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Impact of guided weight-based medication dosing in pediatric patients with obesity

J Am Pharm Assoc (2003). 2023 Feb 12:S1544-3191(23)00028-6. doi: 10.1016/j.japh.2023.02.012. Online ahead of print.

ABSTRACT

BACKGROUND: Obesity is a common disease state within pediatrics, with 19.7% of children in the United States classified as obese. Medication dosing in this population is a challenge not commonly examined in clinical drug trials. Dosing based on total body weight may not always be appropriate; therefore, ideal body weight (IBW) and adjusted body weight (AdjBW) may provide more effective dosing.

OBJECTIVE: The goal was to implement a dosing protocol for pediatric patients with obesity to improve adherence. The primary endpoint was to evaluate adherence to evidence-based dosing recommendations and the secondary endpoints included cost saving analysis for immune globulin and accurate charting of IBW and AdjBW.

METHODS: This was a single center, quality improvement project composed of pre- and post-implementation groups. An IBW and AdjBW calculator were implemented in our electronic health record, as customized enhancements, along with specific weight ordering options. A literature search of pharmacokinetic and pharmacodynamic dosing recommendations based on IBW and AdjBW was conducted. For both groups, patients were included if they were 3-18 years old, had a body mass index greater than or equal to the 95th percentile, and if they received a specified medication.

RESULTS: A total of 618 patients were identified with 24 and 56 patients included for the pre- and post-implementation groups. There were no statistically significant differences in baseline characteristics of the comparator groups. The usage of correct body weight increased from 1.2% to 24.2% after implementation and education (P < 0.001). Cost savings was analyzed for immune globulin with the potential for a net savings of $9423 ± 3626.92.

CONCLUSION: Dosing medications for our pediatric patients with obesity improved with the implementation of calculated dosing weights in the electronic health record, provision of an evidence-based dosing chart, and education of providers.

PMID:36870938 | DOI:10.1016/j.japh.2023.02.012

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Short-term effect of orthodontic clear aligners on muscular activity and occlusal contacts: A cohort study

Am J Orthod Dentofacial Orthop. 2023 Mar 3:S0889-5406(23)00033-1. doi: 10.1016/j.ajodo.2022.10.025. Online ahead of print.

ABSTRACT

INTRODUCTION: The simultaneous presence of maxillary and mandibular clear aligners alters the vertical dimension and the quantity and quality of occlusal contacts. Few data in the literature explain how this occurs and the effects on neuromuscular coordination. This study aimed to evaluate occlusal contacts and muscular balance during treatment with clear aligners over a short follow-up time.

METHODS: Twenty-six female adult patients were enrolled in this study. The center of occlusal force (COF) was evaluated using a T-Scan II device, whereas muscular symmetry and balance were determined through surface electromyography using a standardized protocol that reduces anthropometric and electrode variations. Both evaluations were performed in centric occlusion and with aligners worn before treatment, after 3 months, and after 6 months.

RESULTS: A statistically significant variation in COF position was reported in the sagittal plane but not in the transverse plane. The shift in the COF position was followed by a change in muscular balance evaluated through surface electromyography.

CONCLUSIONS: Treatment with clear aligners resulted in an anterior shift of the COF when biting in centric occlusion and a posterior shift when the aligners were worn in healthy female patients after 6 months of observation. This change in occlusal contact was followed by an improvement in muscular function symmetry in the short term when aligners were worn, compared with the centric occlusion during treatment.

PMID:36870918 | DOI:10.1016/j.ajodo.2022.10.025

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Association between dietary patterns and biomarkers in connection with diabetes mellitus in adolescents: A systematic review

Nutr Metab Cardiovasc Dis. 2022 Dec 26:S0939-4753(22)00492-6. doi: 10.1016/j.numecd.2022.12.005. Online ahead of print.

ABSTRACT

AIMS: To perform a systematic review to investigate the association between adolescents’ a posteriori dietary patterns with diabetes-related biomarkers (fasting blood glucose, fasting insulinemia, glycated hemoglobin and homeostatic model assessment insulin resistance index (HOMA-IR)).

