Tag: statistics

Clin Exp Dent Res. 2023 Nov 28. doi: 10.1002/cre2.819. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to validate our Cox proportional hazards prognostic model for autotransplantation of teeth with complete root formation using prognostic index (PI) and determine whether the prognosis can be predicted.

PATIENTS AND METHODS: The Protocol group, as a training data set for validation, consisted of 259 autotransplanted teeth to create a PI using the Cox model, as described previously. The Pre-protocol group, as the first validation data set, consisted of 95 autotransplanted teeth treated without a protocol. The Post-protocol group, as the second validation data set, consisted of 61 autotransplanted teeth obtained after the establishment of the prognostic model. Because four prognostic factors, including history of root canal treatment (yes), number of roots (multirooted), source of donor tooth (maxillary tooth), and duration of edentulism (≥2.5 months), were selected as a Cox prognostic model, 16 patterns of PI were constructed. First, the autotransplantated teeth in the Protocol group were divided into low- and high-risk groups respectively according to the median of PI as the cutoff value. The survival curves of low- and high-risk groups were calculated using the Kaplan-Meier method and tested using the log-rank test. Then, in the Pre- and Post-protocol groups, all transplanted teeth were divided into low-and high-risk teeth by the median of PI and the survival curves of low- and high- risk teeth were analyzed statistically in a similar manner.

RESULTS: The survival curves of the low- and high-risk groups diverged significantly in the Protocol and Post-protocol groups. In the Pre-protocol group, the curves of the low- and high-risk groups were separated, and the low-risk survival rate was improved.

CONCLUSIONS: Our Cox prognostic model for autotransplantation of teeth with complete root formation was useful in predicting the prognosis by external validation using PI.

PMID:38018345 | DOI:10.1002/cre2.819

Epilepsia Open. 2023 Nov 28. doi: 10.1002/epi4.12873. Online ahead of print.

ABSTRACT

OBJECTIVE: In patients with Dravet syndrome (DS), fenfluramine reduced convulsive seizure frequency and provided clinical benefit in nonseizure endpoints (e.g., executive function, survival). In zebrafish mutant scn1 DS models, chronic fenfluramine treatment preserved neuronal cytoarchitecture prior to seizure onset and prevented gliosis; here, we extend these findings to a mammalian model of DS (Scn1a^+/- mice) by evaluating the effects of fenfluramine on neuroinflammation (degenerated myelin, activated microglia) and survival.

METHODS: Scn1a^+/- DS mice were treated subcutaneously once daily with fenfluramine (15 mg/kg) or vehicle from postnatal day (PND) 7 until 35-37. Sagittal brain sections were processed for immunohistochemistry using antibodies to degraded myelin basic protein (D-MBP) for degenerated myelin, or CD11b for activated (inflammatory) microglia; sections were scored semi-quantitatively. Apoptotic nuclei were quantified by TUNEL assay. Statistical significance was evaluated by 1-way ANOVA with post-hoc Dunnett’s test (D-MBP, CD11b, and TUNEL) or Logrank Mantel-Cox (survival).

RESULTS: Quantitation of D-MBP immunostaining per 0.1 mm² unit area of the parietal cortex and hippocampus CA3 yielded significantly higher spheroidal and punctate myelin debris counts in vehicle-treated DS mice than in wild-type mice. Fenfluramine treatment in DS mice significantly reduced these counts. Activated CD11b+ microglia were more abundant in DS mouse corpus callosum and hippocampus than in wild-type controls. Fenfluramine treatment of DS mice resulted in significantly fewer activated CD11b+ microglia than vehicle-treated DS mice in these brain regions. TUNEL staining in corpus callosum was increased in DS mice relative to wild-type controls. Fenfluramine treatment in DS mice lowered TUNEL staining relative to vehicle-treated DS mice. By PND 35-37, 55% of control DS mice had died, compared with 24% of DS mice receiving fenfluramine treatment (P=0.0291).

SIGNIFICANCE: This is the first report of anti-neuroinflammation and pro-survival after fenfluramine treatment in a mammalian DS model. These results corroborate prior data in humans and animal models and suggest important pharmacological activities for fenfluramine beyond seizure reduction.

PMID:38018342 | DOI:10.1002/epi4.12873

Hepatol Res. 2023 Nov 29. doi: 10.1111/hepr.13995. Online ahead of print.

ABSTRACT

AIM: We evaluated the safety and efficacy of vascular endothelial growth factor receptor (VEGFR) -targeted peptide vaccines for the immunization of patients with unresectable hepatocellular carcinoma who had responded to transarterial chemoembolization.

