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Enhanced Skin Deposition of Betamethasone Dipropionate from a Novel Formulation and Drug Delivery Technology

Dermatol Ther (Heidelb). 2023 Jun 23. doi: 10.1007/s13555-023-00959-3. Online ahead of print.

ABSTRACT

INTRODUCTION: Effective topical drug delivery is the essence of dermatologic treatment. The drug must be applied to the skin surface, be released from the vehicle, enter the stratum corneum, traverse the epidermis, and enter the dermis pharmacologically intact. New advances have improved emulsion-type formulation and drug delivery technology by encapsulating dispersed oil droplets in a robust multimolecular aqueous film of surfactants, oil, and water, enabling a multifold decrease in surfactant concentration compared to conventional creams. In the research reported here, we studied this new concept, termed polyaphron dispersion (PAD) technology, by comparing skin delivery of betamethasone dipropionate from a novel oil-in-water emulsion system of calcipotriene and betamethasone dipropionate (CAL/BDP) cream to that from a traditional topical suspension (CAL/BDP TS) utilizing in vitro and in vivo detection methods.

METHODS: The amount of BDP released from the CAL/BDP cream and CAL/BDP TS was evaluated using both in vitro Franz cell analysis and in vivo human tape stripping from ten female human volunteers after a single application of CAL/BDP cream or CAL/BDP TS. For the tape stripping analysis, 20 circular tape strips were taken from forearm application sites at 1, 2, 4, and 8 h after application and analyzed for the amount of BDP in the tape strip using liquid chromatography-mass spectrometry (LC-MS).

RESULTS: The in vitro Franz cell analysis demonstrated that the cumulative amount of BDP that diffused through the epidermis was statistically significantly greater for the CAL/BDP cream compared to the CAL/BDP TS at all time points. In addition, consistently higher amounts of BDP were recovered following CAL/BDP cream application than following CAL/BDP TS application at 1, 2, 4, and 8 h following application utilizing the in vivo tape stripping technique.

CONCLUSION: The novel PAD technology-based cream formulation delivered more BDP into the upper stratum corneum and lower epidermis than a traditional topical suspension.

PMID:37351830 | DOI:10.1007/s13555-023-00959-3

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Prediction of in-hospital deterioration in normotensive pulmonary embolism remains elusive: external validation of the calgary acute pulmonary embolism score

J Thromb Thrombolysis. 2023 Jun 23. doi: 10.1007/s11239-023-02853-3. Online ahead of print.

ABSTRACT

Acute pulmonary embolism (PE) is a frequently diagnosed condition. Prediction of in-hospital deterioration is challenging with current risk models. The Calgary Acute Pulmonary Embolism (CAPE) score was recently derived to predict in-hospital adverse PE outcomes but has not yet been externally validated. Retrospective cohort study of normotensive acute pulmonary embolism cases diagnosed in our emergency department between 2017 and 2019. An external validation of the CAPE score was performed in this population for prediction of in-hospital adverse outcomes and a secondary outcome of 30-day all-cause mortality. Performance of the simplified Pulmonary Embolism Severity Index (sPESI) and Bova score was also evaluated. 712 patients met inclusion and exclusion criteria, with 536 patients having a sPESI score of 1 or more. Among this population, the CAPE score had a weak discriminative power to predict in-hospital adverse outcomes, with a calculated c-statistic of 0.57. In this study population, an external validation study found weak discriminative power of the CAPE score to predict in-hospital adverse outcomes among normotensive PE patients. Further efforts are needed to define risk assessment models that can identify normotensive PE patients at risk for in hospital deterioration. Identification of such patients will better guide intensive care utilization and invasive procedural management of PE.

PMID:37351823 | DOI:10.1007/s11239-023-02853-3

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Venous thromboembolism and bleeding after hepatectomy: role and impact of risk adjusted prophylaxis

J Thromb Thrombolysis. 2023 Jun 23. doi: 10.1007/s11239-023-02847-1. Online ahead of print.

