Tag: nevin manimala

Expert Rev Neurother. 2023 Apr 6:1-11. doi: 10.1080/14737175.2023.2195551. Online ahead of print.

ABSTRACT

BACKGROUND: The following study evaluated the clinical outcomes of patients enrolled in the UK Medical Cannabis Registry, who were treated with inhaled dried flower (Adven® EMT2, Curaleaf International, Guernsey), and sublingual/oral medium-chain triglyceride-based oils (Adven, Curaleaf International, Guernsey) for chronic pain.

METHODS: In this cohort study, the primary outcomes were changes in validated patient reported outcome measures (PROMs) at 1, 3, and 6 months compared to baseline, and adverse event analysis. Statistical significance was defined as p < 0.050.

RESULTS: Three hundred and forty-eight (45.7%), 36 (4.7%), and 377 (49.5%) patients were treated with oils, dried flower, or both, respectively. Patients treated with oils or combination therapy recorded improvements within health-related quality of life, pain, and sleep-specific PROMs at 1, 3, and 6 months (p < 0.050). Patients treated with combination therapy recorded improvements in anxiety-specific PROMs at 1, 3, and 6 months (p < 0.050). 1,273 (167.3%) adverse events were recorded, with previously cannabis naïve users, ex-cannabis users, and females more likely to experience adverse events (p < 0.050).

CONCLUSIONS: This study observed an association between initiation of CBMP treatment and improved outcomes for chronic pain patients. Prior cannabis use and gender were associated with adverse event incidence. Placebo-controlled trials are still necessary to establish the efficacy and safety of CBMPs for chronic pain.

PMID:37021592 | DOI:10.1080/14737175.2023.2195551

J Oncol Pharm Pract. 2023 Apr 6:10781552231167554. doi: 10.1177/10781552231167554. Online ahead of print.

ABSTRACT

BACKGROUND: Despite robust evidence and international guidelines, to support routine pharmacogenetic (PGx) testing, integration in practice has been limited. This study explored clinicians’ views and experiences of pre-treatment DPYD and UGT1A1 gene testing and barriers to and enablers of routine clinical implementation.

METHODS: A study-specific 17-question survey was emailed (01 February-12 April 2022) to clinicians from the Medical Oncology Group of Australia (MOGA), the Clinical Oncology Society of Australia (COSA) and International Society of Oncology Pharmacy Practitioners (ISOPP). Data were analysed and reported using descriptive statistics.

RESULTS: Responses were collected from 156 clinicians (78% medical oncologists, 22% pharmacists). Median response rate of 8% (ranged from 6% to 24%) across all organisations. Only 21% routinely test for DPYD and 1% for UGT1A1. For patients undergoing curative/palliative intent treatments, clinicians reported intent to implement genotype-guided dosing by reducing FP dose for DPYD intermediate metabolisers (79%/94%), avoiding FP for DPYD poor metabolisers (68%/90%), and reducing irinotecan dose for UGT1A1 poor metabolisers (84%, palliative setting only). Barriers to implementation included: lack of financial reimbursements (82%) and perceived lengthy test turnaround time (76%). Most Clinicians identified a dedicated program coordinator, i.e., PGx pharmacist (74%) and availability of resources for education/training (74%) as enablers to implementation.

CONCLUSION: PGx testing is not routinely practised despite robust evidence for its impact on clinical decision making in curative and palliative settings. Research data, education and implementation studies may overcome clinicians’ hesitancy to follow guidelines, especially for curative intent treatments, and may overcome other identified barriers to routine clinical implementation.

PMID:37021580 | DOI:10.1177/10781552231167554

J Magn Reson Imaging. 2023 May;57(5):1518-1528. doi: 10.1002/jmri.28386. Epub 2022 Aug 13.

ABSTRACT

BACKGROUND: The identification of combined precapillary and postcapillary pulmonary hypertension (CpcPH) in patients with pulmonary hypertension (PH) due to left heart disease (LHD) can influence therapy and outcome and is currently based on invasively determined hemodynamic parameters.

