Nevin Manimala

Int Ophthalmol. 2023 Sep 14. doi: 10.1007/s10792-023-02838-4. Online ahead of print.

ABSTRACT

PURPOSE: We aim to contribute to the literature in terms of treatment safety with our real world data by examining the anterior segment complications and follow-up results of patients who underwent dexamethasone implants in our clinic.

METHODS: The records of patients treated with at least one intravitreal dexamethasone implant for various retinal diseases: diabetic macular edema (265 eyes), central retinal vein occlusion (45 eyes), retinal vein branch occlusion (91 eyes), postoperative cystoid macular edema (18 eyes), non-infectious uveitis (37 eyes) and other (14 eyes) between July 2013 and April 2020 were reviewed.

RESULTS: After 925 injections were applied to 470 eyes of a total of 383 patients, the eyes were controlled during a mean follow-up of 24 months. No complications were detected in 328 eyes. Intraocular pressure (IOP) above 25 mmHg was detected in 97 eyes (20.6%) that had no previous history of ocular hypertension. Of these 97 eyes, 71 (73.1%) eyes with increased IOP were treated with topical monotherapy, 26 (26.8%) eyes were treated with topical combined therapy and 1 (1.03%) patient had glaucoma surgery. Cataracts requiring surgical intervention developed in 55 (%21.73) of 253 phakic eyes. Three patients have anterior chamber dislocation of dexamethasone, 1 patient was hospitalized with sterile endophthalmitis on the 7th day after the injection, and pars plana vitrectomy was performed.

CONCLUSION: This study is the first long-term follow-up study in our country evaluating the safety of dexamethasone implant injections in various retinal diseases and presenting the first real world data. Cataract progression and increased IOP were found to be the most common side effects. We observed that the patient’s diagnosis did not cause a statistically significant change in the observation of side effects. As a result of our findings, close follow-up of IOP after the injection of dexamethasone implants would be appropriate.

PMID:37707746 | DOI:10.1007/s10792-023-02838-4

Aging Clin Exp Res. 2023 Sep 14. doi: 10.1007/s40520-023-02529-1. Online ahead of print.

ABSTRACT

BACKGROUND: Frailty has been associated with a higher incidence of overall postoperative complications and mortality. However, the influence of frailty on the risk of venous thromboembolism (VTE) in patients with hip fracture following surgery remains unclear. We performed a meta-analysis to systematically evaluate the above association.

METHODS: PubMed, Embase, Cochrane Library, Wanfang and CNKI were searched for relevant observational studies comparing the incidence of postoperative VTE in patients of hip fracture with and without frailty. Data collection, literature searching, and statistical analysis were conducted independently by two authors. Using a heterogeneity-incorporating random-effects model, the results were pooled.

RESULTS: In this meta-analysis, 9509 patients from nine cohort studies were included. Pooled results showed that compared to those without frailty, patients with frailty at admission had a higher incidence of postoperative VTE (odds ratio [OR]: 2.59, 95% confidence interval [CI]: 1.25-5.39, p = 0.01; I² = 66%). Subgroup analysis suggested the association between frailty and postoperative VTE was more remarkable in studies of patients with frailty prevalence < 50% (OR 6.28, 95% CI 3.31-11.90, p < 0.001; I² = 8%) as compared to those ≥ 50% (OR 1.30, 95% CI 0.80-2.11, p = 0.28; I² = 0%; p for subgroup difference < 0.001). Further meta-analyses showed that frailty at baseline was associated with a higher incidence of deep venous thrombosis (OR 3.15, 95% CI 1.33-7.47, p = 0.009; I² = 59%), but not pulmonary embolism (OR 1.13, 95% CI 0.59-2.16, p = 0.72; I² = 0%).

CONCLUSION: Frailty is associated with a higher incidence of postoperative VTE in patients with hip fracture.

PMID:37707745 | DOI:10.1007/s40520-023-02529-1

Infection. 2023 Sep 14. doi: 10.1007/s15010-023-02093-w. Online ahead of print.

ABSTRACT

BACKGROUND: Several studies suggested pancreatic stone protein (PSP) as a promising biomarker to predict mortality among patients with severe infection. The objective of the study was to evaluate the performance of PSP in predicting intensive care unit (ICU) mortality and infection severity among critically ill adults admitted to the hospital for infection.

METHODS: A systematic search across Cochrane Central Register of Controlled Trials and MEDLINE databases (1966 to February 2022) for studies on PSP published in English using ‘pancreatic stone protein’, ‘PSP’, ‘regenerative protein’, ‘lithostatin’ combined with ‘infection’ and ‘sepsis’ found 46 records. The search was restricted to the five trials that measured PSP using the enzyme-linked immunosorbent assay technique (ELISA). We used Bayesian hierarchical regression models for pooled estimates and to predict mortality or disease severity using PSP, C-Reactive Protein (CRP) and procalcitonin (PCT) as main predictor. We used statistical discriminative measures, such as the area under the receiver operating characteristic curve (AUC) and classification plots.

