Diffusion tensor imaging (DTI) is a well-established magnetic resonance imaging (MRI) technique used for studying microstructural changes in the white matter. As with many other imaging modalities, ...DTI images suffer from technical between-scanner variation that hinders comparisons of images across imaging sites, scanners and over time. Using fractional anisotropy (FA) and mean diffusivity (MD) maps of 205 healthy participants acquired on two different scanners, we show that the DTI measurements are highly site-specific, highlighting the need of correcting for site effects before performing downstream statistical analyses. We first show evidence that combining DTI data from multiple sites, without harmonization, may be counter-productive and negatively impacts the inference. Then, we propose and compare several harmonization approaches for DTI data, and show that ComBat, a popular batch-effect correction tool used in genomics, performs best at modeling and removing the unwanted inter-site variability in FA and MD maps. Using age as a biological phenotype of interest, we show that ComBat both preserves biological variability and removes the unwanted variation introduced by site. Finally, we assess the different harmonization methods in the presence of different levels of confounding between site and age, in addition to test robustness to small sample size studies.
•Significant site and scanner effects exist in DTI scalar maps.•Several multi-site harmonization methods are proposed.•ComBat performs the best at removing site effects in FA and MD.•Voxels associated with age in FA and MD are more replicable after ComBat.•ComBat is generalizable to other imaging modalities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Russell and Koenig discuss prehospital transfusion in pediatric trauma. Trauma is the leading cause of mortality and hemorrhagic shock in pediatric patients, and sustained injuries are one of the ...most common causes of preventable mortality in these patients. An estimated 1000 to 2000 preventable traumatic deaths in children per year occur after injury in the US because of inadequate or delayed care. Some of these deaths may represent pediatric patients with unrecognized hemorrhagic shock who are not promptly treated with hemorrhage control and appropriate hemostatic resuscitation.
A 15-year-old patient with cystic fibrosis with a disseminated Mycobacterium abscessus infection was treated with a three-phage cocktail following bilateral lung transplantation. Effective lytic ...phage derivatives that efficiently kill the infectious M. abscessus strain were developed by genome engineering and forward genetics. Intravenous phage treatment was well tolerated and associated with objective clinical improvement, including sternal wound closure, improved liver function, and substantial resolution of infected skin nodules.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
ABSTRACT
Damage-control resuscitation (DCR) consists of rapid control of bleeding, avoidance of hemodilution, acidosis, and hypothermia; early empiric balanced transfusions with red blood cells, ...plasma and platelets, or whole blood when available, and the use of intravenous or mechanical hemostatic adjuncts when indicated. The principles used in pediatric and adult trauma patients are quite similar. There are very important recognized physiologic differences in children with traumatic hemorrhagic shock that warrant slight variations in DCR. In pediatric trauma patients, early physiologic signs of shock may be different from adults and the early recognition of this is critical to enable prompt resuscitation and utilization of damage control principles. This review details the current principles of pediatric DCR based on the best available literature, expert consensus recommendations, and also describes a practical guide for implementation of DCR strategies for pediatric trauma patients.
