Nevin Manimala

Stat Med. 2022 Dec 24. doi: 10.1002/sim.9632. Online ahead of print.

ABSTRACT

Multivariate outcomes are common in pragmatic cluster randomized trials. While sample size calculation procedures for multivariate outcomes exist under parallel assignment, none have been developed for a stepped wedge design. In this article, we present computationally efficient power and sample size procedures for stepped wedge cluster randomized trials (SW-CRTs) with multivariate outcomes that differentiate the within-period and between-period intracluster correlation coefficients (ICCs). Under a multivariate linear mixed model, we derive the joint distribution of the intervention test statistics which can be used for determining power under different hypotheses and provide an example using the commonly utilized intersection-union test for co-primary outcomes. Simplifications under a common treatment effect and common ICCs across endpoints and an extension to closed-cohort designs are also provided. Finally, under the common ICC across endpoints assumption, we formally prove that the multivariate linear mixed model leads to a more efficient treatment effect estimator compared to the univariate linear mixed model, providing a rigorous justification on the use of the former with multivariate outcomes. We illustrate application of the proposed methods using data from an existing SW-CRT and present extensive simulations to validate the methods.

PMID:36565050 | DOI:10.1002/sim.9632

Int Endod J. 2022 Dec 24. doi: 10.1111/iej.13884. Online ahead of print.

ABSTRACT

AIM: To explore the effects of phase-transited lysozyme (PTL) coated dentine slices on cell adhesion, migration and odontogenic differentiation of human dental pulp cells (HDPCs).

METHODOLOGY: Cell growth and cell cycle analysis were conducted to verify the biocompatibility of PTL for HDPCs. Cell adhesion, cell morphology and proliferation were explored by DiI staining, Scanning electron microscopy (SEM), and MTT assay. Cell migration was investigated by Transwell assay. The effects of PTL on the odontogenesis and mineralization of HDPCs were assessed by Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB). The mineralization of HDPCs was evaluated by Alizarin red staining. HDPCs were isolated from extracted third molars. The level of statistically significant difference was accepted at P<0.05.

RESULTS: PTL showed no negative effect on cell cycle of HDPCs and compared with the blank group, HDPCs labelled with DiI staining showed significantly more adhered cells at 48h (P<0.05), extending cell processes and more finger-like or reticular pseudopodia on PTL-coated dentine slices. The results of MTT and Transwell assay showed that PTL promoted the proliferation (P<0.05) and migration (P<0.01) of HDPCs respectively. Compared with the blank group, the gene expression of dentine sialophosphoprotein (DSPP), osteopontin (OPN) and bone sialoprotein (BSP) in HDPCs cultured on PTL was significantly upregulated on day 3 and 7 (P<0.05), while the protein expression of DSPP showed no significant change on both day 7 and day 14. Alizarin red staining showed that PTL promoted more mineralization nodules formation of HDPCs (P<0.05).

CONCLUSIONS: PTL promoted the adhesion, proliferation and migration of HDPCs on dentine slices, and positively affected odontogenic differentiation and mineralization of HDPCs.

PMID:36565046 | DOI:10.1111/iej.13884

Mol Nutr Food Res. 2022 Dec 24:e2200615. doi: 10.1002/mnfr.202200615. Online ahead of print.

ABSTRACT

SCOPE: The primary aim of the present study was to study the effect of acute ketosis on parameters of appetite regulation in prediabetes. The secondary aim was to investigate whether the effect is influenced by eating behaviours.

