Individual Variation in Adaptive Immune Responses and Risk of Hip Fracture—A NOREPOS Population-Based Cohort Study

Immune-mediated bone loss significantly impacts fracture risk in patients with autoimmune disease, but to what extent individual variations in immune responses affect fracture risk on a population level is unknown. To examine how immune responses relate to risk of hip fracture, we looked at the individual variation in a post-vaccination skin test response that involves some of the immune pathways that also drive bone loss. From 1963 to 1975, the vast majority of the Norwegian adult population was examined as part of the compulsory nationwide Norwegian mass tuberculosis screening. These examinations included standardized tuberculin skin tests (TSTs). Our study population included young individuals (born 1940 to 1960 and aged 14 to 30 years at examination) who had all received Bacille Calmette-Guerin (BCG) vaccination after a negative TST at least 1 year prior and had no signs of tuberculosis upon clinical examination. The study population ultimately included 244,607 individuals, whose data were linked with a national database of all hospitalized hip fractures in Norway from 1994 to 2013. There were 3517 incident hip fractures during follow-up. Using a predefined Cox model, we found that men with a positive or a strong positive TST result had a 20% (hazard ratio [HR] = 1.20, 95% confidence interval [CI] 1.01–1.44) and 24% (HR = 1.24, 95% CI 1.03–1.49) increased risk of hip fracture, respectively, compared with men with a negative TST. This association was strengthened in sensitivity analyses. Total hip bone mineral density (BMD) was available for a limited subsample and similarly revealed a non-significantly reduced BMD among men with a positive TST. Interestingly, no such clear association was observed in women. An increased immune response after vaccination is associated with an increased risk of hip fracture decades later among men, possibly because of increased immune-mediated bone loss. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Do educational meetings and group detailing change adherence to drug formularies in hospitals? A cluster randomized controlled trial

Purpose

The aim of this study was to examine whether educational meetings and group detailing could increase the use of drugs from the ward lists or the drug formulary in hospitals.

Methods

Twelve medical wards from two hospitals were randomized into three groups: control, basic and extended intervention. All wards had a ward list review before interventions. Moreover, the basic intervention consisted of an educational meeting, and the extended intervention included two group detailing sessions. The proportion of drugs used from the ward list or hospital drug formulary (HDF) was the primary outcome. Data (defined daily doses [DDDs], numbers and cost [Euros]) on drugs sold to the wards were retrieved from the two hospitals from 1 July 2011 to 31 August 2012. Baseline data: from July to September 2011, and follow-up data: from June to August 2012.

Results

The proportion of formulary drugs used increased for the extended intervention group (0.04, range ?0.02 to 0.09) and basic intervention group (0.03, range ?0.03 to 0.09) in comparison with a decrease in the control group (?0.01, range ?0.03 to ?0.02). The interventions did not significantly change odds for selecting drugs from the formulary in comparison with the control group (basic intervention: OR 1.09 [95 % CI 0.81 to 1.46]; extended intervention: OR 1.00 [95 % CI 0.75 to 1.35]).

Conclusions

In this study, educational meetings and group detailing do not significantly improve adherence to ward lists or HDF. The adherence to the formularies at baseline was relatively high, which may explain why the interventions did not have a significant effect.     

Unlocked nucleic acid modified primer-based enzymatic polymerization assay: towards allele-specific genotype detection of human platelet antigens

Accurate detection of single nucleotide polymorphisms (SNPs) is paramount for the appropriate therapeutic intervention of debilitating diseases associated with SNPs. However, in some cases current nucleic acid probes fail to detect allele-specific mutations, for example, human platelet antigens, HPA-15a (TCC) and HPA-15b (TAC) alleles associated with neonatal alloimmune thrombocytopenia. Towards this, it is necessary to develop a novel assay for detection of allele-specific mutations. In this study, we investigated the potential of unlocked nucleic acid (UNA)-modified primers in SNP detection utilising an enzymatic polymerisation-based approach. Our results of primer extension and asymmetric polymerase chain reaction by KOD XL DNA polymerase revealed that UNA-modified primers achieved excellent allele-specificity in discriminating the human platelet antigen DNA template, whereas the DNA control primers were not able to differentiate between the normal and mutant alleles, demonstrating the scope of this novel UNA-based enzymatic approach as a robust methodology for efficient detection of allele-specific mismatches. Although further evaluation is required for other disease conditions, we firmly believe that our findings offer a great promise for the diagnosis of neonatal alloimmune thrombocytopenia and other SNP-related diseases.

We investigated the potential of UNA-modified primers for mismatch recognition capabilities using enzymatic polymerisation approach. Efficient allele-specific discrimination was achieved with the UNA-modified primers unlike the DNA primers.     

Tying up Nicotine: New Selective Competitive Antagonist of the Neuronal Nicotinic Acetylcholine Receptors

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Carry-over of host nutrients during sampling enhances undesired growth of Staphylococcus aureus in liquid Amies transport medium

Optimal transportation of bacteria is important for accurate clinical interpretation, quantitative assays, and microbiome studies. A transport medium should ideally keep the bacteria alive without supporting growth or altering the relative proportions of the constituent species. We investigated the effect of nasal mucus and mucin on the growth and survival of two Staphylococcus aureus strains in liquid Amies transport medium at room temperature and 4?°C for 14?days. The study showed that the presence of nasal mucus in microbiological samples stimulated undesired S. aureus growth at room temperature in a dose-dependent manner. These findings underscore that microbiological samples from humans and animals should be stored at 4?°C until analysis to avoid undesired S. aureus growth.     

The effect of training in an interactive dynamic stander on ankle dorsiflexion and gross motor function in children with cerebral palsy

Objective: To study the effect of active stretching of ankle plantarflexors using an interactive dynamic stander in children with cerebral palsy (CP).

Methods: Six children in Gross Motor Function Classification System classes I–III, aged 4–10 years, trained intensive active dorsiflexion in an interactive dynamic stander using ankle movement to play custom computer games following a 10-week control period. Gross Motor Function Measure Item Set, gait performance and passive and active dorsiflexion with extended and flexed knee were chosen as outcome parameters.

Results: Median active and passive ankle dorsiflexion increased significantly (5 and 10 degrees, respectively) with extended knee. There was a small but clinically significant increase in gross motor function. The intervention had no effect on temporospatial gait parameters.

Conclusion: In spite of the low number of participants, these results may indicate that intensive active stretching in an interactive dynamic stander could be an effective new conservative clinical treatment of ankle plantarflexor contracture in children with CP.     

Synthesis and Structure–Activity Relationships of N-Benzyl Phenethylamines as 5-HT2A/2C Agonists

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