Tag: pubmed

J Am Assoc Lab Anim Sci. 2021 Jul 19. doi: 10.30802/AALAS-JAALAS-20-000151. Online ahead of print.

ABSTRACT

Although buprenorphine is the most frequently used opioid analgesic in common marmosets (Callithrix jacchus), thereis limited information in the literature supporting current dosing regimens used for this species. The purpose of this study was to determine the pharmacokinetic profiles of single-dose buprenorphine HCl administered intramuscularly (IM) at 0.01 mg/kg in 6 adult marmosets (1.8 to 12.8 y old; 2 males, 4 females) and subcutaneously (SQ) at 0.01 mg/kg in 6 adult marmosets(2.3-4.4 y old; 3 males, 3 females) by mass spectrometry. Blood was collected at multiple time points from 0.25 to 24 h from unsedated animals following a hybrid sparse-serial sampling design. The maximal observed plasma concentration of buprenorphine (Cmax) administered IM (2.57 ± 0.95 ng/mL) was significantly higher than administered SQ (1.47 ± 0.61 ng/mL). However, the time to Cmax (Tmax) was not statistically different between routes (17.4 ± 6 min for IM and 19.8 ±7.8 min for SQ). The time of the last quantifiable concentration of buprenorphine was 5 ± 1.67 h for IM compared with 6.33 ± 1.51 h for SQ, which was not statistically different. The mean buprenorphine plasma concentration-time curves were used to propose a dosing frequency of 4 to 6 h for buprenorphine at 0.01 mg/kg IM or SQ based on a theoretical therapeutic plasma concentration threshold of 0.1 ng/mL. Based on the mean pharmacokinetic parameters and plasma-concentration time curves, both IM and SQ routes of buprenorphine at this dose provide a rapid increase in the plasma concentration of buprenorphine above the therapeutic threshold, and may be more effective for acute rather than long-lasting analgesia. Further studies are neededto examine repeated dosing regimens and the efficacy of buprenorphine in common marmosets.

PMID:34281629 | DOI:10.30802/AALAS-JAALAS-20-000151

J Perinat Med. 2021 Jul 20. doi: 10.1515/jpm-2020-0468. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare mortality, morbidity and neurodevelopment by mode of delivery (MOD) for very preterm births with low prelabour risk of caesarean section (CS).

METHODS: The study was a population-based prospective cohort study in 19 regions in 11 European countries. Multivariable mixed effects models and weighted propensity score models were used to estimate adjusted odds ratios (aOR) by observed MOD and the unit’s policy regarding MOD. Population: Singleton vertex-presenting live births at 24 + 0 to 31 + 6 weeks of gestation without serious congenital anomalies, preeclampsia, HELLP or eclampsia, antenatal detection of growth restriction and prelabour CS for fetal or maternal indications.

RESULTS: Main outcome measures: A composite of in-hospital mortality and intraventricular haemorrhage (grade III/IV) or periventricular leukomalacia. Secondary outcomes were components of the primary outcome, 5 min Apgar score <7 and moderate to severe neurodevelopmental impairment at two years of corrected age. The rate of CS was 29.6% but varied greatly between countries (8.0-52.6%). MOD was not associated with the primary outcome (aOR for CS 0.99; 95% confidence interval [CI] 0.65-1.50) when comparing units with a systematic policy of CS or no policy of MOD to units with a policy of vaginal delivery (aOR 0.88; 95% CI 0.59-1.32). No association was observed for two-year neurodevelopment impairment for CS (aOR 1.15; 95% CI 0.66-2.01) or unit policies (aOR 1.04; 95% CI 0.63-1.70).

CONCLUSIONS: Among singleton vertex-presenting live births without medical complications requiring a CS at 24 + 0 to 31 + 6 weeks of gestation, CS was not associated with improved neonatal or long-term outcomes.

PMID:34280959 | DOI:10.1515/jpm-2020-0468

Oncology. 2021 Jul 19:1-9. doi: 10.1159/000517344. Online ahead of print.

ABSTRACT

INTRODUCTION: Patients with unresectable or recurrent gastric cancer who have an objective response (OR) to nivolumab monotherapy are expected to have a good long-term prognosis. However, the OR rate for nivolumab treatment is low at 11%, and there is a need for biomarkers to predict the treatment response. This study aimed to analyze the significance of systemic inflammation-related variables and clinicopathologic characteristics as predictive markers of response to nivolumab monotherapy in patients with advanced gastric cancer.

METHODS: In this retrospective cohort study, we enrolled 71 consecutive patients who received nivolumab monotherapy for unresectable or recurrent gastric cancer. Receiver operating characteristic curve analysis was performed to determine the cutoff values of systemic inflammation-related variables, predictors of treatment response, and other prognostic factors related to nivolumab therapy. We focused on systemic inflammation-related variables measured before nivolumab induction and 2 weeks after its first administration and performed multivariate analysis to assess whether they could be used as prognostic factors.

