Tag: pubmed

Oncologist. 2023 Dec 21:oyad319. doi: 10.1093/oncolo/oyad319. Online ahead of print.

ABSTRACT

INTRODUCTION: In advanced basal cell carcinoma (BCC), the issue of whether Hedgehog inhibitors (HHIs) should be stopped or not after clinical complete response (cCR) achievement remains an unmet clinical need.

MATERIALS AND METHODS: We conducted a retrospective, multicenter study across 7 Italian dermato-oncology units including patients with BCC who continued vismodegib after cCR between 2012 and 2019. We assessed the relationship between the duration of vismodegib intake (days to cCR [DTCR], days to stop after cCR [DTS], total treatment days [TTD]), and disease-free survival (DFS). Reasons to stop vismodegib were (R1) toxicity and (R2) disease recurrence. The relationship between DTCR, DTS, TTD, and DFS in the whole population and in R1 subgroup was assessed by Pearson’s correlation coefficient (P < .05) and Bayesian statistics (BF10).

RESULTS: Sixty-eight BCC patients with a median (m) age of 75.5 years (39-100) were included. Most patients were male (N = 43, 63%), without Gorlin syndrome (N = 56, 82%) and with head and neck area as primary site (N = 51, 75%). After cCR, out of 68 patients, 90% (N = 61/68) discontinued vismodegib: 82% (N = 50/61) due to toxicity (R1), and 18% (N = 11/61) due to recurrence (R2). Conversely, 10% (N = 7/68) continued vismodegib until last follow-up. In the whole population (N = 68), cCR was achieved with a mDTCR of 180.50 days. DFS showed a significant correlation with DTS (P < .01, BF10 = 39.2) and TTD (P < .01, BF10 = 35566), while it was not correlated to DTCR (BF10 < 0.1). The analysis of R1 subgroup (N = 50) confirmed these results. DFS correlated with DTS in all recurrent patients (N = 38, r = 0.44, P < .01) and in the recurrent patients who stopped vismodegib for toxicity (N = 26, r = 0.665, P < .01). DFS was longer when vismodegib was maintained for >2 months after cCR (mDFS > 2 months, N = 54 vs. ≤ 2 months, N = 14: 470 vs. 175 d, P < .01).

CONCLUSIONS: Our retrospective results suggest that HHIs should be continued after cCR to improve DFS in BCC.

PMID:38127280 | DOI:10.1093/oncolo/oyad319

Hormones (Athens). 2023 Dec 21. doi: 10.1007/s42000-023-00520-z. Online ahead of print.

ABSTRACT

PURPOSE: Prostate cancer patients are a heterogeneous group as regards the aggressiveness of the disease. The relationship of steroid hormones with the aggressiveness of prostate cancer is unclear. It is known that the anti-Müllerian hormone (AMH) inhibits prostate cancer cell lines in vitro. The aim of this study is to investigate the relationship of AMH and steroid hormones with the aggressiveness of prostate cancer.

METHODS: This was a prospective study of consecutive radical prostatectomy patients. We measured the following hormones: total testosterone, sex hormone-binding globulin, albumin, luteinizing hormone, follicle-stimulating hormone, estradiol, dehydroepiandrosterone sulfate, androstenedione, and AMH. The minimum follow-up after radical prostatectomy was 5 years. For the aggressiveness of prostate cancer, we considered the following three variables: post-operative Gleason score (GS) ≥ 8, TNM pΤ3 disease, and prostate-specific antigen (PSA) biochemical recurrence (BCR).

RESULTS: In total, 91 patients were enrolled. The mean age and PSA were 64.8 years and 9.3 ng/dl, respectively. The median post-operative GS was 7. Low AMH blood levels were correlated with higher post-operative GS (p = 0.001), as well as with PSA BCR (p = 0.043). With pT3 disease, only albumin was (negatively) correlated (p = 0.008). ROC analysis showed that AMH is a good predictor of BCR (AUC 0.646, 95% CI 0.510-0.782, p = 0.043); a cutoff value of 3.06 ng/dl had a positive prognostic value of 71.4% and a negative prognostic value of 63.3% for BCR. Cox regression analysis showed that AMH is a statistically significant and independent prognostic marker for BCR (p = 0.013). More precisely, for every 1 ng/ml of AMH rise, the probability for PSA BCR decreases by 20.8% (HR = 0.792). Moreover, in Kaplan-Meier analysis, disease-free survival is more probable in patients with AMΗ ≥ 3.06 ng/ml (p = 0.004).

