Category: Statistics

Clin Cancer Res. 2024 Feb 20. doi: 10.1158/1078-0432.CCR-23-1977. Online ahead of print.

ABSTRACT

PURPOSE: BCI (H/I) has been shown to predict extended endocrine therapy (EET) benefit. We examined BCI (H/I) for EET benefit prediction in NSABP B-42, which evaluated extended letrozole therapy (ELT) in hormone receptor-positive breast cancer patients after 5 years of ET.

METHODS: Stratified Cox model was used to analyze RFI as primary endpoint, with DR, BCFI, and DFS, as secondary endpoints. Due to a non-proportional effect of ELT on DR, time-dependent analyses were performed.

RESULTS: The translational cohort included 2,178 patients (45% BCI (H/I)-High, 55% BCI (H/I)-Low). ELT showed an absolute 10-year RFI benefit of 1.6% (P=0.10), resulting in an underpowered primary analysis (50% power). ELT benefit and BCI (H/I) did not show a significant interaction for RFI (BCI [(H/I])-Low: 10y absolute benefit 1.1% [HR=0.70, 0.43-1.12, P=0.13]; BCI [(H/I])-High: 2.4% [HR=0.83, 0.55-1.26, p=0.38]; Pinteraction=0.56). Time-dependent DR analysis showed that after 4y, BCI (H/I)-High patients had significant ELT benefit (HR=0.29, 0.12-0.69, P<0.01), whereas BCI (H/I)-Low patients were less likely to benefit (HR=0.68, 0.33-1.39, P=0.29) (Pinteraction=0.14). Prediction of ELT benefit by BCI (H/I) was more apparent in the HER2- subset after 4y (ELT-by-BCI (H/I) Pinteraction=0.04).

CONCLUSIONS: BCI(H/I)-High vs -Low did not show a statistically significant difference in ELT benefit for the primary endpoint (RFI). However, in time-dependent DR analysis, BCI (H/I)-High patients experienced statistically significant benefit from ELT after 4y, whereas (H/I)-Low patients did not. Because BCI (H/I) has been validated as a predictive marker of EET benefit in other trials, additional follow-up may enable further characterization of BCI’s predictive ability.

PMID:38376912 | DOI:10.1158/1078-0432.CCR-23-1977

J Med Internet Res. 2024 Feb 20;26:e47040. doi: 10.2196/47040.

ABSTRACT

BACKGROUND: Tobacco consumption is a leading cause of death and disease, killing >8 million people each year. Smoking cessation significantly reduces the risk of developing smoking-related diseases. Although combined treatment for addiction is promising, evidence of its effectiveness is still emerging. Currently, there is no published research comparing the effectiveness of blended smoking cessation treatments (BSCTs) with face-to-face (F2F) treatments, where web-based components replace 50% of the F2F components in blended treatment.

OBJECTIVE: The primary objective of this 2-arm noninferiority randomized controlled trial was to determine whether a BSCT is noninferior to an F2F treatment with identical ingredients in achieving abstinence rates.

METHODS: This study included 344 individuals who smoke (at least 1 cigarette per day) attending an outpatient smoking cessation clinic in the Netherlands. The participants received either a blended 50% F2F and 50% web-based BSCT or only F2F treatment with similar content and intensity. The primary outcome measure was cotinine-validated abstinence rates from all smoking products at 3 and 15 months after treatment initiation. Additional measures included carbon monoxide-validated point prevalence abstinence; self-reported point prevalence abstinence; and self-reported continuous abstinence rates at 3, 6, 9, and 15 months after treatment initiation.

RESULTS: None of the 13 outcomes showed statistically confirmed noninferiority of the BSCT, whereas 4 outcomes showed significantly (P<.001) inferior abstinence rates of the BSCT: cotinine-validated point prevalence abstinence rate at 3 months (difference 12.7, 95% CI 6.2-19.4), self-reported point prevalence abstinence rate at 6 months (difference 19.3, 95% CI 11.5-27.0) and at 15 months (difference 11.7, 95% CI 5.8-17.9), and self-reported continuous abstinence rate at 6 months (difference 13.8, 95% CI 6.8-20.8). The remaining 9 outcomes, including the cotinine-validated point prevalence abstinence rate at 15 months, were inconclusive.

CONCLUSIONS: In this high-intensity outpatient smoking cessation trial, the blended mode was predominantly less effective than the traditional F2F mode. The results contradict the widely assumed potential benefits of blended treatment and suggest that further research is needed to identify the critical factors in the design of blended interventions.

TRIAL REGISTRATION: Netherlands Trial Register 27150; https://onderzoekmetmensen.nl/nl/trial/27150.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-doi.org/10.1186/s12889-016-3851-x.

