Category: Nevin Manimala

PLoS Comput Biol. 2021 Sep 7;17(9):e1009347. doi: 10.1371/journal.pcbi.1009347. Online ahead of print.

ABSTRACT

We construct a recursive Bayesian smoother, termed EpiFilter, for estimating the effective reproduction number, R, from the incidence of an infectious disease in real time and retrospectively. Our approach borrows from Kalman filtering theory, is quick and easy to compute, generalisable, deterministic and unlike many current methods, requires no change-point or window size assumptions. We model R as a flexible, hidden Markov state process and exactly solve forward-backward algorithms, to derive R estimates that incorporate all available incidence information. This unifies and extends two popular methods, EpiEstim, which considers past incidence, and the Wallinga-Teunis method, which looks forward in time. We find that this combination of maximising information and minimising assumptions significantly reduces the bias and variance of R estimates. Moreover, these properties make EpiFilter more statistically robust in periods of low incidence, where several existing methods can become destabilised. As a result, EpiFilter offers improved inference of time-varying transmission patterns that are advantageous for assessing the risk of upcoming waves of infection or the influence of interventions, in real time and at various spatial scales.

PMID:34492011 | DOI:10.1371/journal.pcbi.1009347

PLoS Comput Biol. 2021 Sep 7;17(9):e1008363. doi: 10.1371/journal.pcbi.1008363. Online ahead of print.

ABSTRACT

Although combination antiretroviral therapies seem to be effective at controlling HIV-1 infections regardless of the viral subtype, there is increasing evidence for subtype-specific drug resistance mutations. The order and rates at which resistance mutations accumulate in different subtypes also remain poorly understood. Most of this knowledge is derived from studies of subtype B genotypes, despite not being the most abundant subtype worldwide. Here, we present a methodology for the comparison of mutational networks in different HIV-1 subtypes, based on Hidden Conjunctive Bayesian Networks (H-CBN), a probabilistic model for inferring mutational networks from cross-sectional genotype data. We introduce a Monte Carlo sampling scheme for learning H-CBN models for a larger number of resistance mutations and develop a statistical test to assess differences in the inferred mutational networks between two groups. We apply this method to infer the temporal progression of mutations conferring resistance to the protease inhibitor lopinavir in a large cross-sectional cohort of HIV-1 subtype C genotypes from South Africa, as well as to a data set of subtype B genotypes obtained from the Stanford HIV Drug Resistance Database and the Swiss HIV Cohort Study. We find strong support for different initial mutational events in the protease, namely at residue 46 in subtype B and at residue 82 in subtype C. The inferred mutational networks for subtype B versus C are significantly different sharing only five constraints on the order of accumulating mutations with mutation at residue 54 as the parental event. The results also suggest that mutations can accumulate along various alternative paths within subtypes, as opposed to a unique total temporal ordering. Beyond HIV drug resistance, the statistical methodology is applicable more generally for the comparison of inferred mutational networks between any two groups.

PMID:34491984 | DOI:10.1371/journal.pcbi.1008363

J Drugs Dermatol. 2021 Sep 1;20(9):996-1003. doi: 10.36849/jdd.5818.

ABSTRACT

BACKGROUND: Skin aging is a multifactorial process induced by intrinsic factors such as metabolic processes and senescence as well as environmental factors, including smoking, air pollution, and solar radiation. UV-induced production of reactive oxygen species induces skin photoaging. Antioxidants, including vitamin C and E and green tea polyphenols represent a promising strategy for the aesthetic improvement of clinical features associated with aging.

OBJECTIVE: To assess the safety, tolerability, and efficacy of a novel vitamin C and E and green tea polyphenols (CE-GTP) combination serum on photoaged facial skin.

METHODS: 31 healthy females aged 43 to 65 years (mean age, 57.9) participated in this single-center, 12-week clinical trial. Subjects applied CE-GTP serum twice daily for the duration of the study. Clinical grading of efficacy parameters, safety and tolerability evaluations, ultrasound measurements, and self-assessment questionnaires were conducted at several study milestones.

