Tag: statistics

Breast Cancer Res Treat. 2023 Apr 21. doi: 10.1007/s10549-023-06931-1. Online ahead of print.

ABSTRACT

PURPOSE: To determine the genetic and immune features associated with the recurrence of human epidermal growth factor receptor2-positive (HER2 +) breast cancer (BC) after trastuzumab-based treatment.

METHODS: A retrospective cohort study of 48 patients who received trastuzumab-based treatment was divided into recurrent and non-recurrent groups according to clinical follow-up. Baseline samples from all 48 patients were analyzed for genetic variation, HLA allele type, gene expression, and immune features, which were linked to HER2 + BC recurrence. Statistics included logistic regression models, Kaplan-Meier plots, and Univariate Cox proportional hazards models.

RESULTS: Compared with the non-recurrent group, the extracellular matrix-related pathway and 3 Hallmark gene sets were enriched in the recurrent group. The infiltration levels of immature B cells and activated B cells were significantly increased in the non-recurrent group, which correlated remarkably with improved overall survival (OS) in two other published gene expression datasets, including TCGA and METABRIC. In the TCGA cohort (n = 275), activated B cells (HR 0.23, 95%CI 0.13-0.43, p < 0.0001), and immature B cells (HR 0.26, 95%CI 0.12-0.59, p < 0.0001). In the METABRIC cohort (n = 236), activated B cells (HR 0.60, 95%CI 0.43-0.83, p = 0.002), and immature B cells (HR 0.65, 95%CI 0.47-0.91, p = 0.011). Cox regression suggested that immature B cells and activated B cells were protective factors for outcome OS.

CONCLUSIONS: Aberrant activation of multiple pathways and low baseline tumor-infiltrating B cells are related to HER2 + BC trastuzumab-based recurrence, which primarily affects the antitumor activity of trastuzumab.

PMID:37084155 | DOI:10.1007/s10549-023-06931-1

Clin Transl Oncol. 2023 Apr 21. doi: 10.1007/s12094-023-03179-5. Online ahead of print.

ABSTRACT

PURPOSE: Neoadjuvant chemotherapy (NAC) significantly improved the prognosis of patients with locally advanced gastric cancer (LAGC). Several biomarkers, including HER2 and MMR/MSI are crucial for treatment decisions in the advanced stage but, currently, no biomarkers can guide the choice of NAC in clinical practice. Our aim was to evaluate the role of MSI and HER2 status on clinical outcomes.

METHODS: We retrospectively collected LAGC patients treated with NAC and surgery +/- adjuvant chemotherapy from 2006 to 2018. HER2 and MSI were assessed on endoscopic and surgical samples. Pathologic complete response (pCR) rate, overall survival (OS), and event-free survival (EFS) were estimated and evaluated for association with downstaging and MSI.

RESULTS: We included 76 patients, 8% were classified as MSI-H, entirely consistent between endoscopic and surgical samples. Six percent of patients were HER2 positive on endoscopic and 4% on surgical samples. Tumor downstaging was observed in 52.5% of cases, with three pCR (5.1%), none in MSI-H cancers. According to MSI status, event-free survival (EFS) and overall survival (OS) were higher for MSI-H patients to MSS [EFS not reached vs 30.0 months, p = 0.08; OS not reached vs 39.6 months, p = 0.10].

CONCLUSION: Our work confirms the positive prognostic effect of MSI-H in the curative setting of LAGC, not correlated with pathologic tumor downstaging. Prospective ad-hoc trial and tumor molecular profiling are eagerly needed.

PMID:37084152 | DOI:10.1007/s12094-023-03179-5

Pediatr Cardiol. 2023 Apr 21. doi: 10.1007/s00246-023-03156-3. Online ahead of print.

