Tag: nevin manimala

Diabetes Metab Res Rev. 2023 May 27:e3652. doi: 10.1002/dmrr.3652. Online ahead of print.

ABSTRACT

AIMS: Prevention of foot ulcers in persons with diabetes is important to help reduce the substantial burden on both individual and health resources. A comprehensive analysis of reported interventions is needed to better inform healthcare professionals about effective prevention. The aim of this systematic review and meta-analysis is to assess the effectiveness of interventions to prevent foot ulcers in persons with diabetes who are at risk thereof.

MATERIALS AND METHODS: We searched the available scientific literature in PubMed, EMBASE, CINAHL, Cochrane databases and trial registries for original research studies on preventative interventions. Both controlled and non-controlled studies were eligible for selection. Two independent reviewers assessed risk of bias of controlled studies and extracted data. A meta-analysis (using Mantel-Haenszel’s statistical method and random effect models) was done when >1 RCT was available that met our criteria. Evidence statements, including the certainty of evidence, were formulated according to GRADE.

RESULTS: From the 19,349 records screened, 40 controlled studies (of which 33 were Randomised Controlled Trials [RCTs]) and 103 non-controlled studies were included. We found moderate certainty evidence that temperature monitoring (5 RCTs; risk ratio [RR]: 0.51; 95% CI: 0.31-0.84) and pressure-optimised therapeutic footwear or insoles (2 RCTs; RR: 0.62; 95% CI: 0.26-1.47) likely reduce the risk of plantar foot ulcer recurrence in people with diabetes at high risk. Further, we found low certainty evidence that structured education (5 RCTs; RR: 0.66; 95% CI: 0.37-1.19), therapeutic footwear (3 RCTs; RR: 0.53; 95% CI: 0.24-1.17), flexor tenotomy (1 RCT, 7 non-controlled studies, no meta-analysis), and integrated care (3 RCTs; RR: 0.78; 95% CI: 0.58-1.06) may reduce the risk of foot ulceration in people with diabetes at risk for foot ulceration.

CONCLUSIONS: Various interventions for persons with diabetes at risk for foot ulceration with evidence of effectiveness are available, including temperature monitoring (pressure-optimised) therapeutic footwear, structured education, flexor tenotomy, and integrated foot care. With hardly any new intervention studies published in recent years, more effort to produce high-quality RCTs is urgently needed to further improve the evidence base. This is especially relevant for educational and psychological interventions, for integrated care approaches for persons at high risk of ulceration, and for interventions specifically targeting persons at low-to-moderate risk of ulceration.

PMID:37243880 | DOI:10.1002/dmrr.3652

J Pharmacokinet Pharmacodyn. 2023 May 27. doi: 10.1007/s10928-023-09864-w. Online ahead of print.

ABSTRACT

Population pharmacokinetics (popPK) of bempedoic acid and the popPK/pharmacodynamic (popPK/PD) relationship between bempedoic acid concentrations and serum low-density lipoprotein cholesterol (LDL-C) from baseline were characterized. A two-compartment disposition model with a transit absorption compartment and linear elimination best described bempedoic acid oral pharmacokinetics (PK). Multiple covariates, including renal function, sex, and weight, had statistically significant effects on the predicted steady-state area under the curve. Mild (estimated glomerular filtration rate (eGFR) 60 to < 90 mL/min vs. ≥ 90 mL/min) and moderate (eGFR 30 to < 60 mL/min vs. ≥ 90 mL/min) renal impairment, female sex, low (< 70 kg vs. 70-100 kg) and high (> 100 kg vs. 70-100 kg) body weight were predicted to have a 1.36-fold (90% confidence interval (CI) 1.32, 1.41), 1.85-fold (90% CI 1.74, 2.00), 1.39-fold (90% CI 1.34, 1.47), 1.35-fold (90% CI 1.30, 1.41), and 0.75-fold (90% CI 0.72, 0.79) exposure difference relative to their reference populations, respectively. An indirect response model described changes in serum LDL-C with a model-predicted 35% maximal reduction and bempedoic acid IC₅₀ of 3.17 µg/mL. A 28% reduction from LDL-C baseline was predicted for a steady-state average concentration of 12.5 µg/mL after bempedoic acid (180 mg/day) dosing, accounting for approximately 80% of the predicted maximal LDL-C reduction. Concurrent statin therapy, regardless of intensity, reduced the maximal effect of bempedoic acid but resulted in similar steady-state LDL-C levels. While multiple covariates had statistically significant effects on PK and LDL-C lowering, none were predicted to warrant bempedoic acid dose adjustment.