ABSTRACT

Venous thromboembolism (VTE) occurs in 2-6% of post-hepatectomy patients and is associated with increased mortality and morbidity. The use of VTE risk assessment models in hepatectomy cases remains unclear. Our study aimed to determine the use and impact of Caprini guideline indicated VTE prophylaxis following hepatectomy. Hepatectomy cases performed during 2016-2021 were included. Caprini score and VTE prophylaxis were determined retroactively, and VTE prophylaxis was categorized as appropriate or inappropriate. The primary outcome was the receipt of appropriate prophylaxis, and secondary outcomes were postoperative VTE and bleeding. Statistical analyses included Fisher Exact test, Kruskal-Wallis, Pearson Chi-Square test, and multivariate regression models. R Statistical software was used for analysis. A p-value < 0.05 or 95% Confidence Interval (CI) excluding 1 was considered significant. A total of 1955 hepatectomy cases were analyzed. Patient demographics were similar between study cohorts. Inpatient, 30- and 90-day VTE rates were 1.28%, 0.56%, and 1.24%, respectively. By Caprini guidelines, 59% and 4.3% received appropriate in-hospital and discharged VTE prophylaxis, respectively. Inpatient VTE (4.5-fold) and mortality (9.5-fold) were lower in patients receiving appropriate prophylaxis. All discharged VTE and mortality occurred in patients not receiving appropriate prophylaxis. Inpatient, 30- and 90-day bleeding rates were 8.4%, 0.62%, and 0.68%, respectively. Appropriate prophylaxis did not increase postoperative bleeding. Increasing Caprini score inversely correlated with receiving appropriate prophylaxis (OR 0.38, CI 0.31-0.46) at discharge, and appropriate prophylaxis did not correlate with bleeding risk (OR 0.79, CI 0.57-1.12). Caprini guideline indicated prophylaxis resulted in reduced VTE complications without increasing bleeding risk.

PMID:37351821 | DOI:10.1007/s11239-023-02847-1

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Maxillary labial peri-implant hard and soft tissue alteration observed on cross-sectional dimension: a 2-year prospective observational study

Int J Implant Dent. 2023 Jun 23;9(1):16. doi: 10.1186/s40729-023-00477-z.

ABSTRACT

OBJECTIVES: To evaluate how peri-implant hard and soft tissue height (BH, MH) alter after final prostheses placement related to labial hard and soft tissue thickness (BW, MW).

MATERIALS AND METHODS: Forty-five platform-switched implants were classified into four groups according to BW and MW: type 1 (thick BW and thick MW), type 2 (thick BW and thin MW), type 3 (thin BW and thick MW), type 4 (thin BW and thin MW). Tissue resorption was evaluated on cone-beam CT images taken at final prostheses placement, at 1-year follow-up, and at 2-year follow-up. Kruskal-Wallis test and post hoc Mann-Whitney test were applied; significance was set to 0.05.

RESULTS: BH resorption was 0.13 ± 0.12 mm in type 1, 0.26 ± 0.17 mm in type 2, 0.09 ± 0.09 mm in type 3, 0.94 ± 0.19 mm in type 4. Differences between type 1 and 4, type 2 and 4, and type 3 and 4 were statistically significant (p < 0.001, p = 0.005, p < 0.001, respectively). MH resorption was 0.10 ± 0.09 mm in type 1, 0.36 ± 0.16 mm in type 2, 0.12 ± 0.12 mm in Type 3, 0.79 ± 0.23 mm in type 4. Differences between type 1 and 2, type 1 and 4, type 2 and 3, type 2 and 4 and type 3 and 4 were statistically significant (p < 0.001).

CONCLUSIONS: Significantly less BH/MH resorption occurs around implants with thick BW/MW than those with thin BW/MW in 2 years. Implants with thick peri-implant soft tissue resulted in significantly less tissue resorption in second year after final prostheses placement.

PMID:37351804 | DOI:10.1186/s40729-023-00477-z

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Health care impact of implementing a clinical pathway for acute care of pediatric concussion: a stepped wedge, cluster randomised trial

CJEM. 2023 Jun 23. doi: 10.1007/s43678-023-00530-1. Online ahead of print.

ABSTRACT

OBJECTIVES: To test the effects of actively implementing a clinical pathway for acute care of pediatric concussion on health care utilization and costs.

METHODS: Stepped wedge, cluster randomized trial of a clinical pathway, conducted in 5 emergency departments (ED) in Alberta, Canada from February 1 to November 30, 2019. The clinical pathway emphasized standardized assessment of risk for persistent symptoms, provision of consistent information to patients and families, and referral for outpatient follow-up. De-identified administrative data measured 6 outcomes: ED return visits; outpatient follow-up visits; length of ED stay, including total time, time from triage to physician initial assessment, and time from physician initial assessment to disposition; and total physician claims in an episode of care.

RESULTS: A total of 2878 unique patients (1164 female, 1713 male) aged 5-17 years (median 11.00, IQR 8, 14) met case criteria. They completed 3009 visits to the 5 sites and 781 follow-up visits to outpatient care, constituting 2910 episodes of care. Implementation did not alter the likelihood of an ED return visit (OR 0.77, 95% CI 0.39, 1.52), but increased the likelihood of outpatient follow-up visits (OR 1.84, 95% CI 1.19, 2.85). Total length of ED stay was unchanged, but time from physician initial assessment to disposition decreased significantly (mean change – 23.76 min, 95% CI – 37.99, – 9.52). Total physician claims increased significantly at only 1 of 5 sites.

