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Pharmaceuticals (Basel, Switzerland) May 2024The pharmacokinetic (PK) profiles of voriconazole in intensive care unit (ICU) patients differ from that in other patients. We aimed to develop a population...
AIMS
The pharmacokinetic (PK) profiles of voriconazole in intensive care unit (ICU) patients differ from that in other patients. We aimed to develop a population pharmacokinetic (PopPK) model to evaluate the effects of using extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) and those of various biological covariates on the voriconazole PK profile.
METHODS
Modeling analyses of the PK parameters were conducted using the nonlinear mixed-effects modeling method (NONMEM) with a two-compartment model. Monte Carlo simulations (MCSs) were performed to observe the probability of target attainment (PTA) when receiving CRRT or not under different dosage regimens, different stratifications of quick C-reactive protein (qCRP), and different minimum inhibitory concentration (MIC) ranges.
RESULTS
A total of 408 critically ill patients with 746 voriconazole concentration-time data points were included in this study. A two-compartment population PK model with qCRP, CRRT, creatinine clearance rate (CL), platelets (PLT), and prothrombin time (PT) as fixed effects was developed using the NONMEM.
CONCLUSIONS
We found that qCRP, CRRT, CL, PLT, and PT affected the voriconazole clearance. The most commonly used clinical regimen of 200 mg q12h was sufficient for the most common sensitive pathogens (MIC ≤ 0.25 mg/L), regardless of whether CRRT was performed and the level of qCRP. When the MIC was 0.5 mg/L, 200 mg q12h was insufficient only when the qCRP was <40 mg/L and CRRT was performed. When the MIC was ≥2 mg/L, a dose of 300 mg q12h could not achieve ≥ 90% PTA, necessitating the evaluation of a higher dose.
PubMed: 38931333
DOI: 10.3390/ph17060665 -
Nutrients Jun 2024We analyzed the impact of social distancing (SD) on vitamin D status and associated morbidity in neonates during the coronavirus disease (COVID-19) pandemic.
BACKGROUND
We analyzed the impact of social distancing (SD) on vitamin D status and associated morbidity in neonates during the coronavirus disease (COVID-19) pandemic.
METHODS
Serum levels of 25-hydroxy vitamin D (25OHD) and clinical characteristics of newborn infants before (2019) and during SD (2021) were compared.
RESULTS
A total of 526 neonates (263 in 2019 and 263 in 2021) were included. The rate of vitamin D deficiency in neonates (47.1% vs. 35.4 %, = 0.008) decreased and the rate of maternal vitamin D intake increased (6.8% vs. 37.6%, < 0.001), respectively, during SD compared to those in 2019. The rates of hypocalcemia (12.5% vs. 3.8%, < 0.001) and respiratory illness (57.0% vs. 43.0%, = 0.002) decreased during SD. Neonatal vitamin D deficiency during SD was associated with maternal vitamin D supplementation (odds ratio [OR] = 0.463, = 0.003) but was not associated with SD (OR = 0.772, = 0.189). The mediation effect of SD on neonatal morbidity by neonatal vitamin D status was statistically insignificant.
CONCLUSIONS
SD might affect the increased maternal vitamin D intake and decreased neonatal vitamin D deficiency. However, neonatal morbidity was not affected by SD, even with neonatal vitamin D status changes.
Topics: Humans; COVID-19; Vitamin D; Vitamin D Deficiency; Infant, Newborn; Female; Male; Physical Distancing; SARS-CoV-2; Dietary Supplements; Pandemics; Nutritional Status; Hypocalcemia
PubMed: 38931213
DOI: 10.3390/nu16121858 -
Nutrients Jun 2024The metabolic-status-related mechanisms underlying the deterioration of the lung function in obese asthma have not been completely elucidated.
BACKGROUND
The metabolic-status-related mechanisms underlying the deterioration of the lung function in obese asthma have not been completely elucidated.
OBJECTIVE
This study aimed to investigate the basal metabolic rate (BMR) in patients with obese asthma, its association with the lung function, and its mediating role in the impact of obesity on the lung function.