RESULTS: Statistically significant improvements were observed in all clinically graded efficacy parameters. Highlights include reduction in fine lines around the eye area and facial wrinkles and enhanced skin smoothness and radiance. Ultrasound measurements showed a statistically significant increase in skin density at week 12 compared with baseline, indicating thickening of the epidermal and dermal tissue, associated with youthful, healthier skin. Subjects self-reported numerous improvements, including reduction of fine lines and wrinkles, improved skin tone and texture, diminished look of dark spots, and improved skin elasticity.

CONCLUSION: Novel CE-GTP serum is safe and effective, as shown by statistically significant improvements in multiple aesthetically important objective, subjective, and patient reported outcomes. J Drugs Dermatol. 2021;20(9):996-1003. doi:10.36849/JDD.5818.

PMID:34491027 | DOI:10.36849/jdd.5818

Chin J Dent Res. 2021 Sep 7;24(3):185-189. doi: 10.3290/j.cjdr.b1965019.

ABSTRACT

OBJECTIVE: To evaluate the clinical performance of direct composite restorations using the modified stamp technique (MST) in vivo.

METHODS: A total of 30 posterior teeth with undermining caries were randomly divided into two groups and then restored using the MST and conventional technique (CT), respectively. 3D images of the occlusal surface were obtained using an intraoral scanner (CEREC Omnicam, Dentsply Sirona, Charlotte, NC, USA) before and after treatment and the differences between these two 3D images were analysed with reverse engineering software. Statistical analysis was performed using a one-way analysis of variance (ANOVA) combined with a least significant difference (LSD) post hoc test using SPSS 20.0 software (IBM, Armonk, NY, USA).

RESULTS: The statistical analysis revealed that the average root mean square (RMS) values of best fit alignment errors were significantly different between groups (P < 0.01). The average RMS values in the MST and CT groups were 0.0738 ± 0.0279 and 0.1638 ± 0.0682, respectively. The LSD post hoc test revealed that the value was significant smaller in the MST group than in the CT group.

CONCLUSION: The MST was effective in direct composite restoration. The morphological consistency of the occlusal surface using the MST was better than with the CT.

PMID:34491013 | DOI:10.3290/j.cjdr.b1965019

Chin J Dent Res. 2021 Sep 7;24(3):177-183. doi: 10.3290/j.cjdr.b1964993.

ABSTRACT

OBJECTIVE: To assess the prevalence, location, diameter, course and anastomosis of the lateral lingual foramina (LLF) and canals (LLCs) in a northern Chinese population using CBCT.

METHODS: CBCT images of 506 patients (181 male and 325 female, mean age 21.03 ± 8.11 years) were collected. The prevalence, location, diameter, length, angle and anastomosis of the LLF and LLCs were assessed. The measurement variables were analysed by sex and age. Statistical analysis was performed using SPSS (v. 25, IBM, Armonk, NY, USA).

RESULTS: A total of 461 LLF were detected in 307 (60.7%) subjects, 175 (57.0%) of whom had unilateral LLF and 132 (43.0%) of whom had bilateral LLF, with each lateral having one to four LLF. The majority of LLF (375/461, 81.3%) were located below the premolars, particularly the first premolar. The mean diameter of the LLF was 0.58 ± 0.20 mm. The mean vertical distance from the LLF to the inferior border and the alveolar crest was 6.68 ± 1.43 mm and 23.65 ± 2.89 mm, respectively. In total, 197 LLCs were visible in the cancellous bone and evaluated. The mean length of LLCs was 6.26 ± 1.29 mm, and the mean angle of LLCs was 140.64° ± 17.29°. The overwhelming majority (93.4%) of LLCs communicated with the mandibular incisive canal and the rest connected with the mandibular canal.

CONCLUSION: The prevalence of LLCs was high in the northern Chinese population. The presence of LLCs is a significant predictor of communication with the mandibular incisive canal.

PMID:34491012 | DOI:10.3290/j.cjdr.b1964993

Chin J Dent Res. 2021 Sep 7;24(3):159-166. doi: 10.3290/j.cjdr.b1965031.

