Background: Spinal cord injury (SCI) related bradycardia occurs frequently in patients with high cervical spine injuries. In patients with SCI-related symptomatic bradycardia, a variety of agents ...have been used to improve heart rate and reduce the need for vasopressor therapy. The literature concerning the use of theophylline in this disease state is sparse. Objective: The primary objective of this study was to evaluate and describe the use of theophylline for SCI-related symptomatic bradycardia. Methods: This was a retrospective case series of patients with SCI-related symptomatic bradycardia who were treated with theophylline. Patients were evaluated based on clinical response to theophylline. Patients were classified as a responder if vasopressors were discontinued or the number of bradycardia episodes decreased following the initiation of theophylline. Results: A total of twenty-six patients were included in the study. 17 (65.4%) patients were classified as responders, 5 (19.2%) patients were classified as non-responders, and 4 (15.4%) of patients were classified as undetermined. 11 patients (43.31%) were discharged on theophylline with 7 of these patients (41.2%) classified as responders. There were no significant differences between those classified as responders and those who were not. Conclusion and Relevance: This case series suggest that theophylline could be used as adjunctive therapy in patients with bradycardia secondary to acute SCI who achieve an adequate response to theophylline.
People with avascular necrosis of the hip have very limited treatment options currently available to stop the progression of this disease; this often results in the need for a hip replacement. There ...is some weak evidence that a class of drugs called bisphosphonates may delay the course of the disease, and this trial was commissioned and set up to provide robust evidence regarding the use of bisphosphonates in adults aged ≥ 18 years with this condition.
The aim of the Managing Avascular Necrosis Treatments: an Interventional Study ( MANTIS ) trial was to evaluate the clinical effectiveness and cost-effectiveness of a 12-month course of alendronate in the treatment of avascular necrosis.
This was a 66-month, definitive, multisite, two-arm, parallel-group, placebo-controlled, double-blind, randomised controlled trial, with an internal pilot phase.
Eight secondary care NHS hospitals across the UK.
Planned trial size - 280 adult patients with avascular necrosis.
Participants in the intervention group received 70 mg of alendronate (an oral bisphosphonate) weekly for 12 months.
The main outcomes were Oxford Hip Score at 12 months (short-term outcome) and the time to decision that a hip replacement is required at 36 months (long-term outcome).
Twenty-one patients were recruited and randomised to receive either the intervention drug, alendronate, or a placebo-matched tablet.
This trial was principally limited by low disease prevalence. Other limitations included the late disease stage at which participants were identified and the rapid progression of the disease.
This trial was limited by a low recruitment rate. Avascular necrosis of the hip should be treated as a rare disease. Future trials would need to recruit many more sites and recruit over a longer time period, and, for this reason, a registry may provide a more effective means of collecting data pertaining to this disease.
The MANTIS trial was terminated at the end of the pilot phase, because it did not meet its go/no-go criteria. The main issue was a poor recruitment rate, owing to a lower than expected disease prevalence and difficulties in identifying the condition at a sufficiently early stage. Those patients who were identified and screened either were too advanced in their disease progression or were already taking medication. We would not recommend that a short-term interventional study is conducted on this condition until its prevalence, geographic foci and natural history and better understood. The difficulty of acquiring this understanding is likely to be a barrier in most health-care markets. One means of developing this understanding would be the introduction of a database/registry for patients suffering from avascular necrosis of the hip.
The trial is registered as ISRCTN14015902.
This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in
; Vol. 26, No. 43. See the NIHR Journals Library website for further project information.
Background and Purpose
The purpose of this study was to assess the incidence of seizures in patients with spontaneous intracerebral hemorrhage (ICH) who received prophylactic levetiracetam.
