Nevin Manimala

Pulm Pharmacol Ther. 2023 Aug 20:102245. doi: 10.1016/j.pupt.2023.102245. Online ahead of print.

ABSTRACT

INTRODUCTION: The climate crisis poses an immediate threat to human health and well-being, demanding urgent adaptions across sectors, including healthcare. The development of pressurized metered dose inhalers (MDIs) with greater sensitivity to the climate emergency using novel propellants with lower global warming potentials (GWPs), but comparable pharmacokinetic (PK) parameters to currently marketed MDIs, is a vital step toward reducing the impact of healthcare for respiratory disorders on climate change. This study evaluated the relative bioavailabilities of the individual components of a fixed-dose combination of budesonide/glycopyrrolate/formoterol fumarate (BGF) 160/9/4.8 μg per actuation between three different propellant formulations.

METHODS: Healthy male participants (aged 18-60 years) were randomized into a single-blind, three-period, single-dose, single-center, crossover study (NCT04600505). The PK and safety and tolerability profiles of BGF MDI formulated with two novel propellants with low GWP (hydrofluoroolefin-1234ze [HFO]; hydrofluorocarbon-152a [HFC]) were compared with BGF MDI formulated with the propellant used in the currently marketed reference product (hydrofluoroalkane-134a [HFA]). The study included a screening period, three treatment periods (with 3- to 7-day washout periods between each dose), and a follow-up. The primary PK parameters assessed were maximum observed plasma concentration (C_max), area under the plasma concentration curve (AUC) from time zero extrapolated to infinity (AUC_inf), and AUC from time zero to the time of the last quantifiable analyte concentration (AUC_last). The study was not powered to statistically demonstrate bioequivalence.

RESULTS: Forty-seven participants completed the study, and 24 participants were evaluable for PK assessments. Systemic exposure, based on geometric mean ratios (90% confidence interval), to each BGF component from the test propellants delivered in a standard MDI was comparable with the reference propellant for AUC_last (HFO vs. HFA: budesonide, 107.30 [94.53, 121.90]; glycopyrrolate, 106.10 [86.18, 130.60]; formoterol, 98.13 [86.44, 111.40]; HFC vs. HFA: budesonide, 98.80 [84.59, 115.40]; glycopyrrolate, 99.71 [80.84, 123.00]; formoterol, 107.00 [88.82, 128.90]); AUC_inf (where evaluable) and C_max followed the same trend. There were no serious adverse events or adverse events leading to treatment discontinuation. No new safety signals were observed.

CONCLUSIONS: Systemic BGF component exposure was similar for both test propellants (HFO and HFC) compared with the HFA reference propellant, with an acceptable safety profile in the studied population. Therefore, both novel low GWP propellants show strong potential as candidates for development of MDIs with greater sensitivity to the climate crisis, a vital step toward ameliorating the detrimental impact of healthcare on the environment. Further investigation in larger studies is warranted.

PMID:37607661 | DOI:10.1016/j.pupt.2023.102245

J Pediatr. 2023 Aug 20:113680. doi: 10.1016/j.jpeds.2023.113680. Online ahead of print.

ABSTRACT

OBJECTIVE: To develop and implement a resident-led firearm safety curriculum delivered to pediatrics residents and evaluate outcomes STUDY DESIGN: A firearm safety curriculum was developed in 2019 – 2020 at a single academic center, using Kern’s framework and cognitive load theory. The curriculum was organized using the “Be SMART” firearm safety model. Sessions were led by resident peers. The content included workshops on firearm safety counseling, advocacy training, and a gun lock program in collaboration with the local police department. Content was integrated into existing residency didactic curriculum. Impact was measured by a pre/post-test knowledge assessment and a systematic chart review.

RESULTS: The curriculum was provided to 41/66 (62%) pediatrics residents. Knowledge improved (67% to 77% correct) when comparing pre- with post-intervention. A total of 1,477 charts were reviewed. Compared with a historical cohort, participants more often asked about presence of a firearm (27% vs. 69%, p < .0001) and counseled on firearm safety (9% vs. 25%, p < .0001). In the post-intervention group, 25% of eligible families were provided a gun lock.

