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Nevin Manimala Statistics

External apical root resorption 6 months after initiation of orthodontic treatment: A randomized clinical trial comparing fixed appliances and orthodontic aligners

Korean J Orthod. 2021 Sep 25;51(5):329-336. doi: 10.4041/kjod.2021.51.5.329.

ABSTRACT

OBJECTIVE: To compare the magnitude of external apical root resorption (EARR) 6 months after starting orthodontic treatment using orthodontic aligners (OAs) and fixed appliances (FAs).

METHODS: This parallel randomized clinical trial included 40 patients randomized into two groups: OA group (n = 20, 160 incisors) and FA group (n = 20, 160 incisors). For evaluation of the tooth length, periapical radiographs and standardized linear measurements of the maxillary and mandibular incisors were acquired before (T0) and 6 months after treatment initiation (T1). EARR was calculated through the difference in length between the two time points (T1-T0). Statistical comparisons were performed by means of using t-tests, chi-squared test and covariance analysis (a = 5%).

RESULTS: Rounding of the root apex was observed in both groups; the resorption involved 2.88% of the root length, so 97.12% of the tooth length remained intact. Intragroup comparisons between the two time points revealed a significant difference, with (T1-T0) ranging from -0.52 to -0.88 mm in the FA group and from -0.52 to -0.85 mm in the OA group. In the intergroup comparisons, only tooth #21 presented a statistically significant difference (OA: -0.52 ± 0.57 mm, FA: -0.86 ± 0.60 mm); however, the overall differences between groups were not clinically relevant, ranging from 0.03 to 0.35 mm.

CONCLUSIONS: OA and FA treatment resulted in a similar degree of EARR in the maxillary and mandibular incisors at 6 months after treatment initiation. However, the amount of resorption was small and does not impair tooth longevity.

PMID:34556587 | DOI:10.4041/kjod.2021.51.5.329

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Effectiveness of low-level laser therapy and chewing gum in reducing orthodontic pain: A randomized controlled trial

Korean J Orthod. 2021 Sep 25;51(5):313-320. doi: 10.4041/kjod.2021.51.5.313.

ABSTRACT

OBJECTIVE: The purpose of this study was to evaluate the effects of chewing gum and low-level laser therapy in alleviating orthodontic pain induced by the initial archwire.

METHODS: Patients with 3-6 mm maxillary crowding who planned to receive non-extraction orthodontic treatment were recruited for the study. Sixty-three participants (33 females and 30 males) were randomly allocated into three groups: laser, chewing gum, and control. In the laser group, a gallium aluminum arsenide (GaAlAs) diode laser with a wavelength of 820 nm was used to apply a single dose immediately after orthodontic treatment began. In the chewing gum group, sugar-free gum was chewed three times for 20 minutes- immediately after starting treatment, and at the twenty-fourth and forty-eighth hours of treatment. Pain perception was measured using a visual analog scale at the second, sixth, and twenty-fourth hours, and on the second, third, and seventh days.

RESULTS: There were no statistically significant differences between the groups at any measured time point (p > 0.05). The highest pain scores were detected at the twenty-fourth hour of treatment in all groups.

CONCLUSIONS: Within the limitations of the study, we could not detect whether low-level laser therapy and chewing gum had any clinically significant effect on orthodontic pain. Different results may be obtained with a higher number of participants or using lasers with different wavelengths and specifications. Although the study had a sufficient number of participants according to statistical analysis, higher number of participants could have provided more definitive outcomes.

PMID:34556585 | DOI:10.4041/kjod.2021.51.5.313

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Nevin Manimala Statistics

Scene statistics and noise determine the relative arrangement of receptive field mosaics

Proc Natl Acad Sci U S A. 2021 Sep 28;118(39):e2105115118. doi: 10.1073/pnas.2105115118.

