Tag: statistics

J Endocrinol Invest. 2023 Sep 11. doi: 10.1007/s40618-023-02186-1. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the impact of pasireotide (PAS) therapy on hormonal and glycometabolic outcome in patients with acromegaly previously treated with combination medical therapies or unconventional dosages of first-generation somatostatin receptor ligands (fg-SRLs).

METHODS: Retrospective study carried out in two referral centers for pituitary diseases. Twenty-one acromegalic patients were switched to PAS (12 had biochemical control, 9 were uncontrolled). Data were collected after 3- and 6-months PAS treatment, and at the last available visit (median 35 months).

RESULTS: After switching to PAS therapy, a significant reduction in IGF-1 values was observed [median 39%; 0.79 xULN (IQR 0.5-1.01) vs 1.29 xULN (IQR 1.06-1.83); p = 0.009]. IGF-1 reduction was statistically significant in the 9 patients previously uncontrolled (61%, p = 0.016), and in the 12 controlled subjects (33%, p = 0.037). At last follow-up, the number of patients reaching an acceptable biochemical control (IGF-1 < 1.3 xULN) raised from 57 to 90% (p = 0.032). Mean HbA1c levels increased from 5.7% (5.5-5.9) to 6.0% (5.9-7) (p = 0.002), and the percentage of diabetic patients raised from 14% (3/21) to 67% (14/21) (p = 0.004). At the last evaluation HbA1c was ≥ 7.0% in 5 patients (24%). Antidiabetic drugs were initiated in 9 new patients, and in 7 out of 9 metformin alone was effective. Younger age and male sex were predictors for the maintenance of glucose homeostasis.

CONCLUSION: PAS monotherapy can be effective in acromegalic patients previously treated with combination medical therapies or unconventional dosages of fg-SRLs. Glucose imbalance can be managed in the vast majority of cases by use of lifestyle interventions and metformin.

PMID:37695461 | DOI:10.1007/s40618-023-02186-1

Int Endod J. 2023 Sep 11. doi: 10.1111/iej.13973. Online ahead of print.

ABSTRACT

AIM: To evaluate two- and three-dimensionally the effect of resorbable collagen-based bone-filling material on periapical healing of endodontic lesions with four-wall defects following endodontic microsurgery (EMS).

METHODOLOGY: This parallel, randomized controlled superiority clinical trial involved 86 lesions with the strictly endodontic origin and four-wall defect morphology. EMS procedures were performed by calibrated postgraduate residents. Before flap closure, osteotomies were randomized to the control or treatment group. In the control group, the flap was repositioned with no material added. In the treatment group, a collagen-based bone-filling augmentation material was placed into the osteotomy. Clinical and radiographic examinations were completed after 12 months. Periapical healing was evaluated by blinded evaluators using periapical (PA) radiographs according to Molven’s criteria and cone beam computed tomography (CBCT) scans according to PENN’s 3D criteria. Cortical plate healing was scored according to the RAC/B index. The data were analysed using Fisher’s exact test, Logistic regression models and Chi-squared test. The significance level was predetermined at p < .05.

RESULTS: Sixty-six cases were evaluated at the 12-month follow-up, with 30 and 36 cases in the control and treatment groups, respectively. Only the asymptomatic cases (control = 26, treatment = 32) were included in the radiographic evaluation. Twenty-three cases (88.5%) in the control and 28 (87.5%) cases in the treatment group demonstrated complete healing on PA radiographs (p = 1.000). On CBCT, 10 (38.4%) and 21 (65.6%) cases had completely healed in the control and treatment groups, respectively (p = .095). The re-establishment of the buccal cortical plate was detected in 12 (46.2%) and 22 (68.8%) cases in the control and treatment groups, respectively (p = .243).

CONCLUSION: Within the limitations of the present study, the use of collagen-based bone-filling material had no statistically significant effect on the periapical healing of endodontic lesions with four-wall defect following EMS at the 12-month follow-up when evaluated by PA radiographs or CBCT scans. However, the observed higher percentage of a re-established cortical plate in the treatment group could suggest a clinical benefit that is of interest after surgical endodontic treatment.

PMID:37695450 | DOI:10.1111/iej.13973

Acta Neurochir (Wien). 2023 Sep 11. doi: 10.1007/s00701-023-05780-7. Online ahead of print.

ABSTRACT

BACKGROUND: Elective use of intraparenchymal intracranial pressure (ICP) monitoring is a valuable resource in the investigation of hydrocephalus and other cerebrospinal fluid disorders. Our preliminary study aims to investigate ICP changes in the immediate period following dural breach, which has not yet been reported on.