CONCLUSIONS: A firearm safety curriculum designed by pediatrics residents and administered to their peers resulted in a statistically significant improvement in inquiries about firearm ownership and safety counseling in an urban tertiary care continuity clinic. These results demonstrate the promising outcomes of a firearm safety program developed by residents and delivered to peers.

PMID:37607648 | DOI:10.1016/j.jpeds.2023.113680

Sci Total Environ. 2023 Aug 20:166448. doi: 10.1016/j.scitotenv.2023.166448. Online ahead of print.

ABSTRACT

Penguin guano has been considered as a suitable bioindicator of the exposure to environmental contaminants in Antarctic environment. Although trace metal content values in penguin guano have been widely reported, the kinetics of their mobility in seawater have not been determined. In the present study, we have estimated the release rate of dissolved Cd, Co, Cu, Fe, Mn, Mo, Ni, Pb, V, and Zn from Gentoo (Pygoscelis papua) penguins guano to Antarctic seawater by 120 h laboratory and at external natural conditions of temperature and light experiments. A mathematical model using two metal pools guano (labile and equilibrium) and seawater compartments considering pseudo-first-order kinetics, is proposed in order to interpret and predict the release of trace metals. A good statistical agreement between experimental and modelled concentration values allows us obtention of kinetic parameters and partition coefficients (Kd_i). These values allow to estimate releases into seawater from 5400 to 6.3 μg/day·penguin of Cu and V, respectively. More than 50 % of the initial content of all the studied elements are released during the first two hours, reaching 90 % release in the decreasing order of speed Ni ≫ Cu ≈ Mo > Mn > Co > Cd ≈ Pb; periods of up to one hour, Fe, V and Zn reach a maximum release and are then readsorbed. Equilibrium releases >90 % for Mo and Cd, and 55 % – 46 % for Co, Ni, Pb and Mn are obtained; Zn with 5.4 %, V with 1.7 % and Fe with 0.88 % show the lowest values. With an overwhelming growth of estimated population south of 60°S of 259.750 breeding pairs we estimate that the Gentoo penguin population is releasing annually in the Southern Ocean, 716 kg Cu, 188 kg Mn, 113 kg Fe, 102 kg Zn, 17.7 kg Mo, 12.0 kg Ni, 8.70 kg Cd, 4.59 kg Co, 6.27 kg Pb and 0.790 kg V of soluble metals.

PMID:37607628 | DOI:10.1016/j.scitotenv.2023.166448

Environ Res. 2023 Aug 20:116885. doi: 10.1016/j.envres.2023.116885. Online ahead of print.

ABSTRACT

BACKGROUND: Reduced birthweight is associated with adverse perinatal and long-term outcomes. A few studies examined the association between climatic factors and birthweight with inconsistent results probably due to differences in exposure assessment, statistical models, climatic parameters, and study populations.

METHODS: We obtained data from the Republic of Cyprus birth registry from 2007 to 2020, and matched climatic exposures (i.e., temperature, relative humidity, temperature variability, humidity variability) by the hospital district at birth. We used distributed lag models to examine the association between term birthweight, temperature, humidity, and their variability to identify critical windows. Our models were adjusted for coarse particulate matter level (≤10 μm [PM₁₀), and individual-level covariates. Subgroup analysis was conducted to examine effect modification by maternal age and education.

RESULTS: We identified two critical windows of exposure to ambient temperature at early and late pregnancy. The cumulative change of birthweight per 5 °C increases in mean weekly temperature was -57.27 (2%) (95% Confidence Interval [CI]: 99.62 (3.1%), -14.92 (0.5%)) and -79.2 (2.5%) (95%CI: 117.03 (3.5%), -41.52 (1.3%)) grams during weeks 1-8 and weeks 28-37, respectively. There was no significant effect of humidity, temperature variability, or humidity variability on birthweight. Based on subgroup analysis, mothers with post-secondary education were more sensitive to temperature, but the marginal significance of differences in effect estimates may be linked with differences in sample size.

CONCLUSION: Our study suggests that higher ambient temperature exposure during early and late pregnancy is associated with lower birthweight in main and subgroup analysis. The findings demonstrate in a country highly impacted by climate change like Cyprus that rising temperatures may be associated with perinatal outcomes in susceptible populations during sensitive windows of exposure.

PMID:37607623 | DOI:10.1016/j.envres.2023.116885

J Microbiol Methods. 2023 Aug 20:106810. doi: 10.1016/j.mimet.2023.106810. Online ahead of print.

