Category: Statistics

Chem Rev. 2024 Oct 31. doi: 10.1021/acs.chemrev.4c00438. Online ahead of print.

ABSTRACT

Hydrogen-deuterium exchange (HDX) has become a pivotal method for investigating the structural and dynamic properties of proteins. The versatility and sensitivity of mass spectrometry (MS) made the technique the ideal companion for HDX, and today HDX-MS is addressing a growing number of applications in both academic research and industrial settings. The prolific generation of experimental data has spurred the concurrent development of numerous computational tools, designed to automate parts of the workflow while employing different strategies to achieve common objectives. Various computational methods are available to perform automated peptide searches and identification; different statistical tests have been implemented to quantify differences in the exchange pattern between two or more experimental conditions; alternative strategies have been developed to deconvolve and analyze peptides showing multimodal behavior; and different algorithms have been proposed to computationally increase the resolution of HDX-MS data, with the ultimate aim to provide information at the level of the single residue. This review delves into a comprehensive examination of the merits and drawbacks associated with the diverse strategies implemented by software tools for the analysis of HDX-MS data.

PMID:39481095 | DOI:10.1021/acs.chemrev.4c00438

JCO Glob Oncol. 2024 Oct;10:e2400097. doi: 10.1200/GO.24.00097. Epub 2024 Oct 31.

ABSTRACT

PURPOSE: Women with pathogenic variants (PVs) in breast cancer (BC) and ovarian cancer (OC) associated genes are candidates for cancer risk-reducing strategies. Limited information is available regarding risk-reducing surgeries (RRS) among Hispanics. The aim of this study was to describe the uptake of RRS in an international real-world experience of Hispanic women referred for genetic cancer risk assessment (GCRA) and to identify factors affecting uptake.

METHODS: Between July 1997 and December 2019, Hispanic women, living in the United States or in Latin America, enrolled in the Clinical Cancer Genomics Community Research Network registry were prospectively included. Demographic characteristics and data regarding RRS were obtained from chart reviews and patient-reported follow-up questionnaires. Median follow-up was 41 months.

RESULTS: Among 1,736 Hispanic women referred for GCRA, 27.2% women underwent risk-reducing mastectomy (RRM), 25.5% risk-reducing salpingo-oophorectomy (RRSO) and, 10.7% both surgeries. Among BRCA carriers, rates of RRM and RRSO were 47.6% and 56.7%, respectively. In the multivariate analyses, being a carrier of a BC susceptibility gene (odds ratio [OR], 3.44), personal history of BC (OR, 6.22), living in the US (OR, 3.90), age ≤50 years (OR, 1.68) and, family history of BC (OR, 1.56) were associated with a higher likelihood of undergoing RRM. Carrying an OC susceptibility gene (OR, 6.72) was associated with a higher likelihood of undergoing RRSO.

CONCLUSION: The rate of RRS among Hispanic women is suboptimal. PV carriers, women with personal history of cancer, and those with a family history of cancer were more likely to have RRS, with less uptake outside the US. Understanding personal and systemic factors influencing uptake may enable interventions to increase risk appropriate uptake of RRS.

PMID:39481075 | DOI:10.1200/GO.24.00097

JCO Glob Oncol. 2024 Oct;10:e2400249. doi: 10.1200/GO-24-00249. Epub 2024 Oct 31.

ABSTRACT

PURPOSE: Cancer recurrence is an important long-term outcome of cancer survivors that is often not routinely collected and recorded by population-based registries. In this study, we review population-based studies to determine the current availability, landscape, and infrastructure of long-term outcomes, particularly metastatic recurrence, in women initially diagnosed with nonmetastatic breast cancer (MBC).

METHODS: We reviewed the literature to identify studies that used population-based registry data to examine the distribution of metastatic recurrence in women diagnosed with non-MBC. Data on outcomes and methods of ascertainment were extracted. Registry infrastructure including sources and funding was also reviewed.

RESULTS: A total of 23 studies from 11 registries in eight countries spanning Europe, North America, and Oceania were identified and included in the review. Most studies were retrospective in nature and collected recurrence data only for ad hoc studies rather than as part of their routine registration. Definition of recurrence and data sources varied considerably across studies: the cancer-free time interval between the start of follow-up and risk window ranged from the diagnosis of primary tumor (n = 7) to 6 months from diagnosis (n = 1); the start of follow-up differed between initial diagnosis (n = 16) and treatment (n = 7).

CONCLUSION: Cancer surveillance should encompass outcomes among survivors for research and monitoring. Studies are underway, but more are needed. Cancer registries should be supported to routinely collect recurrence data to allow complete evaluation of MBC as an outcome to be conducted and inform health care providers and researchers of the prognosis of both nonmetastatic and metastatic patients with breast cancer.