DATA SYNTHESIS: Review registered with PROSPERO under number CRD42020185369. Studies with adolescents aged 10-19 years that identified dietary patterns by a posteriori methods were included. The databases used included: PubMed, SCOPUS, Web of Science, Food Science and Technology Abstracts, CINAHL, SPORTDiscus, Lilacs/BVS, The Cochrane Central Register of Controlled Trials, ProQuest Dissertations&Theses Global and Capes Theses Bank and Brazilian Digital Library of Theses and Dissertations. Risk of bias was assessed via the Agency for Healthcare Research and Quality tool. Eight cross-sectional studies that evaluated 6438 adolescents (55.5% females) were included. For fasting blood glucose, the results were inconsistent and some studies found no association for the dietary patterns called traditional (57%), Western (42%) and healthy (28%). For the fasting insulinemia and HOMA-IR outcomes, the Western dietary pattern showed a positive association or higher means in 60% and 50% of the studies, respectively. No studies that evaluated glycated hemoglobin were found.

CONCLUSION: Fasting insulinemia and HOMA-IR outcomes were positively associated with the Western dietary patterns. The studies reviewed did not present consistent evidence of an association with western, healthy and traditional dietary patterns with fasting blood glucose, as the results were conflicting or did not show statistical significance.

PMID:36870914 | DOI:10.1016/j.numecd.2022.12.005

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I-CARE: Feasibility, Acceptability, and Appropriateness of a Digital Health Intervention for Youth Experiencing Mental Health Boarding

J Adolesc Health. 2023 Mar 2:S1054-139X(23)00062-9. doi: 10.1016/j.jadohealth.2023.01.015. Online ahead of print.

ABSTRACT

PURPOSE: Youth with suicidality requiring psychiatric hospitalization may first experience boarding at acute care hospitals. Given infrequent provision of therapy during this period, we developed a modular digital intervention (I-CARE; Improving Care, Accelerating Recovery and Education) to facilitate delivery of evidence-based psychosocial skills by non-mental health clinicians. This pilot study describes changes in emotional distress, severity of illness, and readiness for engagement following I-CARE participation, and evaluates the feasibility, acceptability, and appropriateness of I-CARE.

METHODS: A mixed-methods approach was used to evaluate I-CARE, offered to youth 12-17 years from 11/21 to 06/22. Changes in emotional distress, severity of illness, and engagement readiness were evaluated using paired t-tests. Semistructured interviews with youth, caregivers, and clinicians were conducted concurrently with collection of validated implementation outcome measures. Quantitative measure results were linked to interview transcripts, which were analyzed thematically.

RESULTS: Twenty-four adolescents participated in I-CARE; median length of stay was 8 days (IQR:5-12 days). Emotional distress decreased significantly by 6.3 points (63-point scale) following participation (p = .02). The increase in engagement readiness and decrease in youth-reported illness severity were not statistically significant. Among 40 youth, caregivers, and clinicians who participated in the mixed-methods evaluation, 39 (97.5%) rated I-CARE as feasible, 36 (90.0%) as acceptable, and 31 (77.5%) as appropriate. Adolescents’ prior knowledge of psychosocial skills and clinicians’ competing demands were reported barriers.

DISCUSSION: I-CARE was feasible to implement and youth reported reduced levels of distress following participation. I-CARE has the potential to teach evidence-based psychosocial skills during boarding, which may provide a head-start on recovery before psychiatric hospitalization.

PMID:36870901 | DOI:10.1016/j.jadohealth.2023.01.015

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Association of pneumococcal vaccination with cardiovascular diseases in older adults: The vaccine effectiveness, networking, and universal safety (VENUS) study

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

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Shock index is positively correlated with acute blood loss and negatively correlated with cardiac output in a canine hemorrhagic shock model

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

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Genetically Determined Levels of mTOR-Dependent Circulating Proteins and Risk of Multiple Sclerosis

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

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A genetic Study of the Ghanaian Population Using 15 Autosomal STR Loci

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

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3D Visualization System-Assisted Vitrectomy for Rhegmatogenous Retinal Detachment: Leave Out the Perfluorocarbon Liquid

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

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Population Pharmacokinetics and Exposure-Response Analysis for the Phase 3 COSMIC-311 Trial of Cabozantinib for Radioiodine-Refractory Differentiated Thyroid Cancer

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