RESULTS: Multivariate analysis revealed that a lymphocyte-to-monocyte ratio (LMR) of ≤3.28 after 2 weeks of initial nivolumab treatment (2wLMR) is a statistically significant predictor of treatment response (p = 0.012). The progression-free survival (PFS) rate of patients with liver metastasis was significantly worse than that of the other patients (1-year PFS: 0.0 vs. 24.4%, respectively; p = 0.005). The overall survival (OS) of patients with a low 2wLMR was significantly longer than that in patients with a high 2wLMR (1-year OS: 37.4 vs. 18.9%, respectively; p = 0.022).

CONCLUSIONS: Thus, the 2wLMR could be a useful biomarker to predict response to nivolumab treatment and the prognosis of unresectable and recurrent gastric cancer.

PMID:34280933 | DOI:10.1159/000517344

Urol Int. 2021 Jul 19:1-7. doi: 10.1159/000517275. Online ahead of print.

ABSTRACT

BACKGROUND: This study investigates the effect of classical music, music of patients’ own choice, or no music on pain reduction during elective cystoscopy.

OBJECTIVES: The aim of the study was to describe the effect of listening to classical music, music of patients’ own choice, or no music on patient’s pain and satisfaction rates when carrying out an elective cystoscopy and the effect on the assessment capability of the performing urologist.

DESIGN, SETTING, AND PARTICIPANTS: This randomized trial included 127 patients undergoing elective cystoscopy at the Urological Department of the University Clinic of Munich between June 2019 and March 2020. Outcome Measurements and Statistical Analysis: Patients were assigned randomly to 3 groups: group I: listening to standardized classical music (n = 35), group II: listening to music according to the patients’ choice (n = 34), and control group III: no music (n = 44). Prior to cystoscopy, anxiety levels were assessed by the Beck Anxiety Inventory (BAI). The Visual Analog Scale (VAS, range 1-100) was used for a self-assessment of pain, discomfort, and satisfaction. Statistical analysis was done with Spearman’s rank correlation and t-tests.

RESULTS AND LIMITATIONS: The median age was 63 (range 27-91) years. The duration of cystoscopy was 5.7 (1-30) min. Patients had undergone a median of 2.3 cystoscopies in the past. Between giving informed consent and cystoscopy, patients had to wait for a median of 64 (0-260) min. The median VAS pain score was significantly lower in group I at 1.7 and group II at 2.3 versus 5.2 in the control group III (p < 0.001). The control group III had significantly worse pain and patient satisfaction rates compared with groups I and II. Group I had a significant lower VAS pain score than groups II and III (p < 0.001). Classical music also increased the assessment capability of the preforming urologist.

CONCLUSIONS: Listening to music during elective cystoscopy significantly reduces pain and distress and leads to higher patient and surgeon satisfaction. We recommend listening to classical music or music chosen by the patients during outpatient flexible/rigid cystoscopy in daily clinical routine. Patient Summary: In this study, we found that patients who listened to classical music or music of their own choice while undergoing a cystoscopy showed significant reduction of pain and distress.

PMID:34280934 | DOI:10.1159/000517275

Asian J Psychiatr. 2021 Jul 10;63:102753. doi: 10.1016/j.ajp.2021.102753. Online ahead of print.

ABSTRACT

The study provides a comprehensive analysis of trends of the global scientific research on the effects of the COVID-19 Pandemic on Mental health from the first published literature up to June 27, 2021. Relevant documents were searched using mesh terms based on the query of two searches, “COVID-19 & Mental Health” scenarios joined by the Boolean operator “AND” to retrieve relevant literature using the Web of Science (WOS) database. Bibliometric indicators were analyzed using HistCite, Bibliometrix, an R package, and VOSviewer.Var1.6.6. A total of 5449 publications with an h-index of 97 were retrieved from the database. Overall, articles retrieved were written by 24123 authors, published in 1224 journals, 132 countries represented, and 10.01 average citations per document. Kings College London led the list of contributing institutions with 76 articles. The United States Department of Human Health Services, the National Institutes of Health, the USA, and the National Natural Science Foundation of China was the top funding agencies that enhanced research on mental health and supported more than 180 articles. USA contributed the most significant proportion 1157 (21.23 %) of COVID-19 Pandemic on Mental health publication closely followed by China in the number of publications 741(13.60 %). The study provides insight into the global research perspective for the scientific progress on the COVID-19 Pandemic public health emergency and the mental health issues, thus significantly impacting and supporting intervention towards improving people’s mental health post-COVID-19 outbreak.

