Categories
Nevin Manimala Statistics

Is the Availability of Biosimilar Adalimumab Associated with Budget Savings? A Difference-in-Difference Analysis of 14 Countries

BioDrugs. 2023 Dec 8. doi: 10.1007/s40259-023-00636-z. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim was to assess the influence of the presence of biosimilar adalimumab on adalimumab budget savings in 14 high- and upper-middle-income countries.

METHODS: This study analyzed Multinational Integrated Data Analysis System (MIDAS)-IQVIA data from the fourth quarter (Q4) of 2018 to the Q4 of 2019, comparing adalimumab expenditure (in United States dollars) and consumption (in standard units [SU]) across 14 countries (Australia, Austria, Brazil, Canada, France, Germany, Italy, Japan, Korea, Singapore, South Africa, Spain, Sweden, and Taiwan). The countries were divided into two groups based on the availability of adalimumab biosimilars during the study period. A difference-in-difference design was employed to analyze the groups, focusing on changes from Q4 2018 to Q4 2019. Additionally, changes in adalimumab expenditure were decomposed into price, quantity, and drug mix during the study period.

RESULTS: Among countries with adalimumab biosimilars, there was a significant decrease in expenditure (- $371.0 per gross domestic product per capita; p = 0.03) over four quarters, while the consumption significantly increased (1.0 SU per 1000 population; p = 0.02). This was consistent with visual observations and differed from countries without adalimumab biosimilar. Sensitivity analysis with a narrowed list of countries (12 high-income countries) showed a consistent trend. Adalimumab expenditure decreased by 14% during the study period in countries where adalimumab biosimilars were available, mainly due to the price changes (Pt = 0.85; – 15%) and the drug-mix effect (εt = 0.88; – 12%). Yet, adalimumab expenditure (Et = 1.04; +4%) changed in a quantity-dependent manner (Qt = 1.06; +6%) in countries where adalimumab biosimilars were absent.

CONCLUSION: The availability of biosimilars was associated with a decrease in adalimumab expenditure without compromising the consumption of adalimumab.

PMID:38064144 | DOI:10.1007/s40259-023-00636-z

Categories
Nevin Manimala Statistics

Relationship between maxillary sinus mucosal cyst and sinus ostium 2D area in three-dimensional volumetric paranasal CT ımages

Oral Radiol. 2023 Dec 8. doi: 10.1007/s11282-023-00722-6. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the relationship between the maxillary sinus ostium 2D area (SOA) and the development of mucosal cysts of the maxillary sinus (MMC).

METHODS: Thirty patients (≥ 18 years) with unilateral MMC who underwent paranasal sinus CT (PNsCT) were included in this single-center retrospective study. Non-MMC sinus was used as the control group. Cyst and air volume of the maxillary sinuses, diameter, and 2-dimensional area of the ostium of the patients were calculated in the 3-dimensional volumetric analysis program. Both correlation and linear regression model analyses were performed for the relationship between MMC and SOA.

RESULTS: Thirty patients were included (mean age of 42.30 ± 17.62 years). A total of 15/30 (50%) were male. The mean SOA in patients with MMC (8.91 ± 1.10 mm2) was lower than in patients without MMC (12.94 ± 1.35 mm2), which was statistically significant (p < 0.001). The mean sinus ostium diameter in patients with MMC (2.12 ± 0.71 mm) was higher than in patients without MMC (1.91 ± 0.82 mm), which was statistically insignificant (p = 0.295). There was a statistically significant, good level of negative linear correlation between SOA and total cyst volume (TCV) [correlation coefficient (r) = – 0.680, p < 0.001]). As a result, the regression model consisting of “Age, Sinus air volume, and TCV” variables is a good model and has statistically significant relations with SOA.

CONCLUSION: In conclusion, small SOAs contribute to the development of MMC. There was a negative correlation between SOA and TCV. In addition, 2D area measurement may be a more accurate method instead of diameter measurement.

PMID:38064142 | DOI:10.1007/s11282-023-00722-6

Categories
Nevin Manimala Statistics

Correction: Tissue responses to everolimus-eluting stents implanted in severely calcified lesions following atherectomy

Cardiovasc Interv Ther. 2023 Dec 8. doi: 10.1007/s12928-023-00973-4. Online ahead of print.