METHODS
A 12-month prospective cohort study (n = 598) was conducted in a real-world setting, comparing clinical, body composition, BMR, and lung function data between patients with obese (n = 282) and non-obese (n = 316) asthma. Path model mediation analyses for the BMR and skeletal muscle mass (SMM) were conducted. We also explored the effects of the BMR on the long-term lung function in patients with asthma.
RESULTS
Patients with obese asthma exhibited greater airway obstruction, with lower FEV (1.99 vs. 2.29 L), FVC (3.02 vs. 3.33 L), and FEV/FVC (65.5 vs. 68.2%) values compared to patients with non-obese asthma. The patients with obese asthma also had higher BMRs (1284.27 vs. 1210.08 kcal/d) and SMM (23.53 vs. 22.10 kg). Both the BMR and SMM mediated the relationship between obesity and the lung function spirometers (FEV, %FEV, FVC, %FVC, and FEV/FVC). A higher BMR or SMM was associated with better long-term lung function.
CONCLUSIONS
Our study highlights the significance of the BMR and SMM in mediating the relationship between obesity and spirometry in patients with asthma, and in determining the long-term lung function. Interventions for obese asthma should focus not only on reducing adiposity but also on maintaining a high BMR.
Topics: Humans; Asthma; Obesity; Prospective Studies; Male; Female; Basal Metabolism; Middle Aged; Lung; Adult; Muscle, Skeletal; Respiratory Function Tests; Body Composition; Cohort Studies
PubMed: 38931162
DOI: 10.3390/nu16121809 -
Journal of Clinical Medicine Jun 2024SARS-CoV-2 continually mutates, with five identified variants. Many neurological manifestations were observed during the COVID-19 pandemic, with differences between...
SARS-CoV-2 continually mutates, with five identified variants. Many neurological manifestations were observed during the COVID-19 pandemic, with differences between virus variants. The aim of this study is to assess the frequency and characteristics of neurological manifestations during COVID-19 in hospitalized patients over three waves in Poland with comparison and analysis correlation with the course of infection. This retrospective single-center study included 600 consecutive adults with confirmed COVID-19, hospitalized during 3 waves (pre-Delta, Delta and Omicron) in Poland. Demographic and clinical information and neurological manifestations were collected and compared across three periods. The median age of the study group was 68, lower during the Delta wave. In the Omicron period, the disease severity at admission and inflammatory markers concentration were the lowest. Neurological manifestations were observed in 49%. The most common were altered mentation, headache, myalgia, mood disorder, ischemic stroke and encephalopathy. Smell and taste disturbances (STDs) were less frequent in the Omicron period. Neurological complications were predominant in the pre-Delta and Omicron periods. Ischemic stroke was observed more often in pre-Delta period. Altered mentation was related to higher severity at admission, worse lab test results, higher admission to ICU and mortality, while headache reduced mortality. Pre-existing dementia was related to higher mortality. Neurological manifestations of COVID-19 are frequent, with a lower rate of STDs in the Omicron period and more often cerebrovascular diseases in the pre-Delta period. Headache improves the course of COVID-19, while altered mentation, stroke and neurological comorbidities increase severity and mortality.
PubMed: 38930003
DOI: 10.3390/jcm13123477 -
Journal of Clinical Medicine Jun 2024(1) : Dexmedetomidine is a sedative for patients receiving invasive mechanical ventilation (IMV) that previous single-site studies have found to be associated with...
Association between Dexmedetomidine Use and Mortality in Patients with COVID-19 Receiving Invasive Mechanical Ventilation: A U.S. National COVID Cohort Collaborative (N3C) Study.
