Accuracy of six antimicrobial susceptibility methods for testing linezolid against staphylococci and enterococci

A challenge panel of enterococci (n = 50) and staphylococci (n = 50), including 17 and 15 isolates that were nonsusceptible to linezolid, respectively, were tested with the Clinical and Laboratory Standards Institute broth microdilution and disk diffusion reference methods. In addition, all 100 isolates were tested in parallel by Etest (AB Biodisk, Solna, Sweden), MicroScan WalkAway (Dade, West Sacramento, CA), BD Phoenix (BD Diagnostic Systems, Sparks, MD), VITEK (bioMérieux, Durham, NC), and VITEK 2 (bioMérieux) by using the manufacturers' protocols. Compared to the results of the broth microdilution method for detecting linezolid-nonsusceptible staphylococci and enterococci, MicroScan results showed the highest category agreement (96.0%). The overall categorical agreement levels for VITEK 2, Etest, Phoenix, disk diffusion, and VITEK were 93.0%, 90.0%, 89.6%, 88.0%, and 85.9%, respectively. The essential agreement levels (results within +/-1 doubling dilution of the MIC determined by the reference method) for MicroScan, Phoenix, VITEK 2, Etest, and VITEK were 99.0%, 95.8%, 92.0%, 92.0%, and 85.9%, respectively. The very major error rates for staphylococci were the highest for VITEK (35.7%), Etest (40.0%), and disk diffusion (53.3%), although the total number of resistant isolates tested was small. The very major error rate for enterococci with VITEK was 20.0%. Three systems (MicroScan, VITEK, and VITEK 2) provided no interpretations of nonsusceptible results for staphylococci. These data, from a challenge panel of isolates, illustrate that the recent emergence of linezolid-nonsusceptible staphylococci and enterococci is providing a challenge for many susceptibility testing systems.     

Thermal stability of the WHO international standard of interferon alpha 2b (IFN-alpha 2b): application of new reporter gene assay for IFN-alpha 2b potency determinations

A World Health Organization requirement for biological standards is that they should exhibit long-term stability at their recommended storage temperature. Thermal stability is usually predicted in accelerated thermal degradation studies, where ampoules of the lyophilized standard are stored at elevated temperatures for relatively short times before testing. To confirm the predicted thermal stability of the 2nd international standard of human interferon alpha 2b (IFN-alpha2b; 95/566), we tested the potency of the ampouled contents of this standard after 9 years storage at the customary storage temperature of -20 degrees C in comparison with ampoules of the IS which had been stored continuously at temperatures ranging from -150 degrees C to 56 degrees C. Since IFN-alpha2b potency estimates derived from the results of antiviral assays (AVA) showed high within-assay variability, we investigated a novel reporter gene assay (RGA) based on induction of secreted alkaline phosphatase (SEAP) for comparability and precision of such estimations. We show that this RGA generated comparable estimates with overall lower variation. Additionally, the SEAP conversion of p-nitrophenyl phosphate to yellow product could be followed kinetically. Absorbance readings were shown to increase with time in proportion with increasing concentration of IFN-alpha2b. When the time-dependent increments of absorbance were plotted graphically, the slopes of lines corresponded to concentration. This approach enabled single dilutions of IFN samples, identical in molecular structure to an IFN-alpha2b standard, to be used for potency estimates by interpolation of slope value against those of the standard at fixed concentrations. It appears attractive for high through-put potency testing of various R&D IFN-alpha2b samples.     

The prevention of pain from sickle cell disease by trandolapril

A 48-year-old African-American woman with both sickle cell anemia and chronic pain was treated with a hydrophobic angiotensin I-converting enzyme (ACE) inhibitor. This resulted in the complete resolution of her pain. When the ACE inhibitor was deliberately stopped, her pain recurred, only to cease again after the ACE inhibitor was deliberately resumed. The activation of ACE may be an early step in the arterial vaso-occlusion typical of sickle cell disease.     

The effect of orientation on prehension movement time

We explored the relationship between hand orientation and movement time. Three groups of participants (n = 8 per group) were asked to grasp an object rotated in one of the following planes: (1) coronal; (2) sagittal; (3) horizontal. In the coronal plane, the rotational requirements directly mapped onto the neuromuscular demands associated with a single joint-level degree of freedom movement. A simple lawful relationship was found between the extent of rotation (pronation or supination) and duration. Reach-to-grasp movements to objects rotated in the sagittal and horizontal plane produced different movement patterns. These patterns increased the muscle level degrees of freedom recruited (higher neuromuscular demands) and movement duration increased correspondingly though not in a simple manner. The results of the present study show unambiguously that object orientation influences the duration of reach-to-grasp movements.     

Modified Version of Baby-Led Weaning Does Not Result in Lower Zinc Intake or Status in Infants: A Randomized Controlled Trial

Background

Little is known about zinc intakes and status during complementary feeding. This is particularly true for baby-led approaches, which encourage infants to feed themselves from the start of complementary feeding, although self-feeding may restrict the intake of zinc-rich foods.