PMID:38376901 | DOI:10.2196/47040

Ocul Immunol Inflamm. 2024 Feb 20:1-7. doi: 10.1080/09273948.2024.2317416. Online ahead of print.

ABSTRACT

PURPOSE: This study aims to evaluate the ocular surface characteristics in children diagnosed with uveitis and explore the association between uveitis and dry eye disease (DED).

METHODS: We included 84 children, 42 with uveitis and 42 healthy children. We performed the OSDI questionnaire and several ocular surface tests, including osmolarity, NITBUT, Schirmer test, and vital staining. We used Fisher’s exact test and Mann-Whitney to compare variables and a binomial logistic regression to determine the factors associated with DED.

RESULTS: The difference in the prevalence of DED between uveitis (54.8%) and healthy (31%) groups was statistically significant (p < 0.05). Most patients with uveitis had mixed DED, and none of the healthy subjects had a severe form of the disease. There were no statistically significant differences in most of the tear film tests. However, all parameters tended to worsen in the uveitis group, and lipid layer thickness was thinner (p < 0.036). The uveitis group exhibited significantly more symptoms (p < 0.05). In the multivariate logistic regression, uveitis was associated with an odds ratio (OR) of 3.0 (95% CI: 1.07-8.42, p < 0.05) for DED.

CONCLUSIONS: Our findings demonstrate a significantly higher prevalence of DED in children with uveitis compared to their healthy counterparts. Furthermore, our analysis indicates that the risk of DED in pediatric patients with uveitis is threefold higher than in healthy children. Therefore, it is crucial for clinicians to vigilantly monitor the development of DED in pediatric patients with uveitis and consider the implementation of preventive treatments.

PMID:38376892 | DOI:10.1080/09273948.2024.2317416

Phys Chem Chem Phys. 2024 Feb 20. doi: 10.1039/d3cp04140a. Online ahead of print.

ABSTRACT

The partition coefficient (log P) is an important physicochemical property that provides information regarding a molecule’s pharmacokinetics, toxicity, and bioavailability. Methods to accurately predict the partition coefficient have the potential to accelerate drug design. In an effort to test current methods and explore new computational techniques, the statistical assessment of the modeling of proteins and ligands (SAMPL) has established a blind prediction challenge. The ninth iteration challenge was to predict the toluene-water partition coefficient (log P_tol/w) of sixteen drug molecules. Herein, three approaches are reported broadly under the categories of quantum mechanics (QM), molecular mechanics (MM), and data-driven machine learning (ML). The three blind submissions yield mean unsigned errors (MUE) ranging from 1.53-2.93 log P_tol/w units. The MUEs were reduced to 1.00 log P_tol/w for the QM methods. While MM and ML methods outperformed DFT approaches for challenge molecules with fewer rotational degrees of freedom, they suffered for the larger molecules in this dataset. Overall, DFT functionals paired with a triple-ζ basis set were the simplest and most effective tool to obtain quantitatively accurate partition coefficients.

PMID:38376855 | DOI:10.1039/d3cp04140a

JAMA Netw Open. 2024 Feb 5;7(2):e240062. doi: 10.1001/jamanetworkopen.2024.0062.

ABSTRACT

IMPORTANCE: For some low-income people, access to care during pregnancy is not guaranteed through Medicaid, based on their immigration status. While states have the option to extend Emergency Medicaid coverage for prenatal and postpartum care, many states have not expanded coverage.

OBJECTIVE: To determine whether receipt of first prenatal care services and subsequently receipt of postpartum care through extensions of Emergency Medicaid coverage were associated with increases in diagnosis and treatment of perinatal mental health conditions.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used linked Medicaid claims and birth certificate data from 2010 to 2020 with a difference-in-difference design to compare the rollout of first prenatal care coverage in 2013 and then postpartum services in Oregon in 2018 with a comparison state, South Carolina, which did not cover prenatal or postpartum care as part of Emergency Medicaid and only covered emergent conditions and obstetric hospital admissions. Medicaid claims and birth certificate data were linked by Medicaid identification number prior to receipt by the study team. Participants included recipients of Emergency Medicaid who gave birth in Oregon or South Carolina. Data were analyzed from April 1 to October 15, 2023.

EXPOSURE: Medicaid coverage of prenatal care and Medicaid coverage of postpartum care.

MAIN OUTCOMES AND MEASURES: The main outcome was the diagnosis of a perinatal mental health condition within 60 days postpartum. Secondary outcomes included treatment of a mood disorder with medication or talk therapy.

