Category: Statistics

Explore (NY). 2022 Sep 8:S1550-8307(22)00162-8. doi: 10.1016/j.explore.2022.09.001. Online ahead of print.

ABSTRACT

CONTEXT: The aim of neonatal pain management is to reduce pain and help the baby cope with pain.

OBJECTIVE: This study aimed to determine the effect of Helfer skin tap technique (HSTT) on hepatitis B vaccine intramuscular (IM) injection pain in neonetes.

DESIGN: Randomized controlled study SETTING: This study was conducted with neonatal infants born vaginally in the delivery room of a state hospital in Turkey.

PARTICIPANTS: This study was conducted total 60 neonates including 30 in the HSTT group and 30 in the Routine Technique (RT) group.

INTERVENTIONS: Participants were randomized into the HSTT group and the Routine Technique (RT) group.

MAIN OUTCOME MEASURES: Data were collected using a questionnaire form and the Neonatal Infant Pain Scale (NIPS).

RESULTS: While the means of the total pain scores in the HSTT group were found to be 1.73 ± 2.04 during injection and 1.73 ± 0.98 after injection, in the RT group, the mean scores were 5.56 ± 0.92 during injection and 4.90 ± 1.25 after injection. The difference between the groups arising in the comparison of means of the total pain scores obtained during and after injection in HSTT and RT groups was determined to be statistically significant (p <0.05).

CONCLUSION: In conclusion, HSTT was proven to be effective in reducing hepatitis B vaccine intramuscular (IM) injection pain in neonates. This study demonstrates that HSTT is associated with reduced pain in newborns during hepatitis B vaccine IM injections.

PMID:36115789 | DOI:10.1016/j.explore.2022.09.001

Eur Urol Focus. 2022 Sep 14:S2405-4569(22)00204-8. doi: 10.1016/j.euf.2022.08.015. Online ahead of print.

ABSTRACT

BACKGROUND: Bladder cancer (BC) treatment algorithms depend on accurate tumor staging. To date, computed tomography (CT) is recommended for assessment of lymph node (LN) metastatic spread in muscle-invasive and high-risk BC. However, the diagnostic efficacy of radiologist-evaluated CT imaging studies is limited.

OBJECTIVE: To evaluate the performance of quantitative radiomics signatures for detection of LN metastases in BC.

DESIGN, SETTING, AND PARTICIPANTS: Of 1354 patients with BC who underwent radical cystectomy (RC) with lymphadenectomy who were screened, 391 with pathological nodal staging (pN0: n = 297; pN+: n = 94) were included and randomized into training (n = 274) and test (n = 117) cohorts. Pelvic LNs were segmented manually and automatically. A total of 1004 radiomics features were extracted from each LN and a machine learning model was trained to assess pN status using histopathology labels as the ground truth.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Radiologist assessment was compared to radiomics-based analysis using manual and automated LN segmentations for detection of LN metastases in BC. Statistical analysis was performed using the receiver operating characteristics curve method and evaluated in terms of sensitivity, specificity, and area under the curve (AUC).

RESULTS AND LIMITATIONS: In total, 1845 LNs were manually segmented. Automated segmentation correctly located 361/557 LNs in the test cohort. Manual and automatic masks achieved an AUC of 0.80 (95% confidence interval [CI] 0.69-0.91; p = 0.64) and 0.70 (95% CI: 0.58-0.82; p = 0.17), respectively, in the test cohort compared to radiologist assessment, with an AUC of 0.78 (95% CI 0.67-0.89). A combined model of a manually segmented radiomics signature and radiologist assessment reached an AUC of 0.81 (95% CI 0.71-0.92; p = 0.63).

CONCLUSIONS: A radiomics signature allowed discrimination of nodal status with high diagnostic accuracy. The model based on manual LN segmentation outperformed the fully automated approach.

PATIENT SUMMARY: For patients with bladder cancer, evaluation of computed tomography (CT) scans before surgery using a computer-based method for image analysis, called radiomics, may help in standardizing and improving the accuracy of assessment of lymph nodes. This could be a valuable tool for optimizing treatment options.

PMID:36115774 | DOI:10.1016/j.euf.2022.08.015

Br J Clin Pharmacol. 2022 Sep 17. doi: 10.1111/bcp.15538. Online ahead of print.