METHOD: This is a prospective cohort study of patients undergoing elective ICP monitoring, recruited between March and May 2022. ICP readings were obtained at opening and then at 5-min intervals for a 30-min duration.

RESULTS: Ten patients were recruited, mean age 45 years, with indications of a Chiari malformation (n = 5), idiopathic intracranial hypertension (n = 3) or other ICP-related pathology (n = 2). Patients received intermittent bolus sedation (80%) vs general anaesthesia (20%). Mean opening pressure was 22.9 mmHg [± 6.0], with statistically significant decreases present every 5 min, to a total reduction of 15.2 mmHg at 20 min (p = < 0.0001), whereafter the ICP plateaued with no further statistical change.

DISCUSSION: Our results highlight an intracranial opening pressure ‘spike’ phenomenon. This spike was 15.2 mmHg higher than the plateau, which is reached at 20 min after insertion. Several possible causes exist which require further research in larger cohorts, including sedation and pain response. Regardless of causation, this study provides key information on the use of ICP monitoring devices, guiding interpretation and when to obtain measurements.

PMID:37695437 | DOI:10.1007/s00701-023-05780-7

Drugs. 2023 Sep 11. doi: 10.1007/s40265-023-01936-y. Online ahead of print.

ABSTRACT

BACKGROUND: Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has changed in recent years with the approval of new antiseizure medications (ASMs).

OBJECTIVE: The aim of this study was to estimate the comparative efficacy and tolerability of the ASMs for the treatment of seizures associated with DS using a network meta-analysis (NMA).

METHODS: Studies were identified by conducting a systematic search (week 4, January 2023) of the MEDLINE (accessed by PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and US National Institutes of Health Clinical Trials Registry ( http://www.

CLINICALTRIALS: gov ) databases. Any randomized, controlled, double- or single-blinded, parallel-group study comparing at least one ASM therapy against placebo, another ASM, or a different dose of the same ASM in participants with a diagnosis of DS was identified. The efficacy outcomes were the proportions of participants with ≥ 50% (seizure response) and 100% reduction (seizure freedom) in baseline convulsive seizure frequency during the maintenance period. The tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and who experienced at least one adverse event (AE). Effect sizes were estimated by network meta-analyses within a frequentist framework.

RESULTS: Eight placebo-controlled trials were included, and the active add-on treatments were stiripentol (n = 2), pharmaceutical-grade cannabidiol (n = 3), fenfluramine hydrochloride (n = 2), and soticlestat (n = 1). The studies recruited 680 participants, of whom 409 were randomized to active treatments (stiripentol = 33, pharmaceutical-grade cannabidiol = 228, fenfluramine hydrochloride = 122, and soticlestat = 26) and 271 to placebo. Pharmaceutical-grade cannabidiol was associated with a lower rate of seizure response than fenfluramine hydrochloride (odds ratio [OR] 0.20, 95% confidence interval [CI] 0.07-0.54), and stiripentol was associated with a higher seizure response rate than pharmaceutical-grade cannabidiol (OR 14.07, 95% CI 2.57-76.87). No statistically significant differences emerged across the different ASMs for the seizure freedom outcome. Stiripentol was associated with a lower probability of drug discontinuation for any reason than pharmaceutical-grade cannabidiol (OR 0.45, 95% CI 0.04-5.69), and pharmaceutical-grade cannabidiol was associated with a lower proportion of participants experiencing any AE than fenfluramine hydrochloride (OR 0.22, 95% CI 0.06-0.78). Stiripentol had a higher risk of AE occurrence than pharmaceutical-grade cannabidiol (OR 75.72, 95% CI 3.59-1598.58). The study found high-quality evidence of efficacy and tolerability of the four ASMs in the treatment of convulsive seizures in DS.

CONCLUSIONS: There exists first-class evidence that documents the efficacy and tolerability of stiripentol, pharmaceutical-grade cannabidiol, fenfluramine hydrochloride, and soticlestat for the treatment of seizures associated with DS, and allows discussion about the expected outcomes regarding seizure frequency reduction and tolerability profiles.

PMID:37695433 | DOI:10.1007/s40265-023-01936-y

Psychol Trauma. 2023 Sep 11. doi: 10.1037/tra0001581. Online ahead of print.

ABSTRACT

OBJECTIVE: Global emotion dysregulation mediates the relationship between child maltreatment and severe depressive symptoms; however, there is a lack of research on maladaptive personality traits and their contribution to individual differences in global emotion dysregulation within this conceptual model. The present study tested a preliminary serial mediation model where maladaptive personality traits and global emotion dysregulation mediate the relationship between child maltreatment and severe depressive symptoms.