METHODS AND RESULTS: This was a randomised controlled trial. After an overnight fast, 18 adults with prediabetes (defined in line with the American Diabetes Association criteria) were assigned to consume either a ketone monoester (D-β-hydroxybutyrate-(R)-1,3 butanediol) drink (energy content 123 kcal) or a placebo drink (containing virtually no calories) in cross-over fashion. Blood samples were collected every 30 mins, from baseline to 150 minutes. Paired t-test was used to compare the total area under the curve (AUC) for the changes in parameters of appetite regulation (acylated ghrelin, peptide YY (PYY), and hunger) following both drinks. Eating behaviours were determined with the use of the three-factor eating questionnaire. Significant elevation in blood β-hydroxybutyrate from 0.2 mmol/L to 3.5 mmol/L (p < 0.001) was achieved within 30 minutes. Acute ketosis did not result in statistically significant differences in the AUCs for ghrelin, PYY, and hunger. No statistically significant difference in the AUCs was also observed when participants were stratified by their eating behaviours.

CONCLUSION: Acute ketosis consistently did not affect both objective and subjective parameters of appetite regulation in prediabetes. No subset of people with prediabetes according to eating behaviours had a significant effect of acute ketosis on appetite regulation. This article is protected by copyright. All rights reserved.

PMID:36565045 | DOI:10.1002/mnfr.202200615

Int Endod J. 2022 Dec 24. doi: 10.1111/iej.13886. Online ahead of print.

ABSTRACT

INTRODUCTION: Regenerative endodontic procedures have been recently suggested as a treatment of mature permanent teeth with peri-apical periodontitis due to favorable outcomes in the resolution of signs and symptoms and the healing of apical periodontitis. Most of the randomized clinical trials were conducted for anterior teeth rather than mature molar teeth.

AIM: To evaluate the postoperative pain and the healing of necrotic mature permanent mandibular molar teeth with peri-apical periodontitis after conventional endodontic treatment versus after PRP revascularization.

METHODS: The protocol of this randomized clinical trial was registered at www.

CLINICALTRIALS: gov with identification number NCT03350841. Twenty-eight patients were included in the study after confirming the diagnosis clinically and radiographically. In the first visit, the mandibular molar teeth of both groups were mechanically prepared. The double antibiotic paste was injected into the canals and the cavity was sealed using glass ionomer. At the second visit, the patients were randomized either to the control group where the endodontic treatment was completed by lateral condensation technique or assigned to the intervention group where PRP revascularization was used. The degree of spontaneous pain was assessed using a numerical rating scale (NRS) pre-operatively, then post-operatively after 6, 12 hours and daily for 5 days. Patients were given a placebo to be administrated in case of pain. An analgesic (ibuprofen 400mg) was prescribed in case of persistent pain. Clinical and radiographic healing was assessed after 6 and 12 months. All demographic, baseline and outcome data were statistically analyzed.

RESULTS: Regarding the post-revascularization/ obturation pain, there was no statistically significant difference between the severity of pain in the two groups at all time intervals except after 12 hours, revascularization group showed a statistically significantly higher prevalence of no pain than the endodontic treatment group. Regarding the healing; the peri-apical lesions decrease in size significantly from the pre-operative lesion size in both groups without significant difference.

CONCLUSION: Both PRP revascularization and endodontic treatment resulted in a significant reduction in peri-apical lesion size related to mature necrotic mandibular molar teeth but further randomized clinical trials with standardized techniques, larger sample sizes and longer follow-up periods are recommended.

PMID:36565044 | DOI:10.1111/iej.13886

Int Endod J. 2022 Dec 23. doi: 10.1111/iej.13885. Online ahead of print.

ABSTRACT

AIM: To compare the odontogenic differentiation potential of a composite scaffold (CSHA) comprising of nanohydroxyapatite (nHAp) and carboxymethyl-chitosan (CMC) with Biodentine on human dental pulp stem cells (hDPSCs).