(1) : Dexmedetomidine is a sedative for patients receiving invasive mechanical ventilation (IMV) that previous single-site studies have found to be associated with improved survival in patients with COVID-19. The reported clinical benefits include dampened inflammatory response, reduced respiratory depression, reduced agitation and delirium, improved preservation of responsiveness and arousability, and improved hypoxic pulmonary vasoconstriction and ventilation-perfusion ratio. Whether improved mortality is evident in large, multi-site COVID-19 data is understudied. (2) : The association between dexmedetomidine use and mortality in patients with COVID-19 receiving IMV was assessed. This retrospective multi-center cohort study utilized patient data in the United States from health systems participating in the National COVID Cohort Collaborative (N3C) from 1 January 2020 to 3 November 2022. The primary outcome was 28-day mortality rate from the initiation of IMV. Propensity score matching adjusted for differences between the group with and without dexmedetomidine use. Adjusted hazard ratios (aHRs) for 28-day mortality were calculated using multivariable Cox proportional hazards models with dexmedetomidine use as a time-varying covariate. (3) : Among the 16,357,749 patients screened, 3806 patients across 17 health systems met the study criteria. Mortality was lower with dexmedetomidine use (aHR, 0.81; 95% CI, 0.73-0.90; < 0.001). On subgroup analysis, mortality was lower with earlier dexmedetomidine use-initiated within the median of 3.5 days from the start of IMV-(aHR, 0.67; 95% CI, 0.60-0.76; < 0.001) as well as use prior to standard, widespread use of dexamethasone for patients on respiratory support (prior to 30 July 2020) (aHR, 0.54; 95% CI, 0.42-0.69; < 0.001). In a secondary model that was restricted to 576 patients across six health system sites with available PaO/FiO data, mortality was not lower with dexmedetomidine use (aHR 0.95, 95% CI, 0.72-1.25; = 0.73); however, on subgroup analysis, mortality was lower with dexmedetomidine use initiated earlier than the median dexmedetomidine start time after IMV (aHR, 0.72; 95% CI, 0.53-0.98; = 0.04) and use prior to 30 July 2020 (aHR, 0.22; 95% CI, 0.06-0.78; = 0.02). (4) : Dexmedetomidine use was associated with reduced mortality in patients with COVID-19 receiving IMV, particularly when initiated earlier, rather than later, during the course of IMV as well as use prior to the standard, widespread usage of dexamethasone during respiratory support. These particular findings might suggest that the associated mortality benefit with dexmedetomidine use is tied to immunomodulation. However, further research including a large randomized controlled trial is warranted to evaluate the potential mortality benefit of DEX use in COVID-19 and evaluate the physiologic changes influenced by DEX that may enhance survival.
PubMed: 38929961
DOI: 10.3390/jcm13123429 -
Journal of Clinical Medicine Jun 2024Eponyms do not describe any pathogenesis of a disease. So, there is no other way than to memorize the disease or anatomical area. Over the years, new nomenclatures have...
Eponyms do not describe any pathogenesis of a disease. So, there is no other way than to memorize the disease or anatomical area. Over the years, new nomenclatures have been suggested for some diseases due to a better understanding of the pathogenesis. In this article, the changes in the use of Churg-Strauss syndrome were investigated. In the study, a computerized search was performed using the PubMed database. Books and documents, clinical trials, editorials, meta-analyses, reviews, and case reports were included in the study. Data were obtained from the title of the database, and the variations or distribution by year for the nomenclature of the most related studies were evaluated. Overall, 68.3% of the articles included CSS, 25.7% included eosinophilic granulomatous polyangiitis (EGPA), and 6.0% included both nomenclatures. When evaluated in terms of the distribution according to years, it was determined that there was a statistically significant increase in use in terms of EGPA. When evaluated among specific section journals, the highest rate was in Rheumatology (29.4%). The highest rate of using CSS was in the Rheumatology (25.1%) journals, followed by Pulmonary/Respiratory (17%), Cardiovascular (12%), and Allergy/Immunology/Biology (9.8%). The use of EGPA combined with CSS decreased in all the specific journals from 2012 to the present. The findings of the study revealed that the number of articles with the eponym of EGPA showed an increased frequency in contrast to a decreasing frequency for those with CSS during recent years. Today, with the elaboration of the disease pathogenesis and the increase in knowledge, the trend has shifted in this direction.
PubMed: 38929954
DOI: 10.3390/jcm13123424 -
Life (Basel, Switzerland) May 2024Features of cardiovascular autonomic regulation in infants are poorly studied compared with adults. However, the clinical significance of autonomic dysfunction in...
BACKGROUND
Features of cardiovascular autonomic regulation in infants are poorly studied compared with adults. However, the clinical significance of autonomic dysfunction in infants is very high. The goal of our research was to study the temporal and frequency-dependent features, as well as low-frequency synchronization in cardiovascular autonomic regulation in full-term vs. preterm newborns, based on the analysis of their heart rate variability (HRV) and photoplethysmographic waveform variability (PPGV).