Abstract Background Massive transfusion in pediatric trauma has been described in combat populations and other single institutions studies. We aim to define the incidence of massive transfusion in a ...large US civilian pediatric trauma population, identify predictive parameters of MT, and the mortality associated with massive transfusion. Methods Data from the National Trauma Databank (2010-2012), a trauma registry maintained by the American College of Surgeons, was analyzed. We included pediatric trauma patients ≤ 14 years that underwent massive transfusion, as defined by 40 ml/kg of blood products within the first 24 hours following admission. We compared the massive transfusion group with children receiving any transfusion within the same time frame. Univariate and multivariate analysis were performed. Results Of 356,583 pediatric trauma patients, 13,523 (4%) received any transfusion in the first 24 hours and 173 (0.04%) had a massive transfusion. On multivariate analysis, factors predicting massive transfusion were: older patients (5 to 12: OR 2.71, p=0.006, and ≥ 12: OR 5.14, p<0.001), hypothermic patients (Temperature < 35: OR 2.48, p< 0.025), low GCS (GCS<8: OR 2.82, p=0.009), and ISS≥25 (OR 2.01, p=0.03). Overall mortality for the entire group, any transfusion group, and massive transfusion group were 2.5%, 13.6%, and 50.6% respectively (p<0.001). Conclusions Massive transfusion in pediatric trauma is an uncommon event associated with a significant mortality. Patients undergoing massive transfusion are older, more likely to be hypothermic, and have sustained more severe injuries as measured by traditional trauma scoring systems than transfused trauma patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Joint reminiscence groups, involving people with dementia and family carers together, are popular, but the evidence-base is limited. This study aimed to assess the effectiveness and ...cost-effectiveness of joint reminiscence groups as compared to usual care.
This multi-centre, pragmatic randomised controlled trial had two parallel arms: intervention group and usual-care control group. A restricted dynamic method of randomisation was used, with an overall allocation ratio of 1:1, restricted to ensure viable sized intervention groups. Assessments, blind to treatment allocation, were carried out at baseline, three months and ten months (primary end-point), usually in the person's home. Participants were recruited in eight centres, mainly through NHS Memory Clinics and NHS community mental health teams. Included participants were community resident people with mild to moderate dementia (DSM-IV), who had a relative or other care-giver in regular contact, to act as informant and willing and able to participate in intervention. 71% carers were spouses. 488 people with dementia (mean age 77.5)were randomised: 268 intervention, 220 control; 350 dyads completed the study (206 intervention, 144 control). The intervention evaluated was joint reminiscence groups (with up to 12 dyads) weekly for twelve weeks; monthly maintenance sessions for further seven months. Sessions followed a published treatment manual and were held in a variety of community settings. Two trained facilitators in each centre were supported by volunteers. Primary outcome measures were self-reported quality of life for the person with dementia (QoL-AD), psychological distress for the carer (General Health Questionnaire, GHQ-28). Secondary outcome measures included: autobiographical memory and activities of daily living for the person with dementia; carer stress for the carer; mood, relationship quality and service use and costs for both.
The intention to treat analysis (ANCOVA) identified no differences in outcome between the intervention and control conditions on primary or secondary outcomes (self-reported QoL-AD mean difference 0.07 (-1.21 to 1.35), F = 0.48, p = 0.53). Carers of people with dementia allocated to the reminiscence intervention reported a significant increase in anxiety on a General Health Questionnaire-28 sub-scale at the ten month end-point (mean difference 1.25 (0.25 to 2.26), F = 8.28, p = 0.04). Compliance analyses suggested improved autobiographical memory, quality of life and relationship quality for people with dementia attending more reminiscence sessions, however carers attending more groups showed increased care-giving stress. Economic analyses from a public sector perspective indicated that joint reminiscence groups are unlikely to be cost-effective. There were no significant adverse effects attributed to the intervention. Potential limitations of the study include less than optimal attendance at the group sessions--only 57% of participants attended at least half of the intervention sessions over the 10 month period, and a higher rate of study withdrawal in the control group.
This trial does not support the clinical effectiveness or cost-effectiveness of joint reminiscence groups. Possible beneficial effects for people with dementia who attend sessions as planned are offset by raised anxiety and stress in their carers. The reasons for these discrepant outcomes need to be explored further, and may necessitate reappraisal of the movement towards joint interventions.
ISRCTN Registry ISRCTN42430123.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cognitive stimulation therapy (CST) is a well-established group psychosocial intervention for people with dementia. There is evidence that home-based programmes of cognitive stimulation delivered by ...family caregivers may benefit both the person and the caregiver. However, no previous studies have evaluated caregiver-delivered CST. This study aimed to evaluate the effectiveness of a home-based, caregiver-led individual cognitive stimulation therapy (iCST) program in (i) improving cognition and quality of life (QoL) for the person with dementia and (ii) mental and physical health (well-being) for the caregiver.
