Postinfectious hydrocephalus in infants is a major health problem in sub-Saharan Africa. The conventional treatment is ventriculoperitoneal shunting, but surgeons are usually not immediately ...available to revise shunts when they fail. Endoscopic third ventriculostomy with choroid plexus cauterization (ETV-CPC) is an alternative treatment that is less subject to late failure but is also less likely than shunting to result in a reduction in ventricular size that might facilitate better brain growth and cognitive outcomes.
We conducted a randomized trial to evaluate cognitive outcomes after ETV-CPC versus ventriculoperitoneal shunting in Ugandan infants with postinfectious hydrocephalus. The primary outcome was the Bayley Scales of Infant Development, Third Edition (BSID-3), cognitive scaled score 12 months after surgery (scores range from 1 to 19, with higher scores indicating better performance). The secondary outcomes were BSID-3 motor and language scores, treatment failure (defined as treatment-related death or the need for repeat surgery), and brain volume measured on computed tomography.
A total of 100 infants were enrolled; 51 were randomly assigned to undergo ETV-CPC, and 49 were assigned to undergo ventriculoperitoneal shunting. The median BSID-3 cognitive scores at 12 months did not differ significantly between the treatment groups (a score of 4 for ETV-CPC and 2 for ventriculoperitoneal shunting; Hodges-Lehmann estimated difference, 0; 95% confidence interval CI, -2 to 0; P=0.35). There was no significant difference between the ETV-CPC group and the ventriculoperitoneal-shunt group in BSID-3 motor or language scores, rates of treatment failure (35% and 24%, respectively; hazard ratio, 0.7; 95% CI, 0.3 to 1.5; P=0.24), or brain volume (z score, -2.4 and -2.1, respectively; estimated difference, 0.3; 95% CI, -0.3 to 1.0; P=0.12).
This single-center study involving Ugandan infants with postinfectious hydrocephalus showed no significant difference between endoscopic ETV-CPC and ventriculoperitoneal shunting with regard to cognitive outcomes at 12 months. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01936272 .).
Background
Patient-controlled analgesia is a widely used and effective method of controlling pain after THA. This method is associated with substantial undesirable side effects. Local infiltration ...has been introduced in an attempt to reduce opioid requirements postoperatively, but its ability to reduce pain without complications is still questioned.
Questions/Purposes
We evaluated patient-controlled analgesia use, pain and satisfaction scores, complication rates, and ropivacaine levels associated with the use of periarticular multimodal drug infiltration in THA.
Patients and Methods
We randomized 64 patients undergoing THA to receive a periarticular intraoperative multimodal drug injection or to receive no injection. All patients received patient-controlled analgesia for 24 hours after surgery. The final assessment was at 6 weeks.
Results
Patients receiving the periarticular injection used less patient-controlled analgesia 6 hours postoperatively. The 24-hour patient-controlled analgesia requirement postsurgery also was less. The visual analog scale score for pain on activity in the postanesthetic care unit was less for patients who received an injection. The visual analog scale satisfaction score was similar in the two groups throughout the followup period. Recorded unbound ropivacaine levels were 2.5 times lower than toxic levels.
Conclusions
Periarticular intraoperative injection with multimodal drugs can reduce postoperative patient-controlled analgesia requirements and pain on activity in patients undergoing THA with no apparent increase in risk.
Level of Evidence
Level I, therapeutic study. See the guidelines online for a complete description of level of evidence.
Schizophrenia is a disorder characterized by pervasive deficits in cognitive functioning. However, few well-powered studies have examined the degree to which cognitive performance is impaired even ...among individuals with schizophrenia not currently on antipsychotic medications using a wide range of cognitive and reinforcement learning measures derived from cognitive neuroscience. Such research is particularly needed in the domain of reinforcement learning, given the central role of dopamine in reinforcement learning, and the potential impact of antipsychotic medications on dopamine function.
The present study sought to fill this gap by examining healthy controls (
= 75), unmedicated (
= 48) and medicated (
= 148) individuals with schizophrenia. Participants were recruited across five sites as part of the CNTRaCS Consortium to complete tasks assessing processing speed, cognitive control, working memory, verbal learning, relational encoding and retrieval, visual integration and reinforcement learning.
Individuals with schizophrenia who were not taking antipsychotic medications, as well as those taking antipsychotic medications, showed pervasive deficits across cognitive domains including reinforcement learning, processing speed, cognitive control, working memory, verbal learning and relational encoding and retrieval. Further, we found that chlorpromazine equivalency rates were significantly related to processing speed and working memory, while there were no significant relationships between anticholinergic load and performance on other tasks.
These findings add to a body of literature suggesting that cognitive deficits are an enduring aspect of schizophrenia, present in those off antipsychotic medications as well as those taking antipsychotic medications.