METHODS
The study included three groups of newborns: 64 full-term newborns (with a gestational age at birth of 37-40 weeks) with a physiological course of the neonatal adaptation; 23 full-term newborns (with a gestational age at birth of 37-40 weeks) with a pathological course of the neonatal adaptation; and 17 preterm newborns (with a postconceptional age of 34 weeks or more). We conducted spectral analysis of HRV and PPGV, along with an assessment of the synchronization strength between low-frequency oscillations in HRV and in PPGV (synchronization index). We employed several options for the boundaries of the high-frequency (HF) band: 0.15-0.40 Hz, 0.2-2 Hz, 0.15-0.8 Hz, and 0.24-1.04 Hz.
RESULTS
Preterm newborns had higher heart rate, RMSSD, and PNN50 values relative to both groups of full-term newborns. Values of SDNN index and synchronization index (S index) were similar in all groups of newborns. Differences in frequency domain indices of HRV between groups of newborns depended on the considered options of HF band boundaries. Values of frequency domain indices of PPGV demonstrated similar differences between groups, regardless of the boundaries of considered options of HF bands and the location of PPG signal recording (forehead or leg). An increase in sympathetic influences on peripheral blood flow and a decrease in respiratory influences were observed along the following gradient: healthy full-term newborns → preterm newborns → full-term newborns with pathology.
CONCLUSIONS
Differences in frequency domain indices of autonomic regulation between the studied groups of newborns depended on the boundaries of the considered options of the HF band. Frequency domain indices of PPGV revealed significantly more pronounced differences between groups of newborns than analogous HRV indicators. An increase in sympathetic influences on peripheral blood flow and a decrease in respiratory influences were observed along the following gradient: healthy full-term newborns → preterm newborns → full-term newborns with pathology.
PubMed: 38929659
DOI: 10.3390/life14060675 -
Animals : An Open Access Journal From... Jun 2024The evaluation of the reactivity and distress of cattle during corral management, by means of subjective scores, aims at the standardization of behavioral indicators,...
The evaluation of the reactivity and distress of cattle during corral management, by means of subjective scores, aims at the standardization of behavioral indicators, through non-invasive methods, in addition to enabling the development of more appropriate management practices, thus promoting the comfort and well-being of these animals. Therefore, in this study, we aimed to characterize the temperament and distress of cattle managed in a corral using behavioral indicators during the rainiest period. For this, the experiment was conducted on a property located in the municipality of Mojuí dos Campos, during the rainiest quarter (February-April). Thus, 30 male cattle, not castrated, approximately 29 months of age, clinically healthy, and weighing 310 + 20 kg, were divided into three rearing systems: silvopastoral (SP), traditional (SS), and integrated (SI) systems. There were 10 animals per system. Physiological parameters were collected to evaluate rectal temperature (RT) and respiratory rate (RR), as well as body surface temperature (BST), through thermal windows (head and flank infrared temperature and rump infrared temperature). To evaluate temperament and reactivity, scores indicative of corral behavior were used, namely escape speed (ES), tension score (SS_1), tension score (SS_2), reactivity scale (RS), movement score (MS), and temperament scale (TS). The results showed that there was a thermal amplitude of 5.9 °C on average and 8.6 °C at maximum when comparing the structure of the corral and the trees. In addition, the comparisons between the production systems for the behavioral variables did not differ at the 5% significance level, except for ES, where the traditional system differed from the integrated system and the silvopastoral system, showing intermediate average values for both. In addition, there was a positive correlation between the variables RT and RR (r = 0.72; < 0.01), RR and SS_2 (r = 0.38; = 0.04), flank infrared temperature and MS (r = 0.47; = 0.01), rump infrared temperature and RS (r = 0.37; = 0.04), SS_1 and RS (r = 0.41; = 0.02), SS_1 and SS_2 (r = 0.39; = 0.03), RS and SS_2 (r = 0.58; = 0.00), RS and MS (r = 0.50; = 0.01), RS and TS (r = 0.61; = 0.00), SS_2 and MS (r = 0.51; = 0.00), SS_2 and TS (r = 0.47; = 0.01), and MS and TS (r = 0.44; = 0.02), and a negative correlation between ES and TS (r = -0.42; = 0.02). The rainy season had a major influence on the evaluation of temperature and distress levels during handling in the corral, as evidenced by the association between physiological and behavioral parameters.
