Nevin Manimala

Pharmacoeconomics. 2022 Jun 30. doi: 10.1007/s40273-022-01162-6. Online ahead of print.

ABSTRACT

OBJECTIVES: As obesity-associated events impact long-term survival, health economic (HE) modelling is commonly applied, but modelling approaches are diverse. This research aimed to compare the events simulation and the HE outcomes produced by different obesity modelling approaches.

METHODS: An external validation, using the Swedish obesity subjects (SOS) study, of three main structural event modelling approaches was performed: (1) continuous body mass index (BMI) approach; (2) risk equation approach; and (3) categorical BMI-related approach. Outcomes evaluated were mortality, cardiovascular events, and type 2 diabetes (T2D) for both the surgery and the control arms. Concordance between modelling results and the SOS study were investigated by different state-of-the-art measurements, and categorized by the grade of deviation observed (grades 1-4 expressing mild, moderate, severe, and very severe deviations). Furthermore, the costs per quality-adjusted life-year (QALY) gained of surgery versus controls were compared.

RESULTS: Overall and by study arm, the risk equation approach presented the lowest average grade of deviation (overall grade 2.50; control arm 2.25; surgery arm 2.75), followed by the continuous BMI approach (overall 3.25; control 3.50; surgery 3.00) and by the categorial BMI approach (overall 3.63; control 3.50; surgery 3.75). Considering different confidence interval limits, the costs per QALY gained were fairly comparable between all structural approaches (ranging from £2,055 to £6,206 simulating a lifetime horizon).

CONCLUSION: None of the structural approaches provided perfect external event validation, although the risk equation approach showed the lowest overall deviations. The economic outcomes resulting from the three approaches were fairly comparable.

PMID:35771486 | DOI:10.1007/s40273-022-01162-6

Head Neck Pathol. 2022 Jun 30. doi: 10.1007/s12105-022-01466-1. Online ahead of print.

ABSTRACT

BACKGROUND: Lymph node metastasis (LNM) is a well-known prognostic factor in Oral Squamous Cell Carcinoma(OSCC). A biological marker that predicts the Lymph Node Metastasis (LNM) in OSCC cases is the need of the hour. A Disintegrin And Metalloproteinases (ADAMs), a family of proteins that exhibit a metalloproteinase domain play a pivotal role in the pathogenesis of tumor growth and metastasis. This study aims to evaluate whether ADAM 10 can be used as a predictor of lymph node metastasis in OSCC using immunohistochemistry.

METHOD: A total of 90 samples that were categorized into 3 groups were included in the present study. Group I consisted of 30 samples of the normal oral mucosa, and Group II consisted of 30 samples of OSCC without lymph node metastasis. Group III consisted of 30 samples of OSCC with lymph node metastasis. Esophageal Squamous Cell Carcinoma was used as external positive control. Immunohistochemical expression of ADAM10 in their corresponding stained sections was assessed and staining intensity was calculated.

RESULTS: ADAM10 immunoreactivity was considered positive when located in cytoplasm or membrane or both. This method is similar to that used by Bamane et al. for OSCC cases. The mean value of the Staining Index score “AxB” was highest in Group III (7.90), followed by Group II (3.13) and least in Group I (0.27). These values were statistically significant.

CONCLUSION: Considering the findings of a higher percentage of ADAM10 positive cells, higher staining intensity, and higher staining index, the overexpression of ADAM10 can be used as an independent marker for OSCC patients to predict the lymph node metastasis.

PMID:35771404 | DOI:10.1007/s12105-022-01466-1

Patient. 2022 Jun 30. doi: 10.1007/s40271-022-00584-w. Online ahead of print.

ABSTRACT

INTRODUCTION: When determining if changes on patient-reported outcome (PRO) scores in clinical trials convey a meaningful treatment benefit, statistical significance tests alone may not communicate the patient perspective. Appraising within-patient changes on PRO scores against established thresholds can determine if improvements or deteriorations experienced by individuals are meaningful. To evaluate the appropriateness of thresholds for interpreting meaningful improvements and deterioration within individuals on the European Organisation for Research and Treatment of Cancer (EORTC) 30-item core instrument (QLQ-C30) and 13-item lung cancer module (QLQ-LC13), a series of psychometric methods were applied to data from a phase III randomized controlled clinical trial in non-small cell lung cancer.

METHODS: Anchor-based methods of empirical cumulative distribution functions and classification statistics were employed using change scores from Baseline to Week 7 using changes on the QLQ-C30 Global Health Status item as an anchor. Distribution-based methods of one-half standard deviation and standard error of measurement identified the minimum amount of change each domain score can reliably measure.