Working memory (WM) has been a central focus of cognitive neuroscience research because WM is a resource that is involved in many different cognitive operations. The goal of this study was to ...evaluate the clinical utility of WM paradigms developed in the basic cognitive neuroscience literature, including methods designed to estimate storage capacity without contamination by lapses of attention.
A total of 61 people with schizophrenia, 49 with schizoaffective disorder, 47 with bipolar disorder with psychosis, and 59 healthy volunteers were recruited. Participants received multiple WM tasks, including two versions each of a multiple Change Detection paradigm, a visual Change Localization paradigm, and a Running Span task.
Healthy volunteers performed better than the combined patient group on the visual Change Localization and running span measures. The multiple Change Detection tasks provided mixed evidence about WM capacity reduction in the patient groups, but a mathematical model of performance suggested that the patient groups differed from controls in their rate of attention lapsing. The 3 patient groups performed similarly on the WM tasks. Capacity estimates from the Change Detection and Localization tasks showed significant correlations with functional capacity and functional outcome.
The patient groups generally performed in a similarly impaired fashion across tasks, suggesting that WM impairment and attention lapsing are general features of psychotic disorders. Capacity estimates from the Change Localization and Detection tasks were related to functional capacity and outcome, suggesting that these methods may be useful in a clinical context.
There is controversy regarding the superiority of posterior-stabilizing (PS) total knee arthroplasty (TKA) and cruciate-retaining (CR) TKA. Substantial work has made comparisons between PS and CR TKA ...at follow-ups of less than 5 years. It was the goal of the present study to compare the kinematics at greater than 5 years postoperatively between CR and PS TKA, with a secondary goal of comparing patient function.
A total of 42 knees were investigated, with equal representation in the PS and CR TKA groups. Patients underwent radiostereometric analysis imaging at 0°, 20°, 40°, 60° 80°, and 100° of flexion. Contact position, magnitude of excursion, and condylar separation on each condyle were measured. A Timed-Up-and-Go functional test was also performed by patients, with the total test time being measured. Preoperative and postoperative clinical outcome scores were also collected.
There were differences in contact position on both the medial and lateral condyles at multiple angles of flexion (P < .05). There was no difference (P = .89) in medial excursion; however, PS TKA had greater lateral excursion than CR TKA (P < .01). No difference (P > .99) was found in frequency of condylar separation. PS TKA was associated with faster (P = .03) total Timed-Up-and-Go test times. There were no differences in clinical outcome scores between the groups preoperatively or postoperatively.
We found kinematic and functional differences that favor PS TKA. Our results suggest posterior cruciate ligament insufficiency in CR TKA, indicating that perhaps the cam/post systems in PS TKA better maintain knee kinematics and function long term.
Aerobic glycolysis supports proliferation through unresolved mechanisms. We have previously shown that aerobic glycolysis is required for the regulated proliferation of cerebellar granule neuron ...progenitors (CGNP) and for the growth of CGNP-derived medulloblastoma. Blocking the initiation of glycolysis via deletion of
(
) disrupts CGNP proliferation and restricts medulloblastoma growth. Here, we assessed whether disrupting
(
), an enzyme that acts in the terminal steps of glycolysis, would alter CGNP metabolism, proliferation, and tumorigenesis. We observed a dichotomous pattern of PKM expression, in which postmitotic neurons throughout the brain expressed the constitutively active PKM1 isoform, while neural progenitors and medulloblastomas exclusively expressed the less active PKM2. Isoform-specific
deletion in CGNPs blocked all
expression.
-deleted CGNPs showed reduced lactate production and increased SHH-driven proliferation.
C-flux analysis showed that
deletion reduced the flow of glucose carbons into lactate and glutamate without markedly increasing glucose-to-ribose flux.
deletion accelerated tumor formation in medulloblastoma-prone
mice, indicating the disrupting PKM releases CGNPs from a tumor-suppressive effect. These findings show that distal and proximal disruptions of glycolysis have opposite effects on proliferation, and that efforts to block the oncogenic effect of aerobic glycolysis must target reactions upstream of PKM.
.
To support primary care physicians (PCPs) and their patients with knee osteoarthritis (OA), we created a series of evidence-based whiteboard educational videos for patients with knee OA. In a ...previous study we piloted these videos with patients to understand their acceptability and impact. The purpose of this study was to explore PCPs' perspectives to understand the utility of novel patient education videos to support management.
We conducted a qualitative descriptive study using semi-structured interviews of newly practicing and resident PCPs after watching a series of patient education videos. A thematic analysis approach was used combining both inductive and research question driven coding, category formation, and theme identification.
Ten participants were included. Barriers to optimal management were identified including the challenge of patient adherence and access to non-operative treatments. PCPs indicated that the videos would support their management of patients with knee OA by (1) supporting credibility and building trust with their patient, (2) reinforcing patient understanding, and (3) enhancing their own management of patients.