NO ABSTRACT

PMID:38064132 | DOI:10.1007/s12928-023-00973-4

Categories
Nevin Manimala Statistics

Association of Biochemical Parameters and Screening for Mutations in the MCU Gene in Alzheimer’s Disease Patients

Mol Neurobiol. 2023 Dec 8. doi: 10.1007/s12035-023-03820-y. Online ahead of print.

ABSTRACT

The most prevalent form of dementia, Alzheimer’s disease (AD) is a chronic illness that is on the rise among the geriatric population. Even though research into its biochemical, genetic, and cytogenetic pathways has advanced, its aetiology is still unclear and complex. In this study, we recruited sixty-eight participants diagnosed with AD where the cytogenetic, biochemical parameters and genetic mutations were analysed. Our results revealed chromosomal aberrations such as aneuploidies in the peripheral blood of Alzheimer’s disease patients. Biochemical parameters revealed no statistical significance in the study though a pattern could be observed in the serum levels. Further few novel mutations at the c.21 C > T, c.56G > A were observed in the MCU gene of mitochondrial calcium uniporter. All these findings reveal the need for a larger cohort study to gain a better and more detailed understanding of the aetiology of Alzheimer’s disease.

PMID:38064106 | DOI:10.1007/s12035-023-03820-y

Categories
Nevin Manimala Statistics

A simpler diagnostic algorithm of the Japan Esophageal Society classification for Barrett’s esophagus-related superficial neoplasia

Esophagus. 2023 Dec 8. doi: 10.1007/s10388-023-01029-5. Online ahead of print.

ABSTRACT

BACKGROUND: We previously developed a Japan Esophageal Society Barrett’s Esophagus (JES-BE) magnifying endoscopic classification for superficial BE-related neoplasms (BERN) and validated it in a nationwide multicenter study that followed a diagnostic flow chart based on mucosal and vascular patterns (MP, VP) with nine diagnostic criteria. Our present post hoc analysis aims to further simplify the diagnostic criteria for superficial BERN.

METHODS: We used data from our previous study, including 10 reviewers’ assessments for 156 images of high-magnifying narrow-band imaging (HM-NBI) (67 dysplastic and 89 non-dysplastic histology). We statistically analyzed the diagnostic performance of each diagnostic criterion of MP (form, size, arrangement, density, and white zone), VP (form, caliber change, location, and greenish thick vessels [GTV]), and all their combinations to achieve a simpler diagnostic algorithm to detect superficial BERN.

RESULTS: Diagnostic accuracy values based on the MP of each single criterion or combined criteria showed a marked trend of being higher than those based on VP. In reviewers’ assessments of visible MPs, the combination of irregularity for form, size, or white zone had the highest diagnostic performance, with a sensitivity of 87% and a specificity of 91% for dysplastic histology; in the assessments of invisible MPs, GTV had the highest diagnostic performance among the VP of each single criterion and all combinations of two or more criteria (sensitivity, 93%; specificity, 92%).

CONCLUSION: The present post hoc analysis suggests the feasibility of further simplifying the diagnostic algorithm of the JES-BE classification. Further studies in a practical setting are required to validate these results.

PMID:38064022 | DOI:10.1007/s10388-023-01029-5

Categories
Nevin Manimala Statistics

Patient-Reported Outcomes in Patients Undergoing Lumpectomy With and Without Defect Closure

Ann Surg Oncol. 2023 Dec 8. doi: 10.1245/s10434-023-14584-z. Online ahead of print.

ABSTRACT

BACKGROUND: The effect of lumpectomy defect repair (a level 1 oncoplastic technique) on patient-reported breast satisfaction among patients undergoing lumpectomy has not yet been investigated.

METHODS: Patients undergoing lumpectomy at our institution between 2018 and 2020 with or without repair of their lumpectomy defect during index operation, comprised our study population. The BREAST-Q quality-of-life questionnaire was administered preoperatively, and at 6 months, 1 year, and 2 years postoperatively. Satisfaction and quality-of-life domains were compared between those who did and did not have closure of their lumpectomy defect, and compared with surgeon-reported outcomes.

RESULTS: A total of 487 patients met eligibility criteria, 206 (42%) had their partial mastectomy defect repaired by glandular displacement. Median breast volume, as calculated from the mammogram, was smaller in patients undergoing defect closure (826 cm3 vs. 895 cm3, p = 0.006). There were no statistically significant differences in satisfaction with breasts (SABTR), physical well-being of the chest (PWB-CHEST), or psychosocial well-being (PsychWB) scores between the two cohorts at any time point. While patients undergoing defect closure had significantly higher sexual well-being (SexWB) scores compared with no closure (66 vs. 59, p = 0.021), there were no predictors of improvement in SexWB scores over time on multivariable analysis. Patients’ self-reported scores positively correlated with physician-reported outcomes.