ABSTRACT

After Fontan operation, decreased venous capacitance and venoconstriction are adaptive mechanisms to maintain venous return and cardiac output. The consequent higher venous pressure may adversely impact end-organ function, exercise capacity and result in worse clinical outcomes. This pilot study evaluated the safety and effect of isosorbide dinitrate (ISDN), a venodilator, on exercise capacity, peripheral venous pressure (PVP), and liver stiffness in patients with Fontan circulation. In this prospective single-arm trial, 15 individuals with Fontan circulation were evaluated at baseline and after 4 weeks of therapeutic treatment with ISDN. Primary aims were to assess the safety of ISDN and the effect on maximal exercise. We also aimed to evaluate the effect of ISDN on ultrasound-assessed liver stiffness, markers of submaximal exercise, and PVP at rest and peak exercise. Repeated measures t-tests were used to assess change in variables of interest in response to ISDN. Mean age was 23.5 ± 9.2 years (range 11.2-39.0 years), and 10/15 (67%) were male. There was no statistically significant change in peak VO₂ (1401 ± 428 to 1428 ± 436 mL/min, p = 0.128), but VO₂ at the anaerobic threshold increased (1087 ± 313 to 1115 ± 302 mL/min, p = 0.03). ISDN was also associated with a lower peak exercise PVP (22.5 ± 4.5 to 20.6 ± 3.0 mmHg, p = 0.015). Liver stiffness was lower with ISDN, though the difference was not statistically significant (2.3 ± 0.4 to 2.1 ± 0.5 m/s, p = 0.079). Of the patients completing the trial, mild headache was common (67%), but there were no major adverse events. Treatment with ISDN for 4 weeks is well-tolerated in patients with a Fontan circulation. ISDN is associated with an increase in VO₂ at anaerobic threshold, lower peak PVP, and a trend toward lower liver stiffness. Larger, longer duration studies will be necessary to define the impact of ISDN on clinical outcomes in the Fontan circulation.Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT04297241.

PMID:37084132 | DOI:10.1007/s00246-023-03156-3

J Microbiol. 2023 Apr 21. doi: 10.1007/s12275-023-00045-5. Online ahead of print.

ABSTRACT

Microbial communities played a vital role in maintaining homeostasis of ocular surface. However, no studies explored the myopia-associated conjunctiva microbiota changes until now. In this study, conjunctival sac swab specimens were collected from 12 eyes of low myopia (LM), and 14 eyes of high myopia (HM) patients. The V3-V4 region of the 16S rRNA gene was amplified and then sequenced. Statistical analysis was performed to investigate differences in the taxonomy and diversity between two groups. Compared to LM, higher Ocular Surface Disease Index (OSDI) scores were observed in HM group. The Shannon index of the HM was lower than that of the LM group (P = 0.017). Principle coordinate analysis and Partial Least Squares Discrimination Analysis showed distinct microbiome composition between two groups. At the phylum level, there were higher relative abundances of Proteobacteria (68.27% vs 38.51%) and lower abundances of Actinobacteria (3.71% vs 9.19%) in HM, compared to LM group (P = 0.031, 0.010, respectively). At the genus level, the abundances of Acinetobacter in HM (18.16%) were significantly higher than the LM (6.52%) group (P = 0.011). Actinobacteria levels were negatively correlated with the myopic spherical equivalent and OSDI scores. Moreover, positive correlations were found between Proteobacteria levels and OSDI scores, Acinetobacter levels were positively correlated with myopic spherical equivalent and OSDI scores. In conclusion, HM Patients have bacterial microbiota imbalance in the conjunctival sac, compared with LM patients. Proteobacteria, Actinobacteria, Acinetobacter may play roles in the HM associated ocular surface irritation.

PMID:37084130 | DOI:10.1007/s12275-023-00045-5

Arch Osteoporos. 2023 Apr 21;18(1):53. doi: 10.1007/s11657-023-01243-9.

ABSTRACT

This study examined the relationship between hip fractures and weather warnings with the hypothesis higher rates of fractures occur during warnings. National hip fracture database and weather warning records were utilised. Higher rates of hip fractures were found with severe warnings. This has implications for planning in future severe warnings.

BACKGROUND: Hip fractures represent a significant burden on the Irish Health system with 3666 in 2020. The Irish National Meteorological Service operates a colour coded warning system. Yellow being least severe, while orange represents weather with capacity to impact individuals in affected areas and red represents advice to protect themselves and property. Previous studies investigated the seasonality of hip fractures, which remains but none have investigated the relationship between weather warnings and rates of hip fractures. The hypothesis was that increasing weather warnings would be associated with increased hip fractures. The aim was to investigate the relationship between weather warnings and hip fractures in the Republic of Ireland.

METHODS: Comparison of national weather warning archives from 2013 to 2019 to Fracture Database records. Reviews assessed whether fractures occurred on days a weather warning was in place in the individual’s local county. A statistical analysis of warning features and their relationship to hip fractures was then performed. Fractures and weather warnings were stratified by county with both a panel and case crossover analysis performed.