PMID:34280888 | DOI:10.1016/j.ajp.2021.102753

Phys Med Biol. 2021 Jul 19. doi: 10.1088/1361-6560/ac15a5. Online ahead of print.

ABSTRACT

In radiopharmaceutical treatments α-particles are employed to treat tumor cells. However, the mechanism that drives the biological effect induced is not well known. Being ionizing radiation, α-particles can affect biological organisms by producing damage to the DNA, either directly or indirectly. Following the principle that microdosimetry theory accounts for the stochastic way in which radiation deposits energy in sub-cellular sized volumes via physical collisions, we postulate that microdosimetry represents a reasonable framework to characterize the statistical nature of direct damage induction by α-particles to DNA. We used the TOPAS-nBio Monte Carlo package to simulate direct damage produced by monoenergetic alpha particles to different DNA structures. In separate simulations, we obtained the frequency-mean lineal energy (yF) and dose-mean lineal energy (yD) of microdosimetric distributions sampled with spherical sites of different sizes. The total number of DNA strand breaks, double strand breaks and complex strand breaks per track were quantified and presented as a function of either yF or yD. The probability of interaction between a track and the DNA depends on how the base pairs are compacted. To characterize this variability on compactness, spherical sites of different size were used to match these probabilities of interaction, correlating the size-dependent specific energy (z) with the damage induced. The total number of DNA strand breaks per track was found to linearly correlate with yF and zF when using what we defined as effective volume as microdosimetric site, while the yield of DSB per unit dose linearly correlated with yD or zD, being larger for compacted than for unfolded DNA structures. The yield of complex breaks per unit dose exhibited a quadratic behavior with respect to yD and a greater difference among DNA compactness levels. Microdosimetric quantities correlate with the direct damage imparted on DNA.

PMID:34280910 | DOI:10.1088/1361-6560/ac15a5

Stereotact Funct Neurosurg. 2021 Jul 19:1-7. doi: 10.1159/000517426. Online ahead of print.

ABSTRACT

INTRODUCTION: Spinal cord stimulation (SCS) is an efficacious chronic pain treatment most commonly used in middle-aged patients. Results from previous studies that investigated SCS’ effects in older patient populations have been equivocal. We examine whether SCS outcomes correlate with age.

METHODS: We retrospectively examined prospectively collected outcomes from 189 patients who underwent SCS at Albany Medical Center between 2012 and 2020. The patients completed the Numerical Rating Scale (NRS), McGill Pain Questionnaire (MPQ), Oswestry Disability Index (ODI), Beck Depression Inventory (BDI), and Pain Catastrophizing Scale (PCS) preoperatively and 1 year postoperatively. The mean percent change in each outcome was determined and compared via a regression analysis to determine relationships between patient age and each respective outcome metrics. Demographics were compared between patients aged under 65 versus those aged 65 and older via χ2 tests.

RESULTS: All subjects demonstrated the expected improvement on NRS, BDI, PCS, and MPQ from baseline to 1-year follow-up, with several demonstrating statistically significant changes: NRS-worst pain (18.66%, p < 0.001), NRS-least pain (26.9%, p < 0.001), NRS-average pain (26.9%, p < 0.01), NRS-current pain (26.4%, p < 0.001), ODI (19.6%, p < 0.001), PCS (29.8%, p < 0.001), and MPQ (29.4%, p < 0.001). There was no significant difference between patients aged under 65 versus those aged 65 and older based on lead type (p = 0.454). Six patients (3.1%) had lead migration, one of whom was 65 or older. Regression analysis revealed improvements in MPQ-sensory and MPQ-affective scores as age increased (p < 0.001, R2 = 0.09; p = 0.046, R2 = 0.05, respectively). Age did not correlate with NRS, ODI, BDI, or PCS. Diagnosis, spinal level of SCS, and lead type were not found to influence any respective outcome measure based on covariate analysis.

CONCLUSION: This study represents the largest study where age was correlated to specific pain, depression, and disability outcomes following SCS. We provide evidence that SCS outcomes are equivalent, or better, in older patients following SCS. Based on these findings, SCS is a viable option for treatment of chronic pain in elderly patient populations.

PMID:34280929 | DOI:10.1159/000517426

Cortex. 2021 May 1;142:221-236. doi: 10.1016/j.cortex.2021.03.033. Online ahead of print.

