Category: Statistics

Alzheimers Dement. 2022 Mar 2. doi: 10.1002/alz.12615. Online ahead of print.

ABSTRACT

This perspective is a companion to a recent editorial on the use of Bayesian analysis in clinical research. We aim to introduce and highlight the relevance and advantages that Bayesian inference offers to clinical trials using the data on the amyloid antibody aducanumab presented at a Food and Drug Administration hearing in November 2020 as an applied example. We apply Bayesian analysis of model plausibility and effect sizes based on simulated data of the two phase 3 trials of aducanumab in prodromal and mild dementia stages of Alzheimer’s disease (AD). Bayesian analysis can quantify evidence in favor of, or against, the presence of an effect (i.e., provide evidence of absence), as well as assess the strength of the effect. This is in contrast to the binary conclusions provided by frequentist tests.

PMID:35235700 | DOI:10.1002/alz.12615

Ecol Lett. 2022 Mar 2. doi: 10.1111/ele.13982. Online ahead of print.

ABSTRACT

Life-history strategies differ with respect to investment in current versus ‘future’ reproduction, but when is this future? Under the novel ‘temporality in reproductive investment hypothesis’, we postulate variation should exist in the time frame over which reproductive costs are paid. Slow-paced individuals should pay reproductive costs over short (e.g. inter-annual) time scales to prevent reproductive costs accumulating, whereas fast-paced individuals should allow costs to accumulate (i.e. senescence). Using Fourier transforms, we quantify adjustments in clutch size with age, across four populations of blue tits (Cyanistes caeruleus). Fast populations had more prevalent and stronger long-term changes in reproductive investment, whereas slower populations had more prevalent short-term adjustments. Inter-annual environmental variation partly accounted for short-, but not long-term changes in reproductive investment. Our study reveals individuals differ in when they pay the cost of reproduction and that failure to partition this variation across different temporal scales and environments could underestimate reproductive trade-offs.

PMID:35235709 | DOI:10.1111/ele.13982

J Clin Endocrinol Metab. 2022 Mar 2:dgac104. doi: 10.1210/clinem/dgac104. Online ahead of print.

ABSTRACT

CONTEXT: PLIN1 encodes Perilipin-1 which coats lipid droplets in adipocytes and is involved in droplet formation, triglyceride storage and lipolysis. Rare PLIN1 frameshift variants that extend the translated protein have been described to cause lipodystrophy.

OBJECTIVE: To test whether PLIN1 protein-truncating variants cause lipodystrophy in a large population-based cohort.

DESIGN: We identified individuals with PLIN1 PTVs in individuals with exome data in UK Biobank. We performed gene-burden testing for individuals with PLIN1 PTVs. We replicated the associations using data from the T2D Knowledge portal. We performed a phenome-wide association study using publicly available association statistics.

SETTING: A population-based cohort and a T2D case/control study.

PARTICIPANTS: 362,791 individuals in UK Biobank and 43,125 individuals in the T2D Knowledge portal.Main Outcome Measures: Twenty-two diseases and traits relevant to lipodystrophy.

RESULTS: The 735 individuals with PLIN1 protein-truncating variants had a favourable metabolic profile. These individuals had increased HDL cholesterol (0.12mmol/L, 95% CI: 0.09, 0.14, P=2×10 -18), reduced triglycerides (-0.22 mmol/L 95% CI: -0.29, -0.14, P=3×10 -11), reduced waist hip ratio (-0.02, 95% CI: -0.02, -0.01, P=9×10 -12) and reduced systolic blood pressure (-1.67 mmHg, -3.25, -0.09, P=0.05). These associations were consistent in the smaller T2D knowledge portal cohort. In UK Biobank, PLIN1 PTVs were associated with reduced risk of myocardial infarction (OR=0.59, 95% CI: 0.35, 0.93, P=0.02) and hypertension (OR=0.85, 95% CI: 0.73, 0.98, P=0.03), but not Type 2 diabetes (OR=0.99 95% CI: 0.63,1.51, P=0.99).