ABSTRACT

Comparing the microbiome across study arms is a recurrent goal in many studies. Standard statistical methods are often used for this purpose, however, they do not always represent the best choice in this context given the characteristics of microbiota sequencing data, e.g., non-negative, highly skewed counts with a large number of zeros. A multi-part strategy, that combines a two-part test (as described by Wagner et al., 2011), a Wilcoxon sum-rank test, a Chi-square and a Barnard’s test was explored to compare the taxa abundance between study arms. The choice of the test is based on the data structure. The type I error of the multi-part strategy was evaluated by using a simulation study and the method was applied to real data. The script to perform the analysis with the multi-part approach is provided in the statistical software SAS. Several scenarios were simulated and in all of them the type I error was not inflated. Based on the statistical differences resulting from the two-part test (as described by Wagner et al., 2011) and the multi-part strategy (as proposed in this article), different biological implications can be extracted from the same comparison in the same data set. In the comparison of taxa abundance between study arms, we showed that careful attention needs to be paid on the data structure, in order to be able to choose an appropriate analysis method. Our approach selects the most suitable test according to the type of data observed, maintains a good type I error and is easily applicable by using the SAS macro provided.

PMID:37607610 | DOI:10.1016/j.mimet.2023.106810

Am J Perinatol. 2023 Aug 22. doi: 10.1055/a-2158-8422. Online ahead of print.

ABSTRACT

OBJECTIVE: In view of the excessive use of antibiotics in our Neonatal Intensive Care Unit(NICU), we launched a 5 year multidisciplinary quality improvement (QI)initiative in our NICU in 2018. We had set our AIM of decreasing the Antibiotic Use Rate (AUR) from 22% down to 17%.

STUDY DESIGN: The QI initiative was conducted in our 53-bed level 3B NICU. We used the core elements of antibiotic stewardship and focused on improving gaps in knowledge by using updated standards of care and a multidisciplinary approach. Outcome measures included overall antibiotic use rate in NICU. Statistical control chart (P chart) was used to plot the AUR data quarterly.

RESULTS: The AUR demonstrated a decline at the onset , and at the end of the initiative the AUR demonstrated a sustained decline to 13.18 % , a 40% decrease from the baseline AUR of 22%. The changes that were implemented included development of evidence-based guidelines for babies less than and greater than 35 weeks, daily Antibiotic Stewardship Rounds, sepsis risk calculator, antibiotic stop orders (48 hour stop, 36 hour soft stop and 36 hour hard stop) and periodic reviews.

CONCLUSIONS: Our multidisciplinary approach using all the core elements of an Antibiotic Stewardship Program (ASP) significantly decreased AUR in our NICU.

PMID:37607590 | DOI:10.1055/a-2158-8422

Semin Neurol. 2023 Aug 22. doi: 10.1055/s-0043-1771459. Online ahead of print.

ABSTRACT

Increasing research links the gut microbiome to neurodegenerative disorders. The gut microbiome communicates with the central nervous system via the gut-brain axis and affects behavioral and cognitive phenotypes. Dysbiosis (a dysfunctional microbiome) drives increased intestinal permeability and inflammation that can negatively affect the brain via the gut-brain axis. Healthier metabolic and lipid profiles and cognitive phenotypes are observed in individuals with more distinct microbiomes. In this review, we discuss the role of the gut microbiome and gut-brain axis in neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease and related animal models, in cancer and cancer treatments, and in metabolic syndrome. We also discuss strategies to improve the gut microbiome and ultimately brain function. Because healthier cognitive phenotypes are observed in individuals with more distinct microbiomes, increased efforts are warranted to develop therapeutic strategies for those at increased risk of developing neurological disorders and patients diagnosed with those disorders.

PMID:37607587 | DOI:10.1055/s-0043-1771459

Neuropediatrics. 2023 Aug 22. doi: 10.1055/s-0043-1772191. Online ahead of print.

