Category: Nevin Manimala

Vaccine. 2023 Mar 2:S0264-410X(23)00240-2. doi: 10.1016/j.vaccine.2023.02.077. Online ahead of print.

ABSTRACT

The protective effect of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against cardiovascular disease has been investigated in the United States and Europe; however, its effect has not been fully established. This study aimed to investigate the protective effect of PPSV23 on cardiovascular events in adults aged ≥ 65 years. This population-based nested case-control study was conducted using the claims data and vaccine records between April 2015 and March 2020 from the Vaccine Effectiveness, Networking, and Universal Safety (VENUS) Study. PPSV23 vaccination was identified using vaccination records in each municipality. The primary outcome was acute myocardial infarction (AMI) or stroke. The adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for PPSV23 vaccination were calculated using conditional logistic regression. Among 383,781 individuals aged ≥ 65 years, 5,356 and 25,730 individuals with AMI or stroke were matched with 26,753 and 128,397 event-free controls, respectively. Individuals who were PPSV23 vaccinated, compared with the unvaccinated individuals, had significantly lower odds of AMI or stroke events (aOR, 0.70 [95% CI, 0.62-0.80] and aOR, 0.81 [95% CI, 0.77-0.86], respectively). More recent PPSV23 vaccination was associated with lower odds ratios (AMI, aOR 0.55 [95% CI, 0.42-0.72] for 1-180 days and aOR 1.11 [95% CI, 0.84-1.47] for 720 days or longer; stroke, aOR 0.83 [95% CI, 0.74-0.93] for 1-180 days and aOR 0.90 [95% CI, 0.78-1.03] for 720 days or longer). Among Japanese older adults, individuals who were PPSV23 vaccinated, compared with unvaccinated individuals, had significantly lower odds of AMI or stroke events.

PMID:36870877 | DOI:10.1016/j.vaccine.2023.02.077

J Am Vet Med Assoc. 2023 Mar 3:1-7. doi: 10.2460/javma.22.11.0521. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine whether shock index (SI) positively correlates with percentage blood loss and negatively correlates with cardiac output (CO) in a canine hemorrhagic shock model and whether SI and metabolic markers may be used as end point targets for resuscitation.

ANIMALS: 8 healthy Beagles.

PROCEDURES: Between September and December 2021, dogs underwent general anesthesia for experimental induction of hypotensive shock, with the total volume of blood removed, CO, heart rate, systolic blood pressure, base excess, blood pH, and concentrations of hemoglobin, lactate, ionized calcium recorded, and SI calculated at 4 time points (TPs): after anesthetic induction when the dog had been stable for 10 minutes (TP1), 10 minutes after the mean arterial pressure stabilized to a target of 40 mm Hg following jugular removal of up to 60% blood volume to induce hemorrhagic shock (TP2), 10 minutes after autotransfusion of 50% of the removed blood (TP3), and 10 minutes after autotransfusion of the remaining 50% of the removed blood (TP4).

RESULTS: Mean SI increased between TP1 (1.08 ± 0.35) and TP2 (1.90 ± 0.73) and did not return to the prehemorrhage values for TP3 or TP4. SI correlated positively with percentage blood loss (r = 0.583) and negatively with CO (r = -0.543).

CLINICAL RELEVANCE: An increase in SI may support diagnosis of hemorrhagic shock; however, SI cannot be used as the sole end point of resuscitation. Significant differences in blood pH, base excess, and lactate concentration suggested they may be useful markers of hemorrhagic shock and need for blood transfusion.

PMID:36870053 | DOI:10.2460/javma.22.11.0521

Neurol Ther. 2023 Mar 4. doi: 10.1007/s40120-023-00455-y. Online ahead of print.

ABSTRACT

BACKGROUND: Results from observational studies indicate an association between circulating levels of mammalian target of rapamycin (mTOR)-dependent circulating proteins and the risk of multiple sclerosis (MS). However, a causal association has not been fully elucidated. Mendelian randomization (MR) is used to overcome limitations inherent to observational studies, assess the causal association, and minimize bias due to confounding and reverse causation.

METHODS: To explore the causal association between seven mTOR-dependent proteins (AKT, RP-S6K, eIF4E-BP, eIF4A, eIF4E, eIF4G, and PKC-α) and MS, we obtained summary statistics from the genome-wide association study (GWAS) meta-analysis of the International Multiple Sclerosis Genetics Consortium (47,429 patients and 68,374 controls) and the INTERVAL study (genetic associations with 2994 plasma proteins from 3301 healthy individuals). MR analyses were conducted using inverse variance weighted, weighted median estimator, and MR-Egger regression methods/models. Sensitivity analyses were performed to ensure the reliability of the findings. Single nucleotide polymorphisms (SNPs) that are independent (r² < 0.01) and strongly associated to minerals (p < 1e^-5) were selected as instrumental variables.