ABSTRACT

BACKGROUND: Antiretroviral (ARV) therapy reduces inflammation and immune activation in people with HIV, but not down to the levels observed in negative people. Limited drug penetration within tissues has been argued as potential mechanism of persistent inflammation. Data on the inflammation role on ARV plasma/intracellular (IC) pharmacokinetics (PK) through to expression of cytochrome P450 3A/membrane transporters are limited. Aim of this study was to investigate the correlation between inflammation markers (IM) and plasma/IC PK of ARVs regimen in HIV-positive patients.

METHODS: We included ART-experienced patients switching to 3 different ARV regimens. Plasma and IC ARV drugs concentration means at the end of dosing interval (T0), IM on samples concomitantly with ARV PK determination: sCD14, CRP, IL-6 and LPS were analysed.

RESULTS: Plasma and IC drug concentrations were measured in 60 samples. No significative differences between CRP, sCD14, IL-6 and LPS values in the 3 arms were observed. A significant inverse correlation between tenofovir plasma concentration and sCD14 (rho=-0.79, p<0.001), and between DRV IC/plasma ratio and Log10 IL-6 concentrations (rho= -0.36, p=0.040), and a borderline statistical significant positive trend between DRV plasma concentration and sCD14 (rho=0.31, p=0.070) were suggested. Furthermore, a borderline statistical significant inverse trend between DTG IC concentrations and sCD14 (rho=-0.34, p=0.090) was observed in 24 patients on DTG-based-triple therapy.

CONCLUSIONS: Our preliminary data support the hypothesis of lower DRV and DTG IC concentrations and lower TFV plasma exposure in patients with higher plasma IM suggesting an interplay between HIV drug penetration and persistent inflammation in cART-treated HIV-positive patients.

PMID:36115063 | DOI:10.1111/bcp.15538

J Neurosurg Pediatr. 2022 Sep 16:1-9. doi: 10.3171/2022.8.PEDS22144. Online ahead of print.

ABSTRACT

OBJECTIVE: Intraventricular hemorrhage (IVH) is a neurovascular complication due to premature birth that results in blood clots forming within the ventricles. Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) has been investigated as a noninvasive treatment to lyse clots. The authors designed and constructed a robotic MRgHIFU platform to treat the neonatal brain that facilitates ergonomic patient positioning. The clot lysis efficacy of the platform is quantified using a brain phantom and clinical MRI system.

METHODS: A thermosensitive brain-mimicking phantom with ventricular cavities was developed to test the clot lysis efficacy of the robotic MRgHIFU platform. Whole porcine blood was clotted within the phantom’s cavities. Using the MRgHIFU platform and a boiling histotripsy treatment procedure (500 W, 10-msec pulse duration, 1.0% duty cycle, and 40-second duration), the clots were lysed inside the phantom. The contents of the cavities were vacuum filtered, and the remaining mass of the solid clot particles was used to quantify the percentage of clot lysis. The interior of the phantom’s cavities was inspected for any collateral damage during treatment.

RESULTS: A total of 9 phantoms were sonicated, yielding an average (± SD) clot lysis of 97.0% ± 2.57%. Treatment resulted in substantial clot lysis within the brain-mimicking phantoms that were apparent on postsonication T2-weighted MR images. No apparent collateral damage was observed within the phantom after treatment. The results from the study showed the MRgHIFU platform was successful at lysing more than 90% of a blood clot at a statistically significant level.

CONCLUSIONS: The robotic MRgHIFU platform was shown to lyse a large percentage of a blood clot with no observable collateral damage. These results demonstrate the platform’s ability to induce clot lysis when targeting through simulated brain matter and show promise toward the final application in neonatal patients.

PMID:36115058 | DOI:10.3171/2022.8.PEDS22144

J Am Podiatr Med Assoc. 2022 Apr 27;112(2):19-159. doi: 10.7547/19-159.

ABSTRACT

BACKGROUND: Hypertension is a highly prevalent condition in the general population, conferring a high risk of significant morbidity and mortality. Associated with the condition are many well-characterized controllable and noncontrollable risk factors. This study aimed to identify the prevalence of hypertension in the outpatient podiatric medical clinic setting and to determine the relevance of hypertension risk factors in this setting.

METHODS: A survey tool was created to characterize relevant risk factors, and systolic and diastolic blood pressures were recorded. Descriptive statistics were generated after conclusion of enrollment. Analysis was also performed to determine the relationship between individual risk factors and systolic blood pressure.