ABSTRACT

OBJECTIVE: To evaluate adhesives’ enamel bonding performance utilising the traditional microtensile bond strength test (µTBST) and a new double-sided microtensile bond strength test (DµTBST) to assess the suitability of the latter.

METHODS: A ‘tug-of-war’ direct encounter design was employed to compare the enamel bond strengths of two universal adhesives and their different application modes simultaneously under the same tensile load applied to double-sided bonded specimens. Clearfil Universal Bond (CU; Kuraray, Kurashiki, Japan) and Scotchbond Universal Adhesive (SB; 3M ESPE, St Paul, MN, USA) were applied in self-etch (S) and etch-and-rinse (E) mode on 110 human molar samples to perform two experiments. Experiment 1 compared the enamel bond strengths of the combinations of adhesive application modes utilising µTBST. The data were analysed using a Welch analysis of variance (ANOVA), followed by a Games-Howell test. Experiment 2 employed DµTBST to determine the suitability of the new double-sided bonded assembly and ascertain which of the adhesive application mode combinations was superior. The data were analysed using a Kaplan-Meier survival analysis, followed by pairwise comparisons with a Mantel-Cox log-rank test. The level of significance was set at P ˂ 0.05.

RESULTS: The µTBST results did not show significant differences for CUE vs CUS, SBE vs SBS, CUS vs SBS and CUS vs SBE (P ˃ 0.05); however, from DµTBST, the survival distributions for the interventions were statistically significantly different (χ2(3) = 145.130, P ˂ 0.0005), indicating the superiority of universal adhesive CU over SB and application mode E over S with certainty.

CONCLUSION: DµTBST was able to add more discerning outcomes to the µTBST results, indicating that the new technique could become a valuable adjunct to the conventional method.

PMID:34491010 | DOI:10.3290/j.cjdr.b1965031

Pediatr Blood Cancer. 2021 Sep 7:e29336. doi: 10.1002/pbc.29336. Online ahead of print.

ABSTRACT

BACKGROUND: Childrenwith acute lymphoblastic leukemia (ALL) suffer a litany of chemotherapy-induced side effects. Constipation secondary to vinca alkaloids, psychological stressors, and opioid use are common issues for children newly diagnosed with leukemia. This study investigated the morbidity associated with constipation including infections, mucositis, and healthcare utilization in hospitalized children with ALL receiving induction chemotherapy.

METHODS: We analyzed data from 48 children’s hospitals in the Pediatric Health Information System, extracting patients 1-21 years of age with ALL, hospitalized for induction from October 2015 through December 2019. Data were analyzed using nonparametric statistics, and comparisons of outcomes between those with and without constipation were presented as adjusted odds ratios (aOR).

RESULTS: We identified 2586 (56%) patients with constipation out of a total of 4622 unique ALL patients in induction. Compared to patients without constipation during induction, patients with constipation were significantly more likely to have mucositis (aOR = 2.30; p = 0.0010), perirectal issues (aOR = 3.21; p = 0.0092), or abdominal radiograph exposure (aOR = 2.40; p < 0.0001). The median length of induction hospitalization was significantly greater in those with constipation compared to those without constipation (10 days vs. 8 days; p < 0.0001).

CONCLUSIONS: Children with ALL suffering from constipation during induction therapy have increased length of stay, mucositis, imaging, and overall healthcare utilization compared to children without constipation. Further research should explore the causative relationship between constipation and infections. Increased attention should be given to constipation management in patients with ALL at the start of induction therapy, particularly in patients with complications or prolonged hospitalizations.

PMID:34490990 | DOI:10.1002/pbc.29336

Birth Defects Res. 2021 Sep 7. doi: 10.1002/bdr2.1947. Online ahead of print.

ABSTRACT

BACKGROUND: Our aim was to describe the neuroimaging and clinical evaluations of children with antenatal Zika-virus (ZIKV) exposure.