RESULTS: Among the 678 patients included, the pooled ICU mortality was 17.8% (95% prediction interval 4.1% to 54.6%) with a between-study heterogeneity (I-squared 87%). PSP was strongly associated with ICU mortality (OR = 2.7, 95% credible interval (CrI) [1.3-6.0] per one standard deviation increase; age, gender and sepsis severity adjusted OR = 1.5, 95% CrI [0.98-2.8]). The AUC was 0.69 for PSP 95% confidence interval (CI) [0.64-0.74], 0.61 [0.56-0.66] for PCT and 0.52 [0.47-0.57] for CRP. The sensitivity was 0.96, 0.52, 0.30 for risk thresholds 0.1, 0.2 and 0.3; respective false positive rate values were 0.84, 0.25, 0.10.

CONCLUSIONS: We found that PSP showed a very good discriminative ability for both investigated study endpoints ICU mortality and infection severity; better in comparison to CRP, similar to PCT. Combinations of biomarkers did not improve their predictive ability.

PMID:37707744 | DOI:10.1007/s15010-023-02093-w

Environ Sci Pollut Res Int. 2023 Sep 14. doi: 10.1007/s11356-023-29497-3. Online ahead of print.

ABSTRACT

China is the foremost global consumer, producer, and exporter of fresh apples. In 2021, China produced roughly 44 million tons of apples and exported just over 1 million tons, a nearly 2% increase over the previous year. However, the ongoing COVID-19 pandemic has had a detrimental impact on global trade and has led to a decrease in China’s agricultural exports. The present study aims to contribute to the existing body of literature by analyzing plausible macroeconomic determinants that might impact China’s apple exports. We used novel dynamic autoregressive distributed lag (DYARDL) simulations to model causal relationships among fundamental economic parameters. We made use of annual time series data from 1990 to 2020 from the World Bank and China’s national statistical bureau. We found that increases in apple orchard area, apple production, and trade openness had a positive impact on apple exports over both the short and long term. Conversely, decreases in the prices of exported apples, agrochemicals, and carbon emissions in the agricultural sector had a positive impact on the long-term and short-term exportation of apples. Finally, we note that pictographic illustrations from the DYARDL simulations provide corroborative evidence for our findings. Based on the study results, this study proposes that the adoption of technological advancements in apple orchards could potentially enhance apple production while simultaneously upholding environmental sustainability.

PMID:37707739 | DOI:10.1007/s11356-023-29497-3

Environ Sci Pollut Res Int. 2023 Sep 14. doi: 10.1007/s11356-023-29752-7. Online ahead of print.

ABSTRACT

In this study, it was aimed to investigate the effects of melamine exposure since the weaning period on ovarian tissue and ovarian reserve. Melamine is illegally added to milk and formula to provide high false protein positivity. Female rats (the weaning period = 21 days old, n = 18) were divided into 3 groups. 0.1 mL saline was applied to the control group by gavage for 21 days. Fifty mg/kg and seventy-five mg/kg melamine was dissolved in 0.1 mL of saline and applied by gavage for 21 days, respectively. At the end of the experiment, plasma anti-Mullerian hormone (AMH) was measured, follicle count and ovarian diameter measurement were performed in the right ovaries, and flow cytometric analysis for apoptosis was performed in the left ovaries. While a statistically significant decrease was not observed in the number of the follicle and ovarian diameter between the control and melamine-treated groups (p > 0.05), a significant decrease in the corpus luteum and a significant increase in the number of atretic follicles were observed (p < 0.05). Apoptosis (Annexin V) increased in both melamine groups and AMH plasma level decreased significantly in the 75 mg/kg group (p < 0.05). Melamine exposure from the weaning (early postnatal) period may cause a decrease in ovarian reserve in parallel with a dose increase.

PMID:37707728 | DOI:10.1007/s11356-023-29752-7

Pharmacoecon Open. 2023 Sep 14. doi: 10.1007/s41669-023-00436-9. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Risperidone is used in autism spectrum disorder (ASD) to manage aggressive behavior. Budget impact analysis (BIA) assists managers in promoting more sustainable health systems; however, it is unclear whether BIAs underestimate or overestimate the estimates derived from real-world data. This study aimed to compare the estimated BIA values of risperidone use and the monitoring of adverse events in ASD using theoretical and real data.

METHODS: Analyses were conducted based on the clinical protocol and the Brazilian therapeutic guidelines for ASD. The perspective adopted was that of the Unified Health System (SUS), considering a time horizon of 5 years. Three possible scenarios were considered based on the maximum daily dose of risperidone. Expenses related to the acquisition of risperidone and the monitoring of adverse events were taken into account using health databases in Brazil. For the calculation based on theoretical data, the prevalence of ASD was estimated using information from the scientific literature and the Brazilian demographic census. The model calculated from real data was obtained by analyzing the linear trend of the number of users assisted in the SUS from 2017 to 2021.

RESULTS: The population estimated by the theoretical model compared with the model calculated from the real data was higher. Likewise, the 5-year budgetary impact of the theoretical model versus the model calculated from the real data was higher, with statistical significance in all scenarios (p < 0.001). In the real data model, the most economically advantageous scenarios were Scenario 1 for children (International dollars [I$] 7,630,040.73) and Scenario 3 for adults (I$60,329,288.17). Estimated expenditures for monitoring adverse events ranged from 17 to 74% in children and from 50% to 63% in adults.

CONCLUSIONS: The data revealed significant differences in population and cost estimation between theoretical data and real-world data. The expenses associated with monitoring adverse events represented a substantial expenditure estimate for the SUS.

PMID:37707722 | DOI:10.1007/s41669-023-00436-9

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