METHODOLOGY: A CSHA scaffold was prepared through an ultrasonication route by adding nHAp and CMC (1:5 w/w) in water medium followed by freeze-drying. Physico-chemical characterization was achieved using scanning electron microscopy with energy dispersive X-ray spectroscopy, X-ray diffraction and Fourier transform infrared spectroscopy. In-vitro bioactivity and pH assessments were done by soaking in simulated body fluid (SBF) for 28 days. The angiogenic and odontogenic differentiation abilities were assessed by expression of vascular endothelial growth factor (VEGF) and Dentine sialophosphoprotein (DSPP) markers on cultured hDPSCs by flow-cytometry and RT-qPCR at 7,14 and 21 days. Cell viability/proliferation and biomineralization abilities of CSHA were compared with Biodentine by MTT assay, alkaline phosphatase (ALP) activity, Alizarin Red Staining (ARS) and osteopontin (OPN) expression on hDPSCs following 7 and 14 days. Data were statistically analyzed with Kruskal Wallis and Friedman tests as well as one way ANOVA followed by appropriate post hoc tests (p < 0.05).

RESULTS: Characterization experiments revealed a porous microstructure of CSHA with pore diameter ranging between 60-200 μm and 1.67 Ca/P molar ratio along with the characteristic functional groups of both HAp and CMC. CSHA displayed bioactivity in SBF by forming apatite-like crystals and maintained a consistent pH value of 7.70 during 28 days’ in-vitro studies. CSHA significantly upregulated VEGF and DSPP levels on hDPSCs on day 21 compared with day 7 (p < 0.05). Further, CSHA supported cell viability/proliferation over 14 days like Biodentine with no statistical differences (p > 0.05). However, CSHA exhibited increased ALP and ARS activity with an intense OPN staining compared with Biodentine after 14 days (p < 0.05).

CONCLUSION: The results highlighted the odontogenic differentiation and biomineralization abilities of CSHA on hDPSCs with significant VEGF and DSPP gene upregulations. Further, CSHA exhibited enhanced mineralization activity than Biodentine, as evidenced by increased ALP, ARS and OPN activity on day 14. The nHAp-CMC scaffold has the potential to act as an effective pulp capping agent, however, this needs to be further validated through in-vivo animal studies.

PMID:36565040 | DOI:10.1111/iej.13885

Anat Sci Educ. 2022 Dec 23. doi: 10.1002/ase.2247. Online ahead of print.

ABSTRACT

Spatial abilities are cognitive resources used to mentally manipulate representations of objects to solve problems. Haptic abilities represent tactile interactions with real world objects transforming somatic information into mental representations. Both are proposed to be factors in anatomy education, yet spatial abilities and haptic abilities relationships remain unknown. The objective of the current study was to explore spatial abilities – haptic abilities interactions. A haptic abilities test (HAT) was developed based on the mental rotations test (MRT) with three-dimensional (3D) objects. The HAT was undertaken in three sensory conditions: (1) sighted, (2) sighted with haptics, and (3) haptics. Participants (n = 22; 13 females, 9 males) completed the MRT and were categorized into high spatial abilities (HSA) [n = 12, mean (±SD): 13.7 (±3.0)] and low spatial abilities (LSA) (n = 10, 5.6 (±2.0) based on score distributions about the overall mean. Each spatial abilities group’s HAT scores were compared across the three sensory conditions. Spearman’s correlation coefficients between MRT and HAT scores indicated a statistically significant correlation in sighted condition (r = 0.553, P = 0.015), but were not significant in the sighted with haptics (r = 0.0.078, P = 0.212) and haptics conditions (r = 0.043, P = 0.279). These data suggest haptic abilities appear unrelated to spatial abilities. With haptic exploration, LSA HAT scores were compensated; comparing HSA to LSA: sighted with haptics [12 (12-13)] vs [12 (11-13)], P = 0.254, and in haptics conditions [12 (11-13)] vs [12 (10-12)], P = 0.381). Migrations to online anatomy teaching, may unwittingly remove important sensory modalities from the learner. Understanding learner behaviors and performance decrements when haptic inputs are removed from the learning environment represents valuable insight informing future anatomy curriculum and resource development.