RESULTS: While the correlations between the domain scores and the anchor item were modest in size (i.e., r ≥ 0.30 for only 5 of 24 domains), consideration of multiple methods along with the magnitude of possible step changes on the score allowed for patterns to emerge. The triangulation process planned a priori resulted in different methods being the source for different domain scores. Absolute values of the proposed thresholds ranged from 11.11 to 33.33, and all resulted in the same classifications for all EORTC domains, except QLQ-C30 Fatigue, as would the 10-point threshold that is traditionally used.

CONCLUSION: This study confirms the appropriateness of the 10-point EORTC score threshold generally used by the field for interpreting within-patient changes, but the thresholds proposed from this study enhance interpretability by corresponding to only observable locations along the domain score scale.

PMID:35771392 | DOI:10.1007/s40271-022-00584-w

BioDrugs. 2022 Jun 30. doi: 10.1007/s40259-022-00542-w. Online ahead of print.

ABSTRACT

BACKGROUND: Previous observational studies utilizing administrative claims data have largely been unable to consider clinical factors that may be related to patterns of drug use among patients with rheumatoid arthritis (RA).

OBJECTIVE: To understand predictors of treatment changes following initiation of a tumor necrosis factor inhibitor (TNFi) using nation-wide electronic health record (EHR) data in the USA.

METHODS: The Optum Immunology Condition EHR data (01/01/2011-09/30/2019) was used to identify a population of adult patients with RA initiating a TNFi as the first line biologic disease-modifying anti-rheumatic drug (DMARD). The primary outcome was any treatment change during the 1-year post-index period defined as cycling to a different TNFi or switching to non-TNFi biologic or targeted synthetic DMARDs. Secondary outcomes were the individual components of TNFi cycling and switching, examined separately. To identify predictors of DMARD treatment changes, we used a least absolute shrinkage and selection operator (LASSO) regression model. Model c-statistics and odds ratios (ORs, 95% confidence intervals (CIs)) of predictors were reported.

RESULTS: We identified 24,871 patients with RA who initiated a TNFi. The mean age was 55.5 (± 13.7) years and 77.2% were female. Among the TNFi initiators, 22.2% experienced TNFi cycling or switching during the 1-year follow-up time. Predictors that are associated with higher likelihood of TNFi cycling or switching included female gender (OR: 1.26, 95% CI: 1.16-1.36) and glucocorticoid use (OR: 1.30, 95% CI: 1.21-1.40). In contrast, inflammatory bowel disease (OR: 0.62, 95% CI: 0.48-0.78), psoriasis (OR: 0.82, 95% CI: 0.70-0.95), recent use of methotrexate (OR: 0.89, 95% CI: 0.81-0.97), and vitamin D intake (OR: 0.92, 95% CI: 0.85-0.99) were negatively associated with TNFi cycling or switch.

CONCLUSIONS: Gender, glucocorticoid use, inflammatory bowel disease, psoriasis, and vitamin D intake were identified as significant predictors of TNFi cycling or switching for TNFi initiators in the RA population. Predicting treatment change remains challenging even with large detailed EHR data. This study aimed to identify key determinants of treatment changes among patients with rheumatoid arthritis (RA) initiating a tumor necrosis factor inhibitor (TNFi) as their first-line biologic disease-modifying antirheumatic drug (DMARD) in routine care settings using a US nation-wide longitudinal electronic health record (EHR). Among 24,871 patients with RA who initiated a TNFi, 22.2% experienced TNFi cycling or switching during the 1-year follow-up time. Female patients and those who used glucocorticoids were more likely to experience TNFi cycling or switching, whereas inflammatory bowel disease, psoriasis, recent methotrexate use, and vitamin D intake were negatively associated with the outcome. However, predicting treatment change remains challenging even with larger detailed EHR data potentially due to unmeasured factors such as prescriber’s preference or patient’s belief in the medication.

PMID:35771381 | DOI:10.1007/s40259-022-00542-w

Indian J Pediatr. 2022 Jun 30. doi: 10.1007/s12098-022-04195-z. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the effect of macronutrient and micronutrient supplementation on body mass index (BMI), hemoglobin (Hb), CD4 count, triglyceride levels, and morbidity among adolescents with human immunodeficiency virus (HIV) living in India.

METHODS: A prospective, randomized, double-blinded, placebo-controlled trial was conducted among 80 adolescents (10-19 y) with HIV on highly active antiretroviral therapy (HAART) for a minimum of 6 mo using simple randomization. Participants in the intervention arm received 400 kcal and 15 g protein as a powder daily and multivitamin tablets thrice weekly for 3 mo. Those in the placebo arm received a similar-appearing sachet containing 100 kcal and 2 g protein daily and a placebo tablet thrice weekly. Weight, height, BMI, Hb, CD4 count, triglycerides, and number of intercurrent illnesses were measured at 3 and 6 mo.