A single-blind, pragmatic randomised controlled trial (RCT) was conducted at eight study sites across the United Kingdom. The intervention and blinded assessment of outcomes were conducted in participants' homes. Three hundred fifty-six people with mild to moderate dementia and their caregivers were recruited from memory services and community mental health teams (CMHTs). Participants were randomly assigned to iCST (75, 30-min sessions) or treatment as usual (TAU) control over 25 wk. iCST sessions consisted of themed activities designed to be mentally stimulating and enjoyable. Caregivers delivering iCST received training and support from an unblind researcher. Primary outcomes were cognition (Alzheimer's Disease Assessment Scale-cognitive ADAS-Cog) and self-reported QoL (Quality of Life Alzheimer's Disease QoL-AD) for the person with dementia and general health status (Short Form-12 health survey SF-12) for the caregiver. Secondary outcomes included quality of the caregiving relationship from the perspectives of the person and of the caregiver (Quality of the Carer Patient Relationship Scale) and health-related QoL (European Quality of Life-5 Dimensions EQ-5D) for the caregiver. Intention to treat (ITT) analyses were conducted. At the post-test (26 wk), there were no differences between the iCST and TAU groups in the outcomes of cognition (mean difference MD = -0.55, 95% CI -2.00-0.90; p = 0.45) and self-reported QoL (MD = -0.02, 95% CI -1.22-0.82; p = 0.97) for people with dementia, or caregivers' general health status (MD = 0.13, 95% CI -1.65-1.91; p = 0.89). However, people with dementia receiving iCST rated the relationship with their caregiver more positively (MD = 1.77, 95% CI 0.26-3.28; p = 0.02), and iCST improved QoL for caregivers (EQ-5D, MD = 0.06, 95% CI 0.02-0.10; p = 0.01). Forty percent (72/180) of dyads allocated to iCST completed at least two sessions per week, with 22% (39/180) completing no sessions at all. Study limitations include low adherence to the intervention.
There was no evidence that iCST has an effect on cognition or QoL for people with dementia. However, participating in iCST appeared to enhance the quality of the caregiving relationship and caregivers' QoL.
The iCST trial is registered with the ISRCTN registry (identified ISRCTN 65945963, URL: DOI 10.1186/ISRCTN65945963).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Two human pathogenic bacteria, Staphylococcus aureus CIP 68.5 and Pseudomonas aeruginosa ATCC 9025, were adsorbed onto surfaces containing Ti thin films of varying thickness to determine the extent ...to which nanoscale surface roughness influences the extent of bacterial attachment. A magnetron sputter thin film system was used to deposit titanium films with thicknesses of 3, 12, and 150 nm on glass substrata with corresponding surface roughness parameters of R q 1.6, 1.2, and 0.7 nm (on a 4 μm × 4 μm scanning area). The chemical composition, wettability, and surface architecture of titanium thin films were characterized using X-ray photoelectron spectroscopy, contact angle measurements, atomic force microscopy, three-dimensional interactive visualization, and statistical approximation of the topographic profiles. Investigation of the dynamic evolution of the Ti thin film topographic parameters indicated that three commonly used parameters, R a, R q, and R max, were insufficient to effectively characterize the nanoscale rough/smooth surfaces. Two additional parameters, R skw and R kur, which describe the statistical distributions of roughness character, were found to be useful for evaluating the surface architecture. Analysis of bacterial retention profiles indicated that bacteria responded differently to the surfaces on a scale of less than 1 nm change in the R a and R q Ti thin film surface roughness parameters by (i) an increased number of retained cells by a factor of 2−3, and (ii) an elevated level of secretion of extracellular polymeric substances.
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IJS, KILJ, NUK, PNG, UL, UM