RESULTS: The results of the MR analyses revealed that among the seven mTOR-dependent proteins selected for study, the circulating level of PKC-α (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.82-0.98; P = 0.017) and RP-S6K (OR 1.12, 95% CI 1.00-1.25; P = 0.045) were associated with MS risk and that there was no sign of pleiotropy or heterogeneity. PKC-α was negatively related to MS, while RP-S6K was positively related to MS. No significant causation was found between the other proteins studied (AKT, eIF4E-BP, eIF4A, eIF4E, eIF4G) and MS.

CONCLUSION: Molecules in the mTOR signaling pathway may bidirectionally regulate the occurrence and development of MS. PKC-α is a protective factor, while RP-S6K is a risk factor. Further explorations of pathways underlying the association between mTOR-dependent proteins and MS are required. PKC-α and RP-S6K might be used as future therapeutic targets for screening high-risk individuals and potentially improving opportunities for targeted prevention strategies.

PMID:36870011 | DOI:10.1007/s40120-023-00455-y

Biochem Genet. 2023 Mar 4. doi: 10.1007/s10528-023-10347-3. Online ahead of print.

ABSTRACT

Autosomal short tandem repeat (STR) population data collected from a well characterized population are needed to correctly assigning the weight of DNA profiles in the courtroom and widely used for ancestral analyses. In this study, allele frequencies for the 15 autosomal short tandem repeat (STR) loci included in the AmpFlSTR® Identifiler® plus kit (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, VWA, TPOX, D18S51, D5S818, FGA) were obtained by genotyping 332 unrelated individuals of Ghanaian origin. Statistical tests on STR genotype data showed no significant departure from Hardy-Weinberg equilibrium (HWE). The overall match probability, combined power of exclusion and combined power of discrimination for these loci were 1 in 3.85 × 10¹⁷, 0.99999893 and 0.99999998, respectively. Polymorphic information content (PIC) greater than 0.70 was observed for all loci except TH01 and D13S317. These statistical parameters confirm that this combination of loci is valuable for forensic identification and parentage analysis. Our results were also compared with those for 20 other human populations analyzed for the same set of markers. We observed that the Ghanaian population grouped with other African populations in two-dimensional principal coordinate (PCO) and a neighbor-joining (N-J) data mapping and placed closest to Nigerians. This observation reflects cultural similarities and geographical factors, coupled with the long history of migration and trading activities between Ghana and Nigeria. Our report provides what we believe to be the first published autosomal STR data for the general Ghanaian population using 15 loci genotyped using the AmpFlSTR® Identifiler® plus kit methodology. Our data show that the loci tested have sufficient power to be used reliably for DNA profiling in forensic casework and help to elucidate the genetic history of people living in the country.

PMID:36869999 | DOI:10.1007/s10528-023-10347-3

Ophthalmol Ther. 2023 Mar 4. doi: 10.1007/s40123-023-00692-2. Online ahead of print.

ABSTRACT

INTRODUCTION: Pars plana vitrectomy (PPV) is a primary strategy to restore vision for patients who have rhegmatogenous retinal detachment (RRD). Perfluorocarbon liquid (PFCL) is frequently used during PPV surgery. However, the unintended intraocular retention of PFCL may cause retina toxicity and thus lead to possible postoperative complications. In this paper, the experiences and surgical outcomes of a NGENUITY 3D Visualization System-assisted PPV are shown to evaluate the possibility of excluding the application of PFCL.

METHODS: A consecutive series of 60 cases with RRD were presented, all of whom had undergone 23-gauge PPV with the assistance of a three-dimensional (3D) visualization system. Among them, 30 cases used PFCL to assist the drainage of subretinal fluid (SRF), while the other 30 cases did not. Parameters including retinal reattachment rate (RRR), best-corrected visual acuity (BCVA), operation time, and SRF residual were compared between the two groups.

RESULTS: Baseline data showed no statistical significance between the two groups. At the last postoperative follow-up, the RRR of all the 60 cases reached 100% and best-corrected visual acuity (BCVA) gained significant improvement. The BCVA (logMAR) increased from 1.293 ± 0.881 to 0.479 ± 0.316 in the PFCL-excluded group, exhibiting better results than the PFCL included group, whose final BCVA was 0.650 ± 0.371. More importantly, excluding PFCL greatly reduced the operation time (decrease of 20%), therefore, avoiding possible complications caused by both the use of PFCL and the operation process.