CONCLUSION: Our study suggests that PLIN1 haploinsufficiency causes a favourable metabolic profile and may protect against cardiovascular disease.

PMID:35235652 | DOI:10.1210/clinem/dgac104

Math Med Biol. 2022 Mar 2:dqac001. doi: 10.1093/imammb/dqac001. Online ahead of print.

ABSTRACT

Mycobacterium tuberculosis (TB) infection can involve all immune system components and can result in different disease outcomes. The antibiotic TB drugs require strict adherence to prevent both disease relapse and mutation of drug- and multidrug-resistant strains. To overcome the constraints of pathogen-directed therapy, host-directed therapy has attracted more attention in recent years as an adjunct therapy to enhance host immunity to fight against this intractable pathogen. The goal of this paper is to investigate in-host TB models to provide insights into therapy development. Focusing on therapy-targeting parameters, the parameter regions for different disease outcomes are identified from an established ODE model. Interestingly, the ODE model also demonstrates that the immune responses can both benefit and impede disease progression, depending on the number of bacteria engulfed and released by macrophages. We then develop two Itô SDE models, which consider the impact of demographic variations at the cellular level and environmental variations during therapies along with demographic variations. The SDE model with demographic variation suggests that stochastic fluctuations at the cellular level have significant influences on (1) the T-cell population in all parameter regions, (2) the bacterial population when parameters located in the region with multiple disease outcomes and (3) the uninfected macrophage population in the parameter region representing active disease. Further, considering environmental variations from therapies, the second SDE model suggests that disease progression can slow down if therapies (1) can have fast return rates and (2) can bring parameter values into the disease clearance regions.

PMID:35235658 | DOI:10.1093/imammb/dqac001

Cereb Cortex. 2022 Mar 2:bhac081. doi: 10.1093/cercor/bhac081. Online ahead of print.

ABSTRACT

Neuropsychological disturbances in the sense of limb ownership provide unique opportunities to study the neurocognitive basis of body ownership. Previous small sample studies that showed discrete cortical lesions cannot explain why multisensory, affective, and cognitive manipulations alter disownership symptoms. We tested the novel hypothesis that disturbances in the sense of limb ownership would be associated not only with discrete cortical lesions but also with disconnections of white-matter tracts supporting specific functional networks. We drew on an advanced lesion-analysis and Bayesian statistics approach in 49 right-hemisphere patients (23 with and 26 without limb disownership). Our results reveal that disturbances in the sense of ownership are associated with lesions in the supramarginal gyrus and disconnections of a fronto-insular-parietal network, involving the frontal-insular and frontal inferior longitudinal tracts, confirming previous disconnection hypotheses. Together with previous behavioral and neuroanatomical results, these findings lead us to propose that the sense of body ownership involves the convergence of bottom-up, multisensory integration, and top-down monitoring of sensory salience based on contextual demands.

PMID:35235644 | DOI:10.1093/cercor/bhac081

Int J Oral Maxillofac Implants. 2022 Jan-Feb;37(1):153-158. doi: 10.11607/jomi.9087.

ABSTRACT

PURPOSE: Strains transferred to the supporting simulated bone structure by implant-supported full-arch fixed dental prostheses (FAFDPs) were analyzed by digital image correlation (DIC).

MATERIALS AND METHODS: Polyurethane models were made using 3.75 × 11-mm implants and divided into the following groups with different implant numbers and design: EH5 (five implants/external hexagon), MT5 (five implants/internal taper), EH4 (four implants/external hexagon), and MT4 (four implants/internal taper). Both qualitative and quantitative (one-way analysis of variance [ANOVA] statistical comparison) analyses were performed by the DIC method after the application of a 250-N load in the central fossa of the mandibular first molar. Different regions of interest were selected in the polyurethane model for comparison between groups.

