Categories
Nevin Manimala Statistics

Machine-learning derived acetabular dysplasia and cam morphology are features of severe hip osteoarthritis: findings from UK Biobank

J Bone Miner Res. 2022 Jul 10. doi: 10.1002/jbmr.4649. Online ahead of print.

ABSTRACT

The contribution of shape changes to hip osteoarthritis (HOA) remains unclear, as is the extent to which these vary according to HOA severity. In the present study, we used statistical shape modelling (SSM) to evaluate relationships between hip shape and HOA of different severities using UK Biobank DXA images. We performed a cross-sectional study in individuals with left hip DXA scans. Statistical shape modelling (SSM) was used to quantify hip shape. Radiographic HOA (rHOA) was classified using osteophyte size and number, and joint space narrowing. HOA outcomes ranged in severity from moderate (grade 2) or severe (grade ≥3) rHOA, hospital diagnosed HOA, and subsequent total hip replacement (THR). Confounder-adjusted logistic regression between the top ten hip shape modes (HSMs) and OA outcomes was performed. Further models adjusted for alpha angle (AA) and lateral centre-edge angle (LCEA), reflecting acetabular dysplasia and cam morphology respectively. Composite HSM figures were produced combining HSMs associated with separate OA outcomes. A total of 40,311 individuals were included (mean 63.7 years, 47.8% male), of whom 5.7% had grade 2 rHOA, 1.7% grade ≥3 rHOA, 1.3% hospital diagnosed HOA, and 0.6% underwent THR. Composite HSM figures for grade 2 rHOA revealed femoral neck widening, increased acetabular coverage, and enlarged lesser and greater trochanters. In contrast, grade ≥3 rHOA, hospital diagnosed HOA and THR were suggestive of cam morphology and reduced acetabular coverage. Associations between HSMs depicting cam morphology and reduced acetabular coverage and more severe HOA were attenuated by AA and LCEA adjustment, respectively. Relationships between hip shape and HOA differed according to severity. Notably, cam morphology and acetabular dysplasia were features of severe HOA, but unrelated to moderate disease, suggesting possible prognostic utility. This article is protected by copyright. All rights reserved.

PMID:35811326 | DOI:10.1002/jbmr.4649

Categories
Nevin Manimala Statistics

Tumor response to radiotherapy and expression of epidermal growth factor receptor mutation and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase rearrangement in patients with non-small cell lung cancer

J Egypt Natl Canc Inst. 2022 Jul 11;34(1):29. doi: 10.1186/s43046-022-00130-7.

ABSTRACT

BACKGROUND: One of the main limitations of radiation therapy is the resistance of tumor cells. This study aimed at evaluating the relationship between the expression of epidermal growth factor receptor (EGFR) and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) and tumor radiosensitivity in patients with non-small cell lung cancer.

METHODS: Medical case files, pathological results for EGFR and EML4-ALK, and computerized tomography scans of patients with NSCLC treated with thoracic radiation therapy were analyzed.

RESULTS: The sample size was 101 patients with mean age 58.43 ± 9.89 years. Statistically significant differences were observed in the mean reduction of long tumor diameter during the early treatment phase in EGFR-positive versus EGFR-negative patients (p value = 0.04) and in short tumor diameter during the late treatment phase in EGFR-positive versus EGFR-negative patients (p value = 0.04).

CONCLUSION: Patients with overexpression of EGFR mutations are more radiosensitive during the early treatment phase, and EML4-ALK mutations were less radiosensitive regardless of phases.

PMID:35811311 | DOI:10.1186/s43046-022-00130-7

Categories
Nevin Manimala Statistics

A Neuroimaging Signature of Cognitive Aging from Whole-Brain Functional Connectivity

Adv Sci (Weinh). 2022 Jul 10:e2201621. doi: 10.1002/advs.202201621. Online ahead of print.

