Association between frailty and sleep quality in people living with multiple sclerosis and obesity: An observational cross-sectional study.

BACKGROUND: A majority of the people with multiple sclerosis (pwMS) experience sleep disturbances. Frailty is also common in pwMS. The geriatric literature strongly suggests that frailty is associated with worse sleep outcomes in community-dwelling older adults, but this association has yet to be explored among pwMS. This study focused on examining the association between frailty and sleep quality in pwMS. METHODS: Seventy-six people with both MS and obesity (mean age: 47.6 ± 10.9 years, 81.6 % female, mean body mass index (BMI): 37.10 ± 5.5 kg/m2, mean Patient Determined Disease Steps (PDDS): 0.82 ± 1.20) were included in this cross-sectional secondary analysis. A comprehensive frailty index (FI) based on 41 health deficits from various health domains was calculated based on standardized procedures. Sleep quality was determined by the Pittsburgh Sleep Quality Index questionnaire (PSQI). RESULTS: Overall, 67.1 % of the participants were identified as non-frail (FI ≤ 0.25), and 32.9 % were identified as frail (FI > 0.25). A significant correlation was observed between FI scores and global PSQI scores (ρ = 0.43, p < 0.05). Cross-tabulation analyses revealed that frail participants had worse subjective sleep quality, sleep latency, habitual sleep efficiency, sleep disturbances, daytime dysfunction, and higher use of sleep medications compared to non-frail participants (p < 0.05). CONCLUSIONS: The current study identified a significant association between frailty and sleep quality in people with both MS and obesity with minimal disability. These findings underscore the importance of untangling the relationship between frailty and sleep quality in pwMS. These results could lead to a more targeted approach for rehabilitation interventions aiming to improve frailty in MS.

MICDIR: Multi-scale inverse-consistent deformable image registration using UNetMSS with self-constructing graph latent.

Image registration is the process of bringing different images into a common coordinate system - a technique widely used in various applications of computer vision, such as remote sensing, image retrieval, and, most commonly, medical imaging. Deep learning based techniques have been applied successfully to tackle various complex medical image processing problems, including medical image registration. Over the years, several image registration techniques have been proposed using deep learning. Deformable image registration techniques such as Voxelmorph have been successful in capturing finer changes and providing smoother deformations. However, Voxelmorph, as well as ICNet and FIRE, do not explicitly encode global dependencies (i.e. the overall anatomical view of the supplied image) and, therefore, cannot track large deformations. In order to tackle the aforementioned problems, this paper extends the Voxelmorph approach in three different ways. To improve the performance in case of small as well as large deformations, supervision of the model at different resolutions has been integrated using a multi-scale UNet. To support the network to learn and encode the minute structural co-relations of the given image-pairs, a self-constructing graph network (SCGNet) has been used as the latent of the multi-scale UNet - which can improve the learning process of the model and help the model to generalise better. And finally, to make the deformations inverse-consistent, cycle consistency loss has been employed. On the task of registration of brain MRIs, the proposed method achieved significant improvements over ANTs and VoxelMorph, obtaining a Dice score of 0.8013 ± 0.0243 for intramodal and 0.6211 ± 0.0309 for intermodal, while VoxelMorph achieved 0.7747 ± 0.0260 and 0.6071 ± 0.0510, respectively.

Using exterior housing conditions to predict elevated pediatric blood lead levels.

