Immunogenicity and safety of a combination of two serogroup B meningococcal outer membrane vesicle vaccines

MenBvac and MeNZB are safe and efficacious vaccines against serogroup B meningococcal disease. MenBvac is prepared from a B:15:P1.7,16 meningococcal strain (strain 44/76), and MeNZB is prepared from a B:4:P1.7-2,4 strain (strain NZ98/254). At 6-week intervals, healthy adults received three doses of MenBvac (25 microg), MeNZB (25 microg), or the MenBvac and MeNZB (doses of 12.5 microg of each vaccine) vaccines combined, followed by a booster 1 year later. Two-thirds of the subjects who received a monovalent vaccine in the primary schedule received the other monovalent vaccine as a booster dose. The immune responses to the combined vaccine were of the same magnitude as the homologous responses to each individual vaccine observed. At 6 weeks after the third dose, 77% and 87% of the subjects in the combined vaccine group achieved serum bactericidal titers of > or = 4 against strains 44/76 and NZ98/254, respectively, and 97% and 93% of the subjects achieved a fourfold or greater increase in opsonophagocytic activity against strains 44/76 and NZ98/254, respectively. For both strains, a trend of higher responses after the booster dose was observed in all groups receiving at least one dose of the respective strain-specific vaccine. Local and systemic reactions were common in all vaccine groups. Most reactions were mild or moderate in intensity, and there were no vaccine-related serious adverse events. The safety profile of the combined vaccine was not different from those of the separate monovalent vaccines. In conclusion, use of either of the single vaccines or the combination of MenBvac and MeNZB may have a considerable impact on the serogroup B meningococcal disease situation in many countries.     

Feasibility of shock advice analysis during CPR through removal of CPR artefacts from the human ECG

Mechanical activity from chest compressions and ventilations during cardiopulmonary resuscitation (CPR) introduces artefact components into the electrocardiogram (ECG). CPR must therefore be discontinued for reliable shock advice analysis in automated external defibrillators. Reducing or eliminating this detrimental "hands-off" time by removing the CPR artefacts, should significantly improve the defibrillation success rate. The feasibility of this was tested by removing the CPR artefacts using a multichannel adaptive filter, the multichannel recursive adaptive matching pursuit (MC-RAMP) algorithm. Human ECG and reference channel data from episodes with both shockable and non-shockable underlying heart rhythms were recorded from 105 patients with out-of-hospital cardiac arrest. The performance of a shock advice algorithm was evaluated before and after artefact removal using the MC-RAMP algorithm. From a test set consisting of 92 shockable and 174 non-shockable episodes a sensitivity of 96.7% and specificity of 79.9% was achieved, an increase of approximately 15 and 13%, respectively, compared to no filtering. Good sensitivity was achieved, enabling ECG analysis during CPR that would reduce the hands-off time on patients with shockable rhythms. However, CPR artefact removal on non-shockable rhythms proved a more difficult problem. We need a better understanding of the physiological mixing of artefacts and the underlying heart rhythm and suggest clinical trials to investigate the nature of CPR artefacts further.     

Treatment of intra-oral injection phobia: a randomized delayed intervention controlled trial among Norwegian 10- to 16-year-olds

Objective: To evaluate the effect of five sessions of cognitive behavioural therapy (CBT) for 10- to 16-year-olds with intra-oral injection phobia.

Material and methods: This was a randomized delayed intervention controlled trial in 67 patients, fulfilling the DSM-5 criteria for specific phobia. All patients received the same CBT performed by dentists specially trained in CBT. The patients were randomly assigned to either an immediate treatment group (ITG) (34 patients) or a waitlist-control group (WCG) (33 patients). The WCG was put on a waitlist for 5 weeks. After treatment, all patients were combined for post-treatment analyses. Assessments including the psychometric self-report scales Intra-oral injection fear scale (IOIF-s), Children’s Fear Survey Schedule-Dental Subscale (CFSS-DS), Injection Phobia Scale for children (IS-c) and Mutilation Questionnaire for children (MQ-c) and a behavioural avoidance test (BAT) followed by a questionnaire on cognitions during the BAT, occurred pre-, post-treatment/waitlist and at a 1-year follow-up.

Results: CBT had a significant effect compared to no treatment (WCG). After treatment, the scores on the psychometric self-report scales were significantly reduced and higher levels in the BAT were achieved. The results were maintained at 1-year follow-up. Of the 67 patients, 70.1% received intra-oral injections during CBT treatment, whereas 69.4% of those completing the CBT, in need for further dental treatment, managed to receive the necessary intra-oral injections at their regular dentist.

Conclusions: The 10- to 16-year-olds diagnosed with intra-oral injection phobia benefitted positively on CBT performed by specially trained dentists.     

Natural resistance-associated macrophage protein 1 polymorphisms are associated with microscopy-positive tuberculosis

The natural resistance-associated macrophage protein 1 (NRAMP1) is implicated in the pathophysiology of mycobacterial infections. We investigated by polymerase chain reaction previously published Nramp1 genotypes at 4 loci-INT4, N543D, 3'UTR, and 5'(CA)(n) microsatellite markers-in 104 human immunodeficiency virus-negative patients with tuberculosis and 176 healthy control subjects living in Denmark. No significant difference in genotype frequency was found between white patients with tuberculosis and control subjects (P>.16), but carriage of Nramp1 variant alleles at loci INT4 and 5'(CA)(n) conferred a significantly increased risk of having microscopy-positive compared with microscopy-negative tuberculosis (65% vs. 35% [P=.0004] and 63% vs. 38% [P=.047], respectively). The Nramp1 alleles were not associated with increased risk for the development of cavities seen on chest radiographs, or with extrapulmonary tuberculosis. These results indicate that variant alleles in the Nramp1 gene are associated with increased mycobacterial replication rather than susceptibility for tuberculosis and may thus confer increased risk of severe disease.     

