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Repeated, High-dose Fentanyl Administration in Rats Reveals Minimal Tolerance to Unconsciousness, Bradycardia, Muscle Rigidity and Respiratory Depression

Anesthesiology. 2024 Dec 19. doi: 10.1097/ALN.0000000000005324. Online ahead of print.

ABSTRACT

BACKGROUND: Fentanyl is a synthetic opioid that is widely used in anesthesiology, but its illicit use is rapidly increasing. At high doses fentanyl induces unconsciousness and muscle rigidity, the mechanisms of which are poorly understood. Since animal models are needed to study these effects, the aim of this study was to establish a rat model of fentanyl abuse and investigate the effects of repeated high-dose fentanyl injections on loss of righting reflex, heart rate, respiratory depression, muscle, and brain activity.

METHODS: Male and female Sprague-Dawley rats were studied (n=40). A bolus of 100µg/kg fentanyl was administered intravenously twice a week for five consecutive weeks. Time to return of righting reflex (RORR) after fentanyl injection and changes in EMG/EEG activity as well as heart rate were analyzed. Additionally, arterial blood gas analysis for evaluation of ventilation was performed. Mixed-effect models with Dunnet’s test and effect sizes were used for statistical analysis.

RESULTS: Repeated injections resulted in a U-shaped change in time to RORR with the longest latency after the first exposure (median: 50[1st-3rd quartile:36-56]min) and the shortest after the fifth exposure (16[13-33]min). Following fentanyl administration, heart rate dropped immediately by 225[95%CI: 179, 271]bpm (F=3952.16, p<.001), while EMG activity increased by 291[95%CI: 212, 370]% (F=27.51, p<0.001) and PaCO2 inclined by 49.4[95%CI: 40.6, 58.2]mmHg (F=75.97, p<0.001) within 5 minutes after injection. Additionally, pH decreased by 0.48[95%CI: 0.41, 0.54] (F=142.00, p<0.01), and PaO2 decreased by 50.4[40.8, 60.0]mmHg (F=57.90, p<0.001). Repeated fentanyl exposures did not significantly affect the extent of these changes (EMG: F=1.63, p=0.237; PaCO2: F=1.23, p=0.312; HR: F=1.05, p=0.400; pH: F=3.05, p=0.066; pO2: F=3.35, p=0.052). EEG analysis revealed that repeated fentanyl exposures elicited significantly higher absolute power in frequencies >20Hz as indicated by an area under the receiver operator characteristics curve >0.7.

CONCLUSION: We established a rodent model of repeated, high-dose fentanyl administration. Overall, significant evidence of tolerance was not observed after ten exposures of high-dose fentanyl for any of the analyzed parameters. These results suggest that tolerance does not develop for fentanyl-induced unconsciousness, muscle rigidity, or respiratory depression.

PMID:39705671 | DOI:10.1097/ALN.0000000000005324

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Nevin Manimala Statistics

Effect of Food-Simulating Liquids on Hydrolytic Behavior of Resin Matrix Ceramics

Int J Prosthodont. 2024 Dec 20;0(0):1-22. doi: 10.11607/ijp.9267. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to evaluate the hydrolytic behavior of different computer-aided design/computer-aided manufacturing (CAD/CAM) resin matrix ceramics (RMCs) in different food-simulating liquids (FSLs).

MATERIALS AND METHODS: Five different CAD/CAM blocks, one from polymer-infiltrated ceramic networks (PICNs; Vita Enamic (EN)) and four from resin-based composites (RBCs; Lava Ultimate (UL), Cerasmart (CER), Brilliant Crios (BR), and Block HC (HC)) were selected. Forty specimens were prepared for each material, and they randomly distributed to each FSLs. The specimens were kept in a desiccator initially, then placed in 5 ml of liquid at 37±1°C for 30 days and weighed at various time intervals. Percentage mass change (Mg%), sorption (SP), percentage of liquid absorbed (SP%), solubility (SL), percentage solubility (SL%), and percentage of liquid absorbed by the polymer matrix (SPpm) water absorption of the specimens were evaluated. Significance was evaluated at p<0.05 levels.

RESULTS: Hydrolytic behavior of the materials showed statistical differences in terms of SP, SL, SP%, and SL% values depending on the liquid environment (p=0.001). The highest SP values were obtained from the HC material in saliva, and the lowest values were obtained from the BR in ethanol. The highest SL values were obtained from the CER and EN in heptane, and the lowest values were obtained from the HC in ethanol. However, all results detected in the study remained below the ISO threshold values.

CONCLUSIONS: All materials tested exhibited clinically acceptable hydrolytic behavior over the time tested. Not only the material content but also many factors can affect the hydrolytic behavior.