ABSTRACT

Many sensory systems utilize parallel ON and OFF pathways that signal stimulus increments and decrements, respectively. These pathways consist of ensembles or grids of ON and OFF detectors spanning sensory space. Yet, encoding by opponent pathways raises a question: How should grids of ON and OFF detectors be arranged to optimally encode natural stimuli? We investigated this question using a model of the retina guided by efficient coding theory. Specifically, we optimized spatial receptive fields and contrast response functions to encode natural images given noise and constrained firing rates. We find that the optimal arrangement of ON and OFF receptive fields exhibits a transition between aligned and antialigned grids. The preferred phase depends on detector noise and the statistical structure of the natural stimuli. These results reveal that noise and stimulus statistics produce qualitative shifts in neural coding strategies and provide theoretical predictions for the configuration of opponent pathways in the nervous system.

PMID:34556573 | DOI:10.1073/pnas.2105115118

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Nevin Manimala Statistics

Emergent probability fluxes in confined microbial navigation

Proc Natl Acad Sci U S A. 2021 Sep 28;118(39):e2024752118. doi: 10.1073/pnas.2024752118.

ABSTRACT

When the motion of a motile cell is observed closely, it appears erratic, and yet the combination of nonequilibrium forces and surfaces can produce striking examples of organization in microbial systems. While most of our current understanding is based on bulk systems or idealized geometries, it remains elusive how and at which length scale self-organization emerges in complex geometries. Here, using experiments and analytical and numerical calculations, we study the motion of motile cells under controlled microfluidic conditions and demonstrate that probability flux loops organize active motion, even at the level of a single cell exploring an isolated compartment of nontrivial geometry. By accounting for the interplay of activity and interfacial forces, we find that the boundary’s curvature determines the nonequilibrium probability fluxes of the motion. We theoretically predict a universal relation between fluxes and global geometric properties that is directly confirmed by experiments. Our findings open the possibility to decipher the most probable trajectories of motile cells and may enable the design of geometries guiding their time-averaged motion.

PMID:34556571 | DOI:10.1073/pnas.2024752118

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Nevin Manimala Statistics

Projecting the impact of triple CFTR modulator therapy on intravenous antibiotic requirements in cystic fibrosis using patient registry data combined with treatment effects from randomised trials

Thorax. 2021 Sep 23:thoraxjnl-2020-216265. doi: 10.1136/thoraxjnl-2020-216265. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a life-threatening genetic disease, affecting around 10 500 people in the UK. Precision medicines have been developed to treat specific CF-gene mutations. The newest, elexacaftor/tezacaftor/ivacaftor (ELEX/TEZ/IVA), has been found to be highly effective in randomised controlled trials (RCTs) and became available to a large proportion of UK CF patients in 2020. Understanding the potential health economic impacts of ELEX/TEZ/IVA is vital to planning service provision.

METHODS: We combined observational UK CF Registry data with RCT results to project the impact of ELEX/TEZ/IVA on total days of intravenous (IV) antibiotic treatment at a population level. Registry data from 2015 to 2017 were used to develop prediction models for IV days over a 1-year period using several predictors, and to estimate 1-year population total IV days based on standards of care pre-ELEX/TEZ/IVA. We considered two approaches to imposing the impact of ELEX/TEZ/IVA on projected outcomes using effect estimates from RCTs: approach 1 based on effect estimates on FEV1% and approach 2 based on effect estimates on exacerbation rate.

RESULTS: ELEX/TEZ/IVA is expected to result in significant reductions in population-level requirements for IV antibiotics of 16.1% (~17 800 days) using approach 1 and 43.6% (~39 500 days) using approach 2. The two approaches require different assumptions. Increased understanding of the mechanisms through which ELEX/TEZ/IVA acts on these outcomes would enable further refinements to our projections.

CONCLUSIONS: This work contributes to increased understanding of the changing healthcare needs of people with CF and illustrates how Registry data can be used in combination with RCT evidence to estimate population-level treatment impacts.

PMID:34556554 | DOI:10.1136/thoraxjnl-2020-216265

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Self-management intervention to reduce pulmonary exacerbations by supporting treatment adherence in adults with cystic fibrosis: a randomised controlled trial

Thorax. 2021 Sep 23:thoraxjnl-2021-217594. doi: 10.1136/thoraxjnl-2021-217594. Online ahead of print.