PMID:36565014 | DOI:10.1002/ase.2247

Diabetes Obes Metab. 2022 Dec 23. doi: 10.1111/dom.14959. Online ahead of print.

ABSTRACT

OBJECTIVE: Determine whether the twice daily (BID) regimen is superior to the once daily (QD) regimen for managing glycemic variability by comparing the effects of anagliptin 100 mg BID versus sitagliptin 100 mg QD.

RESEARCH DESIGN AND METHODS: A double-blinded, randomized, multicenter study was performed in 89 patients with type 2 diabetes treated with metformin alone (6.5% < HbA1c < 8.5%). Subjects were randomly assigned to anagliptin 100 mg BID or sitagliptin 100 mg QD in a 1:1 ratio for 12 weeks. Continuous glucose monitoring (CGM) was used to measure the mean amplitude of glycemic excursion (MAGE) and postprandial time in range (TIR) before and after DPP-4 inhibitor treatment to compare glycemic variability.

RESULTS: The decrease from baseline in MAGE at 12 weeks after DPP-4 inhibitor treatment was significantly greater in the anagliptin BID group than in the sitagliptin QD group (p<0.05); -30.4 ± 25.6 mg/dL (p<0.001) in the anagliptin group versus -9.5 ± 38.0 mg/dL (p=0.215) in the sitagliptin group. The TIR after dinner increased by 33.0 ± 22.0% (p<0.001) in the anagliptin group and by 14.6 ± 28.2% (p=0.014) in the sitagliptin group, with a statistically significant difference (p=0.009). No statistically significant differences were observed between the groups in the changes in HbA1c and fasting plasma glucose (FPG).

CONCLUSIONS: The anagliptin BID regimen for the treatment of type 2 diabetes was superior in blood glucose control after dinner to improve glycemic variability, as indicated by MAGE and TIR but equivalent to the QD regimen in terms of HbA1c and FPG. This article is protected by copyright. All rights reserved.

PMID:36564983 | DOI:10.1111/dom.14959

Addiction. 2022 Dec 23. doi: 10.1111/add.16116. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Individuals of lower socioeconomic status (SES) display a higher prevalence of smoking and have more difficulty quitting than higher SES groups. The current study investigates whether the within-person associations of key risk (e.g., stress) and protective (self-efficacy) factors with smoking lapse varies by facets of SES.

DESIGN AND SETTING: Observational study using ecological momentary assessment to collect data for a 28-day period following a smoking quit attempt. Multilevel mixed models (i.e., generalized linear mixed models) examined cross-level interactions between lapse risk and protective factors and indicators of SES on smoking lapse.

PARTICIPANTS: A diverse sample of 330 adult U.S. smokers who completed a larger study examining the effects of race/ethnicity and social/environmental influences on smoking cessation.

MEASUREMENTS: Risk factors: momentary urge, negative affect, stress; Protective factors: positive affect, motivation, abstinence self-efficacy; SES measures: baseline measures of income and financial strain; Primary outcome: self-reported lapse.

FINDINGS: Participants provided 43,297 post-quit observations. Mixed models suggested that income and financial strain moderated the effect of some risk factors on smoking lapse. The within-person association of negative (odds ratio [OR] = 0.967, 95% [0.945, 0.990], p<.01) and positive affect (OR = 1.023, 95% confidence interval [CI] [1.003, 1.044], p<.05), and abstinence self-efficacy (OR = 1.020, 95% CI [1.003, 1.038], p<.05) on lapse varied with financial strain. The within-person association of negative affect (OR = 1.005, 95% CI [1.002, 1.008], p<.01), motivation (OR = 0.995, 95% CI [0.991, 0.999], p<.05), and abstinence self-efficacy (OR = 0.996, 95% CI [0.993, 0.999], p<.01) on lapse varied by income. The positive association of negative affect with lapse was stronger among individuals with higher income and lower financial strain. The negative association between positive affect and abstinence self-efficacy with lapse was stronger among individuals with lower financial strain, and the negative association between motivation and abstinence self-efficacy with lapse was stronger among those with higher income. The data were insensitive to detect statistically significant moderating effects of income and financial strain on the association of urge or stress with lapse.

