Category: Nevin Manimala

J Appl Biomech. 2023 Aug 22:1-14. doi: 10.1123/jab.2023-0079. Online ahead of print.

ABSTRACT

In this narrative review, we explore developments in the field of computational musculoskeletal model personalization using the Physiome and Musculoskeletal Atlas Projects. Model geometry personalization; statistical shape modeling; and its impact on segmentation, classification, and model creation are explored. Examples include the trapeziometacarpal and tibiofemoral joints, Achilles tendon, gastrocnemius muscle, and pediatric lower limb bones. Finally, a more general approach to model personalization is discussed based on the idea of multiscale personalization called scaffolds.

PMID:37607721 | DOI:10.1123/jab.2023-0079

Stat Med. 2023 Aug 22. doi: 10.1002/sim.9880. Online ahead of print.

ABSTRACT

In this article, we present a flexible model for microbiome count data. We consider a quasi-likelihood framework, in which we do not make any assumptions on the distribution of the microbiome count except that its variance is an unknown but smooth function of the mean. By comparing our model to the negative binomial generalized linear model (GLM) and Poisson GLM in simulation studies, we show that our flexible quasi-likelihood method yields valid inferential results. Using a real microbiome study, we demonstrate the utility of our method by examining the relationship between adenomas and microbiota. We also provide an R package “fql” for the application of our method.

PMID:37607718 | DOI:10.1002/sim.9880

J Am Vet Med Assoc. 2023 Aug 22:1-8. doi: 10.2460/javma.23.06.0320. Online ahead of print.

ABSTRACT

OBJECTIVE: To define cyclic changes in anti-Müllerian hormone (AMH), inhibin-B, and progesterone concentrations and establish statistically valid, population-based clinical reference ranges in queens.

ANIMALS: Cyclic queens (fertile, n = 6; infertile, 6) from an institutional breeding colony were blood sampled longitudinally, each for over 2 months, between November 2021 and February 2022, and residual serum samples from intact (n = 205) and ovariohysterectomized (49) queens from clinical submissions were used to establish reference ranges for intact and spayed females.

METHODS: AMH and inhibin-B were measured using commercially available ELISAs, progesterone was measured using an in-house ELISA, and 90% CIs were calculated from these data.

RESULTS: AMH and inhibin-B fluctuated in a highly correlated, cyclic pattern in 3 queens that did not ovulate immediately, whereas AMH declined as progesterone increased, indicative of ovulation, which occurred spontaneously early in the sampling period in 3 others; statistically valid reference ranges were established in intact and ovariohysterectomized females.

CLINICAL RELEVANCE: Cyclic changes in hormone profiles were defined, providing relevant context for interpreting results in cases seeking to determine gonadal status (presence or absence of gonadal tissue) on the basis of established, population-based reference ranges reported here for cats for the first time.

PMID:37607677 | DOI:10.2460/javma.23.06.0320

Vasc Endovascular Surg. 2023 Aug 22:15385744231198355. doi: 10.1177/15385744231198355. Online ahead of print.

ABSTRACT

INTRODUCTION: Lower limb venous anomalies, including duplicated veins, are common and have significant impacts on the outcomes and efficacy of venous surgery. Digital subtraction angiography (DSA) guided venography, serving as the tertiary diagnostic option for venous disorders, offers valuable informations to clinical practitioners.

PATIENTS AND METHODS: A retrospective study was conducted on 195 patients with suspected venous disease, evaluating 259 limbs with venography imaging. Two experienced interventional vascularists evaluated the images to determine the incidence and characteristics of variances in the femoral, popliteal, great saphenous, and small saphenous veins. Moreover, blood samples were collected to assess the safety of the venography procedure by monitoring changes in renal function.

RESULT: Duplication variations were found in the lower limb veins, with the highest prevalence in the femoral vein (11.28%, 22/195), followed by the great saphenous vein (4.1%, 8/195), and the popliteal vein (1.54%, 3/195). No severe contrast agent allergies or postoperative complications were reported. No statistically significant differences were found in creatinine and urea levels pre- and post-operation for patients without duplication variations, those with duplication of the great saphenous, femoral, or popliteal vein (P < .05).

CONCLUSION: DSA-guided venography is effective in identifying venous variations in lower limb disease. DFV is the most common recurrent vein, while DPV is the least. Adequate preparation ensures safety, high spatial resolution, dynamic imaging, and low tissue interference.

PMID:37607668 | DOI:10.1177/15385744231198355

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