Future implementation of these resources with attention to barriers that may limit uptake is necessary and may optimize management of knee OA in primary care.
IMPLICATIONS FOR REHABILITATION
The provision of patient educational materials may support patient buy-in regarding appropriate management, enhance patient understanding, and improve physicians' future practice.
Viewing these videos could potentially improve physicians' future resource use, recommendation of non-operative treatments, and the quality of their total knee replacement referrals, which has benefits to both the patient and the healthcare system.
Perceived barriers to implementing evidence-based recommendations may pose a challenge for patients and clinicians and should be considered to help facilitate the uptake of educational interventions.
Background
TKA and unicompartmental knee arthroplasty (UKA) are both utilized to treat unicompartmental knee arthrosis. While some surgeons assume UKA provides better function than TKA, this ...assumption is based on greater final outcome scores rather than on change in scores and many patients with UKA have higher preoperative scores.
Questions/purposes
We therefore asked whether TKA would demonstrate (1) better change in clinical outcome scores from preoperative to postoperative states and (2) better survivorship than UKA.
Methods
We evaluated 4087 patients with 5606 TKAs and 179 patients with 279 UKAs performed between 1978 and 2009. Patients with TKA were older and heavier than patients with UKA (mean age, 68 versus 66 years; mean BMI, 32 versus 29). We compared preoperative, latest postoperative, and change in Knee Society Clinical Rating System (KSCRS), SF-12, and WOMAC scores. Minimum followup was 2 years (UKA: mean, 7 years; range, 2.0–23 years; TKA: mean, 6.5 years; range, 2.0–33 years). Preoperative outcome measure scores (WOMAC, SF-12, KSCRS) were higher in the UKA group.
Results
Patients with UKA had higher postoperative KSCRS and SF-12 mental scores. Changes in score for all WOMAC domains were similar between groups. Total KSCRS changes in score were similar between groups, although patients with TKA had higher knee scores (49 versus 43) but lower function scores than UKA (21 versus 26). Cumulative revision rate was higher for UKA than for TKA (13% versus 7%). Kaplan-Meier survivorship at 5 and 10 years was 95% and 90%, respectively, for UKA and 98% and 95%, respectively, for TKA.
Conclusions
While patients with UKA had higher pre- and postoperative scores than patients with TKA, the changes in scores were similar in both groups and survival appeared higher in patients with TKA.
Level of Evidence
Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
Dosimetric planning studies have described potential benefits for the use of proton radiation therapy (RT) for locally advanced breast cancer. We report acute toxicities and feasibility of proton ...delivery for 12 women treated with postmastectomy proton radiation with or without reconstruction.
Twelve patients were enrolled in an institutional review board-approved prospective clinical trial. The patients were assessed for skin toxicity, fatigue, and radiation pneumonitis during treatment and at 4 and 8 weeks after the completion of therapy. All patients consented to have photographs taken for documentation of skin toxicity.
Eleven of 12 patients had left-sided breast cancer. One patient was treated for right-sided breast cancer with bilateral implants. Five women had permanent implants at the time of RT, and 7 did not have immediate reconstruction. All patients completed proton RT to a dose of 50.4 Gy (relative biological effectiveness RBE) to the chest wall and 45 to 50.4 Gy (RBE) to the regional lymphatics. No photon or electron component was used. The maximum skin toxicity during radiation was grade 2, according to the Common Terminology Criteria for Adverse Events (CTCAE). The maximum CTCAE fatigue was grade 3. There have been no cases of RT pneumonitis to date.
Proton RT for postmastectomy RT is feasible and well tolerated. This treatment may be warranted for selected patients with unfavorable cardiac anatomy, immediate reconstruction, or both that otherwise limits optimal RT delivery using standard methods.
Many applications in the natural and applied sciences require the solutions of partial differential equations (PDEs) on surfaces or more general manifolds. The closest point method is a simple and ...accurate embedding method for numerically approximating PDEs on rather general smooth surfaces. However, the original formulation is designed to use explicit time stepping. This may lead to a strict time-step restriction for some important PDEs such as those involving the Laplace-Beltrami operator or higher-order derivative operators. To achieve improved stability and efficiency, we introduce a new implicit closest point method for surface PDEs. The method allows for large, stable time steps while retaining the principal benefits of the original method. In particular, it maintains the order of accuracy of the discretization of the underlying embedding PDE, it works on sharply defined bands without degrading the accuracy of the method, and it applies to general smooth surfaces. It also is very simple and may be applied to a rather general class of surface PDEs. Convergence studies for the in-surface heat equation and a fourth-order biharmonic problem are given to illustrate the accuracy of the method. We demonstrate the flexibility and generality of the method by treating flows involving diffusion, reaction-diffusion, and fourth-order spatial derivatives on a variety of interesting surfaces including surfaces of mixed codimension.
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