PURPOSE: To investigate the diagnostic value of MRI-derived corrected pulmonary transit time (PTTc) in PH-LHD sub-grouped according to hemodynamic phenotypes.

STUDY TYPE: Prospective observational study.

POPULATION: A total of 60 patients with PH-LHD (18 with isolated postcapillary PH [IpcPH] and 42 with CpcPH), and 33 healthy subjects.

FIELD STRENGTH/SEQUENCE: A 3.0 T/balanced steady-state free precession cine and gradient echo-train echo planar pulse first-pass perfusion.

ASSESSMENT: In patients, right heart catheterization (RHC) and MRI were performed within 30 days. Pulmonary vascular resistance (PVR) was used as the diagnostic “reference standard.” The PTTc was calculated as the time interval between the peaks of the biventricular signal-intensity/time curve and corrected for heart rate. PTTc was compared between patient groups and healthy subjects and its relationship to PVR assessed. The diagnostic accuracy of PTTc for distinguishing IpcPH and CpcPH was determined.

STATISTICAL TESTS: Student’s t-test, Mann-Whitney U-test, linear and logistic regression analysis, and receiver-operating characteristic curves. Significance level: P < 0.05.

RESULTS: PTTc was significantly prolonged in CpcPH compared with IpcPH and normal controls (17.28 ± 7.67 vs. 8.82 ± 2.55 vs. 6.86 ± 2.11 seconds), and in IpcPH compared with normal controls (8.82 ± 2.55 vs. 6.86 ± 2.11 seconds). Prolonged PTTc was significantly associated with increased PVR. Furthermore, PTTc was a significantly independent predictor of CpcPH (odds ratio: 1.395, 95% confidence interval: 1.071-1.816). The area under curve was 0.852 at a cut-off value of 11.61 seconds for PTTc to distinguish between CpcPH and IpcPH (sensitivity 71.43% and specificity 94.12%).

DATA CONCLUSION: PTTc may be used to identify CpcPH. Our findings have potential to improve selection for invasive RHC for PH-LHD patients.

EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

PMID:37021578 | DOI:10.1002/jmri.28386

J Magn Reson Imaging. 2023 May;57(5):1533-1540. doi: 10.1002/jmri.28403. Epub 2022 Aug 16.

ABSTRACT

BACKGROUND: Automated segmentation of the placenta by MRI in early pregnancy may help predict normal and aberrant placenta function, which could improve the efficiency of placental assessment and the prediction of pregnancy outcomes. An automated segmentation method that works at one gestational age may not transfer effectively to other gestational ages.

PURPOSE: To evaluate a spatial attentive deep learning method (SADL) for automated placental segmentation on longitudinal placental MRI scans.

STUDY TYPE: Prospective, single-center.

SUBJECTS: A total of 154 pregnant women who underwent MRI scans at both 14-18 weeks of gestation and at 19-24 weeks of gestation, divided into training (N = 108), validation (N = 15), and independent testing datasets (N = 31).

FIELD STRENGTH/SEQUENCE: A 3 T, T2-weighted half Fourier single-shot turbo spin-echo (T2-HASTE) sequence.

ASSESSMENT: The reference standard of placental segmentation was manual delineation on T2-HASTE by a third-year neonatology clinical fellow (B.L.) under the supervision of an experienced maternal-fetal medicine specialist (C.J. with 20 years of experience) and an MRI scientist (K.S. with 19 years of experience).

STATISTICAL TESTS: The three-dimensional Dice similarity coefficient (DSC) was used to measure the automated segmentation performance compared to the manual placental segmentation. A paired t-test was used to compare the DSCs between SADL and U-Net methods. A Bland-Altman plot was used to analyze the agreement between manual and automated placental volume measurements. A P value < 0.05 was considered statistically significant.

RESULTS: In the testing dataset, SADL achieved average DSCs of 0.83 ± 0.06 and 0.84 ± 0.05 in the first and second MRI, which were significantly higher than those achieved by U-Net (0.77 ± 0.08 and 0.76 ± 0.10, respectively). A total of 6 out of 62 MRI scans (9.6%) had volume measurement differences between the SADL-based automated and manual volume measurements that were out of 95% limits of agreement.