PMID:39705663 | DOI:10.11607/ijp.9267

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Awareness, Knowledge, and Treatment Patterns of Nonmetastatic Inflammatory Breast Cancer in Low- and Middle-Income Countries: The BRIDGES Study

JCO Glob Oncol. 2024 Dec;10:e2400307. doi: 10.1200/GO-24-00307. Epub 2024 Dec 20.

ABSTRACT

PURPOSE: Trimodal therapy (TMT) is the standard treatment for patients with nonmetastatic inflammatory breast cancer (IBC). TMT consists of neoadjuvant systemic therapy, modified radical mastectomy (MRM), and postmastectomy radiation therapy. Although broadly considered the best approach for IBC, in the United States, only a third of patients receive TMT. The rate is unknown in low- and middle-income countries (LMICs).

METHODS: A questionnaire in English and Spanish was constructed to assess the awareness, knowledge, and treatment patterns of IBC among providers in LMICs. It was emailed to the ONCOLLEGE global oncology collaborative group (a network of cancer care providers practicing in LMICs) and through other oncology network providers in LMICs, enhancing the sample size through a snowball sampling approach.

RESULTS: Between June and December of 2023, 145 participants completed the questionnaire, of whom 112 respondents were from 36 LMICs. All the providers reported that standard chemotherapy and MRM were available in their practice; 99.5% responded that radiation therapy was available. A total of 74.1% appropriately reported that IBC is a clinical diagnosis, although 51.8% stated that pathologic evidence of lymphatic emboli was required for IBC diagnosis. A third of the providers responded that >90% of their patients undergo all three parts of TMT.

CONCLUSION: Many patients with IBC in LMICs are not receiving TMT. Barriers to diagnosis and treatment were at least partially related to limited providers’ comfort level and knowledge, suggesting that educational approaches can be impact-oriented interventions. On the basis of our findings, we created educational material, which will be translated into various languages and disseminated broadly to improve providers’ awareness and knowledge of IBC.

PMID:39705637 | DOI:10.1200/GO-24-00307

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Determining the association of hyperoxia while on extracorporeal life support with mortality in neonates following Norwood operation

J Extra Corpor Technol. 2024 Dec;56(4):174-184. doi: 10.1051/ject/2024020. Epub 2024 Dec 20.

ABSTRACT

BACKGROUND: Patients requiring extracorporeal life support (ECLS) support post-Norwood operation constitute an extremely high-risk group.

MATERIALS AND METHODS: We retrospectively aimed to evaluate the relationship of hyperoxia with mortality and other clinical outcomes in patients who required ECLS following Norwood operation between January/2010 and December/2020 in a large volume center.

RESULTS: During the study period 65 patients required ECLS post-Norwood. Using receiver operating characteristic (ROC) curve analysis, mean PaO2 of 182 mmHg in the first 48-hour on ECLS was determined to have the optimal discriminatory ability for mortality (sensitivity 68%, specificity 70%). Of the 65 patients, 52% had PaO2 > 182 mmHg and were designated as hyperoxia group. Patients in the hyperoxia-group had longer cardiopulmonary bypass time (187 vs. 165 min, p = 0.023), shorter duration from CICU arrival to ECLS-cannulation (13.28 vs. 132.58 h, p = 0.003), higher serum lactate within 2-hours from ECLS-canulation (14.55 vs. 5.80, p = 0.01), higher ECLS flows in the first 4-hours (152.68 vs. 124.14, p = 0.006), and higher mortality (77% vs. 39%, p = 0.005). In the unadjusted-analysis, using a derived cut-point, patients in the hyperoxia-group had 5.15 higher odds of mortality (p = 0.003). However, this association was insignificant when adjusting for confounding variables (p = 0.104). Using a functional status scale, new morbidity (38% vs. 21%), and unfavorable outcomes (13% vs. 5%) were higher in the hyperoxia group. Despite being higher in the hyperoxia group, this did not reach statistical significance.

CONCLUSION: Neonates with hyperoxia (PaO2 > 182 Torr) during the first 48-hour of ECLS post-Norwood operation had 5 times higher odds of mortality in the unadjusted analysis, however, this was insignificant when adjusting for confounding variables. Patients in the hyperoxia group had shorter duration from CICU arrival to ECLS-cannulation, higher serum lactate prior to ECLS-canulation, and higher ECLS flows in the first 4-hours, (p < 0.05). Multicenter evaluation of this modifiable risk factor is imperative to improve the care of this high-risk cohort.