PMID:39481072 | DOI:10.1200/GO-24-00249

Neurology. 2024 Nov 26;103(10):e210027. doi: 10.1212/WNL.0000000000210027. Epub 2024 Oct 31.

ABSTRACT

OBJECTIVES: The objective of this study was to estimate the incidence, timing, and type of new cancer diagnosis among patients with cryptogenic stroke.

METHODS: We used data from the ARCADIA trial, which enrolled patients with cryptogenic stroke and atrial cardiopathy. Participants were prospectively followed, and serious adverse events were assessed every 3 months or sooner if investigators were alerted between visits to an event. Kaplan-Meier statistics were used to estimate the cumulative incidence of a cancer diagnosis within the first year after randomization.

RESULTS: Among 878 participants without baseline history of cancer, 13 (1.5%) were diagnosed with incident cancer in the year after randomization, comprising 12 solid cancers (3 prostate, 2 breast, 2 gastrointestinal, and 5 other primary sites) and 1 hematologic cancer (non-Hodgkin lymphoma). The cumulative incidences of a cancer diagnosis were 0% at 3 months, 0.6% (95% CI 0.2%-1.5%) at 6 months, and 2.0% (95 CI 1.1%-3.4%) at 1 year. The median time from index stroke to cancer diagnosis was 261 days (interquartile range 183-358).

DISCUSSION: In a multicenter cryptogenic stroke cohort with prospective follow-up, the 1-year cumulative incidence of a cancer diagnosis was 2%. This rate may be an underestimation because of the clinical trial population and exclusion of cancers diagnosed immediately after stroke.

TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03192215. Registered June 20, 2017. First patient enrolled February 1, 2018.

PMID:39481070 | DOI:10.1212/WNL.0000000000210027

Neurology. 2024 Nov 26;103(10):e209950. doi: 10.1212/WNL.0000000000209950. Epub 2024 Oct 31.

ABSTRACT

BACKGROUND AND OBJECTIVES: Although most spontaneous intracerebral hemorrhages (ICHs) are due to cerebral small vessel diseases (SVDs), between 1 in 7 and 1 in 10 are due to a macrovascular cause. Rapid diagnosis has important therapeutic and prognostic implications but sometimes requires digital subtraction angiography (DSA), an invasive procedure which cannot be performed in all patients. MRI provides optimal sensitivity for markers of SVD but was not included in previous risk stratification scores. We aimed to create and validate a risk stratification score for macrovascular causes of ICH including MRI findings to guide diagnosis and further investigations.

METHODS: We pooled data from 2 large observational study cohorts (London/United Kingdom and Graz/Austria) of consecutive patients with ICH who had brain MRI and at least 1 angiographic modality within 90 days of symptom onset. The primary outcome was a macrovascular cause of ICH (arteriovenous malformation/dural arteriovenous fistula, aneurysm, cavernoma, or cerebral venous thrombosis), with the diagnosis based on neurovascular multidisciplinary meetings. Using lasso logistic regression, we built the MRI Assessment of the Causes of intRacerebral haemOrrhage (MACRO) score to assess the probability of a macrovascular cause. We performed internal validation using bootstrapping and external validation in an independent cohort (Bern/Switzerland).

RESULTS: We included 1,043 patients with ICH (mean age 66 years, 42% female), 78 of whom had a macrovascular cause (7.5%). The final score includes age (0-39, 40-69, or ≥70), location of ICH (lobar, deep, or infratentorial), and SVD markers on MRI (≥1 microbleed, ≥1 lacune, presence of cortical superficial siderosis, or white matter hyperintensities using the Fazekas scale). The MACRO score showed an optimism-adjusted c-statistic of 0.90 (95% CI 0.88-0.93), superior to existing CT-based scores (p < 0.001). In external validation, the c-statistic was 0.87 (95% CI 0.80-0.94). MACRO scores ≥6 (59.5% of patients) indicated a very low risk of a macrovascular cause (0.2%), while scores ≤2 (9% of patients) indicated a high risk (48.9%).

DISCUSSION: The MRI-based MACRO score shows excellent performance in predicting the likelihood of macrovascular causes of spontaneous intracerebral hemorrhage, making it useful in guiding further investigations. Important limitations include the observational study design and the performance of DSA in a minority of patients.

PMID:39481069 | DOI:10.1212/WNL.0000000000209950

Adv Skin Wound Care. 2024 Oct 1;37(10):536-543. doi: 10.1097/ASW.0000000000000211.