METHODS: Twenty-two patients were randomized 1:1 to receive VEGFR-targeted peptides or placebo. The primary endpoint was the safety assessment of the immunization. The secondary endpoints were evaluation of immunological responses and clinical outcomes.

RESULTS: The study agents induced no severe adverse event. Among the 12 patients in the vaccine group, a VEGFR1 specific cytotoxic T lymphocyte (CTL) response was induced in eight (66.7%) patients and a VEGFR2 specific CTL response was induced in ten (83.3%). The median progression free survival (PFS) and overall survival (OS) rates were 4.8 months and 52.0 months in the vaccine group, and 2.7 months and 21.8 months in the placebo group. No statistically significant differences were found between the two groups (PFS P=0.925, OS P=0.190). When divided into two groups according to immunoreactivity, the median PFS of patients with and without a strong immune response to VEGFR1 were 7.4 months and 2.7 months, and that to VEGFR2 were 10.6 months and 2.7 months, respectively; there were significant differences according to the immune response.

CONCLUSIONS: Immunotherapy with peptides vaccines targeting VEGFR1 and VEGFR2 was well tolerated with no serious adverse events. It also effectively induced peptide-specific CTLs in patients with unresectable hepatocellular carcinoma. This article is protected by copyright. All rights reserved.

PMID:38018304 | DOI:10.1111/hepr.13995

J Cachexia Sarcopenia Muscle. 2023 Nov 28. doi: 10.1002/jcsm.13384. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer cachexia is a severe complication of advanced malignancy, with few therapeutic options. To promote interprofessional care for cancer cachexia, healthcare providers’ needs should be addressed in detail. This pre-planned subgroup analysis of the Global Educational Needs Evaluation: a systemic interprofessional study in cancer cachexia (GENESIS-CC) survey aimed to identify barriers to interprofessional care of cancer cachexia in Japan.

METHODS: A nationwide survey was electronically conducted for healthcare providers in oncological or general healthcare facilities from January to March 2021 in Japan. The Japanese Regional Advisory Board developed a barrier scoring system with 33 from the 58 original survey items to quantify six domains of barriers: (1) lack of confidence, (2) lack of knowledge, (3) barriers in personal practice, (4) barriers in perception, (5) barriers in team practice and (6) barriers in education. The largest possible barrier score was set at 100 points. We compared the scores by profession.

RESULTS: A total of 1227 valid responses were obtained from 302 (24.6%) physicians, 252 (20.5%) pharmacists, 236 (19.2%) nurses, 218 (17.8%) dietitians, 193 (15.7%) rehabilitation therapists and 26 (2.0%) other professionals. Overall, 460 (37.5%) were not very or at all confident about cancer cachexia care, 791 (84.1%) agreed or strongly agreed that care was influenced by reimbursement availability and 774 (81.9%) did not have cancer cachexia as a mandatory curriculum. The largest mean barrier score (± standard deviation) was 63.7 ± 31.3 for education, followed by 55.6 ± 21.8 for team practice, 43.7 ± 32.5 for knowledge, 42.8 ± 17.7 for perception and 36.5 ± 16.7 for personal practice. There were statistically significant interprofessional differences in all domains (P < 0.05), especially for pharmacists and nurses with the highest or second highest scores in most domains.

CONCLUSIONS: There is a need to improve the educational system and team practices of cancer cachexia for most Japanese healthcare providers, especially pharmacists and nurses. Our study suggests the need to reform the mandatory educational curriculum and reimbursement system on cancer cachexia to promote interprofessional care for cancer cachexia in Japan.

PMID:38018293 | DOI:10.1002/jcsm.13384

Vox Sang. 2023 Nov 28. doi: 10.1111/vox.13564. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Although the genetic determinants of haemoglobin and ferritin have been widely studied, those of the clinically and globally relevant iron deficiency anaemia (IDA) and deferral due to hypohaemoglobinemia (Hb-deferral) are unclear. In this investigation, we aimed to quantify the value of genetic information in predicting IDA and Hb-deferral.

MATERIALS AND METHODS: We analysed genetic data from up to 665,460 participants of the FinnGen, Blood Service Biobank and UK Biobank, and used INTERVAL (N = 39,979) for validation. We performed genome-wide association studies (GWASs) of IDA and Hb-deferral and utilized publicly available genetic associations to compute polygenic scores for IDA, ferritin and Hb. We fitted models to estimate the effect sizes of these polygenic risk scores (PRSs) on IDA and Hb-deferral risk while accounting for the individual’s age, sex, weight, height, smoking status and blood donation history.