ABSTRACT

INTRODUCTION: Recurrent pulmonary exacerbations lead to progressive lung damage in cystic fibrosis (CF). Inhaled medications (mucoactive agents and antibiotics) help prevent exacerbations, but objectively measured adherence is low. We investigated whether a multi-component (complex) self-management intervention to support adherence would reduce exacerbation rates over 12 months.

METHODS: Between October 2017 and May 2018, adults with CF (aged ≥16 years; 19 UK centres) were randomised to the intervention (data-logging nebulisers, a digital platform and behavioural change sessions with trained clinical interventionists) or usual care (data-logging nebulisers). Outcomes included pulmonary exacerbations (primary outcome), objectively measured adherence, body mass index (BMI), lung function (FEV1) and Cystic Fibrosis Questionnaire-Revised (CFQ-R). Analyses were by intent to treat over 12 months.

RESULTS: Among intervention (n=304) and usual care (n=303) participants (51% female, median age 31 years), 88% completed 12-month follow-up. Mean exacerbation rate was 1.63/year with intervention and 1.77/year with usual care (adjusted ratio 0.96; 95% CI 0.83 to 1.12; p=0.64). Adjusted mean differences (95% CI) were in favour of the intervention versus usual care for objectively measured adherence (9.5% (8.6% to 10.4%)) and BMI (0.3 (0.1 to 0.6) kg/m2), with no difference for %FEV1 (1.4 (-0.2 to 3.0)). Seven CFQ-R subscales showed no between-group difference, but treatment burden reduced for the intervention (3.9 (1.2 to 6.7) points). No intervention-related serious adverse events occurred.

CONCLUSIONS: While pulmonary exacerbations and FEV1 did not show statistically significant differences, the intervention achieved higher objectively measured adherence versus usual care. The adherence difference might be inadequate to influence exacerbations, though higher BMI and lower perceived CF treatment burden were observed.

PMID:34556552 | DOI:10.1136/thoraxjnl-2021-217594

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Nevin Manimala Statistics

Bayesian interpretation of p values in clinical trials

BMJ Evid Based Med. 2021 Sep 23:bmjebm-2020-111603. doi: 10.1136/bmjebm-2020-111603. Online ahead of print.

ABSTRACT

Commonly accepted statistical advice dictates that large-sample size and highly powered clinical trials generate more reliable evidence than trials with smaller sample sizes. This advice is generally sound: treatment effect estimates from larger trials tend to be more accurate, as witnessed by tighter confidence intervals in addition to reduced publication biases. Consider then two clinical trials testing the same treatment which result in the same p values, the trials being identical apart from differences in sample size. Assuming statistical significance, one might at first suspect that the larger trial offers stronger evidence that the treatment in question is truly effective. Yet, often precisely the opposite will be true. Here, we illustrate and explain this somewhat counterintuitive result and suggest some ramifications regarding interpretation and analysis of clinical trial results.

PMID:34556541 | DOI:10.1136/bmjebm-2020-111603

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Nevin Manimala Statistics

Later is not necessarily better: limitations of survival analysis in studies of long-term drug treatment of psychiatric conditions

BMJ Evid Based Med. 2021 Sep 23:bmjebm-2021-111743. doi: 10.1136/bmjebm-2021-111743. Online ahead of print.