ABSTRACT

Ensuring adequate nutrition is vital for maintaining skin health and promoting successful wound healing. Globally, the rise in malnutrition and diet-related diseases is contributing to increased rates of illness and disability. Populations in food deserts and those experiencing food insecurity are particularly at risk. Being at risk for or having malnutrition associated with chronic conditions such as diabetes and cardiovascular disease can increase the incidence of wounds. Healthcare disparities and varied clinical outcomes among ethnic minorities further contribute to these challenges. Research indicates that racial and ethnic minorities experience a higher prevalence and severity of wounds, including pressure injuries. Detecting early-stage wounds in individuals with darker skin tones can be difficult, adding to the disparities.Culturally appropriate nutrition interventions are essential in addressing these health inequities because tailored approaches tend to be more effective than uniform strategies. Understanding diverse dietary patterns and incorporating cultural food preferences into care plans can improve patient adherence and outcomes. Promoting equity in wound care through culturally sensitive practices helps to foster respect, dignity, and trust within healthcare settings, particularly for minority populations.In this review, the authors highlight the need for inclusive interventions that provide culturally aligned nutrition, supporting patients’ clinical and holistic well-being.

PMID:39481061 | DOI:10.1097/ASW.0000000000000211

JCO Glob Oncol. 2024 Oct;10:e2300390. doi: 10.1200/GO.23.00390. Epub 2024 Oct 31.

ABSTRACT

PURPOSE: This study aimed to develop a multivariable, weighted overall survival (OS) risk score (SRS) for nonmetastatic (M0) invasive breast cancer (M0-BC, SRS_M0-BC).

MATERIALS AND METHODS: This study included a training (1,890 patients) and a validation cohort (850 patients) from the Reggio Emilia Cancer Registry (RE-CR). Ten traditional prognostic variables were evaluated.

RESULTS: In the training set, all the variables but the human epidermal growth factor receptor were significantly associated with OS at univariable analysis. A multivariable model identified an increased death risk for estrogen receptor (hazard ratio [HR], 2.0 [95% CI, 1.1 to 3.1]; P = .021), tumor stages T2-T3 (HR, 2.4 [95% CI, 1.3 to 4.7]; P = .009) and T4 (HR, 5.1 [95% CI, 2.0 to 13.0]; P < .001), and age >74 years (HR, 5.7 [95% CI, 4.0 to 8.2]; P < .001). By assigning scores according to HRs, four risk categories were generated (P for trend <.001). The HRs of death in the high- (282 patients, 15.6%), intermediate-high (275 patients, 15.2%), and intermediate-risk (349 patients, 19.2%) categories patients were, respectively, 27.3, 12.9, and 3.5 times higher, compared with the low-risk (909 patients, 50%) group. Harrell’C index was 81.1%, and the explained variation in mortality was 66.6. Internal cross-validation performed on the accrual index dates yielded a Harrell’C index ranging from 79.5% to 82.3% and an explained variation in mortality ranging from 60.3% to 69.4%. In the validation set, the same risk categories (P for trend <.001) were devised. The Harrell’C index and the explained variation in mortality were 76.1% and 53.7%, respectively, in the whole cohort, maintaining an elevated percentage according to the two accrual index dates.

CONCLUSION: SRS_M0-BC using the real-world RE-CR data set may represent a low-cost, accessible, globally applicable model in daily clinical practice, helping to prognostically stratify patients with invasive M0-BC.

PMID:39481052 | DOI:10.1200/GO.23.00390

Gynecol Endocrinol. 2024 Dec;40(1):2381501. doi: 10.1080/09513590.2024.2381501. Epub 2024 Oct 31.

ABSTRACT

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common hormonal disorder among women of reproductive age. The current study sought to assess vitamin D status in women with PCOS compared to the control group and to describe the association between vitamin D deficiency and the features of PCOS.

MATERIAL AND METHODOLOGY: A descriptive retrospective study about 176 women of reproductive age was conducted. The sample was divided into two groups: individuals with PCOS (82 women) and healthy individuals without PCOS (94 women). Vitamin D deficiency was defined as a serum concentration less than 10 ng/ml. We used the Statistical Package for the Social Sciences (SPSS), version 21 for all analyses.

RESULTS: In our study, vitamin D deficiency was observed in 40.2% PCOS patients and 24% controls. The 25(OH)D level was lower in PCOS women and the incidence of vitamin D deficiency and insufficiency were significantly higher in comparison with the control group (p < 0.05). Furthermore, PCOS women with insulin resistance or obesity had lower 25(OH)D levels in comparison with PCOS individuals without IR or obesity. Furthermore, a significant correlation was found between homeostatic model assessment for insulin resistance (HOMA-IR)/body mass index (BMI) and vitamin D status.