CONCLUSIONS: Despite a larger lumpectomy-to-breast volume ratio among patients undergoing defect repair, satisfaction was equivalent among those whose defects were or were not repaired at 2 years postsurgery. Defect repair was associated with clinically relevant improvement in patient-reported sexual well-being.

PMID:38063989 | DOI:10.1245/s10434-023-14584-z

Categories
Nevin Manimala Statistics

Impact of deep brain stimulation therapy on the vertebral sagittal balance in Parkinson’s disease patients

Neurosurg Rev. 2023 Dec 8;47(1):7. doi: 10.1007/s10143-023-02243-6.

ABSTRACT

Parkinson’s disease (PD) is characterized by cardinal motor signs: 4-6 Hz resting tremor, rigidity, and bradykinesia. In addition, 3-18% of PD patients have camptocormia, an abnormal forward flexion of the thoracolumbar spine, which may have a negative impact on patients’ quality of life. Different possible treatments have been suggested for such a condition, but no one is resolutive. This study aims to define the possible impact of DBS, with selective targeting on the dorsal-lateral region of the STN, on the sagittal balance of patients affected by PD. Among all patients that have undergone DBS procedures in our institution, we selected eight subjects, four females and four males, with selective targeting on the dorsal-lateral region of the subthalamic nucleus (STN) because of camptocormia and other severe postural changes. Radiological assessments of spinal balance parameters before surgery and at 6 and 12 months postoperatively were carried out. Comparison of preoperative and postoperative spine X-ray data showed a statistically significant improvement in dorsal kyphosis angle (D-Cobb) 12 months after the operation. Deep brain stimulation with selective targeting of the dorsal lateral part of the STN may induce changes of the posture in patients with Parkinson’s disease 12 months after the operation, which appears to improve in this small sample size, but larger observational and controlled trials would be required to confirm this observation.

PMID:38063935 | DOI:10.1007/s10143-023-02243-6

Categories
Nevin Manimala Statistics

Genome- and Transcriptome-wide Association Studies to Discover Candidate Genes for Diverse Root Phenotypes in Cultivated Rice

Rice (N Y). 2023 Dec 8;16(1):55. doi: 10.1186/s12284-023-00672-x.

ABSTRACT

Root system architecture plays a crucial role in nutrient and water absorption during rice production. Genetic improvement of the rice root system requires elucidating its genetic control. Genome-wide association studies (GWASs) have identified genomic regions responsible for rice root phenotypes. However, candidate gene prioritization around the peak region often suffers from low statistical power and resolution. Transcriptomics enables other statistical mappings, such as transcriptome-wide association study (TWAS) and expression GWAS (eGWAS), which improve candidate gene identification by leveraging the natural variation of the expression profiles. To explore the genes responsible for root phenotypes, we conducted GWAS, TWAS, and eGWAS for 12 root phenotypes in 57 rice accessions using 427,751 single nucleotide polymorphisms (SNPs) and the expression profiles of 16,901 genes expressed in the roots. The GWAS identified three significant peaks, of which the most significant peak responsible for seven root phenotypes (crown root length, crown root surface area, number of crown root tips, lateral root length, lateral root surface area, lateral root volume, and number of lateral root tips) was detected at 6,199,732 bp on chromosome 8. In the most significant GWAS peak region, OsENT1 was prioritized as the most plausible candidate gene because its expression profile was strongly negatively correlated with the seven root phenotypes. In addition to OsENT1, OsEXPA31, OsSPL14, OsDEP1, and OsDEC1 were identified as candidate genes responsible for root phenotypes using TWAS. Furthermore, a cis-eGWAS peak SNP was detected for OsDjA6, which showed the eighth strongest association with lateral root volume in the TWAS. The cis-eGWAS peak SNP for OsDjA6 was in strong linkage disequilibrium (LD) with a GWAS peak SNP on the same chromosome for lateral root volume and in perfect LD with another SNP variant in a putative cis-element at the 518 bp upstream of the gene. These candidate genes provide new insights into the molecular breeding of root system architecture.

PMID:38063928 | DOI:10.1186/s12284-023-00672-x

Categories
Nevin Manimala Statistics

Treatment outcomes of radiotherapy with concurrent weekly cisplatin in older patients with locally advanced head and neck squamous cell carcinoma

Discov Oncol. 2023 Dec 8;14(1):226. doi: 10.1007/s12672-023-00844-7.

