigmine studies. Adverse events were infrequent, and included diaphoresis (one 0.7 percent), seizure (one; 0.7 percent), and bradycardia (one; 0.7 percent). One (0.7%) patient suffered a cardiac arrest 60 minutes after receiving physostigmine to treat antimuscarinic delirium following having received increasing clozapine doses over the previous month. CONCLUSIONS: In this study, physostigmine appears to be a safe and effective treatment for antimuscarinic delirium from second generation antipsychotic exposure. Further studies are needed to validate the safety and effectiveness of physostigmine for this indication.

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Antipsicóticos , Delirio , Fisostigmina , Centros de Control de Intoxicaciones , Humanos , Fisostigmina/uso terapéutico , Estudios Retrospectivos , Delirio/tratamiento farmacológico , Delirio/inducido químicamente , Antipsicóticos/uso terapéutico , Antipsicóticos/efectos adversos , Femenino , Masculino , Centros de Control de Intoxicaciones/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Antídotos/uso terapéutico , Antídotos/administración & dosificación , Inhibidores de la Colinesterasa/uso terapéutico , Anciano , Adulto Joven , Estudios de Cohortes

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To detect and analyze the changes of microorganisms in expressed prostatic secretion (EPS) of patients with IIIB prostatitis before and after low-intensity pulsed ultrasound (LIPUS) treatment, and to explore the mechanism of LIPUS in the treatment of chronic prostatitis (CP). 25 patients (study power was estimated using a Dirichlet-multinomial approach and reached 96.5% at α = 0.05 using a sample size of 25) with IIIB prostatitis who were effective in LIPUS treatment were divided into two groups before and after LIPUS treatment. High throughput second-generation sequencing technique was used to detect and analyze the relative abundance of bacterial 16 s ribosomal variable regions in EPS before and after treatment. The data were analyzed by bioinformatics software and database, and differences with P < 0.05 were considered statistically significant. Beta diversity analysis showed that there was a significant difference between groups (P = 0.046). LEfSe detected four kinds of characteristic microorganisms in the EPS of patients with IIIB prostatitis before and after LIPUS treatment. After multiple comparisons among groups by DESeq2 method, six different microorganisms were found. LIPUS may improve patients' clinical symptoms by changing the flora structure of EPS, stabilizing and affecting resident bacteria or opportunistic pathogens.

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Próstata , Prostatitis , Ondas Ultrasónicas , Humanos , Masculino , Prostatitis/terapia , Prostatitis/microbiología , Prostatitis/metabolismo , Próstata/microbiología , Próstata/metabolismo , Próstata/patología , Adulto , Bacterias/metabolismo , Bacterias/genética , Persona de Mediana Edad , Terapia por Ultrasonido/métodos , Microbiota , ARN Ribosómico 16S/genética

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BACKGROUND: A study to assess the glucose levels of people with type 1 diabetes (T1D) overnight, based on the insulin type and timing. METHODS: A real-world, retrospective study of T1D, using multiple daily insulin injections. Continuous glucose monitoring and insulin injection data were collected for ten hours after dinner using the Insulclock® connected cap. Meal events were identified using the ROC detection methodology. The timing of the rapid insulin, second injections, and the type of insulin analogs used, were evaluated. RESULTS: The nocturnal profiles (n = 775, 49 subjects) were analyzed. A higher glucose AUC of over 180 mg/dL was observed in subjects with delayed injections (number; %; mg/dL × h): -45-15 min (n = 136; 17.5%, 175.9 ± 271.0); -15-0 min (n = 231; 29.8%, 164.0 ± 2 37.1); 0 + 45 min (n = 408; 52.6%, 203.6 ± 260.9), (p = 0.049). The use of ultrarapid insulin (FiAsp®) (URI) vs. rapid insulin (RI) analogs was associated with less hypoglycemia events (7.1 vs. 13.6%; p = 0.005) and TBR70 (1.7 ± 6.9 vs. 4.6 ± 13.9%; p = 0.003). Users of glargine U300 vs. degludec had a higher TIR (70.7 vs. 58.5%) (adjusted R-squared: 0.22, p < 0.001). The use of a correction injection (n = 144, 18.6%) was associated with a higher number of hypoglycemia events (18.1 vs. 9.5%; p = 0.003), TBR70 (5.5 ± 14.2 vs. 3.0 ± 11.1%; p = 0.003), a glucose AUC of over 180 mg/dL (226.1 ± 257.8 vs. 178.0 ± 255.3 mg/dL × h; p = 0.001), and a lower TIR (56.0 ± 27.4 vs. 62.7 ± 29.6 mg/dL × h; p = 0.004). CONCLUSION: The dinner rapid insulin timing, insulin type, and the use of correction injections affect the nocturnal glucose profile in T1D.