DATA CONCLUSIONS: SADL can automatically detect and segment the placenta with high performance in MRI at two different gestational ages.

LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

PMID:37021577 | DOI:10.1002/jmri.28403

Haematologica. 2023 Apr 6. doi: 10.3324/haematol.2023.282733. Online ahead of print.

ABSTRACT

Not available.

PMID:37021537 | DOI:10.3324/haematol.2023.282733

Thorac Cancer. 2023 Apr 6. doi: 10.1111/1759-7714.14882. Online ahead of print.

ABSTRACT

OBJECTIVE: Advanced lung cancers carrying Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation remain a group that lacks effective treatments. Receptor activator of nuclear factor-κB ligand (RANKL) has been demonstrated to drive malignant phenotypes in lung cancer; however, its role in KRAS-mutant (mt) lung adenocarcinoma (LUAD) is not yet fully elucidated.

MATERIALS AND METHODS: The data used to explore expression and prognosis were obtained from The Cancer Genome Atlas, Genotype-Tissue Expression databases, and from our hospital. The proliferation, invasion, and migration capacities of KRAS-mt LUAD cells were evaluated. The prediction model was established via Lasso regression method.

RESULTS: RANKL is strongly expressed in advanced KRAS-mt LUAD, and significantly distinct association exists between high RANKL expression and poor survival. The enriched expression of RANKL in advanced KRAS-mt LUAD was confirmed by specimens from our hospital. Further, although not statistically significant, our clinical cohort (n = 57) revealed a longer median progression-free survival in advanced KRAS-mt LUAD patients treated with RANKL inhibitor than those without (300 vs. 133 days, p = 0.210), but not in KRAS-wt ones (208 vs. 250 days, p = 0.334). Decrease of KRAS-mt LUAD cells’ capacity for proliferation, invasion, and migration was observed when RANKL was knocked down. Enrichment analysis suggested distinct roles of RANKL between KRAS-mt and KRAS-wt LUAD, with adhesion-related pathways and molecules significantly downregulated in the KRAS-mt RANKL-high tumors. Finally, a model for predicting overall survival of KRAS-wt LUAD was established according to four related key genes (BCAM, ICAM5, ITGA3, and LAMA3), which had good performance in prediction concordance.

CONCLUSIONS: RANKL acts as an unfavorable prognostic biomarker for patients with advanced KRAS-mt LUAD. Inhibition of RANKL may be a feasible strategy for this subset of patients.

PMID:37021520 | DOI:10.1111/1759-7714.14882

J Chemother. 2023 Apr 6:1-9. doi: 10.1080/1120009X.2023.2196916. Online ahead of print.

ABSTRACT

This study aims to evaluate the clinical pharmacist’s contribution impact on the appropriate use of colistin. Our study was conducted prospectively in patients in the Internal Diseases Intensive Care Unit of Gazi University Medical Faculty Hospital for eight months. The first four months of the study were with the observation group, while the next four months were with the intervention group. The study determined how the active participation of clinical pharmacists had affected the appropriateness of colistin use. The results showed that the appropriate use of colistin was higher in the intervention group than in the observational group; furthermore, incidence of nephrotoxicity was lower. The difference between both groups was statistically significant (p < 0.001, p < 0.05), respectively. This study showed that the clinical pharmacist’s active intervention by following the patients increased the frequency and percentage of the appropriate use of colistin. This decreased the incidence of nephrotoxicity, colistin’s most important side effect.

PMID:37021512 | DOI:10.1080/1120009X.2023.2196916

Allergy Asthma Immunol Res. 2023 Mar;15(2):262-270. doi: 10.4168/aair.2023.15.2.262.