ABSTRACT

OBJECTIVE: Children with epilepsy have a significantly increased risk of cognitive impairment. EpiTrack Junior is a screening tool developed for fast assessment of cognitive function in children with epilepsy. The tool is validated for German children. This cohort study aims to investigate the differences in cognitive function between healthy Danish children and Danish children diagnosed with epilepsy METHODS: The cognitive function of 204 healthy controls and 90 children and adolescents diagnosed with epilepsy was examined using EpiTrack Junior. The participants of the control group were aged 6 to 16 years. The patients were aged 6 to 20 years. Statistical analyses were performed with the use of SPSS Statistics.

RESULTS: The control group showed significantly higher scores than the patient group in three of six subtests and total test scores (p-values ranging from 0.033 to <0.001). When grouped according to the EpiTrack Junior guidelines, more patients showed scores “below average” or “poor” compared to the control group. The age-corrected total score was not associated with antiepileptic drug treatment (p-value of 0.732) nor with a history of focal seizures (p-value of 0.215). A history of generalized tonic-clonic seizures (GTCS) was associated with a higher EpiTrack Junior score (p-value of 0.035).

CONCLUSION: The patient group showed statistically significant lower test scores compared to the control group confirming the relationship between impaired cognitive function and childhood epilepsy. Furthermore, a correlation between a higher EpiTrack Junior score and the presence of GTCS was found. Focal seizures and antiepileptic drug treatment were not associated with the EpiTrack Junior score.

PMID:37607574 | DOI:10.1055/s-0043-1772191

Gynecol Endocrinol. 2023 Aug 18;39(1):2242956. doi: 10.1080/09513590.2023.2242956.

ABSTRACT

OBJECTIVES: Endometriosis is a common benign gynaecological disease that significantly compromises the quality of life of patients. To date, invasive surgery is the method of choice to visually and histologically confirm endometriosis. Thus, there is a major interest to develop noninvasive diagnostic tools. Oxidative stress is one of the proposed mechanisms of pathogenesis and may be involved in pelvic pain, dysmenorrhea, dyspareunia, and infertility in endometriosis patients. Thus, markers of oxidative stress may serve as diagnostic biomarkers for endometriosis.

DESIGN: This prospective case-control study assessed erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPX), serum hexanoyl lysine (HEL) and peritoneal fluid HEL.

PARTICIPANTS/MATERIALS, SETTING, AND METHODS: We enrolled 86 women with primary infertility; the case group included 57 women with endometriosis, and the control group included 29 women with unexplained primary infertility. All the patients underwent laparoscopy, and the diagnosis was confirmed histologically. RANDOX and RANSEL reagents were used to determine the levels of SOD and GPX, respectively, and ELISA was used to determine the levels of HEL.

RESULTS: We found no statistically significant differences in the erythrocyte levels of GPX (p value 0.623) or SOD (p value 0.122) or the serum or peritoneal fluid levels of HEL (p value 0.562 and 0.329 accordingly).

CONCLUSIONS: SOD, GPX, and HEL levels most likely do not differ between patients with unexplained infertility and patients with endometriosis.

PMID:37607570 | DOI:10.1080/09513590.2023.2242956

J Int Med Res. 2023 Aug;51(8):3000605231193580. doi: 10.1177/03000605231193580.

ABSTRACT

OBJECTIVE: This study was performed to determine the outcomes of patients with coronavirus disease 2019 (COVID-19) who developed hypoxemic respiratory failure necessitating high-flow nasal cannula (HFNC) therapy and to identify the predictors of HFNC therapy success.

METHODS: This retrospective observational study involved all patients treated with HFNC therapy at a center for COVID-19 in Viet Nam from August to October 2021.

RESULTS: The study recruited 302 patients. Of these 302 patients, 171 (56.6%) underwent successful HFNC therapy, and the all-cause mortality rate was 33.44%. Non-critical COVID-19 and a higher respiratory rate-oxygenation (ROX) index at 48 hours after initiating HFNC therapy were independently correlated with HFNC therapy success. The statistically significant predictors of HFNC therapy success were younger age, non-critical COVID-19, a higher platelet count when starting HFNC therapy, and a higher ROX index at 24, 36, and 48 hours after HFNC therapy initiation.

CONCLUSIONS: HFNC therapy appears to be effective in patients with COVID-19 who develop respiratory failure requiring respiratory support. Non-critical COVID-19 and a higher ROX index measured 48 hours after HFNC therapy initiation might serve as predictive factors for the success of HFNC therapy.

PMID:37607569 | DOI:10.1177/03000605231193580