CONCLUSIONS: Low AMH blood levels were correlated with aggressive prostate cancer in this radical prostatectomy cohort of patients. Therefore, AMH could be a prognostic biomarker for the aggressiveness of the disease.

PMID:38127275 | DOI:10.1007/s42000-023-00520-z

Eur J Orthop Surg Traumatol. 2023 Dec 21. doi: 10.1007/s00590-023-03785-7. Online ahead of print.

ABSTRACT

PURPOSE: There is limited evidence for comparing operative and non-operative management of closed, extra-articular distal humeral shaft fractures. This study aims to evaluate these outcomes.

METHODS: A comparative retrospective study was performed for patients who underwent either operative fixation or conservative management with a humeral brace, with clinical and radiological outcomes at minimum 2-year follow-up.

RESULTS: Forty-two patients with median 4.6 years follow-up were included; 24 had surgical fixation and 18 were managed with humeral brace. Assessment of clinical and radiological outcomes demonstrated few statistically significant functional differences between the two groups. Surgical patients achieved faster union for non-comminuted fractures. All patients maintained functional range of motion, with similar complication rates.

CONCLUSION: This study suggests that similar outcomes can be achieved with both managements, though faster union times may be seen in the operative group. Further studies are recommended to evaluate the impact of fracture comminution causing delayed unions.

PMID:38127272 | DOI:10.1007/s00590-023-03785-7

J Thromb Thrombolysis. 2023 Dec 21. doi: 10.1007/s11239-023-02923-6. Online ahead of print.

ABSTRACT

We aim to compare the outcomes in patients with atrial fibrillation detected after stroke (AFDAS) and their counterparts with known AF (KAF) presenting with large vessel occlusion (LVO) treated with mechanical thrombectomy (MT). This observational, prospective study included consecutive patients with acute LVO ischemic stroke of the anterior circulation with AFDAS, KAF and without AF. The primary study outcome was functional independence at 90 days after stroke. The secondary study outcomes were variation of the NIHSS score at 24 h, rate of successful reperfusion, death at 90 days and rate of immediate complications post-procedure. Overall, our cohort included 518 patients with acute ischemic stroke and LVO treated with MT, with 289 (56.8%) without a diagnosis of AF; 107 (21%) with AFDAS; 122 (22.2%) with KAF. There was no significant difference in terms of functional independence at 90 days after stroke between the three groups. Regarding the secondary study outcome, the rate of symptomatic intracranial haemorrhage (sICH) and/or parenchymal hematoma (PH) were significantly higher in the group of patients without AF (respectively, P = 0.030 and < 0.010). Logistic regression analysis showed that the subtypes of AF were not statistically significantly associated with functional independence at 90 days after stroke and with the likelihood of any ICH. Our results suggest that the subtypes of AF are not associated with clinical and safety outcomes of MT in patients with acute stroke and LVO. Further studies are needed to confirm our findings.

PMID:38127260 | DOI:10.1007/s11239-023-02923-6

Qual Life Res. 2023 Dec 21. doi: 10.1007/s11136-023-03560-5. Online ahead of print.

ABSTRACT

PURPOSE: Unsupervised item-response theory (IRT) models such as polytomous IRT based on recursive partitioning (IRTrees) and mixture IRT (MixIRT) models can be used to assess differential item functioning (DIF) in patient-reported outcome measures (PROMs) when the covariates associated with DIF are unknown a priori. This study examines the consistency of results for IRTrees and MixIRT models.

METHODS: Data were from 4478 individuals in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease registry who received cardiac angiography in Alberta, Canada, and completed the Hospital Anxiety and Depression Scale (HADS) depression subscale items. The partial credit model (PCM) based on recursive partitioning (PCTree) and mixture PCM (MixPCM) were used to identify covariates associated with differential response patterns to HADS depression subscale items. Model covariates included demographic and clinical characteristics.

RESULTS: The median (interquartile range) age was 64.5(15.7) years, and 3522(78.5%) patients were male. The PCTree identified 4 terminal nodes (subgroups) defined by smoking status, age, and body mass index. A 3-class PCM fits the data well. The MixPCM latent classes were defined by age, disease indication, smoking status, comorbid diabetes, congestive heart failure, and chronic obstructive pulmonary disease.

CONCLUSION: PCTree and MixPCM were not consistent in detecting covariates associated with differential interpretations of PROM items. Future research will use computer simulations to assess these models’ Type I error and statistical power for identifying covariates associated with DIF.

PMID:38127205 | DOI:10.1007/s11136-023-03560-5

Genet Med. 2023 Dec 18:101050. doi: 10.1016/j.gim.2023.101050. Online ahead of print.

