Impact of pharmacological treatments on outcome in adult rodents after traumatic brain injury: a meta-analysis

Pharmacological treatments have been widely investigated in pre-clinical animal trials to evaluate their usefulness in reducing cognitive, behavioural and motor problems after traumatic brain injury (TBI). However, the relative efficacy of these agents has yet to be evaluated, making it difficult to assess the strength of evidence for their use in a clinical population. A meta-analytic review of research (1980-2009) was therefore conducted to examine the impact of pharmacological treatments administered to adult male rodents after experimental TBI on cognitive, behavioural, and motor outcome. The PubMed and PsycInfo databases were searched using 35 terms. Weighted Cohen's d effect sizes, percent overlap, Fail-Safe N statistics and confidence intervals were calculated for each treatment. In total, 91 treatments were evaluated in 223 pre-clinical trials, comprising 5988 rodents. Treatments that were investigated by multiple studies and showed large and significant treatment effects were of greatest interest. Of the 16 treatments that were efficacious, six improved cognition, 10 improved motor function and no treatment improved behaviour (depression/anxiety, aggression, zoosocial behaviour). Treatment benefits were found across a range of TBI models. Drug dosage and treatment interval impacted on treatment effects.     

Outcome of allogeneic hematopoietic stem-cell transplantation in adult patients with acute lymphoblastic leukemia: no difference in related compared with unrelated transplant in first complete remission.

PURPOSE: The role of unrelated allogeneic stem-cell transplantation in acute lymphoblastic leukemia (ALL) patients is still not clear, and only limited data are available from the literature. We analyzed factors affecting clinical outcome of ALL patients receiving a related or unrelated stem-cell graft from matched donors. PATIENTS AND METHODS: The total study population was 264 adult patients receiving a myeloablative allogeneic stem-cell transplant for ALL at nine bone marrow transplantation centers between 1990 and 2002. Of these, 221 patients receiving a matched related or unrelated graft were analyzed. One hundred forty-eight patients received transplantation in complete remission; 62 patients were in relapse; and 11 patients were refractory to chemotherapy before transplant. Fifty percent of patients received bone marrow, and 50% received peripheral blood stem cell from a human leukocyte antigen-identical related (n = 103), or matched unrelated (n = 118) donor. RESULTS: Disease-free survival (DFS) at 5 years was 28%, with 76 patients (34%) still alive (2.2 to 103 months post-transplantation), and 145 deceased (65 relapses, transplant-related mortality, 45%). We observed an advantage regarding DFS in favor of patients receiving transplantation during their first complete remission (CR) in comparison with patients receiving transplantation in or after second CR (P =.014) or who relapsed (P <.001). We observed a clear trend toward improved survival in favor of B-lineage ALL patients compared with T-lineage ALL patients (P =.052), and Philadelphia chromosome-positive patients had no poorer outcome than Philadelphia chromosome-negative patients. Total-body irradiation-based conditioning improved DFS in comparison with busulfan (P =.041). CONCLUSION: Myeloablative matched related or matched unrelated allogeneic hematopoietic stem-cell transplantation in ALL patients should be performed in first CR.     

Can an app supporting psoriasis patients improve adherence to topical treatment? A single-blind randomized controlled trial

Background

Topical corticosteroid or corticosteroid/calcipotriol preparations are recommended first-line topical treatments of psoriasis, but a main cause for the lack of efficacy of topical treatments is considered low rates of adherence to topical drugs. Patient support by the use of applications (apps) for smartphones is suggested to improve medical adherence.

Methods/design

Design: An investigator-initiated, single-center, single-blind, parallel-group, phase-4 clinical superiority randomized controlled trial (RCT). Participants: 134 patients 18 to 75 years of age with mild-to-moderate psoriasis, who are capable of reading English language, own a smartphone, and are candidates for the study drug calcipotriol and betamethasone dipropionate (Cal/BD) cutaneous foam once daily prn (pro re nata). Intervention: A 28-day adherence-supporting app providing compulsory daily treatment reminders that pop-up on the smartphone screen with a short alert sound. The app synchronizes through Bluetooth® to an electronic monitor (EM) attached to the medication canister. The EM contains a chip registering the amount of foam, day and time the patient use the foam dispenser. The information is displayed in a diary that shows the amount of Cal/BD cutaneous foam used and the number of applied treatment sessions. The app has an optional diary with the patient’s rating of symptoms. Non-intervention: Use of Cal/BD cutaneous foam and EM without the app. All participants are prescribed Cal/BD cutaneous foam prn for the entire study period.Primary outcome obtained in week 4: rates of adherence measured by patient report, weight of medication canisters, and number of treatment sessions measured by the EM. Secondary outcomes obtained at baseline, weeks 4, 8, and 26: Lattice System Physician’s Global Assessment (LS-PGA) and Dermatology Quality of Life Index (DLQI).

