Tag: nevin manimala

Pharmacoeconomics. 2023 Sep 14. doi: 10.1007/s40273-023-01314-2. Online ahead of print.

ABSTRACT

BACKGROUND: When utilities are analyzed by time to death (TTD), this has historically been implemented by ‘grouping’ observations as discrete time periods to create health state utilities. We extended the approach to use continuous functions, avoiding assumptions around groupings. The resulting models were used to test the concept with data from different regions and different country tariffs.

METHODS: Five-year follow-up in advanced non-small cell lung cancer (NSCLC) was used to fit six continuous TTD models using generalized estimating equations, which were compared with progression-based utilities and previously published TTD groupings. Sensitivity analyses were performed using only patients with a confirmed death, the last year of life only, and artificially censoring data at 24 months. The statistically best-fitting model was then applied to data subsets by region and different EQ-5D-3L country tariffs.

RESULTS: Continuous (natural) [Formula: see text] and [Formula: see text] models outperformed other continuous models, grouped TTD, and progression-based models in statistical fit (mean absolute error and Quasi Information Criterion). This held through sensitivity and scenario analyses. The pattern of reduced utility as a patient approaches death was consistent across regions and EQ-5D tariffs using the preferred [Formula: see text] model.

CONCLUSIONS: The use of continuous models provides a statistically better fit than TTD groupings, without the need for strong assumptions about the health states experienced by patients. Where a TTD approach is merited for use in modelling, continuous functions should be considered, with the scope for further improvements in statistical fit by both widening the number of candidate models tested and the therapeutic areas investigated.

PMID:37707719 | DOI:10.1007/s40273-023-01314-2

Diabetes Ther. 2023 Sep 14. doi: 10.1007/s13300-023-01462-w. Online ahead of print.

ABSTRACT

INTRODUCTION: Liraglutide effectively controls blood glucose level and reduces body weight. The aim of this study was to compare the efficacy and safety of a biosimilar liraglutide (Melitide^®; CinnaGen, Tehran, Iran) to the reference liraglutide (Victoza^®; Novo Nordisk, Bagsvaerd, Denmark) in people with type 2 diabetes mellitus (T2DM).

METHODS: In this phase 3 clinical noninferiority trial, adult patients with inadequately controlled T2DM and with hemoglobin A_1C (HbA_1C) levels of 7-10.5% on at least two oral glucose-lowering drugs with stable doses for at least 3 months were randomized to receive Melitide^® (n = 150) or Victoza^® (n = 150) 1.8 mg/day for 26 weeks. The primary outcome was assessment of the noninferiority of Melitide^® to Victoza^® in terms of change in HbA_1C level with a prespecified margin of 0.4%. The secondary outcomes were the assessment of additional efficacy parameters (including the proportion of patients achieving HbA_1C levels of < 7%), the incidence of adverse events, and immunogenicity.

RESULTS: Of the 300 participants enrolled in this study, 235 were included in the per-protocol analysis (112 in the Melitide^® group and 123 in the Victoza^® group). The mean (standard deviation) changes in HbA_1C were – 1.76% (1.22) in the Melitide^® group and – 1.59% (1.31) in the Victoza^® group. The upper limit of the 95% one-sided confidence interval (CI) of the mean difference between Melitide^® and Victoza^® in lowering HbA_1C was lower than the predefined margin (mean difference – 0.18, 95% CI – 0.5 to 0.15). Similar findings were obtained with the intention-to-treat analysis. No statistically significant differences were observed between the two study arms regarding the proportion of patients achieving HbA_1C < 7% (p = 0.210), other efficacy parameters (p > 0.05), and reported adverse events (p = 0.916). Furthermore, none of the patients developed anti-liraglutide antibodies.

CONCLUSION: The biosimilar liraglutide (Melitide^®) was noninferior in efficacy and comparable in safety when compared with the reference liraglutide.

TRIAL REGISTRATION: NCT03421119.