RESULTS: There was a tendency towards increased incidence of hip fractures with weather warnings in adjusted analysis (IRR 1.02; 95%CI 0.99-1.06; p-value 0.123). Orange warnings were associated with a statistically higher incidence of fractures (IRR 1.06; 1.01-1.12; p-value 0.026). In both panel and case crossover analysis, both orange and yellow warnings were associated with fractures. Red warnings were associated with a lower incidence of fracture on day of warning (adjusted incidence rate ratio 0.92; 0.70-1.22; p-value 0.569) but a higher incidence on the following day (adjusted incidence rate ratio 1.14; 0.88-1.46; p-value 0.313).

CONCLUSION: An increased incidence of hip fractures appears to occur during weather warnings. Consideration should be given when preparing for periods of extreme weather, ensuring sufficiently resources.

PMID:37084122 | DOI:10.1007/s11657-023-01243-9

AAPS J. 2023 Apr 21;25(3):44. doi: 10.1208/s12248-023-00795-5.

ABSTRACT

During the write-up of the meeting summary reports from the 2019 dissolution similarity workshop held at the University of Maryland’s Center of Excellence in Regulatory Science and Innovation (M-CERSI), several coauthors continued their discussions to develop a “best-practice” document defining the steps required to assess dissolution profiles in support of certain biowaivers and postapproval changes. In previous reports, current challenges related to dissolution profile studies were discussed such that the steps outlined in the two flow charts (“decision trees”) presented here can be applied. These decision trees include both recommendations for the use of equivalence procedures between reference and test products as well as application of the dissolution safe space concept. Common approaches towards establishing dissolution safe spaces are described. This paper encourages the preparation of protocols clearly describing why and how testing is performed along with the expected pass/fail criteria prior to generating data on the materials to be evaluated. The target audience of this manuscript includes CMC regulatory scientists, laboratory analysts, as well as statisticians from industry and regulatory health agencies involved in the assessment of product quality via in vitro dissolution testing. Building upon previous publications, this manuscript provides a solution to the current ambiguity related to dissolution profile comparison. The principles outlined in this and previous manuscripts provide a basis for global regulatory alignment in the application of dissolution profile assessment to support manufacturing changes and biowaiver requests.

PMID:37084114 | DOI:10.1208/s12248-023-00795-5

J Cancer Res Clin Oncol. 2023 Apr 21. doi: 10.1007/s00432-023-04768-1. Online ahead of print.

ABSTRACT

PURPOSE: To explore the optimal timing of locoregional therapy in patients with colorectal cancer (CRC) recurrence after radical resection and initially unresectable liver metastases but no other metastases and whether maintenance therapy should be performed after achieving no evidence of disease (NED).

METHODS: This study was jointly carried out in six medical institutions in China to collect the clinical data of patients with primary CRC from January 2015 to December 2021. Research participants were identified according to the inclusion criteria of this study for statistical analysis of the clinical characteristics and recurrence time.

RESULTS: 625 patients CRC with metachronous initially unresectable liver metastases but no other metastases were enrolled. Multivariate analysis showed that the number of metastases in the liver and the time from the start of first-line chemotherapy to locoregional therapy significantly affected the progression-free survival (PFS, P < 0.05) following the first-line treatment, and continued maintenance therapy reduced the risk of tumor progression in the patients (P < 0.05). Furthermore, stratified analysis showed that the median PFS of patients with 3-5 metastases in the liver was maximized when the time from the start of first-line chemotherapy to locoregional therapy was 3-4 months. Patients with > 6 metastases in the liver should extend the duration between the start of first-line chemotherapy and locoregional therapy to more than four months. Similarly, with the significant increase in the number of metastases in the liver, subsequent maintenance therapy significantly extended the PFS of the patients.

CONCLUSIONS: The overall therapeutic plan in patients with CRC recurrence after radical resection and initially unresectable liver metastases but no other metastases should consider the individual patients’ situations, especially the number of metastases in the liver at initial recurrence.

PMID:37084112 | DOI:10.1007/s00432-023-04768-1

J Mol Model. 2023 Apr 21;29(5):151. doi: 10.1007/s00894-023-05558-9.