Housing-based lead paint dust is the most common source of lead exposure for US-born children. Although year of housing construction is a critical indicator of the lead hazard to US children, not all housing of the same age poses the same risk to children. Additional information about housing condition is required to differentiate the housing-based lead risk at the parcel level. This study aimed to identify and assess a method for gathering and using observations of exterior housing conditions to identify active housing-based lead hazards at the parcel level. We used a dataset of pediatric blood lead observations (sample years 2000-2013, ages 6-72 months, n = 6,589) to assess associations between observations of exterior housing conditions and housing-based lead risk. We used graphical and Lasso regression methods to estimate the likelihood of an elevated blood lead observation (≥3.5 µg/dL). Our methods estimate a monotonic increase in the likelihood of an elevated blood lead observation as housing conditions deteriorate with the largest changes associated with homes in the greatest disrepair. Additionally we estimate that age of home construction works in consort with housing conditions to amplify risks among those houses built before 1952. Our analysis indicates that a survey of external housing conditions can be used in combination with age of housing in the identification process, at the parcel level, of homes that pose a housing-based lead hazard to children.

Modifying Diet and Exercise in MS (MoDEMS): Study design and protocol for a telehealth weight loss intervention for adults with obesity & Multiple Sclerosis.

Weight loss improves overall health, and reduces inflammation, risk of stroke, heart attack, diabetes, certain cancers, and death among individuals with obesity. Weight loss also improves mobility, increases stamina, and elevates mood. Between 25 and 33% of people with Multiple Sclerosis (pwMS) have obesity. Multiple Sclerosis (MS) and obesity are independently associated with reduced mobility, increased fatigue, and depression. Most behavioral weight loss trials exclude individuals with neurologic disease. Consequently, few studies have examined the effects of weight loss on symptom presentation and health outcomes among pwMS and obesity. This is the first study examining the efficacy of a comprehensive behavioral weight loss intervention designed specifically for pwMS. The purpose of this study is to develop and assess the efficacy of a telehealth administered weight loss intervention tailored for pwMS. Additionally, we aim to determine if weight loss reduces physical and emotional symptoms in individuals with obesity and MS. We will enroll 70 pwMS in a wait-list crossover trial to examine the efficacy of our intervention. If successful, findings will help determine whether we can help participants lose clinically significant weight - and whether weight loss among pwMS and overweight/obesity reduces fatigue, and improves mobility, mood, and quality of life.

Bayesian accrual prediction for interim review of clinical studies: open source R package and smartphone application.

BACKGROUND: Subject recruitment for medical research is challenging. Slow patient accrual leads to increased costs and delays in treatment advances. Researchers need reliable tools to manage and predict the accrual rate. The previously developed Bayesian method integrates researchers' experience on former trials and data from an ongoing study, providing a reliable prediction of accrual rate for clinical studies. METHODS: In this paper, we present a user-friendly graphical user interface program developed in R. A closed-form solution for the total subjects that can be recruited within a fixed time is derived. We also present a built-in Android system using Java for web browsers and mobile devices. RESULTS: Using the accrual software, we re-evaluated the Veteran Affairs Cooperative Studies Program 558- ROBOTICS study. The application of the software in monitoring and management of recruitment is illustrated for different stages of the trial. CONCLUSIONS: This developed accrual software provides a more convenient platform for estimation and prediction of the accrual process.

The association of the rapid assessment of supervision scale score and unintentional childhood injury.

Supervisory neglect is often considered in medical settings when a child presents with an unintentional injury. The Rapid Assessment of Supervision Scale (RASS) is a clinical decision-making tool for the assessment of supervision of young children. As the next step in the development of the RASS, we assessed the association of RASS scores with unintentional injury. This study was a secondary analysis of data from a case-crossover study, which examined the association of parental supervision and unintentional injury in children. Data on supervision characteristics for 3 time periods for each child were available, that is, one injury scenario and two "control" time periods when no injury occurred. Blinded to injury status, four raters independently evaluated adequacy of supervision in 132 supervision scenarios using the RASS. The individual RASS scores of the four raters and the group (mean) RASS score of the four raters were evaluated for associations with injury status. Individual scores from three of the four raters demonstrated significant associations of increasing RASS scores with injury. Increasing group RASS scores (odds ratio = 2.8; 95% confidence interval [1.5, 5.1]) were associated with greater likelihood of injury. Further testing may result in a tool that aids medical personnel in the evaluation of adequacy of supervision.