PMID:39705581 | DOI:10.1051/ject/2024020

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Relations Between Suicide Risk and Patient Safety Attitudes Among the Nursing Team in a Brazilian Context

J Patient Saf. 2024 Dec 23. doi: 10.1097/PTS.0000000000001305. Online ahead of print.

ABSTRACT

OBJECTIVES: To analyze the aspects of suicide risks and their relation to patient safety attitudes among the nursing staff of a large public university hospital in Brazil.

METHODS: A cross-sectional and descriptive study with 226 nursing workers from a large public university hospital in Brazil. Socioprofessional information, health conditions, and family history related to suicide risk were collected through the Mini International Neuropsychiatric Interview Plus and the Safety Attitudes Questionnaire. A 95% CI was considered, and statistical tests such as the Student t test, χ2, analysis of variance, and multiple linear regression were used.

RESULTS: Most of the safety attitudes were below the average score considered positive (mean Safety Attitudes Questionnaire value >0.75), and 41 (18.1%) workers were considered to have any degree of suicide risk. Participants with parents or siblings who had attempted suicide were 3.44 times more likely to have moderate or high suicide risk. Negative safety attitudes were associated with health conditions and family history, considered suicide risk factors. Participants with moderate or high suicide risk were 2.83 times more likely to have worse patient safety attitudes concerning job satisfaction.

CONCLUSIONS: This study reveals significant associations between patient safety attitudes and the mental health of nursing workers, expanding the view of worker health management actions and, consequently, patient safety culture.

PMID:39705531 | DOI:10.1097/PTS.0000000000001305

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Revolutionizing Laminate Veneer Bonding: Laser Versus Acid Etching of Enamel

Int J Periodontics Restorative Dent. 2024 Dec 20;0(0):1-17. doi: 10.11607/prd.7384. Online ahead of print.

ABSTRACT

PURPOSE: This study is designed to explore the effect of Er,Cr:YSGG laser tooth etching versus that of conventional tooth surface treatment on the shear bond strength of ceramic laminate veneers.

METHODS: Seventy-six maxillary premolars were assigned to two groups (n = 38) according to the type of enamel surface treatment approach. Group 1: samples treated with the conventional acid-etch protocol. Group 2: samples subjected to Er,Cr:YSGG laser. Light-curing resin cement was used to bond the restoration to the tooth and specimens were thermocycled for 30,000 cycles. Shear bond strength testing was conducted on all the specimens. The samples were observed using a scanning electron microscope to record enamel topography and a stereomicroscope to monitor the mode of failure. P ≤ 0.05 was considered significant.

RESULTS: There were no statistically significant differences between the acidetch and laser enamel surface treatment groups for the shear bond strength values at maximum load (MPa) (p-value = .627). There was a significantly higher proportion of cohesive failure in the acid-etch group compared to the laser treatment group and a significantly lower proportion of mixed failure in group 1 compared to group 2 (p-value = .022).

CONCLUSIONS: Concerning the bond strength of the laminate veneer, the effects of laser and traditional acid etching on the enamel surface were the same. Enamel surfaces can be successfully etched using a laser as an alternative to the traditional acid-etch method.

PMID:39705512 | DOI:10.11607/prd.7384

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Understanding Cognitive Performance, Psychological Factors, and Personality Traits in Women Exposed to Intimate Partner Violence

Psychol Rep. 2024 Dec 20:332941241308776. doi: 10.1177/00332941241308776. Online ahead of print.

ABSTRACT

Intimate partner violence (IPV) might increase the risk of depression, traumatic stress and affect cognitive performance. We analyzed the cognitive performance, psychological factors, and personality traits of 136 Brazilian women (n = 70 exposed to IPV and n = 66 non-exposed) aged 18 years or older. We utilized clinical interviews, the NEO Personality Inventory, and a neuropsychological testing battery. The statistical analyses employed moderation within variables, resulting in determination coefficients (r2) of 0.15 and 0.35. The husband was the primary aggressor, physical violence was the most frequent (90.6%). Women exposed to IPV exhibited more symptoms of post-traumatic stress disorder (PTSD), depression, neuroticism, difficulties in visual memory, and visuospatial abilities. The analysis indicated the influence of IPV, neuroticism, PTSD, and depression on the cognitive performance of the exposed to IPV.

PMID:39705508 | DOI:10.1177/00332941241308776

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Post-COVID Condition Risk Factors and Symptom Clusters and Associations with Return to Pre-COVID Health-Results from a 2021 Multi-State Survey

Clin Infect Dis. 2024 Dec 20:ciae632. doi: 10.1093/cid/ciae632. Online ahead of print.