ABSTRACT

CONTEXT: Hydrogen bonds play a vital role in the stability and functioning of biomolecules. Suitable binary liquids are often used as prototypes for the study of biologically significant hydrogen bond studies and their intricate networks. Often, such systems show deviations in their physico-chemical properties from ideal conditions. As a continuation of our research interest in biologically important hydrogen-bonded systems, this paper reports the classical molecular dynamic studies on mixtures of aniline with 8 primary alcohols (C_RH_2R+1-OH, R = 1 to 8) for the complete concentration range. The energetics results indicate the predominance of OH–O interactions over other hydrogen bonds. Structures in the network are analyzed using radial distribution function (RDF), hydrogen bond statistics, and graph theoretical analysis (GTA). Coordination numbers, hydrogen bond statistics, and GTA show a bunching of alcohol-alcohol hydrogen bonds for lower aniline concentrations, while the aniline-aniline interactions are not affected by changes in the concentration.

METHODS: Interaction energies are calculated using B3LYP/6-311G++(d, p) density functional theory using Gaussian-09. The molecular dynamics simulations are carried out using GROMACS (V 2020.6) with the OPLS/AA force field and the simulation box is visualized using VMD. The NetworkX Python package is used for GTA calculation.

PMID:37084111 | DOI:10.1007/s00894-023-05558-9

J Glob Health. 2023 Apr 21;13:04047. doi: 10.7189/jogh.13.04047.

ABSTRACT

BACKGROUND: Professional community health workers (CHWs) can help achieve universal health coverage, although evidence gaps remain on how to optimise CHW service delivery. We conducted an unblinded, parallel, cluster randomised trial in rural Mali to determine whether proactive CHW delivery reduced mortality and improved access to health care among children under five years, compared to passive delivery. Here we report the secondary access endpoints.

METHODS: Beginning from 26-28 February 2017, 137 village-clusters were offered care by CHWs embedded in communities who were trained, paid, supervised, and integrated into a reinforced public-sector health system that did not charge user fees. Clusters were randomised (stratified on primary health centre catchment and distance) to care during CHWs during door-to-door home visits (intervention) or based at a fixed village site (control). We measured outcomes at baseline, 12-, 24-, and 36-month time points with surveys administered to all resident women aged 15-49 years. We used logistic regression with cluster-level random effects to estimate intention-to-treat and per-protocol effects over time on prompt (24-hour) treatment within the health sector.

RESULTS: Follow-up surveys between February 2018 and April 2020 generated 20 105 child-year observations. Across arms, prompt health sector treatment more than doubled compared to baseline. At 12 months, children in intervention clusters had 22% higher odds of receiving prompt health sector treatment than those in control (cluster-specific adjusted odds ratio (aOR) = 1.22; 95% confidence interval (CI) = 1.06, 1.41, P = 0.005), or 4.7 percentage points higher (adjusted risk difference (aRD) = 0.047; 95% CI = 0.014, 0.080). We found no evidence of an effect at 24 or 36 months.

CONCLUSIONS: CHW-led health system redesign likely drove the 2-fold increase in rapid child access to care. In this context, proactive home visits further improved early access during the first year but waned afterwards.

REGISTRATION: ClinicalTrials.gov NCT02694055.

PMID:37083317 | DOI:10.7189/jogh.13.04047

Int Health. 2023 Apr 21:ihad012. doi: 10.1093/inthealth/ihad012. Online ahead of print.

ABSTRACT

BACKGROUND: The public health impact of neglected tropical diseases (NTDs) is quite substantial. The objective of this study was to assess the knowledge and response capability of health professionals regarding NTDs in Kaduna State, Nigeria.

METHODS: A pre-tested questionnaire with a Cronbach’s α coefficient of 0.716 was administered to 350 health professionals. The questionnaire assessed the knowledge, resource availability and capacity to handle NTD cases.

RESULTS: Only 38 (12.6%) respondents were familiar with the World Health Organization’s definition of NTDs. Although self-reported knowledge was highest for physicians (37 [82.2%]), there was no statistically significant knowledge disparity between cadres of health professionals. Only 12 (46.2%) practitioners in private health facilities reported adequate knowledge. The tier of practice was significantly associated with management of NTDs (χ2 = 10.545; df 2; p = 0.005). Only 24 (47.1%) medical laboratory scientists and 18 (40.0%) physicians had adequate clinical resources for management of NTDs. Nearly three-quarters (211 (70.1%)] of respondents had never been trained in the management of NTDs. More than half (177 [58.8%]) of facilities lacked pharmaceuticals or standard operating procedures for management of NTDs.

CONCLUSIONS: Self-reported knowledge of NTDs was suboptimal. Physical and clinical resources for the diagnosis and treatment of NTDs were inadequate. Targeted training, increased funding and provision of adequate resources are needed in order to ameliorate the situation.

PMID:37083280 | DOI:10.1093/inthealth/ihad012