Discussion

This trial tests of whether an app can improve rates of adherence to a topical antipsoriatic drug. If the app improves rates of adherence and reduces the burden of psoriasis in a clinically significant way, the app could easily be implemented as a standard routine of care in the clinic.

Trial registration

NCT02858713, registered on August 3, 2016. EudraCT number 2016–002143-42.

     

Unusual retinopathy in a child with severe combined immune deficiency

We describe a case of an infant diagnosed with severe combined immune deficiency (Adenosine Deaminase (ADA), SCID) with severe retinopathy and associated low vision in both eyes at first examination. An extensive infectious work up revealed an enterovirus infection, which suggested an early infectious and severe retinopathy. Genetic causes of congenital retinitis pigmentosa/ Leber’s congenital amaurosis could be excluded by whole exome sequencing.     

Preliminary Screening Recommendations for Patients at Risk of Depression and/or Anxiety more than 1 year Poststroke

Goal: Depression and anxiety are important complications of stroke but are underdiagnosed in community settings. The current study identified which patients were at increased risk of developing either disorder more than1 year poststroke to assist in targeted screening. Methods: Crosssectional survey of 147 adults who had a stroke more than 1 year ago were recruited from stroke advocacy/support groups and an outpatient register. Participants completed the Hospital Anxiety and Depression Scale (HADS) and reported whether they had emotional problems as a stroke inpatient (single item: yes/no). Standardized self-report measures evaluated medical (physical independence, health-related quality of life), cognitive (memory, executive functioning), and psychological (social support) variables. Demographic and stroke-related (stroke type, year) information were also recorded. Findings: Between 53% and 80% of respondents (n = 117) screened positive for depressed mood and/or anxiety (HADS subscale cut-offs: ≥8 or ≥4). Logistic regression analyses indicated that stroke survivors who reported having emotional problems as inpatients (odds ratio [OR]: 0.23), were female (OR: 3.42), and had poor health-related quality of life (OR: 0.45-0.53) and cognitive problems (OR: 0.68-0.74), were more likely to screen positive for either disorder. Models based on these variables predicted screening outcomes with 91% accuracy. Conclusions: Community-based stroke survivors who reported experiencing emotional problems as inpatients, were female, or had poor health-related quality of life (chronic pain, disturbed sleep, communication difficulties) and/or cognitive issues were at greater risk of being depressed/anxious. Targeted screening of these patients may help to identify those who are most in need of more comprehensive clinical assessments and evidence-based interventions.     

Brain and soccer: Functional patterns of brain activity during the generation of creative moves in real soccer decision‐making situations

This fMRI study investigated brain activity while soccer players were imagining creative moves in real soccer decision‐making situations. After presenting brief video clips of a soccer scene, participants had to imagine themselves as the acting player and think either of a creative or obvious move that might lead to a goal. Findings revealed stronger activation during trials in which the generation of obvious moves was required, relative to trials requiring creative moves. The reversed contrast (creative > obvious) showed no significant effects. Activations were mainly left‐lateralized, primarily involving the cuneus, middle temporal gyrus, and the rolandic operculum, which are known to support the processing of multimodal input from different sensory, motor and perceptual sources. Interestingly, more creative solutions in the soccer task were associated with smaller contrast values for the activation difference between obvious and creative trials, or even with more activation in the latter. Furthermore, higher trait creative potential (as assessed by a figural creativity test) was associated with stronger activation differences between both conditions. These findings suggest that with increasing soccer‐specific creative task performance, the processing of the manifold information provided by the soccer scenario becomes increasingly important, while in individuals with higher trait creative potential these processes were recruited to a minor degree. This study showed that soccer‐specific creativity tasks modulate activation levels in a network of regions supporting various cognitive functions such as semantic information processing, visual and motor imagery, and the processing and integration of sensorimotor and somatosensory information.