ABSTRACT

Various therapeutic approaches, including supplemental nutritional support, have been tried for the treatment of atopic dermatitis (AD). Previous studies have reported the role of vitamin D in the treatment of AD with inconsistent results. The aim of this study was to evaluate the effectiveness of vitamin D in the treatment of AD, with considerations on the heterogeneities of AD. Randomized controlled trials (RCTs) on the efficacy of vitamin D supplementation for AD treatment, published before June 30, 2021 were identified in the PubMed, EMBASE, MEDLINE, and Cochrane Library databases. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation system. This meta-analysis included 5 RCTs with 304 cases of AD. We found that vitamin D supplementation did not decrease AD severity, even when AD was classified as severe vs non-severe. However, vitamin D supplementation was found to be effective in the treatment of AD in RCTs that included both children and adults, but not in those that included only children. Geographic location was associated with a significant difference in the therapeutic effect of vitamin D supplementation. Moreover, vitamin D supplementation of > 2,000 IU/day decreased AD severity, but supplementation ≤ 2,000 IU/day did not. Vitamin D supplementation, in general, was not effective for the treatment of AD. However, vitamin D supplementation might provide a therapeutic effect depending on the geographic location and dose of supplementation. The results of the present meta-analysis suggest that vitamin D supplementation might be targeted for patients with AD who may benefit from vitamin D supplementation.

PMID:37021510 | DOI:10.4168/aair.2023.15.2.262

Stat Methods Med Res. 2023 Apr 6:9622802231167437. doi: 10.1177/09622802231167437. Online ahead of print.

ABSTRACT

Response-adaptive randomization allows the probabilities of allocating patients to treatments in a clinical trial to change based on the previously observed response data, in order to achieve different experimental goals. One concern over the use of such designs in practice, particularly from a regulatory viewpoint, is controlling the type I error rate. To address this, Robertson and Wason (Biometrics, 2019) proposed methodology that guarantees familywise error rate control for a large class of response-adaptive designs by re-weighting the usual $z$-test statistic. In this article, we propose an improvement of their method that is conceptually simpler, in the context where patients are allocated to the experimental treatment arms in a trial in blocks (i.e. groups) using response-adaptive randomization. We show the modified method guarantees that there will never be negative weights for the contribution of each block of data to the adjusted test statistics, and can also provide a substantial power advantage in practice.

PMID:37021480 | DOI:10.1177/09622802231167437

Clin Rehabil. 2023 Apr 6:2692155231166220. doi: 10.1177/02692155231166220. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate whether combination of corticosteroid subdeltoid injections and physiotherapy was more effective than either treatment alone in chronic subacromial bursitis.

DESIGN: Prospective, three-arm randomised controlled trial.

SETTING: Rehabilitation department of an academic hospital.

SUBJECTS: Patients with chronic subacromial bursitis.

INTERVENTIONS: Patients were divided into corticosteroid injection (N = 36), physiotherapy (N = 40) and combined (N = 35) groups. Two corticosteroid subdeltoid injections in corticosteroid group, 8-week physical therapy emphasising on therapeutic exercise in physiotherapy group, and combined both treatments in combined group.

MAIN OUTCOME MEASURES: The primary outcome measures were pain visual analogue scale and Shoulder Pain and Disability Index at 8 weeks after finishing treatment. The secondary outcome measures were active range of motion, Shoulder Disability Questionnaire, Western Ontario Rotator Cuff Index, patient’s evaluation of treatment effect, and symptom recurrence.

RESULTS: Group comparison showed significant statistical difference in shoulder flexion (P < 0.003) and patient’s evaluation of treatment effect (P < 0.001). The time and group interactions comparison revealed significant statistical differences in pain score (P < 0.024), external rotation (P < 0.044) and patient’s evaluation of treatment effect (P < 0.001). The above statistics were in favour of the corticosteroid and combined groups rather than physiotherapy group. The percentage of recurrence was 36.1, 7.5 and 17.1 in the corticosteroid, physiotherapy and combined groups, respectively (P < 0.001).

CONCLUSION: Corticosteroid subdeltoid injection, or combined with physiotherapy, was superior to physiotherapy alone, but the recurrence rate was least in the physiotherapy group.

PMID:37021475 | DOI:10.1177/02692155231166220