PMID:37243877 | DOI:10.1007/s10928-023-09864-w

EJNMMI Phys. 2023 May 27;10(1):33. doi: 10.1186/s40658-023-00554-7.

ABSTRACT

BACKGROUND: Total-body PET scanners with axial field of views (FOVs) longer than 1 m enable new applications to study multiple organs (e.g., the brain-gut-axis) simultaneously. As the spatial resolution and the associated partial volume effect (PVE) can vary significantly along the FOV, detailed knowledge of the contrast recovery coefficients (CRCs) is a prerequisite for image analysis and interpretation of quantitative results. The aim of this study was to determine the CRCs, as well as voxel noise, for multiple isotopes throughout the 1.06 m axial FOV of the Biograph Vision Quadra PET/CT system (Siemens Healthineers).

MATERIALS AND METHODS: Cylindrical phantoms equipped with three different sphere sizes (inner diameters 7.86 mm, 28 and 37 mm) were utilized for the PVE evaluation. The 7.86 mm sphere was filled with F-18 (8:1 and 4:1), Ga-68 (8:1) and Zr-89 (8:1). The 28 mm and 37 mm spheres were filled with F-18 (8:1). Background concentration in the respective phantoms was of ~ 3 kBq/ml. The phantoms were measured at multiple positions in the FOV (axial: 0, 10, 20, 30, 40 and 50 cm, transaxial: 0, 10, 20 cm). The data were reconstructed with the standard clinical protocol, including PSF correction and TOF information with up to 10 iterations for maximum ring differences (MRDs) of 85 and 322; CRCs, as well as voxel noise levels, were determined for each position.

RESULTS: F-18 CRCs (SBR 8:1 and 4:1) of the 7.86 mm sphere decreased up to 18% from the center FOV (cFOV) toward the transaxial edge and increased up to 17% toward the axial edge. Noise levels were below 15% for the default clinical reconstruction parameters. The larger spheres exhibited a similar pattern. Zr-89 revealed ~ 10% lower CRCs than F-18 but larger noise (9.1% (F-18), 19.1% (Zr-89); iteration 4, cFOV) for the default reconstruction. Zr-89 noise levels in the cFOV significantly decreased (~ 28%) when reconstructing the data with MRD322 compared with MRD85 along with a slight decrease in CRC values. Ga-68 exhibited the lowest CRCs for the three isotopes and noise characteristics comparable to those of F-18.

CONCLUSIONS: Distinct differences in the PVE within the FOV were detected for clinically relevant isotopes F-18, Ga-68 and Zr-89, as well as for different sphere sizes. Depending on the positions inside the FOV, the sphere-to-background ratios, count statistics and isotope used, this can result in an up to 50% difference between CRCs. Hence, these changes in PVE can significantly affect the quantitative analysis of patient data. MRD322 resulted in slightly lower CRC values, especially in the center FOV, whereas the voxel noise significantly decreased compared with MRD85.

PMID:37243869 | DOI:10.1186/s40658-023-00554-7

Prev Sci. 2023 May 27. doi: 10.1007/s11121-023-01513-5. Online ahead of print.

ABSTRACT

Evidence-based health interventions are frequently translated into real-world settings where practical needs drive changes to intervention protocols. Due to logistical and resource constraints, these naturally arising adaptations are rarely assessed for comparative effectiveness using a randomized trial. Nevertheless, when observational data are available, it is still possible to identify beneficial adaptations using statistical methods that adjust for differences among intervention groups. As implementation continues and more data are collected and assessed, we also require analysis methods that ensure low statistical error rates as multiple comparisons are made over time. This paper describes how to create a statistical analysis plan for evaluating adaptations to an intervention during ongoing implementation. This can be done by combining methods commonly used in platform clinical trials with methods used for real-world data. We also demonstrate how to use simulations based on previous data to decide the frequency with which to conduct statistical analyses. The illustration uses data from large-scale implementation of a school-based resilience and skill-building preventive intervention to which several adaptations were made. The proposed statistical analysis plan for evaluating the school-based intervention has potential to improve population-level outcomes as implementation scales up further and additional adaptations are anticipated.