DISCUSSION AND CONCLUSION: Vitamin D deficiency could be one of the etiological mechanisms of PCOS. In fact, the prevalence of vitamin D deficiency in PCOS women is evident, principally in those with obesity or IR. Also, the serum 25(OH)D level was correlated with parameters of insulin resistance and metabolic syndrome. Therefore, it is proposed that vitamin D supplementation may be beneficial for the management of PCOS patients.

PMID:39481002 | DOI:10.1080/09513590.2024.2381501

Dent Med Probl. 2024 Sep-Oct;61(5):729-738. doi: 10.17219/dmp/186712.

ABSTRACT

BACKGROUND: Polyamide-based materials are suitable for three-dimensional (3D) printing.

OBJECTIVES: The aim of the study is to examine the impact of aging on the mechanical, surface and optical properties of polyamide 12.

MATERIAL AND METHODS: A total of 116 specimens were examined, comprising 58 conventionally processed polyamide 12 (PA12_C) specimens and 58 3D-printed polyamide 12 (PA12_3D) specimens. The modulus of elasticity was determined before and after mechanical and thermal aging with 1,000, 3,000, 9,000, and 1,000, 3,000 and 7,000 cycles, respectively. The surface roughness (Ra), Ra change (ΔRa) and color change (ΔE) were examined before and after chemical aging (1, 12 and 36 days, with artificial saliva, coffee and red wine) using surface profilometry and color spectroscopy. The Kruskal-Wallis test, Mann-Whitney U test and Bonferroni-Holm correction were employed, with a significance level of p < 0.05.

RESULTS: Before and after mechanical aging, the modulus of elasticity for PA12_3D showed significantly higher values (761 MPa and 747 MPa, respectively) in comparison to PA12_C (515 MPa and 455 MPa, respectively; adjusted p < 0.001). Additionally, before and after thermal aging, the modulus of elasticity for PA12_3D exhibited significantly higher values (833 MPa and 705 MPa, respectively) compared to PA12_C (516 MPa and 458 MPa, respectively; adjusted p < 0.001). The Ra of PA12_3D was higher than that of PA12_C at the baseline (0.41 μm compared to 0.31 μm, respectively), and remained higher during the aging process. The ΔRa values were small for both groups. The ΔE was significantly higher for PA12_3D compared to PA12_C after 12 days (6.2 (PA12_3D) compared to 4.8 (PA12_C), adjusted p = 0.003) and 36 days of storage in red wine (8.2 (PA12_3D) compared to 6.8 (PA12_C), adjusted p = 0.003). After 36 days of coffee storage, the observed changes were found to be statistically significant (8.6 (PA12_3D) compared to 6.7 (PA12_C), adjusted p < 0.001).

CONCLUSIONS: The 3D-printed polyamide 12 demonstrated higher rigidity, Ra and discoloration compared to the conventionally processed polyamide 12. However, not all of the observed parameter differences were significant or clinically relevant. These differences may impact clasp retention, biofilm formation and aesthetic appearance. Nevertheless, the clinical efficacy of 3D printing may be significant.

PMID:39480966 | DOI:10.17219/dmp/186712

Dermatol Surg. 2024 Oct 31. doi: 10.1097/DSS.0000000000004472. Online ahead of print.

ABSTRACT

BACKGROUND: One-third of US adults are bothered by excessive sweating, approximately 5% are diagnosed with hyperhidrosis. A topical patch using targeted alkali thermolysis (TAT) was developed for treatment of this condition.

OBJECTIVE: This study was intended to assess the efficacy and safety of the TAT-Patch for axillary sweat reduction.

MATERIALS AND METHODS: A randomized, multicenter, double-blind, sham-controlled, pivotal trial enrolled 120 subjects to a bilateral axillary treatment with a TAT patch (63 subjects) or sham patch (57 subjects).

RESULTS: The primary end point was achieved; 64% of TAT-treated versus 44% of sham-treated subjects (p = .0332) improved from Hyperhidrosis Disease Severity Scale (HDSS) 3/4 to HDDS 1/2 at 4 weeks. Targeted alkali thermolysis treatment also showed a statistically significant improvement over sham treatment for all secondary end points, including gravimetric sweat production and subject-reported quality-of-life (QoL) assessments. The duration of effect is approximately 3 months, determined by the time to return to baseline HDSS. Mild-to-moderate treatment-site adverse events (AEs) were reported in 22% of TAT patch subjects. No serious or severe AEs were reported.

CONCLUSION: HDSS, GSP, and QoL findings confirm clinically meaningful sweat reduction and a significant improvement in quality of life following a single TAT patch treatment. This device has potential to offer a new, noninvasive treatment option that is well tolerated with minimal downtime.

PMID:39480962 | DOI:10.1097/DSS.0000000000004472