Tag: pubmed

Pharm Stat. 2021 Mar 24. doi: 10.1002/pst.2119. Online ahead of print.

ABSTRACT

Umbrella trials are an innovative trial design where different treatments are matched with subtypes of a disease, with the matching typically based on a set of biomarkers. Consequently, when patients can be positive for more than one biomarker, they may be eligible for multiple treatment arms. In practice, different approaches could be applied to allocate patients who are positive for multiple biomarkers to treatments. However, to date there has been little exploration of how these approaches compare statistically. We conduct a simulation study to compare five approaches to handling treatment allocation in the presence of multiple biomarkers – equal randomisation; randomisation with fixed probability of allocation to control; Bayesian adaptive randomisation (BAR); constrained randomisation; and hierarchy of biomarkers. We evaluate these approaches under different scenarios in the context of a hypothetical phase II biomarker-guided umbrella trial. We define the pairings representing the pre-trial expectations on efficacy as linked pairs, and the other biomarker-treatment pairings as unlinked. The hierarchy and BAR approaches have the highest power to detect a treatment-biomarker linked interaction. However, the hierarchy procedure performs poorly if the pre-specified treatment-biomarker pairings are incorrect. The BAR method allocates a higher proportion of patients who are positive for multiple biomarkers to promising treatments when an unlinked interaction is present. In most scenarios, the constrained randomisation approach best balances allocation to all treatment arms. Pre-specification of an approach to deal with treatment allocation in the presence of multiple biomarkers is important, especially when overlapping subgroups are likely.

PMID:33759353 | DOI:10.1002/pst.2119

Int J Numer Method Biomed Eng. 2021 Mar 24:e3458. doi: 10.1002/cnm.3458. Online ahead of print.

ABSTRACT

This paper shows how to obtain in addition to the standard deviations available after a data assimilation procedure based on the ensemble Kalman filter, an apportioning of the total uncertainty in the outputs of a patient-specific blood flow model into small portions of uncertainty due to input parameters. Statistical indicators generally used for identifying the importance of numerical parameters, namely the Sobol’ first order and total indices, are introduced and discussed. These allow the identification of the importance rank of the different input parameters for the patient-specific blood flow model, as well as the influence of the interactions between these parameters on the model output variance. The results show that knowing the importance rank of the model input parameters during the assimilation procedure is useful to avoid unnecessary over-solving and to find a suitable stopping criterion in clinical situations where faster diagnosis is always requested. Indeed, the work permits to reduce typically by a factor of six the time to solution and most importantly with very limited extra calculation using already available information. This article is protected by copyright. All rights reserved.

PMID:33759369 | DOI:10.1002/cnm.3458

Brain Behav. 2021 Mar 23:e01880. doi: 10.1002/brb3.1880. Online ahead of print.

ABSTRACT

OBJECTIVES: Excessive daytime sleepiness (EDS) affects a large percentage of Parkinson’s disease (PD) patients, and it is enhanced by dopamine agonist drugs. Currently, there is no treatment of choice for EDS in PD. Our aim was to check the clinical impression that some patients who were given selegiline, a selective inhibitor of monoamine oxidase B, experienced an improvement in their daytime somnolence.

METHODS: In the present study, we retrospectively identified 45 Parkinson’s disease patients (21 females and 24 males) among those referred to the PD Center in Varese that (a) showed excessive daytime sleepiness, usually developed after the introduction of a dopamine agonist, (b) were given selegiline 10 mg to improve their treatment schedule independently of excessive sleepiness, and (c) in whom the Epworth Sleepiness Scale (ESS) and the Parkinson’s Disease Sleep Scale (PDSS) scores were available both before and 3 months after the introduction of selegiline.

RESULTS: We compared the corresponding scores (ESS, PDSS, and UPDRS III) evaluated before and 3 months after the introduction of selegiline by the nonparametric Mann-Whitney U test: The differences showed a statistically significant improvement of somnolence but no change in the UPDRS III scores.

CONCLUSION: Despite some limitations, our data suggest that selegiline may be a valuable add-on therapy in PD patients to reduce their daytime somnolence.

PMID:33759401 | DOI:10.1002/brb3.1880

J Mother Child. 2021 Jan 29;23(2):117-124. doi: 10.34763/devperiodmed.20192302.117124.

ABSTRACT

OBJECTIVE: The aim of the study was to compare the advantages of semi-elevated and side-lying positioning during bottle-feeding of preterm infants ≤34 weeks gestational age (34+0/7).

MATERIAL AND METHODS: The study included six neonates (n=6) bom ≤34 weeks gestational age who reached the age ≥32 weeks of postmenstrual age on the day when the study began and were hospitalized in the neonatology ward. Four bottle-feeding sessions were tested in each of the newborns: two in the side-lying and two in the semi-elevated position. The position for the first test was chosen randomly. For each of the positions twelve feeding sessions were examined and each preterm infant hod bottle-feeding sessions analyzed both in the semi-elevated and side-lying positions. The level of saturation and heart rate were measured as the parameters indicative of the newborn’s physiological stability. The factors determining the qualitative aspect of feeding included the level of the newborn’s alertness and the occurrence of choking episodes. The amount of food consumed and the duration of the feeding were also recorded.