Modeling and validating Bayesian accrual models on clinical data and simulations using adaptive priors.

Slow recruitment in clinical trials leads to increased costs and resource utilization, which includes both the clinic staff and patient volunteers. Careful planning and monitoring of the accrual process can prevent the unnecessary loss of these resources. We propose two hierarchical extensions to the existing Bayesian constant accrual model: the accelerated prior and the hedging prior. The new proposed priors are able to adaptively utilize the researcher's previous experience and current accrual data to produce the estimation of trial completion time. The performance of these models, including prediction precision, coverage probability, and correct decision-making ability, is evaluated using actual studies from our cancer center and simulation. The results showed that a constant accrual model with strongly informative priors is very accurate when accrual is on target or slightly off, producing smaller mean squared error, high percentage of coverage, and a high number of correct decisions as to whether or not continue the trial, but it is strongly biased when off target. Flat or weakly informative priors provide protection against an off target prior but are less efficient when the accrual is on target. The accelerated prior performs similar to a strong prior. The hedging prior performs much like the weak priors when the accrual is extremely off target but closer to the strong priors when the accrual is on target or only slightly off target. We suggest improvements in these models and propose new models for future research.

Phase I study of tandem high-dose chemotherapy with autologous peripheral blood stem cell rescue for children with recurrent brain tumors: a Pediatric Blood and MarrowTransplant Consortium study.

BACKGROUND: High-dose chemotherapy with autologous stem cell rescue (HDC/SCR) has produced responses and prolonged survival for some children with recurrent brain tumors, but is associated with considerable morbidity and mortality. A Phase I trial of two cycles of HDC/SCR for recurrent brain tumors in children was performed to determine the maximum tolerated doses for a novel regimen. PROCEDURES: Two cycles of HDC/SCR were given. Cycle 1 included thiotepa and carmustine given on days -5, -4, and -3. Four to six weeks later, patients received cycle 2 which included thiotepa and carboplatin given on days -5, -4, and -3. Autologous peripheral blood stem cells (PBSC) were infused on day 0 of each cycle. RESULTS: Thirty-two patients were treated and 25 patients received both cycles of HDC/SCR. Common toxicities included mucositis, emesis, diarrhea, anorexia, and pancytopenia. Eight of 32 (25%) assessable children died from regimen-related toxicity. Pulmonary failure occurred in seven patients. Seven patients had grade 3-4 neurotoxicity. The 3-year event-free survival (EFS) was 25%. CONCLUSIONS: We determined the maximum tolerated regimen to be thiotepa 600 mg/m(2) and carmustine 300 mg/m(2) followed by thiotepa 600 mg/m(2) and carboplatin 1,200 mg/m(2) . Pulmonary toxicity was considerable. The toxic death rate was similar to other trials of HDC/SCR for children with recurrent brain tumors performed during the same time period. The regimen resulted in prolonged time to progression for a significant number of patients and long-term survival for some patients with recurrent medulloblastoma and rhabdoid tumor.

Bioavailability of oral carisoprodol 250 and 350 mg and metabolism to meprobamate: A single-dose crossover study.