RESULTS: Significant variants in GWASs of IDA and Hb-deferral appear to be a small subset of variants associated with ferritin and Hb. Effect sizes of genetic predictors of IDA and Hb-deferral are similar to those of age and weight which are typically used in blood donor management. A total genetic score for Hb-deferral was estimated for each individual. The odds ratio estimate between first decile against that at ninth decile of total genetic score distribution ranged from 1.4 to 2.2.

CONCLUSION: The value of genetic data in predicting IDA or suitability to donate blood appears to be on a practically useful level.

PMID:38018286 | DOI:10.1111/vox.13564

Int J Dermatol. 2023 Nov 28. doi: 10.1111/ijd.16924. Online ahead of print.

ABSTRACT

BACKGROUND: Isotretinoin has been used in the treatment of acne for decades through the reduction of sebaceous secretion. There are reports in the literature that isotretinoin may be associated with decreased skin thickness, especially in patients with thick nasal skin for whom rhinoplasty can be more challenging. The objective of this study was to quantify, through ultrasonography, the effect of the use of oral isotretinoin in patients undergoing rhinoplasty, pre- and postoperatively.

METHODS: Twenty-four patients participated in this randomized, single-blind controlled pilot clinical trial. The intervention group used oral isotretinoin (20 mg/day) for 2 months before rhinoplasty and for 4 months after. Both groups underwent rhinoplasty in the same plastic surgery department and were submitted to high-frequency (22 MHz) ultrasound evaluation of the epidermis and dermis on the nasal dorsum, nasal tip, and left nose wing at the beginning of the study and 6 months after rhinoplasty, with the aim of assessing changes in skin thickness.

RESULTS: Six months after rhinoplasty, a statistically significant reduction was observed in the thickness of the epidermis and dermis of the nasal dorsum and left nose wing, as well as of the epidermis of the nasal tip, but only in the intervention group. The results of the satisfaction questionnaire were better after rhinoplasty in both groups, with no statistical difference between them regarding the specific questions; however, the intervention group had significantly higher satisfaction scores than the control group.

CONCLUSIONS: Isotretinoin was effective in reducing the thickness of the skin covering the nose of the evaluated sites.

PMID:38018283 | DOI:10.1111/ijd.16924

Curr Cardiol Rev. 2023 Nov 23. doi: 10.2174/011573403X256576231017110252. Online ahead of print.

ABSTRACT

BACKGROUND: Congestive Heart Failure with reduced Ejection Fraction (CHFrEF) guidelines adherence is not accessible everywhere, especially in countries with a high prevalence of low socioeconomic status, which resembles many of the middle eastern countries. However, adherence to the guidelines is correlated with lower mortality and morbidity rates.

OBJECTIVE: We are going to investigate the degree of treatment guideline adherence in CHFrEF in a patient population in the Middle East and correlate the compliance level with morbidity and mortality. Methods and Statistics: A retrospective study conducted on patients with CHFrEF in the Middle East region, maintained on Sacubitril/Valsartan for up to 4 years (190 patients), including a follow-up for morbidity and mortality rates, in addition to their correlations to the level of guidelines adherence.

RESULTS: Statistical analysis was done through IBM SPSS® 27th version. NYHA (pretreatment and post-treatment) was statistically significant in the partial adherence group as well as in full adherence. Moreover, Ejection fraction (pretreatment and post-treatment) was statistically significant in the partial adherence group as well as in full adherence, hence regardless of the level of adherence to the use of Sacubitril/Valsartan in CHFrEF, there was an improvement in the morbidity and mortality rates over up to four years of follow up.

CONCLUSION: Despite of our full support to full CHFrEF guideline adherence, we recognize how hard this task to be achieved, nevertheless this study supports the theme that any guideline adherence is correlated with better morbidity and mortality rates over a long term follow up.

PMID:38018202 | DOI:10.2174/011573403X256576231017110252

Curr Pharm Des. 2023 Nov 23. doi: 10.2174/0113816128265009231102063840. Online ahead of print.

ABSTRACT

BACKGROUND: The outbreak of Corona Virus Disease 2019 (COVID-19) has resulted in millions of infections and raised global attention. Bitter almonds and licorice are both Traditional Chinese Medicines (TCM), often used in combination to treat lung diseases. Several prescriptions in the guidelines for the diagnosis and treatment of coronavirus disease 2019 (trial version ninth) contained bitter almond-licorice, which was effective in the treatment of COVID-19. However, the active ingredients, drug targets and therapeutic mechanisms of bitter almonds-licorice for the treatment of COVID-19 remain to be elucidated.