RESULTS: The study sample included 43 889 births to Emergency Medicaid recipients who were mainly aged 20 to 34 years (32 895 individuals [75.0%]), multiparous (33 887 individuals [77.2%]), and living in metropolitan areas (32 464 individuals [74.0%]). Following Oregon’s policy change to offer prenatal coverage to pregnant individuals through Emergency Medicaid, there was a significant increase in diagnosis frequency (4.1 [95% CI, 1.7-6.5] percentage points) and a significant difference between states in treatment for perinatal mental health conditions (27.3 [95% CI, 13.2-41.4] percentage points). Postpartum Medicaid coverage (in addition to prenatal Medicaid coverage) was associated with an increase of 2.6 (95% CI, 0.6-4.6) percentage points in any mental health condition being diagnosed, but there was no statistically significant difference in receipt of mental health treatment.

CONCLUSIONS AND RELEVANCE: These findings suggest that changing Emergency Medicaid policy to include coverage for prenatal and 60 days of postpartum care for immigrants is foundational to improving maternal mental health. Expanded postpartum coverage length, or culturally competent interventions, may be needed to optimize receipt of postpartum treatment.

PMID:38376840 | DOI:10.1001/jamanetworkopen.2024.0062

Vet Ital. 2023 Jul 31;59(2). doi: 10.12834/VetIt.2710.17457.2.

ABSTRACT

Wild birds have been reported to be reservoirs of viral diseases of poultry, and play an epidemiological role in their maintenance and spread. A serological survey was undertaken to determine the evidence of Newcastle disease virus (NDV) antibodies in wild birds in Zaria Kaduna State, Nigeria. A total of 150 apparently healthy wild birds comprising 30 each laughing dove, speckled pigeons, cattle egrets, village weavers and African silver bills were sampled. Sera collected were analysed for the presence of antibodies against NDV and avian paramyxovirus‑2 (APMV‑2) using the haemagglutination inhibition test. The results showed an overall seroprevalence of 4% (95% CI: 2.05‑10.1) to NDV. African silver bill showed a seroprevalence of 10.0% (95% CI: 2.61‑24.9) NDV antibodies while seroprevalence of 3.3% (95% CI: 0.16‑15.4) was recorded for cattle egrets, village weavers and laughing doves respectively. No statistically significant difference existed for NDV seroprevalence (P>0.05) among the different species of wild birds. All the 150 sera tested negative for APMV‑2 antibodies. The result of this study confirmed the exposure of wild birds to NDV in the study area. Continuous surveillance with isolation and characterization of NDV in the wild birds is therefore recommended for strategic planning for control.

PMID:38376832 | DOI:10.12834/VetIt.2710.17457.2

Vet Ital. 2023 Jul 31;59(2). doi: 10.12834/VetIt.2742.17966.2.

ABSTRACT

This study aimed to investigate environmental mastitis causing bacteria counts in the teat end, somatic cell counts (SCC) of milk samples, cleanliness scores and behavior of cows kept on concrete and rubber mat floorings. For this purpose, 19 Holstein-Friesian dairy cows were allocated into concrete and rubber mat groups. Swab samples were taken from the teat ends to determine the bacterial counts causing environmental mastitis. Milk samples were collected from a composite of all four quarters to determine the SCC. Instantaneous sampling method was utilized to observe the behavioral activities of cows. Cows were visually evaluated to determine the udder cleanliness score. Independent samples t-test was utilized in the statistical analysis of the obtained data. Coliform (P<0.05), Escherichia coli, and Klebsiella spp. (P<0.01) counts of the swab samples taken from the cows housed on concrete flooring were significantly higher than rubber mat group. However, no statistically significant differences were found between groups in terms of total bacteria, Streptococcus spp., and Enterobacteriaceae counts. The SCC on samples taken from cows kept on concrete surface were significantly higher (P<0,05) than that of animals housed on rubber mat. Furthermore, cows in the rubber mat group were determined to be significantly cleaner (P<0.05) than those in concrete group. It was also determined that the cows housed on rubber mat spent significantly longer time for lying behavior (P<0.05), which is a significant indicator of animal comfort. The time spent for standing without eating was considerably higher (P<0.01) in concrete group. In addition, the times spent for eating was significantly lower (P<0.01) in the concrete group. It was concluded that, using rubber mat instead of concrete for flooring in tie-stall barns decreases the contamination of environmental mastitis pathogens, increases milk quality and cow cleanliness score as well as animal comfort and welfare.

PMID:38376829 | DOI:10.12834/VetIt.2742.17966.2

J Mol Med (Berl). 2024 Feb 20. doi: 10.1007/s00109-024-02434-8. Online ahead of print.

