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Nevin Manimala Statistics

Does the choice of induction agent in rapid sequence intubation in the emergency department influence the incidence of post-induction hypotension?

Emerg Med Australas. 2023 Nov 29. doi: 10.1111/1742-6723.14355. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe the effects of different induction agents on the incidence of post-induction hypotension (PIH) and its associated interventions during rapid sequence intubation (RSI) in the ED.

METHODS: A single centre retrospective study of patients intubated between 2018 and 2021 was conducted in a regional Australian ED. The impact of induction agent choice, in addition to demographic and clinical factors on the incidence of PIH were determined using descriptive statistics and a multivariate analysis presented as adjusted odds ratios (aORs) and their 95% confidence intervals (CIs).

RESULTS: Ketamine and propofol, used either individually or in conjunction with fentanyl, were significantly associated with PIH (ketamine aOR 4.5, 95% CI 1.35-14.96; propofol aOR 4.88, 95% CI 1.46-16.29). Age >60 years was associated with a greater requirement for vasopressors (aOR 4.46, 95% CI 2.49-7.97) and a higher risk of mortality after RSI (aOR 4.2, 95% CI 1.87-9.40). Patients with a shock index >1.0 were significantly more likely to require vasopressors (aOR 5.13, 95% CI 2.35-11.2) and have a cardiac arrest within 15 min of RSI (aOR 3.56, 95% CI 1.07-11.8).

CONCLUSIONS: Exposure to both propofol and ketamine is significantly associated with PIH after RSI, alongside age and shock index. PIH is likely multifactorial in nature, and this data supports the sympatholytic effect of induction agents as the underlying cause of PIH rather than the choice of agent itself. Further prospective work including a randomised controlled trial between induction agents is justified to further clarify this important clinical question.

PMID:38018391 | DOI:10.1111/1742-6723.14355

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Nevin Manimala Statistics

A longitudinal analysis of brain volume changes in myelin oligodendrocyte glycoprotein antibody-associated disease

J Neuroimaging. 2023 Nov 29. doi: 10.1111/jon.13175. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a relapsing demyelinating condition. There are several cross-sectional studies showing evidence of brain atrophy in people with MOGAD (pwMOGAD), but longitudinal brain volumetric assessment is still an unmet need. Current recommendations do not include monitoring with MRI and assume distinct attacks. Evidence of ongoing axon loss will have diagnostic and therapeutic implications. In this study, we assessed brain volume changes in pwMOGAD over a mean follow-up period of 2 years and compared this to changes in people with multiple sclerosis (pwMS).

METHODS: This is a retrospective single-center study over a 7-year period from 2014 to 2021. MRI brain scans at the time of diagnosis and follow-up in remission were collected from 14 Caucasian pwMOGAD, confirmed by serum myelin oligodendrocyte glycoprotein immunoglobulin G antibody presence, detected by live cell-based assays. Total brain volume (TBV), white matter (WM), gray matter (GM), and demyelinating lesion volumes were assessed automatically using the Statistical Parametric Mapping and FMRIB automated segmentation tools. MRI brain scans at diagnosis and follow-up on remission were collected from 32-matched pwMS for comparison. Statistical analysis was done using analysis of variance.

RESULTS: There is evidence of TBV loss, affecting particularly GM, over an approximately 2-year follow-up period in pwMOGAD (p < .05), comparable to pwMS. WM and lesion volume change over the same period were not statistically significant (p > .1).

CONCLUSION: We found evidence of loss of GM and TBV over time in pwMOGAD, similar to pwMS, although the WM and lesion volumes were unchanged.

PMID:38018386 | DOI:10.1111/jon.13175

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Nevin Manimala Statistics

Timing of conceptions in Phayre’s leaf monkeys: Energy and phytochemical intake

Am J Biol Anthropol. 2023 Nov 29. doi: 10.1002/ajpa.24881. Online ahead of print.

ABSTRACT

OBJECTIVES: Raising offspring imposes energetic costs, especially for female mammals. Consequently, seasons favoring high energy intake and sustained positive energy balance often result in a conception peak. Factors that may weaken this coordinated effect include premature offspring loss and adolescent subfertility. Furthermore, seasonal ingestion of phytochemicals may facilitate conception peaks. We examined these factors and potential benefits of a conception peak (infant survival and interbirth interval) in Phayre’s leaf monkeys (Trachypithecus phayrei crepusculus).

MATERIALS AND METHODS: Data were collected at Phu Khieo Wildlife Sanctuary, Thailand (78 conceptions). We estimated periods of high energy intake based on fruit and young leaf feeding and via monthly energy intake rates. Phytochemical intake was based on fecal progestin. We examined seasonality (circular statistics and cox proportional hazard models) and compared consequences of timing (infant survival and interbirth intervals, t-test, and Fisher exact test).

RESULTS: Conceptions occurred in all months but peaked from May to August. This peak coincided with high fecal progestin rather than presumed positive energy balance. Primipara conceived significantly later than multipara. Neither infant survival nor interbirth intervals were related to the timing of conception.

DISCUSSION: Periods of high energy intake may not exist and would not explain the conception peak in this population. However, the presumed high intake of phytochemicals was tightly linked to the conception peak. Timing conceptions to the peak season did not provide benefits, suggesting that the clustering of conceptions may be a mere by-product of phytochemical intake. To confirm this conclusion, seasonal changes in phytochemical intake and hormone levels need to be studied more directly.

PMID:38018374 | DOI:10.1002/ajpa.24881

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Nevin Manimala Statistics

Publication bias, statistical power and reporting practices in the Journal of Sports Sciences: potential barriers to replicability

J Sports Sci. 2023 Nov 29:1-11. doi: 10.1080/02640414.2023.2269357. Online ahead of print.

ABSTRACT

Two factors that decrease the replicability of studies in the scientific literature are publication bias and studies with underpowered desgins. One way to ensure that studies have adequate statistical power to detect the effect size of interest is by conducting a-priori power analyses. Yet, a previous editorial published in the Journal of Sports Sciences reported a median sample size of 19 and the scarce usage of a-priori power analyses. We meta-analysed 89 studies from the same journal to assess the presence and extent of publication bias, as well as the average statistical power, by conducting a z-curve analysis. In a larger sample of 174 studies, we also examined a) the usage, reporting practices and reproducibility of a-priori power analyses; and b) the prevalence of reporting practices of t-statistic or F-ratio, degrees of freedom, exact p-values, effect sizes and confidence intervals. Our results indicate that there was some indication of publication bias and the average observed power was low (53% for significant and non-significant findings and 61% for only significant findings). Finally, the usage and reporting practices of a-priori power analyses as well as statistical results including test statistics, effect sizes and confidence intervals were suboptimal.

PMID:38018365 | DOI:10.1080/02640414.2023.2269357

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Nevin Manimala Statistics

Validation of a Cox prognostic model for tooth autotransplantation

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

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Nevin Manimala Statistics

Fenfluramine increases survival and reduces markers of neurodegeneration in a mouse model of Dravet syndrome

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

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Nevin Manimala Statistics

A randomized phase I / II study of vascular endothelial growth factor receptor peptide vaccines for patients with hepatocellular carcinoma

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

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Nevin Manimala Statistics

The barriers to interprofessional care for cancer cachexia among Japanese healthcare providers: A nationwide survey

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

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Nevin Manimala Statistics

The value of genetic data from 665,460 individuals in managing iron deficiency anaemia and suitability to donate blood

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

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Nevin Manimala Statistics

Analysis of the use of isotretinoin as an adjuvant in rhinoplasty

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