Nutritional Supplementation Increases Rifampin Exposure among Tuberculosis Patients Coinfected with HIV

Nutritional supplementation to tuberculosis (TB) patients has been associated with increased weight and reduced mortality, but its effect on the pharmacokinetics of first-line anti-TB drugs is unknown. A cohort of 100 TB patients (58 men; median age, 35 [interquartile range {IQR}, 29 to 40] years, and median body mass index [BMI], 18.8 [17.3 to 19.9] kg/m²) were randomized to receive nutritional supplementation during the intensive phase of TB treatment. Rifampin plasma concentrations were determined after 1 week and 2 months of treatment. The effects of nutritional supplementation, HIV, time on treatment, body weight, and SLCO1B1 rs4149032 genotype were examined using a population pharmacokinetic model. The model adjusted for body size via allometric scaling, accounted for clearance autoinduction, and detected an increase in bioavailability (+14%) for the patients in the continuation phase. HIV coinfection in patients not receiving the supplementation was found to decrease bioavailability by 21.8%, with a median maximum concentration of drug in serum (C_max) and area under the concentration-time curve from 0 to 24 h (AUC_0–24) of 5.6 μg/ml and 28.6 μg · h/ml, respectively. HIV-coinfected patients on nutritional supplementation achieved higher C_max and AUC_0–24 values of 6.4 μg/ml and 31.6 μg · h/ml, respectively, and only 13.3% bioavailability reduction. No effect of the SLCO1B1 rs4149032 genotype was observed. In conclusion, nutritional supplementation during the first 2 months of TB treatment reduces the decrease in rifampin exposure observed in HIV-coinfected patients but does not affect exposure in HIV-uninfected patients. If confirmed in other studies, the use of defined nutritional supplementation in HIV-coinfected TB patients should be considered in TB control programs. (This study has the controlled trial registration number ISRCTN 16552219.)     

Knee arthroscopy and arthrotomy under local anesthesia

We report our experience with knee arthroscopy in local anesthesia in 64 patients with subsequent arthrotomy in 14 of these. The effectiveness of the anesthetic method was evaluated by both the patient and the anesthetic personnel. There was no difference in pain assessment between arthroscopy alone and arthroscopy followed by arthrotomy. Half of the patients had no pain and only one regarded the procedure as very painful. Supplementary analgesia with 0.05 mg fentanyl was given to half of the patients not undergoing arthrotomy and to two thirds of those who had arthrotomy. It was not necessary to abandon any arthroscopic or surgical procedure because of pain. We conclude that local anesthesia is a safe and practical method for diagnostic arthroscopy, arthroscopic surgery, and minor arthrotomy.     

Action research: what is it? How has it been used and how can it be used in nursing?

Action research has enjoyed increasing popularity across a wide variety of disciplines including nursing. Action research was designed specifically to bridge the gap between theory, research and practice and incorporates both humanistic and naturalistic scientific methods. As such, action research is a highly compelling method for nursing. However, action research does not easily lend itself to definition. A variety of approaches, definitions and uses have emerged since it was created by Kurt Lewin and have given rise to much debate within social and behavioural sciences. This confusion has carried over into nursing literature without any systematic identification of or debate about the core characteristics of action research or the multitude of approaches or uses that have come to be associated with this method. Thus this paper addresses the central characteristics, three major approaches to action research that exist today and how action research has been used and can be used in nursing.     

Neurological complications to vaccination against Japanese encephalitis

Japanese encephalitis (JE) vaccine has been used for childhood immunization programmes in Asia since the 1960s. Also, travellers from other parts of the world have been vaccinated before travelling to Asian countries. Some JE vaccines are produced from infected mouse brains and contain small amounts of myelin basic protein. Neurological side effects in larger vaccine trials in Asia have been reported in 1–2.3 per million vaccinees. Statens Serum Institut is the only distributor of JE vaccine in Denmark, delivering 384 000 doses from 1983–96. In 1996, evaluation of initial symptoms and findings in 10 adult travellers from Denmark, who developed moderate-severe neurological symptoms within a few weeks of JE vaccination, was performed as well as follow-up magnetic resonance imaging (MRI) and clinical neurological examination. Three patients initially had symptoms varying from severe encephalitis-like illness to paraesthesia, double vision or parkinsonian gait disturbance. MRI showed severe atrophy of the corpus callosum with altered signal intensity indicating gliosis in one patient, another patient had several hyperintense spots located periventricularly in the white matter, while a third patient had spots with increased signals in the pons, the right substantia nigra and the occipital region. Acute disseminated encephalomyelitis (ADEM) is a possible explanation for these MRI changes, although multiple sclerosis is an alternative diagnosis in one or two of the patients. Another three patients had long-lasting headache, concentration difficulty or intellectual reduction. One man had afebrile convulsions, another gait instability and depression and one parkinsonism. A woman developed myelitis. If these findings are due to JE vaccination the frequency of neurological reactions to the vaccine is considerably higher than previously reported and in the future any minor neurological complaints occurring shortly after vaccination should lead to neurological examination and acute MRI scan should be considered.