Economic evaluation of telephone-based weight loss support for patients with knee osteoarthritis: a randomised controlled trial

Background

The prevalence of knee osteoarthritis is increasing worldwide. Obesity is an important modifiable risk factor for both the incidence and progression of knee osteoarthritis. Consequently, international guidelines recommend all patients with knee osteoarthritis who are overweight receive support to lose weight. However, few overweight patients with this condition receive care to support weight loss. Telephone-based interventions are one potential solution to provide scalable care to the many patients with knee osteoarthritis. The objective of this study is to evaluate, from a societal perspective, the cost-utility and cost-effectiveness of a telephone-based weight management and healthy lifestyle service for patients with knee osteoarthritis, who are overweight or obese.

Methods

An economic evaluation was undertaken alongside a pragmatic randomised controlled trial. Between May 19 and June 30, 2015, 120 patients with knee osteoarthritis were randomly assigned to an intervention or usual care control group in a 1:1 ratio. Participants in the intervention group received a referral to an existing non-disease specific 6-month telephone-based weight management and healthy lifestyle service. Quality-adjusted life years (QALYs) was the utility measure and knee pain intensity, disability, weight, and body mass index (BMI) were the clinical measures of effect. Costs included intervention costs, healthcare utilisation costs (healthcare services and medication use) and absenteeism costs due to knee pain. Data was collected at baseline, 6?weeks and 26?weeks. The primary cost-effectiveness analysis was performed from the societal perspective.

Results

Mean cost differences between groups (intervention minus control) were $493 (95%CI: -3513 to 5363) for healthcare costs, $-32 (95%CI: -73 to 13) for medication costs, and $125 (95%CI: -151 to 486) for absenteeism costs. The total mean difference in societal costs was $1197 (95%CI: -2887 to 6106). For QALYs and all clinical measures of effect, the probability of the intervention being cost-effective compared with usual care was less than 0.36 at all willingness-to-pay values.

Conclusions

From a societal perspective, telephone-based weight loss support, provided using an existing non-disease specific 6-month weight management and healthy lifestyle service was not cost-effective in comparison with usual care for overweight and obese patients with knee osteoarthritis.

Trial registration number

ACTRN12615000490572, registered 18th May 2015

     

Health beliefs, disease severity, and patient adherence: a meta-analysis

BACKGROUND: A large body of empirical data exists on the prediction of patient adherence from subjective and objective assessments of health status and disease severity. This work can be summarized with meta-analysis. OBJECTIVES: Retrieval and summary analysis of r effect sizes and moderators of the relationship between patient adherence and patients': (1) beliefs in disease threat; (2) rated health status (by physician, self, or parent); and (3) objective disease severity. METHODS: Comprehensive search of published literature (1948-2005) yielding 116 articles, with 143 separate effect sizes. Calculation of robust, generalizable random effects model statistics, and detailed examination of study diversity with moderator analyses. RESULTS: Adherence is significantly positively correlated with patients' beliefs in the severity of the disease to be prevented or treated ("disease threat"). Better patient adherence is associated with objectively poorer health only for patients experiencing disease conditions lower in seriousness (according to the Seriousness of Illness Rating Scale). Among conditions higher in seriousness, worse adherence is associated with objectively poorer health. Similar patterns exist when health status is rated by patients themselves, and by parents in pediatric samples. CONCLUSIONS: Results suggest that the objective severity of patients' disease conditions, and their awareness of this severity, can predict their adherence. Patients who are most severely ill with serious diseases may be at greatest risk for nonadherence to treatment. Findings can contribute to greater provider awareness of the potential for patient nonadherence, and to better targeting of health messages and treatment advice by providers.     

Dependence of antibody gene diversification on uracil excision

Activation-induced deaminase (AID) catalyses deamination of deoxycytidine to deoxyuridine within immunoglobulin loci, triggering pathways of antibody diversification that are largely dependent on uracil-DNA glycosylase (uracil-N-glycolase [UNG]). Surprisingly efficient class switch recombination is restored to ung(-/-) B cells through retroviral delivery of active-site mutants of UNG, stimulating discussion about the need for UNG's uracil-excision activity. In this study, however, we find that even with the overexpression achieved through retroviral delivery, switching is only mediated by UNG mutants that retain detectable excision activity, with this switching being especially dependent on MSH2. In contrast to their potentiation of switching, low-activity UNGs are relatively ineffective in restoring transversion mutations at C:G pairs during hypermutation, or in restoring gene conversion in stably transfected DT40 cells. The results indicate that UNG does, indeed, act through uracil excision, but suggest that, in the presence of MSH2, efficient switch recombination requires base excision at only a small proportion of the AID-generated uracils in the S region. Interestingly, enforced expression of thymine-DNA glycosylase (which can excise U from U:G mispairs) does not (unlike enforced UNG or SMUG1 expression) potentiate efficient switching, which is consistent with a need either for specific recruitment of the uracil-excision enzyme or for it to be active on single-stranded DNA.