METHOD: A total of 200 patients with mood disorders (M_age = 36.5 years; 54% females) were assessed for maladaptive personality traits (Personality Inventory for Diagnostic and Statistical Manual of Mental Disorders [5th ed.] Brief Form), global emotion dysregulation (Difficulties in Emotion Regulation Scale-Short), childhood trauma (Childhood Trauma Questionnaire), and depressive symptoms (Patient Health Questionnaire-9).

RESULTS: Ordinary least squares regression and partial least squares-structural equation modeling revealed a consistent and significant indirect effect of child maltreatment on severe depressive symptoms through negative affectivity, detachment, psychoticism, and global emotion dysregulation. Among child maltreatment types, only emotional abuse had a significant indirect effect on severe depressive symptoms through maladaptive personality traits and global emotion dysregulation, b = 0.50, SE = 0.09, 95% confidence intervals [0.326, 0.694] after controlling for age, gender, and remaining types of child maltreatment.

CONCLUSIONS: Findings support the view that maladaptive personality traits shed important insights on individual differences in global emotion dysregulation, and this information could aid clinical formulation and treatment of childhood adversity-related psychopathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

PMID:37695361 | DOI:10.1037/tra0001581

J Exp Psychol Gen. 2023 Sep 11. doi: 10.1037/xge0001440. Online ahead of print.

ABSTRACT

Humans are particularly sensitive to relationships between parts of objects. It remains unclear why this is. One hypothesis is that relational features are highly diagnostic of object categories and emerge as a result of learning to classify objects. We tested this by analyzing the internal representations of supervised convolutional neural networks (CNNs) trained to classify large sets of objects. We found that CNNs do not show the same sensitivity to relational changes as previously observed for human participants. Furthermore, when we precisely controlled the deformations to objects, human behavior was best predicted by the number of relational changes while CNNs were equally sensitive to all changes. Even changing the statistics of the learning environment by making relations uniquely diagnostic did not make networks more sensitive to relations in general. Our results show that learning to classify objects is not sufficient for the emergence of human shape representations. Instead, these results suggest that humans are selectively sensitive to relational changes because they build representations of distal objects from their retinal images and interpret relational changes as changes to these distal objects. This inferential process makes human shape representations qualitatively different from those of artificial neural networks optimized to perform image classification. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

PMID:37695326 | DOI:10.1037/xge0001440

Syst Biol. 2023 Sep 11:syad057. doi: 10.1093/sysbio/syad057. Online ahead of print.

ABSTRACT

The popularity of relaxed clock Bayesian inference of clade origin timings has generated several recent publications with focal results considerably older than the fossils of the clades in question. Here we critically examine two such clades: the animals (with focus on the bilaterians); and the mammals (with focus on the placentals). Each example displays a set of characteristic pathologies which, although much commented on, are rarely corrected for. We conclude that in neither case does the molecular clock analysis provide any evidence for an origin of the clade deeper than what is suggested by the fossil record. In addition, both these clades have other features (including, in the case of the placental mammals, proximity to a large mass extinction) that allow us to generate precise expectations of the timings of their origins. Thus, in these instances the fossil record can provide a powerful test of molecular clock methodology, and why it goes astray; and we have every reason to think these problems are general.

PMID:37695319 | DOI:10.1093/sysbio/syad057

J Manag Care Spec Pharm. 2023 Sep 11:1-12. doi: 10.18553/jmcp.2023.23045. Online ahead of print.