PMID:37243867 | DOI:10.1007/s11121-023-01513-5

Ann Neurol. 2023 May 27. doi: 10.1002/ana.26712. Online ahead of print.

ABSTRACT

OBJECTIVE: The Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem-level relations to ataxia severity and patient-focused outcomes) across a large number of ataxias, and provide first natural history data for several of them.

METHODS: Subitem-level correlation- and distribution-based analysis of 1637 SARA assessments in 884 patients with autosomal-recessive/early-onset ataxia (370 with 2-8 longitudinal assessments), complemented by linear mixed-effects modeling to estimate progression and sample sizes.

RESULTS: While SARA subitem responsiveness varied between ataxia severities, gait/stance showed a robust granular linear scaling across the broadest range (SARA<25). Responsiveness was diminished by incomplete sub-scale use at intermediate or upper levels, non-transitions (“static periods”), and fluctuating decreases/increases. All subitems -except nose-finger- showed moderate-to-strong correlations to activities of daily living, indicating that metric properties -not content validity- limit SARA responsiveness. SARA captured mild-to-moderate progression in many genotypes, e.g., SYNE1-ataxia: 0.55 points/year, AOA2: 1.14, POLG-ataxia: 1.56; but no change in others (ARSACS, COQ8A-ataxia). While sensitivity to change was optimal in mild ataxia (SARA≤10), it substantially deteriorated in advanced ataxia (SARA>25; 2.7-fold sample size). Use of a novel rank-optimized SARA without subitems finger-chase and nose-finger reduces sample sizes by 20-25%.

INTERPRETATION: This study comprehensively characterizes COA properties and annualized changes of the SARA across and within a large number of ataxias. It suggests specific approaches for optimizing its responsiveness that might facilitate regulatory qualification and trial design. This article is protected by copyright. All rights reserved.

PMID:37243847 | DOI:10.1002/ana.26712

Mikrochim Acta. 2023 May 27;190(6):241. doi: 10.1007/s00604-023-05819-7.

ABSTRACT

The potential reach of point-of-care (POC) diagnostics into daily routines for exposure to reactive oxygen species (ROS) and Cu in aerosolized particulate matter (PM) demands that microfluidic paper-based analytical devices (μPADs) take into consideration the simple detection of these toxic PM components. Here, we propose μPADs with a dual-detection system for simultaneous ROS and Cu(II) detection. For colorimetric ROS detection, the glutathione (GSH) assay with a folding design to delay the reaction yielded complete ROS and GSH oxidation, and improved homogeneity of color development relative to using the lateral flow pattern. For electrochemical Cu(II) determination, 1,10-phenanthroline/Nafion modified graphene screen-printed electrodes showed ability to detect Cu(II) down to pg level being low enough to be applied to PM analysis. No intra- and inter-interference affecting both systems were found. The proposed μPADs obtained LODs for 1,4-naphthoquinone (1,4-NQ), used as the ROS representative, and Cu(II) of 8.3 ng and 3.6 pg, respectively and linear working ranges of 20 to 500 ng for ROS and 1 × 10^-2 to 2 × 10² ng for Cu(II). Recovery of the method was between 81.4 and 108.3% for ROS and 80.5-105.3% for Cu(II). Finally, the sensors were utilized for simultaneous ROS and Cu(II) determination in PM samples and the results statistically agreed with those using the conventional methods at 95% confidence.

PMID:37243836 | DOI:10.1007/s00604-023-05819-7

Acta Neurochir (Wien). 2023 May 27. doi: 10.1007/s00701-023-05623-5. Online ahead of print.

ABSTRACT

BACKGROUND: Surgical mortality indicators should be risk-adjusted when evaluating the performance of organisations. This study evaluated the performance of risk-adjustment models that used English hospital administrative data for 30-day mortality after neurosurgery.