ABSTRACT

BACKGROUND: Little is known about how symptoms or symptom clusters of Post-COVID Conditions (PCC) impact an individual’s return to pre-COVID health.

METHODS: We used four state-level COVID-19 case reporting systems and patient-reported survey data to identify patients with PCC and associations with an individual’s return to pre-COVID health after laboratory-confirmed SARS-CoV-2 infection. Participants had a positive SARS-CoV-2 test between March-December 2020. Weighted regression models were used to 1) estimate prevalence of PCC; 2) identify risk factors associated with developing PCC; and 3) examine associations between PCC symptom clusters and return to pre-COVID health. Factor analysis was used to statistically identify post-COVID symptom clusters.

FINDINGS: Prevalence of PCC in this population-based sample was 29·9% for persons with SARS-CoV-2 infection, during the pre-delta variant period (March-December 2020); 77·2% of persons experiencing PCC had not returned to pre-COVID health within 8-60 weeks after infection. Female sex, acute COVID-19 illness severity, and number of pre-existing comorbidities were significant risk factors associated with PCC. Myalgic encephalomyelitis/chronic fatigue syndrome-like symptoms, upper-respiratory symptoms, and gastrointestinal symptoms were significantly associated with not returning to pre-COVID health.

INTERPRETATION: Understanding PCC symptom clustering may provide insight into pathophysiology, severity of PCC, and management for patients who have not returned to their usual state of health after SARS-CoV-2 infection. Tracking PCC can help measure the impact of COVID-19 vaccination and acute COVID-19-specific treatments on reducing PCC in the US.

PMID:39705503 | DOI:10.1093/cid/ciae632

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Lipid accumulation product mediating the association between uranium and cerebrovascular diseases mortality: Evidence from National Health and Nutrition Examination Survey

Medicine (Baltimore). 2024 Dec 20;103(51):e40888. doi: 10.1097/MD.0000000000040888.

ABSTRACT

This study investigated the potential association between uranium exposure and mortality from cerebrovascular diseases, with a focus on the mediating effects of lipid indicators. Employing recommended sampling weights to account for National Health and Nutrition Examination Survey’ complex survey design, this analysis drew from data collected between 2005 and 2016. The study examined the impact of uranium on mortality from cerebrovascular diseases using various statistical approaches, including Cox regression to assess linear relationships within metal mixtures. It also evaluated the role of lipid-adjusted plutonium (LAP) as a mediator and verified the persistence of associations across different subgroups. The study encompassed 4312 participants and established a significant direct link between uranium levels and mortality from cerebrovascular diseases (hazard ratio (95%CI) = 20.4243 (20.1347-20.7181), P = .0266). It also identified LAP as a mediating factor in the relationship, accounting for a mediated proportion of 1.35%. The findings highlight a pivotal connection between uranium exposure and increased mortality due to cerebrovascular diseases, with LAP playing a significant intermediary role.

PMID:39705492 | DOI:10.1097/MD.0000000000040888

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Development and validation of the renal dosing questionnaire (RDQ-13) for pharmacists

Medicine (Baltimore). 2024 Dec 20;103(51):e41004. doi: 10.1097/MD.0000000000041004.

ABSTRACT

Pharmacists, as an integral part of the healthcare team, can play a crucial role in preventing drug-related problems in patients with chronic kidney disease that arise due to inappropriate doses. This study aimed to develop and validate a new tool, the renal dosing questionnaire (RDQ-13), for pharmacists working across hospital, community, and retail pharmacy settings. A cross-sectional study was conducted from January to March 2023 among pharmacists working in different settings. The RDQ-13 scale consists of 3-sections, encompassing demographic details, a knowledge section with 6 domains, each having 4 questions with the choice of “yes/no,” an attitude section featuring a Likert scale for 4 items, and a perception section featuring a Likert scale for 3 items. The assessment of construct and discriminative validity was performed along with testing for reliability. The average variance extracted value and the composite reliability value were used for convergent validity. A total of 65 pharmacists completed the RDQ-13, but at retest n = 2 participants were dropped (response rate at retest was 96.9%). Exploratory factor analysis revealed 3-factor loadings with 59.1% of the variance, whereas the Kaiser-Mayer-Olkin value was 0.60. The Cronbach alpha value of 0.700 indicates good internal consistency, whereas the intraclass correlation coefficient (ICC) for the test and retest showed that most domains/scores were statistically significant (P < .001), showing an excellent agreement between the test and retest. The RDQ-13 underwent extensive validation through a cross-sectional survey, demonstrating high content and face validity. The scale showed consistent responses over time (test-retest stability) and good internal consistency.

PMID:39705490 | DOI:10.1097/MD.0000000000041004