CONCLUSIONS: Implementation of a clinical pathway in the ED increased outpatient follow-up and reduced the time from physician initial assessment to disposition, without increasing physician costs. Implementation of a clinical pathway can align acute care of pediatric concussion more closely with existing clinical practice guidelines while making care more efficient.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05095012.

PMID:37351798 | DOI:10.1007/s43678-023-00530-1

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The Impact of COVID-19 on Trends of Violence-Related Offences in Australia

J Epidemiol Glob Health. 2023 Jun 23. doi: 10.1007/s44197-023-00131-2. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the medium-term impacts of the COVID-19 pandemic on violence-related offences in Australia, and whether there was evidence of a ‘dual pandemic’ of family violence in addition to COVID-19.

METHODS: Autoregressive Integrated Moving Average time series were conducted to analyse publicly available violent crime statistics data from January 2017 to November 2021. Population rates of homicide, sexual, domestic and non-domestic assault were assessed across each Australian state and territory, with the effects of COVID-19 being modelled using the average monthly World Health Organization COVID-19 stringency rating for each jurisdiction.

FINDINGS: All jurisdictions in Australia showed increasing or stable domestic assault trends over the past decade, which were not significantly impacted by COVID-19, nor by the subsequent lockdowns. Non-domestic assaults demonstrated a significant, negative relationship with the stringency index for each jurisdiction, except Western Australia. There was no significant change in the rates of homicide or sexual assault across Australia in relation to COVID-19.

CONCLUSION: Overall, there was no evidence of a ‘dual pandemic’ in Australia, and whilst domestic assaults continue to increase across the country, non-domestic assaults showed a notable but brief decline. However, these have returned to levels at least as high as pre-COVID-19 and some states show a continuing upward trend. The findings also suggest that alcohol availability may have played a role in continuing high violence numbers. Given the ongoing increasing and high levels of family violence in Australia, revised conceptual frameworks and interventions are indicated.

PMID:37351780 | DOI:10.1007/s44197-023-00131-2

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Two-dimensional ultrasound results in underestimation of the ovarian follicle size compared to automated three-dimensional imaging in women undergoing IVF

J Ultrasound. 2023 Jun 23. doi: 10.1007/s40477-023-00797-1. Online ahead of print.

ABSTRACT

BACKGROUND: Traditionally, for the assessment of follicle growth during IVF, two-dimensional (2D) transvaginal ultrasound (US) is used. In the past few years three-dimensional (3D) US has also been introduced.

OBJECTIVES: To compare follicular sizes between 2 and 3D ultrasound imaging on the final day of controlled ovarian stimulation.

METHODS: A prospective observational cohort study including 121 women undergoing controlled ovarian stimulation (COS) between January 2017 and July 2018. All women were assessed by transvaginal 2D and 3D ultrasonography to measure ovarian follicle dimensions on the final day of COS.

RESULTS: The mean difference in paired comparisons between the 3D and 2D US measurements in 25 women with monofollicular development was + 1.6 ± 2.5 mm for the x-dimension and + 1.7 ± 2.4 mm for the y-dimension; and in the total number of 1197 paired measurements of follicles the mean difference + 2.1 ± 3.3 mm and + 1.8 ± 3.9 mm for the x- and y-dimension respectively. In all cases the paired t-test showed that differences were statistically significant (p < 0.01). Further it was conjectured that the 2D underestimation results from the inherent difficulty to precisely place the US probe simultaneously on the perpendicular maximal of the x and y follicle diameters, leading to measurement errors that, by theory, are normally distributed. Running Monte-Carlo simulations based on these measurement errors it was found that both the mean difference and standard deviation are of the same magnitude as the ones found in real measurements, thus proving the conjecture.

CONCLUSIONS: The utilisation of 3D US results in different measurements of the follicular dimensions, and volumes, when compared to conventional 2D US. The differences in the x- and y-dimensions may affect the outcome of an IVF cycle as they are used to define the day of triggering final oocyte maturation, which is associated with the yield of mature oocytes and the probability of live birth.

PMID:37351770 | DOI:10.1007/s40477-023-00797-1

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Oversewing and Gastropexy in Laparoscopic Sleeve Gastrectomy – Two Futile Steps of the Procedure? An Observational Case-Control Study

Obes Surg. 2023 Jun 23. doi: 10.1007/s11695-023-06681-5. Online ahead of print.

ABSTRACT

PURPOSE: Laparoscopic sleeve gastrectomy (LSG) is the most popular primary bariatric metabolic procedure worldwide but severe complications are still reported, and there is no ideal technique to avoid them. This study analyses the impact of oversewing (OS) and gastropexy (GP) on complication rate, early dyspeptic and late de novo GERD symptoms after LSG.

