Tag: nevin manimala

Drug Saf. 2023 Sep 14. doi: 10.1007/s40264-023-01346-9. Online ahead of print.

ABSTRACT

INTRODUCTION: During the signal detection process, statistical methods are used to identify drug-event combinations (DECs) which are disproportionately reported when compared with other drugs and events in the entire database. We hypothesise that the high volume of COVID-19 vaccine adverse drug reaction (ADR) reports transmitted to EudraVigilance may have affected the performance of disproportionality statistics used in routine signal detection, potentially resulting in signals either being masked, or false associations being flagged as potential signals.

OBJECTIVE: Our aim was to study the impact of COVID-19 vaccine spontaneous reporting on statistical signal detection in EudraVigilance.

METHODS: We recalculated the reporting odds ratio (ROR) for signals that were previously discussed at the level of the Pharmacovigilance Risk Assessment Committee, or signals that were retrieved from EudraVigilance, by omitting COVID-19 vaccine reports from the standard ROR calculation and then comparing the lower confidence interval (LCI) of the recalculated ROR to the LCI of the actual ROR in EudraVigilance.

RESULTS: In total, 52 signals for 38 active substances were reviewed. For 35 signals, the LCI of the recalculated ROR value was lower than the LCI of the actual ROR (suggesting that COVID-19 vaccine ADR reporting had a positive effect on the strength of the signal) while for 15 signals the LCI of the recalculated ROR value was higher than the LCI of the actual ROR (suggesting that COVID-19 vaccine ADR reporting had an attenuating effect on the strength of the signal). For two signals, no change in the ROR was observed. In our analysis, six significant results were found. Five DECs were found to be masked: bleomycin and immune thrombocytopenia (actual ROR LCI = 0.94, recalculated ROR LCI = 1.02), vortioxetine and heavy menstrual bleeding (actual ROR LCI = 0.3, recalculated ROR LCI = 1.06), caplacizumab and heavy menstrual bleeding (actual ROR LCI = 0.98, recalculated ROR LCI = 3.47), ziprasidone and amenorrhoea (actual ROR LCI = 0.84, recalculated ROR LCI = 1.67), and azacitidine and pericarditis (actual ROR LCI = 0.81, recalculated ROR LCI = 2.01). For the DEC of adalimumab and immune reconstitution inflammatory syndrome, the LCI of the actual ROR value was 1.14 and removing COVID-19 vaccine reporting resulted in an LCI of the recalculated ROR value of 0.94 (below threshold).

CONCLUSIONS: We demonstrated five cases of masking and one case of false-positive association due to the influence of COVID-19 vaccine spontaneous reporting on the ROR. This suggests that the high number of adverse drug reaction reports for COVID-19 vaccines in EudraVigilance has the potential to affect routine statistical signal detection activities. The impact of COVID-19 vaccine ADR reports on current signal detection practices requires further evaluation and solutions to tackle masking issues in EudraVigilance may need to be developed.

PMID:37707778 | DOI:10.1007/s40264-023-01346-9

Biol Trace Elem Res. 2023 Sep 14. doi: 10.1007/s12011-023-03836-4. Online ahead of print.

ABSTRACT

This study evaluated the effect of selenium nanoparticles on growth performance, survival rate, chemical composition, and bioaccumulation of selenium in the muscle of Nile tilapia (Oreochromis niloticus). Fish with an average weight of 33.1 ± 1.0 g were distributed in 12 fiberglass tanks and fed for 56 days with different levels of selenium nanoparticles, 0, 0.5, 1, and 2 mg/kg of diet, considered as control, T1, T2, and T3, respectively. Body weight increase (BWI), specific growth rate (SGR), and food conversion ratio (FCR) were significantly influenced by 2 mg/kg of selenium nanoparticles compared to the other treatments, in particular control and T1 with 0.5 mg/kg selenium (P < 0.05). The survival rate was also significantly affected in T2, especially compared to the control (P < 0.05). In addition, protein, ash, and moisture percentages of muscle showed statistically different levels in fish fed a diet containing 2 mg/kg of selenium nanoparticles compared to the control treatment (P < 0.05). The results of the selenium bioaccumulation in the muscle of trial diets showed a significant difference in selenium nanoparticle bioaccumulation among treatments, with the highest revealed in the 2 mg/kg nanoparticle group (P < 0.05). Overall, selenium nanoparticles significantly improved the growth performance, survival, and chemical composition (protein in particular) of Nile tilapia, especially in the T2 and T3 treatments.

PMID:37707756 | DOI:10.1007/s12011-023-03836-4

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