Methods
...This was a retrospective cohort study evaluating the use of levetiracetam in patients without a history of seizures who experienced a spontaneous intracerebral hemorrhage. Patients were excluded if they were younger than 18 years of age, had a documented history of a seizure disorder, or had an antiseizure drug documented on their home medication list. Patients were based on their exposure to levetiracetam. The primary outcome was incidence of seizure during hospital admission. Secondary outcomes included occurrence of adverse events, intensive care unit (ICU) length of stay (LOS), and hospital LOS.
Results
Of the 229 patients included in the final analysis, 21 were in the levetiracetam group (LEV) and 208 were in the no levetiracetam group (no LEV). No statistical difference in seizure incidence was observed when comparing the LEV and no LEV groups (1 4.8% LEV vs 3 1.4% no LEV; P = .32). There was also no statistical difference in the median ICU LOS (2 days 1 day, 5 days LEV vs 2 days 1 day, 3 days no LEV; P = .27), median hospital LOS (6 days 2 days, 8 days LEV vs 6 days 3 days, 9 days no LEV; P = .27), or adverse events.
Conclusions
This study does not support the use of levetiracetam prophylaxis in patients who have experienced an ICH.
Natural killer (NK) cells kill tumor cells and virally infected cells, and an effective NK cell response requires processes, such as motility, recognition, and directional secretion, that rely on ...cytoskeletal rearrangement. The Rho guanosine triphosphatase (GTPase) Cdc42 coordinates cytoskeletal reorganization downstream of many receptors. The Rho-related GTPase from plants 1 (ROP1) exhibits oscillatory activation behavior at the apical plasma membrane of growing pollen tubes; however, a similar oscillation in Rho GTPase activity has so far not been demonstrated in mammalian cells. We hypothesized that oscillations in Cdc42 activity might occur within NK cells as they interact with target cells. Through fluorescence lifetime imaging of a Cdc42 biosensor, we observed that in live NK cells forming immunological synapses with target cells, Cdc42 activity oscillated after exhibiting an initial increase. We used protein-protein interaction networks and structural databases to identify candidate proteins that controlled Cdc42 activity, leading to the design of a targeted short interfering RNA screen. The guanine nucleotide exchange factors RhoGEF6 and RhoGEF7 were necessary for Cdc42 activation within the NK cell immunological synapse. In addition, the kinase Akt and the p85α subunit of phosphoinositide 3-kinase (PI3K) were required for Cdc42 activation, the periodicity of the oscillation in Cdc42 activity, and the subsequent polarization of cytotoxic vesicles toward target cells. Given that PI3Ks are targets of tumor therapies, our findings suggest the need to monitor innate immune function during the course of targeted therapy against these enzymes.
Objective: to develop a depression screening scale that does not rely on verbal communication. Setting: an acute geriatric unit in a teaching hospital. Subjects: 96 patients (mean age 81 years, range ...68–92, 59 women); 40% of the initial study group of 50 and 22% of the validation group of 46 were diagnosed as depressed. Methods: we devised a scale using nine items which could be rated by an observer; we determined inter‐rater reliability, sensitivity, specificity and predictive values for each item compared with a Geriatric Mental State‐AGECAT diagnosis of depression; we validated a final scale of six items. Results: inter‐rater reliability was poor for two items (irritability and sleep disturbance) while two items (sleep disturbance and night sedation) had poor sensitivity; we omitted these items in a revised scale. Re‐analysis of data from the initial study showed that a cut‐off of ⩾3 on the revised scale gave a sensitivity of 83%, a specificity of 95%, a positive predictive value of 0.89 and a negative predictive value of 0.90. Spearman's correlation coefficient between the six‐item questionnaire and the Hamilton rating scale was 0.79. In the validation study, the cut‐off score of ⩾3 on the revised six‐item scale had a sensitivity of 90%, specificity of 72%, a positive predictive value of 0.69 and a negative predictive value of 0.96. Conclusions: this simple, short, observation‐based screening scale completed by nurses is sensitive and specific in identifying depression in elderly medically ill patients, and may be a useful addition to clinical practice.
PDF