ABSTRACT

Cognitive decline is amongst one of the most commonly reported complaints during normal aging. Despite evidence that age and cognition are linked with similar neural correlates, no previous studies have directly ascertained how these two constructs overlap in the brain in terms of neuroimaging-based prediction. Based on a long lifespan healthy cohort (CamCAN, aged 19-89 years, n = 567), it is shown that both cognitive function (domains spanning executive function, emotion processing, motor function, and memory) and human age can be reliably predicted from unique patterns of functional connectivity, with models generalizable in two external datasets (n = 533 and n = 453). Results show that cognitive decline and normal aging both manifest decrease within-network connections (especially default mode and ventral attention networks) and increase between-network connections (somatomotor network). Whereas dorsal attention network is an exception, which is highly predictive on cognitive ability but is weakly correlated with aging. Further, the positively weighted connections in predicting fluid intelligence significantly mediate its association with age. Together, these findings offer insights into why normal aging is often associated with cognitive decline in terms of brain network organization, indicating a process of neural dedifferentiation and compensational theory, and providing potential connectivity markers for hinting at multiple cognitive deficits.

PMID:35811304 | DOI:10.1002/advs.202201621

Categories
Nevin Manimala Statistics

Addition of Docetaxel to Androgen Receptor Axis-targeted Therapy and Androgen Deprivation Therapy in Metastatic Hormone-sensitive Prostate Cancer: A Network Meta-analysis

Eur Urol Oncol. 2022 Jul 7:S2588-9311(22)00092-X. doi: 10.1016/j.euo.2022.06.003. Online ahead of print.

ABSTRACT

CONTEXT: Randomized controlled trials (RCTs) have shown that addition of docetaxel or androgen receptor axis-targeted therapy (ARAT) to androgen deprivation therapy (ADT) or addition of ARAT to ADT and docetaxel improves overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC). However, it is unknown whether docetaxel, when given as part of triplet therapy, has an independent OS benefit.

OBJECTIVE: To compare the efficacy of ADT plus ARAT with the triplet of ADT, ARAT, and docetaxel through a network meta-analysis (NMA) of RCTs in mHSPC.

EVIDENCE ACQUISITION: Bibliographic databases and conference proceedings were searched in March 2022 for RCTs that evaluated the addition of docetaxel, ARAT, or both to ADT in mHSPC. The primary endpoint was OS. Standard random-effect NMA and Bayesian analyses were performed to compare ADT plus ARAT with triplet therapy.

EVIDENCE SYNTHESIS: Eleven RCTs (n = 11 546) were eligible. Compared with ADT plus ARAT, the triplet had a nonsignificant OS benefit (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.68-1.16), while ADT plus docetaxel (HR 1.16 [0.94-1.43]) and ADT alone (HR 1.46 [1.30-1.64]) had an increased risk of death. By P-score ordering, the triplet was the most effective treatment strategy (P score = 0.936) followed by ADT plus ARAT (P score = 0.704). The triplet had a 77% likelihood of being the best treatment strategy compared with a 23% likelihood for ADT plus ARAT.

CONCLUSIONS: The triplet of ADT, ARAT, and docetaxel was the highest ranked treatment strategy, but it did not confer a statistically significant OS benefit over ADT plus ARAT. This NMA provides the highest-level comparative evidence for these treatment approaches in the initial management of mHSPC.

PATIENT SUMMARY: We synthesized the available evidence from clinical trials conducted in newly diagnosed metastatic prostate cancer to compare the survival of patients receiving triplet therapy (androgen receptor axis-targeted therapy [ARAT], androgen deprivation therapy [ADT], and docetaxel) with those receiving only ARAT and ADT. We conclude that the triplet is a somewhat more effective treatment approach.

PMID:35811293 | DOI:10.1016/j.euo.2022.06.003

Categories
Nevin Manimala Statistics

Designing and Implementing a Population-based Organised Prostate Cancer Testing Programme

Eur Urol Focus. 2022 Jul 7:S2405-4569(22)00135-3. doi: 10.1016/j.euf.2022.06.008. Online ahead of print.

ABSTRACT

BACKGROUND: European guidelines recommend that well-informed men at elevated risk of having prostate cancer (PCa) should be offered prostate-specific antigen (PSA) testing with risk-stratified follow-up. The Swedish National Board of Health and Welfare recommends against screening for PCa but supports regional implementation of organised prostate cancer testing (OPT).

