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Nevin Manimala Statistics

Ultra-high dose rate pencil beam scanning proton dosimetry using ion chambers and a calorimeter in support of first in-human flash clinical trial

Med Phys. 2022 Jul 2. doi: 10.1002/mp.15844. Online ahead of print.

ABSTRACT

PURPOSE: To provide ultra-high dose rate pencil beam scanning proton dosimetry comparison of clinically used plane-parallel ion chambers, PTW Advanced Markus and IBA PPC05, with a proton graphite calorimeter in support of first in-human proton FLASH clinical trial.

METHODS: Absolute dose measurement intercomparison of the plane-parallel plate ion chambers and the proton graphite calorimeter was performed at 5 cm water equivalent depth using rectangular 250 MeV single layer treatment plans designed for the first in-human FLASH clinical trial. The dose rate for each field was designed to remain above 60 Gy/s. The ion recombination effects of the plane-parallel plate ion chambers at various bias voltages were also investigated in the range of dose rates between 5 – 60 Gy/s. Two independent model-based extrapolation methods were used to calculate the ion recombination correction factors ks to compare with the two-voltage technique from most widely used clinical protocols.

RESULTS: The mean measured dose to water with the proton graphite calorimeter across all the pre-defined fields is 7.702 ± 0.037 Gy. The average ratio over the pre-defined fields of the PTW Advanced Markus chamber dose to the calorimeter reference dose is 1.002 ± 0.007 while the IBA PPC05 chamber shows ∼3% higher reading of 1.033 ± 0.007. The relative difference in the ks values determined from between the linear and quadratic extrapolation methods and the two-voltage technique for the PTW Advanced Markus chamber are not statistically significant and the trends of dose rate dependence are similar. The IBA PPC05 shows a flat response in terms of ion recombination effects based on the ks values calculated using the two-voltage technique. Differences in ks values for the PPC05 between the two-voltage technique and other model-based extrapolation methods are not statistically significant at FLASH dose rates. Some of the ks values for the PPC05 that were extrapolated from the three-voltage linear method and the semi-empirical model were reported less than unity possibly due to the charge multiplication effect, which was negligible compared to the volume recombination effect in FLASH dose rates.

CONCLUSIONS: The absolute dose measurements of both PTW Advanced Markus and IBA PPC05 chambers are in a good agreement with the NPL graphite calorimeter reference dose considering overall uncertainties. Both ion chambers also demonstrate good reproducibility as well as stability as refence dosimeters in ultra-high dose rate pencil beam scanning proton radiotherapy. The dose rate dependency of the ion recombination effects of both ion chambers in cyclotron generated PBS proton beams is acceptable and therefore, both chambers are suitable to use in clinical practice for the range of dose rates between 5 – 60 Gy/s. This article is protected by copyright. All rights reserved.

PMID:35780318 | DOI:10.1002/mp.15844

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Postoperative tegafur-uracil for stage I lung adenocarcinoma: first real-world data with an exploratory subgroup analysis

Surg Today. 2022 Jul 2. doi: 10.1007/s00595-022-02546-z. Online ahead of print.

ABSTRACT

PURPOSE: The effect of postoperative tegafur-uracil on overall survival (OS) after resection of stage I adenocarcinoma has been shown in clinical trials. The purpose of this study was to investigate whether findings from randomized trials of adjuvant tegafur-uracil are reproducible in a real-world setting.

METHODS: A retrospective cohort study was performed using a multi-institutional database that included all patients who underwent complete resection of pathological stage I adenocarcinoma between 2014 and 2016. Survival outcomes for patients managed with and without tegafur-uracil were analyzed using the Kaplan-Meier method and a Cox proportional hazards model for the whole patient cohort and in a selected cohort based on eligibility criteria of a previous randomized trial. Propensity score matching was used to adjust for confounding effects.

RESULTS: After propensity score matching, the hazard ratios for OS were 0.57 (95% confidence interval (CI) 0.29-1.14, P = 0.11) in the whole cohort and 0.69 (95% CI 0.32-1.50, P = 0.35) in the selected cohort.

CONCLUSIONS: The effects of tegafur-uracil in this retrospective study appear to be consistent with those found in randomized clinical trials. These effects may be maximized in patients aged from 45 to 75 years.

PMID:35780275 | DOI:10.1007/s00595-022-02546-z

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The Use of a Network Analysis to Identify Associations and Temporal Patterns Among Non-communicable Diseases in Japan Based on a Large Medical Claims Database

Drugs Real World Outcomes. 2022 Jul 2. doi: 10.1007/s40801-022-00310-w. Online ahead of print.

ABSTRACT

BACKGROUND: Reducing the considerable non-communicable disease (NCD) burden in the aging Japanese population depends on better understanding of the comorbid and temporal relationships between different NCDs.