RESULTS: At 6 mo, the intervention group showed an increase in weight from 36.4 ± 10.9 kg to 39.7 ± 8.5 kg and a significant increase in BMI from 16.6 ± 2.3 kg/m² to 17.5 ± 2.3 kg/m². Increase in CD4 count in the placebo arm was more than that in the intervention arm, but the difference between the arms was not statistically significant. Intervention group showed a pronounced rise in Hb from 9.7 ± 2.3 g/dL to 11.4 ± 1.6 g/dL, significant reduction in triglyceride levels from 99.2 ± 92.7 mg/dL to 81.0 ± 12.8 mg/dL and reduction in intercurrent illnesses from 32.5% to none.

CONCLUSIONS: Nutritional supplementation of adolescents with HIV on HAART improves BMI, hemoglobin, and reduces triglyceride levels and intercurrent illnesses.

PMID:35771346 | DOI:10.1007/s12098-022-04195-z

Trop Anim Health Prod. 2022 Jun 30;54(4):222. doi: 10.1007/s11250-022-03215-6.

ABSTRACT

Short tandem repeats (STRs) are co-dominant, highly polymorphic marker loci, distributed throughout the genome and useful for identification and mapping of QTLs associated with variation in traits of economic significance. Allelic variants were identified in STRs located in close vicinity of cattle QTLs for milk production,, viz. BMS713, BM6404, BM4513, BM121, BM6105, TGLA245, BL1100, BMS1948, BMS711, BM1443, BM1706, BM6438, BM143, BM415, ETH131, ETH 2, and BM1329 in 109 water buffaloes of Murrah breed. All loci except TGLA245 exhibited polymorphism of varying degree. The observed number of alleles, effective number of alleles, PIC value, observed heterozygosity, and expected heterozygosity across all STR loci averaged 4.12 ± 0.22, 3.20 ± 0.22, 0.60 ± 0.04, 0.34 ± 0.05, and 0.66 ± 0.03, respectively. Goodness of fit (chi-square) and likelihood ratio (G square) test demonstrated that the population exhibited a deviation from HWE for all the loci. F_IS was positive and ranged from 0.22 to 1.00. Least square analysis of variance exhibited significant effects of BM4513, ETH131, BM713, and BM6105 on first lactational total lactation milk yield, 305-day milk yield, lactation length, and dry period respectively. None of the STRs could exhibit significant effect on peak yield.

PMID:35771345 | DOI:10.1007/s11250-022-03215-6

Gen Thorac Cardiovasc Surg. 2022 Jun 30. doi: 10.1007/s11748-022-01836-0. Online ahead of print.

ABSTRACT

OBJECTIVES: Persistent atrial fibrillation (AF) causes atrial remodeling, which causes myocardial fibrosis and micro-reentry. Fibrosis may reduce wave voltage and micro-reentry may enhance the dominant frequency (DF) of the F-wave. We investigated whether the DF predicts procedural success by the Maze procedure.

METHODS: In 138 consecutive patients who underwent mitral valve surgery and a modified Cox-Maze III procedure for persistent AF in Nagoya University in 2002-2018, 96 (70%) were successfully cardioverted (group S); 42 had persistent or relapsed AF after surgery (group F). Patient data were compared between the groups. Cut-off values were determined by an ROC analysis and predictors of procedural success were evaluated. The DF was obtained from the F-wave of V1 by a high-speed Fourier analysis using the CEPAS software program.

RESULTS: Group F showed a significantly larger LA diameter, better LVEF, lower F-wave voltage, higher DF, and longer duration of AF. The cut-off values were as follows: LA diameter, 56 mm; EF, 64.5%; F-wave voltage, 0.13 mV; DF, 7.3 Hz; and duration of AF, 44 months. Each factor showed statistical significance in a univariate analysis; DF lost significance in the multivariate analysis. The higher (DF ≥ 7.3 Hz) and lower voltage group (≤ 0.13 mV) showed the worst procedural success rate (36%), while the lower DF (< 7.3 Hz) and higher voltage group (> 0.13 mV) showed a good rate (86%).

CONCLUSIONS: The DF of the F-wave is a useful predictor of procedural success after the Maze procedure in addition to the voltage of F-wave.

PMID:35771344 | DOI:10.1007/s11748-022-01836-0

Odontology. 2022 Jun 30. doi: 10.1007/s10266-022-00724-6. Online ahead of print.