OBJECTIVE: To report the process for designing and implementing OPT programmes.

DESIGN, SETTING, AND PARTICIPANTS: Population-based OPT programmes in two Swedish regions, designed to include men aged between 50 and 74 yr, launched in September 2020 for 50-yr-old men.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The number of men invited, the participation rate, and the numbers of magnetic resonance imaging (MRI) scans, urological visits, and biopsies from September 2020 to June 2021 were recorded.

RESULTS AND LIMITATIONS: Two Swedish regions co-designed an OPT programme with a risk-stratified diagnostic algorithm based on prostate-specific antigen (PSA), PSA density, MRI findings, and age. An automated administrative system was developed on a nationwide web-based platform. Invitation letters and test results are automatically generated and sent out by post. Men with PSA ≥3ng/ml, a suspicious MRI lesion, and/or PSA density ≥0.15 ng/ml/cm3 are referred for a prostate biopsy. Test results are registered for quality control and research. By June 2021, a total of 16 515 men were invited, of whom 6309 (38%) participated; 147 had an MRI scan and 39 underwent prostate biopsy. The OPT framework, algorithm, and diagnostic pathways have been working well.

CONCLUSIONS: We designed and implemented a framework for OPT with a high grade of automation. The framework and organisational experiences may be of value for others who plan a programme for early detection of PCa.

PATIENT SUMMARY: We describe the implementation of an organised testing programme for early detection of prostate cancer in two Swedish regions. This model is the first of its kind and may serve as a template for similar programmes.

PMID:35811285 | DOI:10.1016/j.euf.2022.06.008

Categories
Nevin Manimala Statistics

Impact of outpatient antimicrobial stewardship guideline implementation in an urgent care setting

J Am Pharm Assoc (2003). 2022 Jun 16:S1544-3191(22)00217-5. doi: 10.1016/j.japh.2022.06.004. Online ahead of print.

ABSTRACT

BACKGROUND: Urgent care medicine is a rapidly growing health care sector where patients are commonly treated for acute infectious diseases-related conditions. However, there are few antimicrobial stewardship interventions described in these settings.

OBJECTIVE: The objective of this study is to determine whether implementing outpatient antimicrobial stewardship guidelines would improve antibiotic prescribing for acute upper respiratory tract infections (ARTIs), skin and soft tissue infections (SSTI), and urinary tract infections (UTI) at a single urgent care site.

METHODS: This was a pre-post interventional study comparing antibiotic prescribing patterns for ARTI, SSTI, and UTI at a single urgent care site in the preintervention group (November 2019 to January 2020) with the postintervention group (November 2020 to January 2021) after implementation of outpatient stewardship guidelines. A second urgent care site that did not receive any interventions served as a control. The outpatient stewardship guidelines were implemented in October 2020 via didactic provider education and pocket guide distribution. The primary end point was the rate of total guideline-concordant antibiotic prescribing. Secondary end points included the rates of guideline concordance of each component of the prescription, including antibiotic selection, duration, dose, therapy indication, and patient safety outcomes.

RESULTS: The primary outcome of total guideline-concordant antibiotic prescribing significantly improved after implementation of outpatient antimicrobial stewardship guidelines at the study site (50% vs. 70%, P < 0.001), which was also reflected when comparing postintervention study site with postperiod control site (70% vs. 48%, P < 0.001). There was a statistically significant improvement in guideline-concordant duration of antibiotic therapy (43% vs. 61%, P = 0.001), driven by a reduction in antibiotic duration for UTI (7 [interquartile range (IQR) 5-7] vs. 5 [IQR 5-7] days, P = 0.007), which was also observed when comparing the postintervention study site with the postperiod control site (61% vs. 48%, P = 0.02). Patient safety outcomes were similar between groups.

CONCLUSION: An antimicrobial stewardship intervention comprising institutional outpatient guideline implementation and provider education significantly improved total guideline-concordant antibiotic prescribing by 20% for ARTI, UTI, and SSTI in an urgent care site.