PMID:37707701 | DOI:10.1007/s13300-023-01462-w

Diabetes Ther. 2023 Sep 14. doi: 10.1007/s13300-023-01466-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Ready-to-use glucagon represents a significant advancement in the management of severe hypoglycemia for people with diabetes and their caregivers. This indirect treatment comparison (ITC) evaluated the efficacy and safety differences among the three ready-to-use glucagon treatments, Baqsimi^® (nasal glucagon), Gvoke^® (glucagon injection) and Zegalogue^® (dasiglucagon injection), in adults and children with type 1 diabetes (T1D) or type 2 diabetes (T2D).

METHODS: A systematic literature review was conducted to identify randomized clinical trials assessing the efficacy and safety of Baqsimi, Gvoke or Zegalogue versus reconstituted, injectable glucagon (IG) in reversing insulin-induced hypoglycemia. Bayesian fixed-effect network meta-analysis was used to perform the ITC. Study endpoints included proportion of participants achieving treatment success, maximum blood glucose achieved, time to achieve treatment success and maximum blood glucose and treatment-emergent adverse events (TEAE).

RESULTS: Ten clinical trials were included in the ITC (four for Baqsimi, three for Gvoke, and three for Zegalogue). All three treatments achieved high proportions of treatment success (> 98%). In adults, the efficacy results from combined T1D and T2D analysis were consistent with the T1D analysis, except statistically significantly faster in achieving treatment success for Baqsimi vs Gvoke in the combined analysis (13.96 vs 14.66 min). The mean maximum blood glucose values were also statistically significantly lower for Baqsimi (168 mg/dl) vs Gvoke (220 mg/dl) and Zegalogue (190 mg/dl). There was a trend towards a lower number of adults experiencing ≥ 1 TEAE with Baqsimi compared to Gvoke or Zegalogue, but no statistical significance was reached.

CONCLUSION: Baqsimi, Gvoke and Zegalogue had comparable high proportions of treatment success in reversing insulin-induced hypoglycemia. Baqsimi achieved a lower mean maximum blood glucose value, which may have implications for the re-establishment of euglycemia. These findings may help support patients, caregivers and health care providers in their decision-making process when discussing various ready-to-use glucagon treatment options.

PMID:37707700 | DOI:10.1007/s13300-023-01466-6

J Magn Reson Imaging. 2023 Sep 14. doi: 10.1002/jmri.29012. Online ahead of print.

ABSTRACT

BACKGROUND: Lymph node characteristics markedly affect nasopharyngeal carcinoma (NPC) prognosis. Matted node (MN), an important characteristic for lymph node, lacks explored MRI-based prognostic implications.

PURPOSE: Investigate MRI-determined MNs’ prognostic value in NPC, including 5-year overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), progression-free survival (PFS), and its role in induction chemotherapy (IC).

STUDY TYPE: Retrospective cohort survival study.

POPULATION: Seven hundred ninety-two patients with non-metastatic NPC (female: 27.3%, >45-year old: 50.1%) confirmed by biopsy.

FIELD STRENGTH/SEQUENCE: 5-T/3.0-T, T1-, T2- and post-contrast T1-weighted fast spin echo sequences acquired.

ASSESSMENT: MNs were defined as ≥3 nodes abutting with intervening fat plane replaced by extracapsular nodal spread (ENS). Patients were observed every 3 months for 2 years and every 6 months for 5 years using MRI. Follow-up extended from treatment initiation to death or final follow-up. MNs were evaluated by three radiologists with inter-reader reliability calculated. A 1:1 matched-pair method compared survival differences between MN-positive patients with or without IC. Primary endpoints (OS, DMFS, LRFS, PFS) were calculated from therapy initiation to respective event.