METHODS: The Colombian National Institute of Health performed serial clinical evaluations of children with probable antenatal ZIKV exposure (i.e., born to ZIKV symptomatic mothers or born with birth defects compatible with ZIKV infection, regardless of laboratory results) over 2 years that included head circumference (HC), eye examination, and neurodevelopmental assessments. Clinical neuroimaging studies (head computed tomography and/or brain magnetic resonance imaging) were analyzed for abnormalities, two-dimensional measurements were made of the right and left frontal and occipital cortical thickness. Two abnormal patterns were defined: Pattern 1 (sum of four areas of cortex <6 cm) and Pattern 2 (sum of four areas of cortex ≥6 cm and < 10 cm).

RESULTS: Thirty-one children had a neuroimaging study; in 24, cortical thickness was measured. The median age at the first visit was 8 (range: 6-9) months and 22 (range: 19-42) months at the last evaluation. In the 24 cases with cortical measurements, three were normal, 12 were in Pattern 1, and nine were in Pattern 2. Children within Pattern 1 had lower mean HC at birth and in follow-up (both p < .05) and a higher frequency of structural eye abnormalities (p < .01). A trend towards poorer neuromotor development was seen in Pattern 1, although not statistically significant (p = .06).

CONCLUSION: Brain imaging classification based on cortical measurements correlate with ophthalmologic abnormalities and HC. Cortical thickness may be a marker for clinical outcomes in children with congenital ZIKV infection.

PMID:34491004 | DOI:10.1002/bdr2.1947

Risk Anal. 2021 Sep 7. doi: 10.1111/risa.13810. Online ahead of print.

ABSTRACT

Regulatory agencies are required to evaluate the impacts of thousands of chemicals. Toxicological tests currently used in such evaluations are time-consuming and resource intensive; however, advances in toxicology and related fields are providing new testing methodologies that reduce the cost and time required for testing. The selection of a preferred methodology is challenging because the new methodologies vary in duration and cost, and the data they generate vary in the level of uncertainty. This article presents a framework for performing cost-effectiveness analyses (CEAs) of toxicity tests that account for cost, duration, and uncertainty. This is achieved by using an output metric-the cost per correct regulatory decision-that reflects the three elements. The framework is demonstrated in two example CEAs, one for a simple decision of risk acceptability and a second, more complex decision, involving the selection of regulatory actions. Each example CEA evaluates five hypothetical toxicity-testing methodologies which differ with respect to cost, time, and uncertainty. The results of the examples indicate that either a fivefold reduction in cost or duration can be a larger driver of the selection of an optimal toxicity-testing methodology than a fivefold reduction in uncertainty. Uncertainty becomes of similar importance to cost and duration when decisionmakers are required to make more complex decisions that require the determination of small differences in risk predictions. The framework presented in this article may provide a useful basis for the identification of cost-effective methods for toxicity testing of large numbers of chemicals.

PMID:34490933 | DOI:10.1111/risa.13810

Stat Med. 2021 Sep 7. doi: 10.1002/sim.9177. Online ahead of print.

ABSTRACT

Dynamic treatment regimes (DTRs) include a sequence of treatment decision rules, in which treatment is adapted over time in response to the changes in an individual’s disease progression and health care history. In medical practice, nested test-and-treat strategies are common to improve cost-effectiveness. For example, for patients at risk of prostate cancer, only patients who have high prostate-specific antigen (PSA) need a biopsy, which is costly and invasive, to confirm the diagnosis and help determine the treatment if needed. A decision about treatment happens after the biopsy, and is thus nested within the decision of whether to do the test. However, current existing statistical methods are not able to accommodate such a naturally embedded property of the treatment decision within the test decision. Therefore, we developed a new statistical learning method, step-adjusted tree-based reinforcement learning, to evaluate DTRs within such a nested multistage dynamic decision framework using observational data. At each step within each stage, we combined the robust semiparametric estimation via augmented inverse probability weighting with a tree-based reinforcement learning method to deal with the counterfactual optimization. The simulation studies demonstrated robust performance of the proposed methods under different scenarios. We further applied our method to evaluate the necessity of prostate biopsy and identify the optimal test-and-treat regimes for prostate cancer patients using data from the Johns Hopkins University prostate cancer active surveillance dataset.

PMID:34490942 | DOI:10.1002/sim.9177