PMID:35811280 | DOI:10.1016/j.japh.2022.06.004

Categories
Nevin Manimala Statistics

Comparison of Quantitative Ultrasound Methods to Classify Dystrophic and Obese Models of Skeletal Muscle

Ultrasound Med Biol. 2022 Jul 7:S0301-5629(22)00411-2. doi: 10.1016/j.ultrasmedbio.2022.05.022. Online ahead of print.

ABSTRACT

In this study, we compared multiple quantitative ultrasound metrics for the purpose of differentiating muscle in 20 healthy, 10 dystrophic and 10 obese mice. High-frequency ultrasound scans were acquired on dystrophic (D2-mdx), obese (db/db) and control mouse hindlimbs. A total of 248 image features were extracted from each scan, using brightness-mode statistics, Canny edge detection metrics, Haralick features, envelope statistics and radiofrequency statistics. Naïve Bayes and other classifiers were trained on single and pairs of features. The a parameter from the Homodyned K distribution at 40 MHz achieved the best univariate classification (accuracy = 85.3%). Maximum classification accuracy of 97.7% was achieved using a logistic regression classifier on the feature pair of a2 (K distribution) at 30 MHz and brightness-mode variance at 40MHz. Dystrophic and obese mice have muscle with distinct acoustic properties and can be classified to a high level of accuracy using a combination of multiple features.

PMID:35811236 | DOI:10.1016/j.ultrasmedbio.2022.05.022

Categories
Nevin Manimala Statistics

Comparison of coronary CT angiography-based and invasive coronary angiography-based quantitative flow ratio for functional assessment of coronary stenosis: A multicenter retrospective analysis

J Cardiovasc Comput Tomogr. 2022 Jun 30:S1934-5925(22)00100-9. doi: 10.1016/j.jcct.2022.06.002. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the diagnostic performance of coronary CT angiography (CTA)-based quantitative flow ratio (QFR), namely CT-QFR, and compare it with invasive coronary angiography (ICA)-based Murray law QFR (μQFR), using fractional flow reserve (FFR) as the reference standard.

METHODS: Patients who underwent coronary CTA, ICA and pressure wire-based FFR assessment within two months were retrospectively analyzed. CT-QFR and μQFR were computed in blinded fashion and compared with FFR, all applying the same cut-off value of ≤0.80 to identify hemodynamically significant stenosis.

RESULTS: Paired comparison between CT-QFR and μQFR was performed in 191 vessels from 167 patients. Average FFR was 0.81 ​± ​0.10 and 42.4% vessels had an FFR ≤0.80. CT-QFR had a slightly lower correlation with FFR compared with μQFR, although statistically non-significant (r ​= ​0.87 versus 0.90, p ​= ​0.110). The vessel-level diagnostic performance of CT-QFR was slightly lower but without statistical significance than μQFR (AUC ​= ​0.94 versus 0.97, difference: -0.03 [95%CI: -0.00-0.06], p ​= ​0.095), and substantially higher than diameter stenosis by CTA (AUC difference: 0.17 [95%CI: -0.10-0.23], p ​< ​0.001). The patient-level diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio for CT-QFR to identify FFR value ​≤ ​0.80 was 88%, 90%, 86%, 86%, 91%, 6.59 and 0.12, respectively. The diagnostic accuracy of CT-QFR was 84% in extensively calcified lesions, while in vessels with no or less calcification, CT-QFR showed a comparable diagnostic accuracy with μQFR (91% versus 92%, p ​= ​0.595). Intra- and inter-observer variability in CT-QFR analysis was -0.00 ​± ​0.04 and 0.00 ​± ​0.04, respectively.

CONCLUSIONS: Performance in diagnosis of hemodynamically significant coronary stenosis by CT-QFR was slightly lower but without statistical significance than μQFR, and substantially higher than CTA-derived diameter stenosis. Extensively calcified lesions reduced the diagnostic accuracy of CT-QFR.

PMID:35811245 | DOI:10.1016/j.jcct.2022.06.002

Categories
Nevin Manimala Statistics

Comparative analysis of three vs. four cycles of neoadjuvant gemcitabine and cisplatin for muscle invasive bladder cancer

Urol Oncol. 2022 Jul 7:S1078-1439(22)00192-2. doi: 10.1016/j.urolonc.2022.05.023. Online ahead of print.