RESULTS: The side-lying position was more effective with regard to the totol amount of sustenance consumed as compared to the semi-elevated feeding position and the study result was statistically significant (p=0.007). The difference in the number of chokes between the study groups was not statistically significant, although a trend towards a reduced number of choking episodes was observed among infants fed in the side-lying position (p=0.090). There were no significant differences in oxygen saturation, heart rate and level of activity between the study groups.

CONCLUSIONS: The effects of this pilot study demonstrate the efficacy of the side-lying feeding position regarding the final amount of milk intake. The side-lying position may also reduce the number of choking episodes during the feeding. The results suggest the need to extend the study in order to confirm the potential benefits of using the side-lying position.

PMID:33759406 | DOI:10.34763/devperiodmed.20192302.117124

J Appl Res Intellect Disabil. 2021 Mar 23. doi: 10.1111/jar.12866. Online ahead of print.

ABSTRACT

PURPOSE: People with Down syndrome (DS) have a unique medical profile which may impact views of health. We aimed to explore the use of global health measures in DS.

METHODS: Prospective survey in the Mass General Hospital Down Syndrome Program (MGH DSP) from December 2018 to July 2019 with Patient Reported Outcomes Measurement Information System (PROMIS)® instruments of global health. Analyses included use of scoring manuals, descriptive statistics and dependent samples t test.

RESULTS: Seventeen adolescents, 48 adults with DS and 88 caregivers returned surveys; 137 were complete. Incomplete responses and notes showed limitations of the instruments in this population. Global health T-scores did not differ from the available comparative standardized scores to these measures from PROMIS® reference population (p > 0.05).

CONCLUSIONS: In the MGH DSP, pilot global health instruments were completed by some adults with DS and caregivers, with some limitations and scores similar to the PROMIS® reference population.

PMID:33759305 | DOI:10.1111/jar.12866

Int J Clin Pract. 2021 Mar 23:e14170. doi: 10.1111/ijcp.14170. Online ahead of print.

ABSTRACT

AIMS: The aim of the study was to evaluate the possible changes in sleep behavior and nutrition in children during the pandemic period.

METHODS: 114 parents who accepted to participate in the study aged 18 and over and who had children between the ages of 6 and 16 were included in the study. A questionnaire was carried out after written consents were obtained. In the first part of the questionnaire, there were a total of 9 questions including socio-demographic information and nutritional characteristics, and the second part included the “Sleep Disturbance Scale for Children” (SDSC). The data were analyzed with the SPSS 20 statistical program.

RESULTS: The total number of participants was 114 parents; 64 (56%) of the children were girls and 50 (43.9%) were boys. Among the participants, the number of children who had COVID-19 was 38 (33.3%). There was no statistically significant relationship between going through COVID-19 status and the variables examined in general. The proportion of participants who stated that if the pandemic period was prolonged, COVID-19 would not change their diet was found to be statistically significant (p=0.038). The SDSC score was found to be significantly high in girls (p<0.05).

CONCLUSION: Sleep and nutritional disorders affect the quality of life for all ages for both genders, and their importance increases even more in extraordinary periods such as pandemic. Sleep problems increasing especially with an accompanying anxiety state may lead to developmental problems as well as deepening psychological disorders.

PMID:33759311 | DOI:10.1111/ijcp.14170

Int J Clin Pract. 2021 Mar 24:e14161. doi: 10.1111/ijcp.14161. Online ahead of print.

ABSTRACT

OBJECTIVE: Our study was carried out on patients admitted to the emergency ward with acute stroke symptoms that were subsequently diagnosed with cerebrovascular disease. We aimed to examine the relationship between these patients’ admission lactate levels and their 1, 3, and 12-month mortality rates in order to evaluate the prognostic value of lactate levels.

METHODS: Our data was obtained retrospectively from 568 patients diagnosed with acute ischemic stroke at our emergency department between 01/01/2017 and 01/01/2018. Patient data was accessed via the hospital patient database. Included patients’ files were assessed for examination and history taken at admission, comorbid diseases, demographic characteristics, treatments utilized, and laboratory results. Hyperlactatemia was defined as a lactate level of over 2mmol/L. The relationship between lactate levels and survival was investigated. Patients’ complication rates after discharge were assessed alongside their 1, 3, and 12-month mortality.

RESULTS: Our study assessed 568 patients. Out of these patients, 400 patients met our inclusion criteria and constituted the study population. These patients were separated into two groups according to their lactate levels. The hyperlactatemic group had a statistically significant increase in 1, 3, and 12-month mortality rates in comparison to the other group.

CONCLUSIONS: Our study found that hyperlactatemia was associated with a higher risk of 1, 3, and 12 month mortality, suggesting that it has predictive prognostic value. In the future, we believe that prospective observational studies and/or large-scale retrospective studies will be of great value in providing more insight into this topic.