ABSTRACT

Survival analysis is routinely used to assess differences between groups in relapse prevention and treatment discontinuation studies involving people with long-term psychiatric conditions. The actual outcome in survival analysis is ‘time to event’, yet, in the mental health field, there has been little consideration of whether a temporary delay to relapse is clinically relevant in a condition that can last for decades. Moreover, in psychiatric drug trials, a pattern of elevated early relapses following randomisation to placebo or no treatment is common. This may be the result of the withdrawal of previous treatment leading to physiological withdrawal effects, which may be mistaken for relapse, or genuine relapse precipitated by the process of withdrawal. Such withdrawal effects typically produce converging survival curves eventually. They inevitably lead to differences in time to relapse, even when there is little or no difference in the cumulative risk of relapse at final follow-up. Therefore, statistical tests based on survival analyses can be misleading because they obscure these withdrawal effects. We illustrate these difficulties in a trial of antipsychotic reduction versus maintenance, and a trial of prophylactic esketamine in people with treatment-resistant depression. Both illustrate withdrawal-related effects that underline the importance of long-term follow-up and question the use of tests based on time to event. Further discussion of the most relevant outcome and appropriate approach to analysis, and research on patient and carer preferences is important to inform the design of future trials and interpretation of existing ones.

PMID:34556539 | DOI:10.1136/bmjebm-2021-111743

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Improving Timeliness of Insulin Administration by Using an Insulin Dose Calculator

Hosp Pediatr. 2021 Sep 23:hpeds.2020-003103. doi: 10.1542/hpeds.2020-003103. Online ahead of print.

ABSTRACT

OBJECTIVES: Insulin is a high-risk medication, and its dosing depends on the individualized clinical and nutritional needs of each patient. Our hospital implemented an insulin dose calculator (IDC) imbedded in the electronic medical record with the goal of decreasing average wait times in inpatient insulin ordering and administration. In this study, we evaluated whether implementation of an IDC decreased the average wait time for insulin administration for hospitalized pediatric patients.

METHODS: This pre- and postintervention cohort study measured wait times between point-of-care glucose testing and insulin administration. Patients admitted to the inpatient pediatric services who were treated with subcutaneous insulin during the study period were included. Additionally, nurses completed satisfaction surveys on the insulin administration process at our hospital pre- and post-IDC implementation. Descriptive statistics, χ2, Fisher’s exact test, and Student t tests were used to compare groups. Statistical process control charts were used to analyze data trends.

RESULTS: The preintervention cohort included 79 insulin doses for admitted pediatric patients. The postimplementation cohort included 128 insulin doses ordered via the IDC. Post-IDC implementation, the average wait time between point-of-care glucose testing and insulin administration decreased from 37 to 25 minutes (P < .05). The statistical process control chart revealed a 5-month run below the established mean after implementation of the IDC. Before IDC implementation, 15.6% of nurses expressed satisfaction in the insulin-dosing process compared with 69.2% postimplementation (P < .05).

CONCLUSIONS: Implementation of an IDC reduced the average wait time in ordering and administration of rapid-acting insulin and improved nursing satisfaction with the process.

PMID:34556536 | DOI:10.1542/hpeds.2020-003103

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Nevin Manimala Statistics

Relationship between 18F-flortaucipir uptake and histologic lesion types in 4-repeat tauopathies

J Nucl Med. 2021 Sep 23:jnumed.121.262685. doi: 10.2967/jnumed.121.262685. Online ahead of print.

ABSTRACT

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are 4-repeat tauopathies with overlapping, but also morphologically distinct tau immunoreactive lesions that vary in count by brain region. 18F-flortaucipir positron emission tomography uptake has been reported to correlate with overall tau burden, and in one CBD case to have greater affinity to threads than tangles. We determine whether 18F-flortaucipir uptake is associated with histologic lesion type in 4-repeat tauopathies. Methods: We performed semi-quantitative regional lesion counts on pretangles/neurofibrillary tangles, threads, oligodendroglial coiled bodies, tufted astrocytes, and astrocytic plaques in 29 autopsied 4-repeat tauopathies (PSP = 16; CBD=13). Regression models were used for statistical analyses. Results: 18F-flortaucipir uptake marginally correlated with threads in the precentral cortex (P = 0.04) and with astrocytic lesions in the red nucleus (P = 0.05). Conclusion: The findings do not support 18F-flortaucipir having differential affinity to any 4-repeat tau lesion type.

PMID:34556525 | DOI:10.2967/jnumed.121.262685