ABSTRACT

PURPOSE: Hao-Fountain syndrome (HAFOUS) is a neurodevelopmental disorder caused by pathogenic variants in USP7. HAFOUS is characterized by developmental delay, intellectual disability, speech delay, behavioral abnormalities, autism spectrum disorder, seizures, hypogonadism and mild dysmorphic features. We investigated the phenotype of eighteen participants with HAFOUS and performed DNA methylation (DNAm) analysis, aiming to generate a diagnostic biomarker. Furthermore, we performed comparative analysis with known episignatures to gain more insight into the molecular pathophysiology of Hao-Fountain syndrome.

METHODS: We assessed genomic DNAm profiles of eighteen individuals with pathogenic variants and variants of uncertain significance (VUS) in USP7 to map and validate a specific episignature. The comparison between the USP7 cohort and 56 rare genetic disorders with earlier reported DNAm episignatures was performed with statistical and functional correlation.

RESULTS: We mapped a sensitive and specific DNAm episignature for pathogenic variants in USP7 and utilized this to reclassify the VUS. Comparative epigenomic analysis showed evidence of HAFOUS similarity to a number of other rare genetic episignature disorders.

CONCLUSIONS: We discovered a sensitive and specific DNAm episignature as a robust diagnostic biomarker for HAFOUS that enables VUS reclassification in USP7. We also expand the phenotypic spectrum of nine new and five previously reported individuals with HAFOUS.

PMID:38126281 | DOI:10.1016/j.gim.2023.101050

Comput Methods Biomech Biomed Engin. 2023 Dec 21:1-24. doi: 10.1080/10255842.2023.2294264. Online ahead of print.

ABSTRACT

Effective disease diagnosis is a critical unmet need on a global scale. The intricacies of the numerous disease mechanisms and underlying symptoms make developing a model for early diagnosis and effective treatment extremely difficult. Machine learning (ML) can help to solve some of these issues. Recently, various ensemble-based ML models have benefited clinicians in early diagnosis. However, one of the most difficult challenges in multi-level ensemble approaches is the classifier selection and their placement in the ensemble framework as it improves the overall performance. Let m classifiers have to select from n classifiers there are (nm) ways. Again, these (nm) possibilities can be arranged in m! ways. Finding the best m classifiers and their positions from total (nm)m! ways is a challenging and hard problem. To address this challenge, a dynamic three-level ensemble framework is proposed. A nested Genetic Algorithm (GA) and ensemble-based fitness function are employed to optimize the classifier selection and their placement in a three-level ensemble framework. Our approach used eleven classifiers and chose seven classifiers by maximizing the fitness function. The proposed model experiments on 12 disease datasets. The proposed model outperformed in terms of accuracy, F1, and G-measure on the Chronic Kidney Disease (CKD) dataset is 0.987, 0.988, and 0.989, respectively. In terms of AUC on the Heart disease dataset (HDD) is 0.998 and in terms of recall on the Hypothyroid disease dataset (HyDD) is 0.988. In addition, the proposed model superiority is statically evaluated by Wilcoxon-Signed-Rank (WSR) test compared with other ensemble models, such as random forest (RF), bagging classifier (BC), XGBoost (XGB), and gradient boost classifier (GBC) with probability value p < 0.05 results shows all the traditional ensemble model differs with proposed model and also effective size evaluated with using the matched-pairs rank biserial correlation coefficient w_c and statistical results shows effective size is large with RF and BC and effective size is medium with XGB and GBC. Proposed model has outperformed comparing with State-Of-The-Art (SOTA) ensemble and non-ensemble models. Further, the proposed model outperformed in terms of the ROC curve in the majority of the disease datasets. The results suggest the usage of the proposed model for disease diagnosis applications.

PMID:38126276 | DOI:10.1080/10255842.2023.2294264

JBI Evid Synth. 2023 Dec 21. doi: 10.11124/JBIES-23-00129. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this review is to examine and describe global pharmacy practice strategies and interventions designed to achieve health equity for First Peoples.

INTRODUCTION: Access to medicines and quality use of medicines is critical to achieving health equity for First Peoples. Pharmacists are uniquely placed to lead the charge in transforming current health systems, reducing health disparities, and bolstering the movement toward health equity.

INCLUSION CRITERIA: Global studies describing pharmacy practice strategies and interventions designed to achieve health equity for First Peoples will be considered for inclusion in the review. Studies relating to all areas of pharmacy practice, including community and clinical pharmacy, social, administrative, pharmaceutical sciences, practice, teaching, research, advocacy, or service relevant to the review’s objective will also be considered for inclusion. The types of studies to be included are qualitative, quantitative, and mixed methods, systematic reviews, scoping reviews, literature reviews, and gray literature.