RESULTS: Compressive strains were found in the cervical region of the models, and tensile strains were found in the apical region of the models. Significant differences were found in the different analyzed regions of interest for the different number of supporting implants and implant designs (P < .05).

CONCLUSION: Groups with five implants showed more regions with less strain concentration compared to groups with four implants, but strain distribution was similar between groups. The different tested implant designs showed similar strain concentration and distribution to the supporting structures.

PMID:35235634 | DOI:10.11607/jomi.9087

Int J Oral Maxillofac Implants. 2022 Jan-Feb;37(1):159-170. doi: 10.11607/jomi.9107.

ABSTRACT

PURPOSE: The goal of this study was to assess the effect of a liquid platelet-rich fibrin (PRF)-coated implant surface (double acid-etched) on osseointegration, analyzing the stability and the possibility of shortening the rehabilitation period.

MATERIALS AND METHODS: Initially, the blood was centrifuged to obtain the liquid PRF (2,000 revolutions per minute [rpm], 10 minutes), dividing a sample to be analyzed by Luminex, and another was applied onto the implant surface. Fifteen patients (30 implants) were divided into two groups (control and liquid PRF). Following the recommendation provided by the manufacturer, within a controlled torque at a maximum of 34 N.mm, the implant was placed. All patients had 1 year of follow-up.

RESULTS: Eleven analytes were identified for the sample characterization (IP-10, eotaxin, RANTES, macrophage inflammatory protein 1-beta [MIP-1β], VEGF, PDGF-BB, bFGF, IFN-γ, interleukin [IL]-5, IL-10, and IL-15). Regarding clinical evaluation, for control and liquid PRF groups, respectively, (1) the mean torque for implant placement was 26.67 and 27.27 N.mm; (2) the initial stability (implant stability quotient [ISQ]) was 64.87 (SD ± 6.01) and 67.36 (SD ± 7.21); (3) the final ISQ was 67.67 (SD ± 6.13) and 70.14 (SD ± 6.40); (4) it took an average 73 and 71 days to reestablish the masticatory function; (5) the survival rate was 93.3% and 86.6%; and (6) the marginal bone loss was up to 1.0 mm after 1 year (control)-for two patients, it was between 1.0 and 2.0 mm, and for another two subjects, it was up to 1 mm (liquid PRF). No statistical significance was observed for all parameters analyzed (P > .05).

CONCLUSION: Within the limitations of this study, the results indicated that there was no statistical significance when liquid PRF was applied on the implant surface, for all parameters.

PMID:35235635 | DOI:10.11607/jomi.9107

Int J Oral Maxillofac Implants. 2022 Jan-Feb;37(1):114-119. doi: 10.11607/jomi.9116.

ABSTRACT

PURPOSE: The stability and density of the grafted bone in the maxillary sinus are essential for dental implant survival. This study aimed to compare bone density following mineralized allogeneic bone and deproteinized bovine bone and evaluate the volumetric changes as the secondary outcome.

MATERIALS AND METHODS: In this prospective cohort study, subjects were randomly allocated into two groups of mineralized bone and deproteinized bone to augment the maxillary sinus. Subjects underwent CBCT immediately after augmentation and 9 months later. The relative bone density was the primary outcome, and the volumetric change after 9 months was the secondary outcome of the study. The authors used an independent t test for assessing the bone density and volumetric change between the two groups.

RESULTS: Fifty patients were studied (n = 25 in each group). At 9 months after sinus elevation, the mean bone density was 237.20 ± 55.72 Hounsfield units (HU) in group 1 (mineralized bone) and 634.8 ± 166.11 HU in group 2 (deproteinized bone). There was a substantial difference statistically for the mean of HU between groups 1 and 2 (P < .001). The mean volume change was 0.25 ± 0.13 cm³ in group 1 (mineralized bone) and 0.06 ± 0.05 cm³ in group 2 (deproteinized bone). Assessment of the data showed a substantial difference in the mean volume change at 9 months after sinus elevation between groups 1 and 2 (P < .001).