CONCLUSION: With the assistance of the 3D visualization system, it is feasible to treat RRD and perform PPV without using PFCL. The 3D visualization system is highly recommendable, as not only can it achieve the same surgical effect without the assistance of PFCL, but also simplify the operation procedure, shorten the operation time, save costs, and avoid complications related to PFCL.

PMID:36869993 | DOI:10.1007/s40123-023-00692-2

Clin Pharmacokinet. 2023 Mar 4. doi: 10.1007/s40262-023-01210-0. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: In the USA, cabozantinib was approved for the treatment of patients aged ≥ 12 years with radioiodine-refractory differentiated thyroid cancer (DTC) who progressed on prior vascular endothelial growth factor (VEGFR)-targeted therapy based on the Phase 3 COSMIC-311 trial, which evaluated cabozantinib 60 mg/day versus placebo. Approved dosing is 60 mg/day for adults and for pediatric patients aged ≥ 12 years with body surface area (BSA) ≥ 1.2 m², and 40 mg/day for pediatric patients aged ≥ 12 years with BSA < 1.2 m². This report describes a population pharmacokinetic (PopPK) and exposure-response analysis of COSMIC-311.

METHODS: A PopPK model was developed using concentration-time data from COSMIC-311 and 6 other cabozantinib studies. The final (full) PopPK model was used to simulate the effect of sex, body weight, race, and patient population. For exposure-response analysis, derived datasets from COSMIC-311 were constructed for time-to-event analyses of progression-free survival (PFS) and safety endpoints.

RESULTS: The PopPK analysis included 4746 cabozantinib PK samples from 1745 patients and healthy volunteers. Body weight had minimal impact on cabozantinib exposure but increasing body weight was associated with increased apparent volume of distribution. Based on model-based simulation, adolescents < 40 kg had higher maximum plasma concentration at steady state of cabozantinib 60 mg/day compared to adults. Allometric scaling simulation in adolescents < 40 kg demonstrated higher exposure with 60 mg/day relative to adults receiving the same dose, while exposure with 40 mg/day in adolescents < 40 kg was similar to 60 mg/day in adults. The exposure-response analysis included 115 patients. There was no clear relationship between PFS or dose modification and cabozantinib exposure. A statistically significant relationship was demonstrated for cabozantinib exposure and hypertension (Grade ≥ 3) and fatigue/asthenia (Grade ≥ 3).

CONCLUSIONS: These results support the dosing strategy implemented in COSMIC-311 and the BSA-based label recommendations for adolescents. The cabozantinib dose should be reduced to manage adverse events as indicated.

PMID:36869986 | DOI:10.1007/s40262-023-01210-0

Int Ophthalmol. 2023 Mar 4. doi: 10.1007/s10792-023-02646-w. Online ahead of print.

ABSTRACT

PURPOSE: To perform a systematic evaluation of the efficacy and safety of loteprednol etabonate (LE) 0.5% versus fluorometholone (FML) 0.1% for treating patients after corneal refractive surgery with the aim of providing an evidence-based rationale for clinical drug selection.

METHODS: Electronic databases (PubMed, EMBASE, Cochrane Library, Web of Science, WanFang, and CNKI) were searched (from inception to December 2021) for comparative clinical studies that evaluated LE versus FML treatment for post-corneal refractive surgery patients. Meta-analysis was performed using the RevMan 5.3 software. The pooled risk ratio (RR) and weighted mean difference (WMD) with corresponding 95% confidence interval (CI) were calculated.

RESULTS: Nine studies with a total sample size of 2677 eyes were included in this analysis. FML 0.1% and LE 0.5% produced a similar incidence of corneal haze within 6 months after surgery (P = 0.13 at 1 month, P = 0.66 at 3 months, and P = 0.12 at 6 months). There was no statistically significant difference between the two groups in terms of the mean logMAR postoperative uncorrected distance visual acuity (WMD: – 0.00; 95% CI: – 0.01 to 0.00; P = 0.29) and spherical equivalent (WMD: 0.01; 95% CI: – 0.01 to 0.03; P = 0.35). LE 0.5% appears to have a higher tendency to reduce the incidence of ocular hypertension compared FML 0.1%, but there was no statistical significance (RR: 0.63; 95% CI: 0.27 to 1.50; P = 0.30).

CONCLUSION: This meta-analysis demonstrated that LE 0.5% and FML 0.1% had comparable efficacy in preventing corneal haze and corticosteroid-induced ocular hypertension, with no difference in visual acuity in patients after corneal refractive surgery.