METHODS: This retrospective cohort study used Hospital Episode Statistics (HES) data from 1 April 2013 to 31 March 2018. Organisational-level 30-day mortality was calculated for selected subspecialties (neuro-oncology, neurovascular and trauma neurosurgery) and the overall cohort. Risk adjustment models were developed using multivariable logistic regression and incorporated various patient variables: age, sex, admission method, social deprivation, comorbidity and frailty indices. Performance was assessed in terms of discrimination and calibration.

RESULTS: The cohort included 49,044 patients. Overall, 30-day mortality rate was 4.9%, with unadjusted organisational rates ranging from 3.2 to 9.3%. The variables in the best performing models varied for the subspecialties; for trauma neurosurgery, a model that included deprivation and frailty had the best calibration, while for neuro-oncology a model with these variables plus comorbidity performed best. For neurovascular surgery, a simple model of age, sex and admission method performed best. Levels of discrimination varied for the subspecialties (range: 0.583 for trauma and 0.740 for neurovascular). The models were generally well calibrated. Application of the models to the organisation figures produced an average (median) absolute change in mortality of 0.33% (interquartile range (IQR) 0.15-0.72) for the overall cohort model. Median changes for the subspecialty models were 0.29% (neuro-oncology, IQR 0.15-0.42), 0.40% (neurovascular, IQR 0.24-0.78) and 0.49% (trauma neurosurgery, IQR 0.23-1.68).

CONCLUSIONS: Reasonable risk-adjustment models for 30-day mortality after neurosurgery procedures were possible using variables from HES, although the models for trauma neurosurgery performed less well. Including a measure of frailty often improved model performance.

PMID:37243824 | DOI:10.1007/s00701-023-05623-5

Clin Oral Investig. 2023 May 27. doi: 10.1007/s00784-023-05085-0. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to evaluate the effectiveness of Teethmate desensitizer, a dentin bonding agent (DBA), Nd:YAG laser, and Er:YAG laser, which provides dentin tubule occlusion in the pulp chamber with different mechanisms, in preventing tooth discoloration due to regenerative endodontic treatment.

MATERIALS AND METHODS: One hundred five extracted maxillary human incisors with single roots and single canals were included in the study. The apical third of each tooth was resected below the enamel-cementum junction (CEJ) to obtain a standard root length as 10 ± 1 mm. Root canal preparation was performed using the ProTaper Next files up to X5. Root canals were prepared with Gates Glidden (# 2-4) burs to simulate the immature root apex and an apical diameter of 1.1 ± 0.1 mm was obtained. The teeth were randomly divided into 7 groups (n = 15): DBA, Teethmate, Nd:YAG, Er:YAG, Biodentine, Blood, and Negative Control. Relevant dentin tubule occlusion methods were applied to DBA, Teethmate, Nd:YAG, and Er:YAG groups. Following dentin tubule occlusion procedures, Biodentine was placed on the blood clot after filling the root canals with blood up to 4 mm below the CEJ. No dentin tubule occlusion procedure was applied for Blood and Biodentine groups. Color measurement was performed with the spectrophotometer Vita Easyshade Advance before treatment, immediately after treatment, and at days 7, 30, and 90. Data were converted to L*a*b color values of Commission International de I’Eclairage (CIE L*a*b) and ΔE values were calculated. Two-way ANOVA and post hoc Tukey test (p = 0.05) were performed for statistical analysis.

RESULTS: A clinically detectable color change was observed in all groups except for the negative control (ΔE ≥ 3,3). It was observed that Biodentine used alone has a potential for discoloration. It was determined that as the contact time with blood increased, tooth discoloration increased. However, no significant difference was found between dentin tubule occlusion methods in preventing color change (p > 0.05).

CONCLUSIONS: It was determined that no dentin tubule occlusion method could 100% prevent discoloration caused by RET.

CLINICAL RELEVANCE: DBA and Teethmate, which do not have a significant difference in terms of preventing color change, are considered to be suitable for dentin tubule occlusion due to their ease of application and low cost compared to Nd:YAG laser and Er:YAG laser.