METHODS: The active ingredients and targets were derived from the Traditional Chinese Medicine Systems Pharmacology (TCMSP). Meanwhile, targets associated with COVID-19 were obtained from the GeneCards database, PharmGkb database and DrugBank database. Then, the potential targets of bitter almond-licorice against COVID-19 were screened out. Protein-protein interaction (PPI) networks and core targets were analyzed through the String database and Cytoscape software. In addition, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed based on potential targets using R statistical software. Finally, molecular docking was used to validate the binding of the active ingredients to the core targets.

RESULTS: The results of the TCMSP database showed that the bitter almond-licorice had 89 active components against COVID-19, involving 102 targets. PPI network and core target analysis indicated that IL-6, TNF, MAPK1, and IL1B were the key targets against COVID-19. In addition, GO and KEGG enrichment analysis showed that the bitter almond-licorice were involved in various biological processes through inflammation-related pathways such as TNF signaling pathway and IL-17 signaling pathway. Finally, molecular docking approaches confirmed the affinity between the active components of the bitter almond-licorice and the therapeutic targets.

CONCLUSION: The bitter almond-licorice could be used to treat COVID-19 by inhibiting inflammatory responses and regulating cellular stress. This work is based on data mining and molecular docking, and the findings need to be interpreted with caution.</P>.

PMID:38018195 | DOI:10.2174/0113816128265009231102063840

J Biosoc Sci. 2023 Nov 29:1-13. doi: 10.1017/S0021932023000275. Online ahead of print.

ABSTRACT

This study focuses on analysing the heights of 10,953 Korean men aged 20 to 40 years who were measured during the Joseon dynasty, the Japanese colonialisation period, and the contemporary period, the latter including both North and South Korea. This study thus provides rare long-term statistical evidence on how biological living standards have developed over several centuries, encompassing Confucianism, colonialism, capitalism, and communism. Using error bar analysis of heights for each historical sample period, this study confirms that heights rose as economic performance improved. For instance, economically poorer North Koreans were expectedly shorter, by about 6 cm, than their peers living in the developed South. Similarly, premodern inhabitants of present-day South Korea, who produced a gross domestic product (GDP) per capita below the world average, were about 4 cm shorter than contemporary South Koreans, who have a mean income above the world average. Along similar lines, North Koreans, who have a GDP per capita akin to that of the premodern Joseon dynasty, have not improved much in height. On the contrary, mean heights of North Koreans were even slightly below (by about 2.4 cm) heights of Joseon dynasty Koreans. All in all, the heights follow a U-shaped pattern across time, wherein heights were lowest during the colonial era. Heights bounced back to Joseon dynasty levels during the interwar period, a time period where South Korea benefitted from international aid, only to rise again and surpass even premodern levels under South Korea’s flourishing market economy.

PMID:38018165 | DOI:10.1017/S0021932023000275

J Exp Orthop. 2023 Nov 29;10(1):124. doi: 10.1186/s40634-023-00709-6.

ABSTRACT

PURPOSE: According to the homeostasis model, patellofemoral pain (PFP) results from disturbed homeostasis due to vascular insufficiency in the anterior knee. Near-Infrared Spectroscopy (NIRS) measures relative changes in concentrations (in µmol/cm²) of (de-)oxygenated hemoglobine (HHb and O₂Hb). The aims were to: 1) investigate the characteristics of the NIRS signal derived from the patella during experiments affecting hemodynamics in healthy controls, and 2) determine the test-retest reliability of NIRS in positions clinically relevant for PFP patients.

METHODS: Two experiments were conducted on 10 healthy controls and analysed using Student’s t-test. Reliability (ICC_2,1) was evaluated for two activities (‘Prolonged Sitting’ and ‘Stair Descent’) in five PFP patients and 15 healthy controls, performed twice within five days.

RESULTS: The NIRS signal (HHb and O₂Hb) showed a statistically significant increase (p < .001 – .002) on all optodes (30, 35, 40 mm) during ‘Venous Occlusion’ (M = 1.0 – 2.0), while it showed no statistically significant change (p = .075 – .61) during ‘Skin Compression’ (M = -0.9 – 0.9) on the 30 and 35 mm optode. Reliability of NIRS (HHb and O₂Hb) ranged from moderate to almost perfect (ICC_2,1 = .47 – .95) on the 30 mm optode for ‘Prolonged Sitting’, and from moderate to substantial (ICC_2,1 = .50 – .68) on the 35 mm optode for ‘Stair Descent’.

CONCLUSIONS: Patella NIRS measurements are affected by venous occlusion, but not by skin compression, and are sufficiently reliable as research application to compare real-time patellar bone hemodynamics. These insights may assist to improve effectiveness of evidence-based treatment strategies for PFP.

TRIAL REGISTRATION: ISRCTN Trial Registration under number: 90377123.

PMID:38017345 | DOI:10.1186/s40634-023-00709-6