CONCLUSION: Some risk factors (e.g. momentary negative affect) exert a weaker influence on smoking lapse among lower compared to higher socioeconomic status groups.

PMID:36564898 | DOI:10.1111/add.16116

J Prim Care Community Health. 2022 Jan-Dec;13:21501319221141792. doi: 10.1177/21501319221141792.

ABSTRACT

BACKGROUND: Since the 1980s, primary care (PC) in the US has been recognized as the backbone of healthcare providing comprehensive care to complex patients, coordinating care among specialists, and rendering preventive services to contain costs and improve clinical outcomes. However, the effect of PC visits on total patient care cost has been difficult to quantify.

OBJECTIVE: To assess the effect of PC visits on total patient care cost.

METHODS: This is a retrospective study of over 5 million patients assigned to a PC provider in the Veterans Health Administration (VHA) in each of the 4 fiscal years (FY 2016-2019). The main outcome of interest is total annual patient care cost. We assessed the effect of primary care visits on total patient care cost first by descriptive statistics, and then by multivariate regressions adjusting for severity of illness and other confounders. We conducted in-depth sensitivity analyses to validate the findings.

RESULTS: On average, each additional in-person PC visit was associated with a total cost reduction of $721 (per patient per year). The first PC visit was associated with the largest savings, $3976 on average, and a steady diminishing return was observed. Further, the higher the patient risk (severity of illness), the larger the cost reduction: Among the top 10% of high-risk patients, the first PC in-person visit was associated with a reduction of $16 406 (19%).

CONCLUSIONS: These findings, substantiated by our exhaustive sensitivity analyses, suggest that expanding PC capacity can significantly reduce overall health care costs and improve patient care outcomes given the former is a strong proxy of the latter.

PMID:36564889 | DOI:10.1177/21501319221141792

Pediatr Allergy Immunol. 2022 Dec;33(12):e13896. doi: 10.1111/pai.13896.

ABSTRACT

BACKGROUND: Prevention guidelines have changed over the past decade and now recommend the earlier introduction of peanut and egg without delaying the introduction of other food allergens. This paper explored caregiver practices regarding the introduction of food allergens during infancy.

METHODS: A survey was administered (2021) to a US population-based sample of 3062 caregivers (children 7 months – 3.5 years). Demographics and feeding practices were collected. Weighted frequencies and proportions were calculated using the svyr package in R 4.1. Survey-weighted chi-square statistics and covariate-adjusted, survey-weighted logistic regression models were used for statistical inference.

RESULTS: Cow’s milk, wheat, and soy were the top three allergens introduced. Peanut and egg were introduced by 17.2% and 15.5% of caregivers before 7 months and 58.8% and 66.4% before 1 year, respectively. The age of peanut and egg introduction differed significantly by race/ethnicity (p < .001) and caregiver age (p < .001). Peanut and egg introduction before 7 months was significantly associated with the increased introduction of other allergenic foods before 1 year (p = <.001; peanut and p = < .001; egg). Caregivers who introduced peanut and egg before 7 months infant age fed an additional mean of 5.4 and 4.5 food allergens, respectively, before 1 year. Few caregivers (0.9%) reported feeding an “early food allergen introduction product” ≥ 3 times, which was significantly associated with parental food allergy (OR = 2.2) and previously seen an allergist (OR = 6.7).

CONCLUSION: More than half of the caregivers are not introducing peanut by age of one year and one-third are not introducing egg, though an observed shift toward earlier peanut and egg introduction was seen in the past 5 years. Peanut and egg introduction seem to co-occur and are associated with increased intake of other food allergens.

PMID:36564881 | DOI:10.1111/pai.13896