STATISTICAL TESTS: Kappa values assessed inter-reader reliability. Correlation between MN, ENS, and LNN was studied through Spearman’s correlation coefficient. Clinical characteristics were calculated via Fisher’s exact, Chi-squared, and Student’s t-test. Kaplan-Meier curves and log-rank tests analyzed all time-to-event data. Confounding factors were included in Multivariable Cox proportional hazard models to identify independent prognostic factors. P-values <0.05 were considered statistically significant.

RESULTS: MNs incidence was 24.6%. MNs independently associated with decreased 5-year OS, DMFS, and PFS; not LRFS (P = 0.252). MN-positive patients gained significant survival benefit from IC in 5-year OS (88.4% vs. 66.0%) and PFS (76.4% vs. 53.5%), but not DMFS (83.1% vs. 69.9%, P = 0.145) or LRFS (89.9% vs. 77.8%, P = 0.140).

DATA CONCLUSION: MNs may independently stratify NPC risk and offer survival benefit from IC.

EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

PMID:37706438 | DOI:10.1002/jmri.29012

J Minim Access Surg. 2023 Jul 5. doi: 10.4103/jmas.jmas_168_22. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective is to investigate if laparoscopic-dominant abdominoperineal resection (LDAPR) with individualised levator ani resection inhibits local recurrence (LR) and prolongs survival as compared to laparoscopic abdominoperineal resection (APR).

MATERIALS AND METHODS: Rectal cancer surgery cases were retrospectively identified from September 2014 to December 2019. LDAPR-treated group (55 patients) and the APR-treated group (71 patients) were included in the study. The operation time, circumferential resection margin (CRM), intraoperative tumor surgery (ITP), post-operative complications, the 2-year overall survival (OS) and LR were compared in the two groups.

RESULTS: The CRM and ITP were significantly reduced in the LDAPR as compared to the APR group (3.6% vs. 16.9%, t = 5.522, P = 0.019; 3.6% vs. 14.1%, t = 3.926, P = 0.048). In terms of post-operative complications, the incidence of urinary retention in LDAPR was significantly reduced than the APR group (10.9% vs. 25.4%, χ² = 4.139, P = 0.041). Similarly, perineal pain at 6 months or 1 year after surgery was significantly down-regulated in LDAPR than in the APR group (72.7% vs. 88.7%, χ² = 5.320, P = 0.021; 18.2% vs. 43.2%, χ² = 8.288, P = 0.004). However, there was no statistically significant difference in the post-operative complications between the LDAPR and APR groups. Finally, LDAPR led to a significantly improved 2-year OS and a reduced LR compared to APR.

CONCLUSION: LDAPR reduces CMR, ITP and LR and simplified the perineum operation, subsequently protecting the pelvic autonomic nerves. Compared to the conventional APR, LDAPR is a promising procedure worth adopting for rectal cancer treatment.

PMID:37706404 | DOI:10.4103/jmas.jmas_168_22

Ann Card Anaesth. 2023 Apr-Jun;26(2):183-189. doi: 10.4103/aca.aca_68_22.

ABSTRACT

BACKGROUND: Aortic stenosis (AS) grading discrepancies exist between pre-cardiopulmonary (pre-CPB) transesophageal echocardiography (TEE) and preoperative transthoracic echocardiography (TTE). Prior studies have not systematically controlled blood pressure.

AIMS: We hypothesized that normalizing arterial blood pressure during pre-CPB TEE for patients undergoing valve replacement for AS would result in equivalent grading measurements when compared to TTE.

SETTING: Single University Hospital.

DESIGN: Prospective, Interventional.

METHODS: Thirty-five adult patients underwent procedures for valvular AS between February 2017 and December 2020 at Medical University of South Carolina. Study participants had a TTE within 90 days of their procedure that documented blood pressure, peak velocity (V_p), mean gradient (PG_m), aortic valve area (AVA), and dimensionless index (DI). During pre-CPB TEE, if a patient’s mean arterial pressure (MAP) fell more than 20% below their baseline blood pressure obtained during TTE, measurements were recorded as “out of range.” Phenylephrine was administered to restore MAP to the baseline range and repeat TEE measurements were recorded as “in-range.”