OBJECTIVE: We aimed to identify associations between NCDs and temporal patterns of NCDs in Japan using data from a large medical claims database.

METHODS: The study used three-digit International Classification of Diseases, Tenth Revision codes for NCDs for employees and their dependents included in the MinaCare database, which covers the period since 2010. Associations between pairs of NCDs were assessed by calculating risk ratios. The calculated risk ratios were used to create a network of closely associated NCDs (risk ratio > 15, statistically significant) and to assess temporal patterns of NCD diagnoses (risk ratio ≥ 5). The Infomap algorithm was used to identify clusters of diseases for different sex and age strata.

RESULTS: The analysis included 4,200,254 individuals (age < 65 years: 98%). Many of the temporal associations and patterns of the diseases of interest identified in this study were previously known. Regarding the diseases of interest, these associations can be classified as comorbidities, early manifestations initially diagnosed as something else, diseases attributable to or that cause the disease of interest, or caused by pharmacological treatment. International Classification of Diseases, Tenth Revision chapters that were most associated with other chapters included L Diseases of the skin and subcutaneous tissue. In the age-stratified and gender-stratified networks, clusters with the highest numbers of International Classification of Diseases, Tenth Revision codes included I Diseases of the circulatory system and F Mental and behavioral disorders.

CONCLUSIONS: Our findings reinforce established associations between NCDs and underline the importance of comprehensive NCD care.

PMID:35780274 | DOI:10.1007/s40801-022-00310-w

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Machine learning-based time series models for effective CO2 emission prediction in India

Environ Sci Pollut Res Int. 2022 Jul 2. doi: 10.1007/s11356-022-21723-8. Online ahead of print.

ABSTRACT

China, India, and the USA are the countries with the highest energy consumption and CO2 emissions globally. As per the report of datacommons.org , CO2 emission in India is 1.80 metric tons per capita, which is harmful to living beings, so this paper presents India’s detrimental CO2 emission effect with the prediction of CO2 emission for the next 10 years based on univariate time-series data from 1980 to 2019. We have used three statistical models; autoregressive-integrated moving average (ARIMA) model, seasonal autoregressive-integrated moving average with exogenous factors (SARIMAX) model, and the Holt-Winters model, two machine learning models, i.e., linear regression and random forest model and a deep learning-based long short-term memory (LSTM) model. This paper brings together a variety of models and allows us to work on data prediction. The performance analysis shows that LSTM, SARIMAX, and Holt-Winters are the three most accurate models among the six models based on nine performance metrics. Results conclude that LSTM is the best model for CO2 emission prediction with the 3.101% MAPE value, 60.635 RMSE value, 28.898 MedAE value, and along with other performance metrics. A comparative study also concludes the same. Therefore, the deep learning-based LSTM model is suggested as one of the most appropriate models for CO2 emission prediction.

PMID:35780266 | DOI:10.1007/s11356-022-21723-8

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Peripherally inserted central venous catheters decrease central line-associated bloodstream infections and change microbiological epidemiology in adult hematology unit: a propensity score-adjusted analysis

Ann Hematol. 2022 Jul 2. doi: 10.1007/s00277-022-04908-6. Online ahead of print.

ABSTRACT

Peripherally inserted central venous catheters (PICCs) have a potential advantage in preventing central line-associated bloodstream infection (CLABSI) compared with the centrally inserted ones (CICCs). However, due to a limited number of studies with insufficient statistical evaluation, the superiority of PICCs is difficult to be generalized in adult hematology unit. We conducted a single-center retrospective study and compared the risk of CLABSI between 472 CICCs and 557 PICCs inserted in adult patients with hematological disorders through conventional multivariate models and a propensity score-adjusted analysis. The overall CLABSI incidence in CICCs and PICCs was 5.11 and 3.29 per 1000 catheter days (P = 0.024). The multivariate Cox regression analysis (hazard ratio [HR]: 0.48; 95% confidence interval [CI]: 0.31-0.75; P = 0.001) and Fine-Gray subdistribution analysis (HR: 0.59; 95% CI: 0.37-0.93; P = 0.023) demonstrated that PICC was independently associated with a reduced risk of CLABSI. Moreover, the stabilized inverse probability of treatment weighting analysis, which further reduced the selection bias between CICCs and PICCs, showed that PICCs significantly prevented CLABSI (HR: 0.58; 95% CI: 0.35-0.94; P = 0.029). Microbiologically, PICCs showed a significant decrease in gram-positive cocci (P = 0.001) and an increase in gram-positive bacilli (P = 0.002) because of a remarkable reduction in Staphylococci and increase in Corynebacterium species responsible for CLABSI. Our study confirmed that PICC was a superior alternative to CICC in preventing CLABSI in the adult hematology unit, while it posed a microbiological shift in local epidemiology.

