A systems analysis of the chemosensitivity of breast cancer cells to the polyamine analogue PG-11047

Background

When this trial was initiated, the combined measles, mumps and rubella (MMR) vaccine was licensed for subcutaneous administration in all European countries and for intramuscular administration in some countries, whereas varicella vaccine was licensed only for subcutaneous administration. This study evaluated the intramuscular administration of an MMR vaccine (M-M-RvaxPro^®) and a varicella vaccine (VARIVAX^®) compared with the subcutaneous route.

Methods

An open-label randomised trial was performed in France and Germany. Healthy children, aged 12 to18 months, received single injections of M-M-RvaxPro and VARIVAX concomitantly at separate injection sites. Both vaccines were administered either intramuscularly (IM group, n = 374) or subcutaneously (SC group, n = 378). Immunogenicity was assessed before vaccination and 42 days after vaccination. Injection-site erythema, swelling and pain were recorded from days 0 to 4 after vaccination. Body temperature was monitored daily between 0 and 42 days after vaccination. Other adverse events were recorded up to 42 days after vaccination and serious adverse events until the second study visit.

Results

Antibody response rates at day 42 in the per-protocol set of children initially seronegative to measles, mumps, rubella or varicella were similar between the IM and SC groups for all four antigens. Response rates were 94 to 96% for measles, 98% for both mumps and rubella and 86 to 88% for varicella. For children initially seronegative to varicella, 99% achieved the seroconversion threshold (antibody concentrations of ≥ 1.25 gpELISA units/ml). Erythema and swelling were the most frequently reported injection-site reactions for both vaccines. Most injection-site reactions were of mild intensity or small size (≤ 2.5 cm). There was a trend for lower rates of injection-site erythema and swelling in the IM group. The incidence and nature of systemic adverse events were comparable for the two routes of administration, except varicella-like rashes, which were less frequent in the IM group.

Conclusion

The immunogenicities of M-M-RvaxPro and VARIVAX administered by the intramuscular route were comparable with those following subcutaneous administration, and the tolerability of the two vaccines was comparable regardless of administration route. Integration of both administration routes in the current European indications for the two vaccines will now allow physicians in Europe to choose their preferred administration route in routine clinical practice.

Trial registration

ClinicalTrials.gov NCT00432523     

Elucidating the role of hypoxia-inducible factor in rheumatoid arthritis

Inflammopharmacology - Rheumatoid arthritis (RA) is a chronic multifactorial disease, provocative, and degenerative autoimmune condition that impacts millions of individuals around the globe. As a...     

Voluntary turnover among nurses working in Kuwaiti hospitals

BACKGROUND: Voluntary turnover rates are high among staff nurses working in Kuwaiti hospitals. It is a major problem, costly and it is presumed to impact on the quality of nursing care delivered. AIMS: The two aims of this study were to (1) find out if nurses' resignations in Kuwaiti hospitals could be ascribed to failure in the recruitment process and (2) examine the feelings of nurses who resigned. METHODS: Two sets of exit interviews with 60 nurses who had resigned were conducted. RESULTS: No evidence emerged that any false information or misleading information was provided except for the salary adjustments. The real insight lay in what might not have been said in the recruitment interviews. While feelings of discontent emerged in the interviews relating to the loss of income, the greatest source of complaint related to the failure of managers to solve the evident problems. CONCLUSIONS: High rates of voluntary turnover require more attention from administrators and policy makers because of its potential consequences in terms of the quality of nursing care delivered. Implications for nursing management This paper identifies many causes of nurses' voluntary turnover. It also shows the need for nursing managers to explore these causes and suggests successful strategies for recruitment and retention practices and policies.     