CONCLUSION: Considering the results of this study, the deproteinized bone was associated with higher relative bone density than the mineralized bone 9 months after sinus elevation. The volume change of the deproteinized bone was less than the mineralized bone in the study time.

PMID:35235629 | DOI:10.11607/jomi.9116

Int J Oral Maxillofac Implants. 2022 Jan-Feb;37(1):135-142. doi: 10.11607/jomi.9064.

ABSTRACT

PURPOSE: Primary stability is the most important prognostic index for predicting osseointegration. It is generally thought that to achieve high primary stability, it is necessary to insert an implant with a high insertion torque (IT). To date, it has not yet been determined whether IT and implant stability quotient (ISQ) values are correlated. The primary aim of the study was to determine the correlation between IT and ISQ values at the time of implant insertion (T0); at 2 months, the time of healing (T1); and at 6 (T2) and 12 months (T3) after loading. The secondary aims were to determine the influence of different macroscopic implant designs and of a different insertion arch on this correlation; and to assess whether implants inserted with a high IT, that is, > 50 Ncm, had higher levels of implant stability at 2-, 6-, and 12-month follow-ups.

MATERIALS AND METHODS: STROBE guidelines were followed. Partially or monoedentulous patients were randomly assigned to receive taper thread on straight-body implants with microthreads (group A) or without microthreads (group B). At implant insertion, IT and ISQ values were recorded. At 2-, 6-, and 12-month follow-ups, the ISQ values were recorded. A spring-style torque wrench was used to assess the IT. The Osstell device was used to determine the ISQ values. Descriptive statistics, Pearson correlation, and t test were used. P was set at ≤ .005.

RESULTS: Two hundred fifty subjects were assessed; 142 were included. Two hundred sixty-eight implants were inserted (group A, 137 implants; group B, 131 implants). No subject dropped out, and no implant failed. A statistically significant correlation between ISQ and IT was determined at the time of implant insertion (T0; P = .000). The implant morphology and arch did not influence the correlation. An IT > 50 did not determine a higher secondary stability.

CONCLUSION: There is a strong correlation between IT and primary stability, but IT is not correlated with the secondary stability. A different implant macroscopic design and a different arch of insertion did not influence this correlation. Moreover, implants inserted with IT > 50 Ncm do not result in greater secondary stability.

PMID:35235632 | DOI:10.11607/jomi.9064

Int J Oral Maxillofac Implants. 2022 Jan-Feb;37(1):e29-e40. doi: 10.11607/jomi.9098.

ABSTRACT

PURPOSE: To investigate whether titanium mesh exposure is influenced by the type of titanium mesh, the type of bone graft material, or the associated employment of absorbable membranes.

MATERIALS AND METHODS: Electronic literature searches were conducted using four databases: PubMed, EMBASE, Web of Science, and Cochrane. Articles reporting titanium mesh exposure rates were included, and exposure rates in different subgroups were compared to determine whether a factor significantly influenced titanium mesh exposure. The review protocol was registered in the PROSPERO registry (CRD42020210187).

RESULTS: Twenty and 12 articles were included in the qualitative and quantitative synthesis, respectively. The weighted exposure rates of employing conventional titanium mesh or 3D-customized titanium mesh were 19.9% and 15.2% (P = .34). When employing autogenous bone combined with anorganic bovine bone material as bone graft material, the weighted exposure rate was 21.7%, whereas when using other bone graft material, the exposure rate was 23.5% (P = .74). The weighted exposure rate of using titanium mesh associated with absorbable membranes is 23.9%, while the weighted exposure rate of using titanium mesh without absorbable membranes is 20.2% (P = .36). Meta-regression showed that when analyzing one factor, the other two confounding factors did not influence the result (P = .28).

CONCLUSION: It seemed that the type of titanium mesh, the type of bone graft material, or the combined employment of absorbable membranes did not statistically significantly influence the titanium mesh exposure rate in guided bone regeneration.

PMID:35235627 | DOI:10.11607/jomi.9098