PMID:35780253 | DOI:10.1007/s00277-022-04908-6

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A randomized controlled trial on mobile phone text messaging to improve sexo-reproductive health among adolescent girls in Cameroon

Contracept Reprod Med. 2022 Jul 3;7(1):12. doi: 10.1186/s40834-022-00180-1.

ABSTRACT

BACKGROUND: We conducted a single-centered randomized controlled single-blinded trial (i.e. trained interviewers; blinded to group allocation). The target population included adolescent girls in the Kumbo West Health District (KWHD) of Cameroon. This trial tested the efficacy of weekly educational one-way text messages to improve perception of adolescent girls on sexo-reproductive health.

METHODS: Allocation concealment (1:1) was determined by sequentially numbered sealed opaque envelopes. A total of 398 participants either received the mobile phone sexo-reproductive health text messages (199) or not (199). A blinded program secretary send out text messages and recorded delivery. Data was collected and managed at baseline and at 6 month intervals using an interviewer-administered questionnaire before and after intervention, then analysed using the independent T-test (mean differences) and ANOVA on SPSS version 21.

RESULTS: The mean knowledge, attitude and practice scores respectively increased significantly from 6.03, 4.01 and 3.45 at baseline to 7.99, 5.83 and 4.99 at the end of the study. After performing ANOVA for the overall correct knowledge, positive attitudes and good practices respectively for between and within the intervention groups, we obtained: (F = 15.12, P = 0.023), (F = 60.21, P = 0.001) and (F = 57., P = 0.013) which showed statistical significance thus indicating the overall improvement in adolescents girls perception as a result of the intervention and not by chance. Majority (65.3%) of the participants were satisfied with the Short Message Service (SMS).

CONCLUSION: This trial has contributed to the body of knowledge and evidence on the use of mobile phone technology using educative SMS to improve adolescent girl’s perception on sexo-reproductive health in Cameroon.

TRIAL REGISTRATION: Pan African Clinical Trials Registry, PACTR201805003259293 . Registered 28 March 2018.

PMID:35780241 | DOI:10.1186/s40834-022-00180-1

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Direct pulp capping in asymptomatic carious primary molars using three different pulp capping materials: a prospective clinical trial

Eur Arch Paediatr Dent. 2022 Jul 2. doi: 10.1007/s40368-022-00720-y. Online ahead of print.

ABSTRACT

PURPOSE: Τo assess the outcome of direct pulp capping in asymptomatic carious primary molars using three pulp capping materials.

METHODS: In this prospective clinical trial, carious primary molars free of irreversible pulp inflammation signs and symptoms, with negative pain history and pulp exposure following caries removal were included. Teeth were divided into groups: A: Ca(OH)2, B: Pure Portland cement®, C: Biodentine™. Following anaesthesia, isolation, caries removal, pulp exposure, hemorrhage control, pulp capping, additional lining in groups A, B, teeth were restored with composite resin. Descriptive statistics, Chi-squared and Fisher’s exact tests, Kaplan-Meier survival curves, multivariable random effects Cox regression model were performed.

RESULTS: Sixty-six patients (25 girls, 41 boys) with mean age 7.2 (± 1.7) years participated. The mean follow-up time was 13 months. Seventy-nine primary molars were assigned to groups A (n = 27), B (29), C (n = 23). The overall failure was 16% and the distribution by group was: A: 5 teeth, B: 5 teeth, C: 3 teeth. No significant differences in failure rates between capping materials, tooth types, age bands and genders were identified.

CONCLUSIONS: Direct pulp capping in asymptomatic carious primary molars may be an acceptable option, when treating an exposed pulp with bioceramic materials as pulp capping agents.

PMID:35780237 | DOI:10.1007/s40368-022-00720-y

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Metabolomics-guided discovery of cytochrome P450s involved in pseudotropine-dependent biosynthesis of modified tropane alkaloids

Nat Commun. 2022 Jul 2;13(1):3832. doi: 10.1038/s41467-022-31653-1.

ABSTRACT

Plant alkaloids constitute an important class of bioactive chemicals with applications in medicine and agriculture. However, the knowledge gap of the diversity and biosynthesis of phytoalkaloids prevents systematic advances in biotechnology for engineered production of these high-value compounds. In particular, the identification of cytochrome P450s driving the structural diversity of phytoalkaloids has remained challenging. Here, we use a combination of reverse genetics with discovery metabolomics and multivariate statistical analysis followed by in planta transient assays to investigate alkaloid diversity and functionally characterize two candidate cytochrome P450s genes from Atropa belladonna without a priori knowledge of their functions or information regarding the identities of key pathway intermediates. This approach uncovered a largely unexplored root localized alkaloid sub-network that relies on pseudotropine as precursor. The two cytochrome P450s catalyze N-demethylation and ring-hydroxylation reactions within the early steps in the biosynthesis of diverse N-demethylated modified tropane alkaloids.