ABSTRACT

Many emerging technologies are attempting to leverage the tactile domain to convey complex spatiotemporal information translated directly from the visual domain, such as shape and motion. Despite the intuitive appeal of touch for communication, we do not know to what extent the hand can substitute for the retina in this way. Here we ask whether the tactile system can be used to perceive complex whole hand motion stimuli, and whether it exhibits the same kind of established perceptual biases as reported in the visual domain. Using ultrasound stimulation, we were able to project complex moving dot percepts onto the palm in mid-air, over 30 cm above an emitter device. We generated dot kinetogram stimuli involving motion in three different directional axes (‘Horizontal’, ‘Vertical’, and ‘Oblique’) on the ventral surface of the hand. Using Bayesian statistics, we found clear evidence that participants were able to discriminate tactile motion direction. Furthermore, there was a marked directional bias in motion perception: participants were both better and more confident at discriminating motion in the vertical and horizontal axes of the hand, compared to those stimuli moving obliquely. This pattern directly mirrors the perceptional biases that have been robustly reported in the visual field, termed the ‘Oblique Effect’. These data demonstrate the existence of biases in motion perception that transcend sensory modality. Furthermore, we extend the Oblique Effect to a whole hand scale, using motion stimuli presented on the broad and relatively low acuity surface of the palm, away from the densely innervated and much studied fingertips. These findings highlight targeted ultrasound stimulation as a versatile method to convey potentially complex spatial and temporal information without the need for a user to wear or touch a device.

PMID:34280867 | DOI:10.1016/j.cortex.2021.03.033

Gait Posture. 2021 Jul 16;89:126-131. doi: 10.1016/j.gaitpost.2021.07.007. Online ahead of print.

ABSTRACT

BACKGROUND: Increased terminal swing knee flexion (TSKF) impacts on step length, walking efficiency and may lead to knee flexion in stance in cerebral palsy (CP). Surgical lengthening of the hamstrings is often used to address this issue, but outcomes are inconsistent. There is an established association between TSKF and functional shortening or reduced lengthening velocity of the hamstrings. However, the aetiology of increased TSKF in CP is complex and additional associated factors are not well understood. An examination of clinical and kinematic factors associated with increased TSKF may demonstrate this complexity, highlight the multifactorial nature of this feature and provide a basis for enhanced treatment decision making.

RESEARCH QUESTION: What kinematic and clinical factors are associated with TSKF in individuals with CP?.

METHODS: A retrospective database review was conducted. Individuals with bilateral CP were identified and a subset was extracted which represented the full spectrum of degree of TSKF in the database. The total dataset for analysis was n = 88. Associations between absolute clinical and kinematic data and TSKF were explored using correlation analysis, linear and multivariate regression. Time series data were examined across quartiles using statistical parametric mapping analysis of variance (SPM ANOVA).

RESULTS: Increased TSKF was associated with overall gait impairment (GDI), degree of knee flexion throughout the stride, knee extension velocity, hamstring lengthening characteristics and functional status (GMFCS). There was no relationship to walking speed or clinical measures of hamstring extensibility on clinical assessment.

SIGNIFICANCE: TSKF is associated with multiple factors which clinicians need to consider when devising treatment strategies. Caution is advised when relying on degree of TSKF to independently guide surgical decision-making.

PMID:34280883 | DOI:10.1016/j.gaitpost.2021.07.007

Comput Biol Med. 2021 Jul 12;135:104648. doi: 10.1016/j.compbiomed.2021.104648. Online ahead of print.

ABSTRACT

BACKGROUND: Machine learning (ML) and artificial intelligence are emerging as important components of precision medicine that enhance diagnosis and risk stratification. Risk stratification tools for hypertrophic cardiomyopathy (HCM) exist, but they are based on traditional statistical methods. The aim was to develop a novel machine learning risk stratification tool for the prediction of 5-year risk in HCM. The goal was to determine if its predictive accuracy is higher than the accuracy of the state-of-the-art tools.

METHOD: Data from a total of 2302 patients were used. The data were comprised of demographic characteristics, genetic data, clinical investigations, medications, and disease-related events. Four classification models were applied to model the risk level, and their decisions were explained using the SHAP (SHapley Additive exPlanations) method. Unwanted cardiac events were defined as sustained ventricular tachycardia occurrence (VT), heart failure (HF), ICD activation, sudden cardiac death (SCD), cardiac death, and all-cause death.

RESULTS: The proposed machine learning approach outperformed the similar existing risk-stratification models for SCD, cardiac death, and all-cause death risk-stratification: it achieved higher AUC by 17%, 9%, and 1%, respectively. The boosted trees achieved the best performing AUC of 0.82. The resulting model most accurately predicts VT, HF, and ICD with AUCs of 0.90, 0.88, and 0.87, respectively.

CONCLUSIONS: The proposed risk-stratification model demonstrates high accuracy in predicting events in patients with hypertrophic cardiomyopathy. The use of a machine-learning risk stratification model may improve patient management, clinical practice, and outcomes in general.

PMID:34280775 | DOI:10.1016/j.compbiomed.2021.104648