RESULTS: Of the 176 patients, 56 (31.8%) had an incidentally high blood pressure at intake, including 18.5% of patients without a known history of hypertension and 38.5% with a known history of hypertension. Three risk factors were found to be significantly associated with increasing systolic blood pressure: weight (P = .022), stress level (P = .017), and presence of renal artery stenosis (P = .021). There was also a near-statistically significant inverse relationship between systolic blood pressure and amount of time spent exercising (P = .068).

CONCLUSIONS: Overall, a relatively high prevalence of incidental hypertension was identified, including among patients not previously diagnosed as having hypertension. Consideration of risk factors and awareness of the prevalence of the condition can be useful for practitioners, even as they manage presenting podiatric medical concerns. Future investigations may consider interventional or preventive strategies in the outpatient clinic setting.

PMID:36115033 | DOI:10.7547/19-159

J Am Podiatr Med Assoc. 2022 Apr 27;112(2):20-244. doi: 10.7547/20-244.

ABSTRACT

BACKGROUND: Plantar fasciitis is a common cause of musculoskeletal discomfort. Minimally invasive interventions are preferred as second-line treatments following failure of conservative management. We report on a novel technique of ultrasound-guided percutaneous release of the medial third of the plantar fascia with the use of a fine cutting device for the treatment of persistent plantar fasciitis.

METHODS: This is a retrospective case series of all patients treated with the technique between 2013 and 2015. Patients had failed conservative management for a minimum of 6 months. The procedure was performed in an outpatient setting under local anesthesia. Under continuous ultrasound guidance, release of the medial third of the plantar fascia from the calcaneus was performed using an ophthalmic V-Lance knife through a medial stab wound entry point.

RESULTS: Fifteen patients (six men and nine women) with an average age of 54.7 years were included. The mean (standard deviation [SD]) visual analogue scale score for pain improved significantly, from 66.0 (SD, 18.8) preoperatively to each consecutive follow-up point: 29.3 (SD, 25.2) at 2 weeks, 30.0 (SD, 27.8) at 4 weeks, and 34.0 (SD, 26.1) at 12 weeks (P < .001). The mild increase in visual analogue scale score between 4 and 12 weeks was statistically significant (P = .018). Average duration of required analgesia was 5.5 days and average time required to return to usual activities was 5.7 days. Two patients suffered with refractory neuropathic pain over the lateral border of the foot without any obvious abnormality.

CONCLUSIONS: Ultrasound-guided percutaneous release with the use of a fine cutting device could be an alternative option for the treatment of persistent plantar fasciitis. The technique is not without complications, and a mild but statistically significant decline in pain levels from early to short term has been detected. Therefore, the long-term outcomes of this technique need to be investigated before we can advocate its routine use.

PMID:36115031 | DOI:10.7547/20-244

Angew Chem Int Ed Engl. 2022 Sep 17. doi: 10.1002/anie.202205726. Online ahead of print.

ABSTRACT

α-Synuclein (α-syn) is an intrinsically disordered protein (IDP) that undergoes liquid-liquid phase separation (LLPS), fibrillation, and forms insoluble intracellular Lewy’s bodies in neurons, which are the hallmark of Parkinson’s Disease (PD). Neurotoxicity precedes the formation of aggregates and might be related to α-syn LLPS. The molecular mechanisms underlying the early stages of LLPS are still elusive. To obtain structural insights into α-syn upon LLPS, we take advantage of cross-linking/mass spectrometry (XL-MS) and introduce an innovative approach, termed COMPASS (COMPetitive PAiring StatisticS). In this work, we show that the conformational ensemble of α-syn shifts from a ‘hairpin-like’ structure towards more ‘elongated’ conformational states upon LLPS. We obtain insights into the critical initial stages of LLPS and establish a novel mass spectrometry-based approach that will aid to solve open questions in LLPS structural biology.

PMID:36115020 | DOI:10.1002/anie.202205726

NMR Biomed. 2022 Sep 17:e4832. doi: 10.1002/nbm.4832. Online ahead of print.

ABSTRACT

INTRODUCTION: Monitoring renal allograft function after transplantation is key for early detection of allograft impairment, which in turn could contribute to preventing the loss of the allograft. Multiparametric renal MRI (mpMRI) is a promising non-invasive technique to assess and characterize renal physiopathology, however, few studies have employed mpMRI in renal allografts with stable function (maintained function over a long time period).