Non-convulsive status epilepticus; the rate of occurrence in a general hospital

BackgroundNon-convulsive status epilepticus (NCSE) has been increasingly recognized as a cause of impaired level of consciousness in the ICU and emergency rooms. The diagnosis can be easily missed without an electroencephalogram (EEG) given the paucity of overt clinical signs in this condition. Recently few published data estimated the prevalence to be between 3% and 8%.ObjectiveTo assess the rate of occurrence of NCSE among patients with various degrees of impaired consciousness referred to the Neurophysiology Laboratory at Vancouver General Hospital.MethodWe conducted a retrospective analysis of 451 adult patients (>16 years of age) with a question of NCSE or with an unknown cause of impaired level of consciousness between the years 2002 and 2004. NCSE was defined according to the Young's criteria of electrographic status epilepticus. NCSE was categorized into focal and generalized epileptic activity based on the continuous EEG monitoring (CEEG). Further analysis of age, gender and etiology was performed.ResultsOf 451 patients, EEG demonstrated electrographic status epilepticus with no overt clinical signs in 42 patients (9.3%). Median age was 61.8 years (range 21–94). According to etiology, 38.1% of patients with NCSE had hypoxic–anoxic injury, 19% had intracerebral hemorrhage (including trauma), 11.9% had the diagnosis of idiopathic or cryptogenic epilepsy, 7.1% had ischemic stroke, 4.8% were secondary to tumors and 4.8% to viral encephalitis.ConclusionThe rate of occurrence of NCSE in patients with decreased level of consciousness was 9.3%. The cohort represented a group of patients who were comatose and required assisted ventilation or had altered level of consciousness. Hypoxic brain injury was the most responsible etiology of NCSE in the cohort studied.     

Association between CD226 polymorphism and soluble levels in rheumatoid arthritis: Relationship with clinical activity

Objective: To study the relation between CD226 rs763361 gene polymorphism and CD226 serum level and to evaluate their role in susceptibility and disease activity of RA in a cohort of Egyptian individuals.

Methods: The serum level of CD226 was measured using a suitable ELISA kit and the CD226 rs763361 gene polymorphism was typed by PCR-RFLP for 112 RA patients and 100 healthy controls.

Results: Significant association with RA was found with CD226 T allele (OR (95%CI) = 1.6 (1.04–2.4), P = 0.032), and higher CD226 serum level (P = 0.001). Higher CD226 levels were associated with higher ESR values (P = 0.035), positive CRP (0.048), increased number of tender joints (P = 0.045), and higher DAS score (P = 0.035). Serum CD226 is an independent risk factor for the prediction of RA (P = 0.001). No correlations were found between the serum level of CD226 and different CD226 genotypes and also between them and RA activity grades.

Conclusion: The CD226 T allele may be susceptibility risk factors for the development of RA and the higher serum level of CD226 may be involved in the pathogenesis of RA in Egyptian patients. The serum level of CD226 and not CD226 genotypes could be considered as an independent risk factor for the prediction of RA within healthy individuals and also for RA disease activity.     

Transcatheter closure of congenital and acquired muscular ventricular septal defects using the Amplatzer device

Surgical closure of congenital or post-myocardial infarction (MI) muscular ventricular septal defect (MVSD) is associated with significant mortality and morbidity; therefore, both surgeons and cardiologists would welcome a safe non-surgical approach. The aim of this study is to report the combined experience of 2 cardiac centers in the transcatheter occlusion of both congenital and acquired MVSDs using the Amplatzer MVSD occluder device (AGA Medical Corporation, Golden Valley, Minnesota). Thirty-two patients underwent attempted transcatheter closure of an MVSD. Nineteen of these patients had congenital unoperated MVSD, twelve had post-MI MVSD and 1 patient had an acquired VSD post-surgical repair of hypertrophic cardiomyopathy. The median age of patients was 11.5 years (range, 0.1 86.0 years) and median weight was 34.5 kg (3.4 123.0 kg). All patients had significant shunt documented by echocardiography with a median Qp/Qs ratio of 1.7 (range, 1.0 5.3). The VSD location was mid-muscular in 14 patients, posterior in 10, apical in 5 and anterior in 3. The systolic pulmonary artery pressure ranged from 10 85 mmHg (median, 34.5 mmHg). The device was implanted successfully in 30 patients. The device size ranged from 6 26 mm (2 of these were ASD devices). There was immediate complete closure of the defect in 15 patients and 14 patients had residual shunt (foaming through the device). The median fluoroscopy time was 56.7 minutes (range, 11.7 146.0 minutes). Complications included: tamponade in 1 patient resulting in death; device malposition in 1 patient requiring surgical removal; severe hemolysis in 2 patients; and transient junctional rhythm in 1 patient. Among the 30 patients with successful implantation, three died in the hospital and 2 died later. On follow-up evaluation, there were no episodes of endocarditis, thromboembolism, hemolysis or wire disruption. We conclude that the Amplatzer MVSD occluder is a safe and effective device for closure of MVSDs up to 14 mm in diameter. Further clinical trials with this device are underway.     

Acute Kidney Injury in a National Cohort of Hospitalized US Veterans with COVID-19

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