ABSTRACT

BACKGROUND: Tri-weekly cisplatin and radiotherapy (CDDP + RT) is a standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) but is sometimes challenging to complete in older patients. Weekly CDDP + RT has shown mild toxicity compared to tri-weekly CDDP + RT for LA-HNSCC and is a promising option for older adults. We aimed to report the treatment outcomes and prognostic factors in patients with LA-HNSCC treated with weekly CDDP + RT.

METHODS: We analyzed patients aged ≥ 70 years who started weekly CDDP + RT for LA-HNSCC between July 2006 and October 2022. LA-HNSCC includes cancer in the oropharynx, hypopharynx, or larynx with a clinical stage of 3 or 4 without distant metastases based on the Union for International Cancer Control staging system 8th edition. The radiation dose of 70 Gy was delivered in 35 fractions by 3-dimensional conformal radiotherapy, intensity-modulated radiotherapy, or proton beam therapy. The primary endpoint was the 3-year overall survival (OS), and the secondary endpoints were the 3-year progression-free survival (PFS) and 3-year cause-specific survival (CSS). The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used to evaluate statistical significance. A Cox proportional hazards model was used for the multivariate analysis of prognostic factors.

RESULTS: The median age of the 49 patients was 72 (range: 70-78) years. The median CDDP dose was 200 (40-280) mg/ m2, and 47 patients completed scheduled radiotherapy. Forty-eight patients (98.0%) had a performance status of ≥ 1 at the initial visit. The 3-year OS, PFS, and CSS were 80.9% (95% confidence interval [CI]: 64.8-90.7), 68.3% (95% CI 51.8-81.2), and 85.0% (95% CI 68.7-93.4), respectively. In the multivariate analysis, the cumulative CDDP dose (< 200 or ≥ 200 mg/m2) was a significant factor for OS (hazard ratio: 0.29 [95% CI 0.08-0.97], p = 0.044). There was one case of early mortality. Grade 3 or higher late adverse events were observed in four patients (8.2%).

CONCLUSIONS: Weekly CDDP + RT in older patients led to good survival outcomes with an acceptable rate of adverse events. CDDP should be administered at a dose of at least 200 mg/m2 in older patients. Trial registration Retrospectively registered.

PMID:38063923 | DOI:10.1007/s12672-023-00844-7

Categories
Nevin Manimala Statistics

Efficacy of transauricular vagus nerve stimulation for the treatment of chemotherapy-induced painful peripheral neuropathy: a randomized controlled exploratory study

Neurol Sci. 2023 Dec 8. doi: 10.1007/s10072-023-07229-2. Online ahead of print.

ABSTRACT

BACKGROUND: Chemotherapy-induced painful peripheral neuropathy (CIPN) is a common adverse event in cancer patients, and there is still a lack of effective treatment. Transauricular vagal nerve stimulation (taVNS) is a minimally invasive treatment, but there are few reports regarding its efficacy for CIPN.

OBJECTIVE: To investigate the efficacy and possible mechanism of taVNS in patients with CIPN.

METHODS: Twenty-seven patients with CIPN were randomly divided into a taVNS group (n = 14) and a sham stimulation (SS) group (n = 13). A numerical rating scale (NRS) for pain, NCICTCAE 4.0 (neurotoxicity classification), quantitative sensory test (QST), Short-Form-Health Survey-12 (SF-12), and Athens Insomnia Scale (AIS) were administered before the intervention (D-10) and on the day after the intervention (D0), and the inflammatory cytokines in plasma were also measured. The NRS, NCI-CTCAE 4.0, SF-12, and AIS were administered again at D30 and D90.

RESULTS: Compared with the SS group, the NRS and AIS in the taVNS group were significantly lower at D0. The impact lasted until D30. There were no statistically significant differences in the NRS and AIS between the 2 groups at D90. On D30, the mental component score of the SF-12 was significantly higher in the taVNS group than in the SS group. No adverse events were found. There was no significant difference in QST and plasma inflammatory cytokines between the 2 groups.

CONCLUSION: taVNS can relieve chemotherapy-induced neuropathic pain in the short term, can improve sleep status and quality of life, and is expected to become a novel clinical treatment method for CIPN.

PMID:38063922 | DOI:10.1007/s10072-023-07229-2