METHODS: This review will be conducted in accordance with JBI methodology for scoping reviews. Embase, MEDLINE, Scopus, CINAHL, and gray literature sources will be searched from 1998 to present. Titles, abstracts, and full texts will be screened against the inclusion criteria. Strategies and interventions identified in the included reviews will be mapped to a published framework, outlining actionable strategies for pharmacy practice inclusion in sustainable efforts to achieve health equity. Qualitative content analysis and descriptive statistics will be utilized with data presented in tables, accompanied by a narrative.

REVIEW REGISTRATION: Open Science Framework osf.io/qa64b.

PMID:38126268 | DOI:10.11124/JBIES-23-00129

Histol Histopathol. 2023 Dec 14:18690. doi: 10.14670/HH-18-690. Online ahead of print.

ABSTRACT

We aimed to study the effects of different extensive confluent necrosis on complete biochemical remission, side effects of immunosuppressants, and outcomes in patients with autoimmune hepatitis (AIH). Patients with liver biopsy, receiving standard immunosuppressive therapy (IST), and regular follow-up were retrospectively recruited. Demographic and clinicopathological characteristics between Ishak confluent necrosis scores ≤4 (the non-severe AIH group) and ≥5 (the severe AIH group) were compared. The Kaplan-Meier Survival analysis, Cox regression analysis, and log-rank test were performed. Bilateral p<0.05 was considered statistical significance. One hundred and forty-two patients were enrolled, the median age was 56.0, and 83.8% were female. There were no significant differences in aminotransferases and immunological markers between the two groups. Patients in the severe AIH group had significantly worse liver synthetic function, a higher proportion of cirrhosis, and histologically a higher degree of portal inflammation, interface hepatitis, fibrosis stage, and a higher histological activity index score (all p<0.05). Patients in the severe AIH group had a lower response than the other group after four weeks (57.1% vs. 86.3%, p=0.002). However, differences in complete biochemical remission (CBR) were insignificant. Eight patients experienced end-point events. Kaplan-Meier survival analysis showed no significant difference between the two groups (p=0.343). For adverse effects of IST, patients in the severe group tended toward a higher incidence of corticosteroid adverse effects without statistical significance. Our study indicated that patients with histologically severe confluent necrosis (Ishak score≥5) had significantly worse liver synthetic function and a higher degree of liver fibrosis before IST. Compared with their counterparts, this subgroup of patients showed delayed biochemical response but eventually comparable CBRs, side effects, and long-term outcomes.

PMID:38126225 | DOI:10.14670/HH-18-690

Pharmacoepidemiol Drug Saf. 2023 Dec 21. doi: 10.1002/pds.5747. Online ahead of print.

ABSTRACT

PURPOSE: Antipsychotic agents, which may increase the risk of infection through dopaminergic dysregulation, are prescribed to a fraction of patients following critical illness. We compared the rate of recurrent sepsis among patients who filled a prescription for antipsychotics with high- or low-D₂ affinity.

METHODS: Population-based cohort with active comparator design. We included sepsis survivors older than 65 years with intensive care unit admission and new prescription of antipsychotics in Ontario 2008-2019. The primary outcome were recurrent sepsis episodes within 1 year of follow-up. Patients who filled a prescription within 30 days of hospital discharge for high-D₂ affinity antipsychotics (e.g., haloperidol) were compared with patients who filled a prescription within 30 days of hospital discharge for low-D₂ affinity antipsychotics (e.g., quetiapine). Multivariable zero-inflated Poisson regression models with robust standard errors adjusting for confounding at baseline were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI).

RESULTS: Overall, 1879 patients filled a prescription for a high-D_2, and 1446 patients filled a prescription for a low-D₂ affinity antipsychotic. Patients who filled a prescription for a high-D₂ affinity antipsychotic did not present a higher rate of recurrent sepsis during 1 year of follow-up, compared with patients who filled a prescription for a low-D₂ affinity antipsychotic (IRR: 1.12; 95% CI: 0.94, 1.35).

CONCLUSIONS: We did not find conclusive evidence of a higher rate of recurrent sepsis associated with the prescription of high-D₂ affinity antipsychotics (compared with low-D₂ affinity antipsychotics) by 1 year of follow-up in adult sepsis survivors with intensive care unit admission.

PMID:38126218 | DOI:10.1002/pds.5747