BACKGROUND: Carisoprodol is a skeletal muscle relaxant indicated for use in the treatment of acute, painful musculoskeletal conditions. Two randomized, controlled clinical trials have reported that carisoprodol 250 mg QID was equally effective as and better tolerated than carisoprodol 350 mg QID. OBJECTIVES: The primary objective of the current study was to determine the relative bioavailability of carisoprodol and its metabolite, meprobamate, with singledose administration of 250- and 350-mg tablets. A secondary objective of the study was to determine whether lowering the carisoprodol dose would decrease plasma meprobamate concentrations. METHODS: This single-dose, randomized, open-label, crossover study enrolled healthy volunteers. Each dose was administered with water in the morning; after a 7-day washout, subjects received the alternate dose. Blood samples were drawn at prespecified times over a 48-hour period. For tolerability assessment, subjects underwent a physical examination, including 12-lead ECG. RESULTS: A total of 24 subjects were enrolled (12 men, 12 women; mean age, 22.8 years). The dose-adjusted AUC0-∞ values for carisoprodol were 5.29 µg/mL/h with the 250-mg tablet and 5.75 µg/mL/h with the 350-mg tablet (relative bioavailability, 92%). The mean (SD) Cmax values of carisoprodol and meprobamate after administration of the 250-mg carisoprodol tablet were 1.24 (0.49) and 1.84 (0.31) µg/mL, respectively, compared with 1.78 (0.97) and 2.46 (0.47) µg/mL with the 350-mg tablet. AUC0-∞ was dose proportional, and the apparent t1/2 values at the terminal phase were 1.74 hours with the 250-mg tablet and 1.96 hours with the 350-mg tablet. There were 3 mild adverse events considered possibly treatment related (weakness, dizziness, and drowsiness); these were reported in 2 subjects with 350-mg carisoprodol. CONCLUSIONS: In this small study in healthy fasting subjects, the exposure to carisoprodol and meprobamate was dose proportional between the single 250- and 350-mg doses. Both doses were generally well tolerated.

Use of the multipurpose drainage catheter for the provision of acute peritoneal dialysis in infants and children.

BACKGROUND: Prior experience with the Cook (Cook Inc, Bloomington, IN) Teflon rigid catheter (CTC) showed it to be a suboptimal access for acute peritoneal dialysis (PD) treatment in infants and children because of the frequency of catheter-related complications associated with its use. The objective of this study is to report our experience with the bedside-placed flexible Cook Mac-Loc Multipurpose Drainage catheter (CMMDC) for acute PD in critically ill infants, comparing it with the historic Tenckhoff catheter (TC) and CTC use. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: All patients with acute renal failure (ARF) seen in our institution between December 2003 and April 2005 who underwent CMMDC placement for acute PD are included. PREDICTOR: CTCs versus CMMDCs versus TCs. OUTCOMES & MEASUREMENTS: Catheter-related complications and catheter-free survival. RESULTS: 21 infants and children with ARF were treated with acute PD using a CMMDC; 16 patients were post-cardiac surgery and 5 had other diagnoses. Mean patient age was 6.9 +/- 14.4 (SD) months (range, 4 days to 5.2 years; median, 1.6 months). Of 21 catheters, 3 had complications, and in 2 patients, this precluded continuation of PD therapy. In the remaining 18 patients, catheter use continued until recovery from ARF or nonrenal death. All patients achieved target fluid and solute removal with no catheter-related infectious complications. Mean complication-free survival of CMMDCs was 10.5 +/- 7.9 days (range, 2 to 29 days), with the 90% probability of survival at 14 days. Although there was no significant difference between lengths of complication-free survival of CMMDCs and TCs (58 days; P = 0.57), the difference between CMMDCs and CTCs (6 days) was significant (P < 0.001). Likewise, incidences of catheter-related complications with TCs and CMMDCs were similar, and in both cases, significantly less than the incidence associated with CTCs (49%; P < 0.01). LIMITATIONS: Small number of patients and comparison with historic experience. CONCLUSIONS: Use of CMMDCs is associated with the provision of effective dialysis with a satisfactory complication-free survival and should be considered when bedside placement of an acute PD access in infants and children is desired.

Prevention of peritonitis in children receiving peritoneal dialysis.