ABSTRACT

BACKGROUND: Research conducted in 2017 by Runyan et al concerning the current and future management of oncology drugs in the United States formed the basis for this research. The authors concluded that despite the high cost of oncology drugs, US payers relied on traditional management tools to manage the category, although these tools were ineffective at controlling costs. Innovative tools were not common in 2017. OBJECTIVE: To compare findings from the 2017 research with findings from a 2022 payer survey to understand how payer management of oncology drugs changed over 5 years. The study evaluates changing trends in oncology drug management. METHODS: The survey that informed the publication by Runyan et al in 2017 was reviewed, updated, and completed by 21 pharmacy and medical directors across 18 organizations representing 121.9 million covered lives. Both surveys included questions about management tools being employed in oncology and challenges to managing oncology. They used case studies in non-small cell lung cancer and chronic lymphocytic leukemia. These disease areas were chosen again in 2022 because they were included in the 2017 survey and because of the increase in competition in both categories from 2017 to 2022. The payer sample was designed to match the 2017 sample. The research was fielded from March to May 2022. The results were analyzed in Microsoft Excel; basic statistical analysis was conducted. Payers’ responses for each question were weighted by the number of reported covered lives at their organization so that the organization’s site was represented. RESULTS: On average, payers rated the management priority of oncology as a 5.3 and the budget impact as a 6.3 on a scale of 1 to 7, where 1 was low and 7 was high. Traditional tools remain dominant in this therapeutic area. However, there has been an increase in use of innovative tools. Pathways of care are trending upward since the initial survey in 2017. The Institute for Clinical and Economic Review (ICER) also influences payers’ decision-making in oncology more than it did 5 years ago. Despite these shifts, most payers allow for unrestricted access of targeted therapies in non-small cell lung cancer and chronic lymphocytic leukemia, in line with each drug’s US Food and Drug Administration-approved label. CONCLUSIONS: The increased use of pathways of care, shifting financial risk to providers, and the influence of ICER should continue to be monitored. Future research should focus on the role of pathways of care, comprehensive, evidence-based treatment protocols, in influencing prescribing decisions of hematologists and oncologists. DISCLOSURES: The authors work for Envision Pharma Group (formerly Two Labs), a company that provides consulting services to the pharmaceutical and biotech industries. As such, clients in these industries pay Envision Pharma Group for their services. This study was funded independently by Envision Pharma Group.

PMID:37695273 | DOI:10.18553/jmcp.2023.23045

Sci Total Environ. 2023 Sep 8:166915. doi: 10.1016/j.scitotenv.2023.166915. Online ahead of print.

ABSTRACT

Ground hardening in urban areas increases the risk of thermal enrichment in surface rainwater runoff. Moreover, the thermal pollution from rainwater runoff has become an important problem that damages the urban aquatic environment. Current studies have focused mainly on the potential hazard caused by runoff thermal pollution to aquatic microorganisms. However, there are few studies on the efficacy of controlling runoff thermal load through low-impact development (LID) and renovation in urban areas. The effects of LID modification were evaluated by monitoring the characteristics of the runoff thermal load on each underlying surface in the study area and conducting laboratory-scale bioretention experiments. The results showed that the initial thermal effect of each underlying surface was significant after the start of rainfall, based on the thermal load. Ceramic granules are remarkable bioretention fillers. Their average heat load and volume reduction rates are 55.6 % and 32.7 %, respectively. After LID modification, the thermal load of surface runoff in the study area decreased to 73.42 % under similar rainfall conditions. After the secondary treatment of the bioretention facility, the total thermal load of the outflow facility was 31.40 % of that before renovation. The peak thermal load reduced by 69.15 % and was delayed for 10 min. The control effect differed statistically.

PMID:37690765 | DOI:10.1016/j.scitotenv.2023.166915

Chem Biol Interact. 2023 Sep 8:110699. doi: 10.1016/j.cbi.2023.110699. Online ahead of print.

ABSTRACT

Parabens have been used for decades as preservatives in food, drugs and cosmetics. The majority however, were banned in 2009 and 2014 leaving only methyl-, ethyl-, propyl-, and butyl-derivates available for subsequent use. Methyl- and propylparaben have been extensively tested in vivo, with no resulting evidence for developmental and reproductive toxicity (DART). In contrast, ethylparaben has not yet been tested for DART in animal experiments, and it is currently debated if additional animal studies are warranted. In order to perform a comparison of the four currently approved parabens, we used a previously established in vitro test based on human induced pluripotent stem cells (iPSC) that are exposed to test substances during their differentiation to neuroectodermal cells. EC₅₀ values for cytotoxicity were 906 μM, 698 μM, 216 μM and 63 μM for methyl-, ethyl-, propyl- and butylparaben, respectively, demonstrating that cytotoxicity increases with increasing alkyl chain length. Genome-wide analysis demonstrated that FDR-adjusted significant gene expression changes occurred only at cytotoxic or close to cytotoxic concentrations, for example 1720 differentially expressed genes (DEG) at 1000 μM ethylparaben, 1 DEG at 316 μM, and no DEG at 100 μM or lower concentrations. The highest concentration of ethylparaben that did not induce any cytotoxicity nor DEG was 1670-fold above the highest published concentrations reported in biomonitoring studies (60 nM ethylparaben in cord blood). In conclusion, cytotoxicity and gene expression alterations of ethylparaben occurred at concentrations of approximately three orders of magnitude above human blood concentrations; moreover, the substance fitted well into a scenario where toxicity increases with the alkyl chain length, and gene expression changes only occur at cytotoxic or close to cytotoxic concentrations. Therefore, no evidence was obtained suggesting that in vivo DART with ethylparaben would lead to different results as the methyl- or propyl derivates.

PMID:37690743 | DOI:10.1016/j.cbi.2023.110699