STATISTICAL ANALYSIS: Differences between imaging modalities and grading parameters were examined using a series of linear mixed models. P values were Bonferroni-adjusted to account for multiple comparisons.

MAIN RESULTS: Significant discrepancies between TEE and TTE were observed for V_p, PG_m, and DI despite blood pressure normalization across all subjects and for out-of-range measures and corrected measures. There were no statistically significant differences between TEE and TTE for AVA.

CONCLUSIONS: Blood pressure normalization during pre-CPB TEE is not sufficient to avoid AS grading discrepancies with preoperative TTE.

PMID:37706384 | DOI:10.4103/aca.aca_68_22

Indian J Med Res. 2023 Sep 14. doi: 10.4103/ijmr.ijmr_3629_21. Online ahead of print.

ABSTRACT

BACKGROUND & OBJECTIVES: Cerebral contusion (CC) results in a release of catecholamines, autonomic dysfunction and neural stimulation that can lead to a number of cardiac adverse events, so it is critical to determine these. So the objective of this study was to investigate the prognostic significance of electrocardiographic changes, particularly the effects of a prolonged corrected QT (QTc) interval in CC.

METHODS: In this retrospective cohort study, 110 patients with CC were evaluated. Age, sex, concomitant diseases, Glasgow Coma Scale on admission, radiological assessment of the contusion (location, size, course and presence of cerebral oedema), need for surgical intervention, length of hospital stay and the extended Glasgow Outcome Scale (GOS-E) were statistically analysed within the QTc interval by routine electrocardiography (ECG) on admission.

RESULTS: The prolonged QTc interval was found to be associated with a higher incidence of cerebral oedema and a significantly higher risk of needing surgery. Patients with a prolonged QTc interval had a significantly larger contusion volume, greater midline shift and longer hospital stay, so their GOS-E score was significantly lower. A prolonged QTc interval on admission resulted in a hospital stay of more than eight days (sensitivity: 0.97 and specificity: 0.86), a higher risk of midline shift of more than 0.45 cm (P=0.006, sensitivity: 0.80 and specificity: 0.99) and a GOS-E score of <7 (sensitivity: 0.97 and specificity: 0.85).

INTERPRETATION & CONCLUSIONS: ECG changes on admission showing a prolonged QTc interval have prognostic significance in CC. This simple and easily applicable information should be taken into consideration at the time of clinical decision making which may prevent an adverse events survivor.

PMID:37706372 | DOI:10.4103/ijmr.ijmr_3629_21

J Clin Nurs. 2023 Sep 14. doi: 10.1111/jocn.16872. Online ahead of print.

ABSTRACT

AIM: To examine the multidimensional properties of caregiver burden among family caregivers of patients with advanced cancer in a palliative context.

DESIGN: A sequential, explanatory, mixed-method study was performed.

METHODS: Family caregivers of patients diagnosed with advanced cancer were recruited from a palliative care department of a third-level hospital in Sichuan Province, China. The Caregiver Burden Inventory, Social Support Rating Scale and Connor-Davidson Resilience Scale were used to collect quantitative data, and a total of 150 caregivers were recruited from January 2022 to September 2022. Qualitative data were collected through semi-structured interviews, and a total of 22 caregivers were interviewed from October 2022 to November 2022. Survey data were analysed using descriptive statistics, and the factors of caregiver burden were identified using the Mann-Whitney U test, Kruskal-Wallis H test and Spearman correlations. Interpretative phenomenological analysis was performed to analyse the interview data to initially explore the multidimensions of caregiver burden. The following-a-thread method and convergence coding matrix were used for triangulation to examine the multidimensional properties of caregiver burden.