Peritonitis and catheter-related (exit-site/tunnel) infections are major causes of morbidity in children receiving peritoneal dialysis (PD). Our objective was to evaluate the impact of a combination of prophylactic measures on the rate of peritonitis and catheter-related infections subsequent to their implementation in 2001. This is a single center review of incident patients who received automated peritoneal dialysis (APD) from 1997 to 2004. The causal microorganisms, annualized peritonitis and catheter-related infections rates and the time to infection were reviewed using pooled data from 1997 to 2000 and from 2001 to 2004. Fifty-four patients received PD over 1099 patient months (pm). Twenty-eight peritonitis episodes occurred in 15 patients over 599 pm from 1997 to 2000 (annualized rate (AR): 0.56 infections/patient year). Eight episodes of peritonitis occurred in five patients over 500 pm from 2001 to 2004 (AR: 0.19 infections/patient year) (P = 0.01). Prior to 2001, the median time from dialysis initiation to the first peritonitis episode was 500 days (95% CI, 400-660 days), compared to 1137 days (95% CI, 1050 to +Infinity) from 2001 to 2004 (P = 0.008). The rate of catheter-related infections and time to initial infection during the two periods was not different. We conclude that measures to decrease the frequency of peritonitis can be successfully applied to children and should be incorporated as part of standard care.

Tracking Trichophyton tonsurans through a large urban child care center: defining infection prevalence and transmission patterns by molecular strain typing.

OBJECTIVES: Trichophyton tonsurans is the single most common cause of pediatric dermatophytoses in North America and is observed with increasing frequency in other countries. This investigation was designed to gain insight into the natural course of T. tonsurans infection. PATIENTS AND METHODS: This 2-year prospective, longitudinal study evaluated all preschool-aged children attending a single child care center. Scalp cultures were collected monthly from each child in attendance, and the presence of disease symptoms recorded at each visit. Dermatophyte genotype was assigned based on the combination of stable sequence variations (2 length variants, 8 single-nucleotide polymorphisms, a 10-base pair insertion, a 14-base pair deletion) present in 2 gene loci. RESULTS: A total of 3541 scalp cultures were collected from 446 children during 24 months. Twenty-two percent to 51% of scalp cultures per month were positive, contributing 1390 fungal cultures of which 1048 were typeable. Among children with multiple typeable isolates, 51% exclusively carried the same strain, 37% demonstrated a single predominant strain with secondary strains transiently acquired, and 12% harbored a different strain of T. tonsurans with each typeable culture. The probability that the same strain persisted in subsequent months was 0.898 and unlikely to have arisen by chance. Rates of symptomatic disease were significantly different between exclusive, predominant, and transient carriers of T. tonsurans. CONCLUSIONS: In contrast to dermatophyte infections in older individuals, where symptomatic disease seems to be a consequence of pathogen acquisition and carriers can be traced to an index case, in this preschool-aged population infection was endemic, and symptomatic disease seemed to represent activation of a single strain that persisted on the scalp.

Breakthrough pain in opioid-treated patients with neuropathic pain.

OBJECTIVE: This report aims to describe the prevalence and characteristics of breakthrough pain in patients with neuropathic pain. METHODS: The study represents data from a subset of patients from a larger survey of 228 patients with chronic noncancer pain. Patients were identified from nine pain programs and were administered a telephone questionnaire. The study population comprised 45 chronic noncancer pain patients with primary neuropathic pain diagnoses who were being treated with opioids. RESULTS: Pain had been present for a median of six years. Medications used for pain in addition to opioids included nonsteroidal anti-inflammatory agents (29 percent), antidepressants (60 percent), and anticonvulsants (53 percent). Thirty-five of the patients (78 percent) described a total of 42 distinct types of breakthrough pain. The median number of episodes per day was two; the median time to maximum intensity was 10 minutes, and the median duration of pain was 60 minutes. Patients could identify a precipitant for 62 percent of the pains, and 88 percent of the precipitants were activity related. The onset of breakthrough pain could not be predicted for 48 percent of the pains and could only sometimes bepredicted for 29 percent of the pains. CONCLUSION: Breakthrough pain is common in opioid-treated patients with chronic neuropathic pain. Such pain often has a rapid onset and a relatively short duration, and it is frequently difficult to predict, similar to breakthrough pain in cancer patients.