PURPOSE: To evaluate reproducibility of mpMRI in transplanted patients and to characterize normal values of the measured parameters. To estimate labeling efficiency of PCASL in the infrarenal aorta, using numerical simulations considering experimental measurements of aortic blood flow profiles.

METHODS: Subjects: Twenty transplanted patients with stable kidney function, maintained over one year. MRI protocol: Pseudo-Continuous Arterial Spin Labeling (PCASL), Intravoxel Incoherent Motion (IVIM) and T1 inversion recovery. Phase-contrast to measure aortic blood flow.

DATA ANALYSIS: renal blood flow (RBF), diffusion coefficient D, pseudo-diffusion coefficient D*, flowing fraction f and T1 maps were calculated and mean values were measured in the cortex and medulla. PCASL labeling efficiency was estimated from Bloch equations simulation.

STATISTICAL ANALYSIS: Reproducibility was assessed with the within-subject coefficient of variation, intra class correlation coefficient and Bland-Alman analysis. Correlations were evaluated using Pearson correlation coefficient. Significance level: P < 0.05.

RESULTS: Cortical reproducibility was very good for T1, D, RBF, moderate for f and low for D*, while medullary reproducibility was good for T1 and D. Significant correlations in the cortex between RBF and f (r=0.66), RBF and eGFR (r=0.64) and D* and eGFR (r=-0.57) were found.

CONCLUSION: Normal values of the measured parameters employing mpMRI protocol in transplanted kidney patients with stable function were characterized and the results showed good reproducibility of the techniques.

PMID:36115029 | DOI:10.1002/nbm.4832

Endocrine. 2022 Sep 17. doi: 10.1007/s12020-022-03184-8. Online ahead of print.

ABSTRACT

OBJECTIVES: The sensitivities of the pituitary to thyroxine feedback, and the thyroid to thyrotropin stimulation determine the free thyroxine /thyrotropin feedback loop and can be described mathematically by two curves. It is not well understood how the two curves combine in a healthy population with normal thyroid function to express the individual balance points that are observed. This study was directed at this issue testing the possibilities of random combination and directed linkage between the two curves.

METHODS: We reverse-engineered two sets of population data, on the assumption of independent combinations of thyroid and pituitary sensitivities, to obtain estimates of the curve describing thyroid sensitivity. Sensitivity studies were performed.

RESULTS: No analysis resulted in a physiologically feasible estimate of the curve describing thyroid sensitivity. There was evidence of linkage of the two curves in terms of their combination throughout the normal range. Thyroid response curves reflecting a low free thyroxine response to thyrotropin tended to be combined in individuals with thyrotropin curves reflecting a high thyrotropin response to free thyroxine, and vice versa.

CONCLUSIONS: Thyroid and pituitary sensitivities are linked, being combined in individuals in a non-random directed pattern. Direct mutual interaction may contribute to this linkage. This linkage precludes the derivation of the curves describing these sensitivities from population data of the free thyroxine and thyrotropin relationship and complicates their derivation by physiological experimentation. This linkage and probable interaction may also bestow evolutionary advantage by minimising inter-individual variation in free thyroxine levels and by augmenting homeostasis.

PMID:36115005 | DOI:10.1007/s12020-022-03184-8

Qual Life Res. 2022 Sep 17. doi: 10.1007/s11136-022-03252-6. Online ahead of print.

ABSTRACT

PURPOSE: A joint modeling approach is recommended for analysis of longitudinal health-related quality of life (HRQoL) data in the presence of potentially informative dropouts. However, the linear mixed model modeling the longitudinal HRQoL outcome in a joint model often assumes a linear trajectory over time, an oversimplification that can lead to incorrect results. Our aim was to demonstrate that a more flexible model gives more reliable and complete results without complicating their interpretation.

METHODS: Five dimensions of HRQoL in patients with esophageal cancer from the randomized clinical trial PRODIGE 5/ACCORD 17 were analyzed. Joint models assuming linear or spline-based HRQoL trajectories were applied and compared in terms of interpretation of results, graphical representation, and goodness of fit.

RESULTS: Spline-based models allowed arm-by-time interaction effects to be highlighted and led to a more precise and consistent representation of the HRQoL over time; this was supported by the martingale residuals and the Akaike information criterion.

CONCLUSION: Linear relationships between continuous outcomes (such as HRQoL scores) and time are usually the default choice. However, the functional form turns out to be important by affecting both the validity of the model and the statistical significance.

TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number NCT00861094.

PMID:36115002 | DOI:10.1007/s11136-022-03252-6