MATERIAL AND METHOD: A case-control study was conducted on patients with obesity who underwent LSG. The total cohort was divided in group A (control group) – patients with no oversewing (OS) or gastropexy (GP), group B – patients with OS but no gastropexy and group C – patients with both OS and GP performed during LSG.

RESULTS: We included 272 patients with obesity with a mean BMI 42.9±6.94 kg/m2, 96 patients in group A, 90 patients in group B and 86 in group C with no statistical differences between them. We had 5 cases of postoperative hemorrhage (4 in group A) and three patients who developed leaks (2 in group A and one in group B). Prolonged and severe early dyspeptic episodes and after 6 months reflux symptoms were significantly more in groups A and B (p<0.05). The operative time was longer in group B and C (p<0.05) but with no difference in procedure -related morbidity and in hospital length of stay.

CONCLUSION: Adding both OS and GP to LSG reduce complications rate with no influence on procedure-related postoperative morbidity and in-hospital length of stay. GP reduces early postoperative dyspeptic and de novo GERD symptoms after LSG.

PMID:37351763 | DOI:10.1007/s11695-023-06681-5

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Effect of Transoral Outlet Reduction on Hepatic Fibrosis in Roux-en-Y Gastric Bypass Patients with Weight Regain and Non-alcoholic Fatty Liver Disease

Obes Surg. 2023 Jun 23. doi: 10.1007/s11695-023-06668-2. Online ahead of print.

ABSTRACT

PURPOSE: Weight regain after Roux-en-Y gastric bypass (RYGB) is associated with worsening of liver outcomes. However, the effect of transoral outlet reduction (TORe) on liver fibrosis in RYGB patients with weight regain and possible advanced fibrosis remains unknown.

MATERIALS AND METHODS: This was a retrospective analysis of prospectively collected data of RYGB patients who underwent TORe for weight regain. Only patients with possible advanced fibrosis were included. TORe was performed using either an endoscopic suturing device (S-TORe) or plication device (P-TORe) to reduce the gastrojejunal anastomosis (GJA) and pouch sizes. Primary outcomes included changes in non-invasive tests (NITs) for fibrosis at 6-12 months. Secondary outcomes included weight loss and changes in insulin resistance and lipid profile at 6-12 months.

RESULTS: Fifty RYGB patients were included. Baseline age and BMI were 55 ± 11 years and 40.1 ± 7.3 kg/m2. Baseline GJA and pouch sizes were 20 ± 7 mm and 5 ± 2 cm, respectively. Thirty patients (60%) underwent S-TORe and 20 patients (40%) underwent P-TORe. At 12 months following TORe, there were statistically significant improvements in NITs for fibrosis, including ALT, AST and FIB-4. There was a trend towards significant improvement in liver stiffness measurement on transient elastography. Patients experienced 8.8 ± 11.2% total weight loss (TWL) (p < 0.0001), with 60% experiencing at least 10% TWL. Additionally, there was a significant improvement in HbA1c and a trend toward significant improvement in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), suggestive of improved insulin sensitivity.

CONCLUSION: TORe is associated with an improvement in hepatic fibrosis in patients with NAFLD and possible advanced fibrosis.

PMID:37351762 | DOI:10.1007/s11695-023-06668-2

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Overlapping group screening for binary cancer classification with TCGA high-dimensional genomic data

J Bioinform Comput Biol. 2023 Jun 22:2350013. doi: 10.1142/S0219720023500130. Online ahead of print.

ABSTRACT

Precision medicine has been a global trend of medical development, wherein cancer diagnosis plays an important role. With accurate diagnosis of cancer, we can provide patients with appropriate medical treatments for improving patients’ survival. Since disease developments involve complex interplay among multiple factors such as gene-gene interactions, cancer classifications based on microarray gene expression profiling data are expected to be effective, and hence, have attracted extensive attention in computational biology and medicine. However, when using genomic data to build a diagnostic model, there exist several problems to be overcome, including the high-dimensional feature space and feature contamination. In this paper, we propose using the overlapping group screening (OGS) approach to build an accurate cancer diagnosis model and predict the probability of a patient falling into some disease classification category in the logistic regression framework. This new proposal integrates gene pathway information into the procedure for identifying genes and gene-gene interactions associated with the classification of cancer outcome groups. We conduct a series of simulation studies to compare the predictive accuracy of our proposed method for cancer diagnosis with some existing machine learning methods, and find the better performances of the former method. We apply the proposed method to the genomic data of The Cancer Genome Atlas related to lung adenocarcinoma (LUAD), liver hepatocellular carcinoma (LHC), and thyroid carcinoma (THCA), to establish accurate cancer diagnosis models.

PMID:37350314 | DOI:10.1142/S0219720023500130