PMID:36869982 | DOI:10.1007/s10792-023-02646-w

Int Ophthalmol. 2023 Mar 4. doi: 10.1007/s10792-023-02652-y. Online ahead of print.

ABSTRACT

PURPOSE: To conduct a bibliometric and altmetric analysis of the top 50 most-cited articles on small incision lenticule extraction (SMILE) surgery and assess its correlations with other metrics.

METHODS: The terms “small incision lenticule extraction” or “SMILE” were searched in the title, abstract, and keywords using Web of Science database. The retrieved articles (n = 927, between 2010 and 2022) were analyzed in-depth using altmetric attention scores (AAS), and traditional metrics (citation numbers of articles, impact factor of journals, and other citation-based metrics). A correlation statistics was performed with metrics. The articles’ focus was examined quantitatively and the most prolific parameters were identified. Authorship network and country statistics also was examined.

RESULTS: Citation numbers were between 491 and 45. AASs were between 26 and 0. The altmetric score correlated moderately with citation number (r = 0.44, P = 0.001) and annual mean citations (r = 0.49, P < 0.001), but correlated weakly with impact factor (r = 0.28, P = 0.045), and immediacy index (r = 0.32, P = 0.022). The most articles published from China and the most articles were published in 2014. Modern SMILE surgery was mostly compared to the older LASIK procedure. The highest authorship number of links belonged to Zhou XT.

CONCLUSION: The first bibliometric and altmetric analysis of SMILE research provides novel directions for future work by showing the current research trends, prolific parameters, and zones with potential for the public’s attention, providing useful information about the dissemination of scientific knowledge on SMILE in social media and to the general public.

PMID:36869979 | DOI:10.1007/s10792-023-02652-y

Int Ophthalmol. 2023 Mar 4. doi: 10.1007/s10792-023-02653-x. Online ahead of print.

ABSTRACT

PURPOSE: To investigate microcirculation characteristics of the inner retinal layers at the macula and the peripapillary area using Optical Coherence Tomography Angiography (OCT-A) of patients in early stages of Parkinson’s disease (PD).

METHODS: 32 PD patients and 46 age- and gender-matched healthy controls were included in this cross sectional study. OCT-A imaging was performed to analyze microcirculation characteristics at each separate macular region (fovea, parafovea, and perifovea) and the peripapillary area of the inner retinal layers.

RESULTS: Individuals with PD had significantly lower parafoveal, perifoveal and total vessel density (VD) in the superficial capillary plexus (SCP) than controls (all p < 0.001), while foveal VD was higher in PD eyes than that of controls, though not statistically significant. Similarly, individuals with PD had significantly lower parafoveal, perifoveal and total perfusion in the SCP than control eyes (all p < 0.001), while foveal perfusion was significantly higher in PD eyes than that of controls (p = 0.008). PD eyes had significantly smaller FAZ area and perimeter accompanied by decreased circularity at the SCP as compared to controls (all p < 0.001). Concerning the peripapillary area, individuals with PD had significantly lower radial peripapillary capillary perfusion density and flux index at the SCP than controls (all p < 0.001). All p values remained statistically significant even after using the Bonferroni correction for multiple comparisons, except for that of foveal perfusion.

CONCLUSIONS: Our study indicates alterations of the inner retinal layers at the macula and the peripapillary area at the preliminary stages of PD. OCT-A parameters could potentially comprise imaging biomarkers for PD screening and improve the diagnostic algorithms.

PMID:36869977 | DOI:10.1007/s10792-023-02653-x

Environ Sci Pollut Res Int. 2023 Mar 4. doi: 10.1007/s11356-023-25871-3. Online ahead of print.

ABSTRACT

We use a variety of organization-level datasets to examine the effectiveness and efficiency of the nations for the coronavirus epidemic. COVID-19 subsidies appear to have saved a significant number of jobs and maintained economic activity during the first wave of the epidemic, according to conclusions drawn from the experiences of EU member countries. General allocation rules may yield near-optimal outcomes in favor of allocation, as firms with high ecological footprints or zombie firms have lower access to government financing than more favorable, commercially owned, and export-inclination firms. Our assumptions show that the pandemic has a considerable negative impact on firm earnings and the percentage of illiquid and non-profitable businesses. Although they are statistically significant, government wage subsidies have a modest impact on corporate losses compared to the magnitude of the economic shock. Larger enterprises, which receive a lesser proportion of the aid, have more room to increase their trade liabilities or liabilities to linked entities. In contrast, according to our estimations, SMEs stand a greater danger of insolvency.

PMID:36869958 | DOI:10.1007/s11356-023-25871-3