RESULTS: The participants experienced a moderate level of caregiver burden (32.97 ± 13.09). Through triangulation, six meta-themes and nine meta-subthemes were identified as multidimensional properties of caregiver burden, including physical (too many caring tasks and poor health condition), emotional (strong negative emotions resulting from patients’ suffering and insufficient and ineffective family communication), social (less social interaction and social role conflict) and economic burdens, factors that aggravate burden (prevention and control of COVID-19 and spousal relationship with patients) and factors that mitigate burden (social support).

CONCLUSION: Multiple dimensions of caregiver burden were experienced by family caregivers of patients with advanced cancer in the palliative context. Family-centred palliative care must be further developed.

IMPLICATIONS FOR THE PROFESSION: It is important to develop family-centred palliative care. Therefore, the focus must be on developing a rational understanding of palliative care in public and a culture-oriented death education in palliative units.

IMPACT: This study adopted a mixed-method approach to comprehensively understand the phenomenon of and factors in caregiver burden in the Chinese palliative oncology context. Our findings suggest that family caregivers in palliative oncology experience a moderate level of caregiver burden, with dimensions including physical, emotional, social and economic burdens, among which emotional burden is the most prominent. The findings of this study provide policy makers and nurse practitioners with targets to be addressed in family-centred care in Chinese palliative units.

REPORTING METHOD: The results of this study are reported based on the guidelines of the Mixed-Methods Article Reporting Standards.

PATIENT OR PUBLIC CONTRIBUTION: Eligible caregivers were invited to participate in the study and semi-structured interviews. Nurse managers of the palliative unit helped us access the patient-management system.

PMID:37706353 | DOI:10.1111/jocn.16872

Aesthet Surg J. 2023 Sep 14:sjad303. doi: 10.1093/asj/sjad303. Online ahead of print.

ABSTRACT

BACKGROUND: Textured implants and expanders are associated with an increased risk of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). As a result, plastic surgeons are utilizing smooth expanders, but many perceive these produce undesirable outcomes including infection, seroma, and lateral displacement.

OBJECTIVES: To compare clinical outcomes of smooth and textured expanders.

METHODS: We retrospectively reviewed breast reconstruction patients from January 2018 to May 2021. Included patients underwent placement of tissue expanders at the time of mastectomy. Primary outcomes included postoperative seroma, infection, malposition, days to final reconstruction, explantation, and need for capsulorrhaphy.

RESULTS: 233 patients were reviewed, and 167 patients met both inclusion and exclusion criteria. There was no statistically significant difference in poor outcomes comparing smooth and textured expanders. Days to final reconstruction was lower with smooth expanders per breast (p = 0.0424). The subpectoral group was associated with an increased likelihood of undergoing capsulorrhaphy (p = 0.004). Prepectoral placement was associated with more seromas (p = 0.0176) and infections (p = 0.0245). Demographic factors included older age as a protective factor for undergoing capsulorrhaphy (OR = 0.962, p = 0.038), obesity increased the risk of infection (OR = 5.683, p = 0.0279) and malposition (OR = 6.208, p = 0.0222) and radiation was associated with malposition (OR = 3.408, p = 0.0246).

CONCLUSIONS: There was no significant difference in poor outcomes comparing smooth and textured expanders. Patient demographics and anatomical plane placement had greater effects on infection, seroma and need for capsulorrhaphy compared to tissue expander texturing.

PMID:37706322 | DOI:10.1093/asj/sjad303

Twin Res Hum Genet. 2023 Sep 14:1-3. doi: 10.1017/thg.2023.37. Online ahead of print.

ABSTRACT

A simple model by which Hardy-Weinberg proportions are attained in a single generation while maintaining gene frequencies is stated and illustrated. The title ‘Quasi-random mating’ is proposed. Confusion about the Hardy-Weinberg principle can be avoided only if there is clear separation between the basic deterministic model and factors influencing a population’s structure. Eighty years passed before C. C. Li coined the term ‘pseudo-random mating’. The lesson taught by Li has not been taken on board.

PMID:37706311 | DOI:10.1017/thg.2023.37