PubMed: 38929388
DOI: 10.3390/ani14121769 -
Animals : An Open Access Journal From... Jun 2024The ovariectomy (OVE) procedure can trigger somatosensory and visceral peritoneal nociception. Sacrococcygeal epidural (ScE) anesthesia may complement or replace...
The ovariectomy (OVE) procedure can trigger somatosensory and visceral peritoneal nociception. Sacrococcygeal epidural (ScE) anesthesia may complement or replace systemic analgesia used for feline OVE, reducing opioid consumption and their related undesirable adverse effects and consequently reducing or completely blocking the sympathetic nervous system activation during this procedure. The present study aimed to evaluate the activation of the sympathetic nervous system resulting from adding an ScE injection of bupivacaine 0.25% (0.3 mL kg) in feline OVE and identify whether this translates to hemodynamic variables stability. A Parasympathetic Tone Activity (PTA) monitor was applied given that it performs analysis of heart rate variability (HRV) detecting changes in sympathetic and parasympathetic tone, making it a good tool for detecting activation of the sympathetic nervous system during the study. Two groups of animals were evaluated in five perioperative times, namely, the control group (CG) (n = 18) with systemic analgesia alone and the sacrococcygeal epidural group (ScEG) (n = 20) with 0.25% bupivacaine combined with systemic analgesia. Thirty-eight female cats were selected. All animals assigned to CG and ScEG were premedicated with dexmedetomidine (20 μg kg IM) and methadone (0.2 mg kg IM). General anesthesia was induced with propofol IV ad effectum and maintained with isoflurane in 100% oxygen. Heart rate, non-invasive systolic and median blood pressure, respiratory rate, and instantaneous parasympathetic tone activity were recorded. Compared to systemic analgesia alone (CG), sacrococcygeal epidural (ScEG) reduced the rise of common hemodynamic variables but did not prevent sympathetic nervous system activation.
PubMed: 38929350
DOI: 10.3390/ani14121732 -
International Journal of Environmental... May 2024The Brazilian Amazon, a vital tropical region, faces escalating threats from human activities, agriculture, and climate change. This study aims to assess the...
The Brazilian Amazon, a vital tropical region, faces escalating threats from human activities, agriculture, and climate change. This study aims to assess the relationship between forest fire occurrences, meteorological factors, and hospitalizations due to respiratory diseases in the Legal Amazon region from 2009 to 2019. Employing simultaneous equation models with official data, we examined the association between deforestation-induced fires and respiratory health issues. Over the studied period, the Legal Amazon region recorded a staggering 1,438,322 wildfires, with 1,218,606 (85%) occurring during August-December, known as the forest fire season. During the forest fire season, a substantial portion (566,707) of the total 1,532,228 hospital admissions for respiratory diseases were recorded in individuals aged 0-14 years and 60 years and above. A model consisting of two sets of simultaneous equations was constructed. This model illustrates the seasonal fluctuations in meteorological conditions driving human activities associated with increased forest fires. It also represents how air quality variations impact the occurrence of respiratory diseases during forest fires. This modeling approach unveiled that drier conditions, elevated temperatures, and reduced precipitation exacerbate fire incidents, impacting hospital admissions for respiratory diseases at a rate as high as 22 hospital admissions per 1000 forest fire events during the forest fire season in the Legal Amazon, 2009-2019. This research highlights the urgent need for environmental and health policies to mitigate the effects of Amazon rainforest wildfires, stressing the interplay of deforestation, climate change, and human-induced fires on respiratory health.
Topics: Wildfires; Humans; Brazil; Adolescent; Infant; Seasons; Respiratory Tract Diseases; Forests; Child, Preschool; Infant, Newborn; Child; Hospitalization; Middle Aged; Climate Change; Fires; Young Adult
PubMed: 38928922
DOI: 10.3390/ijerph21060675