PMID:33759312 | DOI:10.1111/ijcp.14161

Eur J Neurol. 2021 Mar 23. doi: 10.1111/ene.14834. Online ahead of print.

ABSTRACT

BACKGROUND: Alzheimer’s disease (AD) is considered a clinical and biological continuum identified via cerebrospinal fluid (CSF) or imaging biomarkers. Chronic hypoperfusion is held as one of the main features of Alzheimer’s disease, as part of the processes causing neuronal degeneration. The mechanism responsible for such condition is still debated, though recently a direct connection with amyloid peptides has been shown. Here we aimed at investigating whether measures of hypoperfusion change along the AD continuum.

METHODS: 70 patients with mild AD were recruited and stratified according to their CSF biomarkers profile – as indicated by the NIA-AA research framework – into patients with either isolated amyloid pathology (A+T-) or full-blown AD (A+T+), and further layered according to ApoE genotype. After evaluation of vascular risk factors, we performed a Trans Cranial Doppler (TCD) on each patient, to evaluate mean flow velocity and pulsatility index in the middle cerebral artery, and to calculate the breath holding index (BHI). Patients were compared to a cohort of 17 healthy controls.

RESULTS: The BHI was reduced in the AD continuum and resulted inversely correlated to CSF Aβ42 levels. Such correlation was stronger in the A+T+ than in A+T- group, and unexpectedly reached statistical significance only in the E3 and not in the E4 genotype carriers.

CONCLUSIONS: These results suggest a tight and effective relationship between Aβ42, vascular hypoperfusion, cerebrovascular reactivity and epsilon genotype.

PMID:33759296 | DOI:10.1111/ene.14834

Muscle Nerve. 2021 Mar 23. doi: 10.1002/mus.27241. Online ahead of print.

ABSTRACT

Pain as a significant symptom in patients with Periodic Paralysis- A cross-sectional survey INTRODUCTION/AIMS: Periodic paralysis (PP) is thought to be limited to episodes of muscle weakness, however, there are reports of fibromyalgia-like pain in PP. We aimed to evaluate pain and comorbid sleep, fatigue, and mood disorders in PP patients.

METHODS: We administered a cross-sectional survey to PP patients at the 2019 Periodic Paralysis Conference. The survey consisted of the Brief Pain Inventory (BPI), Widespread pain index (WPI), Pittsburgh Sleep Quality Index (PSQI), Modified Fatigue Impact Scale (MFIS) and ten question Center for Epidemiologic Studies Depression Scale (CESD-10). Descriptive statistics for PP patients were calculated and compared to prior studies.

RESULTS: 44 persons with PP took the survey. 52.3% reported a moderate to severe interference of pain on their lives. 45.5% of patients met the study criteria for fibromyalgia. Patients with SCN4A mutations had higher rates of fibromyalgia than the next most prevalent gene mutation, CACNA1S. In patients with pain, there were increased rates of comorbid fatigue, depression, and poor sleep quality.

DISCUSSION: Pain, akin to fibromyalgia, is a significant symptom of PP and can affect quality of life. Pain in PP was more prevalent than in the general population, at a rate comparable to other chronic neuromuscular disease groups. PP patients could benefit from a multidisciplinary approach to assess their pain, sleep, fatigue and mood.

PMID:33759219 | DOI:10.1002/mus.27241

Eur J Neurosci. 2021 Mar 23. doi: 10.1111/ejn.15199. Online ahead of print.

ABSTRACT

Emotion regulation is related to recovery after mild traumatic brain injury (mTBI). This longitudinal tractography study examined white matter tracts subserving emotion regulation across the spectrum of mTBI, with a focus on persistent symptoms. Four groups were examined: (1) symptomatic (n=33) and (2) asymptomatic (n=20) patients with uncomplicated mTBI (i.e., no lesions on computed tomography (CT)), (3) patients with CT-lesions in the frontal areas (n=14), and (4) healthy controls (n=20). Diffusion and conventional MRI were performed approximately one and three months post-injury. Whole brain deterministic tractography followed by region of interest analyses were used to identify forceps minor, uncinate fasciculus, and cingulum bundle as tracts of interest. An adjusted version of the ExploreDTI Atlas Based Tractography method was used to obtain reliable tracts for every subject. Mean fractional anisotropy (FA), radial and axial diffusivity (MD, RD, AD), and number of streamlines were studied per tract. Linear mixed models showed lower FA, and higher MD, and RD of the right uncinate fasciculus in asymptomatic patients with uncomplicated mTBI relative to symptomatic patients and healthy controls. Diffusion alterations were most pronounced in the group with frontal lesions on CT, particularly in the forceps minor and uncinate fasciculus; these effects increased over time. Within the group of patients with uncomplicated mTBI, there were no associations of diffusion measures with number of symptoms nor with lesions on conventional MRI. In conclusion, mTBI can cause microstructural changes in emotion regulation tracts, however, no explanation was found for the presence of symptoms.

PMID:33759227 | DOI:10.1111/ejn.15199