PMID:37243821 | DOI:10.1007/s00784-023-05085-0

Clin Oral Investig. 2023 May 27. doi: 10.1007/s00784-023-05067-2. Online ahead of print.

ABSTRACT

OBJECTIVES: This study proposed a conceptual framework for reporting Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) Axis I conditions and investigated the prevalence of TMD subtypes/categories in patients from Confucian heritage cultures. Variances in gender, age, and TMD chronicity between Chinese (CN) and Korean (KR) patients were also explored.

MATERIALS AND METHODS: Subjects were recruited from consecutive patients seeking care at two University-based centers in Beijing and Seoul. Eligible patients completed a demographic survey as well as the DC/TMD Symptom Questionnaire and were clinically examined according to the DC/TMD methodology. Axis I diagnoses were subsequently rendered with the DC/TMD algorithms and documented using the stratified reporting framework. Statistical evaluations were performed with chi-square, Mann-Whitney U tests, and logistic regression analysis (α = 0.05).

RESULTS: Data of 2008 TMD patients (mean age 34.8 ± 16.2 years) were appraised. Substantial differences in female-to-male ratio (CN > KR), age (KR > CN), and TMD duration (KR > CN) were observed. Ranked frequencies of the most common Axis I diagnoses were: CN – disc displacements (69.7%) > arthralgia (39.9%) > degenerative joint disease (36.7%); KR – disc displacements (81.0%) > myalgia (60.2%) > arthralgia (56.1%). Concerning TMD categories, notable differences in the prevalence of intra-articular (CN 55.1% > KR 15.4%) and combined (KR 71.8% > CN 33.4%) TMDs were discerned.

CONCLUSIONS: Though culturally similar, the two countries require disparate TMD care planning/prioritization. While TMJ disorders in children/adolescents and young adults should be emphasized in China, the focus in Korea would be on TMD pain in young and middle-aged adults.

CLINICAL RELEVANCE: Besides culture, other variables including socioeconomic, environmental, and psychosocial factors can influence the clinical presentation of TMDs. Chinese and Korean TMD patients exhibited significantly more intra-articular and combined TMDs respectively.

PMID:37243820 | DOI:10.1007/s00784-023-05067-2

Clin Oral Investig. 2023 May 27. doi: 10.1007/s00784-023-05046-7. Online ahead of print.

ABSTRACT

OBJECTIVES: Previous studies have shown that aligners have limited ability to control root movements. The purpose of this study was to investigate which modification geometry and foil thickness are optimal for generating the force-moment (F/M) systems required for palatal root torque of maxillary central incisors.

MATERIALS AND METHODS: Tooth 11 was separated from a maxillary acrylic model and connected to a movement unit via a 3D F/M sensor. Different modification geometries (crescent, capsular, double-spherical) with different depths were digitally implemented in the labio-cervical region of tooth 11 to induce an increased contact force. We evaluated the F/M systems exerted by aligners with thicknesses of 0.4-1.0 mm. F/M measurements were taken with tooth 11 in the neutral position and during palatal displacement of tooth 11 (simulating its initial clinical movement).

RESULTS: The mechanical requirements of palatal root torque are a palatally directed force (- Fy) and a palatal root torquing moment (- Mx). These requirements were reliably achieved with modification depths > 0.5 mm. The modification depth and foil thickness had a significant influence on – Fy magnitudes (linear mixed-effect models, p < 0.01). With the 0.75-mm aligners combined with 1.5-mm deep modifications, the palatal root torque range (palTR) started after an initial palatal crown displacement of 0.09, 0.12, and 0.12 mm for the capsular, crescent, and double-spherical modification geometries, respectively.

CONCLUSIONS: A relatively early start of the palatal torque range (after a 0.1-mm palatal crown displacement) and appropriate – Fy magnitudes were achieved with 0.75-mm-thick aligners containing 1.5-mm deep capsular or crescent pressure regions. Subsequent clinical trials are required to confirm the clinical effects of these modifications.

CLINICAL RELEVANCE: In vitro testing indicated that modified aligners are capable of generating the F/M components required for palatal root torque of upper central incisors.

PMID:37243819 | DOI:10.1007/s00784-023-05046-7