ABSTRACT

Recurrent aphthous stomatitis (RAS) is a chronic and recurrent inflammatory disease of the mouth. It is characterised by the appearance of painful ulcers in the oral mucosa. RAS is believed to be a multifactorial disease with genetic predisposition, environmental factors and alterations in the immune system. Oxidative stress, caused by an imbalance between free radicals and the antioxidant system, also appears to be involved in the pathogenesis of RAS. Several risk factors, such as smoking, iron and vitamin deficiency and anxiety, may contribute to the development of the disease. Understanding the underlying mechanisms may help in the prevention and treatment of RAS. We searched PubMed, Scopus and Web of Science databases for articles on oxidative stress in patients with RAS from 2000 to 2023. Studies analysing oxidant and antioxidant levels in the blood and saliva of RAS patients and healthy controls were selected. Of 170 potentially eligible articles, 24 met the inclusion criteria: 11 studies on blood samples, 6 on salivary samples and 7 on both blood and salivary samples. Multiple oxidative and antioxidant markers were assessed in blood and saliva samples. Overall, statistically significant differences were found between RAS patients and healthy controls for most markers. In addition, increased oxidative DNA damage was observed in patients with RAS. Patients with RAS show elevated levels of oxidative stress compared to healthy controls, with a significant increase in oxidative markers and a significant decrease in antioxidant defences in saliva and blood samples.

PMID:38376817 | DOI:10.1007/s00109-024-02434-8

Eur J Nucl Med Mol Imaging. 2024 Feb 20. doi: 10.1007/s00259-024-06653-6. Online ahead of print.

ABSTRACT

PURPOSE: In radioguided surgery (RGS), radiopharmaceuticals are used to generate preoperative roadmaps (e.g., PET/CT) and to facilitate intraoperative tracing of tracer avid lesions. Within RGS, there is a push toward the use of receptor-targeted radiopharmaceuticals, a trend that also has to align with the surgical move toward minimal invasive robotic surgery. Building on our initial ex vivo evaluation, this study investigates the clinical translation of a DROP-IN β probe in robotic PSMA-guided prostate cancer surgery.

METHODS: A clinical-grade DROP-IN β probe was developed to support the detection of PET radioisotopes (e.g., ⁶⁸ Ga). The prototype was evaluated in 7 primary prostate cancer patients, having at least 1 lymph node metastases visible on PSMA-PET. Patients were scheduled for radical prostatectomy combined with extended pelvic lymph node dissection. At the beginning of surgery, patients were injected with 1.1 MBq/kg of [⁶⁸Ga]Ga-PSMA. The β probe was used to trace PSMA-expressing lymph nodes in vivo. To support intraoperative decision-making, a statistical software algorithm was defined and optimized on this dataset to help the surgeon discriminate between probe signals coming from tumors and healthy tissue.

RESULTS: The DROP-IN β probe helped provide the surgeon with autonomous and highly maneuverable tracer detection. A total of 66 samples (i.e., lymph node specimens) were analyzed in vivo, of which 31 (47%) were found to be malignant. After optimization of the signal cutoff algorithm, we found a probe detection rate of 78% of the PSMA-PET-positive samples, a sensitivity of 76%, and a specificity of 93%, as compared to pathologic evaluation.

CONCLUSION: This study shows the first-in-human use of a DROP-IN β probe, supporting the integration of β radio guidance and robotic surgery. The achieved competitive sensitivity and specificity help open the world of robotic RGS to a whole new range of radiopharmaceuticals.

PMID:38376805 | DOI:10.1007/s00259-024-06653-6

Int Ophthalmol. 2024 Feb 20;44(1):98. doi: 10.1007/s10792-024-02934-z.

ABSTRACT

PURPOSE: To determine the interrater reliability (IRR) of thyroid eye disease (TED) photographic assessment using the VISA classification. To assess whether a VISA grading atlas improves ophthalmology trainees’ performance in photographic assessment of TED.

METHODS: A prospective, partially randomized, international study conducted from September 2021 to May 2022. Online study invitation was emailed to a volunteer sample group of 68 ophthalmology college accredited consultants and trainees, and 6 were excluded from the study. Participants were asked to score 10 patient photographs of TED using only the inflammation and motility restriction components of the VISA classification. IRR was compared between groups of practitioners by their level of experience. A clinical activity grading atlas was randomized to 50% of the ophthalmology trainees.

RESULTS: Overall rater ICC was 0.96 for inflammation and 0.99 for motility restriction. No statistically significant difference in IRR between rater groups was identified. Trainees with a grading atlas had the highest IRR for inflammation (ICC = 0.95). Each subcomponent of the inflammation and motility restriction components of VISA classification had an ICC considered good to excellent. The mean overall rater score was 4.6/9 for inflammation and 3.5/12 for motility restriction. For motility restriction there was a reduced mean score variance among all raters when scoring photographs with more severe motility restriction.

CONCLUSION: IRR using the inflammation and motility restriction components of the VISA classification was excellent. A VISA grading atlas improved trainee performance in grading inflammation.

PMID:38376802 | DOI:10.1007/s10792-024-02934-z