PMID:35780230 | DOI:10.1038/s41467-022-31653-1

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SARS-CoV-2 herd immunity of the Kyrgyz population in 2021

Med Microbiol Immunol. 2022 Jul 2. doi: 10.1007/s00430-022-00744-7. Online ahead of print.

ABSTRACT

In the fight against coronavirus infection, control of the immune response is of decisive importance, an important component of which is the seroprevalence of antibodies to SARS-CoV-2. Immunity to SARS-CoV-2 is formed either naturally or artificially through vaccination. The purpose of this study was to assess the seroprevalence of antibodies to SARS-CoV-2 in the population of Kyrgyzstan. A cross-sectional randomized study of seroprevalence was carried out according to a program developed by Rospotrebnadzor and the St. Petersburg Pasteur Institute, taking into account WHO recommendations. The ethics committees of the Association of Preventive Medicine (Kyrgyzstan) and the St. Petersburg Pasteur Institute (Russia) approved the study. Volunteers (9471) were recruited, representing 0.15% (95% CI 0.14-0.15) of the total population, randomized by age and region. Plasma antibodies (Abs) to the nucleocapsid antigen (Nag) were determined. In vaccinated individuals, Abs to the SARS-CoV-2 receptor-binding domain antigen (RBDag) were determined. Differences were considered statistically significant at p < 0.05. The SARS-CoV-2 Nag Ab seroprevalence was 48.7% (95% CI 47.7-49.7), with a maximum in the 60-69 age group [59.2% (95% CI 56.6-61.7)] and a minimum in group 1-17 years old [32.7% (95 CI: 29.4-36.1)]. The highest proportion of seropositive individuals was in the Naryn region [53.3% (95% CI 49.8-56.8)]. The lowest share was in Osh City [38.1% (95% CI 32.6-43.9)]. The maximum SARS-CoV-2 Nag seropositivity was found in the health-care sector [57.1% (95% CI 55.4-58.8)]; the minimum was seen among artists [38.6% (95% CI 26.0-52.4)]. Asymptomatic SARS-CoV-2 Nag seropositivity was 77.1% (95% CI 75.6-78.5). Vaccination with Sputnik V or Sinopharm produced comparable Ab seroprevalence. SARS-CoV-2 Nag seropositivity in the Kyrgyz population was 48.75% (95% CI 47.7-49.7), with the mass vaccination campaign undoubtedly benefitting the overall situation.

PMID:35780233 | DOI:10.1007/s00430-022-00744-7

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Vascularized Lymph Node Transfer Improved Outcomes of Elderly Patients with Secondary Upper Extremity Lymphedema

Ann Surg Oncol. 2022 Jul 2. doi: 10.1245/s10434-022-12035-9. Online ahead of print.

ABSTRACT

BACKGROUND: Secondary lymphedema is a debilitating morbidity. This study investigated the outcomes of vascularized lymph node transfer (VLNT) in elderly patients with secondary upper extremity lymphedema.

METHODS: Between 2008 and 2018, elderly (≥65 years) patients with secondary upper extremity lymphedema who underwent VLNT were retrospectively reviewed. Cheng’s Lymphedema Grading, Taiwan Lymphoscintigraphy Staging, and indocyanine green lymphography were used to select the procedures. Outcome measurements included complications, circumferential difference, episodes of cellulitis, and the Lymphedema-Specific Quality of Life questionnaire (LYMQoL).

RESULTS: Eleven patients with a mean age of 70.2 ± 5.3 years (range 65-80 years) who underwent VLNT survived and no major complications were encountered. At a mean follow-up of 6.5 ± 3.6 years (range 2-13 years), the mean limb circumferential difference was significantly improved from 25.6 ± 11.5% to 8.3 ± 4.2% (p = 0.016), and the mean episode of cellulitis was statistically reduced from 2.4 ± 1.3 to 0.4 ± 0.9 times/year (p = 0.007). At a follow-up of 24 months, four domains of Function (from 30.6 ± 2.8 to 14.5 ± 2.5), Appearance (from 18.2 ± 1.9 to 8.5 ± 2.1), Symptoms (from 30.4 ± 5.9 to 10.9 ± 1.0) and Mood (from 29.2 ± 4.4 to 10.7 ± 1.0), as well as overall LYMQoL score (from 3.9 ± 1.1 to 7.4 ± 0.5), showed statistical improvement (all p < 0.05).

CONCLUSIONS: VLNT for secondary upper extremity lymphedema in elderly patients significantly decreased the limb circumferential difference and frequency of cellulitis and improved quality of life without using compression garments postoperatively.

PMID:35780215 | DOI:10.1245/s10434-022-12035-9