ABSTRACT

PURPOSE: Because the optimal number of cycles of neoadjuvant gemcitabine and cisplatin chemotherapy (GC) is unclear, we aimed to compare disease response and survival outcomes of patients receiving either 3 or 4 cycles of neoadjuvant GC for muscle-invasive bladder cancer (MIBC).

METHODS: A total of 166 patients who were treated with neoadjuvant GC and radical cystectomy for clinical stage T2-4N0M0 were identified. Response and effectiveness of different cycle counts were assessed using downstaging (complete pathologic and partial pathologic response), cancer-specific survival (CSS), and overall survival (OS). Response and survival outcomes were examined with adjusted logistic regression and Cox regression models. Statistical significance was defined as P < 0.05.

RESULTS: Of 166 patients who received neoadjuvant GC, 107 (64.5%) received 3 cycles and 59 (35.5%) received 4 cycles. Age, insurance, comorbidity, tumor histology (pure urothelial carcinoma, urothelial with divergent differentiation, variant histology), and tumor stage were similar between the 2 treatment groups. Rates of complete response or any downstaging were similar between groups (21.5% and 40.2% in the 3-cycle group and 20.3% and 44.1% in the 4-cycle group, respectively). While disease response was similar (OR 1.03, 95% CI 0.43-2.45), both cancer-specific survival (HR 1.69, 95% CI 0.87-3.26) and overall survival (HR:1.88, 95% CI:1.02-3.48) were more favorable among patients managed with 4 cycles of neoadjuvant chemotherapy compared to those who received 3 cycles in adjusted models.

CONCLUSIONS: Our analysis demonstrated that survival outcomes tended to be better among patients who received 4 cycle of neoadjuvant GC compared to those treated with 3 cycles. Although potential benefits of omission of fourth cycle may include expedited time to surgery, reduced chemotherapy-associated toxicity, and lower treatment costs, continuation of treatment with a fourth cycle of neoadjuvant GC chemotherapy may benefit patients with muscle-invasive bladder cancer and further improve disease outcomes.

PMID:35811208 | DOI:10.1016/j.urolonc.2022.05.023

Categories
Nevin Manimala Statistics

The relationship between erythema nodosum and prognosis in systemic sarcoidosis: a retrospective cohort study

An Bras Dermatol. 2022 Jul 7:S0365-0596(22)00111-8. doi: 10.1016/j.abd.2021.09.011. Online ahead of print.

ABSTRACT

BACKGROUND: Erythema Nodosum (EN) is the most common skin manifestation in sarcoidosis and has often been associated with a good prognosis.

OBJECTIVES: To compare the clinical characteristics and treatment-related features in patients with sarcoidosis according to whether or not EN was seen as a presenting symptom at the time of diagnosis.

METHODS: A 20-year single-center retrospective study was performed. The following two groups were identified: one group with EN as one of the presenting symptoms at the time of diagnosis of sarcoidosis (EN group) and a second group without EN as a presenting symptom at diagnosis (non-EN group). The clinical characteristics and treatment modalities were collected from the medical records.

RESULTS: A total of 122 patients (31 in the EN group, 91 in the non-EN group) were included. Radiological stages of pulmonary disease were significantly lower in the EN group. Articular involvement was more common in the EN group (p = 0.001), whereas other systemic organ involvements (p = 0.025), especially neurological involvement (p = 0.036), were significantly more common in the non-EN group. In the EN group, a higher percentage of patients were managed without systemic therapy (71.0% vs. 54.9%) and spontaneous remission was more frequent (25.0% vs. 14.1%), however, this wasn’t statistically significant.

STUDY LIMITATIONS: Retrospective design.

CONCLUSIONS: The lower radiological stage of pulmonary sarcoidosis and lower frequency of systemic organ involvement in patients with EN augment the prognostic value of EN highlighted in the literature. However, this study couldn’t confirm that the patients with EN would need less systemic therapy in the course of their disease.

PMID:35811196 | DOI:10.1016/j.abd.2021.09.011