ABSTRACT

To determine the effect of fluoride varnish application combined with a simulated oral environment prior to bracket bonding on the shear bond strength (SBS) between brackets and tooth enamel. Sixty de-identified, extracted teeth were grouped to either receive or not receive fluoride varnish and then stored for 7 days at 37 °C in phosphate-buffered saline (PBS) solution or PBS combined with three 15-min cycles/day in a demineralizing solution to simulate pH variation following meals. Subsequently, brackets were bonded and after 24-h dark cure at 37 °C, debonded using shear forces in a simulated oral environment. The maximum shear force was used to calculate SBS, and the adhesive remnant index (ARI) was determined by image analysis of photos of the bracket mesh pad after debonding. A statistically higher SBS (10.16 MPa) was observed when fluoride varnish was applied prior to storage in PBS + demineralizing solution compared to SBS (6.38 MPa) following storage in the same solution without varnish application. Based on 37% effect size, this difference is also clinically relevant. In contrast, no significant differences in SBS were observed with varnish application combined with PBS with no demineralizing solution or between storage solution alone. Moreover, there was no significant difference in ARI due to varnish combined with either storage method or storage solution only. Results suggest varnish application prior to bracket bonding in combination with simulated oral environment that included acid exposure is beneficial in maintaining higher SBS between bracket and enamel. Despite higher SBS, adhesive remaining on enamel did not increase.

PMID:35771340 | DOI:10.1007/s10266-022-00724-6

Environ Sci Pollut Res Int. 2022 Jun 30. doi: 10.1007/s11356-022-21672-2. Online ahead of print.

ABSTRACT

Bisphenol S (BPS), an analog of bisphenol A (BPA), has been frequently detected in consumer products, food wrappers, plastics, and thermal papers. Since the liver is a hub of metabolic and detoxification pathways, thus intimately related to BPS presence in the environment and body. The current study was designed to investigate the effects of BPS administration in an animal model. Twenty-five male Wistar rats weighing 175 ± 25 g were randomly divided into control and treated groups. The control group was further divided into group I (no treatment) and group II (corn oil), whereas the treatment group was divided into D-I (40 mg/kg/day), D-II (200 mg/kg/day), and D-III (400 mg/kg/day) groups, getting oral doses of BPS for 15 days. Data analysis showed a significant statistical increase in hepatic enzymes ALT (33.4%), AST (25.4%), and ALP (529.6%) in the D-III group along with the development of hypercholesterolemia and hypertriglyceridemia in all BPS groups. Aberrant mRNA expressions of some key hepatic iron regulatory genes and inflammatory mediators were evident through qRT-PCR. Bisphenol S caused congestion of central vein from mild to moderate in hepatic sections. In conclusion, our investigation insinuates BPS intoxication potential and therefore may not be a safe alternative to BPA.

PMID:35771333 | DOI:10.1007/s11356-022-21672-2

Pediatr Obes. 2022 Jun 30:e12958. doi: 10.1111/ijpo.12958. Online ahead of print.

ABSTRACT

OBJECTIVES: Determine whether the negative impact of the COVID-19 pandemic on weight gain trajectories among children attending well-child visits in New York City persisted after the public health restrictions were reduced.

STUDY DESIGN: Multicenter retrospective chart review study of 7150 children aged 3-19 years seen for well-child care between 1 January 2018 and 4 December 2021 in the NYC Health and Hospitals system. Primary outcome was the difference in annual change of modified body mass index z-score (mBMIz) between the pre-pandemic and early- and late-pandemic periods. The mBMIz allows for tracking of a greater range of BMI values than the traditional BMI z-score. The secondary outcome was odds of overweight, obesity, or severe obesity. Multivariable analyses were conducted with each outcome as the dependent variable, and year, age category, sex, race/ethnicity, insurance status, NYC borough, and baseline weight category as independent variables.

RESULTS: The difference in annual mBMIz change for pre-pandemic to early-pandemic = 0.18 (95% confidence interval [CI]: 0.15, 0.20) and for pre-pandemic to late-pandemic = 0.04 (95% CI: 0.01, 0.06). There was a statistically significant interaction between period and baseline weight category. Those with severe obesity at baseline had the greatest mBMIz increase during both pandemic periods and those with underweight at baseline had the lowest mBMIz increase during both pandemic periods.

CONCLUSION: In NYC, the worsening mBMIz trajectories for children associated with COVID-19 restrictions did not reverse by 2021. Decisions about continuing restrictions, such as school closures, should carefully weigh the negative health impact of these policies.

PMID:35770679 | DOI:10.1111/ijpo.12958